Contributors

Michael Adler

John Richens

Professor, Department of Sexually Transmitted Diseases, Royal

Lecturer, Department of Sexually Transmitted

Free and University College Medical School, London

Diseases, Royal Free and University College Medical School,

London

Frances Cowan

Senior Lecturer, Department of Sexually Transmitted Diseases,

Ian Weller

Royal Free and University College Medical School, London

Professor, Department of Sexually Transmitted Diseases,

Royal Free and University College Medical School, London

Patrick French

Consultant Physician in Genitourinary Medicine, Honorary

Beryl West

Senior Lecturer, Department of Sexually Transmitted Diseases,

Medical Research Council Laboratories, Banjul, Gambia

Royal Free and University College Medical School, London

Ian G Williams

Richard Gilson

Senior Lecturer, Department of Sexually Transmitted

Senior Lecturer, Department of Sexually Transmitted Diseases,

Diseases, Royal Free and University College Medical School,

Royal Free and University College Medical School, London

London

Helen Mitchell

Consultant Physician in Sexual and Reproductive Health,

Honorary Senior Lecturer, Department of Sexually Transmitted

Diseases, Royal Free and University College Medical School,

London

Why sexually transmitted infections are

important

Michael Adler

What are sexually transmitted

infections?

Sexually transmitted infections (STIs) are infections whose

primary route of transmission is through sexual contact. STIs

can be caused by mainly bacteria, viruses, or protozoa. In the

developed world, viral diseases have become increasingly

common and important, whereas bacterial STIs are more

common in developing countries, but even this is changing

Why STIs are important

with the increasing recognition of viral diseases.

●

Common

The three most common presenting symptoms of an STI

●

Often asymptomatic

are urethral discharge, genital ulceration, and vaginal discharge

●

Major complications and sequelae

●

Expensive

with or without vulval irritation. The three most common STIs

●

Synergy with HIV

seen in clinics in the United Kingdom are genital warts,

chlamydial infections, and gonococcal infections.

Trichomoniasis, pediculosis pubis, and genital herpes are

common and are sexually transmitted. Scabies and vaginal

candidiasis often are diagnosed in STI clinics, although

they are not usually acquired sexually. Finally, sexually

transmitted hepatitis (A, B, and C) and HIV are becoming

more common.

Sexually transmitted infections and associated presenting symptoms

Urethral

Vaginal

Genital

Skin

discharge

ulceration

symptoms

Other

Bacteria

Chlamydia trachomatis

Neisseria gonorrhoeae

Treponema pallidum

Gardnerella vaginalis

Haemophilus ducreyi

Klebsiella granulomatis

Shigella

Mycoplasmas

Ureaplasma urealyticum

Mycoplasma genitalium

Parasites

Sarcoptes scabiei

Phthirus pubis

Viruses

Herpes simplex virus types 1

( )

and 2

Wart virus (papillomavirus)

( )

Molluscum contagiosum

(pox virus)

Hepatitis A, B, and C

HIV

Protozoa

Entamoeba histolytica

Giardia lamblia

Trichomonas vaginalis

( )

Fungi

Candida albicans

( )

Common. - Less common

ABC of Sexually Transmitted Infections

The consequences

Sexually transmitted infections are a major public health

problem and are one of the most common causes of illness,

Male

and even death, in the world today. They have far reaching

Female

health, social, and economic consequences, particularly in the

developing world. The World Bank estimated that for women

aged 15-44 years, STIs (excluding HIV) were the second most

common cause of healthy life lost after maternal morbidity.

Other studies have estimated that 5% of the total discounted

healthy life years lost in sub-Saharan Africa are caused by STIs,

excluding HIV, and that HIV alone accounts for 10% of healthy

life years lost.

Complications and cost

Most STIs are easy to diagnose and cheap to treat; however, viral

conditions, such as herpes and HIV, are costly and incurable.

Many infections remain unrecognised and undiagnosed, which

results in considerable long term morbidity, which can be costly

Top ten causes of healthy life lost in young adults aged 15-44 years

in human and monetary terms. The complications of untreated

infections are far reaching, and include cancer, reproductive

problems, and pregnancy related problems. Reproductive ill

health (death and disability related to pregnancy and childbirth,

STIs, HIV, AIDS, and reproductive cancers) has been calculated

Major sequelae of STIs

to account for 5-15% of the global burden of disease. Data on

Women

Men

Infants

the monetary costs of the complications of STIs are sparse,

Cancers

Cervical cancer

Penile cancer

particularly for the developing world. American data give

Vulval cancer

Anal cancer

estimates of total direct and indirect costs attributable to STIs to

Vaginal cancer

Liver cancer

Anal cancer

T cell

be $9.9 m annually, rising to $16.6 m if HIV and AIDS are

leukaemia

included. In the United Kingdom only limited data are available.

Liver cancer

Kaposi’s

For example, the prevention of unplanned pregnancy by NHS

sarcoma

contraception services probably saves over £2.5 billion per year,

T cell leukaemia

and the average lifetime treatment cost for an HIV positive

Kaposi’s

sarcoma

person is between £135 000 and £180 000, with a monetary value

Reproductive

Pelvic

Epididymitis

of preventing a single onward transmission of somewhere

health

inflammatory

between £0.5 m to £1 m in terms of individual health benefits and

problems

disease

treatment costs. Finally, but not calculated accurately, dramatic

Infertility

Prostatitis

cost savings can be made by preventing infertility.

Ectopic

Infertility

Few economic data exist in the developing world in relation

pregnancy

Spontaneous

to the consequences of STIs, which are considerable and

abortion

personally devastating. Many women become infertile without

Pregnancy

Preterm delivery

Stillbirth

even realising that they have suffered from pelvic inflammatory

disease. Estimates of the burden of infections for women in

problems

urban Africa have shown that chlamydial infection causes an

Premature

Low birth weight

rupture of

average of 4.8 lost days of productive life and syphilis leads to

membranes

8.2 days per capita per year. Estimates suggest that with the

Puerperal sepsis

Pneumonia

high prevalence of syphilis in pregnant women, for example

Postpartum

Neonatal sepsis

10%, up to 8% of all pregnancies (beyond 12 weeks) would

infection

have an adverse outcome.

Acute hepatitis

Congenital

abnormalities

Neurological

Neurosyphilis

Cytomegalo-

Synergy between STIs and HIV

problems

virus

Herpes simplex

It is now recognised that there is a synergy between most STIs

virus

and HIV (particularly ulcerative and inflammatory conditions).

Syphilis

Many research studies in both the developed and developing

associated

world have shown that HIV transmission and acquisition are

neurological

problems

enhanced by the presence of STIs, probably because of the

Other common

Chronic liver

inflammatory effect of STIs in the genital mucosa. HIV negative

health

disease

people with an ulcerative STI seem to be particularly vulnerable

consequences

to infection, probably because in addition to the genital

Cirrhosis

inflammation that occurs, ulceration causes physical disruption

of the skin or mucous membrane, thus making it more

permeable to infection. Non-ulcerative STIs also facilitate HIV

acquisition and transmission but to a lesser degree. As they are

Why sexually transmitted infections are important

so common in many parts of the world, however, their impact

Role of STIs in the acquisition of HIV

on the HIV epidemic is likely to be considerable. HIV positive

●

HIV acquisition increases by twofold to fivefold in the presence

people with intercurrent ulcerative and non-ulcerative STIs

of other STIs

have increased rates of genital shedding of HIV, which diminish

●

Ulcers disrupt mucosal integrity and increase the presence or

when the STI is resolved. Clinical studies have shown that HIV

activation, or both, of HIV susceptible cells (for example, CD4

positive patients with a urethral infection have an eightfold

lymphocytes)

increase in HIV-1 RNA in semen, which falls after treatment.

●

Non-ulcerative STIs (such as gonorrhoea, chlamydia,

The likelihood of infection per exposure to HIV for any sexual

Trichomonas vaginalis, and bacterial vaginosis) increase the

presence or activation, or both, of HIV susceptible cells

contact is in the order of 0.1, which will increase considerably

if an STI is present by the order of threefold to fivefold. This

synergy, and a realisation that the control of STIs can have a

profound effect on the incidence of HIV, has led to an

increased drive and interest in STI control programmes.

Eastern Europe and Central Asia

22 million

Western Europe

Size of the problem

17 million

North America

East Asia and Pacific

The size of the global burden of STIs is uncertain because of

14 million

18 million

the lack of effective control and notification systems in many

North Africa and Middle East

10 million

countries. The World Health Organization (WHO) has

South and South East Asia

151 million

estimated a total of 340 million new cases of curable STIs in

adults per annum, mainly in South and South East Asia

Latin America and Caribbean

(151 million new cases per year), and sub-Saharan Africa

38 million

Sub-Saharan Africa

(69 million). In eastern Europe and Central Asia, the estimate

69 million

Australasia

is 22 million, and 17 million in western Europe. The prevalence

1 million

and incidence per million of the population varies regionally,

Estimated new cases of curable STIs among adults (global total 340 million).

for example between sub-Saharan Africa and western Europe it

Data source: World Health Organization

is eightfold and fourfold, respectively.

1.6

England

1.4

Scotland

New diagnoses of selected STIs in GUM clinics

1.2

Wales

(England, Wales, and Northern Ireland, 2002)

Northern Ireland

1.0

% change

0.8

2002

1996-2002

0.6

Chlamydia

81 680

139

0.4

Genital warts

69 417

Gonorrhoea

24 953

106

0.2

Genital herpes

18 392

1990

1992

1994

1996

1998

2000

2002

Syphilis

1193

870

Year

All diagnoses and workload at genitourinary medicine clinics by country,

1990-2002. Data are unavailable currently for Scotland for 2000-2 and

Northern Ireland for 1990. Adapted from slide from Health Protection

Agency (www.hpa.org.uk), Communicable Disease Surveillance Centre. Data

from KC60 statutory returns and ISD(D)5 data

The United Kingdom has a network of clinics dealing with

Estimated prevalence and incidence of STIs by region

STIs (departments of genitourinary medicine (GUM)), and

such clinics have seen a very substantial increase in the number

Region

Prevalence per

Incidence per

of attendances over the past decade. Such attendances have

million

doubled, reaching 1.5 million in the year 2002. Even in the last

Sub-Saharan Africa

seven years, increases of over 100% have been seen in cases of

South and South East

151

chlamydia, gonorrhoea, and syphilis.

Asia

Latin America and

18.5

Gonorrhoea

Caribbean

To interpret differences between countries and even trends is

Eastern Europe and

difficult because of the variation in reporting practices and the

Central Asia

provision of facilities. Rates of gonorrhoea vary between

North America

European countries. During the early to mid 1970s the number

Australasia

0.3

of cases of gonorrhoea peaked in most European countries.

Western Europe

The subsequent advent of HIV and AIDS in the 1980s led to

Northern Africa and

3.5

safer sexual practices and a reduction in the incidence of

Middle East

gonorrhoea, which has not been sustained in all countries. For

East Asia and Pacific

example, between 1996 and 2002 an increase has been seen in

TOTAL

116.5

340

both male and female cases of gonorrhoea in England

ABC of Sexually Transmitted Infections

and Wales (114% increase in the number of cases in

heterosexual men from 8051 to 17 260, and an 86% increase in

14000

Men (heterosexually acquired)

cases in women from 4045 to 7542). The incidence of

12000

gonorrhoea has increased since 1996 in homosexual men,

Men (homosexually acquired)

particularly in those living in London, as has that of other STIs.

10000

Women

In 2002, 16% of gonorrhoea diagnoses in men, and 19% of

8000

those in London, were acquired through homosexual sex.

6000

Other western European and Scandinavian countries have

also seen recent increases, for example in France and Sweden.

4000

Eastern Europe, and particularly the newly independent states

2000

of the former Soviet Union, has seen an epidemic of STIs, with

high rates of gonorrhoea in Estonia, Russia, and Belarus.

1995

1996

1997

1998

1999

2000

2001

2002

Year

Uncomplicated gonorrhoea

Genital warts (first attack)

Cases of uncomplicated gonorrhoea seen in genitourinary medicine clinics

Genital herpes simplex virus (first attack)

by sex and male sexual orientation in England, Wales, and Northern

Genital chlamydial infection

Ireland, 1995-2002. Adapted from slide from Health Protection Agency

Infectious syphilis (primary, secondary, and early latent)

(www.hpa.org.uk), Communicable Disease Surveillance Centre. Data from

3000

1000

KC60 statutory returns

2500

800

2000

600

1500

400

600

1000

Men (heterosexually acquired)

200

500

Men (homosexually acquired)

400

Women

1995

1996

1997

1998

1999

2000

300

Year

200

New diagnoses of selected STIs in men who have sex with men, England and

100

Wales, 1995-2000. Adapted from slide from Health Protection Agency

(www.hpa.org.uk), Communicable Disease Surveillance Centre

1995

1996

1997

1998

1999

2000

2001

2002

Year

Syphilis

Syphilis is now rare in western Europe and North America,

Cases of infectious syphilis (primary and secondary) seen in genitourinary

which is mainly due to the control of early acquired infectious

medicine clinics by sex and male sexual orientation in England, Wales, and

syphilis in women and screening of pregnant women for

Northern Ireland, 1995-2002. Adapted from slide from Health Protection

Agency (www.hpa.org.uk), Communicable Disease Surveillance Centre

syphilis. In most western European countries the incidence

of syphilis has continued to decline to below five per 100 000.

As mentioned above, an epidemic of most STIs has occurred in

eastern Europe, with a recent epidemic of syphilis in all the

newly independent states of the former Soviet Union. This

epidemic is the vanguard of an HIV epidemic, and outbreaks of

HIV have been reported in intravenous drug users, particularly

in Belarus, Russia, and Ukraine. Likewise, syphilis is still a

Men

Women

major clinical problem and a cause of genital ulceration in the

1200

Age (years)

developing world.

<16

It is of concern that syphilis also is increasing again in the

1000

16-19

United Kingdom. In the past seven years, the cases of infectious

20-24

syphilis have increased by 870%, particularly in men

800

25-34

heterosexual and homosexual.

35-44

600

>45

Chlamydia

400

Chlamydia is still a major public health problem in most of

Europe and North America. In the United Kingdom, infection

200

with Chlamydia trachomatis is now the most common curable

bacterial STI. Since 1996 the number of cases has increased,

with cases in women outnumbering cases in men. In 2002,

81 680 people with chlamydial infections attended clinics.

Year

This condition is most commonly seen in young people; the

peak age is between 20 and 24 years in men and between 16

Diagnoses of uncomplicated genital chlamydial infection in genitourinary

medicine clinics by sex and age group in the United Kingdom, 1995-2002.

and 19 years in women. Screening surveys performed outside

Data are unavailable for Scotland for 2000-2. Adapted from slide from Health

normal STI clinic environments also show high levels in

Protection Agency (www.hpa.org.uk), Communicable Disease Surveillance

antenatal and gynaecology clinics, general practice, and family

Centre. Data from KC60 statutory returns and ISD(D)5 data

Why sexually transmitted infections are important

planning and pregnancy termination clinics, with the

prevalence rate ranging from 4.5% to 12%.

Genital herpes and warts

Compared with gonorrhoea and chlamydia, the increase in

cases of genital herpes and warts has slowed down in British

GUM clinics in the past few years.

Global totals—gonorrhoea 62 million, syphilis 12 million, chlamydia 92 million

Eastern Europe and Central Asia

Gonorrhoea 3 million

Syphilis 100 000

Chlamydia 6 million

Western Europe

Gonorrhoea 1 million

Syphilis 140 000

Chlamydia 5 million

East Asia and Pacific

North America

Gonorrhoea 3 million

Gonorrhoea 1.5 million

Syphilis 240 000

Syphilis 100 000

Chlamydia 5.3 million

Chlamydia 4 million

North Africa and Middle East

Gonorrhoea 1 million

Syphilis 370 000

South and South East Asia

Chlamydia 3 million

Gonorrhoea 27 million

Syphilis 4 million

Chlamydia 43 million

Latin America and Caribbean

Gonorrhoea 7.5 million

Syphilis 3 million

Sub-Saharan Africa

Australasia

Chlamydia 9.5 million

Gonorrhoea 17 million

Gonorrhoea 120 000

Syphilis 4 million

Syphilis 10 000

Chlamydia 16 million

Chlamydia 340 000

Estimated new cases of the three most common STIs among adults

STIs in developing countries

Sexually transmitted infections have a much higher incidence

and prevalence in developing countries and are among the top

five reasons for consultation in general health services in many

African countries. Routine and accurate surveillance data are

often lacking, and an understanding of the burden of infection

High rates of syphilis, chlamydia, and gonorrhoea are

tends to come from WHO estimates and ad hoc surveys, usually

seen particularly in sub-Saharan Africa and South and

in high risk groups.

South East Asia

Particularly high rates of infections are seen in groups such

as female prostitutes and their clients and truck drivers.

Prostitution continues to be an important factor in the

transmission of STIs in developing countries. For example, in

an urban Kenyan STI clinic, 60% of men with a diagnosis of

gonorrhoea or chancroid reported commercial sex exposure as

the probable source of infection. Genital ulcer disease is more

Commercial sex workers

17.4

STI clinics

Family planning clinics

8.4

6.7

2.5

Gonorrhoea

Chlamydia

Syphilis

Cameroon

South Africa

Central African

Burkina Faso

Republic

STIs in women in Africa

Syphilis prevalence rates (%) in pregnant women in Africa in 1990s

ABC of Sexually Transmitted Infections

frequent in developing countries (syphilis, chancroid,

lymphogranuloma venereum, and granuloma inguinale), and

Men

Women

in sub-Saharan Africa, 20-70% of patients who attend clinics

1990

present with ulcers. In commercial sex workers, the prevalence

2000

of gonorrhoea can reach nearly 50%, and the prevalence of

syphilis ranges from 2% to 30% for acute or previous infection.

Infection with herpes simplex virus (type 2) is almost universal

among commercial sex workers in various African countries, for

example Zimbabwe. Rates of syphilis in women who attend

antenatal clinics are high, with rates reaching 17% in

Cameroon. Levels of chlamydia can be as high as 30%.

The incidence of STI complications and their sequelae is

3-4

5-9

3-4

5-9

much higher in developing countries because of the lack of

No of Partners

resources and adequate diagnosis and treatment. Particular

complications are adverse pregnancy outcomes for mother and

Percentage distribution of heterosexual partners in lifetime by sex,

baby, neonatal and infant infections, infertility in both sexes,

1999 and 2000. Adapted from National Survey of Sexual Attitudes and

Lifestyles, 2000

ectopic pregnancy, urethral strictures in males, and blindness in

infants caused by gonococcal and chlamydial ophthalmia

neonatorum and in adults caused by gonococcal

keratoconjunctivitis, as well as genital cancers, particularly

cancers of the cervix and penis.

Men

Women

Homosexual

Why are STIs increasing?

partner <5 years

Like many other medicosocial conditions, for example suicide,

Concurrency

<1 year

alcoholism, cancer, and heart disease, the explanation for the

increase is multi-factorial. Attitudes towards sex and sexual

Intravenous

drug use

behaviour have changed. The survey of Sexual Attitudes and

<5 years

Lifestyle carried out in the United Kingdom plotted changes

Paid for sex

1990

between 1990 and 2000.

<5 years

2000

●

Age at first intercourse has declined, and half of all teenagers

have sex before they are 17 years of age

●

The number of lifetime male and female heterosexual

partners has increased since 1990, with the highest increases

Changes in behaviour over time. Adapted from National Survey of Sexual

in young people

Attitudes and Lifestyles, 2000

●

The proportion of men and women who have concurrent

relationships (having more than one sexual partner at the

same time) has increased

●

Condom use has increased in the United Kingdom but may

Men

Women

be offset by the increase in the number of sexual partners.

Anal sex

For example, the proportion of the population who reported

< one year

two or more partners in the past year and who did not use

condoms consistently has increased since 1990 from 13.6% to

15.4% for men and from 7.1% to 10% for women

Consistent use

of condoms

●

The proportion of men in the United Kingdom who have

ever had a homosexual partner in the last five years increased

between 1990 and 2000. Unsafe sex in homosexual men has

"Unsafe sex"

1990

< one year

increased, particularly in London

2000

●

Populations are now more mobile nationally and

internationally. Certain groups (tourists, professional

travellers, members of the armed forces, and immigrants) are

at risk. They are separated from their families and social

"Unsafe sex" means > 2 partners last year and inconsistent use of condoms in last four weeks

restraints and are more likely to have sexual contact outside a

Changes in behaviour over time. Adapted from National Survey of Sexual

stable relationship. In addition, poverty, urbanisation, war,

Attitudes and Lifestyles, 2000

and social migration often result in increased levels of

prostitution.

Further reading

Conclusion

●

Adler MW, Cowan FM. Sexually transmitted infections. In:

Detek R, McEwen J, eds. Oxford textbook of public health: the practice

Sexually transmitted infections are a major public health

of public health. 4th ed, vol 3. Oxford: Oxford University Press,

problem throughout the world, in terms of morbidity and

2002, pp 1441-52

●

Adler M, Foster J, Grosskurth H, Richens J, Slavin H. Sexual health

mortality and in their facilitatory role in the acquisition and

and care: sexually transmitted infections, guidelines for prevention and

transmission of HIV. Prevention programmes are essential to

treatment. London: Overseas Development Administration, 1996

deal with these issues (see Chapter 2).

Control and prevention

Frances Cowan

Sexually transmitted infections (STIs) represent one of the

major public health problems in the world today, as outlined in

Chapter 1. The demographic, sociological, economic, and

behavioural changes seen throughout the world in the past

40 years will continue to drive the spread of STIs.

Determinants of STI spread

Ro cd

Pattern of spread

Ro average number of new infections that result from one

infection

Several factors are known to be important in maintaining the

transmissibility

spread of STIs in communities. A simple arithmetic formula

c average rate of acquiring partners

has been developed that makes it possible to anticipate the

d duration of infection

pattern of spread of STIs in communities under certain

circumstances. If the average number of infections that result

from one infection is greater than one, then the rate of that

STI will increase in the community. Conversely, if the average

number of infections is less than one, then the rate of spread

of the STI will fall. Reductions in any of these variables at a

community level will decrease the average number of new

infections that result from one infection in that community.

R_O >1

R_O <1

Principles of control

= individual with infection

The approach to controlling STIs and the emphasis placed on

= individual who

different components will depend on the local pattern and

remains uninfected

distribution of STIs in the community and whether one is

working in a setting that is resource rich or resource poor.

Pattern of spread

However, the same general principles will apply.

Prevention can be aimed at uninfected people in the

community to prevent them from acquiring infection (primary

prevention) or at infected people to prevent the onward

transmission of the infection to their sexual partners (secondary

prevention). Although effective primary prevention can

theoretically reduce the prevalence of viral and bacterial STIs,

Principles of effective STI control

secondary prevention is much more effective at reducing the

●

Reduce infectiousness of STIs

prevalence of bacterial STIs, which all are curable with

●

Condoms

antibiotics. In fact, the population prevalence of a bacterial STI

●

Reduce duration of infection

can be reduced entirely through effective secondary prevention

●

Encourage diagnosis and treatment of symptomatic infection

activities without any reduction in risky sexual behaviour

(encourage health seeking behaviour) and asymptomatic

occurring.

infection (screening, partner notification, and mass or

Countries that combine primary and secondary prevention

targeted treatment)

approaches, at the individual and population levels, have

●

Reduce risky behaviour

●

Reduce rate of partner change

managed substantially to reduce the burden of infection in

●

Delay onset of sexual intercourse

their population. Effective implementation of prevention

●

Improve selection of partners

programmes requires strong political leadership and genuine

commitment, without which the most well designed and

appropriate programmes are likely to founder. Countries such

as Thailand, Brazil, Uganda, and Senegal have seen a dramatic

impact on their rates of STIs and HIV, which has been

facilitated greatly by political support at the highest level.

Interventions that reduce the rate of STI can be aimed at

Primary prevention

the entire community or targeted at specific groups who are at

●

Behavioural interventions are aimed at enhancing knowledge,

high risk of, or are particularly vulnerable to, infection. One to

skills, and attitudes to help people protect themselves against

one prevention interventions can take place in clinic settings,

infection (for example, health promotion to decrease partner

as outlined in Chapter 3.

change and increase condom use)

●

Structural interventions are aimed at broader societal and

economic issues that drive the spread of STIs

Primary prevention

●

Biomedical interventions include condoms, vaccines, vaginal

microbicides, or male circumcision to prevent the acquisition of

Primary prevention interventions aim to keep people

infection

uninfected. These approaches are obviously not mutually

ABC of Sexually Transmitted Infections

exclusive. Individual behaviour change probably will be best

Ways for an individual to reduce their risk of contracting

sustained in a community that is broadly supportive. In

an STI

addition, the broader cultural mores of the community will

●

Abstain

influence greatly the feasibility of delivering education in that

●

Have a mutually monogamous relationship with someone who is

community and will also affect how people respond to it.

uninfected

●

Select partners whose past and current behaviour puts them at

Education and information

low risk of infection. Consider both being screened for infection

The aim of sexual health promotion is broader than

before unprotected sex

minimising the risks associated with sexual intercourse and

●

Reduce the numbers of sexual partners

●

Avoid sex with people who have symptoms of a STI or oral “cold

other sexual practices. It also aims to facilitate development of

sores”

healthy sexual behaviour patterns and relationships. Although

●

Use condoms consistently on every occasion with all partners

supplying appropriate and timely factual information is very

●

In open relationships couples agree to have only non-penetrative

important and the first step in this process, evidence shows that

or protected sex outside their main relationship

providing information alone is not enough to bring about a

change in behaviour. Widely available information about STIs

(or contraception) has not been proved to encourage immoral

or promiscuous behaviour.

Health education needs to inform people of the advantages

of discriminate and safer sex and the means to prevent or

reduce the risk of infection. Although the best way to avoid

STIs is to avoid sexual intercourse, this is not a realistic or

acceptable message. People need health messages that are

tailored to their lifestyles and needs, which allow them to make

informed choices about their behaviour. Factors other than

lack of knowledge contribute to an individual’s ability to

practice safer sexual behaviour, however, including perception

of health risk, low self esteem, poor self efficacy, peer pressure,

and power and sex inequalities. Drug and alcohol use also have

an influence. Increasingly, health promotion interventions aim

to address some or all of these factors.

That health promotion campaigns address the issues

directly related to the infections themselves is also important,

including what the various infections are; how to recognise the

symptoms; the short and long term consequences of infection;

and where to access appropriate advice, diagnosis, and

treatment. As most of those infected with an STI have either

asymptomatic or unrecognised infection, however, people also

The Department of Health’s website (www.playingsafely.co.uk) uses

interactive quizzes to show the difficulty in distinguishing infected from

need to be aware that they cannot rely on symptoms alone to

uninfected people

distinguish infected people from uninfected people and that

they themselves can be infected even if asymptomatic.

Structural or societal interventions

Clearly it may be unrealistic to expect individual behaviour

change when the broader societal and cultural context is not

supportive of this change.

Structural factors that may hinder behaviour change

include physical, social, cultural, organisational, economic, and

Interventions that are most effective are those that draw on

legal or policy aspects of the environment. For example,

social and psychological theories of behaviour change

derived from research that seeks to understand the origins

interventions that promote condom use and partner reduction

and control of sexual behaviour

strategies for impoverished heterosexual women in developing

countries may be impractical, because women lack the power to

negotiate condom use, particularly with their regular partners

or husbands, and because they may be economically dependent

on sex work to provide income for basic necessities, such as

food or their children’s school fees. In this scenario,

interventions need to include men and, more broadly, tackle

women’s rights regarding inheritance, owning property, and

Structural interventions

earning income legitimately.

These can take place at various levels, including

●

Community level (for example, legislating to change the age of

Biomedical interventions

consent for homosexual men or inheritance laws)

Male condoms, if used properly and consistently, can reduce

●

Organisational level (for example, providing reproductive health

the risk of transmission of many STIs. They are more effective

clinics in schools or the workplace)

for some STIs than for others, however, and their use does not

●

Individual level (for example, microfinance initiatives that seek

guarantee that infection will not occur. Female condoms are

to train women to become less economically dependent)

also advocated to reduce STI and HIV transmission and are

attractive because they are under the control of the woman,

Control and prevention

although evidence of their effectiveness is less than for the

male condom.

Hepatitis B vaccine is the only vaccine that effectively

prevents acquisition of an STI, although vaccines for other STIs

are currently in development or being evaluated. In addition,

several other biomedical approaches for reducing the risk of

STIs are currently being explored, including presumptive

periodic treatment for people who are at high risk of STIs,

male circumcision, and vaginal microbicides. However, all these

interventions are in the early stages of evaluation.

Secondary prevention

Secondary prevention interventions aim to reduce the risk of

individuals infected with an STI transmitting this infection to

their sexual partners. These approaches entail increasing

screening and appropriate treatment of symptomatic and

asymptomatic people; encouraging health seeking behaviour;

and tracing, screening, and treating sexual partners of infected

people (contact tracing). Other more experimental approaches

have included presumptive treatment of people at high risk of

infection.

The Department of Health’s website

(www.playingsafely.co.uk) promotes the use of

Screening and treatment

condoms for sexual health

Early diagnosis and treatment are cheap, whereas the late

sequelae of untreated disease are expensive. For example, if

gonorrhoea and chlamydial infection (a major cause of pelvic

inflammatory disease (PID)) are well controlled, then PID and

all its serious long term sequelae can be prevented.

In many parts of the world specialised STI clinics have been

Secondary prevention

established to provide screening and treatment for people with

●

Enhancing health seeking behaviour

symptoms of, or who feel they are at risk of, an STI. These

●

Improving access to for STIs diagnosis and treatment

clinics provide prompt laboratory or microbiological based

●

Ensuring appropriate case management

diagnosis (or both) and treatment, minimise the incidence of

●

Early detection and treatment of symptomatic and

complications and disability, trace and treat sexual contacts,

asymptomatic infection

●

Partner notification (contact tracing)

and provide education. These are sometimes known as vertical

services.

Clearly the extent of screening will vary according to the

laboratory facilities available. In most western countries, clinics

screen for syphilis, gonorrhoea, chlamydia, Trichomonas

vaginalis, bacterial vaginosis, and Candida as a matter of course

and offer HIV antibody testing. Those presenting with

To be most effective, clinics should be open access and

symptoms will have additional screening tests (see

provide confidential, non-judgmental care and appropriate

Chapters 3-7). Screening at an STI clinic, however, does not

health care for which there is no charge. Health education

guarantee that a person is free of all infections. It is not routine

can be used to enhance health seeking behaviour and to

to screen asymptomatic individuals for herpes simplex virus or

encourage people without symptoms to attend for screening

human papillomavirus. Those people found to be infected

if they are at high risk of infection

should be managed according to local treatment guidelines.

Increasingly, single dose treatments are available for STIs, and

the use of these will maximise compliance and minimise the

development of drug resistance.

In countries without access to a laboratory, most people

Specialist services for STIs in the United Kingdom

who present to clinic will be symptomatic, and screening

●

Genitourinary medicine—269 clinics and 273 consultants

may be limited to clinical examination with or without

●

Features of service

●

Open access and free

microscopy. The sensitivity and specificity of clinical

●

Confidential

examination for distinguishing STI causes of genital symptoms

●

Screening and treatment for STIs

from non-STI causes, particularly in women, has improved

●

Screening and treatment for HIV

somewhat by using a system for scoring risk. For example,

●

Contraception and psychosexual problems

having had a new partner recently greatly increases an

●

Miscellaneous care (for example, for urinary tract

person’s risk of contracting an STI. The services are

infections and genital dermatological conditions)

non-specialised and provided as part of other general medical

●

Partner notification

●

Health promotion, counselling, and advice

services, for example in primary health centres, maternal and

●

Outreach and special services

child health centres, and family planning clinics, and by private

●

Training and research

practitioners, pharmacists, traditional healers, and street

ABC of Sexually Transmitted Infections

vendors. Vertical and integrated services for managing

Vertical services for STIs

individuals with STIs have both advantages and disadvantages.

Advantages

Disadvantages

In resource poor settings where clinics have limited access

●

Specialists

●

Expensive

to diagnostic facilities, the World Health Organization

●

Accurate laboratory

●

Delays in diagnosis

recommends that the syndromic approach is used for patient

diagnosis with appropriate

●

Limited availability

management. This uses algorithms based on the common

treatment

●

Limited coverage of population

presenting signs and symptoms, for example genital ulceration

●

Reference laboratory

●

Stigmatisation

and urethral or vaginal discharge. Rather than healthcare

●

Training

●

Poor sustainability

●

Monitoring, surveillance,

worker trying to decide on the aetiology of the symptoms on

and research

the basis of examination alone, the relevant algorithm shows

●

Asymptomatic infection

treatment for all the common STI causes of that syndrome in

may be detected

that setting. Syndromic management algorithms differ in

different parts of the world, which reflects the local disease

profile and antimicrobial resistance patterns (examples are

given in Chapters 5 and 7). In some countries where much of

the treatment for STIs is delivered through pharmacists and

street vendors, preprepared drug treatment packages have

been developed and marketed. These packs include the

Integrated services for STIs

appropriate drug for the relevant syndrome, a contact slip

Advantages

Disadvantages

advising that the sexual partner should be treated, and will

●

Problem orientated

●

Low sensitivity and specificity

often include condoms as well.

●

Immediate presumptive

for cervical gonococcal or

In addition to managing people who present with

diagnosis and treatment

chlamydial infection in

symptoms, the syndromic approach has been supplemented in

of possible aetiologies

women

●

Non-specialist

●

Asymptomatic infection not

some settings by presumptively treating people who are at high

●

Inexpensive

detected but treatment possible

risk of bacterial STIs with appropriate antibiotics. For example,

●

Standardisation of

by active partner notification

in South Africa, a programme that provides monthly antibiotic

management and

and epidemiological treatment

treatment to sex workers seems to have reduced the rates of

monitoring of drug use

of partners

bacterial STIs among sex workers and their clients. This

and antibiotic resistance

●

Not always acceptable to

approach is attractive because it allows treatment of

medical staff

symptomatic and asymptomatic people, although it needs to be

evaluated more formally to see if it results in the development

of antimicrobial resistance or any other adverse effects. An

extension of this is the concept of mass treatment of whole

populations who have or might be at risk of STIs.

Contact tracing

Tracing sexual contacts is an important part of any control

programme. Sexual contacts have an increased likelihood of

infection with an STI and are often (although not always)

Contact tracing

unaware that they are infected. It is essential, therefore, to get

●

Patient (index) referral, whereby the patient informs their sexual

in touch with contacts as soon as possible and advise them to

partners themselves

●

Provider referral, whereby the index patient asks the healthcare

attend a clinic. Although contact tracing is primarily conducted

worker to inform partners on their behalf

for its public health benefit, it also is of direct benefit to the

●

Contract (conditional) referral, whereby the index patient

people concerned. For someone in an ongoing relationship,

undertakes to notify partners themselves in a given timeframe.

treatment of their partner is essential if they are not to become

If the partners are not notified in this period, the contact tracer

reinfected. If the contact remains unaware of their infection

or health adviser will attempt to notify them with the patient’s

risk, they may go on to develop sequelae of infection or to

consent. This uses a combination of the patient and provider

referral techniques

infect other people unwittingly.

Further reading

●

Mathews C, Coaetzee N, Zwarenstein M, Lombard C,

●

Holmes KK. Human ecology and behaviour and sexually

Guttmacher S. Strategies for partner notification for sexually

transmitted bacterial infections. Proc Nat Acad Sci 1994;91:2448-55

transmitted diseases. Cochrane Database Syst Rev 2004;(1):CD002843

●

Parker R, Easton D, Klein C. Structural barriers and facilitators in

●

Sumartojo E, Doll L, Holtgrave D, Gayle H, Merson M.

HIV prevention: a review of international research. AIDS

Enriching the mix: incorporating structural factors into HIV

2000;4:22-3

prevention. AIDS 2000;14:S1-2

●

Evidence of effectiveness of HIV prevention interventions.

JAIDS 2002;30:S1-134

The clinical process

Patrick French

People with sexually transmitted infections (STIs) are often

Summary of the clinical process

asymptomatic or have symptoms that they do not recognise as

●

Presentation to STI service

being related to an STI. They also may not have access to care

●

Sexual history and risk assessment

or be unaware of how to access care. They can be identified in

●

Clinical and genital examination

many ways, however, in a wide range of differing services and

●

Investigations

settings. The most appropriate site for STI care will reflect local

●

Treatment

epidemiology, the resources available for care, and the

●

Condoms

●

Health promotion

pre-existing structure of health services. This will mean that,

●

Partner management

according to local circumstances, STI care could be provided by

●

Follow up

primary or secondary care, pharmacies, or outreach services

(see Chapter 2). In the United Kingdom, STIs often are

managed by specialists in genitourinary medicine in dedicated

clinics.

Despite the need for clinical services to reflect diversity, it

is also important to ensure that some key principles regarding

Ways STIs can be identified

the care of people with STIs are adopted. They should

●

Screening

receive effective treatment and care as promptly as possible.

●

Case finding (“opportunistic” screening)

This approach reduces the risk of the patient developing

●

Presentation to non-STI clinical services

complications and reduces the chances of onward transmission.

●

Presentation (including self referral) to STI services

Facilitation of the access of people with STIs or at risk of

STIs to services that provide assessment and care is an essential

step in establishing good control of STIs. Linking services to

any health promotion activity in the community that is

designed to raise awareness of STIs and establishing care

pathways with other non-specialist clinical services are all part

Principles of STI care

of this access strategy.

●

Access to care must be easy, rapid, and preferably

Another vital component is service advertising. The media

free

used for advertising will depend on the target populations of

●

Systematic risk assessment of all patients is needed

●

Investigations should support but not delay care

the local STI programme and the resources available.

●

Rapid and “bedside” tests are important

Services for people who seek care for STIs should

●

Therapy that is easy to adhere is preferable (single

encourage destigmatisation of these conditions and also

dose if possible)

acknowledge that such stigma exists. Establishing an

●

Condom and sexual health promotion

environment that is confidential, private, and free of judgment

●

Partner management

encourages openness and allows a full and accurate risk

assessment to be undertaken. This lays the groundwork for

future care and health promotion.

Care of individuals with STIs often requires the

participation of a multidisciplinary team of practitioners

including nurses, doctors, administration staff, laboratory

workers, and counsellors. Staff who are responsible for helping

to identify and trace sexual contacts are an essential part of the

team. In the United Kingdom, this work often is undertaken by

sexual health advisers. The effectiveness of the team is

enhanced greatly by shared clinical guidelines and operational

An example of service advertising—Playing Safely website created by the

Department of Health, United Kingdom (www.playingsafely.co.uk)

An example of service advertising—STI care in the developing world

ABC of Sexually Transmitted Infections

policies, which include a description of the roles and

Good management of STIs is not complex but does include

responsibilities of each staff group.

a number of important components that need to be

addressed during clinical care. For this reason many units

have developed proformas to ensure that a systematic and

Core components of STI assessment

comprehensive approach to management is followed. Such

forms also facilitate the routine auditing and improvement

The core components of an STI assessment are history taking

of clinical practice

(especially sexual history), examination (particularly genital

examination), and investigations.

Sexual history taking

●

Symptoms (including duration)

The communication skills required to take a good sexual

●

Last sexual intercourse

●

Sex of partner

history are an extension of the skills already possessed by many

●

Relationship with partner (casual, long term,

healthcare workers. It is important to establish rapport and

traceable, etc)

trust between the doctor and patient and to acknowledge that

●

Use of barrier contraception

many people find it difficult to discuss their sexual lives openly.

●

Sites of exposure (oral, vaginal, or anal)

The scope and detail of the sexual history will vary

●

Last previous partner or partner change (with site

according to the site of care, available resources (particularly

of exposure and barrier contraception history as

consultation time), and the particular patient group being

above)

●

Partners’ symptoms

seen. However, to allow for basic risk assessment and further

●

Previous STIs or testing for STIs including HIV

management several crucial components must be discussed.

The specific issues that relate to sexual history taking in men

and women are detailed in Chapters 5 and 7, respectively.

The sexual history will guide the clinical examination and

will allow for a more rational approach to selecting

Name:

Date:

investigations. The sexual history will also form the basis for

Sex:

Number:

partner management and sexual health promotion. The

Age:

Scen by:

period of time over which a sexual history should look back will

depend on a number of factors, including duration of symptoms

Status:

(if any symptoms are present), the date of previous STI

Main symptom:

Sexual History:

assessments, and incubation periods of any STIs diagnosed or

suspected. In practice, most clinicians would elicit a risk history

for at least the previous three months or until the last partner

change, whichever is the longer. Ideally, the sexual history

Previous STI:

Examination findings:

should form part of a wider risk history that should include a

general medical history, including current drug use and misuse

Condom knowledge:

(including injecting drug use) and allergies. In women cervical

Condom use:

cytology, gynaecology, and contraception histories should be

taken. For proformas see Appendix on pages 85-6.

Treatment received so far:

Clinical examination

Drug allergy:

The clinical examination is an important part of the assessment

for an STI and will be guided by the sexual history. Often

Diagnosis:

Treatment:

during the examination, clinical specimens are obtained and

some STIs are diagnosed. Sexually transmissible conditions,

such as scabies, pediculosis pubis, molluscum contagiosum, and

Counselling:

Signature:

genital warts, are almost always diagnosed clinically; diagnostic

Compliance

procedures are reserved for atypical presentations.

Contacts

An appropriate environment for an examination is important.

Condoms

STI/HIV prevention

It is essential to explain and discuss the purpose and nature of

the examination to the patient and to acknowledge that many

Follow up:

patients find it distressing and intrusive. Good visualisation of

Developing world proforma: a case record can be designed on one page to

the genital area is vital for a proper examination. However, the

record essential information about STI patients

autonomy and dignity of the patient must be recognised and

protected as much as possible.

Examination setting

●

Clear explanation to patient

Investigations

●

Comfortable for patient and clinician

The role of the laboratory is discussed in detail in Chapter 17,

●

Private

and sampling during the clinical examination is discussed in

●

Good illumination

Chapter 4.

●

Chaperoning for patient

Diagnostic tests often are taken during the clinical

examination but increasingly “non-invasive” tests (including

vaginal and vulval tests), in which urine or saliva specimens

The diagnostic investigations undertaken will depend on

taken by the patient, are used for diagnosis. Because

the findings during risk assessment and clinical

non-invasive tests are easy to take and samples can be obtained

examination, as well as the resources available to the

from patients at venues with minimal clinical facilities, they are

doctor

The clinical process

particularly well suited to screening and case finding

People with STIs or attending STI services are much more

programmes.

likely than the general population to have HIV infection.

In some settings, the most effective form of STI care and

Offering and recommending HIV testing should be a

control is syndromic management (see Chapters 5, 7, 8,

routine part of all STI consultations

and 11), so that no investigations are taken to establish an

aetiological diagnosis. This approach will usually include the

components described earlier and health promotion and

partner management, but treatment is administered according

to local knowledge of the cause or aetiology of the presenting

syndrome (such as treating men presenting with urethral

discharge for gonorrhoea and chlamydia).

In other environments, rapid and bedside investigations aid

diagnosis during the initial clinic visit. These are particularly

useful in the rapid diagnosis of urethral gonorrhoea in men

and determining the aetiology of vaginal discharge. The range

Treatment guidelines*

of tests currently undertaken in STI clinics in the United

●

Clinical effectiveness produced by the British Association for

Kingdom is discussed in Chapters 4-7.

Sexual Health and HIV (UK) 2002 (www.bashh.org)

●

International Union against STIs (European) 2001

(www.iusti.org)

Treatment of STIs

●

Centers for Disease Control (American) 2002

(www.cdc.gov/cdc/std/treatment/SumCont.htm)

Treatments for STIs need to be effective and administered as

●

World Health Organization 2002

promptly as possible. A relatively small number of drugs are

(www.who.int/docstore/hiv/STIManagemntguidelines/)

needed to provide effective therapy for most of the infections,

*All treatment recommendations cited in the text are taken from

and this allows many services to develop small onsite

one or more of the guidelines above

dispensaries.

National and international guidelines for STI treatment

have been developed to improve and standardise care. They

are evidence based and updated on a regular basis. With the

exceptions of gonorrhoea and chancroid, little clinically

important resistance to the recommended antimicrobials is

seen. An effective single dose treatment is now available for

most bacterial and protozoal STIs, including gonorrhoea,

chlamydia, syphilis, chancroid, and trichomoniasis. This allows

onsite observed therapy and removes concerns about treatment

Treatment of STIs

adherence.

Treatment for viral STIs is more complex and will often

Features of effective therapy

require long term follow up and care. The role of treatment in

●

Prompt administration

reducing the infectiousness of viral STIs is being elucidated at

●

Observed therapy or single dose treatment

●

Well tolerated or easy adherence

present, but it is probable that sexual health promotion and

●

Guidelines followed (local gonorrhoea or

condom promotion have equally important roles.

chancroid sensitivities)

The dosing schedule, rationale, and possible toxicities must

be discussed with the patient, as well as potential interactions

Treatment discussion

with other therapies, for example antibiotics and oral

●

Nature or rationale of therapy

contraceptives.

●

Written information

●

Treatment adherence

●

Sexual abstinence during treatment

●

Partner notification

Condom and sexual health

●

Follow up (if needed)

promotion

A consultation with patients who have STIs or are at risk of

developing an STI is a valuable opportunity to provide sexual

health promotion, prevention, education, and condom

promotion on a one to one basis.

The areas covered in a sexual health promotion discussion

will be similar in all consultations but can be tailored to the

needs of the individual patient. Hepatitis A and B are currently

Sexual health promotion

the only STIs that can be prevented by vaccination (herpes

simplex type II infection and HPV-16 vaccines are being

●

Behaviour change

●

Safer sex and risk reduction

developed).

●

Condom promotion

Many STI services and prevention programmes offer

●

Hepatitis B vaccination

hepatitis B vaccination to all STI patients or to some who are

●

Future STI care

perceived as being at particularly high risk of acquiring

hepatitis B (see Chapter 15).

ABC of Sexually Transmitted Infections

Partner management

All patients with STIs will have had at least one partner who

currently has or who has previously had an infection. Partner

notification is an essential part of care (see Chapter 2).

Encouraging the sexual partners of patients with an STI to

attend for assessment, treatment, and care reduces the risk of

reinfection of the index patient, allows identification of STIs in

individuals who are asymptomatic or who have unrecognised

symptoms, and provides an opportunity to discuss sexual health

promotion with someone at high risk of an STI.

Partner notification entails a sensitive discussion that relies

on establishing trust between the patient and healthcare

worker. The rationale and importance of partner notification

should be explained clearly to the patient. Most patients will

take on the responsibility of informing their sexual contacts

(patient referral), but some patients may request or need the

clinic to undertake partner notification on their behalf

(provider referral).

Contact slips and written information for patients and their

sexual contacts may facilitate this process. Mechanisms for

monitoring the outcome of partner management should be

established.

Follow up

Many patients with infections will need follow up care. This

may be related to directly reviewing the outcome of previous

treatment and the management of viral STIs. However, it may

also include testing for STIs with long incubation periods (such

as HIV and syphilis) and further health promotion activity.

It is essential that follow up appointments check for

●

Symptom resolution

Contact slip

●

Treatment adherence

●

Further sexual exposure

●

Partner notification resolution

●

Test of cure or treatment response

The developing world proforma is adapted from Providing Health

●

Further STI screening

Services in Sexual Health Interventions. West Bengal: Project Management

●

Health promotion.

Unit of the West Bengal Sexual Health Project, 1998.

Examination techniques and clinical sampling

Patrick French

The general principles and appropriate environment for the

General examination

examination were covered in Chapter 3. In practice, the

Skin

examination of patients in a clinic is often confined to the

●

Scabies—rash (especially on wrists, between

genitals, but if a sexually transmitted infection (STI) that has

the fingers, and on as the buttocks and

extragenital manifestations is suspected (such as scabies,

areolae)

syphilis, or HIV), then a general examination will also be

●

Secondary syphilis and HIV (seroconversion

necessary, even if the patient has no symptoms outside the

illness)—generalised rash and lesions on palms

genitalia. This examination will concentrate on the skin,

and soles

mouth, and lymph nodes but a more thorough examination is

Lymph nodes

essential if the late complications of HIV or syphilis are

●

Secondary syphilis, HIV, and primary herpes

suspected.

simplex—generalised lymphadenopathy

Mouth

Examination of the male patient

●

Secondary syphilis—ulceration and mucous

patches

Examination of the male genitalia may be done standing

●

HIV—oral hairy leukoplakia, oral candidiasis,

(useful for hernia and varicocoele) or lying. It should include

Kaposi’s sarcoma, and angular cheilosis

●

Herpes simplex—ulceration

●

inspection of areas covered with hair for pediculosis pubis

●

Warts

●

examination of genital skin for ulceration, inflammation,

warts, and molluscum contagiosum

●

palpation of inguinal lymph nodes for enlargement and

tenderness

●

retraction of the prepuce and a search for subpreputial skin

lesions (such as chancre or warts ) and balanitis

●

urethral meatus for discharge and meatitis (the patient or

doctor may try to squeeze out the discharge)

●

palpation of the testes and epididymes to diagnose

epididymo-orchitis and screen for testicular cancer.

The anus should be inspected externally for warts that

occur in both homosexual and heterosexual males. Men who

report anal symptoms, receptive anal intercourse, or receptive

oroanal sexual contact should undergo proctoscopy to inspect

the anal and rectal mucosa for inflammation, pus, or ulcers.

Digital examination may assist in diagnosing prostatic disorders,

such as cancer and prostatic inflammation.

As previously mentioned, clinical sampling often will be

taken during examination, and the routine tests taken are

described below. Other tests will be dictated by clinical

Bladder

Spermatic

presentation and local epidemiology. All patients should be

cord

offered and recommended serological tests for syphilis and HIV

Rectum

Prostrate

(after pre-test discussion).

gland

Epididymis

Urethra

Sampling of the male patient

Anus

Shaft of

Scrotum

penis

Urethra

A plastic loop is inserted to a depth of 2 cm and smeared on to

Testis

Corona

a glass slide for Gram staining and enumeration of polymorphs

Prepuce

Urethral

to diagnose urethritis. It can then be streaked on to gonococcal

meatus

Glans

culture medium. A second specimen is taken for chlamydia

testing.

Urine

All tests listed above can also be done on a spun urine deposit.

Male genitalia including scrotal contents (adapted from Sexually transmitted

Some services use leucocyte esterase testing to indicate a

infections: history taking and examination CD, The Wellcome Trust, 2003)

possible diagnosis of urethritis.

Throat (if indicated)

A Dacron tipped swab is taken from the tonsillar crypts and

posterior pharynx and plated on to gonococcal culture

medium. Gram stained smears from this site are not helpful.

ABC of Sexually Transmitted Infections

Rectum (if indicated)

The rectal mucosa is sampled through a proctoscope with a

plastic loop that is smeared on to a glass slide for Gram staining

Clitoris

and streaked on to gonococcal culture medium.

External

urethral

meatus

Prostate (if indicated)

Vaginal orifice

Sampling prostatic fluid requires firm massage of the prostate

Labium majus

gland with a gloved finger inserted in the rectum to express

prostatic secretions through to the urethral meatus. Material

Vestibule

Labium minus

obtained can then be examined in stained smears and cultured.

Opening of

Perineum

Bartholin's

Examination of the female patient

glands

Examination of the female patient begins with an inspection of

Fourchette

Anus

the external genitalia, followed by vaginal and cervical

examination after passing a vaginal speculum (usually a Cusco

speculum). Finally, a bimanual pelvic examination is done.

Female external genitalia (adapted from Sexually transmitted infections: history

taking and examination CD, The Wellcome Trust, 2003)

External genitalia

●

Examine genital skin for inflammation, ulcers, warts,

molluscum contagiosum, and pediculosis pubis

●

Examine vestibule and introitus for any discharge or

Bartholin’s cyst or abscess

●

Palpate inguinal lymph nodes.

Cervix and vagina

●

Inspect discharge

●

Examine vaginal walls for inflammation

●

Examine cervix for ectropion, cervicitis, and mucopurulent

Fallopian tube

discharge.

Ovary

Rectouterine

pouch

Pelvis

Uterus

●

Examine uterus and cervix for pain on palpation or

Cervix

movement

Bladder

●

Examine for adnexal tenderness and masses.

Cervical os

Urethra

Fornix

Sampling of the female patient

Vagina

Anus

Vagina

Vaginal discharge samples are taken from the posterior fornix

with a small plastic loop. The discharge is tested with narrow

Female internal genitalia (adapted from Sexually transmitted infections: history

range pH paper and potassium hydroxide to help elucidate the

taking and examination CD, The Wellcome Trust, 2003)

cause of the vaginal discharge.

A further vaginal sample is examined in wet preparation for

Trichomonas vaginalis and clue cells and with gram stain for

Candida albicans. The vaginal sample is sent for T vaginalis and

C albicans culture.

Cervix

After mucus and secretions have been wiped off the cervix with

a cotton wool ball, the endocervix is sampled. A loop is used to

take a sample for Gram staining and Neisseria gonorrhoeae

culture. A further swab is taken for the identification of

Chlamydia trachomatis.

Urethra

A small plastic loop is used to collect a sample from the

proximal urethra that is smeared on to a glass slide for Gram

staining and streaked on to a slide for N gonorrhoeae culture.

Proctoscopy and tests for N gonorrhoeae

should be done for all women who report

A full description of laboratory diagnostic tests used in the

anal sex

field of STIs is given in Chapter 17.

Main presentations of sexually transmitted

infections in male patients

John Richens

Some sexually transmitted infections (STIs), such as

gonorrhoea and chlamydial infection, have very different

Causes of urethritis in men

presentations in the two sexes because of differences in genital

Common diagnoses among men with urethritis

anatomy. This chapter focuses on infections of the male

●

Gonorrhoea

urethra, epididymis, testis, and prostate. Anal and oral

●

Chlamydial infection

symptoms are also covered because these are encountered

●

Non-specific urethritis

more often among men, especially men who have sex with

Less common diagnoses among men with urethritis

men. Chapter 6 deals with a variety of other genital symptoms

●

Ureaplasma urealyticum infection

in men that usually are not related to STIs but often come to

●

Mycoplasma genitalium infection

the attention of healthcare professionals who work in sexual

●

Trichomoniasis

health services.

●

Herpes simplex virus infection

●

Escherichia coli infection

●

Bacteroides infection

●

Cystitis

Urethral discharge and dysuria

●

Pyelonephritis

●

Trauma

Spontaneous discharge of fluid from the urethral meatus,

●

Foreign body

usually most noticeable after holding the urine overnight and

●

Reactive arthritis, Reiter’s syndrome, and allied conditions

often accompanied by burning discomfort during urination

(dysuria), strongly indicates a sexually acquired urethral

infection.

Symptomatic gonorrhoea usually develops in a few days of

exposure. Chlamydia infections take slightly longer. Mild

infections may cause urethral discomfort and dysuria without

discharge and may be confused with cystitis.

Management of urethritis in male patients

1 Take history, including sexual history

2 Examine, looking especially for evidence of discharge

3 Take samples from urethra

4 Treat for gonorrhoea and chlamydia if urethral Gram stain is

positive for Gram negative intracellular diplococci

5 Give treatment for Chlamydia if the urethral smear shows five or

more polymorphs per high power field and the Gram stain

does not suggest gonorrhoea

6 Explain diagnosis, treatment, and methods of prevention

7 Advise to avoid sex until treatment and follow up are completed

8 Advise partner treatment

9 Review patient after treatment for symptoms, adherence,

treatment of partners, and test of cure if gonorrhoea has

Gonococcal urethral discharge

been diagnosed

Where laboratory investigation is not feasible, steps 3, 5, and the

test of cure can be omitted

Patient complains of

urethral discharge

or dysuria

Take history and

examine. Milk

urethra if necessary

Discharge?

Any other

• Educate and counsel

genital disease?

• Promote and provide

Yes

condoms

Yes

• Offer HIV counselling

Treat for gonorrhoea and Chlamydia

and testing if both

• Educate and counsel

Use appropriate

facilities are available

• Promote and provide condoms

flow chart

• Review if symptoms

• Offer HIV counselling and testing if

persist

both facilities are available

• Partner management

• Advise to return in seven days if

symptoms persist

Gram negative intracellular diplococci

Urethral discharge flow chart (World Health Organization)

ABC of Sexually Transmitted Infections

Overview of chlamydial and gonorrhoea infection

Gonorrhoea

Chlamydia

Cause

●

Neisseria gonorrhoeae, a Gram negative coccus

Cause

●

Initial sites of infection: columnar epithelium of urethra,

●

Chlamydia trachomatis, types D-K (see also lymphogranuloma

endocervix, rectum, pharynx, or conjunctiva depending on

venereum, p 45). C trachomatis is an obligate intracellular

mode of exposure

bacterium

Incubation period

Initial sites of infection

●

Two to five days in 80% of men who develop urethral symptoms

●

Epithelial cells of urethra, cervix, rectum, pharynx, and

●

Asymptomatic infections common in both sexes, especially

conjunctiva depending on mode of exposure

infections of pharynx, cervix, and rectum

Incubation period

Main symptoms in men

●

Less than four weeks for men; unknown in women

●

Urethral discharge, dysuria, and tender inguinal lymph nodes

●

Asymptomatic infections are common in both sexes and can

persist for many months

Less common genital symptoms in men

●

Epididymo-orchitis, abscesses of paraurethral glands, and

Main symptoms in men

urethral stricture

●

Urethral discharge and dysuria

Main symptoms in women

Less common symptoms in men

●

Vaginal discharge, dysuria, abnormal bleeding

●

Proctitis, conjunctivitis, epididymo-orchitis, and reactive arthritis

●

Examination may show mucopurulent discharge from the

Main symptoms in women

cervical os, urethra, Skene’s glands, or Bartholin’s glands

●

Dysuria, vaginal discharge, and intermenstrual bleeding

Less common genital symptoms in women

Less common symptoms in women

●

Lower abdominal pain and vulvovaginitis (pre-pubertal girls)

●

Pelvic inflammatory disease (with sequelae of infertility and

Extragenital symptoms and complications that affect both sexes

ectopic pregnancy), perihepatitis (Fitz-Hugh-Curtis syndrome),

●

Pharyngitis, rectal pain and discharge, and conjunctivitis

and conjunctivitis

●

Disseminated infection involving skin, joints, and heart valves,

Symptoms affecting neonates

secondary infertility after damage to Fallopian tubes, or epididymis

●

Conjunctivitis and pneumonia

Main methods of diagnosis

●

Detection of Gram negative intracellular diplococci in smears

●

Enzyme immunoassay and DNA amplification (ligase chain

and culture for N gonorrhoeae

reaction (LCR) and polymerase chain reaction) (see Chapter 17)

Treatments recommended for uncomplicated gonorrhoea

Recommended treatments for uncomplicated Chlamydia

in the following guidelines

●

Doxycyline: 100 mg twice daily for seven days (C, E, U, W)

●

Ciprofloxacin: 500 mg single dose by mouth (C, E, U, W)

●

Azithromycin: 1 g single dose (C, E, U, W)

●

Ofloxacin: 400 mg single dose by mouth (C, E, U, W)

●

Erythromycin base: 500 mg twice daily for 14 days (E (2), U(2))

●

Levofloxacin: 250 mg single dose by mouth (C)

●

Erythromycin base: 500 mg four times daily for seven days

●

Ceftriaxone: 125 mg single dose given intramuscularly (C, E,

(C (2), E(2), U(2), W)

U(2), W)

●

Erythromycin ethylsuccinate: 800 mg four times daily for seven

●

Cefotaxime: 500 mg single dose given intramuscularly (C(2), U(2))

days (C(2))

●

Cefixime: 400 mg single dose given by mouth (C, E, W)

●

Tetracycline: 500 mg four times daily for seven days (U(2), W)

●

Spectinomycin: 2 g single dose given intramuscularly (C(2), E,

●

Ofloxacin: 200-300 mg twice daily or 400 mg once daily for seven

U(2), W)

days (C(2), E(2), U(2), W)

●

Ampicillin: 2 g or 3 g plus probenecid 1 g as a single oral dose

●

Levofloxacin: 500 mg daily for seven days (C)

(U, E(2)) (in areas with

5% resistance to penicillin)

●

Amoxicillin: 500 mg three times daily for seven days has been

Resistance

validated in pregnant patients (C, E, U, W)

●

Resistance to penicillin and tetracyclines is widespread

Follow up testing

Resistance to quinolones is increasing and resistance to

●

Not recommended routinely and should not be done before

azithromycin and spectinomycin has been reported

●

Choice of treatment should take into account local

three weeks if PCR or LCR is used, because these tests can detect

non-viable organisms

susceptibility data

Follow up

(C Centers for Disease Control, USA; E European STI guidelines;

●

A test of cure culture is recommended when available

U UK National Guidelines; W World Health Organization; (2)

second line recommendation).

In clinics with laboratory facilities, the usual approach is to

test for gonorrhoea and chlamydial infection. The first step is

microscopy of a urethral smear. Optimal results for this are

obtained from patients who have held their urine for four

hours or more.

Urethritis is confirmed if the urethral smear shows five or

more polymorphs per high power field. If the smear shows

Gram negative intracellular diplococci, the patient is treated for

gonorrhoea and Chlamydia to cover the possibility of a mixed

infection. Meanwhile, confirmatory tests for gonorrhoea and

Chlamydia are carried out (see Chapter 17).

Patients without evidence of gonorrhoea receive

doxycycline (100 mg twice daily for one week), erythromycin

(500 mg twice daily for two weeks), or azithromycin (1 g single

N gonorrhoeae culture

STIs in male patients

dose), which are active against chlamydial infection and most

other pathogens associated with non-gonococcal urethritis.

100

Penicillin

Doxycycline can cause photosensitivity. Absorption is impaired

Tetracycline

by antacids, iron, calcium, and magnesium salts. Gastrointestinal

Quinolones

upset is common with erythromycin and azithromycin.

This approach will relieve symptoms in most patients, but

some will report persistent symptoms or show a persistently

abnormal smear without symptoms. The options are then to

investigate for treatment failure or reinfection or for infection

by less common pathogens (for example, Trichomonas vaginalis)

and to repeat, continue, or change the antibiotic therapy or

await spontaneous resolution of symptoms.

East and Central

South East

Australasia South America

United

When access to laboratory testing is not available, the

Africa

Asia

Kingdom

simplest approach to managing urethritis is to administer blind

treatment for gonorrhoea and Chlamydia.

Antimicrobial resistance of N gonorrhoeae in selected countries in the 1990s

Scrotal swelling and pain

Mild testicular discomfort in the absence of abnormal physical

signs is encountered commonly in young male attenders in

Causes of scrotal swelling and pain in adults and

STI clinics. Many such patients can be reassured if testicular

adolescents

examination and a screen for STIs are carried out and found to

●

Infections of testis and epididymis: gonorrhoea, Chlamydia,

be normal. In some cases, anxiety about infection, sexual

tuberculosis, mumps virus, and Gram negative bacteria

function, or cancer is present. More marked scrotal pain has a

●

Torsion of testis (mainly adolescents) or appendix testis (mainly

variety of causes.

three to seven year olds)

Acute inflammation of the scrotal contents (usually

●

Pain after vasectomy

unilateral) in young men is usually caused by gonorrhoea or

●

Fournier’s gangrene

Chlamydia. In older men, Escherichia coli, klebsiella,

●

Vasculitis: Henoch-Schönlein purpura, Kawasaki disease, and

pseudomonas, and proteus are found more often. The first

Buerger’s disease

●

Amiodarone therapy

consideration in diagnosis is to exclude acute torsion, which

●

Tumour

requires emergency surgery. Torsion predominates in the

●

Hernia

teenage years, usually has an acute onset, and is often

●

Trauma

accompanied by vomiting. An immediate surgical opinion

should be sought for any possible case. Doppler scanning is

useful for demonstrating impaired blood flow. The

distinguishing features of a mumps orchitis are usually onset

several days after parotid swelling, severe testicular pain, and

marked systemic symptoms, although the parotitis may be

absent. Useful tests for cases of suspected epididymo-orchitis

are a urethral smear, mid stream urine culture, and

investigations for gonorrhoea and chlamydia. Presumptive

treatment for gonorrhoea and chlamydia is appropriate in

younger males when investigation is not feasible. Severe cases

require treatment in hospital with parenteral antibiotics.

Analgesia, scrotal support, and elevation may reduce

discomfort and promote recovery.

Painless swellings in the scrotum are common. Most of

these are small, round, epididymal cysts or spermatocoeles that

require no investigation or treatment. Lesions in the testis can

be due to tuberculosis, syphilis, or malignancy and require

urgent ultrasound examination. Varicocoeles feel like a bag of

Acute epididymo-orchitis due to STI

worms in the scrotum and can be associated with infertility.

Therefore, referral to a urologist is advised if pain, testicular

atrophy, infertility, or the threat of infertility are concerns.

Measures occasionally found helpful in men with chronic

pelvic pain syndrome

Pelvic pain in the male

●

Simple analgesia

●

Non-steroidal anti-inflammatory drugs

The prostate can be affected by a variety of infectious and

●

Two to four weeks of ciprofloxacin or doxycycline

poorly defined non-infectious conditions that present as acute

●

Alpha blocking drugs (alfuzosin, terazosin, tamsulosin)

or chronic pelvic pain with a range of accompanying urinary

●

Finasteride

and systemic symptoms. Gonorrhoea, chlamydial infections,

●

Quercetin

and trichomoniasis can affect the prostate, but most acute

●

Low dose amitriptyline

●

Repetitive prostatic massage (contraindicated in bacterial

infections are caused by other bacteria such as E coli, proteus,

prostatitis)

Streptococcus faecalis, Klebsiella, and Pseudomonas. STIs and

●

Regular ejaculation

non-sexually transmitted bacterial infections of the prostate

ABC of Sexually Transmitted Infections

account for only a few painful prostatic syndromes. Most

Differential diagnosis of prostatic pain (NIH classification

patients with prostatic pain fall into a category recently

of prostatitis syndromes)

designated “chronic pelvic pain syndrome” (CPPS) by the newly

Acute bacterial prostatitis

adopted National Institutes of Health (NIH) classification of

prostatitis syndromes.

Chronic bacterial prostatitis

In patients who present with pelvic pain, the prostate

III

CPPS

should be examined for enlargement and tenderness. Patients

IIIA CPPS, inflammatory (leucocytes in prostatic secretion, semen,

with prostatitis should undergo a normal screen for STIs. The

or urine after prostatic massage)

value of subjecting patients to the unpleasant procedure of

IIIB CPPS, non-inflammatory (as above without leucocytes)

prostatic massage to examine prostatic secretions for bacteria

IV Asymptomatic inflammatory prostatitis

and inflammatory cells is now questioned by many experts.

Other causes of pain in region of prostate

Transrectal ultrasonography and urodynamic studies are

●

Pudendal neuralgia (sometimes due to tumour)

helpful in some patients. Confirmed infections respond well to

●

Bladder outlet obstruction

antibiotics, the first choice often being a 28 day course of a

●

Bladder tumours

●

Urinary stone disease

quinolone or tetracycline, which have better prostatic

●

Inguinal ligament enthesopathy

penetration than other antibiotics.

●

Ejaculatory duct obstruction

Treating the more common CPPS is difficult. None of the

●

Seminal vesicle calculi

treatments are well validated, and response rates are often

●

Bowel disorders

poor. A recently published NIH symptoms index for chronic

prostatitis is a useful way to record and monitor symptoms.

Anal symptoms

Anorectal STIs

Sexually transmitted infections can be transmitted by penile-anal

contact, oroanal contact, or fingering, resulting in asymptomatic

infection, ulceration (for example, herpes and syphilis), warts,

or proctitis, the main manifestations of which are pain,

tenesmus, bleeding, and discharge. Ulceration is investigated in

the same way as genital ulceration (see Chapter 11). Discharges

require investigation by proctoscopy, during which samples can

be taken from the rectum to test for Gonorrhoea and Chlamydia.

The management of a sexually acquired rectal discharge

parallels that of urethritis. Anorectal infections are a potent

cofactor for HIV transmission.

Anal intercourse can lead to the transmission of a wide variety

of other organisms normally transmitted by the faeco-oral route.

These include hepatitis A, Shigella, Salmonella, and Giardia. Anal

intraepithelial neoplasia and invasive carcinoma may follow

infection with certain subtypes of human papillomavirus.

Rectal gonorrhoea

Non-infectious anal conditions

Patients who practise receptive anal sex often present to STI

services with anal fissure, haemorrhoids, perianal haematomas,

and pruritus ani. It is important to provide training and

guidelines for the management and referral of these common

conditions in clinics that see clients who practise anal sex.

Oral and perioral symptoms

Oral STIs usually are asymptomatic. Gonorrhoea and Chlamydia

infect the pharyngeal mucosa readily but rarely cause acute

inflammation. Primary syphilis may present on the tongue or

lips, and secondary syphilis can produce an oral mucositis. HIV

has an important array of oral manifestations that include oral

candidiasis (both erythematous and pseudomembranous),

angular cheilitis, gingivitis, oral hairy leucoplakia, and Kaposi’s

sarcoma. Warts may develop in and around the mouth as a

Perioral warts. With permission of the Wellcome Trust

result of orogenital sexual activity.

Further reading

●

Galejs LE. Diagnosis and treatment of the acute scrotum. Am Fam

●

Management of STI syndromes in men. In: Holmes KK,

Physician 1999;59:817-24

Mårdh PA, Sparling PF, Lemon S, Stamm W, Piot P, et al. Sexually

●

Krieger JN, Ross SO, Deutsch L, Riley DE. The NIH Consensus

transmitted diseases. 3rd ed. New York: McGraw Hill, 1999:833-71

concept of chronic prostatitis/chronic pelvic pain syndrome

●

Morton RS, ed. Gonorrhoea 3rd ed. London: WB Saunders, 1977

compared with traditional concepts of nonbacterial prostatitis

●

Ostrow DG, Sandholzer TA, and Felman YM, eds. Homosexual

and prostatodynia. Curr Urol Rep 2002;3:301-6

men: diagnosis, treatment, and research. New York: Plenum, 1983

Other conditions of the male genital tract

commonly seen in sexually transmitted

infection clinics

John Richens

Conditions affecting the glans and

prepuce

The glans and prepuce are susceptible to many local and

generalised skin conditions. Mild irritation often responds to

simple advice to avoid soap, wash with a weak salt solution, and

use emollients. A number of other conditions respond to

topical steroid treatment. Persistent conditions may require

biopsy because a number of chronic skin conditions of the

glans can undergo malignant transformation. The insertion of

rings through the urethral meatus (the “Prince Albert”) has

become popular in recent years. Such rings rarely give rise to

local infections; however, infections are more likely to be

associated with anal rings.

Infectious conditions

Ring through the urethal meatus

Candida balanoposthitis can produce soreness, pruritus,

erythema, and fissuring. Dry, dull, red, glazed plaques and

papules, sometimes eroded, may be seen. The condition is

often linked to diabetes. Treatment with an imidazole cream

(see Chapter 20) is recommended, together with advice to

avoid soap and to bathe with water. Treatment of infected

partners has not been shown to benefit men or women with

symptomatic Candida infection.

Bacterial infections

Purulent infections of the glans are most often seen in

uncircumcised males with phimosis. Important organisms

involved include anaerobes, streptococci, staphylococci, and

Gardnerella. Treatment according to microbiological reports is

recommended. When a foul smelling discharge is present,

anaerobic infection is likely and treatment with metronidazole

400 mg twice daily for one week is recommended.

Candida balanitis

Dermatoses of the glans penis

Any persistent lesion that fails to respond to simple measures

should undergo biopsy. Three histologically similar forms of

penile intraepithelial neoplasia (carcinoma in situ) of the male

genitalia have been described. They are the erythroplasia of

Queyrat, which produces velvety plaques on the glans, Bowen’s

disease, characterised by erythematous plaques on the shaft or

more proximally, and Bowenoid papulosis, which produces

multiple lesions after infection with human papilloma virus

type 16. Lichen sclerosus (in men sometimes called balanitis

xerotica obliterans) produces striking white patches on the

glans that may undergo malignant transformation. Treatment is

with strong topical steroids and, occasionally, circumcision and

meatotomy for cases complicated by phimosis and meatal

stricture. Other steroid responsive conditions of the

glans are plasma cell (Zoon’s) balanitis, which produces

Erythroplasia of Queyrat

Conditions of male genital tract

Phimosis, paraphimosis, and

lymphocoele

A painful inability to retract the prepuce can result from any

chronic inflammatory condition of the prepuce. The condition

can be relieved by application of topical steroids or surgical

means. Paraphimosis results from prolonged retraction of the

prepuce, which leads to constriction of the distal shaft and

oedema of the glans. In the early stages, the prepuce can be

pushed back by applying firm pressure. This is made easier by

first reducing the swelling with ice packs, compression

bandaging, or local injections of hyaluronidase. Late cases may

require multiple needle puncture and expression of fluid

under local anaesthetic (Dundee technique) or surgical

intervention.

The term lymphocoele is used to describe a lesion of

Lymphocoele

unknown aetiology that feels like a transverse thrombosed

lymphatic vessel close to the corona. This harmless condition

develops quite quickly (often after vigorous sex) and resolves

spontaneously, usually in a few days.

Common lesions of scrotal skin

Angiokeratomas are harmless small papules with a deep-red or

purplish colour, which increase in number with age. Multiple

epidermal (sebaceous) cysts are sometimes observed on the

scrotum. These conditions are usually left untreated.

Tinea cruris and erythrasma

Tinea cruris is a superficial fungal infection that affects the skin

of the groin; it is seen mostly in men. Patients complain of

soreness and itching. Examination shows a well demarcated

discoloration of the affected skin. Fungal hyphae can be seen

in skin scrapings. Treatment with topical or oral imidazole

drugs clears the infection.

Angiokeratoma

Erythrasma is a bacterial condition caused by

Corynebacterium minutissimum. It occurs in the same area as tinea

cruris but tends to have a browner colour and a less well

demarcated edge. Porphyrins produced by the bacteria give the

lesion a coral pink colour when viewed by Wood’s light. It can

be treated with erythromycin.

Semen abnormalities

The observation of blood in the ejaculate causes considerable

anxiety. The great majority of cases settle quickly and no

underlying disease is detected. A screen for sexually transmitted

infections (STIs), urinalysis, examination of prostate, and a blood

pressure check are advised. Further investigation is only indicated

if symptoms persist. It very occasionally can be associated with

hypertension or rare conditions involving the male genital tract in

older men. Abnormal lumpiness of semen has been described in

patients infected with Schistosoma haematobium. A history of

exposure to potentially contaminated water in tropical areas

should be followed by investigation for schistosomiasis. Patients

with prostatis sometimes complain of changes in semen colour or

consistency or ejaculatory pain. It is common to encounter

individuals from South Asia who are convinced that they are

losing semen unnaturally, giving rise to feelings of lethargy and

tiredness. This condition is known as “dhat” in India and is

sometimes dignified with the pseudoscientific name

“prostatorrhoea.” It is closely bound up with cultural concepts of

semen and vitality and has no identifiable organic basis.

Tinea cruris

ABC of Sexually Transmitted Infections

Peyronie’s disease

Fibrosis in the tunica albuginea of the penile shaft can give rise

to deformity, which is accentuated during erection. Patients

complain of deformity and sometimes pain and difficulty with

intercourse. The diagnosis is made by palpating thick fibrous

plaques in the penile shaft. Surgery may be required for some

patients.

Disorders of male sexual function

A study of new heterosexual male attenders at a London

genitourinary medicine clinic in London in 1997 found that

24% of patients reported sexual dysfunction. Disorders of

Peyronie’s disease caused by the presence of a dorsal

sexual function are often psychological; however, neurological,

plaque in the penis. Reproduced from Tomlinson J(ed)

endocrinological, and other disorders contribute to a

ABC of sexual health

considerable proportion of cases of erectile dysfunction.

Sexually transmitted infections rarely interfere directly with

Conditions that can cause disorders of male sexual function

sexual function, although concerns about STIs or HIV often

●

Hypertension

are expressed by patients with dysfunction. Loss of libido and

●

Sickle cell disease

erectile dysfunction are reported commonly by men infected

●

Vascular disease (for example, Leriche syndrome)

with HIV and may be exacerbated by antiviral treatment.

●

Diabetes

Once an individual has experienced sexual dysfunction,

●

Neurological disease (for example, multiple sclerosis)

●

Endocrine disease (for example, deficiencies of testosterone,

performance anxiety readily develops, which exacerbates

gonadotrophins, hypothyroidism, and prolactinoma)

the problem. Reducing performance anxiety is a key aim of

●

Alcoholism and substance abuse

psychological therapies.

●

Liver and kidney diseases

●

Adverse effects of drugs (for example, antihypertensive and

antidepressant medication)

Erectile dysfunction

●

After prostate and abdominal surgery

Patients complain of failure to achieve or maintain an erection.

Psychological factors can be identified by careful history taking.

If the patient does not experience spontaneous erections on

waking and cannot masturbate to orgasm, an organic disease is

more likely.

Patients should be evaluated carefully for the possibility of

organic disease, including measurement of blood pressure,

genital examination, and, in some cases, peripheral pulse and

neurological examinations. Screening for diabetes and dipstick

urinalysis is recommended for all patients. In selected cases,

measuring free plasma testosterone (patients with small testes

or who report low libido), blood lipids, haemoglobin

electrophoresis, follicle stimulating hormone, luteinising

hormone, prolactin, thyroid, renal, and liver function tests, or

vascular imaging may be indicated.

Treatment options (for which guidelines have recently been

published in the BMJ ) include psychosexual counselling,

intracavernosal or intraurethral alprostadil, or oral sildenafil.

Mechanical devices and surgical treatments are used

Intracavernosal injection of alprostadil. Reproduced

occasionally. Treatment should be supervised by specialist

from Tomlinson J (ed) ABC of sexual health

centres that can arrange prompt referral for dangerous

(albeit rare) complications of therapy, such as priapism.

Further reading

●

Chadda RK. Dhat syndrome: is it a distinct clinical entity? A study

Premature ejaculation

of illness behaviour characteristics. Acta Psychiatr Scand

1995;9:136-9

An organic cause is unlikely to be found. Therapy is usually

●

Edwards S. Balanitis and balanoposthitis: a review. Genitourin Med

1996;72:155-9

behavioural and involves training the patient to delay

●

McKenna G, Schousboe M, Paltridge G. Subjective change in

ejaculation by using a variety of graduated stop-start exercises

ejaculate as symptom of infection with Schistosoma haematobium in

first, alone, using masturbatory exercises, and then with a

travellers. BMJ 1997;315:1000-1

partner.

●

McMillan A. Lymphocoele and localized lymphoedema of the

The best known approach with partners is the “sensate

penis. Br J Vener Dis 1976;52:409

focus” technique pioneered by Masters and Johnson, which

●

Reynard JM, Barua JM. Reduction of paraphimosis the simple

initially prohibits genital contact and progresses gradually to

way: the Dundee technique. Br J Urol 1999;83:859-86

●

Tomlinson J. ABC of sexual health. London: BMJ Publishing

more intimate contact as more control is achieved. As an

Group, 1999

alternative, clomipramine and other antidepressants can be

taken four to six hours before intercourse with some benefit.

Vaginal discharge—causes, diagnosis,

and treatment

Helen Mitchell

Vaginal discharge is a common presenting symptom seen by

What may influence physiological discharge?

doctors in many services (primary care, gynaecology, family

Age

planning, and departments of genitourinary medicine

● Pre-pubertal

● Post-menopausal

(GUM)). Vaginal discharge may be physiological or

● Reproductive

pathological. Although abnormal vaginal discharge often

Hormones

prompts women to seek screening for sexually transmitted

● Hormonal contraception

● Pregnancy

infections (STIs), vaginal discharge is poorly predictive of the

● Cyclical hormonal changes

presence of an STI. This chapter focuses on the causes and

Local factors

diagnosis of vaginal discharge and treatment of the most

● Menstruation

● Semen

common infective causes.

● Post partum

● Personal habits and hygiene

● Malignancy

Aetiology

Pathological vaginal discharge

Physiological discharge

Infective discharge

Normal vaginal flora (including lactobacilli) colonise the

Common causes

vaginal epithelium and may play a role in defence against

● Organisms

infection. They maintain the normal vaginal pH between 3.8

● Candida albicans

● Chlamydia trachomatis

and 4.4. The quality and quantity of vaginal discharge may alter

● Bacterial vaginosis

● Neisseria gonorrhoeae

in the same woman in cycles and over time; each woman has

● Trichomonas vaginalis

her own sense of normality and what is acceptable or excessive

● Infective conditions

for her.

● Acute pelvic inflammatory

disease (see Chapter 8)

● Post-abortal sepsis

● Post-operative pelvic infection

● Puerperal sepsis

Pathological vaginal discharge

Less common causes

Vulvovaginal candidiasis is a common infective cause of vaginal

● Human papillomavirus

● Ureaplasma urealyticum

discharge that affects about 75% of women at some time

● Primary syphilis

● Escherichia coli

during their reproductive life, with 40-50% having two or more

● Mycoplasma genitalium

episodes. Bacterial vaginosis is one of the most common

Other conditions

diagnoses in women attending GUM clinics. As 50% of cases of

Common causes

bacterial vaginosis are asymptomatic, the true prevalence of this

● Retained tampon or condom

● Endocervical polyp

condition in the community is uncertain. Bacterial vaginosis is

● Chemical irritation

● Intrauterine device in situ

associated with a new sexual partner and frequent change of

● Allergic responses

● Atrophic changes

sexual partners. A reduced rate of bacterial vaginosis is seen

● Ectropion

among women in monogamous sexual relationships, but it can,

Less common causes

occur in virginal women. Increased rates of bacterial vaginosis

● Physical trauma

● Rectovaginal fistula

occur in certain groups of women, such as black African

● Vault granulation tissue

● Neoplasia

women, lesbians, and smokers.

● Vesicovaginal fistula

Recurrence of bacterial vaginosis after treatment is

common and can be increased by personal hygiene practices,

such as vaginal douching, that disrupt the normal vaginal flora.

Bacterial vaginosis may also be associated with concurrent STIs,

commonly Trichomonas vaginalis. Bacterial vaginosis is associated

with pelvic infection after induced abortion and in pregnancy

with pre-term delivery and low birth weight (see Chapter 9).

Trichomoniasis is less common in affluent countries but

reaches high levels (often 10-20%) among poor women in

developing countries as well as among disadvantaged women in

affluent countries. Although vulvovaginal candidiasis and

bacterial vaginosis often develop independently of sexual

Gonorrhoea Candidosis Non-specific

Warts

Herpes

Other

activity, trichomoniasis is mainly sexually transmitted and has

genital

conditions

infection

been ranked by the World Health Organization as the most

Concurrent infections: trichomoniasis

prevalent non-viral STI in the world, with an estimated 172

million new cases per annum.

Concurrent STIs found in a survey of women with T vaginalis

ABC of Sexually Transmitted Infections

Overview of genital candidiasis and bacterial vaginosis

Genital candidiasis

Bacterial vaginosis

Cause

●

Candida albicans in 80-95% of cases; C glabrata in about 5%

●

Bacterial vaginosis has a polymicrobial aetiology. Organisms

involved in the aetiology of bacterial vaginosis include anaerobes

Associated conditions

●

Diabetes mellitus, pregnancy, antibiotic usage, and

Mobiluncus sp. and Prevotella sp., Gardnerella vaginalis, and

Mycoplasma hominis

immunosuppression

Main symptoms

Transmission

●

Vaginal discharge with fishy odour that increases after

●

Mostly non-sexual

unprotected sexual intercourse and with menstruation

Site of infection

●

Vulva, vagina, glans, prepuce, and rectum

Main methods of diagnosis

●

Amsel’s diagnostic criteria (three out of four of these criteria

Symptoms in women

need to be present to diagnose bacterial vaginosis)

●

Vulvar pruritus, white curdy discharge with “cottage cheese”

●

Vaginal pH

4.5

appearance and sour milk odour, external dysuria, and

●

Homogeneous grey vaginal discharge

superficial dyspareunia

●

10% potassium hydroxide produces fishy odour “whiff test”

Symptoms in men

●

Clue cells present on wet mount

●

Soreness, pruritus, redness, and fissuring of glans and prepuce

●

Nugent’s diagnostic criteria (see Chapter 17)

●

Note that culture for Gardnerella is no longer a recommended

Examination findings in women

●

Redness, fissuring, excoriation of vulva, swelling of labia,

approach to diagnosis

intertrigo, and lichenification. Thick, white, adherent discharge

Recommended treatments

with vaginal wall erythema

●

Treatment regimes have similar cure rates of 70-80% after four

Examination findings in men

weeks. Compliance with therapy may result in a symptomatic

●

Dry, dull, red, glazed plaques and papules on glans and prepuce

cure but not a microbiological cure, so relapse after single dose

metronidazole (2 g) treatment is common; 60% of women

Main methods of detection

relapse in three months

●

Fungal hyphae and budding yeasts in smears and culture

●

Clindamycin is effective but also kills lactobacilli, and topical

Recommended intravaginal treatments for women

treatment may predispose patient to vulvovaginal candidiasis.

●

Treatment regimes offer 80-95% clinical and mycological cure

Intravaginal clindamycin can cause condom failure

rates in acute vulvovaginal candidiasis in non-pregnant women

●

Metronidazole 2 g single dose (C (2), E (2), U, W (2))

●

Vaginal

●

Metronidazole 400 mg twice daily for five to seven days (C, E, U, W)

●

Butoconazole 2% cream 5 g for one to three days (C)

●

Metronidazole 0.75% gel daily for five days (C, E, U, W (2))

●

Clotrimazole pessary 500 mg single dose (C, E, U, W), 200 mg for

●

Clindamycin 2% cream 5 g daily for seven days (C, E, U, W (2))

three days (C, E, W), or 100 mg for six to seven days (C, U, W)

●

Clindamycin ovules 100 mg daily for three days (C)

●

Econazole pessary 150 mg for one to three days (U)

●

Clindamycin 300 mg orally twice daily for seven days (C, E, W (2))

●

Miconazole ovule 1.2 g single dose (E, U)

●

Prophylaxis for surgical interventions: rectal metronidazole 1 g

●

Recurrent infection

or intravenous metronidazole 500 mg

●

Nystatin vaginal pessary 1-200 000 units for two weeks (C, U)

or fluconazole 100 mg per week (see recurrent vaginal

Candida)

●

Recommended oral therapies

●

Fluconazole 150 mg single dose (C, E, U, W)

●

Itraconazole 200 mg twice daily for one day (E, U)

●

Topical symptomatic relief suitable for both sexes

●

Clotrimazole 1% cream

C Centers for Disease Control, USA; E European STI guidelines;

●

Miconazole nitrate 2%

U UK National Guidelines; W World Health Organization,

●

Clotrimazole 1% with 1% hydrocortisone

(2)

second line recommendation.

●

A large number of other preparations are available

Questions to ask women who complain of vaginal

discharge

Discharge

Associated symptoms

Principles of management

●

Onset

●

Itching

●

Duration

●

Soreness

As mentioned, self reported symptoms and the clinical

●

Amount

●

Dysuria

appearance of vaginal discharge are both very variable and do

●

Colour

●

Intermenstrual or post-coital bleeding

●

Blood staining

●

Lower abdominal pain

not permit accurate determination of the presence or absence

●

Consistency

●

Pelvic pain

of a specific STI. If a full screen to exclude STIs is not carried

●

Odour

●

Dyspareunia—superficial and deep

out this, may lead to delayed diagnosis and possible long term

●

Previous episodes

complications.

An assessment of an individual woman’s STI risk can be

made by taking a sexual history. A practitioner working in a

Risk factors for presence of STIs

primary care setting can then decide whether it is appropriate

●

Age under 25 years

to refer a woman with identified risk factors in her history

●

No condom use

directly to a GUM clinic for further management.

●

Symptoms developed after recent change of sexual partner or

The advantage of managing vaginal discharge in a GUM

multiple contacts

clinic is that full microbiological tests are done to establish an

●

Recurrent or persistent symptoms

●

Symptoms in partner

accurate diagnosis. Microscopy is also carried out routinely for

●

Symptoms imply complications

symptomatic cases, so an immediate diagnosis will be available

●

Partner’s risk behaviour

for many women.

Vaginal discharge—causes, diagnosis, and treatment

The presence of lower abdominal pain, cervical excitation

pain, and adnexal tenderness in association with abnormal

vaginal discharge implies pelvic inflammatory disease (see

Chapter 8).

Syndromic management

Patient complains of vaginal discharge, vulval itching, or burning

Syndromic management is based on the symptoms and signs

that a client presents with and can be undertaken without

Take history, examine patient (external,

laboratory support. A flow chart is used to guide the healthcare

speculum and bimanual), and assess risk*

provider to the most appropriate treatment choice for a given

set of symptoms and signs in a woman with a specifically

Yes

Lower abdominal tenderness or

Use flow chart

defined risk history. Ideally, these flow charts are based on the

cervical motion tenderness present?

for lower

abdominal pain

local prevalence of STIs, their associated risk factors, and

antibiotic sensitivities.

Cervical mucopus or high GC/CT prevalence

setting or both? Was risk assessment positive?

Patient complains of vaginal

Yes

discharge, vulval itching, or

burning

Treat for C trachomatis and gonococcal infection

plus vaginal infection according to speculum

and microscope examination findings

Take history, examine patient,

and assess risk*

Perform wet mount or Gram stain microscopy of vaginal specimen

Abnormal discharge present

Any other

• Educate and counsel

or vulval erythema?

genital disease?

• Promote and provide

Clue cells seen

condoms

Motile

plus pH >4.5

Budding yeasts

No abnormal

Yes

or pseudohyphae

• Offer HIV counselling

trichomonads?

Potassium

findings?

and testing if both

hydroxide positive

seen?

Use appropriate

facilities are available

flow chart for

additional

Treat for

treatment

Treat for

Trichomonas

bacterial

C albicans

vaginalis

vaginosis

Lower abdominal tenderness?

High GC/CT

Treat for bacterial

prevalence

vaginosis and

Yes

setting or risk

T vaginalis

Educate, counsel, promote and provide condoms, partner management, and offer HIV

assessment

counselling and testing if both facilities are available; return if necessary

positive?†

Yes

*Risk factors need adaptation to local social, behavioural, and epidemiological situations

Use flow chart for

Treat for

Vulval oedema or curd

lower abdominal pain

Chlamydia

like discharge,

trachomatis,

erythema, and

Vaginal discharge flow chart (bimanual, speculum, and microscope).

gonococcal

excoriations present

GC/CT gonorrhoeal/chlamydial infection. Both vaginal discharge flow

infection,

charts are adapted from the World Health Organization guidelines found at

bacterial

Yes

www.who.int/docstore/hiv/STIManagemntguidelines

vaginosis, and

Trichomonas

Treat for

vaginalis

C albicans

• Educate and counsel

• Promote and provide

* Risk factors need adaptation to local social,

condoms

behavioural, and epidemiological situations

• Offer HIV counselling

† The determination of high prevalence

and testing if both

needs to be made locally

facilities are available

Vaginal discharge flow chart. GC/CT = gonorrhoeal/chlamydial infection

Investigations

Where laboratory facilities are available a woman with

abnormal vaginal discharge should be investigated for

gonorrhoea, Chlamydia, trichomoniasis, bacterial vaginosis, and

candidiasis with samples taken from the vagina and cervix (see

Chapters 3 and 4).

Treatment

Women with vulvitis caused by vulvovaginal candidiasis may

respond best to a combination of intravaginal and topical vulval

therapy. It should be noted that some of these treatments,

Examples of treatments for vaginal candidiasis

ABC of Sexually Transmitted Infections

e.g. miconazole and econazole, have an adverse effect on latex

condoms, which could cause condom failure. Oral

metronidazole, which is used for treating both bacterial

vaginosis and T vaginalis, is associated with a metallic bad taste

in the mouth, gastrointestinal disturbance, and a disulfiram

reaction with alcohol. Patients should be advised to avoid

alcohol during and for 48 hours after treatment. In the past,

questions have been raised about the safety of metronidazole in

pregnancy, especially during the first trimester. The current

British treatment guidelines advise that no toxicity in pregnant

humans has been established. Treatment of symptomatic

patients during pregnancy may produce more benefit than

harm, and low dose treatment can be used in the first trimester,

where clinical indications are present.

Management

Trichomonas vaginalis

Many women self diagnose and self treat episodes of vaginal

infection with over the counter treatments and may

subsequently present with a history of “recurrent thrush”, never

having had this diagnosis confirmed by microbiological tests.

It is important to confirm the diagnosis and ensure that a

full sexual health screen has been done to exclude concurrent

infection. Management of vaginal discharge requires an

empathic approach with reassurance and psychological support

as necessary.

Overview of trichomoniasis

Cause

Recommended treatments

● Trichomonas vaginalis, a flagellated protozoon

● Metronidazole 2 g orally stat dose (C, E (2), U, W)

● Tinidazole 2 g orally single dose (W)

Incubation period

● Metronidazole 400 mg orally twice daily for five to seven days (C, E,

● Usually seven days (range 3-21 days)

U, W (2))

Transmission

● Tinidazole 500 mg orally twice daily for five days (W (2))

● Usually sexual. Trichomonas may be acquired perinatally.

● World Health Organization recommends five days’ treatment in

Infection in pre-pubescent girls is unusual, and the possibility of

preference to single doses for men

sexual abuse should always be considered

● Cure rates 95%

Symptoms in women

● Compliance can be a problem with the longer regimen because

● Can be asymptomatic. Classically, profuse, frothy, yellow vaginal

of the nausea and metallic taste in the mouth associated with

discharge but also can be scant and watery. Associated symptoms

metronidazole treatment

include marked vulvar irritation or soreness (or both), external

● In cases of allergy, no effective alternative to imidazole

dysuria, and superficial dyspareunia

compounds exists

Symptoms in men

● Patients should be advised to abstain from sexual intercourse

during treatment and until their sexual partner has been seen

● T vaginalis can cause relapsing non-gonococcal urethritis.

T vaginalis in men can be asymptomatic and has a spontaneous

Follow up

cure rate of about 20-25%, which results in a low rate of isolation

● A test of cure should be done at one week with microscopy and

in male contacts of about 30-40%

culture

Examination findings

Management of contacts

● External genital examination may be normal in men and

● Sexual contacts should be offered a screen for T vaginalis and

women

other STIs and given epidemiological treatment with

● Vulvar and vaginal wall erythema may be present; the “strawberry

metronidazole 2 g oral stat dose

cervix” appearance caused by inflammatory punctate haemorrhage

Treatment failure

is uncommon

● Recalcitrant trichomoniasis can result from poor compliance

Main methods of diagnosis

with treatment, reinfection, and poor absorption of treatment,

● Direct microscopy of discharge and culture

for example because of vomiting

● Longer courses of oral metronidazole or higher dose regimens

2 g a day for three to five days may be effective. Unusually

imidazole resistant strains may be responsible.

● No standard effective treatments are available for recalcitrant

T vaginalis infection. haemolytic streptococci in the vagina may

contribute to metronidazole treatment failure and empirical

treatment with amoxicillin or erythromycin before retreatment

should be considered in such cases

C Centers for Disease Control, USA; E European STI guidelines; U

UK National Guidelines; W World Health Organization;

(2)

second line recommendation.

Vaginal discharge—causes, diagnosis, and treatment

Recurrent vulvovaginal candidiasis

What can we offer women with recurrent vulvovaginal

candidiasis?

Recurrent vulvovaginal candidiasis is defined as four or more

● Longer courses of treatment or empirical self treatment with an

episodes of symptomatic infection annually, which occurs in 5%

intravaginal azole at identified cyclical trigger points over a

of healthy women. Candida glabrata and other non-albicans

three month period

species are found in 10-20% of cases. It is important to consider

● Maintenance treatment regimes

the following

● Fluconazole 100 mg weekly for six months

● Clotrimazole 500 mg pessary weekly for six months

● Medical conditions, such as diabetes mellitus, frequent

● Non-albicans species may respond to intravaginal nystatin

antibiotic use, and long term steroid therapy

pessaries for 14 days

● Vulvar symptoms may be caused by an underlying genital

● Modifying the allergic component of the problem

dermatological condition, such as dermatitis or lichen sclerosus

● Hydrocortisone ointment 1% topically

● Immunosuppression, for example HIV infection

● Antihistamines may relieve nocturnal irritation and

scratching (chlorpheniramine 4 mg orally)

● Candida species sensitivities if there is an azole resistant

isolate. Intravaginal nystatin or boric acid pessaries are

alternative treatment options

● An association between atopy, particularly allergic rhinitis,

and increased severity of symptoms in recurrent vulvovaginal

candidiasis has been described.

Recurrent bacterial vaginosis

Women may report psychosexual symptoms with lack of libido

and anxiety about infection as a consequence of recurrent

episodes of bacterial vaginosis and associated malodour.

The bacteria responsible do not persist in the male partner,

and concurrent treatment of the male partner does not affect

the rate of relapse.

Condom use with male sexual partners may help reduce the

risk of recurrence of bacterial vaginosis. Use of hormonal

contraception does not increase the incidence of bacterial

Candidal vulvovaginitis

vaginosis. Women with an intrauterine contraceptive device or

system in situ have an increased risk of bacterial vaginosis.

What can we offer women with recurrent bacterial

Women who use the diaphragm that have Escherichia coli urinary

vaginosis?

tract infections also have an increased incidence of concurrent

● Give a clear explanation about bacterial vaginosis

bacterial vaginosis.

● Carefully go through their daily personal hygiene practices to

Once again, no robust evidence supports the various

identify those that may disrupt the normal balance of vaginal

alternative treatments available. However, some evidence exists

flora

to support the use of intravaginal acetic acid preparations in

● Explain that although short course treatments often relieve

the management of recurrent bacterial vaginosis.

symptoms, the imbalance in bacteria may persist, and this is why

symptoms can recur after treatment

● A longer course of antibiotics such as metronidazole (400 mg)

Persistent vaginal discharge

twice daily for up to seven days can be more effective in

preventing or delaying recurrence

It can be difficult to know what to do for women who complain of

● Explore the impact on the patient’s personal and sexual life

persistent vaginal discharge with repeated negative STI screens

and offer psychological support and psychosexual counselling

and negative cervical cytology. When minimal discharge is evident

when appropriate

on examination, it is worth discussing once again personal

● If a woman with recurrent bacterial vaginosis has an

hygiene practices and douching, the basis for physiological

intrauterine device in situ, alternative contraception could be

discussed

discharge and enquiring whether there are psychosexual

difficulties as a result of the patient’s continued symptoms.

If use of spermicides and lubricants is contributing to

Further reading

symptoms, then alternative contraception choices should be

● Hay PE, Taylor-Robinson D. Defining bacterial vaginosis: to BV or

discussed. An extensive cervical ectropion can cause heavy

not to BV, that is the question. Int J STD AIDS 1996;7:233-35

mucoid discharge, which, if troublesome to a woman with

● Irving G, Miller D, Robinson A, Reynolds S, Copas AJ.

normal cervical smears, may be helped by intravaginal acetic

Psychological factors associated with recurrent vaginal

acid. Some cases may warrant cryocautery to relieve symptoms.

candidiasis: a preliminary study. Sex Transm Inf

After the menopause, atrophic vaginal changes may

1998;74:334-8

● Ison CA, Taylor-Robinson D. Bacterial vaginosis. Int J STD AIDS

predispose women to infective vaginitis. Intravaginal oestrogen

1997;8:1-42

replacement, with pessaries or cream, gradually will improve

● Rodgers CA, Beardall AJ. Recurrent vulvo-vaginal candidiasis:

the condition of the vaginal epithelium and reduce the

why does it occur? Continuing medical education. Int J STD AIDS

susceptibility to infection.

1999;10:435-41

Underlying gynaecological disease must be considered in all

● Vaginal discharge. In: Holmes KK, Mårdh PA, Sparling PF,

women with unexplained persistent vaginal discharge.

Lemon S, Stamm W, Piot P, et al. Sexually Transmitted Diseases.

Gynaecological neoplasms, such as benign endocervical and

3rd ed. New York: McGraw Hill, 1999:285-312

● Working Group of the British Society for Medical Mycology.

endometrial polyps, can present with vaginal discharge, and

Management of genital candidiasis. BMJ 1995;310:1241-4.

malignancy needs to be excluded.

www.bashh.org (last accessed 26 Nov 2003)

Referral to a gynaecologist allows for further investigations

that may include transvaginal ultrasonography, endometrial

sampling, and hysteroscopy.

Pelvic inflammatory disease and pelvic pain

Helen Mitchell

Acute pelvic inflammatory disease (PID) is most commonly

Differential diagnosis of lower abdominal

caused by infection ascending from the vagina or cervix, which

pain

causes inflammation of the upper genital tract. This can result

● Ectopic pregnancy

in any combination of salpingitis, endometritis, oophoritis,

● Urinary tract infection

parametritis, pelvic peritonitis, and tubo-ovarian abscess

● Ovarian cyst complications—torsion and

formation.

rupture

The organisms commonly responsible for acute PID depend

● Endometriosis

on the local prevalence of sexually transmitted infections (STIs).

● Ovarian malignancy

Chlamydia trachomatis is the most common treatable bacterial STI

● Bowel disease

● Irritable bowel syndrome

in the United Kingdom and is implicated in more than 50% of

● Appendicitis

cases of acute PID. Ten to 20% of cases are associated with

Neisseria gonorrhoeae, this rate will be higher in areas with higher

local prevalence. Studies have shown that 8-39% of women with

C trachomatis related genital infection will develop acute PID.

In addition, it is estimated that for every overt case of chlamydial

pelvic infection there are three covert (asymptomatic) cases.

Risk factors for PID in patient’s history

The role of Mycoplasma genitalium and Ureaplasma

Presence of an STI

urealyticum in acute pelvic infection is still unclear, but they

● New sexual partner in past month

have been implicated in the pathogenesis of acute endometritis

● Frequent change of sexual partner

and chorioamnionitis associated with pre-term labour.

● No condom use

Other organisms connected with acute pelvic infection

● Age under 25 years

include anaerobes, Bacteroides fragilis, peptostreptococci,

● Partner with symptoms

Escherichia coli, and Lancefield group B haemolytic streptococci.

● Previous medical history of an STI

Bacterial vaginosis is associated with ascending infection and

● Involuntary infertility

acute PID after induced abortion and post partum.

Gynaecological interventions that can cause

ascending infection

● Intrauterine contraceptive device insertion or

change in 20 days

Clinical diagnosis of PID

● Termination of pregnancy—induced abortion

The most common presenting symptoms are lower abdominal

● Hysterosalpingogram

● Endometrial sampling

pain and abnormal vaginal discharge. Other symptoms associated

● Hysteroscopy

with PID include intermenstrual and post-coital bleeding, dysuria,

● Dilatation and curettage

deep dyspareunia, and fever. Low backache and rectal discomfort

● Evacuation of retained products of conception

may also be present. Right upper quadrant pain from

perihepatitis is a feature of the uncommon Fitz-Hugh-Curtis

syndrome in association with C trachomatis related PID.

The history for pain should include onset, site, and nature,

as well as aggravating and relieving factors. A full menstrual,

contraception, and gynaecological history should be taken to

Clinical diagnosis of PID

make a risk assessment for unplanned pregnancy, including

Presenting symptoms

ectopic pregnancy, and ovarian disease. The sexual history will

● Lower abdominal pain

provide a risk assessment for the presence of an STI. It is also

● Abnormal vaginal discharge

● Intermenstrual or post-coital bleeding (or

important to ask about urinary or bowel symptoms.

both)

Dysuria

Backache

Fever

With additional clinical signs from list below

● Adnexal tenderness

● Cervical excitation pain

● Mucopurulent cervical discharge

Pyrexia above 38 C

Rebound

Guarding

Adnexal mass

Mucopurulent cervical discharge with cervicitis

Pelvic inflammatory disease and pelvic pain

A history of abdominal surgery for infertility, ovarian

disease, appendicectomy, and bowel disease can provide useful

Patient complains of lower abdominal pain

diagnostic pointers. If the onset of lower abdominal pain has

occurred after a recent gynaecological intervention, then the

Take history (including gynaecological

intervention may have introduced an infection or transmitted

history) and examine (abdomen and vagina)

an infection from the cervix to the upper genital tract.

Any of the following present?

Is there cervical

Any other

• Missed or overdue period

excitation tenderness

illness

Investigations and clinical decisions

• Recent delivery, abortion, or miscarriage

or lower abdominal

found?

• Abdominal guarding or rebound

tenderness and

Yes

It is most important to exclude ectopic pregnancy by testing

tenderness, or both

vaginal discharge?

• Abnormal vaginal bleeding

urine for human chorionic gonadotrophin with a sensitive

Yes

Manage

• Abdominal mass

appro-

pregnancy testing kit (if available).

Manage for pelvic

Yes

priately

Other immediate investigations that should be carried out

inflammatory disease

Refer patient for surgical or

Review in three days

include dipstick urinalysis to exclude urinary tract infection. If

gynaecological opinion and assessment.

this is positive, a midstream urine sample should be sent for

Before referral, set up an intravenous

line and apply resuscitatory measures

Has patient

Refer

microscopy and culture. The appropriate specimens should be

if necessary

improved?

patient

collected for Chlamydia nucleic acid amplification testing and

Yes

gonorrhoea culture. These results will not be available

immediately, so treatment needs to be started if the healthcare

Continue treatment until completed

• Educate and counsel

professional suspects acute PID.

• Promote and provide condoms

If the woman is seen at a genitourinary medicine (GUM)

• Offer HIV counselling and testing if both facilities are available

clinic, immediate microscopy can exclude bacterial vaginosis

and may show gonorrhoea infection, but, again, treatment is

Lower abdominal pain flow chart

started once the clinical diagnosis is made.

In a hospital setting, a full blood count, blood chemistry,

and blood cultures should be carried out in all patients

with high fever or acute abdominal pain with peritonitis.

Ultrasonography can identify adnexal disease and exclude

Indications for hospital admission for

ectopic pregnancy in a woman with a positive pregnancy test.

women with acute PID

Clinical symptoms and signs of PID only have a 65%

●

Uncertain diagnosis

positive predictive value when compared with laparoscopy. The

●

High fever and rigors with dehydration

routine use of diagnostic laparoscopy to diagnose acute PID,

●

Diffuse peritonism

however, is limited by the risks and cost of this procedure.

●

Adnexal mass

Laparoscopy usually is carried out only in patients in whom the

●

HIV positive women with immunosuppression

diagnosis remains uncertain.

if pelvic abscess suspected

●

Intravenous drug users if poor treatment

compliance and social circumstances

●

Intercurrent medical illness, for example

Treatment of acute PID

sickle cell disease, insulin dependent diabetes

Treatment should be started immediately to reduce the risk of

mellitus

long term sequelae. In the United Kingdom, the incidence of

gonorrhoea and genital chlamydial coinfection has increased

over the past decade; therefore, the antibiotic regimen used to

treat PID should cover N gonorrhoea, C trachomatis, and

anaerobic infections. There may be local variations in N

gonorrhoea antibiotic sensitivities, and the local microbiology

laboratory should be able to advise on appropriate antibiotic

choices. When prescribing for women it is important to check

Oral antibiotic regimens

● Ofloxacin 400 mg twice daily for 14 days (U and C)

● Metronidazole 400 mg twice daily 14 days

● Doxycycline 100 mg twice daily 14 days

● Metronidazole 500 mg twice daily 14 days

● Ceftriaxone 250 mg intramuscular stat

● Amoxyl 3 g orally with 1 g probenicid CW E

Where these specified antibiotics are not available, the alternative

regimen is used. It should

● Cover N gonorrhoeae according to local known antibiotic sensitivities

● Include appropriate treatment for 14 days to cover C trachomatis

and anaerobic bacteria

In pregnancy, erythromycin 500 mg twice daily for 14 days should

be used as an alternative to doxycycline. If a long acting

preparation is not available four times daily dosing is required

Adhesions over liver capsule associated with perihepatitis in chlamydial

pelvic infection

ABC of Sexually Transmitted Infections

the risk of early pregnancy, current combined oral

Adverse sequelae of PID

contraception use, and any history of antibiotic allergies.

Chronic PID

The risk of developing chronic PID increases with each episode of

acute PID. Chronic pelvic infection is a debilitating condition,

Further management

with general malaise and fatigue, that results in frequent time off

work and incapacity. Symptoms include irregular menses with

The woman should be advised to return for review two or three

congestive dysmenorrhoea, secondary deep dyspareunia, chronic

days after taking oral treatment if her symptoms are no better.

pelvic pain, and low backache. Women with chronic PID have

If the symptoms have worsened during this time, she should be

increased hysterectomy rates.

advised to visit the emergency department.

Tubal factor infertility (TFI)

No evidence supports the routine removal of the

The risk of TFI increases with each episode of acute infection

intrauterine contraceptive device (IUCD) in acute PID;

● one episode

12% risk of TFI

however, removal should be considered if no clinical response

● two episodes

35% risk of TFI

to treatment is seen. In such situations, oral emergency

● three episodes

70% risk of TFI

contraception may be required.

95% of infertile women with a history of PID will have TFI and

The patient must be advised to complete the full course of

30% of women with no history of PID will also have TFI, probably

antibiotics, abstain from sexual intercourse, and attend the

as a result of “silent” subclinical infection

GUM clinic for a follow up appointment.

Ectopic pregnancy

Admission to hospital will allow intravenous antibiotic

Ectopic pregnancy can be life threatening. The risk of ectopic

therapy and fluid rehydration, provision of adequate analgesia,

pregnancy is 1:100 of all pregnancies, which is increased

sevenfold after acute PID

and regular clinical review of symptoms and signs.

Indications for laparotomy in acute pelvic infection include

generalised peritonitis, bilateral or enlarging abscess and where

the clinical condition has not improved or has deteriorated

after 48 hours on intravenous antibiotics.

Recommended parenteral treatment regimens include

cefoxitin with doxycycline and a combination of clindamycin

with gentamicin when a tubo-ovarian abscess is present.

Partner notification and aftercare

Partner notification and epidemiological treatment is essential

to prevent reinfection, with the consequent increase in long

term sequelae.

Women with negative STI test results should be advised that

their diagnosis is non-specific PID and that because of the risks

of sequelae, doctors have a low threshold for starting antibiotic

treatment in sexually active women. Partner notification and

epidemiological treatment is still necessary because the male

partner may have non-specific urethritis.

Many women will express anxieties over future fertility and

may even request tests for tubal patency; however, these tests

Laparoscopic view of ectopic pregnancy

should only be done in the course of formal investigation after

a period of involuntary infertility. It is important to emphasise

the need for continued contraception to avoid unplanned

pregnancy.

Prevention of pelvic infection

Management of the complications and reproductive sequelae of

Chlamydia infection in women costs national health

programmes millions each year.

The introduction of screening programmes for genital

C trachomatis infection has reduced substantially the incidence of

acute PID and ectopic pregnancy. Screening programmes are

cost effective when the local prevalence rate is 6% and a nucleic

acid amplification diagnostic test assay is used.

Studies have shown that bacterial vaginosis is common in

women attending for legal abortion and, if left untreated, it is

associated with an increased risk of post-abortal pelvic

infection. Prophylaxis and treatment for bacterial vaginosis is

metronidazole (1 g suppository given rectally at time of

operation).

Blocked tube at laparoscopy

Pelvic inflammatory disease and pelvic pain

Evidence also shows that antibiotic prophylaxis effective

Opportunities for Chlamydia screening to prevent pelvic

against bacterial vaginosis given before total abdominal and

infection*

vaginal hysterectomy prevents post-operative vaginal vault

All women and men

infection.

● Younger than 25 years

Although PID can occur after the insertion of an IUCD no

● Older than 25 years with a new sexual partner or two or more

evidence at present recommends routine screening or

partners in the previous year

antibiotic prophylaxis for bacterial vaginosis before insertion of

● Of any age with symptoms

the device. Bacterial vaginosis does not affect conception rates

● Attending GUM clinics

during in vitro fertilisation procedures, but it is an independent

All women

● Younger than 35 years before surgical uterine instrumentation—

risk factor for subsequent miscarriage.

for example, hysteroscopy

● Before IUCD insertion

The photograph of mucopurulent cervical discharge with cervicitis is

● Before induced abortion (termination of pregnancy)

the copyright of Dr Marc Steben, Clinique de l’Ouest, Montreal,

Canada. The photographs of adhesions over the liver capsule and the

*British guidelines from Chief Medical Officer and Royal College of

ectopic pregnancy are courtesy of Mr Alfred Cutner

Obstetricians and Gynaecologists

Further reading

● Berger GS, Westrom LV, eds. Pelvic inflammatory disease. New York:

● Recommendations from the 31st RCOG study group. In:

Raven Press, 1992

Templeton A, ed. The prevention of pelvic infection. London: RCOG

● Bevan CD, Johal BJ, Mumtaz G, Ridgway G, Siddle NC. Clinical,

Press, 1996:267-70

laparoscopic and microbiological findings in acute salpingitis:

● Robinson AJ, Greenhouse P. Prevention of recurrent pelvic

report on a United Kingdom cohort. Br J Obstet Gynaecol

infection by contact tracing: a common-sense approach. Br J

1995;102:407-14

Obstet Gynaecol 1996;103:859-61

● Mann SN, Smith JR, Barton SE. Pelvic inflammatory disease.

● Walker CK, Kahn JG, Peterson HB, Sweet RL. Pelvic

Continuing medical education. Int J STD AIDS 1996;7:315-21

inflammatory disease: meta-analysis of antimicrobial regimen

● Royal College of Obstetrics and Gynaecology’s website

efficacy. J Infect Dis 1993;168:969-78

www.RCOG.org.uk

Sexually transmitted infections in pregnancy

Helen Mitchell

Pregnant women may be unaware they have an existing

Screening in pregnancy guidelines

asymptomatic sexually transmitted infection (STI) or they may

Routine antenatal screening

be still at risk of acquiring an STI during pregnancy. Therefore,

● In the United Kingdom the current programme includes

it is necessary to overcome a natural hesitancy to discuss risk

serology for syphilis, Hepatitis B, and HIV antibody testing with

factors for STIs. Infections at this time can affect the fetus and

a pre-test discussion

neonate by vertical transmission, which may result in serious

Hepatitis C

and life threatening consequences. Screening for infections in

● Screening for anti-hepatitis C virus (anti-HCV) antibodies should

pregnancy and starting early treatment can prevent adverse

be done in high risk groups, such as intravenous drug users and

outcomes for the mother and neonate.

women that received organ transplant or blood transfusion

The management of STIs in pregnancy should be guided by

before HCV screening commenced

expert advice because certain treatments are contraindicated

Other STIs

during pregnancy. A test of cure should be carried out after

● Screening for gonorrhoea, chlamydia, and T vaginalis in

pregnancy should be considered in women with STI risk factors,

treatment and before delivery for women testing positive for

young women under 25 years and those with a history of STIs or

Chlamydia trachomatis, Trichomonas vaginalis, and Neisseria

pelvic inflammatory disease, or both.

gonorrhoeae.

● Routine antenatal screening for gonorrhoea and chlamydia to

prevent complications of maternal infection in pregnancy and

neonatal infection is appropriate in high prevalence countries

Gonorrhoea

● No evidence currently supports routine antenatal screening

using type specific antibody testing for herpes simplex virus

Mother

(HSV-1 and HSV-2)

Uncomplicated gonorrhoea rates in young women have

increased dramatically over the past decade in the United

Kingdom. Worldwide gonorrhoea prevalence varies, with

particularly high rates reported in Africa.

Partner notification and epidemiological treatment is

essential to prevent reinfection during the antenatal period

Baby

and further risk of vertical transmission

Intrapartum infection occurs in about 30-50% of babies born

to untreated mothers and is associated with

● Conjunctivitis (ophthalmia neonatorum) “sticky eye” with

onset of purulent conjunctival discharge between two and

five days after birth

● Disseminated neonatal infection

Gonorrhoea

● Diagnosis is by Gram stained smear and culture of

Gonorrhoea in pregnancy is associated with

conjunctival swab.

● Low birth weight

● Treatment of established infection is with systemic antibiotics,

● Premature delivery

for example ceftriaxone.

● Pre-term rupture of membranes

● Chorioamnionitis

● Postpartum sepsis

● Secondary infertility

C trachomatis

Appropriate treatment regimes include a single

Mother

intramuscular dose of ceftriaxone (250 mg),

Genital chlamydial infection rates in young women have also

cefotaxime (500 mg), and spectinomycin (2 g)

increased substantially in the United Kingdom. Non-invasive

(see Chapter 5). Ciprofloxacin and tetracyclines

testing for chlamydia using nucleic acid amplification tests, for

should be avoided in pregnancy.

example polymerase chain reaction (PCR) on self taken

vulval-introital swabs, may be appropriate in late pregnancy and

in situations in which the woman declines a speculum

examination.

C trachomatis

C trachomatis in pregnancy is associated with

Baby

● Low birth weight

Intrapartum infection in babies born to untreated mothers is

● Premature delivery

associated with

● Pre-term rupture of membranes

● Chorioamnionitis

● Conjunctivitis (ophthalmia neonatorum) in 30-50% of babies

● Postpartum sepsis

with onset occurring 3-14 days after birth

● Otitis media

Treatment in pregnancy is with erthromycin (500 mg twice daily)

for two weeks or amoxycillin (500 mg three times daily) for seven

● Nasopharyngitis

days. Doxycyline and tetracycline are both contraindicated in

pregnancy

Sexually transmitted infections in pregnancy

●

Chlamydial pneumonitis, which presents with staccato cough,

Ophthalmia neonatorum

tachypnoea, and failure to thrive, occurs after 4-12 weeks in

●

Ophthalmia neonatorum is conjunctivitis that develops within

10-20% of exposed babies.

21 days of birth. In the United Kingdom it is a notifiable

Diagnosis is by culture of C trachomatis or nucleic acid test

condition

●

Chlamydial or gonococcal infection should always be excluded

(NAAT) on conjunctival, nasopharyngeal, and rectal swabs.

Chlamydial ophthalmia is more common but it is not possible

Treatment of established infection is with systemic antibiotics,

to distinguish them clinically

for example erythromycin.

●

Untreated gonococcal ophthalmia neonatorum can lead to

corneal ulceration and perforation with permanent loss of vision

●

Diagnosis is by Gram stained smear and culture of a swab from

the conjunctiva for N gonorrhoea, culture for C trachomatis, and

ligase chain reaction

●

Established infection is treated with systemic antibiotics

●

In areas of high STI prevalence without routine antenatal

screening ocular prophylaxis should be given routinely to all

newborn babies within one hour of birth, using a 1%

tetracycline or 0.5% erythromycin eye ointment

●

Prophylactic systemic ceftriaxone should be considered for

babies born vaginally to mothers with known untreated

gonorrhoea

Chlamydial pneumonitis

Genital herpes simplex infection

Mother

The diagnosis of genital herpes simplex infection (HSV-1 and

HSV-2) in women has seen a slow but steady increase and about

5% of antenatal attendees in the United Kingdom have a history

Ophthalmia neonatorum

of symptomatic genital herpes. On serological testing, 25% of

genitourinary medicine clinic attendees and 20% of adult

Americans have type specific antibodies to HSV-2. However, only

Advice for pregnant women with known recurrent genital

35% of infected adults are aware that they have genital herpes.

herpes

Maternal primary HSV infection during pregnancy is

●

Women with recurrent genital herpes can deliver vaginally if

associated with

they do not have overt genital ulcers at the time of delivery

●

Repeated viral cultures during pregnancy are of no clinical

●

Spontaneous abortion

●

Low birth weight

value in predicting recurrences or viral shedding at the time of

delivery

●

Premature delivery

●

Women with a recurrence at the time of delivery are currently

●

Stillbirth.

delivered by lower segment caesarean section to prevent

intrapartum viral transmission

It is important to ascertain whether a pregnant women

●

If recurrent lesions are present at the time of delivery there is a

presenting with genital ulceration has a recurrent infection or a

low risk of neonatal herpes even with vaginal delivery. This risk

true primary HSV infection. In tropical countries it is important

must be offset against the maternal risks of surgical delivery and

to exclude other causes of genital ulceration (see Chapter 11).

some obstetricians may agree to vaginal delivery after discussion

Differentiation of primary from non-primary infection is by

with the pregnant woman to obtain her informed consent

serology because history is a poor indicator. Seroconversion in

●

Suppression therapy during the third trimester may reduce the

risk of recurrence at the time of delivery in women with

primary infection takes between three and six weeks and can be

frequent recurrence but this does not reduce viral shedding so

tracked using immunoglobulin G and immunoglobulin M type

the benefit is uncertain

specific antibody testing.

ABC of Sexually Transmitted Infections

Women presenting with suspected primary genital herpes

acquired during the third trimester of pregnancy should be

offered aciclovir antiviral treatment and delivered by elective

lower segment caesarean section if labour commences within

a six week period after diagnosis.

Pregnant women should be informed of the risks of

The risks of primary HSV-2 are highest in the last trimester

acquiring HSV infection during pregnancy. Receptive oral

and if, during this time, the male partner has an episode of

sex with a partner with orolabial HSV-1 is a risk factor for

recurrent genital HSV-2 sexual intercourse should be avoided.

women with no personal history of orolabial or genital

herpes infection.

Baby

Antepartum HSV transmission is rare and may cause stillbirth.

Neonatal HSV infection is rare in the United Kingdom and the

United States (2 per 100 000 and 7 per 100 000 live births,

respectively). The highest risk of intrapartum transmission and

Neonatal herpes simplex infection can be localised or

neonatal infection is 40% for babies born by vaginal delivery in

disseminated affecting multiple organs, including hepatitis

a woman with primary genital herpes infection at the time of

and encephalitis. If neonatal HSV is suspected immediate

delivery. In women with recurrent herpes at vaginal delivery the

intensive treatment with intravenous antiviral therapy

risk of neonatal herpes is less than 1%. Postnatal infection can

should be started. Disseminated infection has a high

occur if a relative or caregiver with a herpetic whitlow or

mortality rate (70%) even with effective antiviral therapy.

orolabial HSV-1 handles or kisses the child.

Surviving neonates are at a high risk of neurological

Confirmation of diagnosis is essential and the method used

sequelae.

will depend on the laboratory services available from EM of

vesicle fluid to viral PCR testing.

HIV

Mother

HIV testing in pregnancy

By the end of 2002 an estimated 42 million adults and children

● All pregnant women should be offered HIV screening routinely

worldwide are living with HIV and 50% of infected adults are

by HIV antibody testing with a pre-test discussion

women. In some of the countries in Sub-Saharan Africa one in

● Women may not be able to accurately assess their personal risk

three women attending antenatal services will be HIV positive.

of HIV infection

● The universal offer of HIV testing in pregnancy that allows

In the United Kingdom, data obtained by national

women to opt out is more effective than selective offer or

unlinked anonymous monitoring of HIV infection show that

allowing women to choose if they feel HIV testing is necessary

one in 200 women attending antenatal clinics in Central

● The medical benefit of knowing a women’s HIV status is that

London are HIV positive, but in rural areas only one in 2500

women who test positive can be offered interventions that

women are HIV positive. During 2002, 720 births took place to

effectively reduce the risks of vertical transmission of HIV

HIV positive women in the United Kingdom, of which 80%

● Mother-to-child transmission without interventions during

were to previously diagnosed women.

pregnancy is 15-30%, which is further increased by breast

feeding

Worldwide, HIV in pregnancy is associated with

● The transmission risk can be effectively reduced to less than 1%

● Low birth weight

by the following interventions during pregnancy

● Premature delivery

Antiretroviral therapy for the mother which includes

● Stillbirth.

zidovudine or nevirapine. Strong evidence shows that both

treatments effectively reduce the risk of vertical transmission

Pregnancy does not seem to have an adverse effect on the

Elective caesarean section delivery

health of an HIV positive woman or her long term prognosis

Avoiding breast feeding

unless she has AIDS or a concurrent infection, such as

Antiretroviral therapy for the neonate after delivery

tuberculosis.

● In high prevalence countries women should be retested in the

third trimester

Baby

Each day 2000 children in Africa are newly infected with HIV

and many millions of children have been orphaned by HIV.

The risk of mother-to-child transmission is related to the

Total: 2.1 million-2.9 million

maternal viral load, stage of HIV disease, duration of pregnancy

Eastern Europe and Central Asia

at the time of delivery and the risk is increased by vaginal

9000-15 000

delivery.

Western Europe

The highest transmission rates occur in resource poor

5000-7000

countries with high HIV prevalence where interventions to

East Asia and Pacific

North America

prevent transmission are not widely available. The additional

8000-12 000

6000-12 000

risks of transmission in resource poor countries include breast

North Africa and Middle East

Caribbean

31 000-49 000

feeding after delivery. In some societies, bottle-feeding is

19 000-31 000

South and South East Asia

110 000-190 000

associated with social stigma and a substantial risk of infant

death from acute gastroenteritis.

Latin America

All babies born to infected mothers will exhibit maternal

37 000-50 000

Sub-Saharan Africa

HIV antibodies; in uninfected babies 50% will lose the

2 million-2.2 million

Australasia

<200

antibodies by 10 months. All uninfected babies should be

confirmed as HIV negative at six months using HIV PCR testing

Number of children (younger than 15 years) estimated to be living with HIV

and at 18 months by serial antibody titre.

and AIDS as of end 2003. Adapted from www.UNAIDS.org

Sexually transmitted infections in pregnancy

Syphilis

Clinical features of congenital syphilis

Early congenital syphilis is a multi-organ disease that can present

Mother

with hepatosplenomegaly

Worldwide, syphilis (Treponema pallidum) is still a common

● Anaemia

infection in pregnancy. The rates are low in the United

● Petechiae

Kingdom; nevertheless, routine antenatal screening is still

● Periostitis

carried out. In high prevalence countries congenital syphilis can

Latent (early and late)

occur as a result of acquisition in late pregnancy and infected

● No clinical signs of active infection

women not attending for antenatal care. The treatment regimen

Late (more than two years is similar to adult late disease)

used in pregnancy depends on the stage of maternal infection,

● Osteoperiostitis

history of antibiotic allergy and is usually with intramuscular

● Joint effusions usually knees—Clutton’s joints

benzathine penicillin injections. Effective maternal treatment

● Gummata

will prevent congenital syphilis in the unborn child except when

● Neurological and cardiovascular complications

treatment has commenced late in the third trimester.

The lesions of early and late syphilis may heal but result in classical

stigmata of congenital syphilis

Baby

● Sabre shaped tibial deformity

Syphilis is associated with 25% of stillbirths in rural Sub-

● Saddle nose deformity

Saharan Africa and congenital syphilis accounts for 30% of

● Frontal bossing of the skull

● Linear scars around the mouth

perinatal deaths. The risk of congenital syphilis in untreated

● Small notched incisors

cases is related to the stage of maternal syphilis with the risk

● Corneal opacities

decreasing with advancing stage of maternal disease. Up to 50%

of babies born to mothers with untreated primary or secondary

infection will be infected compared with less than 5% of babies

born to mothers with late latent infection.

Transplacental transfer of maternal antibodies occurs but if

the baby is not infected the treponemal antibody will be lost by

six months. Diagnosis of congenital infection occurs by

demonstrating the presence of treponemes in lesions and by

serology using the fluorescent treponemal antibody absorption

test for immunoglobulin M. Treatment of an infected neonate

is with intravenous penicillin.

Hepatitis B

In the United Kingdom the prevalence of hepatitis B carriage

in the antenatal population is low. In women from endemic

areas carriage is higher and vertical transmission can occur,

especially when the mother is hepatitis Be antigen positive.

Parental consent for immunisation should be obtained

before birth so that babies born to high risk carriers can be

given hepatitis B virus immunoglobulin passive vaccination and

active immunisation shortly after birth to prevent both neonatal

Congenital syphilis on teeth

infection and the risk of chronic carriage.

Hepatitis C

The risk of vertical transmission with hepatitis C is estimated

to be 6%. Transmission may be increased in co-infection

with HIV. No specific intervention has been identified to

reduce the transmission rate.

Genital warts

Genital warts may appear for the first time or increase in size

and number during pregnancy as a result of changes in local

cellular immunity. There is a very small risk of vertical

transmission resulting in neonatal laryngeal, mucous

membrane, or genital human papillomavirus infection.

Imiquimod, podophyllin, and podophyllotoxin topical

treatments are all contraindicated in pregnancy.

T vaginalis

Trichomonae infection in pregnancy is associated with adverse

pregnancy outcomes, including pre-term delivery and low birth

Congenital syphilis on mouth

ABC of Sexually Transmitted Infections

weight. Pregnant women can be treated with oral

Further reading

metronidazole treatment regimes but high dose metronidazole

●

Genc M, Ledger, WJ. Syphilis in pregnancy. Sex Transm Inf

treatment regimes should be avoided in the first trimester and

2000;76:73-9

also during breast feeding because they may cause breast milk

●

Guidelines on STIs in pregnancy. www.rcog.org.uk (accessed

to taste bitter to the infant.

26 Nov 2003) and www.bashh.org (accessed 26 Nov 2003)

●

PHLS Communicable Disease Surveillance Centre and PHLS

Syphilis Working Group. Antenatal syphilis screening in the UK: a

Bacterial vaginosis

systematic review and national options appraisal with recommendations.

London: Public Health Laboratory Service, 1998

At present, no evidence supports routine antenatal screening

www.hpa.org.uk (accessed 26 Nov 2003)

●

Reducing mother to child transmission of HIV infection in the United

for bacterial vaginosis for all pregnant women or that treating

Kingdom. Recommendations of an intercollegiate working party for

asymptomatic women with bacterial vaginosis in general

enhancing voluntary confidential HIV testing in pregnancy. London:

antenatal clinics reduces their risk of pre-term labour. However,

Royal College of Paediatrics and Child Health, 1998

some evidence shows that treating bacterial vaginosis reduces

www.hpa.org.uk (accessed 26 Nov 2003)

pre-term labour in women with a history of pre-term delivery

and it may be that this subgroup of women could benefit from

early screening and oral treatment. Further trials are needed to

show that such screening and antenatal treatment reduces

The photograph of opthalmia neonatorium is reproduced from

perinatal mortality and morbidity. Symptomatic pregnant

King A, Nicol C. Venereal diseases. London: Baillière Tindall, 1969

women should be treated with oral metronidazole (400 mg

twice daily) for between five and seven days.

Other conditions that affect the female

genital tract

Helen Mitchell

Bartholin’s gland conditions

A Bartholin’s cyst is a painless enlargement that may

The Bartholin’s glands can become enlarged by abscess or cyst

increase or decrease in size over time, and the history is

formation. In abscess formation, common infecting pathogens

often longer or intermittent

include Neisseria gonorrhoeae, Chlamydia trachomatis, Escherichia coli,

haemolytic streptococci, Staphylococcus aureus, and anaerobes.

Investigations

All sexually active patients who present with a cyst or abscess

A Bartholin’s abscess is a painful genital swelling and on

should be offered a full sexually transmitted infection (STI)

examination the gland is tensely enlarged with pain, local

screen. However, if the client is too uncomfortable for an

redness, and warmth. The swelling may become fluctuant

examination, the screen can be deferred until follow up. If the

“pointing” and will eventually discharge pus, after which

abscess is discharging pus, additional swabs of pus should be

the intense throbbing pain is relieved

taken for microscopy, culture, and sensitivity.

Vulvar symptoms

Women may present with complaints of genital skin itching,

burning, soreness, and discomfort during sexual intercourse.

Some women experience longstanding symptoms and despite

frequent clinic attendances may fail to receive a diagnosis and

appropriate advice or treatment with consequent psychological

and psychosexual morbidity. In some women, relationship

difficulties, psychosexual problems, and depression can lead to

Discharging Bartholin’s abscess.

Reproduced from King A, Nicol C.

somatisation and genital symptoms with no clinically apparent

Venereal diseases. London: Baillière

cause.

Tindall, 1969

Clinical management

A detailed history is very important and should include onset

and duration of symptoms and whether any topical treatments

have been used and with what degree of success.

Management of Bartholin’s gland conditions

Details of personal habits and hygiene should be covered,

Abscess

●

Painful non-discharging abscess—refer urgently to on call

such as use of perfumed soaps, bath additives, douching,

gynaecology for a marsupialisation or incision and drainage

depilatory preparations, alternative remedies, laundry

procedure

detergents, and fabric conditioners. If the patient admits to

●

Abscess has spontaneously discharged and pus is weeping

scratching, ask whether this is worse at night and if they

freely—oral flucloxacillin (500 mg four times daily orally) should

regularly wear fingernail varnish, because this can contain

be prescribed for five days. Refer the patient to routine

formaldehyde, which is a contact irritant. A personal and family

gynaecology outpatients because recurrence is common and may

history of atopy, asthma, hayfever, eczema, other dermatological

require interval marsupialisation

●

Advise rest, loose clothing, and analgesia as required, for

conditions, and nickel and food allergies can be relevant.

example, ibuprofen

●

Use Sitz baths (one cup of salt in bowl of water) and cotton balls

General principles

to gently clear away pus

●

The external genital area should be examined carefully. The skin

●

Pat the area dry after washing or dry with a hairdryer on a low

of the rest of the body, scalp, mouth, eyes, and fingernails may

heat setting

need to be examined as appropriate. The inguinal lymph nodes

●

Follow up appointment for results or to perform full STI screen

should be palpated and the vaginal mucosa inspected by

speculum examination

Cyst

●

Offer full STI screen

●

Vulvar symptoms often are caused by recurrent vulvovaginal

●

No antibiotics are required

Candida infection

●

Referral to routine gynaecology outpatient appointment to

●

If symptoms persist and tests for STIs and other genital infections

are negative, it is important to consider whether there is an

consider interval marsupialisation

underlying dermatological disorder

●

Scratching and rubbing to relieve symptoms can result in both

secondary skin changes and infection that can further alter the

Common causes of vulvar symptoms

clinical appearances

●

Vulvar skin biopsy may be required to make a definitive diagnosis

●

Genital infections

●

Referral to specialist services with the combined clinical

●

STIs

expertise of a dermatologist, gynaecologist, or genitourinary

●

Vulvodynia

medicine physician should be considered for all women with

●

Genital dermatoses

persistent vulvar symptoms

●

Psychosexual problems

ABC of Sexually Transmitted Infections

Vulvar and perianal itching

Threadworm infestation should be considered if the

itching is predominately perianal (pruritus ani) rather

than vulvar (pruritus vulvae). A “sticky tape” test should

carried out by applying a clear sticky tape strip to the

perianal skin in the morning before washing. The tape is

applied to a glass microscopy slide and examined for

threadworm ova.

General advice for patients with vulvar symptoms, including

genital itching

●

Aqueous cream can be used a soap substitute for washing

●

A bland emollient is useful as a skin moisturiser

●

Avoid perfumed products, bath additives, talcum powder,

Non-specific vulvar appearance with oedema, redness, and introital splitting

vaginal deodorant sprays, and sanitary pads with perfume or

deodorisers

●

Change laundry detergent to a skin sensitive brand or a non-

biological brand

●

Do not use fabric conditioner for undergarments

●

Shaving or use of depilatory creams in the genital area may

Causes of genital itching

exacerbate symptoms

Infection

●

Patients sensitive to spermicide or latex condoms can try using

●

Candidiasis

washed latex condoms or those with only a lubricant

●

Trichomonas vaginalis

●

Perfumed oils and creams should not be used as lubricants

●

Genital warts

●

Avoid self treatment with over the counter or alternative

●

Genital herpes simplex

remedies

●

Molluscum contagiosum

●

Try not to scratch because this can damage the skin and set up a

Infestation

cycle of itch-scratch-itch, which then needs to be broken by using

●

Pediculosis pubis (crab lice)

a moderate potency topical steroid initially then reducing the

●

Threadworms

dose as symptoms resolve

Genital dermatoses

●

A tepid bath, ice pack, or cold soaked cotton pad applied locally

●

Non-allergic contact or irritant dermatitis

may help reduce an intense need to scratch

●

Eczema

●

Itching can often be worse at night. A mildly sedating

●

Psoriasis

antihistamine, such as chlorpheniramine, at night may help

●

Lichen sclerosus

reduce nocturnal scratching

●

Lichen planus

●

Seborrhoeic eczema

Neoplastic conditions

●

Pre-malignant intraepithelial neoplasia

●

Invasive neoplasia

Genital dermatoses

Systemic conditions

Lichenification

●

Diabetes mellitus

●

Renal or hepatic dysfunction

This can occur in any itchy skin condition and describes

the appearance where the skin is thickened and pale with

accentuated skin line markings and folds. When scratching

is marked, evidence of excoriation with areas of broken skin

and traction hair loss will be seen. Post-inflammatory

hypopigmentation and hyperpigmentation can be

present.

Irritant contact dermatitis

This is commonly caused by skin sensitisers present

in products used in general and genital hygiene. Avoidance

of some common contact irritants may relieve

symptoms.

Allergic contact dermatitis

This can occur with self treatment with essential oils, local

anaesthetic creams, and pile relieving ointments common in

patients with chronic symptoms. Contact dermatitis

medicamentosa is an allergic contact dermatitis usually caused

by excipients or additives in topical treatment.

Patch testing may be useful for identifying specific allergens

in atopic eczema and allergic contact dermatitis. Nickel allergy

is a form of allergic contact dermatitis and may be relevant in

Hyperpigmentation secondary to contact dermatitis caused by the use of

women with poor quality genital piercings.

depilatory creams in the genital area

Other conditions affecting the female genital tract

Psoriasis

The appearance of affected genital areas may be altered, with

red, glazed, well defined patches that are often not scaly. It is

important to examine the limb flexures for characteristic

“silvery” plaques and the nails for pitting.

Eczema

The characteristic appearance of eczema can be altered on the

vulva because it is a moist area prone to friction from clothing

and during sexual intercourse. Other skin sites may be affected

and there may be a personal or a family history of atopy, such

as hayfever and asthma.

Seborrhoeic eczema

This can affect the vulva and also may be evident on the face,

chest, scalp, and eyebrows. It is treated with a mild steroid

Early stages of lichen sclerosus in a young woman, affecting the labia minora

containing an antifungal component.

on left

Lichen simplex chronicus

Plaques of lichenification are seen in this condition, but it is

not a specific diagnosis. It is important to review the skin

appearance once symptoms are controlled by a topical steroid

to exclude an underlying dermatosis, particularly lichen

sclerosus.

Lichen sclerosus

Lichen sclerosus is an autoimmune condition linked with

alopecia areata and vitiligo. There may be predisposing genetic

factors and, in some cases, infective trigger agents. Lichen

sclerosus can occur at any age and affects both sexes, but is

most common in women over 50 years of age.

The anogenital area is commonly affected in a classic figure

of eight distribution around the vulva and anus. Common

presenting symptoms are itching, soreness, dyspareunia, and

painful fissures at the introitus. The affected skin is dull and

white, with horizontal skin wrinkling, telangiectasia, and small

More advanced lichen sclerosus with loss of architecture and marked pallor

ecchymoses. In chronic, untreated cases, loss of normal

with telangiectasia

anatomy may result with fusion of the clitoral hood, abnormal

clitoral sensation, resorption of the labia minora, and

narrowing of the introitus.

Diagnosis can be made clinically in overt cases or by skin

biopsy that shows characteristic histological appearances.

Treatment is with a potent topical steroid twice daily until

symptoms resolve and the condition is quiescent. Maintenance

treatment continues with weekly or fortnightly applications.

The lifetime risk of squamous cell carcinoma in lichen

sclerosus is 4-5% and women should be taught how to examine

themselves and when to seek medical attention, for example for

ulceration, raised lesions, and localised persistent symptoms.

Surgical treatment is indicated rarely but may be useful

when introital narrowing precludes satisfactory sexual

intercourse.

Lichen planus

Lichen planus is considered to be an autoimmune disorder

that affects skin or mucosal surfaces, or both. Women may

Suspicious lesion with pigmentation that should be referred for expert

present with pruritus and dyspareunia with associated oral

opinion and histological diagnosis

symptoms. The classical appearances are itchy, purple papules

or plaques on the vulva, which can be white or have post-

inflammatory hyperpigmentation. These lesions may exhibit

Köebnerisation with local extension along trauma and scar

Malignant melanoma is the second most frequent vulvar

lines. Wickham’s striae is a lacy white appearance on the surface

malignancy, and it is important to refer any patient with a

of the affected genital mucosa and may also be identified on

suspicious pigmented genital lesion for an expert opinion to

the flexor aspects of the wrists, gingival margins, and oral

exclude pre-malignant or malignant change

mucosa.

ABC of Sexually Transmitted Infections

Clinical findings are important to establish the diagnosis

because the histological appearances on skin biopsy often show

only non-specific inflammatory changes.

Treatment is with topical steroids. In vulvovaginal gingival

syndrome, the vagina is also affected with painful red erosions,

and consequent synechiae formation can distort the vaginal

anatomy, causing severe dyspareunia. In such cases, systemic

and topical intravaginal steroids are necessary.

Pigmentary changes

Areas of pigmentation change may be seen on examination,

and it is important to ascertain whether any localised symptoms

are present.

● Lentigines are areas of darker pigmentation caused by a

Suspicious lesion with variable pigmentation (VIN III) that should be

localised increase in melanocytes

referred for expert opinion and histological diagnosis

● Post-inflammatory hypopigmentation and hyperpigmentation

can occur in women with chronic itching area with well

circumscribed areas of depigmentation and scratching

● Vitiligo is an autoimmune skin condition with well

circumsribed areas of depigmentation that can involve the

genital area.

Vulval intraepithelial neoplasia

and invasive vulval neoplasia

Vulval intraepithelial neoplasia (VIN) can be low grade (VIN I)

or high grade (VIN II/III). Pre-malignant lesions in the genital

area can be difficult to identify clinically because there are no

consistent diagnostic features, and VIN can be warty or flat,

single or multiple, asymptomatic or symptomatic, and varied in

coloration.

Squamous cell carcinoma is responsible for 90% of all vulvar

malignancies and is associated with the presence of a high risk

Red raised suspicious lesion (squamous cell carcinoma) that should be

human papillomavirus (for example, types 16, 18, 33, and 35).

referred urgently for expert opinion and histological diagnosis

Specialist advice is recommended for persistent genital

skin lesions and genital warts that do not respond to

topical treatment. Urgent referral is required for suspicious

lesions with ulceration, bleeding, or dark or patchy

ISSVD classification of vulval pain syndromes

pigmentation.

● Vulvar vestibulitis (provoked localised vulval dysaesthesia or

vestibulodynia)

● Cyclical vulvodynia

Vulval pain syndromes

● Dysaesthetic vulvodynia (unprovoked generalised vulval

dysaesthesia)

Vulval pain can be caused by local infection, trauma, topical

● Vulvar dermatoses

wart treatments, and pelvic floor disorders, and can occur in

● Vulvar papillomatosis

association with systemic disease. Vulvodynia is defined by the

International Society for the Study of Vulvovaginal Disease

(ISSVD) as chronic burning, soreness, or rawness. Vulvodynia

has features in common with other pain syndromes and

psychological support and psychosexual counselling are

important in long term management.

Vulvar vestibulitis syndrome is a triad of symptoms and signs

with superficial dyspareunia on attempted penetration or

tampon insertion, erythema, and point tenderness localised in

the vestibule. The aetiology is uncertain, and it is thought to be

a self limiting condition. Approaches to treatment include

general vulvar symptoms advice, topical local anaesthetic, and

lubricants to facilitate sexual intercourse.

Cyclical vulvodynia occurs when recurrent vulval

symptoms happen in relation to menstruation and coitus. It

may be caused by changes in vaginal pH or associated

vulvovaginal candidiasis and bacterial vaginosis. Intravaginal

azole treatment at the cyclical trigger points may be

beneficial.

Vulvar papillomatosis with characteristic club shaped papillae

Other conditions affecting the female genital tract

Dysaesthetic vulvodynia is characterised by a history of

Causes of dyspareunia

diffuse and constant burning pain and affects an older age

Superficial

group of women. This condition has closer parallels with

glossodynia and is thought to be a disorder of cutaneous

Infection

● Candidiasis, T vaginalis, and genital herpes simplex

sensory perception. Treatment is with tricyclic antidepressants

or the newer antiepileptic drugs, for example gabapentin.

Trauma

Vulvar papillomatosis describes the appearance of small

● Episiotomy scars, introital fissures, or tears caused by sex toys

lobular papillae on the inner surface of the labia minora and

Vulval disorders

around the vestibule. These papillae now are thought to be a

● Lichen sclerosus

● Lichen planus

normal anatomical variant, and in most women are

● Vulval pain syndromes

asymptomatic and do not require treatment.

● Post-menopausal vulvovaginal atrophy

● Iatrogenic self treatment, post-radiotherapy, and 5-fluorouracil

Psychosexual

● Vaginismus

Deep

● Ovarian disease

● Endometriosis

● Acute and chronic pelvic inflammatory disease

● Uterine fibroids

Further reading

● Edwards A, Wojnarowska F. The vulval pain syndromes. Int J

STD AIDS 1998;9:74-9

● Institute of Psychosexual Medicine website www.ipm.org.uk

(accessed 26 Nov 2003)

Localised redness in the vestibule with associated point tenderness elicited

Nunns D. Vulval pain syndromes. Br J Obstet Gynecol

●

using a cotton tip swab

2000;107:1185-93

● Powell JJ, Wojnarowska F. Lichen sclerosus. Lancet

Psychosexual problems

1999;353:1777-83

Chronic vulvovaginal symptoms can interfere seriously with

● Ridley CM, Robinson AJ, Oriel. Vulval disease: a practical guide

sexual and emotional relationships, resulting in reduced libido

to diagnosis and management. London: Arnold Publishers, 2000

and avoidance of sexual intercourse if it exacerbates symptoms.

● Skrine R. Blocks and freedoms in sexual life. A handbook of

Psychosexual problems can occur after an acute STI diagnosis

psychosexual medicine. Oxford: Radcliffe Medical Press, 1997

or recurrent episodes of genital herpes or vaginal discharge.

● Skrine R, Montford H, eds. Psychosexual medicine. An

Repeat clinic attendances by a woman complaining of

introduction. London: Arnold, 2001

abnormal vaginal discharge or vulvar symptoms with no

● Vulval pain patient information website

apparent physical cause may be a covert way for the woman to

www.vul-pain.dircon.co.uk (accessed 7 Jan 2005)

raise concerns or feelings about their genital area. Therefore, it

is important that all doctors are able to recognise psychosexual

problems and, where appropriate, offer referral for

psychosexual counselling.

Genital ulcer disease

Frances Cowan

Several sexually transmitted infections (STIs) can affect both

Most sexually transmitted causes of ulceration are said to be

sexes and do not differ substantially in their presentation

either “multiple and painful” or “solitary and painless,”

between men and women. The next chapters deal with such

although, of course, exceptions exist and it is unwise to

infections, namely genital ulceration, genital growths and

make a presumptive diagnosis on the basis of these signs

infestations, hepatitis, HIV, and AIDS.

and symptoms alone

Genital ulceration

Multiple

Solitary

Genital ulceration (or erosion) is a common symptom in both

Painful Herpes genitalis

Balanitis or vulvitis

Tuberculosis

Herpes zoster

(Candida, Trichomonas,

(recurrent herpes genitalis)

sexes and may be caused by a sexually transmitted agent, other

Vincent's organisms)

infectious agents, a dermatological condition, or trauma.

Behçet's

Erythema multiforme

syndrome

Stevens-Johnson

Particular points that need to be elicited from the patient to

syndrome

aid diagnosis are the number of ulcers, the time they have been

Chancroid

Folliculitis

present, the degree of discomfort they cause, and when they

Furuncle

appeared in relation to sexual intercourse, trauma, or lesions

Scabies

elsewhere on the body.

Crohn's

Multiple painful ulcers

Painless Secondary syphilis

Primary

disease

syphilis

Carcinoma

Multiple painful ulcers are most commonly caused by the

Trauma

Gumma

herpes simplex virus (discussed in detail below). The

Circinate balanitis

Lymphogranuloma

first episode of genital herpes may occur within one to two

(Reiter's syndrome)

venereum

weeks of infection, but it also may occur some time later. It

Granuloma inguinale

may be associated with systemic symptoms in addition to

Leukoplakia

ulceration, including fever, headache, myalgia, and urinary

Lichen sclerosis et atrophicus

Balanitis xerotica obliterans

or faecal retention (or both). Some people get ulceration at

Carcinomas

multiple sites (mouth, nipples, and fingers) during their

Causes of genital ulceration and erosions

first episode. Occasionally, herpes zoster gives rise to genital

ulceration, but recurrent ulceration on the genitals,

buttocks, or thighs almost always is caused by herpes simplex

Chancroid (soft sore)

infection.

Cause

Other infections that can cause multiple painful ulcers or

●

Haemophilus ducreyi (Gram negative bacillus)

erosions include balanititidis (due to Candida, Trichomonas, and

Distribution

haemolytic streptococci) and infestations with scabies or

●

Widespread in tropical countries, occasional outbreaks in large

pubic lice (in which the ulceration is secondary to scratching).

cities in wealthier countries. Large epidemic reported from

People (or sexual contacts) who have travelled or live in areas

Greenland

in which chancroid occurs (parts of sub-Saharan Africa, the

Incubation period

Americas, and Asia) may have multiple painful ulcers. These

●

Three to 10 days

ulcers are caused by Haemophilus ducreyi, which has a short

Main symptoms

incubation period of just two to five days.

●

Soft, painful, anogenital ulcers, painful inguinal adenopathy

A number of dermatological conditions can occur on the

(mostly unilateral). Ulcers single or multiple. Purulent base,

genitalia (see Chapters 6 and 10) and many of these can cause

contact bleeding, and undermined edge characteristic

superficial ulceration or erosions (for example psoriasis,

Complications

●

Destructive (phagaedenic) ulceration, inguinal abscess formation

Diagnosis

●

Usually clinical in endemic areas. Can be confirmed by culture

on special media. Polymerase chain reaction tests have been

developed

Treatment

●

Ciprofloxacin: 500 mg orally twice daily for three days (C, E, U, W)

●

Ceftriaxone 250 mg intramuscularly in a single dose (C, E, U, W)

●

Azithromycin 1 g orally in a single dose (C, E, U, W)

●

Erythromycin 500 mg orally four times daily for seven days

(E, U, W), three times daily for seven days (C)

●

Abscesses—aspiration or incision and drainage indicated for

fluctuant lesions

●

Resistance—commonly found to co-trimoxazole

●

HIV co-infection—treatment failure possible and extended

therapy is sometimes required

C= Centers for Disease Control, USA; E=European STI guidelines;

U=UK National Guidelines; W= World Health Organization

Chancroid

Genital ulcer disease

dermatitis, lichen planus, and drug eruptions). These often but

not always are associated with dermatological problems

elsewhere. Behçets disease causes genital ulceration that is

usually associated with oral lesions.

Single painless ulcers

The most common cause of painless genital ulceration is

primary syphilis (see Chapter 12). The incubation period

is usually 21 days, but lesions may show from 9-90 days

after sexual intercourse with an infected partner. The

gumma that occur in tertiary syphilis are also solitary and

painless.

Behçets disease

Other causes of solitary, painless ulcers are carcinoma,

circinate balanitis, or lichen sclerosis et atrophicus (previously

known as balanitis xerotica obliterans). Lymphogranuloma

venereum and donovanosis are two tropical STIs that should be

considered in people living in or travelling to endemic areas or

those who are in sexual contact with people from such areas.

Self inflicted trauma (dermatis artefacta) may result in large,

solitary, apparently painless, ulcers.

Lymphogranuloma venereum (LGV)

Cause

●

Chlamydia trachomatis, L1, L2, and L3 serotypes

Distribution

●

Mainly tropical countries, rare compared with other STIs

Incubation period

●

Three to 30 days

Primary syphilis

Main symptoms

●

Characteristically a very small genital ulcer is the first sign. May

also start with urethritis or proctitis. Presentation is most

common at the next stage where painful, usually unilateral

inguinal adenopathy develops usually with fever and malaise.

Donovanosis (Granuloma inguinale)

Untreated patients may subsequently develop discharging

Cause

inguinal sinuses, genital lymphoedema, fistulas, and rectal

●

Klebsiella (formerly Calymmatobacterium) granulomatis

strictures

Distribution

Diagnosis

●

Localised areas of India, Brazil, South Africa, Papua New Guinea

●

Usually clinical. The most specific confirmatory test is the

Incubation period

demonstration of high levels of antibody to L1-3 serotypes of C

●

Two to 40 days

trachomatis. The diagnosis may be supported by less specific forms

of chlamydia testing—for example, polymerase chain reaction

Main symptoms

tests on material taken from ulcers or lymph nodes

●

Slow-growing, painless, friable genital and inguinal lesions that

often stand out from the skin

Treatment

●

Doxycycline: 100 mg twice a day for 14 days (W), 21 days (E,

Complication

U, C)

●

Genital lymphoedema, pelvic lesions in women, rarely

●

Azithromycin: 1 g weekly for three weeks

haematogenous dissemination to bone and other viscera

●

Erythromycin: 500 mg four times daily for 14 days (W), 21 days

Diagnosis

(E, U, C)

●

Demonstration of intracellular bacteria (Donovan bodies) in

material taken from lesions

C= Centers for Disease Control, USA; E=European STI guidelines;

Treatment

U=UK National Guidelines; W= World Health Organization

All treatments given until cured or at least two weeks (E) or three

weeks(C):

●

Azithromycin: 500 mg daily (C, E, U, W) or 1g weekly (C, E, U)

●

Doxycyline: 100 mg twice daily (C, E, U, W)

●

Erythromycin: 500 mg four times daily (C, E, U, W)

Multiple painless ulcers

●

Ceftriaxone: 1 g intramuscularly daily

Secondary syphilis can result in multiple eroded papules or

●

Ciprofloxacin: 750 mg daily (C)

mucous patches.

C= Centers for Disease Control, USA; E=European STI guidelines;

Trauma as a result of sex or other causes can cause multiple

U=UK National Guidelines; W= World Health Organization

or solitary erosions or ulcers.

ABC of Sexually Transmitted Infections

Diagnosis of genital ulcers

Patient complains of a

●

Although some people who present with genital ulceration have

genital sore or ulcer

the classic signs and symptoms described above, many individuals

present atypically

Take history and examine

●

Basing the diagnosis on appearance alone has been shown to be

suboptimal

Sore or ulcer

• Educate and counsel

●

Where laboratory facilities exist, every attempt should be made

Only vesicles present?

present?

• Promote and provide

to confirm the diagnosis either microbiologically or

Yes

condoms

histologically, as appropriate

Yes

• Offer HIV counselling

●

In the absence of laboratory facilities, syndromic management

and testing if both

Treat for HSV-2. Treat for

Treat for syphilis

facilities are available

should be used to cover treatment for the most probable

syphilis if indicated*

and chancroid

infectious causes, with onward referral if the ulceration fails to

Treat for HSV-2†

respond to first and second line therapy

• Educate and counsel on risk reduction

• Promote and provide condoms

• Offer HIV counselling and testing if both facilities are available

• Review in seven days

Genital herpes

Ulcer(s) healed?

Ulcer(s) improving?

Refer

Genital herpes is a common infection caused by the herpes

Yes

simplex virus (HSV). HSV has two viral subtypes: type 1

(HSV-1) and type 2 (HSV-2). Classically, genital herpes is caused

• Educate and counsel on risk reduction

Continue treatment

by infection with HSV-2. In recent years, however, childhood

• Promote and provide condoms

for a further seven

infection with HSV-1, the cause of orolabial herpes (cold sores),

• Offer HIV counselling and testing if both facilities are available

days

• Partner management

has become less common, at least in western countries. This

means that an increasing number of people are becoming

* Indications for syphilis treatment: RPR positive; no recent syphilis treatment

sexually active when they are uninfected with HSV-1 and hence

† Treat for HSV-2 where prevalence is 30% or higher, or adapt to local conditions

are susceptible to infection.

Genital HSV-1 acquired through orogenital contact is the

Genital ulcer disease flow chart

most common cause of first episode genital herpes in the

United Kingdom, particularly in young people. Genital

infection with HSV-1 is clinically indistinguishable from HSV-2.

Duration of viral shedding

Natural course

Vesticular

Wet ulcer

Dry crusts

The incubation period for HSV is one to two weeks; however,

pustule

only about half of the people that get infected have symptoms

of genital herpes at the time of their infection with either

HSV-1 or HSV-2. Some people will become symptomatic at

later date and others will remain asymptomatic. Therefore,

the reported cases of symptomatic disease greatly

underestimate the total burden of infection. Infected

individuals who are totally asymptomatic and unaware of their

-4

-2

Days

infection can transmit the infection to their partners.

Seroepidemiological studies from the United States indicate

Sexual

Lesions

New

Lesions

Symptoms

Lesions

that 22% of the adult population are infected with HSV-2. The

contact

noted

lesion

start

gone unless

healed

formation

to heal

lesions

rates in Europe are lower, with rates in the United Kingdom

common

irritated

around 7%. Studies from developing countries indicate very

high rates of infection, for example over 40% of Tanzanian

Course of first episode genital herpes

women have become infected by age 19 years.

Genital herpes is a lifelong chronic condition. After

Duration of viral shedding

infection, the virus becomes latent in the local sensory

ganglion, periodically reactivating to cause symptoms, such as

genital ulceration (a recurrence) or asymptomatic, but

Wet ulcer

Dry crusts

nonetheless infectious, viral shedding.

Genital HSV-2 recurs and is shed more often than genital

HSV-1 (the converse is true for oral infection). On average,

people with symptomatic genital HSV-2 get a symptomatic

recurrence around four times per year (although the range is

wide—from none to more than twelve recurrences per year).

Asymptomatic shedding may be more frequent than this. As a

general rule, the frequency of recurrences and shedding

reduces over time.

–2

Days

People with symptomatic genital HSV-1 typically have

around one recurrence per year (again the range is wide).

Prodromal

Lesions

New

Symptoms

Lesions

Although symptoms usually occur at the site where HSV enters

signs

noted

lesion

gone unless

healed

formation

lesions

the body, such as the genital area, recurrences may occur

common

irritated

anywhere in the distribution of that dermatome, typically on

the buttocks or thighs.

Course of recurrent genital herpes

Genital ulcer disease

Clinical presentation: first episode infection

The first time a person has clinical symptoms of genital

herpes is called the “first episode.” It usually presents with

multiple painful genital ulcers. Typical lesions start as vesicles,

which then become superficial ulcers that crust and heal.

Separate lesions may coalesce to form substantial areas of

superficial ulceration. Viral shedding lasts until lesions have

crusted over.

More recently, it has been recognised that atypical

presentations are common. Small erosions or fissures may be

First episode

caused by HSV, as can dysuria in the absence of any obvious

genital herpes

lesions. One third of patients may have constitutional symptoms

including fever and malaise. About 10% of patients have

a headache and photophobia, and symptoms of viral

meningitis can occur. A few people complain of retention of

urine, either because it is too painful to pass urine over the

Clinical presentation of first episode genital herpes

lesions (urinating in a bath of warm water, which dilutes the

Site

Symptoms

urine as it passes over the ulcers, may help) or because of

temporary viral autonomic neuritis.

Pain Dysuria Retention Constipation Discharge None

Penis (glans,

coronal sulcus

Clinical presentation: recurrent episodes

and shaft)

Recurrent episodes are generally less severe and are not

Urethra (male)

caused by reinfection. It is common not to have an identifiable

Anus/rectum

trigger, although trauma (for example due to sexual

Buttocks/thighs/

intercourse) and ultraviolet light can both precipitate

scrotum

infections. Recurrences generally occur more often in the first

Vulva/urethra

year of infection, and genital HSV-2 infection is more likely to

Vagina

become recurrent than genital HSV-1. Some people notice

Cervix

prodromal symptoms before a recurrence, typically tingling in

the distribution of the sciatic nerve. However, prodromal

symptoms are not always followed by a clinical recurrence.

Infectious viral shedding can occur during prodromal

symptoms.

Diagnosis

Counselling

Genital herpes is diagnosed by isolating the virus directly

When counselling patients with first episode genital herpes, the

from genital lesions by culture, polymerase chain reaction, or

following issues should be discussed

antigen detection. Other causes of genital ulceration may

●

Possible source of infection

need to be excluded. Infection can also be confirmed by

●

Natural course, including risk of subclinical viral shedding

detecting antibodies to HSV-1 or HSV-2 in a blood sample

●

Future treatment options

●

Risk of transmission by sexual and other means

using type specific antibody tests. Although these antibody

●

Risks of transmission to the fetus during pregnancy and the

tests can be used to confirm or refute infection, they do not

advisability of the obstetrician or midwife being informed

give information about the site of infection or whether

●

Sequelae of infected men infecting their uninfected partners

the individual is symptomatic. In people with their

during pregnancy

first symptoms of genital herpes it can be determined

●

The possibility of partner notification

whether it was acquired recently by taking serial blood

samples. The first blood sample is taken at the time of

presentation (which will be negative if herpes is recently

acquired) and the second sample is taken three weeks later

(by which time it should be positive).

Treatment: first episode

A minority of people have persistent psychological distress

Patients who present within five days of the start of the episode or

and need ongoing psychological support. Providing correct

while new lesions are still forming should be given oral antiviral

information and support may prevent the development of

drugs, such as aciclovir, famciclovir, or valaciclovir, which are all

more severe psychological sequelae

highly effective in reducing the severity and duration of the

episode. They should be started as soon as possible after the

start of symptoms. Even if the symptoms and signs of the first

episode seem to be minor, treatment should be started, as this

may prevent much more severe symptoms developing.

Couples in which only one of the partnership is infected

Supportive therapy, such as analgesics, should also be

with genital herpes need to decide how important it is to

considered.

prevent transmission and, therefore, to use condoms on a

Lay perceptions of herpes are that it is a severe and

long term basis. Some uninfected partners will prefer to

“risk” acquiring HSV rather than use condoms indefinitely,

stigmatising condition. Because infection can only be managed,

whereas others will continue to use condoms for the

not eradicated, many people need time and support to come to

foreseeable future

terms with the diagnosis.

ABC of Sexually Transmitted Infections

Treatment: recurrent infection

Overview of genital herpes

Genital herpes recurrences are self limiting and generally cause

Cause

minor symptoms. Decisions about how best to manage clinical

●

HSV-1 and HSV-2

recurrences should be made with the patient. Treatment may

be supportive therapy only, episodic antiviral treatments, and

Site of infection

●

Site of exposure

suppressive antiviral therapy. The most appropriate strategy

●

HSV-1 acquired through orogenital contact

for managing an individual patient may vary over time,

●

HSV-2 through genital contact

according to recurrence frequency, symptom severity, and

Incubation period

relationship status.

●

One to two weeks

Supportive treatment includes saline bathing and

●

Asymptomatic infection can occur

application of petrolatum. Oral aciclovir, valaciclovir, and

●

Genital herpes is a lifelong chronic condition

famciclovir given at the time of the episode are effective at

●

The virus becomes latent in a local sensory ganglion

reducing the duration and severity of a recurrence (the median

Main symptoms

reduction in duration is one to two days for most patients). If

First episode

●

Multiple painful genital ulcers starting as vesicles

given early in the episode, treatment may abort the recurrence.

●

Constitutional symptoms, for example fever, malaise, headache,

For patients with frequent recurrences, continuous daily

photophobia, and occasional retention of urine

antiviral drugs greatly reduce the frequency of recurrences.

Recurrent episodes

●

Less severe ulceration, sometimes preceded by prodromal

Transmission

symptoms, for example tingling

Herpes simplex is transmitted when the infectious virus comes

Diagnosis

in contact with mucous membranes or abraded skin. The

●

Isolate virus from genital lesions by culture, polymerase chain

infectious virus can be shed during a period of clinical

reaction, or antigen detection

symptoms, prodromal symptoms, or in the absence of

symptoms. Therefore, people infected with genital herpes

Treatment of first episode (all for five days)

●

Aciclovir (200 mg five times daily)

should be advised to abstain from sex during clinical

●

Famciclovir (250 mg three times daily)

recurrences or when they have prodromal symptoms. However,

●

Valaciclovir (500 mg twice daily)

people should be aware that they may be infectious to their

Episodic treatment (all for five days)

sexual partners between recurrences. The frequency of

●

Aciclovir (200 mg four times daily)

asymptomatic shedding, is linked closely to the frequency of

●

Valaciclovir (500 mg twice daily)

clinical shedding, so that people with frequently recurring

●

Famciclovir (125 mg twice daily)

symptoms will probably shed virus often between clinical

Suppressive therapy

recurrences.

●

Aciclovir (400 mg twice daily)

●

Valaciclovir (250 mg twice daily or 500 mg once daily)

Infection is much more easily transmitted from men to

●

Famciclovir (250 mg twice daily)

women than from women to men. However, recent research

showed that male condom use can reduce the risk of male to

female transmission substantially. As female to male

transmission occurs much less often, it has been more difficult

Further reading

to show whether condoms are effective in preventing

●

American Social Health Association website

transmission.

www.ashastd,org/hrc/educate/html (accessed 26 Nov 2003)

Antiviral drugs such as aciclovir, valaciclovir, or famciclovir

●

Corey L, Wald A. Genital Herpes. In: Holmes KK, Mårdh PA,

dramatically reduce levels of asymptomatic genital shedding of

Sparling PF, Lemon S, Stamm W, Piot P, et al. Sexually

virus. Trials are underway to see if this results in a reduced

Transmitted Diseases. 3rd ed. New York: McGraw Hill,

transmission risk. One large study of once daily valaciclovir has

1999:285-315

confirmed that this reduction results in a reduced risk of

●

Corey L, Wald A, Patel R, Sacks S, Tyring S, Warren T, et al.

transmission between sexual partners.

Once-daily valacyclovir to reduce the risk of transmission of

genital herpes. N Engl J Med 2004;350:11-20

Partner notification

●

Herpes Virus Association (SPHERE), 41 North Road, London

Partners of people with first episode genital herpes may benefit

N7 www.herpes.org.uk (accessed 26 Nov 2003)

from partner notification because they may have unrecognised

●

Wald A. Genital herpes. Clinical Evidence 2002;7:1416-25

genital herpes that can be appropriately diagnosed and

●

Wald A, Link K. Risk of human immunodeficiency virus

managed.

infection in herpes simplex virus type 2 seropositive persons:

a meta-analysis. J Infect Dis 2002;185:45-52

The line drawings showing the courses of first episode and recurrent

genital herpes are with permission of Dr L Corey

Syphilis—clinical features, diagnosis, and

management

Michael Adler, Patrick French

The advent of penicillin had a dramatic and rapid impact on

the incidence of early infectious syphilis throughout the world

12 000

in the late 1940s. In England and Wales, the number of cases of

Men

Women

syphilis seen in the sexually transmitted infection (STI) clinics

10 000

has declined substantially since the peak after the second world

war. More recently, since 1998, the rate of infectious syphilis has

8000

increased substantially. Outbreaks have occurred in Brighton,

Manchester, and London, mostly as a result of homosexual

6000

transmission. Between 1996 and 2002, new diagnoses have

increased tenfold (122 to 1193 cases).

4000

Elsewhere in the world, syphilis still presents a major

clinical problem and the World Health Organization

2000

estimates that 12 million new cases of infectious syphilis are

diagnosed worldwide each year. Most of these cases occur in

1931

1940

1950

1960

1970

1980

1990

2001

South and South East Asia (4 million) and sub-Saharan Africa

(4 million). In other countries, such as the United States and

Year

Russia, syphilis is still a major problem. In the United States,

New cases of infectious syphilis seen in genitourinary medicine clinics in

infectious syphilis increased substantially during the 1990s,

England and Wales, 1931-2001. Adapted from the PHLS Communicable

particularly affecting the African-American community. The

Diseases Surveillance Centre. Communicable Disease Report 1997;7:22

numbers of cases are now declining but are still high.

Infectious syphilis has reached epidemic proportions in

Eastern Europe, particularly the newly independent states of

the former Soviet Union.

Acquired syphilis has been classified traditionally as either

early infectious or late non-infectious. The arbitrary cut off

point between these stages is usually two years

Time after exposure

Early infectious

Primary

9-90 days

Secondary

Six weeks to six months

(Four to eight weeks after primary

Sites of primary syphilis

lesion)

Genital

●

Vaginal wall

Latent (early)

Two years

●

Shaft of penis

●

Cervix

Late (non-infectious)

●

Coronal sulcus

Extragenital

Latent (late)

Two years

●

Glans penis

●

Lip

Neurosyphilis

3-20 years

●

Prepuce

●

Tongue

Cardiovascular syphilis

10-40 years

●

Fraenum

●

Mouth, tonsil, pharynx

Gummatous syphilis

3-12 years after primary infection

●

Urethral meatus

●

Fingers

●

Anal margin and canal

●

Eyelid

●

Rectum

●

Nipple

●

Labia minora, labia majora

●

Any part of the skin or

●

Fourchette

mucous membranes

Primary syphilis

●

Clitoris

The incubation period for primary syphilis is 9-90 days (mean

21 days). Lesions are found at the site of inoculation, which

may sometimes be extragenital.

The lesion is normally solitary and painless. It first

develops as a red macule that progresses to a papule and

finally ulcerates. This ulcer is usually round and clean with

an indurated base and edges. Inguinal lymph nodes are

moderately enlarged, rubbery, painless, and discrete.

The primary lesions will heal within 3-10 weeks and may

go unnoticed by the patient. Lesions on the cervix, rectum,

and anal canal and margin may, in particular, be

asymptomatic.

Primary chancre of vulva

Primary chancre of penis

ABC of Sexually Transmitted Infections

Secondary syphilis

Clinical features of secondary syphilis

Skin lesions

75-80%

The lesions of secondary syphilis usually occur four to eight

Mucous membrane lesions

30%

weeks after appearance of the primary lesion. In about one

Generalised lymphadenopathy

50-60%

third of cases the primary lesion is still present. The lesions

Arthritis, arthralgia, and periostitis

are generalised, affecting both skin and mucous membranes.

Hepatitis

The skin lesions are usually symmetrical and non-itchy.

Glomerulonephritis and nephritic syndrome

Rare

They can be macular, papular, papulosquamous, and, very

Iridocyclitis and choroidoretinitis

(

10%)

rarely, pustular. The macular lesions (0.5-1 cm in diameter)

Neurological disease (meningitis and

appear on the shoulders, chest, back, abdomen, and arms.

cranial nerve palsies)

The papular lesions are coppery red and are the same size as

Alopecia

the macules. They may occur on the trunk, palms, arms, legs,

soles, face, and genitalia. Skin lesions are commonly a

mixture of macular and papular lesions (maculopapular).

In warm, opposed areas of the body, such as the anus and

labia, papular lesions can become large and coalesce to form

Lesions of secondary syphilis

large, fleshy masses (condylomata lata). The papulosquamous

Skin

Macular or papular

lesions are found when scaling of the papules occurs and can

Condylomata lata

be seen in association with straightforward papular lesions. If

Papulosquamous

papulosquamous lesions occur on the palms or soles they are

Pustular

sometimes described as psoriasiform.

Mucous membranes

Erosions

Pustular lesions are rare and occur when the papular

lesions undergo central necrosis. Mucous membrane lesions are

shallow, painless erosions that are usually found in association

with papular skin lesions and affect the mucous surface of the

lips, cheeks, tongue, face, pharynx, larynx, nose, vulva, vagina,

glans penis, prepuce, and cervix. They have a greyish

appearance and are sometimes described as “snail track” ulcers.

The lesions of the skin and mucous membrane may be

associated with non-specific constitutional symptoms of malaise,

fever, anorexia, and generalised lymphadenopathy. The

secondary stage is one of bacteraemia, and any organ may show

evidence of this, for example hepatitis, iritis, meningitis, and

optic neuritis with papilloedema.

Without treatment, the symptoms and signs of secondary

syphilis resolve. About one quarter of untreated patients have

recurrent episodes of secondary syphilis. Recurrent secondary

syphilis is rare after the first year of infection.

Maculopapular rash on hands

Syphilis in HIV positive patients

Syphilis enhances HIV acquisition and transmission. Although

most HIV positive patients with syphilis present with typical

features, the classical clinical features described previously can

be modified and altered. Features of syphilis can be mistaken

for clinical signs of HIV infection.

Clinical manifestations shared by syphilis and

HIV

●

Generalised lymphadenopathy

●

Skin rashes or alopecia or both

●

Oral manifestations (mouth ulcerations)

●

Cognitive impairment

●

Meningitis

●

Cranial nerve palsies

●

Myelopathies

●

Uveitis

Maculopapular rash on chest (left) and condylomata lata (right)

Syphilis in HIV positive patients

Latent syphilis

●

Increased risk of multiple and larger ulcers in primary syphilis

●

Increased risk of genital ulceration in secondary syphilis

People with untreated syphilis but no signs or symptoms of

●

Possibly accelerated development of neurosyphilis, uveitis, and

infection have latent syphilis. This latent period is divided into

gummata

an early stage, in which the disease has been present for less

Syphilis—clinical features, diagnosis, and management

than two years, and a late stage, in which the disease has been

present for more than two years. The condition is diagnosed by

●

Positive results from serological tests

●

No clinical evidence of early or late syphilis in any system

●

Normal results on chest radiography and screening

Untreated primary or secondary syphilis

●

Examination of cerebrospinal fluid to exclude cardiovascular

syphilis or neurosyphilis.

About 65% of patients with untreated syphilis will not

15% Gummatous syphilis

10% Neurosyphilis

develop late clinical sequelae of the disease. However, about

10% of patients will develop neurological lesions, 10% will

10% Cardiovascular syphilis

65% No clinical sequelae

develop cardiovascular lesions, and 15% will develop

gummatous lesions. It is extremely rare to see late syphilis in

Course of untreated syphilis

the developed world because of the decline in infectious

syphilis and improved clinics and treatment facilities.

Neurosyphilis

Neurosyphilis is classified as asymptomatic, meningovascular,

and parenchymatous (general paralysis of the insane and tabes

Epilepsy, confusion, aphasia, monoplegia,

dorsalis). The widespread use of antibiotics for other unrelated

hemiplegia, or paraplegia are just some of

the ways in which late meningovascular

conditions has probably resulted in neurosyphilis that does not

syphilis can present

always fit the older classical clinical forms and descriptions.

Meningovascular syphilis

This can be present in the early and late stages of syphilis.

Patients can present with acute meningeal involvement during

the secondary stages of the disease, which often coincides with

the development of skin lesions. Headache is the main symptom.

Signs of meningitis are found with third, sixth, and eighth

General paralysis of the insane

cranial nerve involvement, papilloedema, and, rarely,

Early

Signs

●

Irritability

●

Expressionless facies

homonymous hemianopia or hemiplegia. Late meningovascular

●

Fatigability

●

Tremor of lips, tongue, and

syphilis presents less acutely but headaches may still be a

●

Inefficiency

hands

presenting symptom. Cranial nerve palsies (third, sixth, seventh,

●

Personality changes

●

Dysarthria

and eight) and pupillary abnormalities are seen. The pupils are

●

Headaches

●

Impairment of handwriting

small and unequal in size and react to accommodation but not

●

Impaired memory

●

Hyperactive tendon reflexes

light (Argyll Robertson pupils). Cerebral and spinal cord

●

Tremors

●

Pupillary abnormalities

(anterior spinal artery) vessels may be affected.

●

Optic atrophy

Late

●

Convulsions

●

Defective judgment

●

Extensor plantar responses

●

Lack of insight

Parenchymatous neurosyphilis

●

Depression or euphoria

This may present as general paralysis of the insane or tabes

●

Confusion and disorientation

dorsalis, or, rarely, as a combination of the two. General

●

Delusions

paralysis with resulting cerebral atrophy occurs 10-20 years

●

Seizures

after the original primary infection.

●

Transient paralysis and

Tabes dorsalis is characterised by increasing ataxia, failing

aphasia

vision, sphincter disturbances, and attacks of severe pain. These

pains are described as “lightning” because they occur as acute

stabbing pain mostly in the legs. The signs of tabes dorsalis are

largely caused by degeneration of the posterior columns: absent

ankle and knee reflexes (rarely biceps and triceps), impaired

vibration and position sense, and a positive Romberg’s sign.

Tabes dorsalis

Asymptomatic neurosyphilis

Symptoms

Signs

As the name implies, no neurological symptoms or signs are

●

Lightning pains

●

Argyll Robertson pupils

detected in asymptomatic neurosyphilis and the diagnosis is

●

Ataxia

●

Absent ankle reflexes

based entirely on changes in the cerebrospinal fluid and serum.

●

Bladder disturbance

●

Absent knee reflexes

●

Paraesthesiae

●

Absent biceps and triceps

●

Tabetic crises

reflexes

Cardiovascular syphilis

●

Visual loss

●

Romberg’s sign

●

Rectal incontinence

●

Impaired vibration sense

This most commonly occurs in large vessels, particularly the

●

Deafness

●

Impaired position sense

aorta, but medium and small sized vessels may also be affected.

●

Impotence

●

Impaired sense of touch and

The aorta is affected by an aortitis (with or without coronary

pain

●

Optic atrophy

ostial stenosis), aneurysm of the ascending part, and aortic

●

Ocular palsies

incompetence. The symptoms of an aneurysm affecting the

●

Charcot’s joints

arch usually result from the pressure on structures within the

ABC of Sexually Transmitted Infections

superior mediastinum. Thus, stridor and cough (trachea),

dysphagia (oesophagus), breathlessness (left bronchus),

hoarseness (left recurrent laryngeal nerve), and Horner’s

syndrome (sympathetic chain) may occur. Finally, pressure on

the superior vena cava can result in congested veins in the head

and neck as well as cyanosis. The signs of cardiovascular disease

are no different from those of aortic incompetence and

aneurysms from other causes.

Gummas

These are granulamatous lesions that develop 3-12 years after

the primary infection. Gummas may occur on the skin or

mucous membranes and in bone or viscera. Skin lesions are

usually nodular. They can occur anywhere on the skin and are

Cardiovascular

found as small groups of painless lesions that are indolent,

syphilis—

firm, coppery red, and about 0.5-1 cm in diameter.

aneurysm of the

ascending aorta

If subcutaneous tissue is affected, the lesions start as

and

smooth, hard swellings that eventually break down to well

cardiomegaly

circumscribed, punched out ulcers, which, when they heal,

leave typical tissue paper scarring. These often occur on the

leg, face, and scalp. Lesions in mucous membrane are punched

out ulcers on the hard and soft palate, uvula, tongue, larynx,

pharynx, and nasal septum. Bone and visceral gummas are

extremely rare, but affect the tibia, skull, clavicle, sternum,

femur, liver, brain, oesophagus, stomach, lung, and testes.

Diagnosis and management

Establishing a diagnosis of syphilis can sometimes be difficult,

and it is reasonable for all suspected cases to be referred to or

discussed with an STI specialist. The diagnosis can be confirmed

by history, physical examination, and one or all of dark ground

microscopy, serology, examination of cerebrospinal fluid, and

radiology. The application and interpretation of these

investigations depend on the clinical stage of the syphilis.

Gummas on the

lower limb

History and examination

Assessment of an individual suspected to have syphilis should

(in addition to the assessment outlined in Chapters 3 and 4)

Diagnostic criteria for syphilis

include a careful history of previous syphilis screening and

●

History

previous diagnosis of syphilis. If a diagnosis of syphilis has been

●

Physical examination

made in the past, then it is important to attempt to determine

●

Dark ground microscopy

the stage of disease, the treatment given, and the serological

●

Serology

●

Lumbar puncture

response to treatment, particularly the venereal disease

●

Chest radiography and screening

research laboratory (VDRL) or the rapid plasmin reagin (RPR)

titre (see below). History taking should also inquire about

possible symptoms of early and late syphilis.

An examination should focus on determining whether the

Dark ground microscopy

patient has any signs of early syphilis or the manifestations

This test can be used to establish the diagnosis from the lesions

of late complications, particularly neurological and

cardiovascular disease

of primary and secondary syphilis or occasionally from material

obtained by puncture of the inguinal nodes (especially if a

topical antiseptic or antibiotic has been applied or if lesions are

healed or concealed). The presence of oral commensal

treponemes makes microscopy unreliable for mouth lesions.

Three separate specimens from the lesion(s) should be

examined by dark ground microscopy initially and, if necessary,

on three consecutive days. This is done by cleaning the lesion

with a gauze swab soaked in normal saline and squeezing it to

encourage a serum exudate. The serum is then scraped off the

lesion and placed on the three slides.

Dark ground microscopy is a vital test in primary syphilis

because it may be the only means of establishing a positive

Dark ground microscopy of

diagnosis. Considerable experience is required to recognise

Treponema pallidum

Syphilis—clinical features, diagnosis, and management

Treponema pallidum. It is bluish white, closely coiled (8-24 coils),

Serological tests

and 6-20

m long. The treponeme has three characteristic

Non-specific

movements: watch spring, corkscrew, and angular.

●

Venereal Disease Reference Laboratory (VDRL)

●

Rapid Plasmin Reagin (RPR)

Serological tests

Specific

The serological tests used to diagnose syphilis are either non-

●

T pallidum EIA test

specific (non-trepomenal) or specific (trepomenal). Specific

●

Absorbed fluorescent treponemal antibody (FTA) test

tests for syphilis are useful for confirming the diagnosis

●

T pallidum haemagglutination (TPHA) test

particularly at first presentation; however, these tests usually

remain positive throughout a patient’s life, even after successful

treatment. Non-specific tests are useful to monitor the response

to treatment and for diagnosing reinfection of syphilis. However,

they may also give false positive tests in a variety of conditions.

Biological false positive reactions

The most widely used non-specific tests are either the VDRL

test or the RPR test. These tests depend on the appearance of

antibody (reagin) in the serum, and this usually occurs between

Acute

Chronic

three and five weeks after the patient has contracted the

infection. They are both quantitative tests and this can be useful

in assessing the stage and activity of the disease. Decreasing

After

Autoimmune

Infections

Leprosy

immunisation

disease

titres are associated with treatment response and increasing

titres are associated with treatment failure and reinfection.

However, VDRL and RPR titres also decay naturally without

Biological false positive reactions to serological tests

treatment, so untreated patients may have active disease despite

low titre or negative RPR and VDRL results.

Both tests may yield biological false positive reactions to

acute infections (such as herpes viruses, measles, and mumps)

or after immunisation against typhoid or yellow fever. Chronic

causes of biological false positive reactions include autoimmune

It is possible that all serological tests may be negative in

diseases and rheumatoid arthritis.

early primary infection. The TPHA test is the last of the

commonly used tests to become positive (between four and

Specific tests

eight weeks after infection). The positive syphilis serology

The specific tests include the more recently available T pallidum

can only be interpreted in the light of the history and

enzyme immunoassay (EIA) tests that are beginning to replace

clinical findings so is important to use a systematic approach

the fluorescent treponemal antibody test (FTA) and T pallidum

to both the screening and subsequent confirmatory tests

haemagglutination assay (TPHA) test as the specific tests of

before making a diagnosis

syphilis screening. The EIA tests have the advantage of

becoming positive early on in the course of infection and are

easier to automate. The FTA and EIA tests are usually the first

to become positive—between three and four weeks after

infection. These tests are positive in 85-90% of cases of primary

syphilis. In early syphilis these may be the only positive

Diagnosis and serological interpretation

serological tests.

Results positive

Diagnosis

Specific and non-specific tests are also positive in other

None

Syphilis not present or very early

trepomenal conditions that are similar to syphilis, such as yaws,

primary syphilis

bejel, and pinta. Bejel and pinta are unusual conditions;

All

Untreated, recently treated, or

however, yaws remains endemic in a number of countries

latent syphilis

around the world. Yaws is caused by the spirochaete T pertenue.

T pallidum EIA (or FTA) and

Primary syphilis

It is usually an infection acquired in childhood and is

VDRL

characterised by skin ulceration, usually of the lower limbs.

T pallidum EIA (or FTA) and

Treated syphilis or untreated late

TPHA

latent or late syphilis

Abnormalities of the cerebrospinal fluid may be found at

T pallidum EIA or FTA only

Early primary syphilis—untreated

any stage of syphilis and are common in early syphilis

or recently treated early syphilis

(particularly the secondary stage). Lumbar puncture is not

VDRL/RPR only

False positive reaction

routinely required in early syphilis or in asymptomatic late

syphilis; however, it is important that all patients with suspected

neurosyphilis have a full neurological examination and

cerebrospinal fluid (CSF) assessment. Some specialists also

recommend that all patients with HIV infection and syphilis for

more than two years should have a lumbar puncture to assess

possible neurological involvement (see below).

Most patients with neurosyphilis will have a cell count above

Cerebrospinal fluid and radiology

10⁶ lymphocytes/l and a protein level above 40 g/l. Provided

●

CSF investigations

●

Radiology

that the CSF is not contaminated with macroscopic blood, the

●

Cell count

●

Chest x ray (posteroanterior

trepomenal and non-trepomenal tests are useful to diagnose

and lateral)

neurosyphilis. Most patients with positive CSF RPR, or VDRL

●

Total protein

tests will have neurosyphilis, although people with probable

●

VDRL or RPR, TPHA, and FTA

neurosyphilis have negative non-specific tests. Although many

ABC of Sexually Transmitted Infections

Trepomenal antibody screening and confirmatory testing screening test—EIA (or TPHA and VDRL or RPR combination)

Reactive

Negative

Confirm with trepomenal test different from that used in screening (for example TPHA if

Report: Trepomenal antibody NOT detected

EIA screen). Perform quantitative non-trepomenal test (VDRL or RPR)*

but advise repeat if at risk of recent infection

Confirmatory test reactive

Confirmatory test

Confirmatory test negative

Non-trepomenal test reactive

reactive

Non-trepomenal test negative or reactive

Non-trepomenal

test negative

Consider Immunoglobulin M (IgM) EIA depending

Perform additional confirmatory test(s) or refer

on non-trepomenal test titre and clinical details

to reference laboratory for further testing

IgM EIA

Additional confirmatory

IgM reactive

IgM negative†

(Either) reactive

Both negative

EIA

Non-trepomenal

test negative

test reactive

IgM reactive

IgM negative

Report: Consistent

Report: Consistent with

Report: Consistent

Report: Consistent with

Report: Trepomenal

with recent or active

with trepomenal

trepomenal infection

with recent or active

trepomenal infection

antibody not detected

trepomenal infection

infection**

at some time

trepomenal infection

at some time

(false-positive

(biological false-positive

Advise repeat to confirm

screening test)

non-trepomenal test)

Testing up to a dilution of 1 in 16 will detect a prozone; reactive sera should be titrated to the endpoint.

†

In the absence of a history of adequate treatment, a negative result does not exclude the need for treatment.

** Add: “at some time” if VDRL titre less than one in 16.

Syphilis (treponemal) screening and interpretation algorithm, Public Health Laboratory Service, United Kingdom, 2000

individuals have positive FTA or TPHA in the CSF, negative

tests virtually rule out neurosyphilis.

The final diagnostic procedure in the assessment of a patient

with latent syphilis or suspected cardiovascular disease is chest

radiography (posterior and anterior and left lateral) to show the

arch of the aorta and to screen for aortic dilatation. If the

examination and investigations show aortic involvement then

more specialised tests and referral to cardiologists are usually

indicated.

Treatment and prognosis

The Jarisch-Herxheimer reaction is common in primary

and secondary syphilis and patients must be warned that

Penicillin remains the cornerstone of treatment for all types of

fever and flu like symptoms may occur 3-12 h after the first

syphilis. In primary and secondary syphilis, treatment can be

injection; occasionally the chancre or skin lesions enlarge

either given in a form of benzathine penicillin as a single

or become more widespread. Reassurance and antipyretics,

injection or 10 days of procaine penicillin. Patients with

such as paracetamol and non-steroid anti-inflammatory

penicillin allergy or patients who decline parenteral treatment

agents, are usually all that is required

can be prescribed doxycycline therapy.

Some specialists recommend that steroids should be used at

the start of treatment for late syphilis because of a potential risk

that focal oedema and swelling may lead to cerebral or

coronary artery occlusion.

The prognosis of treated syphilis depends on the stage of the

disease and the degree of tissue damage in cardiovascular and

neurological syphilis. Adequate treatment of primary, secondary

and latent syphilis will always halt the progression of the disease.

The prognosis in symptomatic neurosyphilis is variable.

Although, in general, the inflammatory process is arrested by

adequate treatment, tissue damage may be too great to prevent

an improvement in symptoms. In cardiovascular disease, the

Syphilis—clinical features, diagnosis, and management

onset of symptoms usually indicates established aortic medial

Serological tests in HIV positive patients are usually reliable

necrosis that is not reversed by treatment.

in syphilis and most specialists treat patients with syphilis

For a patient with early infectious syphilis, contact tracing

with the same regimens that are recommended for

must be carried out on all sexual contacts in the previous three

individuals who are HIV negative. However, some specialists

to six months. In late syphilis when a patient is no longer

remain concerned that early neurological involvement of

infectious, serological testing is probably only practicable in the

syphilis in HIV positive individuals is a considerable

patient’s regular partner(s). If late syphilis is diagnosed in a

problem and, therefore, recommend neurological

mother it may be necessary to test her children (see Chapter 9).

evaluation, lumbar puncture, and syphilis treatment

regimens that adequately treat neurosyphilis for all HIV

HIV infection and syphilis

positive individuals with active syphilis

Although more rapid progression to late stage syphilis has been

reported when associated with HIV infection, most HIV positive

individuals who have syphilis present with symptoms and signs

identical to those individuals who are HIV negative. However, all

patients who have syphilis should be offered HIV testing and all

HIV positive individuals should be screened for syphilis.

Treatment of syphilis

Stage

Standard treatment

Alternatives

Primary and secondary

Benzathine penicillin 2.4 megaunits

Doxycycline 100 mg orally twice a day for

intramuscularly as a single dose or aqueous

14 days

procaine penicillin 600 000 units

intramuscularly per day for 10 days

Latent early (less than two years)

Benzathine penicillin 2.4 megaunits

Doxycycline 100 mg orally twice a day for

intramuscularly as a single dose or aqueous

14 days

procaine penicillin 600 000 units per day for

10 days intramuscularly

Latent late (more than two years)

Aqueous procaine penicillin 900 000

Doxycycline 100 mg orally twice a day for

units intramuscularly per day for 17 days or

30 days

benzathine penicillin 2.4 megaunits

intramuscularly weekly over two weeks (three

injections)

Neurosyphilis

Aqueous procaine penicillin 2.4 megaunits

Doxycycline 200 mg orally twice daily for

intramuscularly per day for 17 days (with or

30 days

without oral prednisolone 20 mg per

day starting the day before

penicillin treatment and continuing

at the same dose for two days after)

and oral probenecid 500 mg four times daily

Cardiovascular syphilis

Aqueous procaine penicillin 600 000 units

Doxycycline 100 mg orally twice daily for

intramuscularly per day for 17 days (with or

30 days

without oral prednisolone 20 mg per

day—dosing as above)

Gummatous syphilis

Aqueous procaine penicillin 600 000

Doxycycline 100 mg orally twice daily for

units intramuscularly per day for 17 days

30 days

Overview of syphilis

Cause

Neurosyphilis

●

T pallidum, a spirochaete bacterium

●

“General paralysis of the insane”—10-20 years after primary

infection

Initial site of infection

●

Takes dorsalis (dorsal column impairment)—10-20 years after

●

Site of exposure, usually genitals, perianal area, or mouth

primary infection

Incubation period

●

Usually two to three weeks (range 9-90 days) to primary syphilis

Meningovascular syphilis

●

Early (a part of secondary syphilis)

Primary syphilis

●

Late (2-20 years)

●

Ulceration at site of exposure (incubation as above)

Cardiovascular syphilis

Secondary syphilis

●

Aortic regurgitation, angina, and aortic aneurysm

●

Systemic illness two to three months (range one to six months)

●

Clinical history and examination 10-40 years after primary

after primary syphilis)

infection

Early latent syphilis

Diagnosis

●

Asymptomatic syphilis of less than two years’ duration

●

Identification of T pallidum in early syphilis

Late latent syphilis

●

Serology (specific or non-specific)

●

Asymptomatic syphilis of more than two years’ duration

●

Identification of complications of late syphilis

Gummata

Treatment

●

Necrotic nodules or plaques—3-12 years after primary infection

●

Parenteral penicillin (see text)

●

Alternative—doxycycline

Genital growths

Michael Adler

Genital warts

Even though genital warts (condyloma acuminatum) are

commonly seen in departments of genitourinary medicine

(GUM) (about 131 000 new and recurrent cases a year in the

United Kingdom), many more cases are diagnosed and treated

by general practitioners, surgeons, gynaecologists, and

dermatologists. Not only are warts common, but they also are

difficult and time consuming to treat, and certain types are

associated with cervical dysplasia.

Genital warts are caused by a small DNA virus, a

papillomavirus belonging to the papovavirus group that cannot

be cultured. They differ from skin warts histologically and

antigenically and are most commonly caused by human

papillomavirus (HPV) types 6 or 11 (types 16, 18, 31, 33, and 35

Papillomavirus

also cause genital warts). Genital warts nearly always are

transmitted by sexual contact; autoinoculation from hand to

genitals is unusual. Infants and young children may develop

laryngeal papillomas as a result of infection from maternal

genital warts at delivery. The incubation period is long, varying

from two weeks to eight months (mean incubation period is

three months).

Clinical features

Genital warts are often asymptomatic and painless. Patients may

give a history of suddenly noticing them or noticing them only

once their sexual contact has acquired them. Women are more

likely to be unaware of warts because it is harder for them to

examine their genitalia. Warts flourish in warm, moist

conditions, particularly if discharge or other infections are

present.

Warts may be solitary but are usually multiple by the time

the patient attends for consultation. In men they may be found

on the glans and shaft of the penis, prepuce, fraenum and

coronal sulcus, urethral meatus, scrotum, anus, and rectum. In

women the most common site of infection is the introitus and

vulva, but warts may also affect the vagina and (as flat warts)

the cervix. Other infected sites are the perineum, anus, and

rectum.

Penile warts

Intrameatal wart

Vulval (left) and perianal (right) warts

Genital growths

Diagnosis

Genital warts are one of the few sexually transmitted conditions

Differential diagnosis of genital warts

that are diagnosed solely from their clinical features. Diagnosis

●

Condylomata lata

is not usually difficult but the differential diagnosis of

●

Molluscum contagiosum

condylomata lata of secondary syphilis, molluscum

●

Sebaceous cysts

contagiosum, sebaceous cysts, and benign and malignant

●

Tumours

tumours should be remembered. Warts often may herald other

sexually transmitted infections. For example, one third of

women who attend GUM departments with genital warts have

one or more additional diseases diagnosed concurrently.

All women with genital warts, even in the absence of any

other symptoms, must have a full set of microbiological tests to

Contact tracing and examination of regular sexual partners

exclude infection with Candida albicans, Trichomonas vaginalis,

must be undertaken as well as full microbiological

Neisseria gonorrhoeae, Chlamydia trachomatis, and bacterial

investigations for other sexually transmitted infections.

vaginosis. Heterosexual and homosexual men with penile warts

Condom usage is recommended to reduce the level of

should have urethral tests for gonorrhoea, C trachomatis and

infection among heterosexual partners

non-gonococcal urethritis even if they are asymptomatic.

Likewise, homosexual men with anal warts should have

proctoscopy to exclude the presence of additional warts in the

rectum as well as other rectal diseases such as gonorrhoea.

Finally, serological tests for syphilis should be carried out in

both men and women.

Complications

Complications of genital warts are rare. Occasionally they may

increase alarmingly in size during pregnancy and present as

large cauliflower like masses (see Chapter 9). In men, similar

giant, benign but destructive warts (Buschke-Löwenstein

tumour) may occur on the penis, or existing small ones may

rapidly become enlarged. Malignant transformation of vulval,

cervical, penile, and anal warts has been reported.

Flat warts on the cervix are not usually apparent to the

naked eye. Cervical dysplasia is strongly associated with HPV

types 16, 18, 31, 33, and 35, particularly types 16 and 18.

Therefore, all women who have had genital warts should have

regular cytology by following national guidelines. No changes

in screening intervals are required.

Massive warts in

Treatment

pregnancy

Initial treatment is usually with locally applied caustic agents. It

is usual to start with podophyllin (a cytotoxic agent), which

should be applied to the lesions in strengths of 10% or 15% in

industrial spirit and repeated once or even twice a week. As it is

an irritating substance it can cause bad burns. Therefore,

patients must be told to wash it off between three and four

hours after application. Patients may often want to apply

podophyllin themselves, but this is undesirable because they

Overview of genital wart infection

may be overzealous in their justifiable desire to get rid of their

Cause

warts and apply the substance too often, without washing it off,

●

Papillomavirus, particularly types 6 and 11 (also 16, 18, 31, 33,

on the basis that “if it hurts it must be doing me good.” Severe

and 35)

systemic effects of peripheral neuropathy, coma, and

Site of infection

hypokalaemia can occur after application of large quantities.

●

Site of exposure—that is the penis, urethral meatus, scrotum,

Podophyllotoxin (0.5%) has less severe side effects and can

anus, rectum, vulva, vagina, and cervix

be used by the patient at home. The patient is told to administer

Complications

●

Rare. Increased size during pregnancy, and associated cervical

it twice a day for three days and to repeat the application four

dysplasia (particularly type 16 and 18)

days later if necessary. Up to four cycles can be administered.

Incubation

If podophyllin is ineffective after regular application for two

●

Two weeks to 18 months (average three months)

or three weeks, the more caustic agent glacial trichloroacetic

Diagnosis

acid (80-90%) may be used, again with great caution. This agent

●

Clinical features

is more often used for hyperkeratotic warts but, even so, these

Treatment

warts are often resistant and electrocautery or cryotherapy

●

Ablation

(cryoprobe or cryac spray) will be needed. This can be applied

ABC of Sexually Transmitted Infections

weekly. Trichloroacetic acid is very corrosive, so it must be

applied with care, protecting the surrounding skin with

petroleum jelly. Cautery or surgical excision should be

considered at an earlier stage if the warts are particularly large

or numerous.

Other treatments can be used, such as fluorouracil,

interferons, and imiquimod. Fluorouracil is a DNA

antimetabolite that is made up as a 5% cream. It probably has a

limited use because of severe local side effects, such as vulval

burning and neovascularisation. It has been used for

intrameatal and intravaginal warts in conjunction with laser

therapy. Interferons have been used; however, they are

expensive, with systemic side effects, and the response rate is

not superior to other therapies. Finally, imiquimod, an immune

response modifier, can be used as a 5% cream and is most often

used for external genital warts by inducing a cytokine response.

It is applied to the lesions three times per week and washed off

by the patient about 6-10 hours after application. The

Cryac spray

application can continued for up to 16 weeks as the response to

treatment can be delayed for some weeks.

Approaches to the treatment of genital warts

Site or type of warts

Start

One week

Two weeks

Three weeks

Four weeks

Few, small, and soft

10-25% podophyllin or

→

Trichloroacetic

Cryotherapy,

podophyllotoxin solution or

acid

electrocautery

cryotherapy

Solitary, large, and

Electocautery diathermy,

discrete

excision, and cryotherapy

Extensive, multiple

10-25% podophyllin,

→

Cryotherapy,

vegetations

podophyllotoxin solution, or

surgical excision

trichloroacetic acid

Hyperkeratotic or

Trichloroacetic acid or

→

Electrocautery,

keratinised

cryotherapy

diathermy

Intrameatal

Cryotherapy

→

Electrocautery,

cryotherapy

Cervical

Colposcopy biopsy

?→cryotherapy, laser

Vaginal

Cryotherapy or trichloroacetic

acid

Perianal

Cryotherapy or podophyllotoxin

cream

Pregnancy

None—unless discrete small

Note: do not use

vaginal, vulval, or introital,

podophyllotoxin,

then use trichloroacetic

podophyllin,

acid or cryotherapy—?

fluorouracil, or

electrocautery

imiquimod

During pregnancy it is best to offer on treatment (see

Chapter 9). Podophyllin is contraindicated because of its

toxicity and possible mutagenic action. Warts usually diminish

in size once pregnancy has ended. Trichloroacetic acid may be

used if the lesions are discrete, small, and occur on the vaginal

wall or vulva. Alternatively, cryotherapy or electrocautery may

be offered. In addition, fluorouracil and imiquimod should not

be used during pregnancy. Occasionally, caesarean section is

necessary if the warts are likely to obstruct labour. Laryngeal

Treatment of warts outside GUM

and anogenital papilloma can occur in neonates, infants, and

departments

children, possibly transmitted transplacentally, perinatally, or

●

Sexual history

postnatally. Whether these are prevented by treating the

●

Exclude a concurrent sexually transmitted

mother during pregnancy is not known, and it is certainly not

infection

an indication on its own for caesarean section.

●

Trace regular sexual contacts

Doctors who treat genital warts outside GUM departments

or sexually transmitted infections clinics should remember,

firstly, that an accurate and detailed sexual history is needed;

Genital growths

secondly, that concurrent sexually acquired conditions should

be excluded; and, thirdly, that contact tracing must be

carried out.

Molluscum contagiosum

Molluscum contagiosum may be transmitted sexually but this is

not the only route. It is a contagious viral condition that may be

spread by close bodily contact, clothing, or towels. Transmission

(outbreaks) is possible in swimming pools, sauna baths, schools,

after massage, and between siblings. The agent that causes

molluscum contagiosum is one of the pox viruses and has a

variable incubation period of 2-12 weeks. Cases are seen in

clinics but far more are likely to be seen by general

practitioners and dermatologists. The immunocompromised

patient with HIV may exhibit lesions, particularly on the face.

The clinical lesions of molluscum contagiosum are

characteristic. The pearly white, umbilicated papules are found

in the genital area (penis, scrotum, vulva, perineum, abdomen,

and thighs), but if transmission is non-sexual they may also be

found in any part of the body but particularly on the arms,

face, eyelids, and scalp. The lesions are usually small (2-5 mm

in diameter).

Molluscum

contagiosum

Diagnosis is usually based on clinical appearance because

the virus cannot be grown successfully. Material expressed from

the centre of lesions shows viral inclusions in Giemsa stain or

on electron microscopy. As the condition may be sexually

transmitted, other sexually transmitted infections should be

Further reading

excluded if the patient’s history or the site of the lesions

●

National Guidelines for the Management of Anogenital Warts

(proximity to genital area) indicates that this could be the

www.agum.org.uk (accessed 27 Nov 2003)

●

Clinical Effectiveness Group (Association of Genitourinary

route of infection.

Medicine and the Medical Society for the Study of Venereal

Treatment is by applying phenol on the end of a sharpened

Diseases). National guidelines for the management of

stick to the central umbilicated core of the lesions. This may

anogenital warts and sexually transmitted infections. Sex Transm

need to be repeated several times. Alternatively, electrocautery

Infect 1999;75:S71-75

or cryotherapy may be used.

Genital infestations

Michael Adler

Pediculosis pubis

This infestation is caused by the pubic louse, Phthirus pubis,

which is a different species from the one that causes head and

body louse infestation (pediculosis capitis and pediculosis

corporis). The insect is small and round (1-2 mm long) and has

three sets of legs. The adult is a blood sucker and adheres not

only to pubic hair but also to other hairy areas (perineum,

thighs, abdomen, axillas, eyebrows, and eyelashes). The female

lays eggs (nits) at the base of the hairs and these usually hatch

within seven days. The adult louse is transferred from person to

person during close bodily contact. As lice do not leave the

host, the infestation is not spread by wearing infested clothing

or sleeping in infested sheets. The patient may complain of

irritation. Sometimes the condition is asymptomatic and the

patient may be horrified to find the adult louse or nits on

their body.

P pubis

Diagnosis is usually based on clinical appearances alone.

A hand lens is useful during the examination and a suspected

louse or eggs (nits) on a hair may be removed and viewed

under a low power microscope. Bluish grey macules

occasionally occur on the abdomen, buttocks, or thighs at the

site of the bites. As the condition is usually acquired sexually, a

full sexual history should be taken and the patient examined

for other sexually transmitted infections.

Pediculosis pupis is treated by applying malathion (0.5%),

permethrin (1% cream rinse), phenothrin (0.2%), or carbaryl

0.5% Malathion

(0.5-1%) to all hairy areas except the scalp but including the

0 hours

beard and moustache. The patient should not wash this off for

24 hours, after which a bath should be taken. Usually one

0.5% Carbaryl, 1% permethrin, and 0.2% phenothrin

application is enough, but a heavy infestation will necessitate

further treatment within 7-10 days. Sexual partners should also

24 hours

Bath

be seen and treated. Shaving body hair is not necessary.

Sexual and family contacts seen and treated

Seven days

Repeat treatment if necessary

Scabies

A scabies infestation is caused by the mite Sarcoptes scabiei. The

Management of pediculosis pubis

clinical features of scabies are caused by the female burrowing

in the uppermost layer of the skin (stratum corneum), laying

eggs and defecating. The disease and associated symptoms are

largely caused by an allergy to intestinal enzymes. The female is

about twice the size (0.3 mm long) of the male and can just be

seen by the naked eye as a black dot (mouth parts) at the distal

part of the burrow. Infestation usually occurs as a result of close

physical, but not necessarily sexual, contact. Close contact

needs to be reasonably prolonged because the insect moves

slowly (at 25 mm/minute). Outbreaks of non-sexually acquired

scabies may occur among schoolchildren and within whole

households or long stay hospitals. Outbreaks are also common

in impoverished communities in the tropics.

Symptoms are first noticed between two and six weeks after

infestation. Reinfection may give rise to symptoms within a few

hours. The patient complains of itching, which is often

unbearable, intractable, and worse at night, when the body is

warm. The sites of itching and burrows bear no relation to the

mode of transmission. Thus, lesions may often be found in the

clefts of fingers and on the wrists and elbows as well as on the

genitals. On examination, the burrows may be the typical

sinuous, scaling, reddish grey lesions (5-15 mm long),

S scabiei

History and examination

Burrow

sometimes with small vesicles at their end. However, scratching

Finger cleft

may alter their appearance by producing excoriation, ulceration,

crusting, and bleeding. The lesions on the penis and scrotum

may resemble red papules. Associated rashes are sometimes

found in sites distant from the actual burrows, in particular

erythematous urticarial papules in the armpits, abdominal wall,

and the anterior and posterior aspects of the upper thighs.

In some cases, indurated nodules, eczematous changes, and

secondary infection with pustule formation may occur.

Diagnosis is based on the clinical history and examination

and may be confirmed by finding the mite, eggs, or scybala.

This is achieved by scraping the top off the whole length of a

burrow (from distal to proximal end) with a scalpel, putting the

material on a slide with 10% potassium hydroxide solution, and

looking for the mite under the microscope. As with pediculosis

pubis, if the history implies sexual transmission then other

sexually transmitted infections must be excluded.

Scabies is treated by applying malathion (0.5%) or

permethrin (5%) to the whole body and washing it off after

12 hours. Patients should be told that the initial itching may

persist for several weeks despite successful treatment with either

preparation. Unless this explanation is given, patients may

equate the symptoms with continuing infection, re-treat

themselves, and run the risk of chemical dermatitis. Sexual

Areas affected by scabies infestation

contacts should be seen if sexual transmission is suspected. If

the condition was not acquired by this route, other members of

the family or school friends will need to be treated. When

contacts are seen they may be asymptomatic, but they should be

treated because they may be incubating the disease. No special

treatment of clothing or bed linen is necessary.

Viral hepatitis

Richard Gilson

Most cases of acute hepatitis present with jaundice associated

with some gastrointestinal and systemic symptoms of recent

onset and are caused by one of the hepatitis viruses A to E.

The clinical features associated with each infection do not

distinguish them, but the history will often give a clue to the

Hepatitis B and hepatitis C virus infections are often

aetiology, particularly in relation to sexual or parenteral

diagnosed at the stage of chronic infection

exposure. Other cases are identified incidentally because of

abnormal liver function tests, which may also lead to the

diagnosis of chronic viral hepatitis. Hepatitis B and hepatitis C

virus infections are often diagnosed at the stage of chronic

infection. Some patients only present having developed the late

sequelae of chronic viral hepatitis, such as cirrhosis or

hepatocellular carcinoma.

Comparison of hepatitis virus infections A-E

Hepatitis type

Incubation period

Transmission routes

Carrier state

Two to six weeks

Faecal-oral

None

8-12 weeks, but up to 24 weeks

Parenteral, perinatal, or sexual

5% adults, 90% infants

(homosexual and heterosexual)

Four to eight weeks but up to

Parenteral (particularly

60-70%

24 weeks

blood or blood products, if not

screened, and injecting drug

use) and sexual and perinatal

(lower risk)

Six to eight weeks

Parenteral (coinfection with acute

About 2% if acute coinfection,

hepatitis B or superinfection of

70-80% if superinfection

hepatitis B carrier)

Two to six weeks

Faecal-oral

None

Causes and epidemiology

Hepatitis A is caused by a small RNA virus that is excreted in

the stools for up to two weeks before the onset of symptoms.

Hence, transmission is by faecal-oral spread, usually through

contaminated food or water in endemic areas. Person to person

transmission occurs within households, which may, therefore,

include sexual partners. Transmission during sexual contact

can occur and has been associated with oral-anal contact.

Outbreaks in homosexual men have been reported, but

prevalence studies show that sexual transmission contributes

little to the risk of hepatitis A in homosexual men. In

developing countries, childhood infection remains very

common, but in developed countries, the rates of infection

have declined so that an increasing proportion of adults are

susceptible; for example, only about 20-25% of young adults in

London are immune.

Hepatitis B is caused by a small DNA virus that is

detectable in serum for several weeks before the onset of acute

illness. At the same time a large excess of hepatitis B surface

antigen is produced in infected liver cells, which is released in

the bloodstream as small spherical or filamentous particles.

Patients who fail to clear the infection after six months are

persistent virus carriers, some of whom maintain high levels of

viraemia and consequently are infectious. Chronic carriers

represent the main pool of infectious individuals. In low

Electron micrograph of hepatitis B virus particles in serum showing small

spheres and filaments comprising hepatitis B surface antigen. Large

prevalence regions, including northern Europe, Scandinavia,

spherical structures are virus particles that contain hepatitis B core protein

and North America, the prevalence of hepatitis B virus (HBV)

and viral DNA. With permission of the Division of Viral Hepatitis at the

carriers is less than 1% (0.1% in the United Kingdom), and

Centers for Disease Control and Prevention

Viral hepatitis

most infections occur in adults due to sexual or parenteral

Groups at risk of infection with hepatitis B

transmission. Those at greatest risk are homosexual men who

Endemic areas

practice unprotected anal intercourse and injecting drug users

●

Whole population (peak incidence in neonates, early childhood,

who share any of their injecting equipment. Up to 5% of

and adolescence)

homosexual men and injecting drug users who attend sexually

Areas of low endemicity (for example, United Kingdom)

transmitted infection (STI) clinics in the United Kingdom are

●

Babies born to hepatitis B carrier mothers

carriers and 25-50% are immune because of a previous

●

Homosexual men

infection. In many parts of the world, the carrier rate in the

●

Injecting drug users

general population is much higher, up to 20%, and the highest

●

Prostitutes

●

Sexual contacts of acute cases and carriers

incidences are found in the perinatal period (because of

●

Household contacts of acute cases and hepatitis Be antigen

mother to baby transmission), early childhood, and later in

positive carriers

adolescence with the start of sexual activity.

●

Laboratory and medical staff exposed to blood or blood

Hepatitis D is caused by a defective RNA virus that needs

products

concurrent infection with hepatitis B virus for the virus to

●

Staff and inmates of closed institutions

replicate productively. Simultaneous acute infection usually

resolves. Superinfection in a hepatitis B carrier causes an

exacerbation of any pre-existing chronic hepatitis, which can be

severe and leads to persistent dual infection. Hepatitis D is

parenterally and sexually transmitted, but injecting drug users

are at greater risk than, for example, homosexual men.

The hepatitis C virus was identified in 1989 and is the cause

Hepatitis D is rare in the United Kingdom but has been

reported in up to 14% of carriers of hepatitis B virus in

of over 90% of cases of non-A, non-B hepatitis. Historically, the

southern Europe

greatest risk of infection with hepatitis C was exposure to

untested or untreated blood or blood products and sharing of

any injecting equipment by injecting drug users. Since the

introduction of blood donor screening (September 1991 in the

United Kingdom), infections related to blood or blood

products have been almost eliminated. The reuse of needles

and other medical equipment is an important source of

infection in some countries. Up to 10-20% of patients have no

history of parenteral exposure, indicating transmission by

person to person or sexual contact. Studies of sexual partners

(homosexual and heterosexual) of patients with hepatitis C

In studies of homosexual men, the prevalence of

found a low prevalence of infection. These data are consistent

hepatitis C, typically about 1%, is much lower than that

with a low rate of transmission of hepatitis C by sexual contact.

of hepatitis B or HIV, although this may still be higher

Vertical transmission occurs at a low rate, about 5%.

than in heterosexual controls

Hepatitis E, caused by a small RNA virus, is the principal

cause of the enterically transmitted form of non-A, non-B

hepatitis. Spread by the faecal-oral route, the hepatitis E virus

causes sporadic cases and waterborne epidemics in the Indian

subcontinent, South East and Central Asia, Africa, and North

America. In Europe, cases are only likely to be seen in

travellers who return from these regions. Like hepatitis A, no

carrier state exists, and sexual transmission has not been

implicated.

TT virus (named after the patient from whom it was

Other causes of viral hepatitis are more speculative, and

isolated) is another infection linked to blood or blood

none are believed to be important causes of sexually acquired

product exposure. Other viral infections that can be sexually

hepatitis. Hepatitis F has yet to be characterised. The hepatitis

acquired and may cause hepatitis include cytomegalovirus

and Epstein-Barr virus

G virus was believed to be another cause of non-A, non-B

hepatitis. Structurally related to hepatitis C, it is transmitted in

blood or blood products and is often found in association with

hepatitis C. However, it now seems that hepatitis G rarely, if

ever, causes liver disease.

Clinical evaluation

The clinical illness associated with acute hepatitis begins

Most cases of acute hepatitis diagnosed in primary care and in

with non-specific symptoms, such as fever, headache, and

STI clinics are caused by infection with either hepatitis A or B.

fatigue, followed by jaundice. More than half of all acute

A history of travel, injecting drug use, tattoos, recent transfusion,

infections are subclinical

or other percutaneous exposure may provide clues to the

diagnosis. However, it is also important to ask about sexual

orientation and household or sexual contacts and whether they

have had symptoms of hepatitis. Hepatotoxins such as alcohol

and drugs should be excluded as a cause of liver disease. No

major differences are seen in the clinical features of the acute

ABC of Sexually Transmitted Infections

illness caused by any of the hepatitis viruses. In addition, chronic

hepatitis B or C cannot be distinguished clinically. Occasionally,

extrahepatic manifestations, such as cryoglobulinaemia

Symptoms

associated with hepatitis C, may be present. Symptoms and signs

of other concurrent STIs should be looked for.

Diagnostic tests

Faecal

HAV

Virological diagnosis relies on serological tests. Routine liver

Total anti-HAV

function tests help to distinguish between hepatitis and

Anti-HAV-IgM

cholestasis caused by extrahepatic or intrahepatic lesions, but

ALT

prolonged cholestasis occurs occasionally with acute viral

hepatitis. Tests of synthetic function, such as prothrombin time

and serum albumin, are useful to assess the severity of both

Exposure (months)

acute and chronic hepatitis.

A patient who has had hepatitis A at any time in the past

Hepatitis A: typical serological course. HAV hepatitis A virus;

will have antibodies that can be detected by a test for total

IgM immunoglobulin M; ALT alanine aminotransferase

anti-hepatitis A virus (HAV). A patient with acute hepatitis A

will also have antibodies that are picked up by a class-specific

test for anti-HAV immunoglobulin M (IgM) antibodies. These

remain detectable for three to four months after the acute

episode.

Acute hepatitis B can be diagnosed by the presence of IgM

antibodies to the hepatitis B core (anti-HBc IgM). Hepatitis B

surface antigen (HBsAg) is detectable during the acute illness,

Total anti-HBc

HBsAg

often before any antibody response or rise in transaminase has

IgM anti-HBc

anti-HBs

occurred. Patients with acute hepatitis B who resolve their

infection usually clear HBsAg from their serum within a few

Symptoms

weeks. Occasionally, detectable HBsAg is lost even before the

HBeAg

anti-HBe

patient becomes symptomatic. In these cases, the diagnosis is

made by tracing the evolution of the anti-HBc IgM response

and the appearance of antibodies to HBsAg (anti-HBs). After

the clearance of detectable serum HBsAg, a delay of a few

weeks or months may occur before anti-HBs can be detected,

which is the best marker of immunity to the hepatitis B virus.

By definition, patients who remain HBsAg positive after six

months are persistent virus carriers. One additional serological

marker is the hepatitis Be antigen (HBeAg), which is a soluble,

truncated form of the core protein and the corresponding

100

antibody (anti-HBe). HBeAg can be detected during acute

Exposure (weeks)

infection but disappears quickly in those individuals who do

not become carriers. The detection of HBeAg is associated

Hepatitis B: typical serological course of resolving acute infection.

HBc hepatitis B core. HBsAg hepatitis B surface antigen.

with other measures of virus replication such as hepatitis B

Anti-HBs antibody to hepatitis B surface antigen. IgM immunoglobulin M.

virus DNA in the blood. Carriers who are HBeAg positive are

HBeAg hepatitis Be antigen. HBe hepatitis Be

much more likely to transmit infection during sexual contact

or from mother to baby at birth. They are also more likely to

experience progression of chronic liver disease.

Hepatitis B serology: interpretation of common patterns of results

HBsAg

Anti-HBs

Anti-HBc

Anti-HBc-IgM

HBeAg

Anti-HBe

Never infected

Immune after a

course of vaccine

Immune after a

natural infection

Acute infection

Early or pre-

symptomatic

Late or symptomatic

Chronic infection

High infectivity

Low infectivity

HBsAg hepatitis B surface antigen; Anti-HBs antibody to hepatitis B surface antigen; anti-HBc antibody to hepatitis B core;

IgM immunoglobulin M; HBeAg hepatitis Be antigen; anti-HBe antibody to hepatitis Be antigen

Viral hepatitis

Screening for hepatitis C is done with an antibody test. The

sensitivity and specificity of current assays is much higher than

the first generation of tests developed in the early 1990s. The

early tests relied on a single recombinant protein from a

non-structural region of the virus. Current assays incorporate

additional peptides from the nucleocapsid and envelope regions.

With these tests, acute hepatitis C can be diagnosed at the time

of presentation, although the antibody response may be delayed

Acute phase

Chronic phase

for up to four weeks and diagnosis of an acute infection then

(6 months)

(years)

relies on detecting the hepatitis C virus genome with a

HBeAg

anti-HBe

polymerase chain reaction or signal amplification assay. These

assays are also used in patients with detectable antibodies to

determine whether they have persistent viraemia. The presence

of antibodies alone does not distinguish individuals who are

currently infected from those who may have cleared their

hepatitis C virus (HCV) infection, although this only occurs in

Total anti-HBc

30-40% of infected individuals. Finally, assays for HCV RNA can

IgM anti-HBc

be used as quantitative measures of viral load for monitoring

HBsAg

treatment. Tests for the hepatitis C virus genotype are available

and are used when considering treatment for chronic hepatitis

16 20 24

C, genotype being the strongest predictor of response.

Exposure (weeks)

(years)

Hepatitis D and E are diagnosed by antibody assays. Hepatitis

D can be diagnosed only in a patient with serological markers of

Hepatitis B: typical serological course of chronic infection. HBc hepatitis

B core; IgM immunoglobulin M; HBsAg hepatitis B surface antigen;

hepatitis B. Immunoglobulin M antibody tests help to distinguish

HBe hepatitis Be; HBeAg hepatitis Be antigen

between acute and chronic infections. In patients with hepatitis

that may have been acquired sexually, screening for other STIs

including HIV and syphilis should always be considered.

Natural course of viral hepatitis

Most cases of hepatitis A are asymptomatic, but the risk of

severe disease, including fulminant hepatic failure, increases

with age and in those with concurrent chronic liver disease. No

carrier state exists for hepatitis A and immunity is lifelong. As

the incidence of hepatitis A in childhood falls, a higher

proportion of cases will occur in adults and, therefore, be

symptomatic.

Up to 90% of neonates infected with hepatitis B become

Some patients with anti-HBe carry viruses

chronic carriers, the proportion falling rapidly with age up to

with mutations in the hepatitis B pre-core

five years. Thereafter, about 5% of patients with acute hepatitis B

or core promoter gene sequence. These

become carriers, but fewer if the acute infection is symptomatic.

patients are more likely to have detectable

Fulminant hepatitis occurs in less than 1% of cases and never

viraemia and have an intermediate risk of

leads to chronic infection. Initially, chronic carriers have high

progression to end stage liver disease

amounts of viral replication, with HBeAg detectable in the

serum. The rate of viral replication falls with time, and most

patients will seroconvert spontaneously from HBeAg positive to

anti-HBe positive. This occurs at a rate of about 10% per year of

follow up. Chronic hepatitis B carriers with anti-HBe typically

have little inflammatory liver disease and their risk of developing

more severe disease is low. Those in whom HBeAg to anti-HBe

seroconversion is delayed are more likely to progress to cirrhosis

and end stage liver disease. Cirrhosis also is associated with an

increased risk of primary hepatocellular carcinoma.

The clinical course of chronic hepatitis C is similar to

Acute infection with hepatitis C virus is

that of chronic hepatitis B. The proportion of individuals who

rarely symptomatic (10%), but it becomes

develop clinically important liver disease is uncertain

chronic in about 60-70% of cases; the exact

(estimated to be 10-30%), but it rarely occurs within 10 years of

proportion is uncertain and may depend

infection. The average time to the development of cirrhosis is

on the route of transmission

30-40 years. Those who do not develop chronic infection may

lose detectable antibodies.

HIV coinfection

Concomitant infection with hepatitis B or hepatitis C and HIV

is common. Interactions between hepatitis B and HIV include

an increase in the proportion of those infected people who

ABC of Sexually Transmitted Infections

become HBV carriers to about 20%, higher HBV replication,

Interactions between infection with HIV and hepatitis B

and a reduction in the rate of spontaneous HBeAg to anti-HBe

virus

seroconversion. Infection with HIV may also lead to reactivation

●

Incidence of fulminant hepatitis—possibly decreased

of HBV infection. The effect on the epidemiology of HBV

●

Incidence of carrier state after infection—increased

infection is to increase the pool of infectious carriers. Although

●

Infectivity of HBV carriers—increased

the activity of HBV associated inflammatory liver disease may be

●

Hepatic inflammatory activity—decreased in early disease

reduced in the early stages of HIV coinfection, cases of rapidly

●

Response rate to vaccine—decreased

progressive liver disease are seen; in cohort studies, mortality is

●

Loss of natural and vaccine induced immunity—increased

still determined largely by other HIV related complications.

●

Response to antiviral treatment—decreased (but some

antiretroviral agents also have anti-HBV activity)

HIV coinfection can accelerate the progression of

●

Risk of cirrhosis and hepatocellular carcinoma—possibly

HCV related chronic liver disease, as well as increasing the HCV

increased

viral load. It increases the risk of mother to child transmission

and may also increase the risk of sexual transmission.

Management

Acute viral hepatitis is usually self limiting and management is

largely supportive. Most patients can be managed in the

community, but acute liver failure and its complications

demand urgent hospital admission. In uncomplicated cases,

a low fat, high energy diet is more palatable and bed rest

advisable during the early phase of the illness. Usual advice is to

Indications for admission to hospital with

avoid alcohol until the liver function tests are normal.

acute hepatitis

The prospects for treatment for both chronic hepatitis B

Complications

and C have improved. Treatment of hepatitis B with interferon

●

Symptoms and signs of acute liver failure

for four to six months results in 20-40% loss of HBeAg,

(signs of hepatic encephalopathy)

depending upon the pre-treatment characteristics. Predictors of

Doubts about the diagnosis

response include a lower serum HBV DNA concentration,

●

Possible extrahepatic cause for jaundice

higher transaminase activity, and more inflammatory disease on

Social factors

liver biopsy, although these also predict a higher rate of

●

Patient living alone

spontaneous seroconversion of HBeAg to anti-HBe. Treatment

with lamivudine, a nucleoside analogue, has the advantage of

being an oral therapy that is much better tolerated. Sustained

HBeAg seroconversion occurs in only 10% of patients, and viral

resistance develops in most patients who are given long term

therapy. Adefovir, a nucleotide analogue, recently has been

licensed in the United States and Europe and has similar

efficacy to lamivudine but with a much lower incidence of

resistance. It is effective against lamivudine resistant and

Although treatment should be considered

pre-core mutant infections and improves the liver histology in

for HBV carriers, the efficacy is still poor

patients with anti-HBe and active liver disease. Current

for a large group of patients, particularly in

treatments are not indicated for carriers with anti-HBe and

regions of high endemicity where patients

normal biochemical and histological findings, although they

are HBeAg positive but have normal liver

still have a small excess risk of developing chronic liver disease.

function

Chronic hepatitis C may also respond to interferon

therapy; however, combination treatment with oral ribavirin

improves the response rate. The recommended treatment

duration is six months for HCV genotype 2 or 3 and 12 months

for other types. New forms of pegylated interferon have longer

half lives that allow once weekly, rather than three times weekly,

dosing, and improve the response rate, particularly for

genotype 1.

Screening and prevention

Prevention of hepatitis as a sexually transmitted disease

●

Contact tracing

The transmission of hepatitis A can be prevented by applying

●

Counselling of HBeAg positive carriers

simple precautions to reduce faecal-oral contamination. Recent

●

Passive immunisation

sexual contacts of acute cases can be protected by passive

Hepatitis A—normal human immunoglobulin

immunisation with human normal immunoglobulin within

Hepatitis B—hepatitis B immunoglobulin (HBIg)

14 days. Hepatitis A vaccine provides protection when given

●

Active immunisation—vaccine

within seven days of exposure and, with a booster dose at

Hepatitis A—in outbreak situations in homosexual men

6-12 months, will provide long term immunity. Immunisation

Hepatitis B—targeted immunisation

●

Safer sex or barrier contraception

of homosexual men whose sexual behaviour places them at risk

Hepatitis C (no vaccine available)

has been recommended, but those at risk are not well defined.

Hepatitis A (avoid oral-anal exposure)

Routine prophylaxis of all homosexual men is not currently

Viral hepatitis

recommended. The main groups to be offered vaccine

Overview of hepatitis B and C

routinely are travellers and patients with chronic liver disease,

Importance

the latter because of an increased risk of adverse outcomes.

Hepatitis B and C are the main causes of chronic viral hepatitis

Currently, more widespread screening is not indicated in either

(defined as viral persistence for more than six months) and occurs

primary care or STI clinics.

in 5% of cases of hepatitis B in adults and 60-70% cases of hepatitis

Hepatitis B transmission to carers and other contacts can be

C. Both may lead to liver fibrosis, cirrhosis, and liver failure or

limited by careful handling of blood, blood contaminated

hepatocellular carcinoma

material, and instruments; however, those at risk should be

Virology

given vaccine. Sexual and household contacts of patients with

Hepatitis B is a DNA virus; hepatitis C is an RNA virus. Diagnosis is

acute hepatitis B should be traced and offered vaccine. If seen

by serology. Screening tests for hepatitis B are for HBsAg, anti-HB

core, and anti-HB surface; hepatitis C tests are for anti-HCV and

within 72 hours of an isolated sexual or parenteral exposure,

HCV RNA (both are detectable in persistently infected patients)

hepatitis B immunoglobulin can be given as additional passive

Transmission

prophylaxis. Tracing the contacts of a case of acute hepatitis B

Both hepatitis B and C are spread by parenteral, sexual, and

may identify the source, who is usually an HBeAg positive

mother to baby exposure. Cases of acute hepatitis B and HBeAg

carrier. Source contacts can be counselled about their

positive carriers are the most infectious by all routes. Parenteral

infectivity and protection of other non-immune sexual contacts

exposure is a much greater risk than vertical or sexual exposure for

and be offered further assessment and treatment. In most parts

hepatitis C

of the world, programmes of universal infant immunisation

Symptoms and presentation

against hepatitis B have been established, sometimes with

Most cases of acute hepatitis are asymptomatic, but all types of

“catch up” immunisation of adolescents. In the United

acute viral hepatitis may present similarly with fever, headaches,

and fatigue before jaundice is seen. Most cases of hepatitis B and C

Kingdom, the strategy is still for targeted immunisation.

are diagnosed only during the chronic phase as a result of

Current British recommendations on screening apply equally to

screening or investigation of abnormal liver function tests

primary care and STI clinics and include gay and bisexual men,

Treatment

injecting drug users, contacts of individuals with acute or

No specific treatment is available for acute hepatitis B or C.

chronic hepatitis B, and sex workers. Those who are not already

Individuals with chronic hepatitis B who have active virus

immune should be given vaccine. In addition, individuals from

replication and liver disease can be treated with interferon,

high prevalence countries should be screened to identify

lamivudine, or adefovir. Treatment for hepatitis C with interferon

hepatitis B carriers who may be at risk of infecting others, as

or ribavirin is recommended with similar indications

well as being candidates for treatment.

Prevention

A vaccine is available for hepatitis B; no specific prophylaxis has

Current hepatitis B vaccines contain a recombinant

been developed yet for hepatitis C

hepatitis B S-protein. In some parts of the world, plasma

derived vaccines are still used. Both types of vaccine are safe

and protect over 90% of immunocompetent vaccinees for at

least five years. The standard course is three doses at zero, one,

and six months, or four doses at zero, one, two, and 12 months.

More rapid vaccine courses, for example zero, seven, and

21 days, have been proposed. These produce protective

concentrations of anti-HBs antibody sooner, but the titre is low

and the long term efficacy is uncertain without a booster at six

or 12 months. Vaccines containing preS1 and preS2 proteins

may overcome a non-response to the standard vaccine and

produce an equivalent response with only two doses, but none

are yet available in the United Kingdom.

In low prevalence countries, such as the United Kingdom,

the hepatitis B vaccine policy is to target those most at risk,

Recent evidence shows that after hepatitis B vaccination

whereas in most countries, universal immunisation of infants or

most patients will be protected for at least 15 years. HIV

adolescents (or both initially) is being implemented. In a

positive and other immunosuppressed patients may not be

targeted strategy, and depending upon the prevalence, savings

protected as effectively and may need booster doses when

anti-HBs titres drop below 100 IU/l

can be made by pre-vaccine testing for HBV markers.

Post-vaccine testing to confirm a response (or detect current

infection if not excluded by pre-vaccine screening) is advised.

Non-responders or poor responders may benefit from further

doses of vaccine. The need for routine booster doses is

questionable. Booster doses are not cost effective at a

population level.

HIV

Ian G Williams, Ian Weller

HIV was first detected in 1983 in a patient with AIDS.

Centers for Disease Control revised classification system for

Serological tests for antibodies to HIV infection were

HIV infection, 1993

subsequently developed in 1984, and the natural course of HIV

infection was characterised in prospective cohort studies in the

Clinical categories

1980s. Chronic HIV infection over several years results in

Asympto-

Sympto-

AIDS

progressive damage to the immune system, which leads to

matic, acute

matic, not (A)

indicator

severe immune deficiency, opportunistic infections, cancers,

CD4

T cell

(primary) HIV

or (C)

conditions

categories

or PGL

conditions

and death. In recent years, marked improvements have been

made in treatments, resulting in dramatic decreases in the

500

10⁶/l

incidences of AIDS and death in the developed world. HIV and

200-499

10⁶/l

AIDS remains, however, a major cause of mortality and

200

10⁶/l

morbidity in the developing and other parts of the world. The

classification and staging of HIV disease have been defined by

the Centers for Disease Control (CDC) in the United States

and the World Health Organization (WHO). The CDC system

is used widely in the developed world, and the WHO system is

4000

used in the developing world.

HIV diagnoses

3500

AIDS diagnoses

3000

Epidemiology

Deaths

2500

HIV is transmitted sexually, in blood or blood products, and

2000

perinatally. The number of reported cases continues to

increase; by the end of 2001, the United Nations estimated

1500

that 40 million adults and children worldwide were living

1000

with HIV and AIDS, of whom 28.5 million were in living in

sub-Saharan Africa. In the UK by June 2002, 51 081 cases of

500

HIV infection had been reported. Within the developed

1986

1988

1990

1992

1994

1996

1998

2000

world, most of those infected are men (79% in the United

Kingdom and 54% in the United States), of whom the majority

Year of diagnosis

are either homosexual or injecting drug users. Most of the

HIV diagnoses, AIDS case reports, and deaths in HIV infected individuals in

affected women are either injecting drug users, have had

the United Kingdom, by year of diagnosis or occurrence. Adapted from

sexual contact with injecting drug users or bisexual men,

slide from the Health Protection Agency website (www.hpa.org.uk). Data

or are from countries where heterosexual transmission is a

from Communicable Disease Surviellance Centre, Scottish Centre for

Infection and Environmental Health, and the Institute of Child Health

prominent risk factor. Paediatric cases usually occur as a result

of the mother having AIDS or belonging to a group at risk of

acquiring AIDS.

In patients newly diagnosed every year, the proportion that

is heterosexual has increased. In the United Kingdom and the

Sex between men

Blood or blood factor

United States, more than 50% are heterosexual. In the United

Sex between men and women

Mother to infant

States this largely reflects the epidemic among intravenous

drug users, whereas in the United Kingdom the increase

Injecting drug abuse

Other or undetermined

2500

reflects acquired HIV infection in Africa. Worldwide

heterosexual intercourse is the main route of transmission. In

sub-Saharan Africa and South and South East Asia, the ratio of

2000

infected men to infected women is virtually 1:1.

Since 1996 in the developed world, both the incidence

1500

of new cases of AIDS and the mortality have fallen

dramatically as a result of the use of highly active

1000

antiretroviral therapies (HAART). Reducing the prevalent

population of undiagnosed cases of HIV infection, earlier

500

diagnosis, and improved access to care are essential for

further reducing the incidence of AIDS and AIDS related

death. In the United Kingdom 30% of the total population

1984

1986

1988

1990

1992

1994

1996

1998

2000

infected with HIV are estimated to remain undiagnosed, and

Year of diagnosis

a high proportion of these are black African heterosexual

men and women, who are more likely to be diagnosed in

Reports to Communicable Disease Surveillance Centre of all HIV infected

advanced disease or with an AIDS defining illness compared

individuals by year of diagnosis. Adapted from slide from the Health

with other affected groups.

Protection Agency website (www.hpa.org.uk). Data from Communicable

Disease Surviellance Centre, Scottish Centre for Infection and

Environmental Health, and the Institute of Child Health

HIV

Immunology

Range of immune dysfunction

●

↓ T helper cells (CD4

)

Depletion and impaired function of the T helper lymphocyte

●

Expansion of CD8 cells and impairment of

subset (lymphocytes bearing the CD4 cluster differentiation

cytotoxic T cell responses

antigen) is the primary abnormality of immune dysfunction.

●

Depletion of T cell antigen repertoire

The CD4 molecule, however, is also displayed at lower density

●

↑ immunoglobulins: polyclonal B cell activation,

on other cells, such as monocytes, macrophages, and some

↓ de novo antibody response

B lymphocytes. The CD4 lymphocyte has a pivotal role in the

immune response (interacting with macrophages, other T cells,

B cells, and natural killer cells, either by direct contact or by the

influence of lymphokines such as interferon and interleukin 2).

The mechanism for CD4 lymphocyte loss remains uncertain, but

probably includes enhanced apoptosis (programmed cell death)

and inhibition of CD4 lymphocyte growth.

The virus

HIV has a cylindrical core and its nucleic acid has been cloned

and sequenced. It has a basic gene structure common to all

retroviruses, but it is very different from the other human

retroviruses (human T lymphotropic viruses I and II). The

CD4 antigen is a major component of the viral receptor

required for cell entry. Only cells bearing this antigen are

susceptible to infection. The chemokine receptors (CCR5

and CXCR4) also act as coreceptors for HIV entry and their

expression of the cell surface determines the susceptibility of

CD4 bearing cell lines to different HIV strains.

On entry to the infected cell, the viral reverse transcriptase

enzyme (hence retrovirus) makes a DNA copy of the RNA

genome (proviral DNA). The proviral DNA is able to integrate

into the host cell DNA. Latent, non-productive, or productive

viral replication may occur. During productive replication,

RNA, transcripts are made from the proviral DNA, and

complete virus particles are assembled and released from

Electron micrograph of virus. Properties: retrovirus, two strands of

infected cells by characteristic budding.

RNA (100-120 nm diameter); genes are gag (core proteins), pol (polymerase

or reverse transcriptase), env (envelope proteins), and accessory genes that

regulate viral protein synthesis and replication; wide genomic diversity, most

Natural course

pronounced in env region. CD4 tropism; cytopathic effect in susceptible cell

lines; latency; antibodies to core and envelope proteins (weak neutralising

Acute infection

activity)

Acute infection with HIV may be accompanied by a transient

non-specific illness similar to glandular fever; it includes fever,

malaise, myalgia, lymphadenopathy, pharyngitis, and a rash.

A transient aseptic meningoencephalitis may also occur. Most

acute infections, however, are subclinical. The acute infection is

accompanied by the development of antibodies to the core

(p24) and surface (GP 41, 120, 160) proteins, usually in two to

six weeks, although delayed seroconversions have been

observed. Antibodies usually are detected by enzyme linked

Diagnosis of acute HIV infection is confirmed by a positive

immunoassays, and their presence can be confirmed by

virus detection assay (plasma HIV RNA, cellular proviral

immunofluorescence or western blotting.

DNA, or p24 antigen) in the presence of a negative or

Initial concentrations of plasma viraemia detected by

evolving (rising titre) antibody profile

polymerase chain reaction are very high but then decline

rapidly within a few days to weeks as the immune response to

HIV develops. It is not clear which immune mechanisms are

primarily responsible for this initial fall in viraemia, but the

breadth and strength of HIV specific CD4 and CD8 T cell

responses that develop during primary infection are important

for long term virological control in chronic HIV infection.

The effectiveness of these specific immune responses

determines the efficacy of virological control and, thus, plasma

viraemia. A high plasma RNA concentration is associated with a

more rapid decline in CD4 count over time and a quicker

progression to symptomatic disease, whereas a very low

concentration is predictive of slow or non-progression. The

efficacy of the immune response in acute primary infection,

ABC of Sexually Transmitted Infections

therefore, seems to determine a “set point” for which viral

application is controlled over time.

CD4+ T-lymphocyte

Count (cells/mm³)

Chronic infection

<200

In the early stages chronic infection is asymptomatic. Physical

201-350

351-500

examination may show no abnormality, but about one third of

501-750

patients have persistent, generalised lymphadenopathy (nodes

100

>750

of 1 cm or more in diameter in two or more non-contiguous

extrainguinal sites that cannot be explained by any other

infection or condition). The commonest sites of

lymphadenopathy are the cervical and axillary lymph nodes; it

is unusual in the hilar lymph nodes. Biopsy usually shows

a benign profuse follicular hyperplasia.

Later in infection, as the CD4 count declines, non-specific

constitutional symptoms develop, which may be intermittent or

persistent and include fevers, night sweats, diarrhoea, and

weight loss. Patients may also have several “minor”

opportunistic infections or conditions that tend to affect the

mucous membranes and skin, such as oral candidiasis, oral

Viral load

hairy leucoplakia, herpes zoster, recurrent oral or anogenital

values

herpes simplex, and other skin conditions such as seborrhoeic

MACS

>30k

10k-30k

3k-10k

501k-3k

<500k

Plasma load

dermatitis, folliculitis, impetigo, and tinea infections. This

bDNA

>60k

20k-60k

6k-20k

1k-5k

<1k

(copies/ml)

RT-PCR

>110k

41k-110k

14k-41k

3k-14k

<3k

collection of symptoms and signs, which are often a prodrome

to the development of major opportunistic infection or tumour,

Likelihood of developing AIDS within three years by CD4 and viral load

is called asymptomatic non-AIDS (CDC stage B).

(bDNA branched DNA; MACS Multicenter AIDS Cohort Study;

A high plasma viral RNA concentration, CD4 count

RT-PCR reverse transcriptase polymerase chain reaction). Adapted from

200

10⁶/l, and the presence of stage B symptoms are

Mellors et al. Ann Intern Med 1997;126:946-54

associated with an increased risk of progression to an AIDS

defining illness. Clinical monitoring of the CD4 count, plasma

HIV RNA concentrations, and stage B symptoms determines

when to start antiretroviral therapy to prevent clinical disease

From cohort studies, it is estimated that without therapy

progression.

about 75% of HIV infected people can be expected to

develop symptomatic (CDC stage B and C) disease within

9-10 years of primary infection

AIDS

AIDS is defined as an illness characterised by one or more

indicator diseases. In the absence of another cause of immune

Diseases diagnostic of AIDS if laboratory evidence of HIV

deficiency and without laboratory evidence of HIV infection (if

exists

the patient has not been tested or the results are inconclusive),

●

Recurrent or multiple bacterial infections—child aged under

certain diseases when definitely diagnosed indicate AIDS.

13 years

Regardless of the presence of other causes of immune

●

Candidiasis—pulmonary

deficiency, if there is laboratory evidence of HIV infection,

●

Candidiasis—oesophageal*

other indicator diseases that require a definitive, or in some

●

Cervical carcinoma—invasive

●

Coccidioidomycosis—disseminated

cases only a presumptive, diagnosis also constitute a diagnosis

●

Cryptococcosis—pulmonary

of AIDS.

●

Cryptosporidiosis—with diarrhoea persisting for more than one

month

●

Cytomegalovirus retinitis*

●

Cytomegalovirus disease—not in liver, spleen, or nodes

●

HIV encephalopathy

Diseases diagnostic of AIDS without laboratory evidence

●

Herpes simplex virus infection—mucocutaneous ulceration that

of HIV

lasts for more than one month or pulmonary, oesophageal

●

Candidiasis—oesophageal, pulmonary

infection

●

Histoplasmosis—disseminated

●

Cryptococcosis—extrapulmonary

●

Isosporiasis—with diarrhoea that persists for more than one

●

Cytomegalovirus disease—disseminated

●

Cryptosporidiosis—diarrhoea that persists for more than one

month

●

Kaposi’s sarcoma*

month

●

Lymphoid interstitial pneumonia—child younger than 13 years*

Herpes simplex virus infection

●

Non-Hodgkin’s lymphoma—Burkitt’s or immunoblastic

Mucocutaneous ulceration that lasts more than one month

●

Primary cerebral lymphoma

Pulmonary, oesophageal infection

●

Disseminated mycobacterosis—for example Mycobacterium avium*

Kaposi’s sarcoma—patient younger than 60 years

●

Mycobacterial tuberculosis—extrapulmonary, pulmonary*

Primary cerebral lymphoma—patient younger than 60 years

●

P carinii pneumonia*

Lymphoid interstitial pneumonia—child younger than 13 years

●

Recurrent pneumonia within a 12 month period*

Mycobacterium avium—disseminated

●

Progressive multi-focal leukoencephalopathy

Mycobacterium kansasii—disseminated

●

Salmonella septicaemia—recurrent

Pneumocystis carinii pneumonia

●

Wasting syndrome due to HIV

Progressive multi-focal leukoencephalopathy

●

Cerebral toxoplasmosis

*These indicator diseases may be diagnosed presumptively

HIV

WHO’s AIDS case definition for AIDS surveillance

Expanded WHO case definition for AIDS surveillance

For the purposes of AIDS surveillance, an adult or adolescent

(older than 12 years of age) is considered to have AIDS if at least

(older than 12 years of age) is considered to have AIDS if a test for

two of the following major signs are present in combination with at

HIV antibody gives a positive result and one or more of the

least one of the minor signs listed below and if these signs are not

following conditions are present:

known to be caused by a condition unrelated to HIV infection.

●

10% body weight loss or cachexia, with diarrhoea or fever, or

Major signs

both, intermittent or constant, for at least one month, not known

●

Weight loss

10% of body weight

to be caused by a condition unrelated to HIV infection

●

Cryptococcal meningitis

●

Chronic diarrhoea for more than one month

●

Pulmonary or extrapulmonary tuberculosis

●

Prolonged fever for more than one month (intermittent or

●

Kaposi’s sarcoma

constant)

●

Neurological impairment, which is sufficient to prevent

Minor signs

independent daily activities, not known to be caused by

●

Persistent cough for more than one month*

a condition unrelated to HIV infection (for example, trauma or

●

Generalised pruritic dermatitis

cerebrovascular accident)

●

History of herpes zoster

●

Candidiasis of the oesophagus (which may be presumptively

●

Oropharyngeal candidiasis

diagnosed based on the presence of oral candidiasis

●

Chronic progressive or disseminated herpes simplex infection

accompanied by dysphagia)

●

Generalised lymphadenopathy

●

Clinically diagnosed life threatening or recurrent episodes of

The presence of generalised Kapsosi’s sarcoma or cryptococcal

pneumonia, with or without aetiological confirmation

●

Invasive cervical cancer

meningitis is sufficient for the diagnosis of AIDS for surveillance

purposes.

The boxes on WHO’s case definition for AIDS surveillance are

* For patients with tuberculosis, persistent cough for more than

reproduced from Grant A, De Cock KM. HIV and AIDS in the

one month should not be considered as a minor sign

developing world. In Adler M (ed) ABC of AIDS. 5th ed, London:

BMJ Publishing Group, 2001

In 1993, the CDC extended the definition of AIDS to

include all people who are severely immunosuppressed (CD4

count

200

10⁶/l) irrespective of the presence or absence of

an indicator disease. For surveillance purposes this definition

has not been accepted within the United Kingdom and Europe.

In these countries, AIDS continues to be a clinical diagnosis by

Common AIDS defining diseases

one or more of the indicator diseases.

Developed world

In most developing countries, sophisticated laboratory

●

Pneumocystis pneumonia

investigations usually are not available. For this reason, the WHO

●

Oesophageal candida

●

Non-Hodgkin’s lymphoma

introduced a clinical case definition that could be used for

●

Tuberculosis (pulmonary and extra pulmonary)

epidemiological surveillance in settings where laboratory facilities

are inaccessible. In 1994, this case definition was expanded to

Developing world

incorporate HIV serology and to take into account the revisions

●

Tuberculosis (pulmonary and extra pulmonary)

●

HIV wasting syndrome

to the CDC’s case definition. If serological testing is unavailable,

●

Cerebral toxoplasmosis

the clinical case definition should be used; if serological testing is

●

Cryptococcus meningitis

available, the expanded case definition should be used.

The frequency of specific AIDS defining illnesses differs

between the developed and the developing world. In the

developed world, pneumocystis pneumonia remains the

most common AIDS defining opportunistic infection and

non-Hodgkin’s lymphoma is accounting for an increased

proportion of first AIDS cases. In the developing world,

tuberculosis is by far the most common opportunistic infection,

together with diarrhoeal disease and wasting syndrome.

Tumours

Kaposi’s sarcoma

Kaposi’s sarcoma is the most common neoplasm that occurs in

patients with AIDS, although the incidence has fallen over recent

years. It is more common in homosexual men than in the other

at risk groups. Before the era of HAART, the median survival

time was about two years, although death usually is caused by

a supervening life threatening opportunistic infection. The

Kaposi’s sarcoma of AIDS differs from classic Kaposi’s sarcoma,

in that widespread skin, mucous membrane (particularly the oral

cavity and palate), visceral, and lymph node disease occurs.

Visceral, particularly gastrointestinal, lesions are present in as

many as half of all patients at presentation.

Nodules of Kaposi’s sarcoma also occur in the lungs. Chest

radiography appearances vary from confluent irregular masses

Kaposi’s sarcoma

ABC of Sexually Transmitted Infections

to interstitial nodularity. Computed tomography of the thorax

may be useful in differential diagnosis. At bronchoscopy,

endobronchial lesions may be seen. Kaposi’s sarcoma consists

of spindle shaped cells arranged in nodules and broad bands

that contain vascular slits filled with extravasated erythrocytes.

The diagnosis of Kaposi’s sarcoma in very early skin lesions

may be extremely difficult because little more may be seen than

a few irregular dilated vascular channels in the mid dermis and

a mild inflammatory cell infiltrate.

Kaposi’s sarcoma associated herpes virus (KSHV or human

herpes virus 8) has been identified in nearly all Kaposi’s

sarcoma lesions and, when detected in blood, predicts the later

development of Kaposi’s sarcoma. Patient populations that have

the highest risk of developing Kaposi’s sarcoma (homosexual

and bisexual men and Africans) have a high prevalence of

antibodies to KSHV, and this correlates with the number of

sexual partners and some past sexually transmitted infections

(STIs) in homosexual men. Epidemiological evidence is

supportive of sexual transmission and a causal role for KSHV in

the pathogenesis of Kaposi’s sarcoma. The mechanism for this

Spindle cell proliferation of nodular Kaposi’s sarcoma

is probably an interaction between KSHV replication, HIV

proteins, inflammatory cytokines, and immune deficiency,

which leads to a microenvironment that promotes the

development of Kaposi’s sarcoma.

Non-Hodgkin’s lymphoma

Extranodal disease is common and affects the central nervous

system, bone marrow, and gastrointestinal tract. A diagnosis of

non-Hodgkin’s lymphoma should also be considered in patients

with weight loss, constitutional symptoms, and anaemia. The

tumours originate from B cells, are of high or intermediate

grade, and generally have an aggressive clinical course. More

than 50% of AIDS related lymphomas have been associated

with the Epstein-Barr virus (EBV) or KSHV infection (or

both). Although the incidence of AIDS related lymphoma has

fallen as a result of HAART, it accounts for an increased

proportion of the cause of AIDS related deaths. Non-Hodgkin’s

lymphoma unfortunately is difficult to treat and generally

responds poorly to cytotoxic chemotherapy.

Opportunistic infections

The organisms responsible for the opportunistic infections that

occur in patients with AIDS are unusual pathogens. Most

Extranodal lymphoma in the neck

infections are caused by reactivation of latent organisms in the

host or, in some cases, ubiquitous organisms to which we are

continually exposed. The infections are frequently difficult to

diagnose because conventional serological tests are unhelpful.

Treatment often suppresses rather than eradicates the organisms.

Therefore, without effective antiretroviral therapy, relapses are

common. With effective antiretroviral therapy, the incidence of

recurrent or new opportunistic infection falls dramatically.

Three main organ systems are affected: the respiratory

system, the gastrointestinal tract, and the central nervous

Other neoplasms

system. In addition, patients may present with a history of night

●

The incidence of cervical intraepithelial neoplasm and cancer

sweats, chronic ill health, fevers, or weight loss.

is increased in HIV positive women

●

Similarly, squamous intraepithelial lesions and cancer of the

anus are increased in HIV infected men and women

Pulmonary complications

●

Both cervical intraepithelial neoplasia and squamous

intraepithelial lesions are associated with human papillomavirus

Pneumocystis jiroveci (previously carinii) pneumonia is one of the

infections

most common life threatening opportunistic infections in

●

An increased incidence of other cancers has been observed

patients who progress from chronic HIV infection to AIDS. The

including Hodgkin’s lymphoma and skin cancers

presentation is subacute, and malaise, fatigue, weight loss, and

shortness of breath often develop over several weeks. Typical

retrosternal or subcostal chest discomfort associated with

HIV

increasing shortness of breath, a dry cough, and fever finally

Effect on respiratory system—typical results from

causes the patient to seek help. The chest radiograph at

bronchoscopy series

presentation may be normal or show bilateral fine infiltrates,

which are typically perihilar. The arterial oxygen tension is

Condition

Percentage

usually depressed and the carbon monoxide transfer factor,

Pneumocystis jiroveci pneumonia

when available, is low and may be the earliest detectable

Cytomegalovirus

abnormality. The diagnosis is confirmed by cytological

Kaposi’s sarcoma

examination of induced sputum or by fibre optic bronchoscopy

Bacterial infection

and bronchial lavage. Transbronchial biopsy is now performed

(pneumococcal, caused by

rarely. Bronchoscopy can exclude other causes of pneumonia

Haemophilus influenzae or

or coexistent infection such as cytomegalovirus, mycobacteria,

mycobacterial atypical or

caused by Mycobacterium tuberculosis)

and fungi.

Pyogenic bacterial causes of pneumonia should always be

Miscellaneous

considered, particularly as its presentation may be atypical. The

radiological appearances may include diffuse infiltrates as well

as the more typical focal or lobar patterns. Another cause of

diffuse abnormality is lymphocytic interstitial pneumonitis,

more common in children than adults with AIDS.

Infection with Mycobacterium tuberculosis may also occur and,

since 1993, constitutes a diagnosis of AIDS. Among Africans

who present with AIDS, it is the most common opportunistic

infection and may present as pulmonary or extrapulmonary

disease. In patients with advanced immunodeficiency, the

presentation of pulmonary tuberculosis may be atypical and

should be considered in all patients with respiratory symptoms.

Multi drug resistant tuberculosis occurs. Atypical mycobacteria

infection may occur but usually complicates severe immune

depression of advanced AIDS.

Gastrointestinal and hepatic

complications

Oral and oesophageal candidiasis is the most common cause of

dysphagia or retrosternal discomfort. Oral candidiasis alone

Chest radiograph of patient with typical appearances of

P jiroveci pneumonia

does not fulfil the criteria for AIDS. Oesophageal infection is

best shown by culture or biopsy at endoscopy, although plaques

of Candida albicans often can be seen during a barium swallow.

Ulceration may be focal or diffuse. Cytomegalovirus and herpes

simplex virus may both cause a similar pattern of ulceration in

the oesophagus (and also may affect the stomach and

Gastrointestinal complications of AIDS

duodenum). Histopathology is needed to confirm the

Complications

Causes

diagnosis.

Diarrhoea is a common symptom of patients with chronic

Retrosternal discomfort and

Candidiasis

dysphagia

Cytomegalovirus

HIV infection, with or without other manifestations of AIDS.

Herpes simplex virus

In the majority of cases, a pathogen is found, although an

Diarrhoea, weight loss, and

Unknown—enteropathy

enteropathy with malabsorption has been described as being

malabsorption

Cryptosporidiosis, Isospora belli,

secondary to HIV infection.

and microsporidial infection

Cryptosporidium is a coccidian protozoal parasite and one

Cytomegalovirus and herpes

of the most common pathogens isolated from AIDS patients

simplex virus

who have diarrhoea. It is also the most common of the

Mycobacteria

Enteric bacteria—salmonella,

protozoal causes of diarrhoea, which also include Isospora belli

campylobacter

and microsporidia. In immunocompetent human hosts,

Neoplasia

cryptosporidium produces a transient diarrhoeal illness. In

Hepatitis and cholestasis

Mycobacteria

people infected with HIV, it can cause transient, intermittent,

Cytomegalovirus

or persistent diarrhoea ranging from loose stools to watery

Drugs

diarrhoea, colic, and severe fluid and electrolyte loss. Oocysts

Cryptosporidium

can be found in stools. If direct smears of unconcentrated

Perianal ulceration

Herpes simplex virus

faecal samples stained with iodine or modified acid fast stains

? Cytomegalovirus

fail to show the oocysts, the samples should be concentrated.

Neoplasia and miscellaneous Kaposi’s sarcoma

The diagnosis should not be discounted without examining

Lymphoma

multiple specimens.

Hairy leukoplakia

Microsporidia, small obligate intracellular protozoa, have

Recalcitrant anorectal warts

? Squamous oral or anal carcinoma

been identified as a cause of diarrhoea in patients with AIDS

(or both)

where no other pathogen had previously been found.

ABC of Sexually Transmitted Infections

Cysts of

cryptosporidium

Severe

(modified

mucocutaneous

Ziehl-Neelsen

herpes simplex

stain)

virus infection

Cytomegalovirus and herpes simplex virus can cause focal or

diffuse ulceration of the gut, from the mouth to the anus. Herpes

simplex virus most commonly causes mucocutaneous lesions at

the upper and the lower ends of the gastrointestinal tract,

whereas cytomegalovirus may mimic inflammatory bowel disease.

Atypical mycobacteria of the avium intracellular complex

are ubiquitous organisms that have little virulence for the

immunocompetent host. Disseminated infection of several

organs including the gastrointestinal tract occurs in patients

with AIDS and may be associated with fever, weight loss,

diarrhoea, and malabsorption. Diagnosis of disseminated

infection is usually made on culture of blood or bone marrow

biopsy. Mycobacterium tuberculosis infection of the bowel does

occur but is less common. Campylobacter and Salmonella species

infections may cause diarrhoea, but the latter more commonly

presents as a fever of unknown origin with bacteraemia.

Hepatitis in patients with AIDS may present as fever,

abdominal pain, and hepatomegaly, and liver function test

Dilated common bile duct with

results, particularly raised alkaline phosphatase activity, may be

stricture at lower end and

irregularities of extrahepatic and

abnormal. If ultrasonography does not show dilated bile ducts,

intrahepatic ducts

needle biopsy may show granulomatous hepatitis, usually

caused by atypical mycobacteria rather than M tuberculosis. The

herpes viruses also occasionally may cause hepatitis as part of

a disseminated infection. Clinically the most common causes of

hepatitis are drugs or coinfection with hepatitis B or C, which

occurs most often among homosexual and bisexual men and

injecting drug users than other patient populations.

Acalculous cholecystis and cholangitis show an endoscopic

retrograde cholangiographic picture similar to that of primary

Rough incidence of conditions in patients with neurological

sclerosing cholangitis, with strictures and dilatation of the biliary

complications

tree. Cryptosporidium and cytomegalovirus have been shown or

isolated and are implicated as a cause of this syndrome.

Site of infection

Central nervous system

Percentage

Viral infections

Neurological complications

AIDS related dementia

HIV related meningitis

Chronic HIV infection is associated with several syndromes that

Cytomegalovirus retinitis

affect the nervous system, in addition to the transient

Cytomegalovirus encephalitis

meningoencephalitis, myelopathy, and peripheral neuropathy

Progressive multifocal

of acute infection. These neurological diseases are believed to

leukoencephalopathy

0.5

be caused by the direct or indirect effects of HIV and not to

Vacuolar myelopathy

Intracranial mass lesions

opportunistic infection. AIDS related dementia, also referred to

Cerebral toxoplasmosis

as “HIV associated motor cognitive complex,” has been

Primary central nervous system lymphoma

estimated to occur in 10-40% of patients with symptomatic

Undefined mass lesions

disease before the era of HAART. At necropsy, up to 90% of

Lymphoma

patients dying of AIDS have chronic subcortical encephalitis

Peripheral nervous system

characterised by infected macrophages and microglial cells that

Sensory neuropathy

fuse to form multinucleate giant cells. There is also patchy

Inflammatory demyelinating neuropathy

Cranial neuropathy

demyelination and astrogliosis.

Multiple mononeuropathies

The clinical features are characterised by cognitive and

Polyradiculopathy

behavioural changes that include memory loss, apathy, and

Miscellaneous

impaired concentration and attention. Neurological

Cryptococcal meningitis

examination may show hypereflexia, hypertonia, and frontal

Neurosyphilis

0.5

release signs. Computed tomography or magnetic resonance

Metabolic encephalopathy

Cerebrovascular accident

0.5

imaging often show cerebral atrophy and non-specific changes

in the white matter. The findings in cerebrospinal fluid are

*may be as high as 20% at necropsy

HIV

non-specific. Opportunistic infections, intracranial mass lesions,

Recommendations for starting antiretroviral therapy in

metabolic encephalopathy, and neurosyphilis should be

adults

excluded.

HIV infection is also implicated in vacuolar myelopathy that

Disease stage

BHIVA

USDHHS

affects primarily the posterior and lateral spinal cord,

Symptomatic

Treat

meningitis, and the following neuropathies: axonal sensory,

Asymptomatic

Treat

chronic inflammatory demyelinating, and mononeuropathies.

CD4

200

10⁶/l

Cytomegalovirus infection may produce a polyradiculopathy.

CD4 count

Consider treatment

Treatment should

The nervous system also is affected by opportunistic

200-350

10⁶/l

depending upon

generally be

viral load, rate of

offered

infection and tumours. Cerebral toxoplasmosis is the most

CD4 count decline,

common cause of intracranial mass lesions and usually

symptoms, and

presents with focal symptoms and signs. Cytomegalovirus

patient wishes

commonly causes a retinitis and presents with blurring or

CD4

350

10⁶/l

Defer

Defer or consider

partial loss of vision, or both. It may eventually lead to

treatment if high

blindness.

viral load

BHIVA, British HIV Association Guidelines, March 2001; USDHHA,

United States Department of Health and Human Services, February

Treatment

2001. Reproduced from Weller I, Williams I. Treatment of infections

and antiviral therapy. In Adler M (ed). ABC of AIDS. 5th ed.

Antiretroviral therapy

London: BMJ Publishing Group, 2001

In the developed world, combined antiretroviral therapies have

led to dramatic falls in the incidence of new AIDS cases and

AIDS associated deaths. The biological rationale for achieving

and maintaining a clinical response to treatment has been

established. Sustained inhibition of viral replication results in

reconstitution of the immune system in most patients,

substantially reducing the risk of clinical disease progression

and death. Reservoirs of HIV in latently infected resting

Drug toxicities

T lymphocytes and other long lived cell populations make it

unlikely, however, that HIV can be eradicated by antiretroviral

Drug

Toxicity

therapy alone.

NRTIs

Class associated

Lactic acidosis

Three main classes of antiretroviral drugs currently are

Hepatitic steatosis

licensed for inclusion in treatment regimens. The nucleoside

Lipodystrophy (peripheral fat

analogues and a non-nucleoside agent inhibit the viral reverse

wasting)

transcriptase enzyme that produces a DNA copy from the single

Drug specific

strand of viral RNA. The protease inhibitors inhibit post-

Zidovudine

Bone marrow suppression, nausea,

translational processing of viral proteins. Current standard

vomiting, myopathy

regimens combine two nucleoside reverse transcriptase

Stavudine

Peripheral neuropathy, hepatitis

Zalcitabine

Peripheral neuropathy, mouth

inhibitors with either one non-nucleoside reverse transcriptase

ulcers

inhibitor (NNRTI) or a protease inhibitor. Various

Didanosine

Pancreatitis, dry mouth, peripheral

combinations are recommended in national guidelines and the

neuropathy

choice of therapy for an individual patient depends on the

Lamivudine

Few side effects

drug toxicity profile, pill burden and dosing schedule,

Abacavir

Hypersensitivity reaction, nausea

likelihood of adherence to a particular regimen, and drug

NNRTIs

interactions. Large randomised clinical trials are ongoing to

Nevirapine

Rash, hepatitis, Stevens-Johnson

evaluate whether starting with a NNRTI or protease inhibitor

syndrome

Efavirenz

Rash, dysphoria, mood changes,

containing regimen is associated with a better treatment

vivid dreams, hypercholesterolaemia,

outcome in the long term.

hepatitis

Where possible, the objective of antiretroviral therapy is to

Protease inhibitors

reduce and sustain plasma viral load concentrations to below

Class specific

Lipodystrophy (fat wasting or

what can be detected by recurrent ultrasensitive viral load

accumulation), hyperlipidaemia,

assays (

50 copies/ml). Failure to suppress a viral load to this

diabetes mellitus

Drug specific

level of treatment is associated with increased risk of

Nelfinavir

Diarrhoea, rash

subsequent viral load rebound and the emergence of viral

Saquinavir

Few side effects

genotypic mutations associated with reduced drug

Indinavir

Hyperbilirubinaemia,

susceptibility. Even in those patients with advanced disease who

nephrolithiasis, nail changes,

start antiretroviral therapy at very low CD4 counts, sustained

dry skin

inhibition of viral replication does result in substantial immune

Ritonavir

Perioral dysathesia, flushing,

reconstitution and a decreased incidence of AIDS defining

hepatitis, diarrhoea, nausea,

vomiting

illnesses and death. It has been estimated from cohort studies

Amprenavir

Rash, nausea, vomiting

that the incidence of new AIDS illnesses or death in patients

Lopinavir

Diarrhoea

with a CD4 count persistently below 50

10⁶/l is 55-70 events

per 100 person years, whereas in those patients whose CD4

Reproduced from Weller I, Williams I. Treatment of infections and

count rises to above 200

10⁶/l, this event rate falls to between

antiviral therapy. In Adler M (ed). ABC of AIDS. 5th ed.

three and six events per 100 person years.

London: BMJ Publishing Group, 2001

ABC of Sexually Transmitted Infections

Although the clinical effectiveness of antiretroviral therapy

Drug toxicity is important in determining tolerability and

has improved, only about 70% of clinic patients sustain their

adherence to a regimen. Problems include peripheral

plasma viral loads to

50 copies/ml at one year. An important

neuropathy, cytopenia, pancreatitis, hepatitis, rash,

factor associated with treatment success is adherence. Patients

hyperlipidaemia, and lipodystrophy. Peripheral lipoatrophy

who are able to tolerate and adhere to their treatment regimen

and visceral adiposity are features of the lipodystrophy

successfully are more likely to achieve and sustain suppression

syndrome. Although related to therapy, the pathogenic

of plasma viral load than those who do not. Adherence is

mechanisms remain uncertain

a factor in the choice of regimen and an important aspect of

clinical care in patients on long term therapy.

Randomised clinical studies have not established when to

initiate therapy. Recommendations are based on the knowledge

of the risk of clinical disease progression (as determined by

CD4 count and plasma viral load) and the likelihood of clinical

benefit of therapy versus the likelihood of drug toxicity in the

short term. Clinical practice across Europe and North America

varies, but most clinicians will consider initiating therapy at

some point between a CD4 count of 200-350

10⁶/l and in all

patients who have symptomatic disease. Patients on therapy

New formulations of current drugs and new agents are

should have CD4 count and plasma viral load concentrations

being developed. In addition to new reverse transcriptase

monitored at regular intervals. On effective therapy, the plasma

and protease inhibitors, new drugs that act at different

sites in the viral replication cycle are being developed.

viral load falls rapidly, as viral replication is inhibited. By four

These include HIV entry inhibitors that affect CD4 and

weeks, a fall of greater than 1 log and by three to six months

coreceptor attachment and fusion. Immunotherapeutic

a fall to less than 50 copies per ml should be expected.

approaches are also being assessed, including the use of

Problems with the current therapies include drug resistance

cytokines such as interleukin 2

and long term drug toxicity. Mutations associated with drug

resistance will develop in patients who experience virological

failure on therapy. For some drugs, the emergence of a single

point mutation confers a very high decrease in susceptibility,

whereas for other drugs the decrease in susceptibility is much

lower and multiple mutations may be needed to confer high-

level drug resistance. Cross resistance between drugs can also

occur. Genotypic resistance testing is useful in guiding the

choice of second and third line treatment regimens. Drug

resistant viruses can be transmitted, and various recent studies

in different parts of the developed world have shown that

10-15% of patients who present with primary HIV infection

have genotypic mutations associated with drug resistance.

Opportunistic infections and tumours

Opportunistic infections: recommendations for initiation of

Advances in managing and preventing opportunistic infections

primary prophylaxis

have occurred and contributed substantially to the

Opportunistic infection

Recommendations

improvement and survival of patients with symptomatic disease

P jiroveci pneumonia

CD4 count

200

10⁶/l

that occurred before 1996. Both primary and secondary

Cerebral toxoplasmosis

CD4 count

100

10⁶/l and

prophylaxis of opportunistic infections remain important in

positive immunoglobulin

patients with severe immunodeficiency. However, the most

toxoplasma serology

effective strategy to prevent new AIDS defining illnesses or

Mycobacterium avium

CD4 count

10⁶/l

relapse of opportunistic infections is treatment with

complex

antiretroviral therapy, which results in the sustained control of

Cytomegalovirus disease

Under evalulation: may consider if

virus replication and an increase in CD4 count. Both primary

CD4

10⁶/l and positive

and secondary prophylaxis can be discontinued once the CD4

cytomegalovirus viraemia

count rises (

200

10⁶/l) without risk of recurrence.

Tuberculosis

If recent close contact of smear

positive index patient and no

Primary care

evidence of active clinical disease.

The care of patients with HIV infection has, in the most part,

National guidelines for use of

been the responsibility of specialist centres, which has reflected

tuberculin skin testing for

screening varies

the complexity of the disease management, including therapy.

Primary care physicians, however, can play an important role in

Reproduced from Weller I, Williams I. Treatment of infections and

certain areas. The first is diagnosis in people unaware of their

antiviral therapy. In Adler M (ed). ABC of AIDS. 5th ed.

HIV infection. Many patients first present to their doctor with

London: BMJ Publishing Group, 2001

the first symptoms of HIV associated immune deficiency.

Awareness by the doctor of the signs and symptoms that might

indicate HIV infection can lead to earlier diagnosis and referral

for therapy. A substantial proportion of newly diagnosed

patients continue to present late with an AIDS defining illness,

and this is associated with increased mortality.

HIV

Opportunistic infections: treatment recommendations

Infection

Drug

Duration

Side effects

Comments

Pneumocystis pneumonia

Cotrimoxazole

21 days

Nausea, fever, rash, bone

80% of patients will

(trimethoprim

marrow suppression

respond to treatment

component 15-20

Secondary prophylaxis

mg/kg/day) orally or

with low dose

intravenously

cotrimoxazole, dapsone,

or pentamidine

21 days

Hypotension,

or nebulised

isetionate

hypoglycaemia, renal

pentamidine is required

4 mg/kg/day as slow

failure, hepatitis, bone

until CD4 count

intravenous infusion

marrow suppression

increases to

200

10⁶/l

or clindamycin 600 mg

21 days

Nausea, diarrhoea, rash,

on antiretroviral

six hourly orally or

hepatitis

therapy

intravenously

plus primaquine

Nausea,

15 mg/daily orally

methaemoglobinaemia,

haemolytic anaemia,

leucopenia

Toxoplasmosis

Pyrimethamine

6 weeks

Rash, nausea, bone

Doses usually halved

50 mg/day orally and

marrow suppression

during maintenance

either

Treatment is continued as

Sulphadizine 4-6 g/day

secondary prophylaxis

orally or intravenously

until CD4 count

or clindamycin 600 mg

increases to

200

10⁶/l

four times a day

on antiretroviral

orally or intravenously

therapy

Cryptosporidiosis

Paromomycin 600 mg

28 days

Epigastric pain, dysphagia

Although observational

four times a day orally

studies report clinical

improvement,

paromomycin is an

unlicensed drug

Improving CD4 count

with antiretroviral

therapy can result in

resolution of symptoms

and infection

Herpes simplex infection

Aciclovir 200 mg

10-14 days

Suppressive treatment

five times/day orally or

with aciclovir 400 mg

5-10 mg/kg eight hourly

twice daily often

intravenously

required

Cytomegalovirus

Ganciclovir 5 mg/kg

21 days

Anaemia, neutropenia

Marrow suppression

twice daily intravenously

potentiated with

or valganciclovir 200 mg

zidovudine

twice daily orally

Secondary prophylaxis

or foscarnet 90 mg/kg

21 days

Nephrotoxicity,

with lower doses is

twice daily intravenously

hypocalcaemia,

required until CD4

headache

count increases

or cidofovir 5 mg/kg

14 days

Nephrotoxicity,

100

10⁶/l on

weekly intravenously*†

hypocalcaemia

antiretroviral therapy

Candidiasis local

Nystatin oral suspension

As required

Relapse common, many

treatment

or pastilles, miconazole

patients with persistent

oral gel, or

severe immune

amphotericin lozenges

deficiency require

systemic treatment

Candidiasis systemic

Fluconazole

7-14 days

Hepatitis

Relapse common on

treatment

50-200 mg/day

cessation of treatment

or Itraconazole

7-14 days

Hepatitis

Relapse common on

cessation of treatment

Cryptococcosis

Amphotericin B 0.7-1

6 weeks

Nausea, vomiting, rash,

Liposomal preparations of

mg/kg/day with or

bone marrow

amphotericin associated

without flucytosine

suppression, renal

with reduced risk of

75-100 mg/kg/day in

damage, hypocalcaemia

nephrotoxicity

four divided doses

Secondary prophylaxis

or fluconazole

6 weeks

Nausea, hepatitis

with fluconaxole

400-800 mg/day

200-400 mg/day is

required until CD4

count increases to

200

10⁶/l on

antiretroviral therapy

*Dose titrated to creatinine clearance

†Pre-dosing and post-dosing with probenecid limits risk of nephrotoxicity

ABC of Sexually Transmitted Infections

Symptoms and signs suggestive of immune deficiency should

Symptoms and signs of symptomatic (non-AIDS) HIV

prompt enquiry of previous high risk behaviour and possible

disease

exposure to HIV, particularly in those patient populations

The presence of these features should prompt discussion of HIV

associated with higher prevalence.

testing in those unaware of their HIV status

Primary care is also important in the long term care of a

●

Oral hairy leucoplakia

patient, particularly the management of psychosocial and

●

Recurrent of multi-dermatomal herpes zoster

mental health problems, drug side effects, pain control, and

●

Unexplained weight loss, chronic diarrhoea, and night sweats

palliative care—issues that are common to the treatment of

●

Recurrent or persistent oral candida

other chronic and disabling conditions. For this reason and as

●

Unexplained persistent generalised lymphadenopathy

the ongoing care of other general medical problems in primary

●

Chronic severe skin conditions, for example seborrhoeic fungal

care will be better managed if the doctor is aware of the HIV

infections

●

Peripheral neuropathy

status of the patient, it is important that all patients are

registered with a doctor.

In addition, doctors can play an important role in

prevention, by promoting safer sex behaviour and by improving

diagnosis and treatment of STIs in primary care.

Therapy in the developing world

The challenge to provide effective therapy in the developing

world is immense. In 2001, the United Nations declared that

treatment and care services, including access to antiretroviral

drugs, is an essential element of the response to the global HIV

United Nations AIDS declaration (2001): features of

and AIDS epidemic and described the features of comprehensive

comprehensive care for people living with HIV and AIDS

care that need to be developed. Several major problems exist in

●

Available, accessible voluntary counselling and testing services

the developing world. These include the unavailability of HIV

●

Prevention and treatment of HIV related illnesses

diagnostic tests such that the majority of people with HIV remain

●

Provision of antiretrovirals

unaware of their status, the cost of antiretroviral drugs, which,

●

Prevention and treatment of tuberculosis and other infections

despite reductions, still greatly exceed the annual per capita

●

Prevention and treatment of STIs

health expenditures of most developing counties, the fact that

●

Prevention of further HIV transmission

healthcare systems are ill equipped to deliver effective care, and

●

Palliative care

●

Family planning

the widespread fear and stigma associated with HIV and AIDS.

●

Good nutrition

Despite these problems, the provision of care and access to

●

Social, spiritual, psychological, and peer support

antiretroviral therapy is improving in many countries through

●

Respect for human rights

both government and private industry initiatives. These include

●

Reduction of the stigma associated with HIV and AIDS

increased access to treatments of opportunistic infections and

improved healthcare systems at a community level to support

the provision of antiretroviral therapy. However, at every level,

regional, governmental, and community multiple challenges

remain.

In June 2002, the WHO produced guidelines for scaling up

the antiretroviral therapy in resource limited settings.

●

When to start therapy is based on clinical plus CD4 count or

total lymphocyte criteria

●

An assessment of viral load is not considered essential before

Antiretroviral therapy in a resource limited setting: WHO

therapy

recommendations, June 2002

●

It is recommended that within each country’s treatment

When to start therapy

programmes, therapy regimens should be standardised, with

●

WHO stage IV of HIV disease (clinical AIDS), regardless of CD4

a single first line regimen and a limited number of second

count

line regimens for large scale use

●

WHO stages I, II, or III of HIV disease, with a CD4 count below

●

Programmes should recognise that people who cannot

200/mm³

●

WHO stages II or III of HIV disease with total lymphocyte count

tolerate or who fail standardised regimens should be referred

below 1200/mm³

for individualised care by specialist physicians

●

Triple combination regimens are recommended, dual

Recommended first line regimens

●

Zidovudine and lamivudine plus nevirapine or efavirenz

nucleoside analogue regimens are no longer reasoned to be

●

Zidovudine and lamivudine plus abacavir

acceptable

●

Zidovudine and lamivudine plus nelfinavir or low dose ritonavir

●

Changing therapy because of treatment failure should be

boosted protease inhibitor

based on clinical and CD4 count criteria

Other nucleoside analogue components can be substituted

●

The absolute minimum tests required for a treatment

depending on country specific preferences

programme is HIV serology and haemoglobin

●

Basic recommended laboratory tests, largely to monitor for

drug toxicity, include a white blood cell count, differential,

serum alanine or aspartate aminotransferase, serum

creatinine or blood urea (or both), serum glucose, and

pregnancy tests. CD4 counts are considered desirable and

viral load testing optional.

HIV

Prevention and control

As no cure or vaccine is currently available, our main weapon is

●

Surveillance

prevention and control. An “information vaccine” is required.

●

Counselling and health education

In any epidemic an accurate appreciation of the size of the

●

Screening of people and donated blood

problem and how it is changing is essential. With HIV infection

●

Heat treatment of blood products

this can be achieved by counting the number of patients with

●

Strategies to reduce high risk behaviour in targeted populations

AIDS and monitoring the prevalence of HIV antibodies in

●

Antiretroviral therapy to reduce mother to child transmission

low-risk and high-risk populations.

●

Protection of healthcare staff

●

Treatment and control of STIs

Of fundamental importance is good and accurate health

education for those at low risk and those at high risk. People

who are known to be infected or may have been exposed are

advised not to donate blood, organs, or semen, to modify their

The evidence for the efficacy of post-exposure prophylaxis

sexual behaviour, and to avoid behaviour that is particularly

after either occupational or sexual exposure to HIV is

likely to transmit the virus. The screening of blood donors for

limited. However, in clinical practice it is common to

HIV antibodies and the heat treatment of blood products have

consider post-exposure prophylaxis after considerable

virtually eliminated the risk to recipients. The treatment and

exposure to HIV, usually by a needle stick injury. It is

control of STIs is also important, as they are cofactors in

recommended that combination antiretroviral therapy be

transmission. Reductions in mother to child transmission rates

started as soon after the exposure incident as possible,

have been achieved through the use of antiretroviral therapy

preferably within 24 hours, for duration of four weeks

and in developed countries the rate has fallen to only 1-2%.

Proposed WHO staging system for HIV infection and disease

Clinical staging

Patients with HIV infection who are

13 years are clinically staged on the basis of the presence of the clinical condition or performance

score, belonging to the highest level.

●

Clinical stage 1: asymptomatic or persistent generalised lymphadenopathy, performance scale 1 (asymptomatic, normal activity)

●

Clinical stage 2: weight loss

10% of body weight, minor mucocutaeneous manifestations, varicella zoster within the last five years,

recurrent upper respiratory tract infections (bacterial sinusitis), performance scale 2 (symptomatic but normal activity)

●

Clinical stage 3: weight loss

10% of body weight, unexplained chronic diarrhoea for more than one month, unexplained chronic fever

for more than one month, oral candidiasis, oral hairy leukoplakia, pulmonary tuberculosis within the past year, severe bacterial

infections, performance scale 3 (bedridden

50% of day during the last month)

●

Clinical stage 4: most other CDC AIDS defining diseases (but not pulmonary tuberculosis), performance scale 4 (bedridden

50% of

day during the last month)

Proposed WHO clinical and laboratory classification for HIV infection and disease

Laboratory axis

Clinical axis

Lymphocytes

or CD4

(

10⁶/l)

(

10⁶/l)

Asymptomatic

Early

Intermediate

Late

2000

500

1000-2000

200-500

1000

200

The tables above are reproduced from Grant A, De Cock KM. HIV and AIDS in the developing world. In Adler M (ed) ABC of AIDS.

5th ed, London: BMJ Publishing Group, 2001

Laboratory diagnosis of sexually transmitted

infections

Beryl West

Laboratory diagnosis plays an important part in sexually

Some methods used in the diagnosis of N gonorrhoeae

transmitted infection (STI) control, both in treatment decisions

Specimen collection

for individual patients and in aetiology studies for designing

●

Use sterile swabs or loops, prepare smear at bedside or clinic,

control programmes. However, constraints that limit what

and inoculate directly onto culture media or put immediately in

laboratory services are available and practical in many settings

a non-nutritive transport media, such as Stuart or Amies media

exist in terms of costs, available expertise, and support systems.

Gram stain

Some of the methods available for diagnosis, the equipment and

●

Microscopy—detects leucocytes and intracellular Gram negative

expertise needed to perform the tests, and the suitability for use

diplococci

in clinics or specialised laboratories are discussed. The quality of

Culture (direct or inoculated from swabs in transport media)

samples and testing methods, bedside/clinic rapid diagnostic tests

●

Incubation in 5% carbon dioxide atmosphere—use selective

are also covered.

media (such as modified Thayer Martin media) for 24-48 hours

at 35 C. Presumptive colonies are picked for identification

Gonorrhoea

Presumptive identification

●

Typical Gram negative diplococci seen on Gram stain, positive

The causative organism is Neisseria gonorrhoeae (see Chapter 5).

oxidase test

A number of different tests are available for laboratory

lactamase testing

diagnosis, identification, and classification of N gonorrhoeae,

●

Chromagenic cephalosporin—rub growth from five colonies

ranging from a simple Gram stain to complicated molecular

onto rehydrated nitrocefin disc or emulsify in nitrocefin reagent

on slide—a positive reaction (red colour) detects penicillin

techniques. The method used depends on several logistical

resistance

factors, such as equipment, technical expertise and space

Antimicrobial susceptibility testing

available, support services, availability of supplies, and the

●

Minimum inhibition concentration testing or disc diffusion tests

intended use of the results, as well as financial constraints.

detect trends in resistance to antibiotics and plasmid carriage

Certain factors need to be taken into consideration when

choosing testing methods in different healthcare settings. Thus,

a simple Gram staining method could be established at

Choosing appropriate diagnostic testing methods

Setting

Diagnostic tests

Equipment and

Expertise required

Usefulness

consumables

Primary level health

Gram stain

Microscope,

Smear interpretation

Diagnosis of gonorrhoea and non-

provision or general

Gram stains

gonococcal urethritis in men.

practice

Sensitivity and specificity in male

urethral smears are 95%

and 97%, respectively

In females, cervical Gram films only

detect 40-60% culture positive

samples

Rectal swabs are only useful

if rectal mucosa is sampled

through a proctoscope, this

yields easily interpretable results

Pharyngeal swabs are not useful as

morphologically similar organisms

are in the pharynx

Intermediate level

Gram stain, culture,

Microscope, incubator,

Smear interpretation,

Culture yields the most

health provision or

presumptive

carbon dioxide jar,

recognition and

accurate diagnosis of

district general

identification

Gram stains, culture

identification of

gonorrhoea from all sites

hospital

media, oxidase

N gonorrhoeae

Enables collection of isolates

reagents

on culture plates

for further epidemiological

studies and antimicrobial

susceptibility

Central laboratory or

Gram stain, culture,

Microbiology laboratory

Trained microbiologist

Diagnosis, epidemiology,

reference laboratory

identification strain

equipment and

aetiology, susceptibility

or teaching hospital

typing, antimicrobial

supplies, typing

with laboratory

susceptibility testing,

reagents, molecular

attached

ligase chain reaction

biology systems,

or polymerase chain

minimum inhibitory

reaction

concentration

testing systems

Laboratory diagnosis of sexually transmitted infections

a primary healthcare setting with a minimum of equipment

and staff training; however, the more advanced tests require

a well equipped laboratory and trained staff.

Gram staining method

●

Prepare smear by rolling the swab over the surface of a glass slide

or inoculating from loop, dry, and fix by passing rapidly three

times through a flame

●

Flood the smear with crystal violet for one minute, rinse under

tap

●

Flood the slide with Lugols iodine for one minute, rinse under

Colonies of a pure

the tap

culture of N

●

Decolorise with acetone-ethanol for 10-20 seconds until blue is

gonorrhoeae growing on

removed from smear, rinse well with water

a modified Thayer

●

Counter stain with safranin or fuchsin for one minute, rinse well,

Martin plate

and gently blot dry

●

Examine microscopically using

100 objective

●

N gonorrhoeae appear as Gram negative (red) diplococci often

Detection of Chlamydia trachomatis

within polymorphonuclear leucocytes. Describe what is seen on

the smear, types of cells, extracellular or intracellular bacteria,

Specimen collection

●

Preferable to use cervical or urethral specimens collected by swab

and count the numbers of leucocytes per high power field

or loop; however, first void urine then self administered vaginal

swabs or tampons can be used with some detection techniques.

●

Use appropriate swabs, non-toxic for tissue culture and Dacron

Chlamydia infections

for nucleic acid detection methods. Cytobrush samples also give

The causative organism, Chlamydia trachomatis, has a unique

good yields.

●

Put swabs immediately in appropriate transport media. Store

growth cycle. The elementary body is the infectious form that is

cold before transport to the laboratory

adapted to live in an extracellular environment and is the usual

target of detection methods.

Direct microscopy

●

Giemsa staining, useful for eye infections but lacks sensitivity for

All diagnostic tests for Chlamydia require special equipment

genital specimens

and technical expertise, which make them unsuitable for use in

Culture

primary healthcare settings. Ocular staining could be carried

●

Tissue culture with McCoy cells; this used to be the most sensitive

out at intermediate level laboratories if expertise in reading

method but is time consuming and has now been superseded by

slides is available. Fluorescence detection, enzyme linked

nucleic acid detection in many laboratories

immunosorbent assay (ELISA) techniques, and polymerase

Direct immunofluorescence

chain reaction (PCR) and ligase chain reaction (LCR) methods

●

Direct antibody staining with fluorescence labelled antibody, has

must be used in specialised laboratories equipped with

92% sensitivity, 97% specificity in symptomatic men, 79%

fluorescence microscopy, ELISA readers, washers, and

sensitivity, and 98% specificity in women with intermediate

molecular biology systems.

prevalence

Enzyme immunoassays

●

ELISA techniques to detect Chlamydia lipopolysaccaride antigens.

Sensitivity low: 50-80% depending upon population and test

used. Specificity is good at around 95%

Nucleic acid detection

●

LCR and PCR kits are available. Good sensitivity and specificity:

sensitivity ranges from 95% in male urine to 98% in female

cervical swabs, and specificity around 99% for all samples

Overview of vaginal discharge infections

Specimen collection

●

Vaginal swab, preferably from the wall of posterior fornix. Either

do direct microscopy immediately or place swab in transport

Green and yellow fluorescent stained inclusions of

media, this must be read within two hours

C trachomatis in tissue culture cells

Wet preparation

●

Microscopic examination for the presence of T vaginalis,

Vaginal discharge infections

Candida, and the presence and approximate percentage of clue

cells

The most common causes of vaginal discharge are Trichomonas

Potassium hydroxide preparation

vaginalis, Candida, and bacterial vaginosis. Trichomonas and

●

Smell for typical amine smell of whiff test, microscopically

Candida can be detected with wet preparation microscopy at the

examine for Candida

clinic or by culture methods in a laboratory (see Chapter 7).

Bacterial vaginosis can be determined with clinical criteria,

pH test with pH paper

Amsel’s score, or by using a Gram staining method, such as

Gram stain

Nugent’s score.

●

Nugent’s score for bacterial vaginosis

A positive Amsel’s score is based on the presence of three of

T vaginalis or candida culture

four of the following

●

InPouch or Diamond media for T vaginalis, Sabouraud agar

plates for Candida. Feinberg-Whittington media can be used for

●

Characteristic homogeneous, white-grey, adherent discharge

both Candida and T vaginalis

●

Vaginal pH

4.5

ABC of Sexually Transmitted Infections

●

Release of a fishy odour from vaginal fluid mixed with 10%

Wet preparation method

potassium hydroxide solution (whiff test)

●

Add one drop of saline to one end of a clean glass slide and one

●

20% clue cells.

drop of 10% potassium hydroxide to the other end

●

Mix vaginal swab first in the saline and then in the potassium

hydroxide drop to form an even suspension

●

Smell the potassium hydroxide drop to detect any fishy odour

●

Cover drops with cover slips

●

Examine saline drop first using

10 objective to scan the slide

and the

40 objective to examine more closely. Look for

T vaginalis and clue cells and note the presence of any other cells

●

T vaginalis is a pear shaped flagellate, 12-25

m long, with

Gram stain vaginal smear

flagella attached to an undulating membrane that extends the

showing bacterial vaginosis as

length of its body; it is recognised by typical motility

detected by Nugent’s score

●

Clue cells are squamous epithelial cells covered with many small

of 10

coccobacillary organisms, which give a granular effect, with the

A positive Nugent’s score is based on the types of bacteria

edges of cells not clearly defined. In bacterial vaginosis, 20% of

cells will be clue cells

present in a Gram stained vaginal smear and the numbers

●

Examine potassium hydroxide preparation in the same way, look

of Gram positive lactobacilli and the numbers of Gram

for yeast cells. Yeasts are round to ovoid (4 m) and show typical

negative or Gram variable coccobacilli are estimated per high

budding and presence of mycelia

power field.

●

Predominance of lactobacilli—0-3 (negative)

●

Mixed flora—4-6 (intermediate)

●

Predominance of Gram negative coccobacilli—7-10 (positive

Serological testing for syphilis

for bacterial vaginosis).

Non-treponemal tests

●

Most common are rapid plasma reagin (RPR) and Venereal

The sensitivity of a wet preparation for detecting T vaginalis

Disease Reference Laboratory (VRDL) tests—a positive result

is 36-60%, depending upon patients, and the sensitivity of

may indicate a current infection, recent past infection, or a

cultural methods is 80-95%. A positive wet preparation has a

biological false positive (1-3%). These can be quantitatively

high diagnostic value for Candida. However, a positive culture

tested to give a known titre; false positives usually have a titre

does not necessarily indicate a need to treat, because more

below 1:4. Confirm positives with a treponemal test

than 20% of healthy women are carriers. Culture is useful if the

Specific treponemal tests

wet preparation is negative and Candida is suspected clinically.

●

Commonly used Treponema pallidum haemagglutination particle

Amsel’s score has a sensitivity of around 78% for bacterial

agglutination (TPHA), fluorescent antibody detection (FTA-Abs),

or antibody detection immunoglobulin G and immunoglobulin

vaginosis compared with Nugent’s score.

M fluorescent immunoassays(EIA)—a positive result may indicate

A wet preparation and Amsel’s score give immediate and

current infection or past infection

very useful results for managing vaginal discharge and can be

Diagnosis of “active syphilis”

incorporated at the primary healthcare level. Culture methods

●

Screen serum with non-treponemal test and confirm with specific

and the interpretation of Nugent’s score need more facilities

treponemal test or use a single enzyme immunoassay. Simple

and expertise.

RPR testing can be done at primary healthcare settings and can

be used for screening in STI and antenatal clinic populations.

The more complex serological techniques need specialised

Syphilis

equipment and are more suited for confirmatory testing in

centralised laboratories

Venereal syphilis is caused by the spirochaete Treponema

pallidum and can be diagnosed directly from clinical lesions

by dark ground microscopy. However, the use of dark

Methods for testing for herpes

ground microscopy is limited by the need for strict technical

Sample collection

conditions and expertise to produce reliable results, which

●

Swab lesion exudate where possible, use appropriate swabs, non-

makes it difficult to use. Alternative methods to detect syphilis

toxic for tissue culture and Dacron for nucleic acid detection

in genital lesions are the direct fluorescent antigen test or the

methods. Put swabs immediately in appropriate transport media.

newer DNA amplification tests, such as the polymerase chain

Store cold before transporting to the laboratory

reaction (PCR) method.

●

Take whole blood sample to collect serum for serology

Traditionally, syphilis has been diagnosed by serological

Methods for detection of herpes simplex virus type 2 (HSV-2)

testing for antibodies (see Chapter 12).

antigen in lesions or in asymptomatic carriers

●

Viral isolation using tissue culture—use cells such as human

●

Swab ulcerated lesions—use Dacron swabs for nucleic acid

diploid fibroblasts or Vero cell lines

detection methods

●

Direct detection of antigen with fluorescent labelled specific

●

Store cold before transport to the laboratory

monoclonal antibody to HSV-2—this can be done using lesion

●

Take whole blood sample to collect serum for serology.

exudate on a slide and examining with fluorescent microscopy

●

Direct detection of antigen using an antigen detection ELISA,

available as a kit—when compared with viral isolation in

Herpes

symptomatic patients sensitivity is 70-95% and specificity is

94-100%; however, sensitivity is low in asymptomatic patients

Genital herpes is most frequently caused by infection with

●

Nucleic acid detection—several good polymerase chain reaction

(PCR) methods are available

herpes simplex virus type 2 (HSV-2) but can also be caused by

HSV-1 (see Chapter 11). Genital HSV-1 acquired through

Serological antibody detection

●

Can show present or past infection. A wide range of assays are

orogenital contact is increasingly common in western Europe

commercially available, the most sensitive assays are enzyme

and North America. Recurrent genital herpes episodes occur

immunoassay based on glycoproteins specific to HSV-2

more commonly in infections caused by HSV-2.

Laboratory diagnosis of sexually transmitted infections

Although mainly diagnosed on clinical grounds, laboratory

diagnosis is important for differential diagnosis to exclude

other genital ulcer diseases and in giving appropriate advice

and counselling. However, the diagnostic methods are not

suitable for use in primary or intermediate healthcare

facilities and need to be carried out in specialised

laboratories.

Chancroid

Sample collection

Chancroid is an acute ulcerative STI caused by the bacteria

●

Collect a swab from ulcer exudate, choose appropriate swab.

Haemophilus ducreyi. Laboratory diagnosis is based on detection

Prepare smear and immediately directly inoculate culture plate

of the organism from lesions.

or store in transport media

Direct examination

●

Preparation of Gram stained smears is possible at primary level,

look for typical small Gram negative bacilli grouped in chains or

Other STI organisms

“schools of fish.” Typical slides are seen infrequently, however,

and sensitivity is less than 50%

Other organisms than those referred to here can be responsible

Culture

for STI infections. These can depend upon geographical location,

●

Haemophilus ducreyi requires enriched media and microaerophilic

such as Calymmatobacterium or Klebsiella granulomatis the causative

conditions for growth. Good laboratory conditions are needed

organism of granuloma inguinale (donovanosis). Hence,

to isolate and identify. Isolates can be used to determine

knowledge of local aetiologies is important when looking at what

antimicrobial susceptibility patterns

diagnostic tests to use.

Antigen detection

Other organisms have more tenuous links to STIs and at

●

Fluorescent labelled monoclonal antibodies, blot

radioimmunoassay

present are not part of routine screening—for example,

mycoplasma and ureaplasma. It is also important to note that it is

Nucleic acid detection

●

Polymerase chain reaction methods are available

not possible to identify a pathogen in all STI cases and these have

to be treated symptomatically or syndromically.

Rapid tests

A new generation of rapid bedside tests are now available for

STI diagnosis that can be used in the clinic to aid diagnosis and

treatment decisions. A large variety of such tests are on the

market for measuring syphilis serology and Chlamydia and

All rapid tests give results within 20

minutes with a minimum of technical

gonorrhoea antigens, and latex agglutination tests for

procedures and require little training and

T vaginalis and Candida. The efficiency of these tests varies

no equipment

widely between the types of test and manufacturer and

reported sensitivity and specificities may be based on limited

evaluations. If they are to be used, the rapid test must be

chosen carefully with all available evaluation data.

At present, the most useful rapid screen in cases of genital

discharge, particularly in women, is for gonorrhoea and

Chlamydia. For this purpose, rapid testing technology is based

on antigen detection, either with immunochromatographic

detection or optical immunoassay.

Tests for Chlamydia are more advanced and several are

available commercially, such as Clearview (Unipath, UK),

Quickvue (Quidel, USA), and Chlamydia OIA

(ThermoBioStar, USA). The most rapid tests for gonorrhoea

are still in development but a few are available now, such as

OIA Gonorrhea (ThermobioStar USA) and NOW CC

(Binax, USA).

The main disadvantages of rapid tests are that many are

not properly validated, some are not as easy to read or

as easy to perform as stated in the product literature, and

they are relatively expensive. Availability and costs are a

major hurdle to introducing syndromic management

programmes in resource poor settings. At present, the

World Health Organization’s Rapid Diagnostics Evaluation

Scheme for STIs is evaluating rapid tests for performance and

Rapid test for syphilis

operational characteristics that are appropriate to use in

ABC of Sexually Transmitted Infections

primary health care settings. This may result in the most

Quality control

promising rapid tests being made more widely available

Quality of samples taken

and at affordable rates.

●

Adequate samples must be obtained, particularly when collecting

cervical swabs for Chlamydia, which are intracellular. The correct

swabs must be use, for example, Dacron for the PCR method

Quality control

Quality of sample processing at bedside

●

Label samples and process immediately in appropriate transport

A laboratory test is only as good as the specimen taken, the

media or direct plate inoculation and Gram smear preparation.

quality of the testing procedures, and the carefulness and

Do not make the Gram smear too thick

expertise of the tester.

Quality of testing procedures

●

Tests chosen have different specification. The sensitivity and

specificity will give an idea of the expected false positive and false

negative rates

Expertise of tester

●

Good training and standard operating procedures are needed to

ensure tests run correctly and uniformly

Internal and external quality control measures

●

Internal quality control can be practised with a second reader to

repeat read a proportion of wet preparations and Gram stain

smears. Culture methods have inbuilt quality control on media.

●

External quality control is only really appropriate for

The photograph of the gram stain vaginal smear is courtesy of

intermediate or reference laboratories. Schemes are available for

Dr Catherine Ison, Department of Infectious Diseases and

microbiology and serology

Microbiology, Imperial College School of Medicine, London.

Index

Page numbers in bold type refer to figures; those in italics refer to tables.

abdominal pain

clue cells 81, 82

differential diagnosis 30

condoms

flow chart 31

female 8

alprostadil, intracavernous injection 24

promotion 13

Amsel’s score 81, 82

condylomata lata 50

angiokeratoma, scrotal 23

conjunctivitis, neonatal 34, 35

antiretrovirals, drug toxicities 75, 75

contact tracing 10, 14, 57

ascending infection, gynaecological

control and prevention 7-10

interventions 30

biomedical interventions 8-9

contact tracing 10, 14, 57

bacterial infections, presenting

education/information 8

symptoms 1, 21

primary prevention 7-9

balanitis

screening 9-10

circinate 22

secondary prevention 9-10

multiple painful ulcers 44

societal/structural interventions 8

plasma cell 21, 22

treatment 9-10

Zoon’s 21, 22

cryptococcosis, treatment 77

balanitis xerotica obliterans 21, 22

cryptosporidiosis 73, 77

balanoposthitis 21

cytomegalovirus infections 73, 77

Bartholin’s gland conditions 39

Behcet’s disease, multiple painful ulcers

dermatitis, allergic v irritant contact

40-1

biomedical interventions 8-9

dermatoses 40-2

Bowenoid papulosis 21

donovanosis 83

Bowen’s disease 21

dyspareunia 41, 42, 43

Buschke-Löwenstein tumour 57

ectopic pregnancy 32

Calymmatobacterium infection 83

eczema 41

Candida glabrata, vulvovaginitis 29

seborrhoeic 41

candidal infections

education

laboratory investigations 81, 82

behavioural changes 6, 8

male 21, 26

sexual health/condom promotion

opportunistic, treatment 77

epididymo-orchitis 19

presenting symptoms 1

erectile dysfunction 24

vulvovaginitis 25, 29

erythrasma of groin 23

cervix, examination/sampling 16

erythroplasia of Queyrat 21

chancroid

laboratory investigations 83

female examination 16

multiple painful ulcers 44

Fitz-Hugh-Curtis syndrome, and PID

chlamydial infections

epidemiology 4-5

genital itching 39-41

laboratory investigations 81

genital ulcers 44-5

rapid tests 83

multiple painful 44

maternal transmission 34-8

single 45

overview 18

genital warts 56-9

pelvic inflammatory disease (PID)

30-3

epidemiology 5

pneumonitis 35

intrameatal 56

pregnancy 34-5

molluscum contagiosum 59

presentation 17-20

penile 56

screening, prevention of PID 33

perianal 56

treatment 18

pregnancy 37, 57, 58

vaginal discharge flow chart 27

treatment 57-8

clinical processes 11-14

vulval 56

assessment 12-13

genitalia, examination 15, 16

clinical examination 12

genitourinary medicine (GUM) clinics

follow up 14

consultants 9

investigations 12-13

numbers 9

partner management 14

UK countries, workload 3

sexual histories 12

gonorrhoea

see also sexually transmitted infections

acute PID 31-2

clinical sampling 15-16

epidemiology 3-4

Index

gonorrhoea continued

quality control 84

laboratory investigations 80

rapid tests 83

wet preparation method, 82

maternal transmission 34-8

lichen planus 22, 41-2

ophthalmia neonatorum 34, 35

lichen sclerosus 21, 22, 41

overview 18

lichen simplex chronicus 41

presentation 17-20

liver failure, viral hepatitis

treatment 18

vaginal discharge flow chart 27

male examination 15