Editors

Denis Tindyebwa

Janet Kayita

Philippa Musoke

Brian Eley

Ruth Nduati

Hoosen Coovadia

Raziya Bobart

Dorothy Mbori-

Ngacha

Mary Pat Kieﬀer

Handbook on Pædiatric AIDS in Africa

by the African Network for the Care of Children Aﬀected by AIDS

full or in part, provided the source is acknowledged. is book may not be sold or used in

conjunction with commercial purposes.

Handbook on Pædiatric AIDS in Africa

by the African Network for the Care of Children Aﬀected by AIDS

Editors

Denis Tindyebwa

Janet Kayita

Philippa Musoke

Brian Eley

Ruth Nduati

Hoosen Coovadia

Raziya Bobart

Dorothy Mbori-Ngacha

Mary Pat Kieﬀer

Contributors

Gabriel Anabwani; MBChB; MMed (Paed); MSc; Clinical Professor of Paediatrics,

Baylor College of Medicine; Director, Botswana-Baylor Children’s Centre of Excellence,

Princess Marina Hospital, Gaborone, Botswana

Augustine Massawe; MD; MMed; Senior Lecturer, Consultant and Neonatologist,

Muhimbili University College of Health Sciences and Muhimbili National Hospital,

Dar es Salaam, Tanzania

Paul Bakaki; MBChB; MMed (Paed); Paediatrician/Investigator, Makerere University/

John Hopkins University Research Collaboration, Uganda

Sabrina Bakera-Kitaka; MBChB; MMed (Paed); Paediatrician, Mulago Hospital,

Uganda

G. Bhat; MD; MRCP; Former Head of Department of Paediatrics, University Teaching

Hospital, Lusaka, Zambia

Raziya Bobart; MBChB; FC Paed; MD; Associate Professor/Principal Specialist, Depart-

ment of Paediatrics & Child Health, Nelson Mandela School of Medicine, University

of Kwazulu-Natal, South Africa

Inam Chitsike; MBChB; MMed (Paed); MClin Epi; Regional Advisor PMTCT, Division

of Family and Reproductive Health, WHO Africa Region, Congo

Hoosen Coovadia; Paediatrician; Victor Daitz Professor of HIV/AIDS Research and

Director of Centre for HIV/AIDS Networking (HIVAN), Nelson Mandela School of

Medicine University of Kwazulu-Natal, Durban, South Africa

Brian Eley; MBChB; BSc; FC Paed (SA); Senior Specialist and Senior Lecturer, Red Cross

Children’s Hospital and University of Cape Town, South Africa

Laura A. Guay; MD; Associate Professor of Pathology/Paediatrics, John Hopkins

University School of Medicine, USA

Irene Inwani; MBChB; MMed (Paed); Consultant Paediatrician, Kenyatta National

Hospital, Nairobi, Kenya

Israel Kalyesubula; MBChB; MMed (Paed); DTCH; Consultant Paediatrician, Mulago

Hospital, Uganda

Janet Kayita; MBChB; MMed (Paed); MPH; Regional Senior Technical Oﬃcer, Care

and Treatment Division, Family Health International, Kenya

Mary Pat Kieﬀer; MSc; Senior Regional Technical Advisor on PMTCT and Paediatric

AIDS, USAID/REDSO, Kenya

Lawrence Marum; MD; FAAP; MPH; Medical Epidemiologist and Paediatrician Global

AIDS Program, Centers for Disease Control and Prevention, Kenya

Dorothy Mbori-Ngacha; MBChB; MMed (Paed); MPH; Senior Lecturer, Department of

Paediatrics, University of Nairobi, Kenya; Senior Technical Advisor, Centers for Disease

Control and Prevention Global AIDS Program, Kenya

Philippe Msellati; MD; PhD; Epidemiologist and Director of the Institute of Research for

Development, Burkina Faso

Peter Mugyenyi; MBChB; MRCP; Director, Joint Clinical Research Centre, Kampala,

Uganda

Angela Munyika Mushavi; MBChB, MMed (Paed); Consultant Paediatrician, Harare

Hospital, Zimbabwe

Philippa Musoke; MBChB; FAAP; Senior Lecturer and Head of Department of Paediat-

rics and Child Health, Makerere University, Uganda

Robert Mwadime; MPH; MSc; PhD; Nutritionist, FANTA/Regional Centre for Quality of

Health Care, Makerere University, Uganda

Charles Mwansambo; MBChB; BSc; DCH; MRCP; MRCPCH; Consultant Paediatrician,

Kamuzu Central Hospital, Lilongwe, Malawi

Grace Ndezi; MBChB; MMed (Paed); Senior Lecturer, Department of Paediatrics and

Child Health, Makerere University, Uganda

Ruth Nduati; MBChB; MMed (Paed); MPH (Epid); Senior Lecturer, Department of

Paediatrics, University of Nairobi, Kenya

Neema Rusibamaliya; MD; MMed (Paed); Paediatrician, Muhimbili National Hospital,

Dar es Salaam, Tanzania

Deborah Nakiboneka Senabulya; MBChB; MMed (Paed); Paediatrician, Mulago Hospi-

tal, Uganda

Ismail Ticklay; MSc, MBChB, MMed (Paed), Consultant Paediatrician, Harare Hospital;

Honorary Lecturer, University of Zimbabwe, Zimbabwe

Denis Tindyebwa; MBChB; MMed (Paed); Senior Consultant Paediatrician, HIV/AIDS

Advisor, Regional Centre for Quality of Health Care, Makerere University, Uganda

Acknowledgments

We sincerely thank the oﬃce of USAID REDSO/ESA, based in Nairobi, Kenya, for agreeing to fund

the entire production of this handbook, including the many meetings the authors and editors

held to put the chapters together. We are grateful to Family Health International for managing the

copyediting, design, and printing.

USAID/REDSO funded this activity through the Regional Centre for Quality of Health Care

(RCQHC) at Makerere University, to which we are also grateful.

We also thank USAID/REDSO for funding the African Network for the Care of Children Aﬀected by

AIDS (ANECCA) in its broader eﬀorts to improve the care of HIV-aﬀected and -infected children

in Africa.

ANECCA is an informal network of health workers and social scientists committed to ﬁnding ways

to improve care for HIV-exposed and -infected children in Africa. Members of the network identi

ﬁed the fact that while there are widespread knowledge gaps in the care of HIV-infected children

in Africa, there are nonetheless scattered experiences across the continent that need to be shared.

ey thus volunteered their time to put together this book. It was a long and sometimes stressful

process. Because some issues concerning paediatric AIDS had no clear-cut international or national

guidelines, network members had to reach consensus, sometimes through intense discussions. I

thank them for the mature and professional manner in which they held these discussions to reach

the consensus reﬂected in this handbook.

As much as possible, and where they do exist, we have tried to remain within the available interna

tional guidelines from WHO or UNICEF, and these are acknowledged.

ANECCA members who are authors of this handbook also form the core of their respective

national committees on paediatric AIDS care, and some sections resemble what appears in their

national guidelines. We therefore acknowledge these national guidelines and the individual authors

who provided us with the materials therein. Special mention goes to our colleagues in South Africa

(Prof. H. Coovadia, Prof. Raziya Bobart, Dr. Brian Eley, and Dr. Tammy Meyers).

We would also like to acknowledge comments received after the launch of the preliminary edition

at the International AIDS Conference in Bangkok in July 2004. Special thanks go to Dr. Peter Salama

of the USAID Africa Bureau in Washington and Dr. Timothy Quick of the USAID Global Health

Bureau, also in Washington.

We would like to thank all of the enthusiastic readers who have sent in numerous requests for cop

ies of the initial handbook and who, in the process, have expedited this ﬁnal edition.

Dr Denis Tindyebwa

Chairperson

African Network fo r the Care of Children Aff ected by AID S (ANECCA)

ANECCA Secretariat

Regional Centre for Q uality of H ealth Care

PO Box 291 40

Kampala, Uganda

Tel 256-41-530888

Fax 256-41-530876

Email dtindyebwa@rcqhc.org or anecca@rcqhc.org

e handbook will be available at the Regional Centre for Quality of Health Care Web site:

www.rcqhc.org

Handbook on Pædiatric AIDS in Africa

Table of Contents

Acronyms and Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Chapter 1: Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Introduction

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Chapter 2: Epidemiology, Pathogenesis, and Natural History . . . . . . . . . . . . . . . . . . . 15

Epidemiology

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

HIV Virology and Pathogenesis

. . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

Natural History

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

Chapter 3: Preventing Paediatric HIV Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

HIV Transmission Modes in Children . . . . . . . . . . . . . . . . . . . . . . . . . .

Preventing Paediatric HIV Infection

. . . . . . . . . . . . . . . . . . . . . . . . . . 38

Preventing Other Modes of Horizontal Transmission . . . . . . . . . . . . . . . . . . .

Post-Exposure Prophylaxsis for Healthcare Providers

. . . . . . . . . . . . . . . . . . . 51

Chapter 4: Approach to Care of HIV-Exposed or HIV-Infected Child . . . . . . . . . . . . . . 53

Interventions Common to Both HIV-Exposed and HIV-Infected Infants

. . . . . . . . . . . 57

Services Speciﬁc for HIV-Infected Children

. . . . . . . . . . . . . . . . . . . . . . . 65

Children Whose Parents/Guardians Have AIDS or Who Are Orphaned by AIDS

. . . . . . . 69

Chapter 5: Diagnosis and Clinical Staging of HIV Infection . . . . . . . . . . . . . . . . . . . . . 73

Why Is It Important to Make a Diagnosis of HIV Infection?

. . . . . . . . . . . . . . . . 75

Laboratory Assays (Tests)

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79

Virologic Tests

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80

Staging HIV Infection and Disease in Children . . . . . . . . . . . . . . . . . . . . . .

Chapter 6: Common Clinical Conditions Associated with HIV . . . . . . . . . . . . . . . . . . 91

Diarrhoea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Malnutrition

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96

Neurological Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

102

Other Neurological Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . .

104

Dermatitis and Other Skin Manifestations . . . . . . . . . . . . . . . . . . . . . . . .

107

Oral and Dental Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

109

Malignancy

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .110

Parotid Enlargement

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .110

Persistent Generalised Lymphadenopathy . . . . . . . . . . . . . . . . . . . . . . . .

111

Other Medical Conditions

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .111

Chapter 7: Pulmonary Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .115

Bacterial Pneumonia

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .117

Managing Bacterial Pneumonia

. . . . . . . . . . . . . . . . . . . . . . . . . . . .119

Managing Severe Pneumonia

. . . . . . . . . . . . . . . . . . . . . . . . . . . . .119

Pneumocystis Pneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

121

Handbook on Pædiatric AIDS in Africa

Chronic Lung Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .124

Tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

124

Drug/Drug Interactions

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .129

Lymphoid Interstitial Pneumonitis

. . . . . . . . . . . . . . . . . . . . . . . . . . .129

Bronchiectasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

131

Viral Pneumonitis

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .132

Other Pulmonary Conditions

. . . . . . . . . . . . . . . . . . . . . . . . . . . . .133

Chapter 8: Antiretroviral erapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .135

Principles of ART

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .138

ART for Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

139

Organisational Issues

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .140

Opportunities and Entry Points for ART in Children

. . . . . . . . . . . . . . . . . . .141

Requirements Before Treatment Is Started . . . . . . . . . . . . . . . . . . . . . . . .

142

Pre-Treatment Assessment

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .144

First-Line erapy

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .144

Monitoring and Follow-Up

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .147

Antiretroviral erapy and TB Treatment

. . . . . . . . . . . . . . . . . . . . . . . .149

Indications for Changing erapy

. . . . . . . . . . . . . . . . . . . . . . . . . . .149

Second-Line erapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

151

Chapter 9: Adolescent Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .159

Adolescents Requiring HIV-Related Services . . . . . . . . . . . . . . . . . . . . . . .

163

Risk Factors for HIV Infection Among Adolescents

. . . . . . . . . . . . . . . . . . . .163

HIV Preventive Services for Youth

. . . . . . . . . . . . . . . . . . . . . . . . . . .165

Services for HIV-Infected Youth

. . . . . . . . . . . . . . . . . . . . . . . . . . . .167

Support for Youth-Friendly Policies and Programmes

. . . . . . . . . . . . . . . . . . .174

Chapter 10: Long-Term and Terminal Care Planning for Children Aﬀected by HIV/AIDS and

eir Families

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .177

Is Chronic Disease Management Relevant to Children Infected with HIV?

. . . . . . . . . .179

What Is the Starting Point for Planning Long-Term Care?

. . . . . . . . . . . . . . . . .180

Needs of the Well Child

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .181

Needs of the Sick Child

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .182

Needs of the Terminally Ill Child

. . . . . . . . . . . . . . . . . . . . . . . . . . . .183

Symptom Relief

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .185

Pain Management

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .188

Child with Terminally Ill Parents

. . . . . . . . . . . . . . . . . . . . . . . . . . . .192

Requirements to Ensure that Long-Term Care Is Planned and Executed

. . . . . . . . . . .194

Chapter 11: Counselling and Psychosocial Support . . . . . . . . . . . . . . . . . . . . . . . . .199

Periods of Psychosocial Vulnerability

. . . . . . . . . . . . . . . . . . . . . . . . . .202

Issues to Address in Psychosocial Support for Children Aﬀected by HIV/AIDS

. . . . . . . .203

Handbook on Pædiatric AIDS in Africa

Psychosocial Needs of Children . . . . . . . . . . . . . . . . . . . . . . . . . . . .205

Problems that Can Occur in Infected or Aﬀected Children

. . . . . . . . . . . . . . . .205

Communicating with Children

. . . . . . . . . . . . . . . . . . . . . . . . . . . .205

HIV Testing for Children

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .207

Counselling and Disclosure

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .207

Steps for Counselling HIV-Infected Children . . . . . . . . . . . . . . . . . . . . . . .

211

Chapter 12: Nutrition and HIV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .213

Nutrition Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

215

Prevent or Mitigate Factors Associated with Risk of Malnutrition . . . . . . . . . . . . . .21

Infant Feeding Practices in the Context of HIV . . . . . . . . . . . . . . . . . . . . . .

217

Periodic Nutrition Assessment and Growth Monitoring . . . . . . . . . . . . . . . . . .22

Provide Nutritional Supplementation and Rehabilitation

. . . . . . . . . . . . . . . . .223

Preserving Lean Body Mass

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .229

Additional Strategies

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .229

Appendices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .231

Appendix A: Clinical Situations and Recommendations for the Use of Antiretroviral Drugs in

Pregnant Women and Women of Child-Bearing Potential in Resource-Constrained Settings

. .233

Appendix B: CDC 1994 Revised Human

Immunodeﬁciency Virus

Paediatric Classiﬁcation System: Clinical Categorie

s . . . . . . . . . . . . . . . . . . . .237

Appendix C: Sexual Maturity Rating

. . . . . . . . . . . . . . . . . . . . . . . . . .241

Appendix D: Safe Infant Feeding

. . . . . . . . . . . . . . . . . . . . . . . . . . . .243

Appendix E: Grading of Adverse Events . . . . . . . . . . . . . . . . . . . . . . . . .

250

Tables and Figures

Figure 2.1. Median HIV Prevalence (%) in Antenatal Clinics in Urban Areas,

by Sub-Region, in Sub-Saharan Africa, 1990−2002

. . . . . . . . . . . . . . . . . . . . 18

Figure 2.2. Estimated Impact of AIDS on Under-Five Child Mortality Rates,

Selected African Countries

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Figure 2.3. Infant Mortality Rates in HIV-Exposed and Unexposed Babies: Data

from 5 Diﬀerent Cohort Studies

. . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

Figure 2.4. Estimated Prevalence of HIV-1 env Subtypes by Region (2000) . . . . . . . . . . 23

Figure 2.5. HIV Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

Figure 2.6. HIV Replication Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

Table 2.1. Immunologic Classiﬁcation for HIV-Infected Infants and Children . . . . . . . . . 28

Table 3.1. Estimated Timing of Transmission and Absolute Transmission Rates . . . . . . . . 35

Table 3.2. Risk Factors and Mitigating Interventions . . . . . . . . . . . . . . . . . . . 37

Figure 3.1. Four-Pronged Approach to Paediatric HIV Infection (UN/WHO) . . . . . . . . . 38

Table 3.3. Early MTCT Rates in Breast-Feeding Populations Where Women

Received Antepartum and/or Intrapartum and/or Postpartum Regimens

. . . . . . . . . . 42

Handbook on Pædiatric AIDS in Africa

Figure 3.2. PMTCT Cascade: Women Attending ANC . . . . . . . . . . . . . . . . . . 46

Figure 3.3. HIV-Infected Women Accessing Services . . . . . . . . . . . . . . . . . . . 47

Table 3.4. Drug Dosage for Post-Exposure Prophylaxis . . . . . . . . . . . . . . . . . . 49

Table 4.1. Who Needs PCP Prophylaxis? . . . . . . . . . . . . . . . . . . . . . . . . 62

Table 4.2. Dose of Cotrimoxazole for PCP Prophylaxis . . . . . . . . . . . . . . . . . . 62

Table 4.3. WHO Recommendations for Follow-up of an HIV-Exposed Child . . . . . . . . . 64

Table 5.1. Clinical Signs or Conditions in Child at May Suggest HIV Infection . . . . . . . 78

Table 5.2. WHO Paediatric Staging of HIV/AIDS Disease . . . . . . . . . . . . . . . . . 85

Table 5.3. 1986 WHO Case Deﬁnition of AIDS in Children . . . . . . . . . . . . . . . . 87

Table 5.4. Immunological Classiﬁcation Based on Total and % CD4 Count . . . . . . . . . 88

Table 5.5. What Can Be Done for Diﬀerent Levels of Resources and Certainty of Diagnosis? . . 89

Table 6.1. Opportunistic Infections of the Central Nervous System . . . . . . . . . . . . .106

Table 6.2. Common Skin Manifestations and Treatments . . . . . . . . . . . . . . . . .108

Figure 7.1. reat of PCP: AIDS-Deﬁning Conditions by Age at Diagnosis

Perinatally-Acquired AIDS Cases through 1992, USA

. . . . . . . . . . . . . . . . . . .122

Table 7.1. Evaluation of HIV-Exposed Infant for Tuberculosis Disease . . . . . . . . . . . .125

Table 7.2. Impact of HIV Infection on Value of Commonly Used Criteria for Diagnosis of TB. .126

Table 7.3. Treatment/Prophylaxis of TB in HIV-Exposed or HIV-Infected Infants . . . . . . .128

Table 7.4. Comparison of Miliary TB and LIP . . . . . . . . . . . . . . . . . . . . . .130

Table 8.1. Speciﬁc Issues to Consider When Treating HIV-Infected Children with ART . . . .139

Table 8.1. WHO Recommendations for ART in Children When CD4 Testing Is Available: . . .143

Table 8.2. Antiretroviral Drugs in Paediatric Practice . . . . . . . . . . . . . . . . . . .145

Table 8.3. Clinical Signs, Symptoms, Monitoring, and Management

of Symptoms of Serious Adverse Eﬀects of ART that Require Drug Discontinuation . . . . . .15

Table 9.1. Adolescent Development . . . . . . . . . . . . . . . . . . . . . . . . . .162

Table 10.1. Other Common Symptoms, Causes, and eir Management . . . . . . . . . .187

Table 10.2. Children’s Perceptions of Death and Possible Interventions . . . . . . . . . . .193

Figure 10.2. Long-Term Care Planning for Children with HIV . . . . . . . . . . . . . . .196

Table 11.1. Psychosocial Assessment of Anticipated Family Adaptation . . . . . . . . . . .202

Figure 12.1. Weight-for-Age Before and After Onset of ARV erapy . . . . . . . . . . . .223

Table 12.1. Strategies to Prevent and Treat Malnutrition in HIV-Exposed

and HIV-Infected Children

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .225

Table 12.2. Nutritional Management for Children With and Without Evidence

of Malnutrition

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .228

Handbook on Pædiatric AIDS in Africa

Acronyms and Abbreviations

3TC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Lamivudine

ABC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Abacavir

AIDS

. . . . . . . . . . . . . . . . . . . . . . . Acquired Immune Deﬁciency Syndrome

ANC

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Antenatal Care

ART . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Antiretroviral erapy

ARV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Antiretroviral Drugs

AZT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Zidovudine

BCC

. . . . . . . . . . . . . . . . . . . . . . . . . .Behaviour Change Communication

CBC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Complete Blood Count

CDC

. . . . . . . . . . . . . . . . United States Centers for Disease Control and Prevention

CFR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Case Fatality Rate

CSF

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Cerebrospinal Fluid

CMV

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Cytomegalovirus

CNS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Central Nervous System

CRC . . . . . . . . . . . . . . . . . . United Nations Convention on the Rights of Children

CT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Computerized Tomography

CTZ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Cotrimoxazole

d4T . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Stavudine

ddI

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Didanosine

DNA

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Deoxyribonucleic Acid

DOT

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Directly Observed erapy

EBV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Epstein Barr Virus

EEG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Electroencephalograph

EFV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Efavirenz

ELISA

. . . . . . . . . . . . . . . . . . . . . . . . Enzyme-Linked Immunosorbent Assay

EPI

. . . . . . . . . . . . . . . . . . . . . . . . Expanded Programmes on Immunisation

FHI

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Family Health International

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Glycoprotein

HAART

. . . . . . . . . . . . . . . . . . . . . . . . Highly Active Antiretroviral erapy

HIV . . . . . . . . . . . . . . . . . . . . . . . . . . . .Human Immunodeﬁciency Virus

HPV

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Human Papillomavirus

HRSA

. . . . . . . . . . . . . . . . . . . . . Health Resources and Services Administration

HSV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Herpes Simplex Virus

IDU . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Injecting Drug User

Handbook on Pædiatric AIDS in Africa

IMCI . . . . . . . . . . . . . . . . . . . . Integrated Management of Childhood Illnesses

I/O . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Input and Output

IU . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . International Units

IPT

. . . . . . . . . . . . . . . . . . . . . . . . . . . Intermittent Preventative erapy

IRIS

. . . . . . . . . . . . . . . . . . . . Immune Reconstitution Inﬂammatory Syndrome

KS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Kaposi’s Sarcoma

LBM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Lean Body Mass

LBW

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Low Birth Weight

LIP

. . . . . . . . . . . . . . . . . . . . . . . . . . . Lymphoid Interstitial Pneumonitis

LPV/RTV

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Lopinavir/Ritonavir

LRTI . . . . . . . . . . . . . . . . . . . . . . . . . . . Lower Respiratory Tract Infection

MCH

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Maternal and Child Health

MRI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Magnetic Resonance Imaging

MTB

. . . . . . . . . . . . . . . . . . . . . . . . . . . . Mycobacterium Tuberculosis

MTCT . . . . . . . . . . . . . . . . . . . . . . . . . . . . Mother-to-Child Transmission

mths

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Months

MUAC

. . . . . . . . . . . . . . . . . . . . . . . . . . Mid-Upper-Arm Circumference

NASBA

. . . . . . . . . . . . . . . . . . . . .Nucleic Acid Sequence-Based Ampliﬁcation

NCHS . . . . . . . . . . . . . . . . . . . . . . . . . National Center for Health Statistics

NFV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nelﬁnavir

NNRTI

. . . . . . . . . . . . . . . . . . .Non-Nucleoside Reverse Transcriptase Inhibitors

NRTI

. . . . . . . . . . . . . . . . . . . . . . Nucleoside Reverse Transcriptase Inhibitors

NSI

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Non-Syncitium Inducing

NVP

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nevirapine

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Opportunistic Infection

OVC

. . . . . . . . . . . . . . . . . . . . . . . . . . Orphans and Vulnerable Children

PACTG

. . . . . . . . . . . . . . . . . . . . . . . . .Pediatric AIDS Clinical Trials Group

PCP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Pneumocystis Pneumonia

PCR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Polymerase Chain Reaction

PEP

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Post-Exposure Prophylaxis

PGL . . . . . . . . . . . . . . . . . . . . . . . . Persistent Generalized Lymphadenopathy

PI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Protease Inhibitor

PLHA

. . . . . . . . . . . . . . . . . . . . . . . . . . . . People Living with HIV/AIDS

PML . . . . . . . . . . . . . . . . . . . . . Progressive Multifocal Leukoencephalopathy

PMTCT

. . . . . . . . . . . . . . . . . . . . .Prevention of Mother-to-Child Transmission

Handbook on Pædiatric AIDS in Africa

RNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Ribonucleic Acid

RSV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Respiratory Syncytial Virus

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Reverse Transcriptase

RTV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ritonavir

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Rotavirus

SFT

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Skin-Fold ickness

SMX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sulfamethoxazole

SSA

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Sub-Saharan Africa

STI

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sexually Transmitted Infection

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Tuberculosis

TLC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Total Lymphocyte Count

TMP

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Trimethoprim

UNAIDS . . . . . . . . . . . . . . . . . . . .United Nations Joint Programme on HIV/AIDS

UNFPA

. . . . . . . . . . . . . . . . . . . . . . . . . .United Nations Population Fund

UNFPA

. . . . . . . . . . . . . . . . . . . . . . . . . . United Nations Children’s Fund

URI

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Upper Respiratory Infection

USAID

. . . . . . . . . . . . . . . . . United States Agency for International Development

VCT

. . . . . . . . . . . . . . . . . . . . . . . . . . Voluntary Counselling and Testing

VZIG

. . . . . . . . . . . . . . . . . . . . . . . . . . Varicella-Zoster Immune Globulin

WBC

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . White Blood Count

WHO

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . World Health Organization

wk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Week

wks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Weeks

ZDV

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Zidovudine

Handbook on Pædiatric AIDS in Africa

Chapter 1

Introduction

Handbook on Pædiatric AIDS in Africa

Introduction

HIV/AIDS is a major cause of infant and childhood mortality and

morbidity in Africa. In children under ﬁve years of age, HIV/AIDS

now accounts for 7.7% of mortality worldwide. AIDS already accounts

for a rise of more than 19% in infant mortality and a 36% rise in under-

ﬁve mortality. Together with factors such as declining immunisation,

HIV/AIDS is threatening recent gains in infant and child survival and

health.

Yet, for the most part, HIV infection in children is preventable. In

industrialised countries in North America and Europe, paediatric HIV

infection has largely been controlled. In these settings, HIV testing as

part of routine antenatal care, combinations of antiretroviral (ARV)

drug regimens, elective caesarean section, and complete avoidance

of breast-feeding have translated into mother-to-child transmission

(MTCT) rates of less than 2%.

In Africa, on the other hand, high rates of maternal HIV infection,

high birth rates, lack of access to currently available and feasible in

terventions, and the widespread practice of prolonged breast-feeding

translate into a high burden of paediatric HIV disease. e transmis-

sion risk for a child born to an HIV-infected mother in an African

setting without interventions for prevention of mother-to-child trans-

mission (PMTCT) is about 30–40%. e other 60–70% of children,

although not HIV-infected, still have a 2- to 5-fold risk of mortality as

a direct consequence of the mother’s HIV disease, when compared to

children born to uninfected mothers.

Eﬀorts to expand care and treatment for children must go hand in

hand with eﬀorts to rapidly improve the uptake of available interven

tions for reducing MTCT. Currently these reach less than 10% of the

population in the countries that are most aﬀected. Access to currently

available, eﬀective care and treatment remains a major obstacle.

e fast rate of HIV progression and the high morbidity and mortality

among infants and children with perinatally acquired HIV infection

means that identifying these children and enrolling them in care

Handbook on Pædiatric AIDS in Africa

programmes should be considered an emergency. e window of

opportunity for eﬀective intervention is much too brief for too many

of these children, who often die in infancy and early childhood from

preventable and/or treatable common childhood conditions and op-

portunistic infections (OIs).

While it is true that the diagnosis of HIV/AIDS in children can be

technologically complex and clinically unreliable, we must ensure

that the absence of a deﬁnitive laboratory diagnosis does not become

a disincentive to provide (or an excuse to deny) available care to

children and their families. We must not only continue to improve ac

cess to appropriate diagnostics but must also invest in health workers’

skills in suspecting and/or diagnosing HIV in children, in commu-

nicating diﬃcult news to parents and guardians, and in positioning

families to beneﬁt from the best care available in each setting.

ere is a widespread need to train primary healthcare workers in

the integrated management of childhood infections (IMCI), includ

ing community-based IMCI. is approach empowers households to

practice behaviours that are essential in preventing illnesses and seek-

ing appropriate healthcare, as well as in infant and young child feed-

ing and other traditional child survival strategies that are particularly

critical for HIV-exposed and -infected children.

Collectively, we have the best opportunity to date of making an

impact on the paediatric HIV epidemic. ere is international will

and commitment (for example, WHO’s 3 by 5 initiative, the Global

Fund for AIDS, TB and Malaria, and the U.S. government’s Presiden

tial Emergency Plan for AIDS Relief) to rapidly expand programmes

for identifying HIV-infected adults through voluntary counselling

and testing (VCT), preventing mother-to-child transmission of HIV,

preventing and treating opportunistic infections (OIs) and other

common HIV-related conditions, and providing antiretroviral therapy

(ART) to those who need it.

We must exploit these eﬀorts fully to beneﬁt both adults and children

with HIV infection and disease by implementing child- and fam-

Handbook on Pædiatric AIDS in Africa

ily-centred care and treatment services. Furthermore, the impact of

maternal HIV disease on childhood morbidity and mortality means

also addressing parental health, in order to have a meaningful impact

on child health and well-being. As national eﬀorts to expand access

to HIV prevention, care, and treatment continue, opportunities will

increase to identify other at-risk (including HIV-exposed infants) and

infected family members.

In most of sub-Saharan Africa there are limited paediatric HIV diag

nostic facilities and most HIV-infected children, like adults, are diag-

nosed very late in the course of illness, or not at all. Children under

age 15, who make up nearly 10% of the total HIV-positive population,

must also beneﬁt from the best available HIV prevention, care, and

treatment in their communities.

Whereas few people dispute children’s right to HIV care and treat

ment, few eﬀorts are made to ensure that children actually beneﬁt

from these services. How can we reach children to enroll them in

care programmes? Who will pay for their care? Are appropriate drug

formulations available? How should we monitor the children on treat-

ment, and what if they are in sibling-headed households? Commit-

ment to care and treatment for children must go beyond tokenism;

we must set targets, provide guidance, and plan for paediatric HIV

care. Caring for and treating children with HIV will be as complex—

or as doable—as our will to make it happen.

While there are many books about HIV/AIDS in Africa, they contain

little in the way of practical experiences, insights, or guidelines about

the care of children. Most paediatric HIV handbooks are from de

veloped countries and are, therefore, less relevant for practitioners in

resource-constrained African settings. We recognise that Africa is not

homogeneous—in infrastructure or resources—but our hope is that

this handbook will provide users in various countries with a resource

that can be adapted to meet their speciﬁc needs.

e framework proposed in this handbook follows the United Nations

Convention on the Rights of the Child (CRC) and its four principles:

Handbook on Pædiatric AIDS in Africa

• Right to life, survival, and development

• Right to be treated equally

• Right to participate in activities and decisions that aﬀect them

• All actions should be based on the “best interests” of the child.

is handbook seeks to provide a simple, accessible, and practical

handbook for health professionals involved in preventing infection

and caring for children infected and aﬀected by HIV. e primary

targets are medical students and their lecturers, nurses, clinicians,

community health workers, and other service providers in resource-

poor settings where there is a signiﬁcant HIV/AIDS burden.

Research on HIV/AIDS is global and ongoing, and new informa

tion becomes available continuously, particularly in the areas of

PMTCT and ART; thus, this handbook will be a living document,

updated as we learn from our experiences. ere are many gaps in

our knowledge—not only because there is little experience, but also,

and perhaps more importantly, because many solid, but small-scale,

programmes caring for children are poorly documented.

We hope this handbook will stimulate much-needed dialogue, docu

mentation, dissemination, and learning from these invaluable experi-

ences, however imperfect. In the words of a highly valued colleague

and advocate: “We must not allow the excellent to become the enemy

of the good.” Let’s not wait for perfect conditions in terms of infra-

structure and resources before we provide the care that HIV-infected

children in Africa deserve.

Handbook on Pædiatric AIDS in Africa

Chapter 2

Epidemiology, Pathogenesis,

and Natural History

Summary

• UNAIDS estimated that in 2003 there were 630,000 new paediatric

HIV infections, about 90% of which were in sub-Saharan Africa.

• e high HIV infection rate in children in Africa results directly

from the high HIV infection rate in women of childbearing age and

the eﬃciency of MTCT.

• Compared to adults, there are age speciﬁc diﬀerences in the immu-

nologic markers of disease, virologic (HIV ribonucleic acid) pattern,

and clinical manifestations of perinatal HIV infection.

• e clinical course of paediatric HIV infection is more rapid than

in adults.

• e natural history of children perinatally infected with HIV ﬁts

into one of three categories:

• Category 1: Rapid progressors, who die by age 1 and are thought

to have acquired the infection in utero or during the early

perinatal period (about 25–30%)

• Category 2: Children who develop symptoms early in life, fol-

lowed by a downhill course and death by age 3 to 5 years (about

50–60%)

• Category 3: Long-term survivors, who live beyond age 8 (about

5–25%)

• ere are several reasons for the higher mortality of HIV-infected

African children as compared to their counterparts in developed

countries: intercurrent infections, malnutrition, limited access to

care and treatment and, above all, lack of access to ART, which has

led to dramatic improvements in survival of children in developed

countries.

Handbook on Pædiatric AIDS in Africa

Epidemiology

Historical Perspective

Adult AIDS, and particularly the syndrome “Slim disease,” was ﬁrst

described in Africa in the early 1980s. Paediatric HIV cases were ﬁrst

observed in clinical services in the East Africa region in the early to

mid-1980s.

In Rwanda and Democratic Republic of Congo (in Kinshasa) the ﬁrst

cases of paediatric AIDS were identiﬁed in 1983–1984 in the clinical

services and later in seroprevalence and perinatal studies. In Uganda,

reports of paediatric HIV were documented in 1985 and in a special

ist clinic started in 1988.

In the mid-1980s, longitudinal cohort studies were started in the cit

ies of Kigali, Kampala, Kinshasha, Nairobi, and Blantyre, among oth-

ers, to study the MTCT rate and the natural history of HIV-exposed

and -infected children.

Magnitude of HIV/AIDS Epidemic in Children in Sub-Saharan Africa

e high HIV infection rate in children in Africa results directly from

(1) the high HIV infection rate in women of childbearing age and (2)

the eﬃciency of MTCT.

Of close to 40 million people living with HIV at the end of 2003, 70%

live in sub-Saharan Africa, and 60% of those infected in sub-Saharan

Africa are women. Infection rates among pregnant women in Africa

range from 1% in Senegal to over 40% in Botswana (see

Figure 2.1).

Of the 2.1 million children under the age of 15 years living with HIV

worldwide, at least 90% live in sub-Saharan Africa. UNAIDS estimat

ed that in 2003 there were 630,000 new paediatric HIV infections. It

is currently estimated that in developing countries 1,600 children are

infected daily by their HIV-infected mothers.

Handbook on Pædiatric AIDS in Africa

Figure 2.1. Median HIV Prevalen ce (%) in Antenatal Clin ics in Urban Areas , by

Sub-Region, in Sub-Saharan Af rica, 1990−2002

��

�

��

Impact of the AIDS Epidemic on Children

AIDS aﬀects children in many ways:

• In Africa, more than 400,000 children under 15 died of AIDS in

2003 alone. Demographic data from sub-Saharan Africa clearly

show the estimated impact of HIV on childhood mortality

(Figure 2.2).

• Maternal ill health, especially HIV-related, has a negative eﬀect

on infant survival. Infant and early childhood mortality among

children of HIV-infected mothers (HIV exposed) is 2 to 5 times

higher than that among children of HIV-negative mothers (HIV

unexposed).

Handbook on Pædiatric AIDS in Africa

Figure 2.2. Estimated Impact of AIDS on Under-Five Child Mortality Rates,

Selected African Countries

�

��

• ere are over 13 million orphans worldwide who have lost one or

both parents from AIDS. It is projected that by 2010 the number

of children orphaned by AIDS will increase to more than 25 mil-

lion. In 2001, 10 countries in sub-Saharan Africa had orphan rates

higher than 15%, with at least half of the orphans resulting from

AIDS (see Figure 2.3).

• e impact of AIDS on families and communities also aﬀects non-

orphaned children. With the deepening poverty that results from

sick and dying parents, children are the ﬁrst to suﬀer. ey suﬀer

mental, psychological, and social distress and increasing material

hardships. e children may be the only caregivers for their sick or

dying patients, may drop out of or interrupt school, and are at risk

of discrimination and abuse, both physical and sexual.

Handbook on Pædiatric AIDS in Africa

Figure 2.3. Infant Mortality Rates in HIV-Exposed and Unexposed Babies: Data

from 5 Diﬀerent Cohort Studies

�

��

Modes of HIV Transmission

ere are several potential modes of transmission of HIV to children,

including MTCT, sexual transmission among adolescents, sexual

abuse of children, transfusion of infected blood or blood products,

unsterile injection procedures, and scariﬁcation.

More than 95% of HIV-infected infants in Africa acquire HIV from

their mothers during pregnancy, at the time of delivery, or postnatally

through breast-feeding. Without any intervention, between 30 and

40% of breast-feeding HIV-positive women transmit HIV to their new

borns. e risk factors that increase MTCT are detailed in chapter 3.

Sexual transmission is a signiﬁcant mode of transmission among

adolescents.

e role of child sexual abuse as a source of HIV infection in children

is undocumented, but this mode of transmission is of particular con

cern in countries where both HIV and child sexual abuse are major

Handbook on Pædiatric AIDS in Africa

public health concerns. Orphans are particularly vulnerable to sexual

abuse.

Transfusion of infected blood or blood products is another possible

source of HIV infection in children, but this mode of transmission

has been greatly reduced by national blood safety programmes and

improved blood transfusion services.

HIV can also be transmitted to children by using unsterile injection

needles and procedures, but this is considered rare, even in Africa.

WHO estimates that unsafe injections account for about 2.5% of HIV

infections in both adults and children.

Scariﬁcation from traditional healers may also be a source of in

fection to children. While scariﬁcation may be more frequent in

HIV-infected children, the process may represent desperate attempts

by mothers and guardians to treat recurrent illnesses in the child,

rather than being a source of the HIV infection. However, communal

traditional rituals and therapeutic procedures that involve bleeding

are potential modes of transmission, and communities must be edu-

cated about the potential dangers of these practices.

Handbook on Pædiatric AIDS in Africa

HIV Virology and Pathogenesis

Basic Virology

ere are two types of HIV: HIV-1, which is found worldwide and is

responsible for the worldwide pandemic, and HIV-2, found mainly

in West Africa, Mozambique, and Angola. HIV-2 is less pathogenic

and makes little or no contribution to paediatric AIDS; therefore, all

discussion in this handbook refers to HIV-1.

HIV-1 has many subtypes: A, B, C, D, E (see

Figure 2.4, which shows

subtypes by region). Africa has mainly subtypes A and D (East and

Central), C (Southern Africa), and A recombinants (West Africa).

Subtype C is responsible for over 90% of infections in southern Africa.

Subtype C seems to be more virulent than the other subtypes. It has

higher transcription rates; it is associated with faster disease progres

sion and with higher MTCT rates than subtypes A and D.

Handbook on Pædiatric AIDS in Africa

Figure 2.4. Estimated Prevalence of HIV-1 env Subtypes by Region (2000)

��

�

��

�

��

Osmanov, S et al. Estimated Global Distribution and Regional Spread of HIV-1 Genetic Subtypes in the Year 2000. JAIDS 2002:29

Handbook on Pædiatric AIDS in Africa

HIV Structure

HIV is a spherical ribonucleic acid (RNA) virus particle with a

diameter of 80–100 nanometers (nm) (Figure 2.5). e particle has

an outer double lipid layer derived from the host cell membrane.

Within the lipid layer is the surface glycoprotein (gp120) and the

trans-membrane protein (gp41), which mediate the entry of the virus

into the host cell.

e core (capsid) is made of several proteins: p24 (the main protein),

p17, p9, and p7. Within this capsid are two single strands of identical

pieces of RNA, which are the genetic material of the virus (virion).

e virion contains a number of enzymes, the most important of

which are reverse transcriptase (RT), protease, and integrase. Reverse

transcriptase converts viral single-strand RNA into double-strand

deoxyribonucleic acid (DNA), which is then easily incorporated into

host cells as proviral DNA.

Integrase enables integration of the newly formed double-strand

DNA into the host chromosomal DNA. Proteases split the generated

proteins so that they can be incorporated into the new virions.

Handbook on Pædiatric AIDS in Africa

Figure 2.5. HIV Structure

��

�

��

HIV Life Cycle

e HIV life cycle in the host cell can be divided into several steps

(Figure 2.6): binding, fusion, entry, transcription, integration, replica-

tion, budding, and maturation.

Binding. HIV binds to cell s via interaction betwe en the HIV enve-

lope glycoprotein and the hos t cell receptors (CD4 mol ecule) and

co-receptors. e receptors a re the CD4 antigen found o n some

T lymphocytes, macrop hages, monocytes , glial cells of the bra in,

and Langerhan cells. e maj or co-receptors are CCR 5 and CXCR4.

ese receptors and co-recepto rs determine which cells th e HIV

virus will infect.

Fusion. e HIV envelope protein gp120 binds to the host cell recep-

tors and co-receptors on the outside of the cell. is results in inser-

tion of gp41 into the cell membrane of the host cell, with fusion of the

two membranes.

Handbook on Pædiatric AIDS in Africa

Entry. e virus particle leaves its membrane behind (uncoating) and

the core of the virus is released into the cytoplasm of the host cell.

e host cell enzymes interact with the core of the virus, resulting in

the release of viral enzymes.

Figure 2.6. HIV Replication Cycle

��

Reverse Transcription

For the virus to multiply, the viral (single-strand) RNA must ﬁrst

be converted into (double-strand) DNA. is is done by the viral

enzyme reverse transcriptase, which changes the single-strand viral

RNA into double-strand DNA.

Integration and Replication

e viral DNA is then able to enter the host nucleus and the viral

enzyme integrase is used to insert the viral DNA into the host cell’s

DNA. is is called integration. Once a cell is infected, it remains in-

fected for life because the viral genetic material is integrated into the

cell’s DNA. e host cell is then used as a machine to produce more

viral DNA (replication).

Handbook on Pædiatric AIDS in Africa

Budding

e many viral DNA particles (provirus) that are produced using the

host cell machinery gather at the membrane of the CD4+ cells. e

proviral particles push through the cell membrane by budding, taking

the lipid bilayer with them, ready to form new virus particles.

Maturation

e gp160, embedded in the cell membrane, is cleaved by the enzyme

protease to produce functional gp41 and gp120 to form a mature

virus, which is then ready to infect a new cell.

HIV Viral Load in Infants and Children

In the initial stages of HIV disease in adults, the immune system can

contain viral replication. Use of polymerase chain reaction (PCR) to

detect either the viral DNA or viral RNA can reveal the HIV virus in

the blood of HIV infected individuals. Several methods can be used to

quantify HIV ribonucleic acid. e most commonly used assays have

a lower limit of detection of 50 copies/ml.

e HIV RNA pattern in perinatally infected infants diﬀers from the

pattern in infected adults. HIV RNA levels increase to high values

(>100,000 copies/ml) by 2 months of age, remain high throughout

the ﬁrst year of life, and then decline slowly over the next few years.

is pattern probably reﬂects the inability of the infant’s immature

immune system to contain viral replication and, possibly, the greater

number of HIV-susceptible cells.

Eﬀect on Immune System

e basic eﬀect of HIV on the immune system is CD4+ cell depletion

and dysfunction. e functional defects can occur before cell num-

bers decline. Other immunological defects caused by HIV include

lymphoid tissue destruction, CD8+ cell dysfunction, B-cell abnormali-

ties, thymic dysfunction, and autoimmune abnormalities.

Non-HIV-infected infants and young children normally have higher

CD4+ counts than adults. e normal CD4+ count varies with age

Handbook on Pædiatric AIDS in Africa

(and probably with region), reaching adult levels around 5 or 6 years

of age.

e CD4+ T-cell absolute count identiﬁes a speciﬁc level of immune

suppression, but changes with age. e CD4+ T-cell % that deﬁnes

each immunologic category does not change; CD4 >25% is normal,

while CD4 <15% deﬁnes severe immune suppression (Table 2.1). CD4

% is thus the preferred immunologic marker for monitoring disease

progression in children.

Table 2.1. Immunologic Classiﬁcation for HIV-Infected Infants and Children

Immunologic Category

Age of Child

<12 months 1–5 years 6–12 years

Cells/µL (%) Cells/µL (%) Cells/µL (%)

1: No evidence of suppression ≥1500 (≥25) ≥1000 (≥25) ≥500 (≥25)

2: Evidence of moderate sup-

pression

750–1499 (15–24)

500–999

(15–24)

200–499 (15–24)

3: Severe suppression <750 (<15) <500 (<15) <200 (<15)

Source: CDC, 1994

Mechanism for Decline in CD4 Count

Several mechanisms are involved in causing the decline in CD4 count.

ese include:

• CD4 T-cell depletion through single-cell killing caused by accumu-

lation of HIV DNA in the cell or by inhibition of cell function.

• Cell membranes of infected cells fusing with cell membranes of

uninfected cells (syncitium induction), resulting in giant multi-nu-

cleated cells that are readily destroyed by the immune system.

• Programmed death (apoptosis) also contributes to T-cell depletion.

It is postulated that cross-linking of the CD4 molecule with gp120-

Handbook on Pædiatric AIDS in Africa

anti-gp120 antibody complexes programmes the cell for death

without direct infection of the cell with HIV.

• HIV infection induces neutralizing antibodies against regions of

the HIV envelope; these antibodies may play a role in mediating

antibody-dependent cellular toxicity after binding to natural killer

(cell killing) cells.

• HIV speciﬁc cytotoxic T-cells (CD8 cells) also play a role in killing

HIV-infected cells.

ese events contribute to depletion of CD4 cells and deteriorating

immune function.

Natural History

Clinical Course of Illness

ere are critical diﬀerences between the disease progression in

children and in adults. Stemming largely from the lower eﬃciency of

a child’s immature (but developing) immune system, these diﬀerences

result in much more rapid disease progression and a much shorter

duration for each stage.

Perinatally acquired HIV infection in Africa, as in industrialised coun

tries, demonstrates deﬁned modes of expression of disease (see below),

but with a poorer prognosis in Africa. e higher mortality in HIV-

infected children in Africa may result from intercurrent infections,

malnutrition, lack of access to basic health care, lack of or delayed

deﬁnitive diagnosis, and lack of access to primary HIV care and ART.

With no interventions, the majority of perinatally HIV-infected chil

dren in Africa develop HIV-related symptoms by 6 months of age.

ere are limited data on clinical and biological indicators of disease

progression in HIV-infected children in Africa. Some reports and

clinical experience indicate that children perinatally infected with

HIV ﬁt into one of three categories:

Handbook on Pædiatric AIDS in Africa

• Category 1: Rapid progressors, who die by age 1 and are thought to

have acquired the infection in utero or during the early perinatal

period (about 25–30%)

• Category 2: Children who develop symptoms early in life, followed

by a downhill course and death by age 3 to 5 (about 50–60%)

• Category 3: Long-term survivors, who live beyond age 8 (about

5–25%)

Factors Predicting Prognosis

Factors used to predict a prognosis are derived mainly from stud-

ies performed in industrialised countries; however, these predictors

are also useful in the African context. HIV RNA and CD4 % provide

complementary and independent information about the prognosis for

HIV-infected children. Using the two markers together, at baseline

and with changes over time, provides a more accurate prognosis.

Predictors of disease progression in infants include:

• Infecting viral dose (maternal viral load at delivery)

• Any infection before 4 months of life

• Infant peak viremia

• Low CD4 count and percent

• Rapid decline in CD4 count

• Clinical AIDS

• p24 antigenemia

Maternal predictors of infant disease progression include:

• Maternal viral load at time of delivery

• Maternal CD4 cell count (<200)

• Rapidly progressive maternal disease

Handbook on Pædiatric AIDS in Africa

• Maternal death, which is associated with a 2- to 5-fold increase in

infant mortality when compared to infants born to mothers who

survive

Knowledge Gaps

• ere are limited data on the natural history of paediatric HIV

infection in Africa and other resource-constrained settings beyond

the ﬁrst 3 years of life.

• ere are limited data on the biological markers of HIV disease

among infants and children in sub-Saharan Africa—current as-

sumptions that these are similar to infants and children in industr-

ialised countries have not been validated.

Additional Reading

Pizzo, P. and C. Wilfert, eds. Pediatric AIDS: e Challenge of HIV

Infection in Infants, Children and Adolescents. Williams & Willaims,

edition, 1998.

Essex, M. et al. 2002. AIDS in Africa. Kluwer Academic Publishers.

Obimbo, E. et al, eds. Pediatr Infect Dis J, 23 (6):536–543, June 2004.

Handbook on Pædiatric AIDS in Africa

Chapter 3

Preventing Paediatric

HIV Infection

Summary

• Mother-to-child transmission of HIV accounts for over 95% of

childhood paediatric HIV infections in sub-Saharan Africa.

• ere have been many scientiﬁc and operational advances in strat-

egies to prevent MTCT. ese include testing for HIV during preg-

nancy, modiﬁed obstetric practices, preventive ARV drug regimens,

and modiﬁed infant feeding practices; however, these continue to

be limited in both reach and scope.

• Widespread use of these eﬀective interventions reaﬃrms that

paediatric HIV infection is preventable, as demonstrated by the

dramatic decline in the annual number of new paediatric infections

in industrialised countries.

• In resource-limited settings, the most feasible regimens currently

are an zidovudine (AZT) short-course therapy started during preg-

nancy between 32 and 36 weeks of gestation and/or a single-dose

nevirapine (NVP) to the mother at the onset of labour and to her

infant within the ﬁrst week after birth.

• PMTCT programmes provide opportunities not only to prevent

infection but also to identify and provide care for HIV-exposed and

-infected children, their mothers, and their families.

• Early identiﬁcation of at-risk and infected children is particularly

critical because infants and children in general experience faster

progression of HIV disease and experience high rates of morbidity

and mortality early in life.

Handbook on Pædiatric AIDS in Africa

• Providing care to an infected mother not only improves her health

and well-being, but also signiﬁcantly impacts her infant’s health

and survival.

• Adolescents remain a high-risk group (for both HIV infection and

pregnancy) and have speciﬁc issues that those planning prevention

and care programmes for children must address.

• Post-exposure prophylaxis should be considered in cases of rape,

exposure to contaminated blood, and human bites from an infected

individual.

Handbook on Pædiatric AIDS in Africa

HIV Transmission Modes in Children

Mother-to-Child HIV Transmission

Infants who acquire HIV infection from their mothers do so during

labour and delivery or after birth through breast-feeding. e abso-

lute transmission risk is 5–10% during pregnancy; 10–20% during

labour and delivery, and 10 to 20% during breast-feeding. (Table 3.1).

Table 3.1. Estimated Timing of Transmission and Absolute Transmission Rates

Time of Transmission Absolute Transmission Rate (%)

During pregnancy 5–10

During labour and delivery

10–20

During breast-feeding

5–20

Overall without breast-feeding

15–30

Overall with breast-feeding through 6 months

25–35

Overall with breast-feeding through 18 to 24 months

30–45

Source: JAMA, 2000, 283:1175-1182

Risk Factors for Mother-to-Child HIV Transmission

e risk factors associated with MTCT include the following maternal

and infant factors:

Maternal Factors

• Women with high viral load are more likely to transmit HIV to

their infants, but there is no clear cut-oﬀ point below which trans-

mission does not occur.

• Women with severe immunosupression (CD4 counts below 200)

and those with advanced disease have an increased risk of trans-

mitting HIV to their infants.

• Maternal micronutrient deﬁciencies increase the risk of MTCT of

HIV signiﬁcantly.

Handbook on Pædiatric AIDS in Africa

• Prolonged rupture of amniotic membranes, chorioamnionitis, and

STIs signiﬁcantly increase the risk of MTCT.

• During breast-feeding, cracked nipples and breast abscesses signiﬁ-

cantly increase the risk of MTCT.

• HIV-1 is more readily transmitted from an HIV-infected woman

to her infant than is HIV-2. Subtype C has been associated with

increased risk of MTCT.

Infant factors

• Infant risk factors for MTCT include:

• Prematurity

• Breast-feeding

• Oral thrush and oral ulcers

• Invasive fetal monitoring during delivery

• Birth order (ﬁrst twin) in twin pregnancies

Handbook on Pædiatric AIDS in Africa

Table 3.2 presents interventions to reduce the risk of MTCT and miti-

gate against infection.

Table 3.2. Risk Factors and Mitigating Interventions

Risk Factor Prevention/Mitigating Interventions

High viral load Antiretroviral therapy in pregnancy

Low CD4 count As above, provide pneumocystis pneumonia (PCP) prophylaxis

Advanced disease Antiretroviral therapy, PCP and tuberculosis (TB) prophylaxis, OI

treatment

Chorioamnionitis Identify and treat sexually transmitted infections (STIs); Intermit

tent preventive therapy (IPT) for malaria

Malaria Provide malaria prophylaxis during pregnancy

Low vitamin A Maternal vitamin A supplementation does not reduce the risk

of MTCT

Cracked nipples, abscesses Counselling on optimal breast-feeding practice and breast care

Breast-feeding Counselling on infant feeding options: exclusive breast-feeding,

early and rapid cessation, replacement feeding options, and so on

Prematurity Comprehensive antenatal care, identify at-risk mothers, provide

PCP prophylaxis

Prolonged rupture of

membranes

Comprehensive antenatal care, safer delivery practices, and modi

ﬁed obstetric care

Invasive infant procedures Discourage scalp vein monitoring, vacuum extraction, episiotomy,

and nasal suction

Handbook on Pædiatric AIDS in Africa

Preventing Paediatric HIV Infection

A four-pronged approach has been suggested for PMTCT of HIV.

(Figure 3.1.)

Figure 3.1. Four-Pronged Approach to Paediatric HIV Infection (UN/WHO)

Primary

prevention

of HIV

Prevention of

unintended

pregnancies in

HIV-infected

women

Prevention of

mother-to-

child HIV

transmission

Provision of care and support for HIV-infected

women, their infants, and their families

Prong 1: Primary Prevention of HIV Infection

Primary prevention of HIV infection in men and women reduces

the risk of heterosexual transmission and so directly aﬀects MTCT.

Targeting pregnant and lactating women is a particularly pertinent

strategy for preventing paediatric HIV infection.

Prong 2: Preventing Unintended Pregnancy Among HIV-Infected

Women

Adolescent females in Africa have a six-fold increased risk of HIV

compared to males of the same age. is high risk of HIV acquisi-

tion stems from the young women’s social, biological, and emotional

vulnerabilities.

Measures that may reduce HIV infection in adolescents include train

ing in life skills and communication as a strategy to empower them to

Handbook on Pædiatric AIDS in Africa

delay sexual debut and engage in less risky sexual behaviours. e es-

tablishment of youth-friendly sexual, reproductive, and VCT services

is also an important way to increase access to services.

PMTCT eﬀorts to date have focused almost exclusively on prevent

ing transmission after an HIV-positive woman is already pregnant.

PMTCT programmes could be made more eﬀective by increasing

contraceptive use among non-pregnant, non-contracepting HIV-pos-

itive women who do not want to get pregnant (including those identi-

ﬁed during pregnancy and followed up post-pregnancy) through

integrating family planning and PMTCT services.

ere is a tremendous potential—including marshalling the cur

rent good will and support for VCT and PMTCT programmes—for

strengthening and promoting family planning services to support all

women and integrating family planning information and counselling

into VCT services. e feasibility and acceptability of such a strategy

has been demonstrated in resource-constrained settings in Uganda

and Kenya.

Integrating family planning into PMTCT programmes and vice versa

will require reorienting toward protection against the dual risks of

unintended pregnancies and of HIV infection. Service providers and

HIV-infected clients both need to promote dual protection, (especial

ly by the use of condoms), to guard against unintended pregnancies as

well as STIs.

Prong 3: Preventing Mother-to-Child HIV Transmission

Speciﬁc interventions used to prevent HIV transmission from an

infected mother to her child include use of ARV drugs, safer delivery

practices, infant feeding, counselling, and support. ese interven-

tions present real opportunities to improve services for all women

and children, and healthcare providers should provide them as part of

routine pregnancy, maternity, and post-pregnancy care for mothers

and their infants.

Handbook on Pædiatric AIDS in Africa

Essential Antenatal Care

Establishing PMCT programmes provides an opportunity to strength-

en and improve the quality of antenatal care for all women. Antenatal

care for all women should include regular routine visits to check for

complications such as hypertension, diabetes, and pre-eclampsia that

could lead to maternal death and/or poor infant outcomes.

Nutritional Support

Nutritional education and support (including multivitamin supple-

mentation) is critical for all women and is associated with a decrease

in the incidence of low birth weight and congenital defects. Micro-

nutrient supplementation (excluding vitamin A) during pregnancy

and lactation has a positive impact on the pregnancy outcomes of

HIV-infected women.

Infection Prevention and Treatment During Pregnancy

Malaria during pregnancy is one of the most common causes of

low-birth-weight infants, and intermittent preventive therapy for

malaria signiﬁcantly reduces malaria-related adverse outcomes. Dual

infection with HIV and malaria is associated with increased risk of

maternal, perinatal, and early infant death compared with the risks of

either disease alone. Chorioamnionitis from malaria has been associ-

ated with increased MTCT, further emphasising the importance of

intermittent preventive malaria therapy.

Sexually transmitted infections (STIs) and urinary tract diseases also

precipitate premature delivery and increase an infant’s risk of HIV

infection. Healthcare professionals should routinely screen for syphi

lis. Because STIs are usually asymptomatic in women, health workers

should actively seek symptoms by taking a clinical history and carry-

ing out a genital examination.

To reduce the occurrence of neonatal tetanus, women should receive

immunisation during pregnancy.

Handbook on Pædiatric AIDS in Africa

Counselling and HIV Testing

Eﬀective PMTCT depends on providing routine, on-site antenatal

counselling and HIV testing to all pregnant women and testing all

women presenting with an unknown status at delivery.

Integrating counselling and testing services in maternal and child

health settings requires signiﬁcant planning and, often, reorganisa

tion of services to ensure counselling capacity and services. is will

include: creating private space, re-designing client ﬂow, as well as

orienting, training, and sometimes hiring additional service providers.

e need to introduce and maintain such services, particularly in the

face of typically crowded and understaﬀed antenatal care (ANC) clin

ics, is a signiﬁcant limiting factor to scaling up PMTCT interventions.

Over time this has led to the development of multiple approaches to

counselling and testing in MCH settings.

e ideal approach is to integrate HIV testing into routine antenatal

care, with women reserving the right to refuse testing. HIV testing is

the entry point for speciﬁc PMTCT interventions that include ARV

prophylaxis, modiﬁed obstetric practices, and infant feeding counsel

ling and support. Women who are HIV negative receive counselling

about remaining negative and the high risk of infant transmission

associated with becoming infected during pregnancy and lactation.

Infant Feeding Counselling

Counselling and support on infant feeding choices for HIV-positive

women is a complex and challenging intervention requiring addition-

al factual knowledge and understanding of postnatal HIV transmis-

sion (see chapter 12).

Antiretroviral erapy for PMTCT

In 1994 the Pediatric AIDS Clinical Trials Group (PACTG) in the

United States published the ﬁrst randomised controlled trial demon-

strating that prophylactic ART can reduce perinatal transmission. In

the PACTG 076 study an intensive AZT regimen—starting at the end

of the ﬁrst trimester in the mother and for 6 weeks to the infant—re-

Handbook on Pædiatric AIDS in Africa

duced transmission from 25.5% to 8.3%. Since then several successful

trials have shown that a combination of interventions may reduce

transmission rates signiﬁcantly. A summary of published studies from

African trials is shown on Table 3.3.

Table 3.3. Early MTCT Rates in Breast-Feeding Populations Where Women

Received Antepartum and/or Intrapartum and/or Postpartum Regimens

Regimen Studies Mother Infant

Evaluation

Time

Transmis-

sion Rate

(%)

AZT*

alone

RETROCI

From 36 wks antepartum

to delivery

None 3 mths 16.5

DITRAME

AZT from 36 wks

antepartum and 1 week

postpartum to mother

None 6 wks

12.8

NVP

alone

HIVNET 012 Single dose in labour Single dose 6–8 wks 11.9

SAINT

Single dose in labour +

one dose postpartum

24–48 hrs

Single dose 8 wks 13.3

AZT +

NVP

DITRAME

AZT from 36 wks

antepartum plus single-

dose NVP in labour

Single dose

NVP plus 1

wk ZDV

4–6 wks 6.2

AZT +

3TC

PETRA A

From 36 wks antepartum

to 1 wk postpartum

1 wk 6 wks 5.7

PETRA B

From onset of labour to

1 wk postpartum

1 wk 6 wks 8.9

SAINT

(= PETRA B)

From onset of labour to

1 wk postpartum

1 wk 8 wks 9.3

ddI +

AZT

SIMBA

From 36 wks antepartum

to 1 week postpartum

BF period

3TC or

NVP

4 wks 6

AZT +

NVP

Taha No treatment for mother

NVP alone

vs NVP +

AZT for

1 wk

6–8 wks

20.9

15.3

*AZT=Zidovudine

Handbook on Pædiatric AIDS in Africa

• e decision about which regimen is appropriate should be made

locally, and should take into account the feasibility, pattern of use

of maternal and child health (MCH) clinics, eﬃcacy, acceptability,

ease of dosing, availability and cost, safety and logistical issues, and

the stage of the disease and history of the mother’s use of ARV

drugs.

• In resource-constrained settings such as Africa, the most widely

used regimens are the least complex single drug ones such as single-

dose nevirapine and/or short course AZT.

Single-Dose NVP Regimen (HIVNET 012)

Nevirapine 200 mg given to the mother at onset of labour and

2 mg/kg single dose to the infant within 1 week.

To be eﬀective, the woman must receive maternal NVP dosing more

than 2 hours before delivery. If the maternal dose is taken less than

1 hour prior to delivery or if the mother misses her dose, then the

infant is dosed as soon as possible after birth.

Infant dosing can be prior to discharge from the hospital, but if the

baby is not born at the hospital, then the baby can receive a single-

dose NVP syrup within the ﬁrst 7 days of life, but preferably within

the ﬁrst 3 days.

Short-Course AZT Regimen (Modiﬁed ai)

Regimen: Oral AZT starting at 32–34 weeks gestation, 300 mg every

12 hours during pregnancy and every 3 hours in labour, and for

1 week to the infant, 4 mg/kg/day every 12 hours.

e aim is to provide at least 4 weeks of AZT to the mother and

1 week to the infant. Health workers must make an eﬀort to provide

at least 4 weeks of maternal dosing during pregnancy (beginning at

32–34 weeks or as soon as possible thereafter).

Handbook on Pædiatric AIDS in Africa

Combination Regimens

Regimens that combine more than one drug have been found to be

more eﬃcacious in preventing mother-to-child HIV transmission.

PHPT-2 Regimen (2004 ai Regimen)

e PHP T regimen combines AZT (starting at 28 weeks or as soon

as possible thereafter) with the single-dose maternal and infant

nevirapine (HIVNET 012). is regimen reduces transmission to

below 3% in non-breast-feeding populations.

Triple Combination ART

Highly active antiretroviral therapy (HAART) in pregnancy is

the most eﬀective regimen for reducing MTCT. In places where

HAART is available, make decisions to use HAART during preg-

nancy for prophylaxis against MTCT after discussion between the

woman and her healthcare provider.

Where the mother requires HAART to treat her HIV disease,

guidelines for particular regimens do not diﬀer when used during

pregnancy, but health professionals must consider the safety of

particular drugs, such as efavirenz and abacavir, during the ﬁrst

3 months of pregnancy.

ere is no additional beneﬁt from the single-dose N VP regimen

when a pregnant woman is already well controlled on HAART

because the viral load will be low or undetectable.

Appendix A at the end of the handbook presents detailed recommen-

dations for the use of antiretroviral drugs in pregnant women—for

their own health and to prevent HIV infection in infants.

Safer Delivery Practices

Most HIV transmission occurs around the time of labour and delivery

and the risk increases with prolonged rupture of membranes, invasive

procedures, and prematurity.

Handbook on Pædiatric AIDS in Africa

Chlorhexidine vaginal douches have been shown to reduce the inci-

dence of neonatal infections but not of HIV transmission, unless the

membranes are ruptured for longer than 4 hours.

Healthcare professionals should discourage invasive obstetric proce

dures such as artiﬁcial rupture of membranes before full dilatation,

foetal scalp monitoring, vacuum extraction, and episiotomy. e

infant should be wiped soon after delivery, but vigorous suctioning of

the infant should be avoided.

Elective caesarean section (before the onset of labour or the rupture

of membranes) may reduce the MTCT risk. Caesarean section is not

advocated for PMTCT in resource-limited settings, where feasibil

ity and safety are questionable. When HAART is used for PMTCT,

caesarean section does not have an added beneﬁt.

Infant Feeding

Breast-feeding increases the HIV transmission risk by 10 to 20%;

however, lack of breast-feeding increases children’s risk of malnutri-

tion and infectious diseases other than HIV. e decision about feed-

ing must be on a case-by-case basis and be accompanied by compre-

hensive counselling and support.

Multiple feeding options can be used to reduce HIV transmission by

breast milk. ese include using infant formula, exclusive breast-feed

ing with early cessation, heat-treating expressed breast milk, or using

other breast milk substitutes, for example, cow’s milk (see chapter 12).

Immediate Postpartum Period

Counsel mothers and assist them to initiate the infant feeding op-

tion they have selected as soon as possible after delivery. Tell those

who opt to breast-feed about the appropriate latching-on technique;

give those who opt for replacement feeding demonstrations about

replacement foods such as formula and other replacement milks.

Also counsel them on food hygiene and personal hygiene as well as

issues related to maternal infant bonding, particularly for those whose

infants receive replacement food or are weaned early.

Handbook on Pædiatric AIDS in Africa

Immediate Newborn Care

Ensure appropriate newborn care: keeping the baby warm, wiping oﬀ

the infant, and initiating feeding early.

Challenges of Implementing PMTCT

Low uptake of HIV testing by antenatal women (Figure 3.2) and low

uptake of antiretroviral drugs by HIV-positive women identiﬁed dur-

ing pregnancy (Figure 3.3) are having an adverse eﬀect on the eﬀec-

tiveness of PMTCT programmes in the sub-Saharan African region.

is can be attributed to institutional factors (such as client ﬂow and

low staﬀ levels) that have a negative eﬀect on service delivery and to

inadequate community engagement (especially from male partners).

ere is an urgent need for strategies to improve programme impact.

Figure 3.2. PMTCT Cascade: Women Attending ANC

�

��

Source: Phillipa Musoke. Makerere University/Johns Hopkins University PMTCT programme services data, 2000-2003

(illustrative only)

Handbook on Pædiatric AIDS in Africa

Figure 3.3. HIV-Infected Women Accessing Services

�

��

Source: Phillipa Musoke. Makerere University/Johns Hopkins University PMTCT programme services data, 2000-2003

(illustrative only)

Prong 4: Providing Care and Support to HIV-Infected Women, eir

Infants, and eir Families Synergy Between Prevention and Care

Prevention and care are mutually reinforcing elements of an eﬀec-

tive strategy for dealing with the paediatric HIV epidemic. Access to

care will enhance community support for PMTCT programmes and

increase the uptake of important interventions, such as HIV test-

ing. Psychosocial and nutritional support, treating OIs, and ART are

important in both preventing and treating paediatric HIV infection.

A comprehensive approach to the paediatric epidemic involves treat

ing the parents and other siblings to preserve the family unit, ensure

a stable environment in which to nurture the children’s growth and

development, and reduce the prevalence of orphans.

Creating links between PMTCT programmes and those for the care

and support of HIV-infected women, their infants, and their families

will help to ensure that women themselves have access to the services

they need. Furthermore, access to care and support services also en

hances PMTCT services within communities. Such services include:

Handbook on Pædiatric AIDS in Africa

• Prevention and treatment of OIs

• Psychosocial and nutritional support

• Reproductive healthcare

• Control of STIs

• Family planning

• Antiretroviral therapy

• Young child care:

• Diagnosis of HIV

• Immunisations

• Growth and development monitoring

• Treatment of acute infections

• Routine de-worming

• Multivitamin supplementation

• Improved economic independence of women (poverty alleviation)

Non-Mother-to-Child Transmission

Sexual Abuse

Sexual abuse accounts for a relatively small proportion of infection

in children. It is often diﬃcult to tell if an older child was infected

perinatally or by abuse. Orphans are especially vulnerable to sexual

abuse.

Post-Exposure Prophylaxis

Initiate post-exposure prophylaxis (PEP) after rape or sodomy as soon

as possible because it is most eﬀective if begun within 24 hours of

the assault and is probably ineﬀective after 72 hours. Also consider

prophylaxis in other situations, such as exposure to contaminated

Handbook on Pædiatric AIDS in Africa

medical equipment, blood, or other bodily ﬂuids and after human

bites with disruption to the skin.

Points to keep in mind for post-exposure prophylaxis include:

• Administer AZT plus 3TC for a period of 28 days. On discharge

from facility, issue children enough medication to complete the

28-day course (Table 3.4).

• Administer three-drug prophylaxis if parents can aﬀord it or if

signiﬁcant exposure has occurred (e.g., penetrative sexual assault

with perineal lacerations). Use nelﬁnavir in combination with AZT

and 3TC for 28 days.

• Perform HIV testing at the time of initial contact (baseline test)

after obtaining informed consent. Most seroconversions occur

within 6 to 8 weeks after exposure. Repeat HIV testing at intervals

of 6 to 8 weeks, 3 months, and 6 months after the assault.

• In children who were sexually assaulted, give consideration to

preventing pregnancy and STIs and to collecting forensic evidence,

including appropriate perineal swabs (local guidelines must be

consulted).

Table 3.4. Drug Dosage for Post-Exposure Prophylaxis

Drug Paediatric Dose Adolescent Dose

AZT 180 mg/m

/12 hours 200 mg 8 hourly

3TC 4 mg/kg/12 hours

≥50 kg 150 mg 12 hourly

<50 kg 2mg/kg 12 hourly

Nelﬁnavir 55 mg/kg/12 hours 750 mg 8 hourly

Transfusion of Blood Products

Routine donor screening has largely eliminated blood products as a

route for transmission. However, a small number of such transmis-

sions do occur where there is no safe blood supply or because HIV-in-

fected donors were not detected during the window period. Children

Handbook on Pædiatric AIDS in Africa

in Africa are often transfused daily because of severe anaemia and

every eﬀort must be made to ensure safe blood supplies.

Other Modes of Transmission

In a small number of infants with seronegative parents, the mode of

transmission is uncertain. However, nosocomial transmission can

occur through contaminated or incompletely sterilised instruments

at healthcare facilities, through traditional practices, and through

contaminated expressed breast milk that is inadvertently given to

hospitalized children. Wet-nursing could be another source of unex-

plained transmission.

Adolescents

Adolescents are vulnerable and often acquire HIV when they are in-

volved in risky sexual practices, are sexually abused, or share needles

when experimenting with illicit drugs.

Preventing Other Modes of Horizontal Transmission

Methods for preventing other modes of HIV transmission include:

• Instituting hospital infection control measures such as protective

clothing (including gloves and eye protection), use of antiseptic

techniques, sterilization of instruments and equipment, and ad-

equate waste storage and disposal systems.

• Eliminating the reuse of needles and syringes.

• Taking special care with the administration of expressed breast

milk. Do not use communal breast pumps. Place expressed milk

into labelled bottles and check the labelled bottles before giving

milk to any baby.

• Reviewing infection control measures regularly to minimise noso-

comial infection. Pay attention to practices that are speciﬁc to each

clinical discipline. For example, phase out nappy pins, which may

facilitate the transmission of several viruses, including HIV.

Handbook on Pædiatric AIDS in Africa

Post-Exposure Prophylaxsis for Healthcare Providers

Post-exposure prophylaxis is critical for those exposed to HIV. Local

institutional policy guidelines should be available for all healthcare

providers. Some guidelines include:

• Start prophylaxis within 1 hour of exposure.

• Zidovudine 300 mg twice daily with lamivudine 150 mg twice daily

for a total of 28 days is adequate for most exposures.

• For high-risk exposures (e.g., deep injury with a hollow needle

from an HIV-infected patient, blood containing a viral titre, or a

patient with end-stage AIDS), three-drug prophylaxis is recom-

mended (i.e., zidovudine 300 mg twice daily, lamivudine 150 mg

twice daily, and indinavir 800 mg) thrice daily for a total of 28 days.

• Test the source patient soon after the exposure, and review the

need to continue prophylaxis when the HIV result of the source

patient is known.

• When the source person’s virus is known or suspected to be resist-

ant to one or more drugs considered for the PEP regimen, then

select drugs to which the source person’s virus is unlikely to be

resistant.

• Serial HIV enzyme-linked immunosorbent assay (ELISA) test-

ing of the injured healthcare provider is essential to establishing

whether seroconversion has occurred and for compensation claims.

Perform a baseline HIV ELISA after obtaining informed consent.

Most seroconversions occur within 6 to 8 weeks after exposure.

Repeat ELISA testing 6 to 8 weeks, 3 months, and 6 months after the

incident.

• Provide supportive counselling to the health worker. Advise him or

her on the risk of infecting the sexual partner or on mother to child

transmission if pregnant or breast-feeding.

Handbook on Pædiatric AIDS in Africa

Knowledge Gaps

• Eﬀectiveness of PMTCT programmes in sub-Saharan Africa

• Implications of nevirapine resistance for future ARV therapy

• Role of HAART in sub-Saharan African PMTCT programmes

Additional Reading

Recommendations for the use of antiretroviral drugs in pregnant

HIV-1 infected women. Available at: http://AIDSinfo.nih.gov

Preventing Mother-to-Child Transmission of HIV. A Strategic Frame

work. Family Health International, 2004.

Antiretroviral drugs for treating pregnant women and preventing HIV

infection in infants: guidelines on care, treatment and support

for women living with HIV/AIDS and their children in resource-

constrained settings. World Health Organization, 2004.

Handbook on Pædiatric AIDS in Africa

Chapter 4

Approach to Care of HIV-

Exposed o r HIV-Infected Child

Summary

• Care providers can do more to improve the care and quality of life

of HIV-exposed and infected children.

• Comprehensive care of HIV-exposed children that includes

PMTCT, nutrition counselling, prevention of infections, and

growth monitoring is feasible within resource-constrained settings

and signiﬁcantly improves the survival of these children.

• Early diagnosis ensures timely treatment and entry into ARV pro-

grammes.

• Establishment of follow-up services, and appropriate referral

system for HIV-exposed children and their families are critical

components of their care.

• Extending HIV care to mothers and other family members pro-

vides a support network for the aﬀected child, and improves the

survival of the child.

• Clear communication with the caregiver or parent and the aﬀected

child, and participatory planning for long-term care, increase the

likelihood of treatment success.

Handbook on Pædiatric AIDS in Africa

Introduction

is chapter provides a framework for programmatic interventions

(primarily clinical) that cater to the needs of children exposed to or

infected by HIV, within the broader context of services for children

aﬀected by AIDS.

In most of sub-Saharan Africa there are limited paediatric HIV

diagnostic facilities and therefore most HIV-infected children are

diagnosed very late in the course of illness, or not at all.

e risk of transmission for a child born to an HIV-infected mother in

an African setting without PMTCT interventions is about 30 to 40%.

e other 70% of infants born to HIV-infected mothers, although

they are not infected, have a 2- to 5-fold risk of mortality as a direct

consequence of the mother’s HIV disease, when compared to children

born to HIV-uninfected mothers.

Expansion of PMTCT services leads to identifying greater numbers of

HIV-exposed children and provides opportunities for early interven

tion and care.

Health workers need to integrate PMTCT services into the antena

tal clinic and maternity and encourage pregnant women to use the

services to reduce the numbers of new infant HIV infections and also

as an entry point into their long-term care.

Comprehensive Paediatric HIV Care

Provide comprehensive care for the HIV-exposed or those infected

with HIV in the broader context of other child health strategies and

provide regular presumptive de-worming every 6 months. Health

workers should provide the following, as a minimum, to these children.

Handbook on Pædiatric AIDS in Africa

Ten-Point Package for Comprehensive Paediatric AIDS Care

1. Conﬁrm HIV status as early as possible.

2. Monitor the child’s growth and development.

3. Ensure that immunizations are started and completed according to the

recommended schedule.

4. Provide prophylaxis for opportunistic infections (PCP and TB) (see below).

5. Actively look for and treat infections early.

6. Counsel the mother and family on:

a. Optimal infant feeding to minimise MTCT, prevent malnutrition and

promote growth and development.

b. Good personal and food hygiene to prevent common infections, and

encourage her to seek prompt treatment for any infections or other

health related problems.

c. When the child should be followed up according to the WHO recom

mendations (see below).

7. Conduct disease staging for the infected child.

8. Oﬀer ARV treatment for the infected child, if needed.

9. Provide psychosocial support to the infected child and mother.

10. Refer the infected child for higher levels of specialized care if necessary, or

for other social- or community-based support programs.

In the context of providing child health services, a clinician is likely to

encounter the following categories of children:

• Children born to HIV-infected women who may be infected

but are of unknown HIV status and commonly referred to as

HIV-exposed children

• Children with symptoms suggestive of AIDS

Handbook on Pædiatric AIDS in Africa

• Children known to be HIV-infected

• Children whose parents/guardians are sick with HIV/AIDS

• Children who have been orphaned by AIDS

Interventions Common to Both

HIV-Exposed and HIV-Infected Infants

1. Conﬁrm HIV Infection as Early as Possible

Healthcare workers should counsel every HIV-infected pregnant or

postpartum mother on the need to conﬁrm her child’s infection sta-

tus. Health workers should explain when and where to bring the child

for HIV testing, which will depend on the availability of particular

HIV tests in her locality.

For a child who has clinical signs and symptoms suggestive of HIV in

fection, or whose mother is known to be HIV-infected, it is important

to conﬁrm infection as early as possible because early identiﬁcation

allows for appropriate care and can prevent/reduce early morbidity

and mortality.

Even without sophisticated laboratory tests, the clinician should

always have a high index of suspicion and use clinical criteria to make

a diagnosis of HIV infection. Where laboratory facilities are available,

conﬁrm clinical diagnosis as soon as possible.

When to Test

Provide routine testing for HIV antibodies for all sick children in high

HIV prevalence areas.

Oﬀer HIV testing to women who deliver with unknown HIV status

immediately after delivery and provide post-exposure prophylaxis to

the infants of the HIV-infected women.

If the mother is known to be HIV-positive and the child has clinical

signs and symptoms suggestive of HIV/AIDS and is antibody positive,

but PCR is not available, treat the child presumptively (see

chapter 8).

Handbook on Pædiatric AIDS in Africa

e most widely available HIV tests are antibody-based tests (e.g., HIV

rapid tests, ELISA), which are generally not useful for establishing a

deﬁnitive diagnosis in HIV-exposed infants younger than 18 months

of age. A positive HIV antibody test at a younger age may merely indi-

cate passively transferred maternal antibodies. But a negative test at an

earlier age in an HIV-exposed infant, particularly one who has never

breast-fed or who was completely weaned at least 6 months previously,

is a useful indicator of the absence of HIV infection.

HIV DNA PCR virologic testing, a test more appropriate for younger

infants, is much more expensive and currently available only in

research and referral laboratories. However, there is an urgent need

to explore ways that HIV-antibody-positive children in primary care

facilities can access these tests in referral laboratories.

2. Growth and Development Monitoring and Promotion

Growth and development monitoring and promotion are critical

child survival strategies in resource-poor settings, especially in areas

with high rates of both childhood malnutrition and HIV/AIDS, and

particularly for children in households directly aﬀected by HIV/AIDS.

We know that growth failure is greater in HIV-infected children than

in uninfected children. is may result from:

• Low birth weight (prematurity, small for age)

• HIV infection

• Other underlying disease, such as TB

• Inadequate macro/micronutrient intake

• A combination of any or all of the above

Growth monitoring is a tool that helps identify the vulnerable child

and monitors the eﬀect of interventions.

Nutritional Management

Poor nutrition weakens the immune system and predisposes children

to common infections and, for those who are HIV-infected, to OIs.

Handbook on Pædiatric AIDS in Africa

Both HIV-exposed and -infected children are at increased risk of

malnutrition for many reasons:

• Low birth weight

• Inappropriate/suboptimal infant feeding practices

• Poor weaning practices (timeliness, adequacy of foods, hygiene,

meal frequency, feeding method)

• Household food insecurity

• Orphaning

HIV-infected children are additionally at risk from:

• Decreased intake because of oral disease (thrush)

• Anorexia associated with illness

• Increased loss of nutrients because of diarrhoea, malabsorption

• Increased metabolism because of HIV infection or other infections

• Inadequate child care, if the mother is sick or deceased

Strategies to prevent malnutrition and promote good nutrition

include:

• Providing accurate information and skilled support to mothers and

others responsible for feeding infants and young children

• Ensuring adequate nutrient intake based on locally available foods;

providing universal (vitamin A) or targeted (e.g., iron, folate, zinc)

micronutrient and mineral supplementation

• Providing food fortiﬁcation and nutrient supplementation for the

most vulnerable

• Providing prompt early treatment of common infections and OIs

(e.g., candida)

Handbook on Pædiatric AIDS in Africa

• Ensuring the health and nutritional status of women and other

caretakers of infants and young children

Emphasise good personal hygienic practices (e.g., oral, dental, nail,

and skin care, and hand-washing and boiling drinking water).

Preventing HIV (from routes other than vertical) is critical for chil

dren, particularly those growing up in conditions of hardship imposed

by loss of parents; those subject to sexual abuse, war, and conﬂict; and

those adolescents who start sexual activity early in life (see chapters 3

and 9

3. Immunisation

Studies indicate there is impaired passive transfer of maternal an-

tibodies against common infections from HIV-infected mothers to

their infants, and there may be impaired response following immuni-

sation with a variety of antigens.

Children who are HIV-infected:

• Are more likely to experience progressive primary TB disease after

exposure to TB. e clinician should give BCG at birth to children

in Africa because tuberculosis is endemic.

• Experience more frequent episodes of Haemophilus inﬂuenza

type b infection. Both the conjugate Haemophilus inﬂuenza and

pneumococcal vaccines are eﬀective, even in HIV-positive children,

and are recommended in regions where these vaccines are aﬀord-

able.

• Experience severe forms of disease with measles wild-type virus

infection

Handbook on Pædiatric AIDS in Africa

erefore, administer childhood immunisations as recommended by

national Expanded Programmes on Immunisation (EPI) with the fol-

lowing modiﬁcations:

• When considering BCG vaccination at a later age (re-vaccination

for no scar or missed earlier vaccination), exclude symptomatic

HIV infection.

• Do not give yellow fever vaccine to symptomatic HIV-infected

children; however, asymptomatic children in endemic areas should

receive the vaccine at 9 months of age.

• Although measles vaccine is a live virus, do give it to children,

even when symptoms are present, at 6 and 9 months. Studies from

Uganda indicate that children experience much more severe dis-

ease with wild measles virus, which outweighs the risk of a milder

illness from the vaccine.

• HIV-infected children can receive prophylactic measles immu-

noglobulin (0.5 ml/kg, maximum of 15 ml) within 6 days of expo-

sure.

• Varicella immunoglobulin (0.15ml/kg) is advised within 3 days of

exposure if children are exposed to chicken pox.

4. Prophylaxis Against Pneumocystis Pneumonia (PCP)

Pneumocystis pneumonia (PCP) is a signiﬁcant cause of morbidity

and mortality among young infants in Africa. Cotrimoxazole (CTZ)

prophylaxis signiﬁcantly reduces the incidence and severity of PCP.

Additional beneﬁts of cotrimoxazole include protection against com-

mon bacterial infections, toxoplasmosis, and malaria. A Zambian

study recently demonstrated an overall 45% reduction in mortality

among HIV-infected children who received cotrimoxazole prophy-

laxis, regardless of their CD4 count. Because early diagnostic tests (e.g.,

PCR) are not readily available, all children born to HIV-infected moth-

ers should receive prophylaxis against PCP, at least during the ﬁrst year

of life, or until they are proven to be uninfected (see Table 4.1).

Handbook on Pædiatric AIDS in Africa

Table 4.1. Who Needs PCP Prophylaxis?

• All infants born to an HIV-infected mother irrespective of any antiretroviral during

pregnancy and labour. Prophylaxis continues until infant is 12 months or is PCR negative or

antibody negative whichever comes earlier.

• All infants identiﬁed as HIV infected during the ﬁrst year of life by a PCR test or by a clinical

diagnosis of HIV infection and a positive antibody test.

• Children older than 12 months, with symptomatic HIV disease or an AIDS-deﬁning illness

(WHO stage II and III- see chapter 5) or with CD4 <15% or TLC 1500/mm3

• Any child with a history of PCP, should continue with secondary prophylaxis (daily CTZ) for

life.

Clinicians should clearly inform HIV-infected mothers at delivery that

their children need prophylaxis against PCP starting at 6 weeks of age

until it is established that the child is not HIV-infected. A practical

way to ensure that mother and other health workers are informed is to

make a note on the child’s immunisation card at birth stating “Please

give cotrimoxazole (5 mg/kg/day orally daily) from 6 weeks of age.”

Table 4.2. Dose of Cotrimoxazole for PCP Prophylaxis

Weight

of Child

(kg)

CTZ tablets 20 mg

TMP/100mg SMX

Paediatric strength

(120 mg)

CTZ suspension

40 mg TMP/200

SMX/ 5ml

(240 mg)

CTZ tablets 80 mg

TMP/400mg SMX

Regular strength

(480 mg)

CTZ Tablets 160

mg TMP/800

mg SMX Double

strength (960 mg)

1–4 1 tab 2.5 ml ¼ tab –

5–8 2 tabs 5 ml ½ tab ¼ tab

9–16 10 ml 1 tab ½ tab

17–50 2 tabs 1 tab

>50 2 tabs 1 tab

Use other options for children over 9 kilograms

Use regular or double-strength tablets for children over 16 kilograms

Handbook on Pædiatric AIDS in Africa

Alternative drugs for use if CTZ is contraindicated include:

• Dapsone

• Children >1 month 2 mg/kg/24 hours orally once daily

• Adults 100 mg/24 hours once daily (or twice daily)

If both CTZ and Dapsone are contraindicated (e.g., in children with

G6PD deﬁciency who get haemolysis with CTZ and Dapsone) then

use:

• Pentamidine (children >5 years)

• 4 mg/kg/dose every 2–4 weeks IM/IV

• 300 mg in 6 ml water via inhalation once monthly

• Higher dose 45mg/kg/day for age 3–24 months

• Atovaquone 30mg/kg/day; higher dose 45mg/kg/day for age 3–24

months

Preventing TB

INH prophylaxis against TB should be given to children less than

5 years old who are exposed to smear-positive TB in their house-

hold (HIV-uninfected, -exposed, or -infected) whether the Mantoux

test is positive or not. Active disease must be ruled out ﬁrst. INH

for TB prophylaxis is given as a single oral daily dose of 5 mg/kg for

6 months.

5. Treatment of Acute Infections and Other HIV-Related Conditions

HIV-exposed children are susceptible to common infections and OIs.

HIV may alter the incidence, presentation, and response to conven-

tional therapy. In some cases more aggressive and longer treatment

courses may be necessary, as treatment failures are more frequent.

TB must be ruled out as it is prevalent in most African settings (see

chapters 6 and 7

Handbook on Pædiatric AIDS in Africa

6. Regular Follow-up Care and Referrals

Regular follow-up is the backbone to caring for HIV-exposed children

and ensures optimal healthcare and psychosocial support to the fam-

ily. WHO has made recommendations on frequency of follow-up, as

shown in Table 4.3, below. is is the minimum and more frequent

contacts with the health care system are indicated for infected chil-

dren and especially if they are on anti-retroviral treatment.

Table 4.3. WHO Recommendations for Follow-up of an HIV-Exposed Child

• At birth (for infants delivered at home)

• At age 1 to 2 weeks (mainly for infant feeding counselling)

• At age 6, 10, and 14 weeks (for immunization and infant feeding counselling)

• After age 14 weeks, monthly through age 12 months

• After age 12 months, every 3 months through 24 months

• After 2 years, a minimum of yearly visits

• At 18 months a conﬁrmatory HIV laboratory test should be done (if there are no resources

for an earlier antigen-based test)

Many PMTCT programmes lack mechanisms for follow up of

HIV-exposed infants. A well-informed mother—who knows that at

6 weeks PCP prophylaxis should begin and that at 18 months the

child should receive an HIV antibody test—is the best way to ensure

adequate follow up care. A deﬁnitive laboratory HIV diagnosis (or

clinical AIDS diagnosis) will diﬀerentiate a child who is HIV-exposed

from a child who is infected.

HIV-infected children over the age of 24 months should be followed

yearly if asymptomatic. Symptomatic children should be followed

more frequently as needed.

Age Monitor

6 weeks–12 months Monthly

12–24 months Every 3 months

24 months onwards

Yearly if not symptomatic

If symptomatic, follow up as needed

Handbook on Pædiatric AIDS in Africa

Referrals

Referrals are an important part of managing an HIV-exposed or -in-

fected child. is includes referrals to:

• Higher levels of specialized care for further investigations and

treatment

• Social support programmes

• Community-based care programmes

• VCT sites for parents and siblings

Services Speciﬁc for HIV-Infected Children

1. HIV Disease Staging

Disease staging, with or without laboratory support, follows HIV

diagnosis. Staging HIV disease provides a guide to the prognosis and

interventions needed at the diﬀerent stages (refer to chapters 5 and 8).

2. ARV erapy

• Counsel for and provide ARV drugs. Give children ART according

to international or national guidelines, which take into account that

not all HIV-infected children are eligible for ART (see chapter 8).

• In the absence of laboratory conﬁrmation of HIV, provide ARV

drugs for HIV- exposed younger infants (less than 18 months, with a

positive antibody test) only if there is evidence of immunodeﬁciency

(CD4% <20% or WHO paediatric stage 3 or 4). See chapter 8.

• In all cases where younger infants (

18 months) are started on

ARV drugs in the absence of a virologic test, you must perform an

antibody test at 18 months to determine whether to continue with

ARV drugs.

Strategies to Increase Access to Paediatric ARV Services

Availability of ARV drugs is fairly recent in sub-Saharan Africa. Few

clinicians have practical hands-on experience with ART in general,

Handbook on Pædiatric AIDS in Africa

and even fewer with ART in children. Healthcare providers need

practical insights on how to set up a paediatric ART clinic. In general,

the following strategies open up access for children:

• Provide services speciﬁcally for children (i.e., designated hours/

days and/or designated providers) and make sure that potential

users (e.g., people living with HIV/AIDS [PLHA] groups, providers

who already are providing HIV-related care, and clinicians) know

that these children-speciﬁc services are available

• Provide subsidies (or free services) for care and treatment for chil-

dren, thus removing the biggest barrier to care and treatment

• Extend services to children whose parents and guardians are ac-

cessing HIV-related care services

• Advocate with interest groups already supporting OVC to integrate

clinical care and treatment into their ongoing programmes

Communicating with Care-Provider and Psychosocial Support for the

Child, Mother/Caregiver, and Family

An HIV diagnosis in a child has many direct implications for the other

family members. MTCT is by far the most common HIV transmis-

sion mode to infants (95%) and, in the absence of other risk factors for

HIV, assume maternal HIV infection until proven otherwise. Likewise,

maternal HIV infection has direct implications for a child’s well-being,

even if that child is not HIV-infected.

Communicating with the caregiver is an important part of provid

ing care and support to the child. At the earliest opportunity, health

workers should discuss with the mother/caregiver the possibility of

HIV infection in their child. is requires that health workers develop

the skills necessary to eﬀectively and positively provide counselling

for women (and their partners), communicate bad news, and provide

immediate and ongoing support.

Health workers should ensure that they provide adequate time for

caregivers to ask questions so that they can fully understand the im

Handbook on Pædiatric AIDS in Africa

plications of HIV and HIV testing, for themselves and for their child.

When HIV is suspected in a child, the mother and family should be

counselled and oﬀered testing.

Communicating with the caregiver has direct beneﬁts for the family,

including:

• Helping the mother adopt a positive living attitude.

• Alerting the health worker to the possibility of treatable HIV-re-

lated conditions, such as TB, in the mother/family.

• Oﬀering opportunity for mother/family to access other support

services (e.g., peer support groups and post-test clubs), nutritional

support, and ART.

• Providing relevant counselling to the mother on infant feeding op-

tions, and nutrition for herself and other family members.

• Providing support for mother/father to develop behaviour change

to reduce HIV transmission.

• Counselling the mother to conﬁrm the HIV infection status at a

later age if the child is still young. is is particularly pertinent for

PMTCT programmes, where a follow-up schedule and time point

for infant testing must be carefully explained to the mother.

Parents and/or caregivers need to participate in making decisions

and planning appropriate care for the child, including decisions

about therapy and where the child should receive care. In this respect,

health workers must ensure that the family considers the social needs

of HIV-infected and -aﬀected children.

In addition to providing practical and emotional support to caregivers,

health workers should also deal with other speciﬁc issues, such as the

importance of positive living and ensuring that the educational and

recreational needs of children with HIV are met.

Care of the HIV-infected child should be child-focused, family-

centred, and community-based, and the health worker must be aware

Handbook on Pædiatric AIDS in Africa

that the adolescent child has special considerations of denial, adher-

ence, sexuality, peer pressure, school issues, and other responsibilities

(e.g., child-headed families).

Other care and support services that may be available in MCH and

family care centres include:

• HIV VCT for the mother, partner, and other children

• Sexual and reproductive health counselling and support, including

family planning services

• Prevention and treatment of reproductive tract infections and STIs

• Mental health and psychosocial care and support

• Screening and treatment for TB

• Nutrition care and support services

• Prophylaxis and treatment of HIV-related infections and condi-

tions

• ART for family members who meet treatment criteria

Handbook on Pædiatric AIDS in Africa

Children Whose Parents/Guardians Have

AIDS or Who Are Orphaned by AIDS

Children often feel the impact of HIV/AIDS when their parents are

ﬁrst diagnosed with HIV, long before they become orphans because

of AIDS. e poor understanding of the mental, emotional, spiritual,

and social needs of children aﬀected by HIV/AIDS has resulted in an

extremely limited response to date.

HIV/AIDS-related illness or death in the family leads to:

• Mental, psychological, and social distress in the family and for the

child

• Children left without adult love, adequate care, or protection

• Stigma and discrimination

• Exploitative child labour

• Sexual exploitation

• Life on the streets

• Child-headed household

• Withdrawal from, or interruption of, school

• Inadequate food, shelter, or fulﬁlment of other material needs

• Reduced access to health services

Regardless of which family member is ﬁrst diagnosed with HIV/AIDS,

comprehensive care for an exposed or infected child requires more

than health care. e health worker should therefore enlist the early

support of other sectors to link orphans and other vulnerable children

(OVC) to programmes that provide psychosocial and socio-economic

support and HIV prevention activities.

UNAIDS, UNICEF, and USAID provide the following guiding prin

ciples to respond to the needs of OVC (see chapter 11 for details on

psychosocial support):

Handbook on Pædiatric AIDS in Africa

• Strengthen the protection and care of OVC within their extended

families and communities

• Strengthen the economic coping capacities of families and com-

munities

• Enhance the capacity of families and communities to respond to

the psychosocial needs of OVC and their caregivers

• Link HIV/AIDS prevention activities, care and support for PLHA,

and eﬀorts to support OVC

• Focus on the most vulnerable children and communities, not just

those orphaned by AIDS

• Give particular attention to the roles of boys and girls and men and

women, and address gender discrimination

• Ensure the full involvement of young people as part of the solution

• Strengthen schools and ensure access to education

• Reduce stigma and discrimination

• Accelerate learning and information exchange

• Strengthen partners and partnerships at all levels and build coali-

tions among key stakeholders

• Ensure that external support strengthens and does not undermine

community initiatives and motivation

Knowledge Gaps

ere are still critical gaps in the care of HIV-infected children related

largely to the psychosocial support of the child:

• What is the best way to disclose HIV status to the child and sib-

lings?

• What is the post-disclosure mental status of these children and

how are they best supported?

Handbook on Pædiatric AIDS in Africa

• Older children (from as early as 5 to 7 years), based on their level

of understanding, have communication and psychosocial needs

related to their illness and/or that of their family members. What

are these needs and how are they best met?

• What is the experience with family models of care to date?

Other gaps are related to the logistics of providing ARV in a poor

resource setting. What are the best and most eﬃcient mechanisms

simultaneously to scale up ART for children and adults in resource-

poor settings?

Additional Reading

Guidelines on HIV-Related Care, Treatment, and Support for HIV-In-

fected Women and eir Children in Resource-Constrained Settings

[Draft for Review. December 2003]. Summary of Key Recommenda-

tions of WHO-UNICEF-UNFPA-World Bank-UNAIDS-FHI.

Children on the Brink 2004

: A Joint Report on Orphan Estimates and

Program Strategies. UNAIDS, UNICEF, USAID, July 2004.

Handbook on Pædiatric AIDS in Africa

Chapter 5

Diagnosis and Clinical

Staging of HIV Infection

Summary

• e magnitude of HIV infection among children in sub-Saharan

Africa (SSA) and the rapid progression of the HIV in this age group

mean that there is a limited window of opportunity for eﬀective

intervention. Speciﬁc care and treatment interventions are linked

to the certainty of diagnosis.

• Judicious use of clinical criteria and antibody tests can reliably

diagnose HIV infection and conﬁrm exposure status in many

children in SSA. Every eﬀort must be made to make an early and

deﬁnitive diagnosis of HIV/AIDS as a ﬁrst step to speciﬁc care,

treatment, and support.

• HIV antibody testing continues to be the backbone of laboratory

diagnosis, despite its limitation in children aged <18 months (who

may still be carrying maternal HIV-speciﬁc antibodies).

• More complex (virologic) tests are needed to conﬁrm HIV infec-

tion in children under 18 months of age. Particularly in this age

group, additional laboratory tests (e.g., CD4 counts and CD4% and

total lymphocyte counts) contribute enormously to critical care

and treatment decisions.

• Combining clinical and laboratory criteria to stage HIV disease

ensures timely and rational initiation of care, treatment, and ap-

propriate counselling.

Handbook on Pædiatric AIDS in Africa

Introduction

Clinical signs and symptoms are useful parameters in making an HIV

diagnosis, but in children clinical features of HIV infection overlap

with those of other common childhood diseases (see Table 5.1). Clini-

cal features are more reliable in children with severe clinical disease

(AIDS).

Accurate diagnosis of paediatric HIV infection depends on laboratory

tests, which can be divided into two categories: antibody tests, which

are relatively easy to perform, provided that routine diagnostic labora

tories staﬀed by qualiﬁed personnel are available, and virologic tests,

which are expensive and involve complex laboratory methods.

Passive transfer of maternal antibodies across the placenta means that

babies born to HIV-infected women will have circulating maternal

antibodies in their systems up to the age of 18 months. erefore,

for children younger than 18 months, health workers must perform

virologic tests, which detect the virus directly, to distinguish reliably

the infant’s HIV infection status from that of its mother.

If virologic tests are not available to conﬁrm HIV infection, but CD4

cell assays or total lymphocyte counts are available, critical treat-

ment decisions are necessary for infants who are HIV-positive and

who have advanced disease (WHO Paediatric Clinical Stage III, see

Table 5.2).

Breast-feeding may further complicate diagnosis in infants. HIV-ex

posed infants who are breast-fed are at risk of acquiring HIV infection

throughout the breast-feeding period, a factor that must be taken into

account when requesting or interpreting HIV test results in children.

Why Is It Important to Make a

Diagnosis of HIV Infection?

HIV infection is common among children in sub-Saharan Africa and

is a signiﬁcant contributor to infant and childhood morbidity and

mortality, with more than half of the HIV-infected children dying

before their second birthday. Timely diagnosis of HIV enables timely

Handbook on Pædiatric AIDS in Africa

initiation of treatment. Furthermore, age is an important determi-

nant of the rate of disease progression; the disease progresses much

faster in infants and children than in adults. Resources for HIV care

and treatment are slowly improving for adults in SSA; they must be

similarly mobilised for the beneﬁt of HIV-infected children.

Diagnosis of HIV infection facilitates the following:

• Access to currently available eﬀective interventions, which reduce

morbidity and mortality associated with infection.

• Access to needed interventions for other aﬀected family members.

Diagnosis of HIV in a child is often the ﬁrst indication of infec-

tion among other family members and provides opportunities to

provide care, treatment, and support to parents and siblings.

• Access to social and emotional support for the child and family.

• Appropriate healthcare and social welfare planning at the national,

regional, and local levels.

Approach to Diagnosis

A rational approach to diagnosis of paediatric HIV infection requires

health workers who have a high index of suspicion and are knowl-

edgeable and skilled in diagnosis and management of HIV infection

in children. Basic communication skills are essential to enable health

workers to discuss and oﬀer HIV testing to children and their parents.

Depending on available resources in a given setting, diagnosis may be

• Clinical (based on signs and symptoms), or

• A combination of clinical and laboratory-supported.

HIV-speciﬁc laboratory tests provide a deﬁnitive diagnosis, add to

the strength of a clinical diagnosis (e.g., by conﬁrming exposure), or

can actively aid the exclusion of HIV disease, allowing clinicians to

explore other diﬀerential diagnoses.

Handbook on Pædiatric AIDS in Africa

Other laboratory tests such as total lymphocyte count and CD4 count

and percentage, provide further supportive evidence of HIV infection

and an indication of the degree of immunodeﬁciency.

HIV/AIDS should be suspected among children with suggestive clini

cal signs or HIV-associated conditions (see Table 5.1). Health workers

should extend diagnosis to children born to HIV-infected mothers,

those who are sexually assaulted, or those exposed to potentially

infectious bodily ﬂuids. If HIV infection is suspected or conﬁrmed,

determine the exact clinical stage of disease using one of the two

established staging systems (WHO or CDC system).

Clinical Diagnosis

HIV infection presents with conditions that are frequently found in

children who are not HIV infected, making it diﬃcult to make a clini-

cal diagnosis. Table 5.1 groups these conditions according to whether

they are common in both HIV-infected children and uninfected chil-

dren, common in infected children but less common in uninfected

children, and whether they are very speciﬁc to HIV infection. e

occurrence of these clinical signs or conditions may suggest HIV

infection in a child and should alert the health worker to obtain other

relevant additional history (such as maternal health), and laboratory

data where possible.

Handbook on Pædiatric AIDS in Africa

Table 5.1. Clinical Signs or Conditions in Child at May Suggest HIV Infection

Speciﬁcity for HIV Infection Signs/Conditions

Signs/conditions very speciﬁc

to HIV infection

• Pneumocystis

pneumonia

• Oesophageal candidiasis

• Extrapulmonary cryptococcosis

• Invasive salmonella infection

• Lymphoid interstitial pneumonitis

• Herpes zoster (shingles) with

multi-dermatomal involvement

• Kaposi’s sarcoma

• Lymphoma

• Progressive multifocal encephalopathy

Signs/conditions common

in HIV-infected children and

uncommon in uninfected

children

• Severe bacterial infections, particularly if

recurrent

• Persistent or recurrent oral thrush

• Bilateral painless parotid enlargement

• Generalized persistent non-inguinal

lymphadenopathy

• Hepatosplenomegaly (in non-malaria

endemic areas)

• Persistent and/or recurrent fever

• Neurologic dysfunction

• Herpes zoster (shingles), single dermatome

• Persistent generalized dermatitis

unresponsive to treatment

Signs/conditions common

in HIV-infected children but

also common in ill uninfected

children

• Chronic, recurrent otitis with ear discharge

• Persistent or recurrent diarrhoea

• Severe pneumonia

• Tuberculosis

• Bronchiectasis

• Failure to thrive

• Marasmus

Handbook on Pædiatric AIDS in Africa

Diagnosis Using the IMCI Algorithm

e IMCI guidelines in most countries now include symptoms sug-

gestive of HIV. ree countries (South Africa, Uganda and Ethiopia)

have conducted studies on integrating HIV/AIDS into the IMCI

algorithm, in which a child is classiﬁed as symptomatic HIV if the

IMCI practitioner identiﬁed any four (or any three for South Africa)

of the following:

• Recurrent pneumonia

• Oral thrush

• Present or past ear discharge

• Persistent diarrhoea

• Very low weight

• Enlarged lymph nodes

• Parotid enlargement

e studies found that these symptoms and signs have a high speciﬁ

city but low sensitivity (except for South Africa), meaning that this

approach would be very useful in identifying HIV infection when

applied to an individual child in a clinical setting. However, because

of the low sensitivity, many children would still be missed. Laboratory

testing to conﬁrm infection is therefore necessary.

Laboratory Assays (Tests)

Laboratory tests provide suggestive and/or conﬁrmatory evidence of

HIV infection. ere are two types of laboratory tests:

• Antibody tests: HIV ELISA, rapid tests, and Western Blot

• Virologic tests: HIV DNA PCR assays, RNA assays including viral

load, HIV immune complex-dissociated p24 antigen assays, and

HIV peripheral blood mononuclear viral culture

Handbook on Pædiatric AIDS in Africa

Antibody Tests

Antibody tests are the most widely used HIV diagnostic test and

provide reliable evidence of HIV infection in adults and children who

are older than 18 months. e HIV antibody test is less reliable in

infants aged less than 18 months because they may still be carrying

HIV-speciﬁc antibodies acquired from the mother in utero. e time

it takes for an HIV-positive mother’s maternal antibodies to be elimi-

nated from an infant’s system (seroreversion) varies. e majority of

uninfected non-breast-fed children will serorevert by age 15 months,

but a smaller percentage (ranging from a low of 1% to a high of 18% in

various studies) will not revert until age 18 months.

Despite these limitations, HIV ELISA and rapid tests are the most

widely available tests, and do provide (or exclude) evidence of expo

sure.

Virologic Tests

HIV Immune Complex Dissociated p24 Antigen Assays

e p24 protein (antigen) is from the core proteins of the HIV virus

(see chapter 2). Detection of p24 antigen is deﬁnitive evidence of

HIV infection. e p24 antigen assays use techniques that can be

performed in most routine laboratories. In addition, they can be used

for diagnosis in children less than 18 months of age. Although the

ﬁrst-generation tests were highly speciﬁc, the sensitivity was lower

than that of DNA PCR and RNA assays. e newer, ultra-sensitive

p24 assays are more reliable, but require further evaluation for their

use in infants.

HIV DNA PCR

DNA PCR assays amplify the HIV pro-viral DNA sequences within

mononuclear cells present in peripheral blood and the results of such

assays are the accepted standard for diagnosis of HIV infection during

infancy in developed countries.

Handbook on Pædiatric AIDS in Africa

e sensitivity of HIV DNA PCR is low during the ﬁrst 1 to 2 weeks of

life because this test is not able to detect very low levels of HIV DNA

in babies infected a few minutes/hours/days earlier, during delivery

and early breast-feeding. After 4 to 6 weeks of life, the sensitivity and

speciﬁcity of HIV DNA PCR tests approach 100%, except in babies

who have continuing exposure to HIV through breast-feeding.

Some issues are associated with DNA PCR assays. Although the test

can be completed within one day, blood samples from a number of

patients are often tested in batches to reduce costs, delaying the avail

ability of results for some individuals. HIV DNA PCR tests require

specialized laboratory equipment and skilled personnel, and are

therefore expensive. Also, samples may become contaminated with

HIV DNA from other sources.

New technologies, such as real-time PCR technologies, could provide

a good alternative because they are rapid, simple, cheap, and adapt

able to the diﬀerent clades of HIV. eir usefulness is still being

evaluated.

HIV RNA Assays

HIV RNA assays detect viral RNA in plasma and other body ﬂuids

using a variety of methods (reverse transcriptase PCR, in vitro signal

ampliﬁcation nucleic acid probes [branched chain DNA], and nucleic

acid sequence-based ampliﬁcation [NASBA]).

RNA assays are more widely available than HIV DNA PCR tests, have

a faster turnaround time, and require smaller blood volumes. RNA

assays are also more sensitive for early detection of infection (ﬁrst 2

months of life) than HIV DNA PCR tests.

Quantitative RNA (viral load tests) tests are used to determine the

risk of HIV disease progression and to guide decisions for initiating

ART.

HIV RNA assays require specialized laboratory equipment and skilled

personnel and are, therefore, expensive.

Handbook on Pædiatric AIDS in Africa

HIV Peripheral Blood Mononuclear Viral Culture

e HIV peripheral blood mononuclear viral culture assay was the

gold standard of HIV detection in the past, before the development

of simpler and less expensive tests based on detection of HIV nucleic

acid sequences DNA PCR or RNA PCR assays. is assay has a lower

sensitivity than the other tests described above, and must be per-

formed in protected laboratories (also called P2 labs). Current use is

limited to research laboratories.

Where Laboratory Testing Is Available

Appropriate pre- and post-test counselling should be available and

oﬀered (see chapter 11). It is also important that health workers oﬀer

HIV counselling and testing to parents.

Pre-test counselling should include information about the limitations

of the testing approach, the beneﬁts of early diagnosis for the child,

and the implications of a positive HIV antibody test results for the

family.

Interpretation of Test Results

In children more than 18 months of age:

• HIV infection can be conﬁrmed in those with positive antibody

results

• HIV infection can be excluded in those with negative antibody

results

• HIV-exposed children who continue to breast-feed should be

retested 3 to 6 months after complete cessation of breast-feeding

before HIV infection can be excluded

In children less than 18 months of age:

Virologic test available

• A negative test excludes HIV infection

• A positive test conﬁrms HIV infection

Handbook on Pædiatric AIDS in Africa

Virological tests not available

• HIV infection can be excluded in those with negative antibody

results (particularly if they had a previous positive result).

• Diagnose probable HIV infection in those with clinical features and

positive antibody results. Conﬁrm the result by repeat antibody

testing after the child is more than 18 months of age.

• Retest HIV-exposed children who continue to breast-feed 3 to 6

months after complete cessation of breast-feeding, before HIV

infection can be excluded.

In the presence of a clinical diagnosis, one HIV test is adequate to

inform management. Children of HIV-infected women who are well

and test positive should have a repeat test.

Staging HIV Infection and Disease in Children

Under current guidelines ARV treatment is initiated in patients with

AIDS or those with rapidly progressive disease. Staging is a standard-

ized method for assessing disease stage/progression and for making

treatment decisions. It is important to stage children with HIV infec-

tion because staging:

• Clariﬁes the prognosis of individual patients

• May strengthen the clinical diagnosis of HIV infection when labo-

ratory testing is unavailable

• Aﬀects the type of treatment interventions, including indications

for starting and/or changing ART

Clinical and laboratory parameters are used to stage HIV disease.

ere are two international clinical staging systems that classify the

severity of HIV infection in children: the U.S. Centers for Disease

Control and Prevention (CDC) clinical staging and the WHO Paedi

atric Clinical Staging.

Handbook on Pædiatric AIDS in Africa

e CDC Clinical Staging System (Appendix B) divides infected chil-

dren into one of four clinical categories: Category N (asymptomatic),

Category A (mildly symptomatic), Category B (moderately sympto-

matic), and Category C or AIDS (severely symptomatic). Although

the CDC staging system is more widely used in relatively advanced

paediatric HIV care settings in Africa (e.g., Botswana, South Africa),

the recently developed WHO paediatric staging, which relies more on

readily identiﬁable clinical entities, may be more appropriate for the

majority of HIV care settings in sub-Saharan Africa.

e WHO Paediatric Clinical Staging System (November 2004) also

divides HIV-infected children into four categories.

Handbook on Pædiatric AIDS in Africa

Table 5.2. WHO Paediatric Staging of HIV/AIDS Disease

WHO

Paediatric

Stage 1

• Asymptomatic

• Persistent generalised lymphadenopathy (PGL)

• Hepatosplenomegaly

WHO

Paediatric

Stage 2

• Papular pruritic eruptions

• Seborrheic dermatitis

• Fungal nail infections

• Angular chelitis

• Lineal gingival erythema

• Extensive HPV or molluscum infection (>5% of body area/face)

• Recurrent oral ulcerations (>2 episodes/6 mos)

• Parotid enlargement

• Herpes zoster (>1 episode/12 mos)

• Recurrent or chronic upper respiratory infection (URI): otitis media,

otorrhea, sinsusitis (>2 episodes/6 mos)

WHO

Paediatric

Stage 3

• Unexplained moderate malnutrition (-2 SD or Z score) not responding

to standard therapy

• Unexplained persistent diarrhoea (>14 days)

• Unexplained persistent fever (intermittent or constant, >1 mo)

• Oral candidasis (outside neonatal period)

• Oral hairy leukoplakia

• Pulmonary tuberculosis

• Severe recurrent presumed bacterial pneumonia (>2 episodes/12 mos)

• Acute necrotizing ulcerative gingivitis/periodonitis

• Lymphoid interstitial pneumonistis (LIP)

• Unexplained anemia (<8 gm/dL), neutropenia (<1,000/mm3 ), or

thrombocytopenia (<30,000/mm3) for >1 mo.

• HIV-related cardiomyopathy

• HIV-related nephropathy

Handbook on Pædiatric AIDS in Africa

Table 5.2. WHO Paediatric Staging of HIV/AIDS Disease

WHO

Paediatric

Stage 4

Symptomatic HIV-antibody positive infant age <18 mos*

• Two or more of the following:

• Oral candidiasis/rush

• Severe pneumonia

• Failure to thrive

• Sepsis

* Presumptive diagnosis of Stage 4 disease in HIV-antibody positive

infants <18 mos requires conﬁrmation with HIV virologic tests when

possible, or by antibody tests after age 18 mos.

WHO

Paediatric

Stage 4

(Any Age)

• Unexplained severe wasting or severe malnutrition (-3 SD or Z score)

not responding to standard therapy

• Pneumocystis pneumonia

• Recurrent severe bacterial infections (>2 episodes/12mos, excluding

pneumonia)

• Chronic orolabial or cutaneous HSV (lasting >1 mo)

• Extrapulmonary tuberculosis

• Kaposi’s sarcoma

• Esophageal candidiasis

• CNS toxoplasmosis

• Cryptococcal meningitis

• Any disseminated endemic mycosis

• Cryptosporidiosis or isosporiasis (with diarrhoea >1 mo)

• CMV infection of organ other than liver, spleen, lymph nodes (and

onset age >1 mo)

• Disseminated mycobacterial disease other than tuberculosis

• Candida of trachea, bronchi or lungs

• Acquired recto-vesico ﬁstula

• Cerebral or B cell non-Hodgkins lymphoma

• Progressive multifocal leukoencephalopathy (PML)

• HIV encephalopathy

Handbook on Pædiatric AIDS in Africa

Clinical AIDS and /or severe immune suppression deﬁne those chil-

dren who need the most aggressive care and treatment interventions,

including ART.

e older (1986) WHO Case Deﬁnition of AIDS in Children may be

even more familiar to clinicians and health workers in many primary

care settings. Despite its recognised weaknesses—it has a low sensi

tivity (but high speciﬁcity)—it is still of value in identifying children

needing to be referred for treatment. Because it has a low sensitivity,

these criteria may also identify children with primary malnutrition,

tuberculosis or post-measles complications as having AIDS.

Table 5.3. 1986 WHO Case Deﬁnition of AIDS in Children

Major Signs (presence of at least 2 require d):

• Weight loss or abnormally slow growth

• Chronic diarrhoea (>1 month duration)

• Prolonged fever (>1 month duration)

• Severe or recurrent pneumonia

Minor Signs (presence of a t least 2 required ):

• Generalized lymph node enlargement

• Oropharyngeal candidiasis

• Recurrent common infections (e.g., ear infections, pharyngitis)

• Persistent cough (in the absence of TB disease)

• Generalized rash

• Maternal HIV infection

AIDS is deﬁned as the presence of at least 2 or more major signs and 2 or more minor signs if

there are no other causes of immune suppression

Handbook on Pædiatric AIDS in Africa

Immunologic Staging

e CDC has also developed an immunological staging system based

on CD4 counts by age: no evidence of immune suppression, moderate

suppression, and severe immune suppression.

Table 5.4. Immunological Classiﬁcation Based on Total and % CD4 Count

Immunologic

other skin problems).

Anaemia

Anaemia is a common condition in HIV-infected children and con-

tributes signiﬁcantly to morbidity. e prevalence of anaemia in HIV-

infected infants is determined to a large extent by the prevalence of

other conditions that cause anaemia, such as malaria and helminthic

infections. e prevalence of malnutrition, and especially micronutri-

ent malnutrition, also contributes signiﬁcantly to the prevalence of

anaemia.

HIV-infected children have an equal prevalence of anaemia compared

to uninfected children but have a higher case fatality rate. A study in

Abidjan found an equal frequency of anaemia in HIV-infected and

uninfected children. In the same study, the case fatality rate (CFR)

from anaemia was 13% in HIV-infected children (third commonest

cause of death) compared to a CFR of 8% in uninfected children (ﬁfth

commonest cause of death).

Measles

Measles is one of the major causes of morbidity and mortality in sub-

Saharan Africa and is a severe illness in children with HIV infection,

particularly those with advanced immunodeﬁciency. Severe cases can

occur without the typical rash and may be complicated by pneumo-

nia or encephalitis. HIV-infected children with measles have a high

case fatality and should be treated in hospital. Management should

include 2 doses of vitamin A, calculated on the basis of the child’s age

102

Handbook on Pædiatric AIDS in Africa

(50,000 IU if aged <6 months; 200,000 IU in children aged 12 months

to 1 year).

Measles may occur in early infancy in HIV-infected children because

of inadequate transfer of maternal antibodies and infection may occur

despite history of immunisation.

Give measles immunisation to HIV-infected children at 6 months and

repeat at 9 months.

Neurological Manifestations

HIV is a neurotropic virus that invades the central nervous system by

infecting monocytes, which cross the blood-brain barrier and estab-

lish HIV infection in microphages and microglial cells. Neurological

symptoms are widely prevalent, occurring at all stages of HIV infec-

tion and aﬀecting any part of the nervous system. It is estimated that

40% to 70% of HIV-infected persons develop symptomatic neurologi-

cal disturbances, but the brain is most commonly aﬀected in children.

Neurological manifestations are some of the most common modes

of presentation of HIV/AIDS, but they are infrequently diagnosed in

children. Delay in reaching developmental milestones, in particular,

may be an early indication of HIV infection in HIV-exposed children.

In general, however, neurological manifestations, especially periph

eral neuropathy (and especially in children) are not considered, may

be diﬃcult to diagnose, and even when diagnosed, are inadequately

managed. Encephalopathy and developmental delay are common in

HIV-infected children and indicate advanced clinical disease.

ART is possibly the only way to reverse the eﬀects of HIV infection on

the CNS and allow restoration of growth, development, and mile

stones. However, ART and other medications used in the treatment

can also have neurological side eﬀects, the most common of which is

peripheral neuropathy.

103

Handbook on Pædiatric AIDS in Africa

HIV Encephalopathy

Growth and development of the brain is outwardly manifested by

achievement of childhood milestones (smiling, walking, talking, etc.).

HIV infection of the brain interferes with this process and manifests

as static, slowing, or regression of developmental milestones or as

localized damage. is whole process is referred to as HIV encepha-

lopathy.

HIV encephalopathy has been reported to be about 21% in HIV-

infected African children. Age of onset of developmental delay is

unpredictable, but the onset of encephalopathy may be related to the

presence of other symptoms of HIV disease (e.g., hepatosplenomegaly

and lymphadenopathy).

Diagnosis

Diagnosis is mainly clinical and depends on the presence of least two

of the following for at least 2 months:

• Failure to attain or loss of developmental milestones or loss of

intellectual ability

• Impaired brain growth or acquired microcephaly

• Acquired symmetrical motor deﬁcit manifested by two or more of

the following: paresis, pathologic reﬂexes, ataxia, or gait distur-

bances

• Cerebrospinal ﬂuid is normal or has non-speciﬁc ﬁndings and CT

scan shows diﬀuse brain atrophy.

Management

Managing encephalopathy should include evaluating the child with

the help of a neurologist, if possible. If nothing other than HIV is

found, the treatment goal is to reduce viral load. Depending on the se-

verity, the patient will need a support system, which includes physical

therapy, a social worker, and surgery to minimise contractures.

104

Handbook on Pædiatric AIDS in Africa

Other Neurological Manifestations

Neuropathy

Several types of peripheral neuropathy aﬀecting single or multiple

nerves have been documented (e.g., axonal neuropathy, demyelinated

neuropathy, polyradiculopathy, and radiculopathy). HIV-related

neuropathy is a troublesome condition that occurs in as many as

one-third of patients with a CD4 count <200/µL. It presents with

dysaethesias and numbness in a “glove and stocking” distribution.

Neuropathy in children is more diﬃcult to diagnose and less well

described than in adults. Diagnosis is based on clinical presentations

such as pain or numbness that has a “glove and stocking” distribution.

Treatment is mainly symptomatic. Pain due to neuropathies may re

spond to analgesics combined with amitriptylne, carbamezapine, and

lamotrigine. Use morphine in end-stage disease.

Seizures

Seizures are common non-speciﬁc manifestations of neurological ill-

nesses associated with HIV. Seizures may result from:

• Space-occupying lesions (most often cerebral toxoplasmosis or

tuberculoma)

• Meningitis (most often cryptococcal)

• Metabolic disturbances

• No identiﬁed cause other than HIV infection

Treatment is aimed at the underlying disorder and seizure control

through standard anti-epileptic medication. Drug interactions may be

a problem for patients on HAART; for those on HAART the drug of

choice is valproate.

For patients presenting with focal seizures, consider treatment for

toxoplasmosis, if no other cause is apparent.

105

Handbook on Pædiatric AIDS in Africa

Opportunistic Infections

CNS OIs are seen in cases of severe immunosuppression

(CD4 <200/µL) in older children and adolescents (Table 6.1).

e most common OI in children is, reportedly, CMV infection.

Other viruses, especially herpes simplex and varicella-zoster virus,

can also cause acute encephalitis.

Fungal infections, particularly candida and aspergillus meningitis, are

reported to be the second most common infection in children.

Cryptococccal meningitis is rarely seen in young children with AIDS,

but has been reported among older children and adolescents. Toxoplas

ma encephalitis has rarely been reported in older paediatric patients.

106

Handbook on Pædiatric AIDS in Africa

Table 6.1. Opportunistic Infections of the Central Nervous System

Neurological

Disease

Clinical Presentation Diagnostic Tests Management

Cytomegalo-

virus

• Presents with en

cephalitis with retinitis,

radiculomylitis, or

neuritis

CSF, PCR, MRI, if

available

Intravenous ganciclovir

10mg/kg per day in 2

divided doses for 2 to

3 weeks.

Foscarnet 180mg/kg/

day in 3 divided doses

for 14 to 21 days may

be used when there is

sight threatening CMV

retinitis.

Cryptococcus

• Presents with fever,

headache, seizures,

change in mental

status

• Focal neurological

signs uncommon

CSF-Indian ink positive

Cryptococcal antigen

test, MRI, if available

Induction with

amphotericin B (0.7–1.0

mg/kg/day) for 2 weeks

followed by ﬂuconazole

400mg/day for a mini

mum of 10 weeks, then

200mg/kg maintenance

therapy.

Toxoplasmosis

• Most common mani

festations are encepha

litis, mental changes,

fever headache, and

confusion.

Serology, MRI, if avail

able

Do not do lumbar

puncture if there is

mass lesion.

Pyrimethamine loading

dose 2 mg/kg/day (max

50 mg) for 2 days then

maintenance, 1 mg/kg/

day (max 25mg) plus

sulphadiazine 50 mg/kg

every 12-hours/folinic

acid 5–20 mg 3 times

weekly.

Treat until 1–2 weeks

beyond resolution of

signs and symptoms.

Herpes

simplex virus

• Associated with fever-

altered state of con

sciousness, personality

changes, convulsions,

and usually focal

neurological signs,

particularly temporal

lobe signs

Rising serum HSV

titres and increased

ratio of CSF-to-serum

concentration of HSV

antibody

Viral isolation

IV Acyclovir 20mg/kg

given 3 times a day for

21 days.

107

Handbook on Pædiatric AIDS in Africa

Dermatitis and Other Skin Manifestations

e most common skin manifestation of HIV/AIDS in children is a

non-speciﬁc generalized dermatitis. Other skin lesions are secondary

infections and the frequency is related to the severity of immune sup-

pression. Viral, bacterial, and fungal skin infections are more common,

but also more diﬃcult to treat than in children who are not immuno-

compromised. Treatments for some common skin manifestations are

shown in Table 6.2.

Other non-infectious manifestations include:

• Seborrhic dermatitis

• Atopic dermatitis

• Eczema

• Psoariasis

• Drug eruptions

• Skin lesions associated with nutritional deﬁciency (more prevalent

in children than in adults; drug eruptions are lower in children

than in adults; cotrimoxazole can cause reaction in children who

are immunocompromised)

108

Handbook on Pædiatric AIDS in Africa

Table 6.2. Common Skin Manifestations and Treatments

Skin Manifestation Treatment

Scabies Treatment

Children <1yr

• 25% benzyl benzoate for 12 hours or gamma benzene

hexachloride

• 2.5% sulphur ointment 3x daily for 3 days

• Screen and treat other household contacts where appropriate

• Wash and iron bedding and clothing or hang it out in the sun

Eczema Treatment

• Avoid soap and expose aﬀected areas to sunlight

• Use aqueous cream instead of soap for washing; use moisturizer

on dry areas

• Apply zinc oxide cream 2x daily; if not responding, use 1% hy

drocortisone cream 2x daily

• Cut nails short

Ringworm Treatment

• Apply Whitﬁeld’s ointment (benzoic acid with salicylic acid)

2x daily for 2 to 5 weeks for body lesions; if not successful try

2% miconazole cream

• For scalp lesions give griseofulvin 10m/kg/day for 8 weeks; if not

responding consider ketoconazole

Herpes zoster

Prophylaxis

• Hospitalise all cases and treat, if possible, with IV acyclovir

30mg/kg/day divided into doses every 8 hours for a total of 7

days or 2 days after cessation of new lesion formation, whichever

is longer

• Children who have been exposed to herpes zoster may receive

prophylaxis using varicella-zoster immune globulin (VZIG) 125U

per 10 kg (max 625U) within 48–96 hours of exposure.

Herpes simplex

Treatment

• Local antiseptic (gentian violet)

• Analgesia (paracetamol)

• Admit all children with disseminated or severe herpes simplex

and give acyclovir 5mg/kg intravenously 3 times a day or

200–400mg orally 5 times a day, for 7–10 days.

Impetigo Treatment

• Hygiene, proper washing, cut ﬁngernails, soak crusts oﬀ in soapy

water

• Apply 10% iodine solution 3x daily or zinc oxide cream

• Antibiotics indicated only if pyrexial, lymphadenopathy, or

lesions are resistant to treatment (ﬁrst-line = amoxycillin for 10

days; second-line = ﬂocloxacillin or erythromycin for 10 days)

109

Handbook on Pædiatric AIDS in Africa

Oral and Dental Conditions

Oral and dental conditions are also common in HIV-infected children,

particularly those who are malnourished. erefore, good dental

hygiene is important. e most common oral condition in HIV-

infected children is candidiasis, which may present as oropharyngeal

or oesophageal candidiasis. Oral thrush is predictive of HIV infection

if seen after the neonatal period without prior antibiotic treatment,

if lasting for more than 30 days, or if it is recurrent. Oral thrush is

associated with diﬃculty or pain in swallowing or vomiting. Children

therefore present with reluctance to take food, excessive salivation,

or crying while feeding. Exclude other conditions that cause painful

swallowing and are frequently found in HIV-infected children such as

CMV, Herpes simplex, and lymphomas.

Treatment of Candidiasis

Oral Candidiasis

• Nystatin 1–2 million U/day divided every 6 hours until resolution

Oesophageal Candidiasis

• Fluconazole 3–6 mg/kg once daily or

• Amphotericin B, 0.3mg/kg/day

Other common dental conditions of HIV-infected children include:

• Dental caries

• Aphthous ulceration (Herpes simplex-related ulcer; if diagnosed

early it will be amenable to acyclovir)

• Oral hairy leukoplakia

• Angular stomatitis

• HIV-associated gingivitis

110

Handbook on Pædiatric AIDS in Africa

Malignancy

e major malignancies associated with HIV infection in African chil-

dren are Kaposi’s sarcoma (KS) and non-Hodgkin’s disease lymphoma

(Burkitt’s lymphoma, B-cell lymphoma). B-cell lymphoma is more

prevalent in South Africa than Burkitt’s lymphoma. Clinical experi-

ence indicates that the frequency of occurrence of some malignancies

is increasing.

Kaposi’s Sarcoma

Before the HIV pandemic, KS was rare in children, and adults tended

to have the less aggressive endemic type. Currently, KS is more preva-

lent in East and Central Africa and less prevalent in West and South

Africa.

KS can present as early as the ﬁrst month of life. KS is associated with

human herpes virus 8 and usually presents as generalised lymphaden

opathy, black/purple mucocutaneous lesions (skin, eye, and mouth);

the chest lesions may mimic those of TB.

Diagnosis is conﬁrmed by biopsy of the lesion and histological exami

nation. Treatment requires chemotherapy and radiotherapy, but ART

also often leads to regression of the lesions.

Parotid Enlargement

Bilateral parotid gland enlargement is one of the most speciﬁc signs of

HIV infection in children. Parotid enlargement is usually not tender

and is commonly found in older children who are slow progressors;

it may be associated with lymphoid interstitial pneumonitis. When

parotid enlargement is exceptionally large, it may be disﬁguring and

lead children to be teased and/or emotionally distressed.

Periodically the parotid glands may enlarge and regress over several

months, and intermittently they may become tender from bacterial

super-infection. When they are tender, prescribe antibiotics and anal

gesics. ere should be no surgery.

111

Handbook on Pædiatric AIDS in Africa

Persistent Generalised Lymphadenopathy

Persistent generalised lymphadenopathy is one of the most common

early clinical presentations of HIV-infected children. It may also be

associated with other parotid enlargement or hepatosplenomegaly.

A biopsy may show non-speciﬁc inﬂammation of the nodes. It is

important to remember that disseminated TB, Kaposi’s sarcoma (KS),

and leukaemia can also present with generalised lymphadenopathy.

Other causes include acute toxoplasmosis, rubella, CMV, herpes, and

syphilis.

Other Medical Conditions

Cardiac Disease and HIV

Studies from developed countries indicate that most HIV-infected

children referred for cardiovascular assessment were found to have

abnormalities that were often clinically non-apparent. Few similar

studies have been reported for African children. One such study, in

Uganda, involved 230 symptomatic HIV-infected children. Of these,

51% had abnormal echocardiographic changes. One-quarter of those

with abnormal echocardiographic changes had cardiovascular symp-

toms. erefore, clinicians should evaluate HIV-infected children

for cardiovascular symptoms and manage appropriately (Lubega,

unpublished data).

Renal Disease

Focal segmental glomerulopathy has been reported in up to 15%

of U.S. patients. Focal segmental glomerular sclerosis was the most

typical lesion associated with HIV. Such patients may present with

proteinuria and haematuria. African data are lacking. Although ran-

domised trials have not been performed, prednisone and sometimes

ACE inhibitors may be useful.

Knowledge Gaps

• ere are few comprehensive studies documenting the etiological

cause of infections and death in HIV-infected children in Africa.

112

Handbook on Pædiatric AIDS in Africa

References and Additional Reading

Clinical Spectrum of Disease in HIV-Infected Children

Chintu, C et. al. Impact of the Human immunodeﬁciency virus type-1

on common pediatric illnesses in Zambia. Journal of Tropical Pedi-

atrics 1995, 41: 348-352.

Bakaki, P et. al. Epidemiologic and clinical features of HIV-infected

Ugandan children younger than 18 months. JAIDS 2001, 28:.35-42.

Jeena, PM, HM Coovadia, and V Chrystal. Pneumocystis carinii and

cytomegalovirus infection in severely ill HIV-infected African

children. Annals of Tropical Paediatrics 1996, 16:361-368

Chintu, C et. al. Lung disease at necropsy in African children dying

from a respiratory illness; a descriptive necropsy study. Lancet

2002, 360: 985-90.

Mbori-Ngacha, D et. al. Morbidity and mortality in breast-fed and

formula-fed infants of HIV-infected women; a randomized clinical

trial. JAMA

2001, 286: 2413-2420.

Vetter, KM et. al. Clinical spectrum of human immunodeﬁciency

virus disease in children in a West African city. Pediatr Infect Dis J

1996, 15: 438-42.

Diarrhoea in HIV-Infected Children

ea, DM et. al. A prospective study of diarrhoea and HIV infection

among 429 Zairian infants. N Engl J Med 1993, 329: 1696-702.

Pavia, AT et. al. Diarrhea among African children born to human

immunodeﬁciency virus 1-infected mothers: Clinical and micro

biologic and epidemiologic features. Pediatr Infect Dia J 1992, 11:

996-1003.

Oshitani, H et. al. Association of Rotavirus and humanimmunodeﬁ

ciency virus infection in children hospitalized with acute diarrhoea,

Lusaka, Zambia. JID 1994, 169: 897-900.

113

Handbook on Pædiatric AIDS in Africa

Cunliﬀe, NA et. al. Eﬀect of concomitant HIV infection on presenta-

tion and outcome of rotavirus gastroenteritis in Malawian children.

Lancet 2001, 358: 550-55.

Treatment of Severely Malnourished Children

Bhan, MK, N Bhandari, and R Bahl. Management of the severely

malnourished child: perspective from developing countries. BMJ

2003, 326:146-51.

Miller, T. Nutritional aspects of pediatric HIV infection. In: Walker

WA, and JB Watkins. Nutrition in Pediatrics. London: BC Decker

Inc. 2

edition, 1997.

Bacteraemia

Nathoo, KJ et. al. Community acquired bacteraemia in human immu-

nodeﬁciency virus infected children in Harare, Zimbabwe. Peditr

Infect Dis J 1996,15: 1092-7.

Kaposi’s Sarcoma

Ziegler, JL and E Katongole-Mbidde. Kaposi’s sarcoma in childhood;

an analysis of 100 cases from Uganda and relationship to Kaposi’s

sarcoma. Int J Cancer 1996, 65: 200-203.

114

Handbook on Pædiatric AIDS in Africa

115

Handbook on Pædiatric AIDS in Africa

Chapter 7

Pulmonary Conditions

SUMMARY

• Pneumonia is the leading cause of hospital admissions and death in

HIV-infected children. Recurrent episodes of pneumonia suggest

immune suppression, but this should be investigated further to

exclude other conditions such as TB, foreign body, and lymphoid

interstitial pneumonitis.

• In children less than 1 year, consider PCP a possible cause of severe

pneumonia. Treat infants with severe pneumonia in areas of high

HIV prevalence presumptively for PCP, until it is excluded or they

are HIV antibody negative.

• PCP in an infant may be the ﬁrst AIDS-deﬁning condition in the

child and an indication of HIV infection in the family. erefore

eﬀorts should be made to provide counselling and testing for HIV

for the mother and the family. All HIV-exposed children should

receive prophylaxis against PCP from 6 weeks of age until it is

established that the child is not HIV-infected.

• All HIV-exposed children should receive prophylaxis against PCP

from 6 weeks of age until it is established that the child is not HIV-

infected.

• Children who are co-infected with HIV and TB experience higher

case fatality and it is important to look actively for TB in children

with chronic cough and provide treatment as early as possible.

• Lymphoid interstitial pneumonitis (LIP), is common in children

(about 40% with perinatally acquired HIV), is diagnosed by exclu-

sion, and is often mistaken for miliary pulmonary TB because of

chronic cough and miliary-like pattern on chest x-ray.

116

Handbook on Pædiatric AIDS in Africa

117

Handbook on Pædiatric AIDS in Africa

Introduction

Pneumonia and chronic lung diseases contribute to the increased

morbidity and mortality of HIV-infected children. Most children

present with recurrent bacterial pneumonias, but in children less than

1 year of age PCP also contributes to the high infant mortality. e

incidence of TB in children depends on the prevalence of TB in the

adult community, and other HIV-related chronic lung diseases often

have a similar clinical presentation leading to over diagnosis of TB.

In treatment of diﬀerent pulmonary conditions, it is important to

remember that the standard therapy may need to be adjusted by

increasing the length of treatment, using diﬀerent antibiotics, and/or

providing prophylaxis.

e diﬀerent pulmonary conditions may be diﬃcult to diﬀerentiate

from each other and are often fatal in the immune-compromised

child. e most common include:

1. Bacterial pneumonia

2. Pneumocystis pneumonia (PCP)

3. Tuberculosis

4. Lymphoid interstitial pneumonitis (LIP)

5. Bronchiectasis

6. Viral pneumonitis

1. Bacterial Pneumonia

Pneumonia is the leading cause of hospital admissions and death

in HIV-infected children. It is also the most common pulmonary

condition and presents the same way in both infected and uninfected

children.

Streptococcus pneumoniae is the most common pathogen isolated in

both HIV-infected and -uninfected children. Other organisms include

H. inﬂuenzae

, Klebsiella, Staphlococcus aureus, and enteric gram

118

Handbook on Pædiatric AIDS in Africa

negatives ( E. coli, Enterobacter, Salmonella, Citrobacter, Proteus, and

Pseudomonas). ese bacteria generally colonize the nasopharynx

before the child develops pneumonia.

Recurrent bacterial pneumonia suggests immune suppression (CDC

class C, WHO stage 3, see

chapter 8). Recurrent pneumonia should be

investigated further to exclude other conditions such as tuberculosis,

foreign body, bronchiectasis, LIP, and fungal pneumonias.

Clinical Presentation

Clinical presentation of pneumonia includes the following:

• History of fever, cough, and fast breathing (tachypnoea) with or

without chest in-drawing (retractions), cyanosis, and lethargy

• On auscultation may hear crepitations, decreased breath sounds, or

bronchial breathing (lobar pneumonia)

• When pulse oximetry is available, persistent hypoxia is demon-

strated (oxygen [O

2] saturation less than 90%)

Diagnosis

Diagnosis of pneumonia is purely on clinical grounds (see immediately

above

). However some laboratory tests may help in pointing towards

an aetiological agent.

• An increased white blood count (WBC) with a neutrophilia (gran-

ulocytosis) suggests bacterial pneumonia and growth on blood

cultures (bacteraemia) may result from the causative organism.

• A chest x-ray is not necessary for diagnosis of acute pneumonia,

but it may be done if there is poor response to appropriate treat-

ment or when suspecting TB, foreign body, or tumour.

• Because symptoms of pneumonia and those of malaria often over-

lap, a blood smear for malaria parasites should be done in endemic

areas.

119

Handbook on Pædiatric AIDS in Africa

Managing Bacterial Pneumonia

Outpatient Management (for mild pneumonia)

e management of pneumonia should follow the recommended

national guidelines or IMCI guidelines. If there are no guidelines, or

you are not aware of them, use the following:

• Oral amoxycillin or penicillin is adequate.

• Cotrimoxazole (CTZ) may be used as ﬁrst-line therapy for outpa-

tient pneumonia.

• If a child is already on CTZ prophylaxis, CTZ should not be used

to treat pneumonia unless PCP is suspected. If PCP is suspected,

then use a high dose of CTZ (see management of PCP belo w).

• Analgesics/antipyretics (e.g., paracetamol 15 mg/kg/dose every

6 to 8 hours) should be prescribed for fever and pain.

• Avoid using aspirin to treat children.

• If a child has recurrent pneumonia (more than three times in one

year), the child should be investigated further to rule out TB, for-

eign body, or chronic lung disease.

Managing Severe Pneumonia

Severe pneumonia should be managed in a hospital or other inpatient

facility and should include both supportive and speciﬁc therapy.

Supportive Care

Supportive care of severe pneumonia includes the following consid-

erations:

• Use supplemental oxygen when a child presents with chest in-

drawing, cyanosis, and/or hypoxia.

• Correct severe anaemia (Hb <5 g/dL) by transfusion with packed

red blood cells.

120

Handbook on Pædiatric AIDS in Africa

• Ensure adequate oral hydration and monitor ﬂuid input and output

(I/O chart). If respiratory distress is severe, pass an N/G tube and

give food in small volumes to avoid aspiration during feeding. You

may use IV ﬂuids cautiously to avoid ﬂuid overload, if the child is

vomiting.

• Provide an analgesic (paracetamol) for fever and pain (avoid

aspirin).

• Provide Vitamin A supplementation if the child has not received

vitamin A in the last 3 months.

Speciﬁc erapy

e speciﬁc antibiotic therapy depends on the sensitivity pattern

of the common organisms in the region. However, if unknown, the

recommended therapy is:

• First-line antibiotics include intravenous Chloramphenicol or

Ceftriaxone/Cefotaxime, if available

• Alternatives include Ampicillin/Cloxacillin plus Gentamicin if

cephalosporins are not available and there is a high level of resist-

ance to chloramphenicol.

Other Considerations

Other considerations for treating pneumonia in children include the

following:

• In children less than 1 year of age, clinicians must consider PCP

a possible cause of severe pneumonia and treat accordingly (see

below).

• If pneumonia is associated with typical staphylococcal skin lesions

(e.g,. bullae), chest x-ray with pneumatoceles, a positive blood

culture for staphylococcus (not contaminant), post measles, or

with poor response to ﬁrst-line antibiotics, then you must consider

staphylococcal pneumonia and add cloxacillin or vancomycin to

the treatment.

121

Handbook on Pædiatric AIDS in Africa

• If you suspect enteric gram negatives, then add Gentamicin or

Ceftazidime to the regimen, if available. Suspect enteric gram

negatives if the child has had repeated hospitalisations or repeated

pneumonia with consolidation in the same lobe, poor response

to ﬁrst-line antibiotics, green mucoid sputum, underlying bron-

chiectasis, or chronic lung disease.

2. Pneumocystis Pneumonia

Pneumocystis pneumonia (PCP) is caused by a fungus called pneumo-

cyctis jiroveci (formerly called pneumocystis carinii). PCP is a major

cause of severe pneumonia (15–30%) and death (30–50%) in HIV-in-

fected infants. Infants are usually in a good nutritional state and may

not have clinical features that indicate the presence of HIV/AIDS.

e incidence of PCP is highest during the ﬁrst year of life and usually

peaks at 3 to 6 months of age. It can occur after 1 year of age, but with

decreasing frequency.

Figure 7.1 below, although from the United

States, probably reﬂects similar occurrence in Africa.

122

Handbook on Pædiatric AIDS in Africa

Figure 7.1. reat of PCP: AIDS-Deﬁning Conditions by Age at Diagnosis

Perinatally-Acquired AIDS Cases through 1992, USA

�

��

� � � � � ��

��

Source: Prophylaxis against Pneumocystis carinii pneumonia among children with perinatally acquired human immu-

nodeﬁciency virus infection in the United States. Pneumocystis carinii Pneumonia Prophylaxis Working Group, N Engl J

Med, 1995. March 23:332(12):786-90.

Clinical Features of PCP

Clinical features of PCP in children include the following:

• Low-grade fever or afebrile

• Marked respiratory distress (chest in-drawing, cyanosis, inability

to drink)

• Auscultation: clear chest or diﬀuse ﬁne crepitations

• Poor response to standard antibiotic treatment

• Pulse oximetry: severe persistent hypoxia (paO2 <90%)

123

Handbook on Pædiatric AIDS in Africa

• Occasionally, associated HIV symptoms include oral thrush, lym-

phadenopathy, and/or weight loss

Investigations

Sputum induction with nasophyaryngeal aspirates or bronchoalveolar

lavage may help in diagnosing PCP. ere are no radiological changes

speciﬁc to PCP.

In cases where a deﬁnitive diagnosis of PCP cannot be made, but

where there is a high index of suspicion of PCP, therapy must be initi-

ated promptly, along with treatment for bacterial pneumonia.

Management of PCP

Management of PCP is both supportive and speciﬁc. In supportive

management of PCP:

• Provide oxygen therapy

• Maintain and monitor hydration

• Provide paracetamol for pain

• Continue therapy for bacterial pneumonia

For speciﬁc management of PCP:

• Give intravenous high dose cotrimoxazole (CTZ) 20 mg/kg of

trimethoprim per day OR 80 mg/kg/day of sulphamesoxazole given

every 6 hours for 21 days. Give the same dose orally if IV prepara-

tions are not available.

• Add prednisone at 2 mg/kg/day for 7 to 14 day if child is in severe

respiratory distress (taper if treatment >7days).

Follow-Up

After an acute episode of PCP, provide daily cotrimoxazole

10 mg/kg/day of TMP orally. is secondary prophylaxis is life-long.

PCP may be the ﬁrst AIDS-deﬁning illness in the child and the ﬁrst

indication of HIV infection within the family. erefore, eﬀorts must

124

Handbook on Pædiatric AIDS in Africa

be made to provide counselling and testing for HIV for the mother

and the family. If the mother or another family member is identiﬁed

as HIV-infected, refer to appropriate services for ongoing care and

support.

Chronic Lung Disease

e primary causes of chronic lung disease are TB, LIP, bronchiecta-

sis, and pulmonary Kaposi’s sarcoma or lymphoma.

3. Tuberculosis

TB and HIV Co-Infection

e HIV pandemic has led to a resurgence of TB in both adults and

children, and the burden of TB in children depends on the burden of

the disease in the adult population.

Children also have an increased risk of developing primary progres

sive TB because of the associated severe immune suppression result-

ing from their young age and HIV. Extrapulmonary TB is seen more

often in HIV-infected children.

ere is a higher case fatality rate for children who are co-infected

with TB and HIV. It is important to look actively for TB in children

with a chronic cough and to provide treatment as early as possible.

e reported seroprevalence of HIV in children with TB ranges from

10 to 60%. e highest prevalence of HIV infection in children with TB

has been reported in Southern Africa, the lowest prevalence in West

Africa. In autopsy studies, the prevalence of TB seemed to be much

less, but this may have been the result of selection bias in the studies.

Diagnosing TB in children was diﬃcult even before the HIV/AIDS

pandemic; now it is more diﬃcult because an HIV-positive child may

have many other pulmonary conditions and HIV-related chronic lung

diseases that mimic the symptoms of TB

125

Handbook on Pædiatric AIDS in Africa

Clinical Diagnosis

Table 7.1 below shows the evaluation of a child suspected to have TB.

Table 7.1. Evaluation of HIV-Exposed Infant for Tuberculosis Disease

History (Symptoms and

Signs of TB Disease)

• Unexplained weight loss or failure to grow normally

• Unexplained fever, especially if more than 14 days

• Chronic cough (more than 30 days)

• Failure of response to appropriate antibiotic treatment of

presumed bacterial pneumonia or meningitis

• Exposure to an adult with probable or deﬁnite pulmo

nary infectious TB

Physical Examination

• Fluid on one side of chest (dullness to percussion, re-

duced air entry)

• Enlarged, non tender lymph nodes or abscess, especially

in the neck

• Signs of meningitis, especially if subacute and develop

over several days

• Cerebrospinal ﬂuid contains mostly lymphocytes and

elevated protein

• Abdominal swelling, with or without palpable lumps

• Progressive swelling or deformity of a bone or joint,

including the spine

Laboratory Investigations

• Microscopic examination for acid-fast bacilli (Ziehl-

Nielsen stain) and culture of specimens, such as early

morning gastric aspirates for three consecutive days and

pleural, ascites and cerebrospinal ﬂuid as relevant.

• Chest radiograph for lobar opacity, pleural eﬀusion, mili

ary pattern.

• PPD tuberculin skin test (>5mm is positive).

Modiﬁed from WHO Treatment of TB; Guidelines for National Programs, ird Edition, 2002.

126

Handbook on Pædiatric AIDS in Africa

Most TB diagnostic criteria (chronic symptoms, smear positive con-

tact, positive Mantoux, response to treatment) have lower sensitivity

and speciﬁcity in a co-infected child than in a non-HIV-infected child

(Table 7.2 below).

Table 7.2. Impact of HIV Infection on Value of Commonly Used Criteria for

Diagnosis of TB

Diagnostic Feature of Pulmonary TB Impact of HIV

Chronic symptoms >1 month Less speciﬁc

Smear positive contact Less speciﬁc

Malnutrition Less speciﬁc

Positive Mantoux Less sensitive

Characteristic chest x-ray Less speciﬁc

Response to treatment Less sensitive

Source: Graham et al. Int J Tuberc Lung Dis, 2001 Jan: 5 (1) 12-23.

127

Handbook on Pædiatric AIDS in Africa

Diagnosis of Extra-Pulmonary TB

Clinicians may use the following to diagnose extra pulmonary TB:

• When there are superﬁcial enlarged lymph nodes, biopsy or ﬁne

needle lymph node aspirate may be diagnostic

• Body ﬂuids—ascitic, pleural, or cerebrospinal—can be subjected to

ZN stain and culture, but the yield is usually poor

• Bone marrow aspirate and culture may be diagnostic in dissemi-

nated TB with persistent fever and wasting

• Ultrasound can help diﬀerentiate loculated ﬂuid and consolidation

• Computerised tomography (CT) scan, where available, may assist

in diagnosing abdominal, pulmonary, and CNS disease

• Contrast CT scan can diﬀerentiate inﬂamed mediastinal lymph

nodes from thymic shadows in younger children

Treating TB in Children

In most instances treatment of TB is usually presumptive because it is

diﬃcult to make an aetiological diagnosis.

In treating children who are co-infected with HIV and TB, use nation

al guidelines. Where guidelines may not be available, the following

table can be used:

128

Handbook on Pædiatric AIDS in Africa

Table 7.3. Treatment/Prophylaxis of TB in HIV-Exposed or HIV-Infected Infants

Treatment

· Treat all conﬁrmed or highly suspect cases

· Treatment should be directly observed therapy

Smear-Negative Pulmonary

TB or Non-Severe Disease

· First 2 months: isoniazid + rifampicin + pyrazinamide daily or

3 times a week

Followed by either:

· Next 6 months: isoniazid + ethambutol or isoniazid +

thioacetazone daily

· Next 4 months: isoniazid + rifampicin daily or 3 times weekly

Smear-Positive Pulmonary

TB or Severe Disease

· First 2 months: isoniazid + rifampicin + pyrazinamide +

streptomycin (or ethambutol) daily or 3 times a week

Followed by either:

· Next 6 months: isoniazid + ethambutol daily or isoniazid +

thioacetazone daily

· Next 4 months: isoniazid + rifampicin daily or 3 times weekly

Meningitis, Miliary TB or

Spinal TB with Neurologic

Signs (regardless of Smear

Results)

· First 2 months: isoniazid + rifampicin + pyrazinamide +

streptomycin (or ethambutol) daily or 3 times a week

Followed by:

· Next 7 months: isoniazid + rifampicin daily

Anti-TB Medication Doses

Daily dosing

Isoniazid .................5 mg/kg

(range 4–6)

Rifampicin ............10 mg/kg

(range 8–12)

Pyrazinamide ......25 mg/kg

(range 20–30)

Ethambutol ..........15 mg/kg

(range 15–20)

Streptomycin ......15 mg/kg

(range 12–18)

Intermittent dosing

(3 times weekly)

Isoniazid .................10 mg/kg

(range 8–12)

Rifampicin ............10 mg/kg

(range 8–12)

Pyrazinamide ......35 mg/kg

(range 30–40)

Ethambutol ..........30 mg/kg

(range 25–35)

Streptomycin ......15 mg/kg

(range 12–18)

Prophylaxis

(after active TB

disease is excluded)

· Infants born to HIV-infected women diagnosed with TB

disease who started treatment <2 months before delivery

· Infants and children with exposure to an adult with active TB

disease

Prophylaxis Medication

· Isoniazid 5–10 mg/kg orally once daily for 6 months.

WHO recommendations for therapy (when national guidelines not available)

Source: Adapted from WHO

129

Handbook on Pædiatric AIDS in Africa

Drug/Drug Interactions

TB Treatment and Antiretroviral Drugs

Because of the interaction between protease inhibitors and rifampicin

(in general, serum protease inhibitor levels are lowered substantially

and rifampicin levels increased 2 to 3 times the usual concentration),

treatment in patients who are co-infected with TB and HIV may have

to be modiﬁed (see chapter 8 for details).

4. Lymphoid Interstitial Pneumonitis

Lymphoid intersitial pneumonitis (LIP) is common in children

(occurs in at least 40% of children with perinatal HIV), but rare in

adults (occurs in about 3% of adults with HIV), and usually occurs

in children more than 2 years of age. Various studies in Africa have

documented a 30–40% prevalence of LIP in HIV-infected children,

and up to a 60% prevalence in those with chronic lung disease. LIP

is often mistaken for pulmonary TB (miliary) because of the chronic

cough and the miliary-like pattern on chest x-ray.

Pathogenesis

Possible explanations for LIP include a co-infection of the lungs by

HIV and Epstein Barr Virus (EBV), leading to immune stimulation

with lymphoid inﬁltration and chronic inﬂammation.

Clinical Symptoms

Diagnosis of LIP is usually by exclusion. However the following may

be helpful:

• Patient usually in good general condition despite respiratory

distress

• Recurrent cough and dyspnoea

• Usually associated with parotid enlargement, generalized

lymphadenopathy, and hepatosplenomegaly

• Finger clubbing may be present

130

Handbook on Pædiatric AIDS in Africa

• Poor response to TB therapy

• Terminally chronic lung disease with hypoxia

Radiological Picture

Radiological indicators of LIP include:

• Diﬀuse bilateral reticulonodular inﬁltrates may appear similar to

miliary TB

• Bilateral hilar or mediastinal lymph node enlargement

e table below high lights similarities and diﬀerences between LIP

and TB.

Table 7.4. Comparison of Miliary TB and LIP

Clinical Features Miliary TB LIP

Respiratory distress ‒/+ +++

Persistent fever

++ ++

Wasting +++ ‒/+

Generalized lymphadenopathy ‒/+ +++

Parotid enlargement ‒ ++

Digital clubbing ‒ ++

Hepatomegaly ++ ++

CXR features

• Diﬀuse micronodular

++ +

• Diﬀuse reticulonodular

‒ ++

Lymphadenopathy

‒/+ ++

131

Handbook on Pædiatric AIDS in Africa

Management

Managing LIP includes the following:

• Steroids when children with LIP have signiﬁcant respiratory

distress (exclude TB ﬁrst). Prednisone 2 mg/kg/day initially for 4

weeks daily, then alternate day maintenance for 2 to 3 months and

review.

• Oxygen therapy during episodes of hypoxia

• Bronchodilators (e.g., salbutamol) where wheezing is a problem

• Antibiotics during episodes of concurrent super-infection with

pneumonia

• Chest physiotherapy and postural drainage if there is secondary

bronchiectasis

• Refer for specialist care if resistant to therapy

5. Bronchiectasis

Bronchiectasis may occur as a complication of severe or recurrent

pneumonia, TB, LIP, or measles. It involves damage to the bronchial

lining because of recurrent infection and weakening of the bronchi

with cystic formation and secondary infection.

Clinical Presentation

e clinical presentation of bronchiectasis includes the following:

• Chronic cough, mainly in the morning

• Copious purulent sputum

• Halitosis

• Digital clubbing

• Recurrent pneumonia

132

Handbook on Pædiatric AIDS in Africa

Management of bronchiectasis

Management includes diagnosis of bronchiectasis and its treatment.

Diagnosis

• With the above symptoms and signs, a chest x-ray may show local-

ized inﬁltrates, cystic areas, dilated bronchi (persistent opacity in

one area).

• Where possible collect sputum and culture for bacteria and to

exclude fungi. If the sputum grows a speciﬁc organism, adjust

treatment appropriately.

Treatment

• Supportive treatment includes daily chest physiotherapy and pos-

tural drainage. Caregivers should be trained in daily physiotherapy

and postural drainage.

• Broad-spectrum antibiotics: chloramphenicol, augumentin,

cefuroxime, azithromycin/clarithromycin or third-generation

cephaolosporins (Ceftriaxone, Ceftazidime, Cefpodoxime), if avail-

able. Ciproﬂoxacin may be used as a last resort (be careful about

prolonged use) for in-patients with possible enteric gram-negative

and anaerobic organisms.

• Bronchodilators such as salbutamol/albuterol can be used when

bronchospasms are present.

• Prophylactic antibiotics may be needed for several months if pa-

tient presents with recurrent pneumonia/bronchiectasis. Consider

referral to specialist.

• Surgery may be necessary in cases with segmental lung damage.

6. Viral Pneumonitis

Children with HIV may develop severe viral pneumonitis from

a number of viruses, including respiratory syncytial virus (RSV),

parainﬂuenza virus, inﬂuenza virus, adenovirus, varicella (chicken

133

Handbook on Pædiatric AIDS in Africa

pox), measles, and cytomegalovirus (CMV). However, in most Afri-

can settings it is not possible to conﬁrm the actual aetiological agent.

e clinical presentation may be much more severe and case fatality

higher than in non-HIV infected children. Viral pneumonitis in HIV-

infected children presents as pneumonia rather than bronchiolitis.

Some reports indicate that CMV may be a co-pathogen in infants

with PCP, and that using steroids to treat PCP may aggravate the

CMV pneumonitis. Speciﬁc treatment is ganciclovir, but this is rarely

available and very expensive. HAART may be useful in ameliorating

severity.

Varicella zoster immunoglobulin may reduce the severity of chicken

pox pneumonitis, if it is given within 72 hours of exposure. Alterna

tively, you may use oral acyclovir. Immunisation (measles vaccine) can

prevent measles but you can also give measles immunoglobulin (0.5

ml/kg (maximum 15 ml) within 6 days of measles exposure, regard-

less of previous measles immunisation history.

Other Pulmonary Conditions

A child presenting with an unexplained sudden onset of dyspnoea or

subcutaneous emphysema may indicate spontaneous pneumothorax,

which may be associated with PCP, LIP, or other cause of pneumonia.

Asthma/reactive airway disease may occur in HIV-infected children,

just like in their HIV-negative counterparts, and must be managed

accordingly.

Fungal chest infections (e.g., aspergillosis, nocardia, cryptococosis,

and rarely candida) in Africa are rarely reported. Where there are fa

cilities, further investigation of patients with poorly responding chest

infections should include fungal stains and cultures.

Kaposi’s sarcoma (KS) is the most common HIV-associated malig

nancy associated with the lungs. In addition to the mucocutanoeus

lesions and lymphadenopathy, patients present with progressive

dyspnoea, cough, and rarely haemoptysis. Chest x-rays will show

134

Handbook on Pædiatric AIDS in Africa

mediastinal lymphadenopathy, pleural eﬀusion, or bilateral interstitial

inﬁltrates. Diagnosis of pulmonary KS can be made at bronchoscopy,

where multiple purplish lesions can be visualized. Intra-pulmonary

biopsy should not be done, as it can lead to profuse haemorrhage.

Treatment includes chemotherapy (vincristine and bleomycin or

liposomal preparations of danorubicin and doxorubicin). is needs

referral to experienced centres of cancer treatment.

Lymphomas (both T- and B-cell) may present with non-speciﬁc

symptoms and signs, and chest x-rays showing mediastinal lymphad

enopathy, focal opacities, or pleural eﬀusions.

Future needs

• Easier and more accurate diagnostic tests for pulmonary condi-

tions

• Need to evaluate diﬀerent treatment options for optimal eﬃcacy

among HIV- infected children with pulmonary conditions

Additional Reading

Graham, SM, JB Coulter, and CF Gilks. Pulmonary disease in HIV-in-

fected African children. Int J Tuberc Lung Dis 2001 Jan: 5 (1): 12-23.