United Republic of Tanzania
Ministry of Health and Social Welfare
National Guidelines
for Diagnosis and
Treatment of Malaria
Malaria control series 11
National Malaria Control Programme
January 2006
National Guidelines for Malaria Diagnosis and Treatment 2005
2
National Guidelines for Malaria Diagnosis and Treatment 2005
3
Foreword
The National Guidelines for Malaria Diagnosis and Treatment are a revised and updated
version of similar Guidelines that were issued in the year 2000. The year 2000 version was
revised following a major change in drug policy whereby the former first line drug
Chloroquine was replaced with Sulfadoxine-Pyrimethamine (SP). The change was also
accompanied with the reintroduction of Amodiaquine as second line drug and Quinine
retained its position as the drug of choice for treatment of severe malaria. This shift was
necessary following research results, which indicated very high malaria parasite resistance
to chloroquine that averaged 60%. By then the parasite resistance to Amodiaquine and SP
averaged 6% and 10% respectively. The World Health Organization recommends changing
a drug when parasite resistance against it reaches 25%. The lesson learnt was that we
would have to establish a system to monitor the performance of the drugs as we implement
the new policy in order to ensure effective malaria treatment over time.
In a period of five years since the change of policy, monitoring has indicated that malaria
parasite resistance to SP has gone up to an average of 25.5% in the sentinel sites (from 7.8
to 60.5%). For Amodiaquine the resistance went up to an average of 11.5% (from 6.3 to
18.2%). A decision for another change was therefore unavoidable.
The Ministry therefore, had to look for a suitable, highly efficacious replacement drug to SP.
Currently, new developments in malaria treatment recommend the use of a combination of
drugs that contain one of the Artemesinin compounds (ACTs). The Artemesinin class of
compounds have exhibited very high cure rates for malaria and so far no parasite resistance
against them has been reported. Having them combined with other suitable antimalarial
drugs offers new prospects for achieving high cure rates, delay of development of parasite
resistance and achieving a much longer therapeutic life.
The Ministry after several drug efficacy studies and other important considerations has come
up with these updated Malaria Treatment Guidelines. From now on,
Artemether/Lumefantrine (ALu) is the first line drug for treatment of uncomplicated malaria
for all age groups with the exception of pregnant women during the first trimester and
children weighing below five kilograms whom Quinine would still be the drug of choice.
Quinine is second line drug as well as drug of choice for treatment of severe malaria.
Sulfadoxine/Pyrimethamine (SP) remains the drug of choice for Intermittent Preventive
Treatment (IPT) of m alaria in pregnancy. The aim of IPT is to prevent the worst effects of
malaria infection in pregnancy rather than to ensur e clinical cure and since no suitable
alternative to SP is currently available, a drug with lower efficacy is acceptable.
It is expected that adherence to these new guidelines both in the public and private health
sectors will eventually lead to much reduced malaria mortality and morbidity. It has to be
emphasized that although proper malaria case management is the cornerstone for malaria
control, prevention of malaria by mass usage of insecticide treated nets, environmental
management and other proven measures has to be undertaken. Therefore, public education
is quite important and has to be undertaken.
The Ministry would like to thank all those who participated in the preparations of these
guidelines.
Hon. Prof. David Mwakyusa (MP)
Minister for Health and Social Welfare
January 2006
National Guidelines for Malaria Diagnosis and Treatment 2005
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Acknowledgement
The Ministry would like to thank the following Members of the Task Force, which prepared
and edited the guidelines:
Dr. Elizeus Kahigwa
National Officer, Malaria, WHO Tanzania
Dr. Mathew Kallanga
Obstetrician/Gynaecologist, Muhimbili National Hospital
Dr. Theodora Kazimoto
Paediatrician, Muhimbili University College of Health Sciences
Dr. Andrew Kitua
National Institute for Medical Research
Dr. Julie Makani
Physician, Muhimbili University College of Health Sciences
Dr. Renata Mandike
National Malaria Control Programme
Dr. Mufungo Marero
National Malaria Control Programme
Prof. Amos Massele
Clinical Pharmacologist, Muhimbili University College of
Health Sciences
Dr. Augustine Massawe
Paediatrician, Muhimbili University College of Health Sciences
Prof. Siriel Massawe
Obstetrician/Gynaecologist, Muhimbili National Hospital
Dr. Yassin Mgonda
Physician, Muhimbili University College of Health Sciences
Dr. Sigsbert Mkude
National Malaria Control Programme
Dr. Fabrizio Molteni
Italian Co-operation, National Malaria Control
Programme, Ministry of Health
Mr. Christopher Msemo
Medical Store Department
Mr. Adelard Mtenga
Tanzania Food and Drug Authority
Mr. Joseph Muhume
Chief Pharmacist, Ministry of Health
Dr. Alex Mwita
Manager, National Malaria Control Programme
Ms. Lucy Nderimo
Medical Store Department
Ms. Ritha Njau
National Officer, Malaria, WHO Tanzania
Dr. Stephen Nsimba
Clinical Pharmacologist, Muhimbili University College of
Health Sciences
Prof. Zul Premji
School of Public Health and Social Sciences, Muhimbili
University College of Health Sciences.
Dr. Neema Rusibamayila
IMCI, Ministry of Health
Dr. Azma Simba
National Malaria Control Programme
Dr. Peter Swai
Paediatrician, Muhimbili National Hospital
Dr. Donath Tarimo
School of Public Health and Social Sciences, Muhimbili
University College of Health Sciences
The Ministry also commends the following Guidelines reviewers: L.Mboera (NIMR),
J.Massaga (CEEMI), A.Collins (Malaria Consortium, Kampala), N.Chisaka (WHO Afro),
G.Rotllant and M.Garcia (Medicins sans Frontiere), D.Shellenberg (IHRDC) and E.Sevene
(Eduardo Mondlane University, Maputo).
Participants from councils gave valuable inputs during zonal training sessions on these
guidelines that were conducted countrywide in September 2005. These guidelines were also
shared with all Regional and District Medical Officers. Their valuable views have been
incorporated in this final version. All of them are commended for these efforts. T ribute also
goes to the National Therapeutic and the National Malaria Advisory Committees for
thoroughly reviewing the guidelines and approving them as new malaria policy guidelines for
Tanzania.
Hilda Gondwe
Permanent Secretary
Ministry of Health and Social Welfare
January 2006
National Guidelines for Malaria Diagnosis and Treatment 2005
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List of abbreviations
ACPR
Adequate Clinical Parasitological Response
ACT
Artemisinin Combination Therapy
ADDO
Accredited Drug Dispensing Outlet
ADR
Adverse Drug Reaction
AIDS
Acquired Immunodeficiency Syndrome
ALP
Alkaline Phosphatase
ALT
Alanine aminotransferase
ALu
Artemether-lumefantrine
AO
Acridine Orange
AQ
Amodiaquine
AST
Aspartate aminotransferase
ASU
Artesunate
A-V block
Atrial-Ventricular block
BP
Blood Pressure
BS
Blood Slide
BUN
Blood Urea Nitrogen
BW
Body weight
CEEMI
Centre for Enhancement of Effective Malaria Intervention
CHMT
Council Health management Team
CNS
Central Nervous System
CORP Community Owned Resource Persons
CSF Cerebro Spinal Fluid
CT
Combination Therapy
CT scan Computerised Tomography Scan
DIC Disseminated Intra-vascular Coagulation
DOT
Direct Observed Treatment
ETF
Early Treatment Failure
FBP
Full Blood Picture
FEFO
First Expiry First Out
G6PD
Glucose 6 Phosphate Dehydrogenase
Hb
Haemoglobin
HIV
Human Immunodeficiency Virus
IHRDC
Ifakara Health Research Development Centre
IM (I.M. or i.m.)
Intra-muscular
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IMCI
Integrated Management of Childhood Illness
IPT
Intermittent Preventive Treatment
ITN
Insecticide Treated Net
IV (I.V. or i.v.) Intra-venous
JVP Jugular Venous Pressure
LPF
Late Parasitological Failure
LTF Late Tr eatment Failure
MCH Maternal and Child Health
MCHA
Maternal and Child Health Aide
MTCT
Mother to Child Transmission
NADH
Nicotinamide Adenine Dinucleotide
NIMR
National Institute for Medical Research
OP
Out Patient
ORS
Oral Rehydration Salts
PR
Pulse Rate
Q-T Interval
Interval on the electrocardiogram between the Q and T waves
RBC
Red Blood Cell
RBG
Random Blood Glucose
RDT
Rapid Diagnostic Tests
RNA
Ribonucleic Acid
RR
Respiratory Rate
SP
Sulfadoxine/Pyrimethamine
SPR
Slide Positive Rate
S-T interval
Interval on the electrocardiogram between the S and T waves
TB
Tuberculosis
TFDA
Tanzania Food and Drug Authority
WBC
White Blood Cell Count
WHO
World Health Organization
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Table of contents
Foreword ............................................................................................................................. 3
Acknowledgement .............................................................................................................. 4
List of abbreviations ........................................................................................................... 5
Table of contents ................................................................................................................ 7
Tables and figures ............................................................................................................ 10
CHAPTER 1: INTRODUCTION .......................................................................................... 12
1.1 Background ............................................................................................................... 12
1.2 Broad objective ......................................................................................................... 13
1.3 Specific objectives ..................................................................................................... 13
1.4 Rationale ................................................................................................................... 13
1.5 Choice of antimalarial drugs ...................................................................................... 14
CHAPTER 2: MANAGEMENT OF MALARIA AND HEALTH CARE DELIVERY IN
TANZANIA ......................................................................................................................... 16
2.1 Introduction ............................................................................................................... 16
2.2 Home ........................................................................................................................ 16
2.3 Dispensary ................................................................................................................ 17
2.4 Health centre ............................................................................................................. 17
2.5 Hospital ..................................................................................................................... 19
CHAPTER 3: DIAGNOSIS OF MALARIA .......................................................................... 22
3.1 Introduction ............................................................................................................... 22
3.2 Clinical features of malaria ........................................................................................ 22
3.3 Assessment of the patient ......................................................................................... 22
3.3.1 Clinical assessment ............................................................................................ 22
3.4 Laboratory investigations........................................................................................... 24
CHAPTER 4: MANAGEMENT OF UNCOMPLICATED MALARIA ..................................... 27
4.1 Introduction ............................................................................................................... 27
4.2 Clinical features of uncomplicated malaria ................................................................ 27
4.3 Treatment of uncomplicated malaria using combination therapy ............................... 30
4.4 Treatment of uncomplicated malaria with first line drug: Artemether-Lumefantrine .... 30
4.5 Management of fever. ............................................................................................... 33
4.6 Treatment of uncomplicated malaria with second line drug: Quinine ........................ 34
4.7 Health education for uncomplicated malaria patient/caretakers ................................. 35
CHAPTER 5: MANAGEMENT OF SEVERE MALARIA ..................................................... 37
5.1 Introduction ............................................................................................................... 37
5.2 Features of severe malaria ........................................................................................ 37
5.3 Treatment of severe malaria ...................................................................................... 38
5.4 Management of severe malaria at home, shopkeeper and village health post ........... 38
5.5 Management of severe malaria at dispensary level ................................................... 39
5.6 Management of severe malaria at health centre level ................................................ 40
5.7 Management of severe malaria at hospital level ........................................................ 41
5.8 Monitoring of patients with severe malaria ................................................................. 43
5.9 Non-response to quinine therapy ............................................................................... 45
5.10 Emergency management of severe malaria ............................................................ 45
5.10.1 Convulsions ...................................................................................................... 45
5.10.2 Hypoglycaemia ................................................................................................. 45
5.10.3 Hypotension ..................................................................................................... 46
5.10.4 Pulmonary oedema .......................................................................................... 46
5.10.5 Metabolic Acidosis ............................................................................................ 46
CHAPTER 6: AN AEMIA AND MALAR IA ........................................................................... 48
6.1 Introduction ............................................................................................................... 48
6.2 Definition ................................................................................................................... 48
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6.3 Clinical presentation of anaemia................................................................................ 49
6.4 Classification of anaemia according to severity ......................................................... 49
6.5 Management of life threatening anaemia (Hb < 5g/dl) associated with malaria ......... 50
6.6 Management of severe anaemia (Hb 5 up to 7g/dl) associated with malaria ............. 51
6.7 Management of mild/moderate anaemia (7 up to 11 g/dl) associated with malaria .... 51
6.8 Management of anaemia associated with malaria in pregnancy ................................ 51
CHAPTER 7: MANAGEMENT OF MALARIA IN PREGNANCY......................................... 53
7.1 Introduction ............................................................................................................... 53
7.2 Effects of pregnancy on malaria ................................................................................ 53
7.3 Effects of malaria on pregnancy ................................................................................ 53
7.4 Management of malaria in pregnancy........................................................................ 54
7.5 Uncomplicated malaria in pregnancy ......................................................................... 54
7.5.1 Clinical features of uncomplicated malaria .......................................................... 54
7.5.2 Management of uncomplicated malaria .............................................................. 54
7.6 Severe malaria in pregnancy ..................................................................................... 54
7.6.1 Clinical features of severe malaria in pregnancy ................................................. 54
7.6.2 Management of severe malaria in pregnancy ..................................................... 55
7.7 Anaemia associated with malaria in pregnancy ......................................................... 55
7.7.1 Management of mild/moderate anaemia (Hb 7 up to 11 g/dl) in pregnancy ........ 56
7.7.2 Management of severe anaemia (Hb < 7g/dl) in pregnancy ................................ 56
7.7.3 Prevention of anaemia ........................................................................................ 57
7.8 Prevention of malaria during pregnancy .................................................................... 57
7.8.1 Intermittent preventive treatment (IPT) ............................................................... 57
7.8.2 Insecticide Treated Net ....................................................................................... 58
CHAPTER 8: M ANAGEMENT OF M ALARIA IN THE NEONATE AND INFANTS BELOW 5
KG ...................................................................................................................................... 60
8.1 Introduction ............................................................................................................... 60
8.2 Clinical features ......................................................................................................... 60
8.3 Management of neonatal malaria .............................................................................. 60
8.4 Management of malaria in infants below two months and below five ......................... 61
Kg ................................................................................................................................... 61
CHAPTER 9: MALARIA AND HIV CO-INFECTION ........................................................... 63
9.1 Introduction ............................................................................................................... 63
9.2 Clinical features of malaria in HIV/AIDS .................................................................... 63
9.2.1 Clinical features of uncomplicated malaria in HIV/AIDS ...................................... 63
9.2.2 Clinical features of severe malaria in HIV / AIDS ................................................ 64
9.3 Diagnosis .................................................................................................................. 64
9.4 Treatment of uncomplicated and severe malaria in HIV /AIDS .................................. 64
9.5 Malaria and HIV/AIDS in pregnancy .......................................................................... 64
9.6 Effect of malaria on HIV infected children .................................................................. 65
9.7 Prevention ................................................................................................................. 65
CHAPTER 10: THERAPEUTIC EFFICACY OF ANTI MALARIAL DRUGS........................ 67
10.1 Introduction .......................................................................................................... 67
10.2 Non response to an antimalarial treatment .......................................................... 67
10.3 Parasite Resistance to Antimalarial Drugs (in vivo drug sensitivity tests) ............. 68
CHAPTER 11: MALARIA CHEMOPROPHYLAXIS ............................................................ 70
11.1 Introduction ............................................................................................................. 70
11.2 Indication for malaria chemoprophylaxis .................................................................. 70
11.3 Common antimalarial used as prophylactic agents .................................................. 70
11.3.1 Chemoprophylaxis in patients with sickle cell anaemia ..................................... 70
11.3.2 Chemoprophylaxis for non-immune travelers .................................................... 70
11.3.3 Chemoprophylaxis for non-immune pregnant women ....................................... 71
11.3.4 Chemoprophylaxis for Hyper Reactive Malaria Splenomegaly .......................... 71
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CHAPTER 12: MALARIA EPIDEMICS ............................................................................... 73
12.1 Introduction ............................................................................................................. 73
12.2 Measures to be considered during malaria epidemics ............................................. 73
12.3 Malaria diagnosis in the event of malaria epidemics ................................................ 73
12.4 Disease management in the event of malaria epidemics ......................................... 74
12.4.1 Managing uncomplicated malaria cases ........................................................... 74
12.4.2 Managing severe malaria ................................................................................. 75
12.5 Preparedness .......................................................................................................... 75
12.5.1 Monitoring drug resistance ............................................................................... 75
12.5.2 Central stocks of supplies and equipment ........................................................ 75
12.5.3 Prevention of malaria during epidemics ............................................................ 75
CHAPTER 13: PUBLIC HEALTH EDUCATION ON MALARIA CASE MANAGEMENT .... 77
13.1 Introduction ............................................................................................................. 77
13.2 Health education for malaria diagnosis and treatment ............................................. 77
13.3 The role of health service providers in promoting appropriate malaria case
management and preventive measures .......................................................................... 78
CHAPTER 14: OTHER ANTIM ALARIAL DRUGS AVAILABLE IN T ANZANIA ................. 80
14.1 Introduction ............................................................................................................. 80
14.2 Antimalarial mono-therapies or single component of combination therapies ............ 80
14.2.1 Artemisinin and its derivatives .......................................................................... 80
14.2.2 Sulfadoxine/Pyrimethamine, ............................................................................. 81
14.2.3 Sulfalene/Pyrimethamine (Metakelfin®) ............................................................ 82
14.2.4 Amodiaquine .................................................................................................... 82
14.2.5 Mefloquine ........................................................................................................ 83
14.2.6 Halofantrine ...................................................................................................... 84
14.2.7 Proguanil Hydrochloride ................................................................................... 85
14.2.8 Doxycycline ...................................................................................................... 86
14.3 Other Artemisinin based combination drugs available in Tanzania .......................... 87
14.3.1 Artesunate and Amodiaquine combination ....................................................... 87
14.3.2 Artesunate and Mefloquine combination ........................................................... 87
14.4 Other combination drugs ......................................................................................... 88
14.4.1 Proguanil Hydrochloride/Atovaquone................................................................ 88
CHAPTER 15: MANAGEMENT OF ANTIMALARIAL DRUGS .......................................... 91
15.1 Introduction ............................................................................................................. 91
15.2 Ordering .................................................................................................................. 91
15.3 Storage and inventory control .................................................................................. 91
15.4 Supervision of drug management activities ............................................................. 92
CHAPTER 16: PHARMACOVIGILANCE ........................................................................... 94
16.1 Introduction ............................................................................................................. 94
16.2 Importance of pharmacovigilance ............................................................................ 94
16.3 Clinical presentation of adverse drug reactions ....................................................... 94
16.4 Reporting adverse drug reactions ............................................................................ 95
Appendix 1: Reporting of blood smear results ............................................................... 96
Appendix 1: Reporting of blood smear results ............................................................... 97
Appendix 2a: Integrated Management of Childhood Illness algorithm for child with
fever ................................................................................................................................... 98
Appendix 2b: Algorithm for child with fever (modified from Integrated Management of
Childhood Illness) ............................................................................................................. 99
Appendix 3: Classification and management of anaemia by severity in children one
week up to 5 years of age according to IMCI ................................................................ 100
Appendix 4: Management of uncomplicated malaria in patients aged 5 years and
above ............................................................................................................................... 101
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Appendix 5: Time schedule for 1
st
and 2
nd
dose of Artemether-lumefantrine ............. 102
Appendix 6: The Glasgow coma scale .......................................................................... 103
The Blantyre coma scale ................................................................................................ 103
AVPU scale ...................................................................................................................... 103
Appendix 7: Report of suspected adverse drug reaction including birth defects ...... 104
Tables and figures
Table 1 Distinguishing features of uncomplicated malaria in relation to age groups ............ 23
Table 2 Clinical and laboratory features of severe malaria .................................................. 23
Figure 1 Management of a patient with suspected malaria in health facilities without
laboratory services ...................................................................................................... 28
Figure 2 Management of a patient with suspected malaria in health facilities with laboratory
services ....................................................................................................................... 29
Table 3: Dosage schedule of Artemether 20mg & Lumefantrine 120 mg (ALu) (number of
tablets recommended at approximate timing of dosing) ............................................... 32
Table 4. Treatment schedule for paracetamol (500mg) tablets ............................................ 33
Table 5: Dosage schedule for malaria treatment using oral Quinine (salt, 300mg tablet) for
different age groups .................................................................................................... 35
Table 6: Features of severe malaria ................................................................................... 37
Table 7: Clinical features and laboratory indices of severe malaria in adults and children and
their prognostic values ................................................................................................ 38
Table 8:Dilution schedule for intra-muscular Quinine administration ................................... 40
Table 9: Laboratory Investigations ..................................................................................... 42
Table 10: Dilution schedule and drop rate for intravenous Quinine administration .............. 42
Table 11: Important observations and their implications during treatment of severe malaria
.................................................................................................................................... 43
Table 12: Normal Haemoglobin concentration levels by ages and sex ................................ 48
Table 13: Effects of malaria on morbidity and mortality among pregnant woman, foetus and
newborn ...................................................................................................................... 53
Table 14: Classification of treatment failures ....................................................................... 68
Table 15 Drugs indicated for chemoprophylaxis .................................................................. 70
Table 16 Atovaquone/Proguanil paediatric dosage ............................................................. 71
Table 17: Dosage schedules for treatment of uncomplicated malaria using Amodiaquine
tablets 200 mg base .................................................................................................... 83
Table 18: Dosage for treat ment of uncomplicated malaria using Artesunate + Amodiaquine
tablets ......................................................................................................................... 87
Table 19 Dosing schedule for artesunate plus mefloquine .................................................. 88
National Guidelines for Malaria Diagnosis and Treatment 2005
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Chapter 1
Introduction
National Guidelines for Malaria Diagnosis and Treatment 2005
12
CHAPTER 1: INTRODUCTION
1.1 Background
Malaria remains the most common public health problem in Tanzania. It is the
number one cause of morbidity and mortality especially in children below five years
of age
1
. In 2004 malaria diagnosis in children under five years of age accounted for
43% of all OPD attendances and 40% of deaths recorded in health facilities.
The goal of appropriate malaria diagnosis and treatment is to reduce morbidity,
mortality and socio-economic losses. The use of National Guidelines for
Diagnosis and Treatment of Malaria is key to achieving this goal. In addition, the
aim is to attain uniform malaria case management in the country. The guiding
principle of antimalarial drug policy is to promote safe, effective, good quality,
affordable, accessible and acceptable malaria treatment. At the same time it should
encourage rational drug use in order to minimise the development of drug
resistance.
Tanzania changed its malaria treatment policy from Chloroquine to
Sulfadoxine/Pyrimethamine (SP) monotherapy as the first line drug for the treatment
of acute malaria episodes in August 2001. However, over the last 4 years resistance
to SP has already been reported to be on the increase. Recent studies (2004) in
Tanzania indicate that the mean SP treatment failure is now 25.5%
2
. In addition,
molecular markers of SP resistance have recorded high levels of mutation
3
. The
mean treatment failure of Amodiaquine, the second line antimalarial, is 12%. These
findings indicate that a change in the treatment guidelines is necessary.
Due to the risk of increasing parasite resistance to existing monotherapies, there is
now a global move towards use of combination therapy (CT). Combination therapy
with antimalarial drugs is the simultaneous use of two or more blood schizonticidal
drugs with independent modes of action and different biochemical targets in the
parasite. Combination therapy can be either fixed-combination medicinal products, in
which the components are co-formulated in the same tablet or capsule, or multiple-
drug therapy, in which the components are co-administered in separate tablets or
capsules. Artemisinin based combination therapy (ACT) is antimalarial combination
therapy with artemisinin derivatives as one component of the combination
4
.
Artemisinin based combinations are highly efficacious and have the potential to
delay the spread of drug resistance.
Based on these principles combination therapy is recommended. Specifically, a
combination of Artemether-lumefantrine (ALu) is recommended as first line
therapy for uncomplicated malaria while Quinine is recommended as the second
line drug in case of treatment failure or the presence of a contraindication to the first
1 NMCP, Annual Report 2004
2 East Africa Network for Monitoring Antimalarial Therapy
,, 2004
3 Kefas Mugittu et al. Therapeutic efficacy of SP and prevalence of resistance markers in Tanzania. Am.J.Trop.Med.Hyg 71(6) pp 696-702 (2004)
4 Combination therapy in Malaria, WHO 2004
National Guidelines for Malaria Diagnosis and Treatment 2005
13
line drug for treatment of uncomplicated malaria. Quinine also remains the drug of
choice for the treatment of severe malaria.
Unlike in the past whereby the efficacy of antimalarial treatments lasted for many
years, current rates in development of resistance along with the arrival of more
effective antimalarials, means that malaria chemotherapy may change in the years
to come. In keeping with this new and evolving process these guidelines will have to
be revised accordingly.
1.2 Broad objective
The broad objective of these Guidelines for Malaria Diagnosis and Treatment in
Tanzania is to provide standard management reference for the care of patients with
malaria. They form part of the National Drug Policy. These recommendations
represent the minimum level of care that patients should expect at different levels of
health care in the public and private sectors.
1.3 Specific objectives
• To stipulate at what level of health care delivery specific antimalarial drugs
should be made available at all times
• To promote prompt and accurate malaria diagnosis
• To promote rational antimalarial drug management
• To promote intermittent preventive treatment for malaria in pregnancy
• To provide consistent guidance to prescribers and users on the appropriate use
of chemoprophylaxis for specific at risk groups
• To provide information to health care managers and service providers on the
detection of antimalarial drug resistance
1.4 Rationale
Due to increased resistance of the malaria parasites to antimalarial monotherapies,
in order to preserve the efficacy and effectiveness of the existing drugs and to
ensure an optimal cure, the Ministry of Health and Social Welfare started a
consultative process in mid 2003. The aim was to select alternative options to the
interim antimalarial drug regimen that became operational in 2001 (SP 1
st
line,
Amodiaquine 2
nd
line and Quinine 3
rd
line).
In January 2004 the MoH appointed a task force to explore suitable alternatives. The
task force suggested that Artemisinine based Combination Therapy (ACT) was the
most appropriate option for malaria treatment. The ACTs recommended by WHO for
the African Region were limited: SP-Artesunate (SP-AS), Amodiaquine-Artesunate
(AQ-AS) and Artemether-Lumeantrine (ALu). Since the efficacy of ACT is related to
the good efficacy of the individual single components, the first option (SP-AS) was
considered as unsuitable due to the documented increased resistance of SP. The
two remaining options (AQ-AS and ALu) were thoroughly tested for their therapeutic
efficacy. Since the efficacy profile of the two ACTs was found equivalent in term of
adequate clinical and parasitological response, (89.9% and 92.8% at day 14
respectively for AQ-AS and ALu), other factors were considered in the selection.
National Guidelines for Malaria Diagnosis and Treatment 2005
14
These were: a) potential for creation of parasite resistance, b) pharmacological
safety profile and c) compliance.
• Amodiaquine, one of the component of AQ-AS combination, ha d already shown
some degree of parasite resistance in the country; there were also some
concerns on possible cross resistance with Chloroquine
• The safety profile of Amodiaquine generates concerns among the health care
providers and the public in Tanzania. The risk of potential side effects and the
negative perception of the drug among the users were also considered
• Fixed formulations were found to have a better compliance
Therefore, the task force recommended ALu as the drug of choice for treatment of
uncomplicated malaria for Tanzania Mainland.
1.5 Choice of antimalarial drugs
The following antimalarial drugs are recommended for treatment of malaria in
Tanzania.
• The first line drug is Artemether-Lumefantrine
• The second line drug, where Artemether-Lumefantrine has failed or is
contraindicated, is Quinine
• The drug of choice for treatment of severe malaria is Quinine
• The drug of choice for pregnant women during the first trimester and children
weighting below 5 Kg is Quinine
National Guidelines for Malaria Diagnosis and Treatment 2005
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Chapter 2
Management
of Malaria and
health care
delivery in
Tanzania
National Guidelines for Malaria Diagnosis and Treatment 2005
16
CHAPTER 2: MANAGEMENT OF MALARIA AND HEALTH
CARE DELIVERY IN TANZANIA
2.1 Introduction
In Tanzania, the levels of health care delivery are divided into four categories:
Category I: Home, Village/Community Primary Health Care Post, Pharmacy, Drug
stores including Accredited Drug Dispensing Outlet (Duka la Dawa Muhimu)
Category II: Dispensary
Category III: Health Centre
Category IV: Hospital
The categories mentioned above should not be looked at as a rigid sequence of
referral from category I - II - III - IV. Instead, a well-trained health worker should be
able to recognize the severity of malaria and refer the patient directly to the most
appropriate category of care consistent with that condition.
2.2 Home
Staffing
• Parents/guardians
• Community Health Workers (CHW ) and other Community Owned Resource
Persons (CORPs)
• Dispensing staff of drug store (duka la dawa muhimu)
Diagnosis
The diagnosis of malaria should be based on:
• Symptoms such as fever, headache, malaise, joint pains, etc.
• A few basic clinical observations including feeling for body hotness and taking
armpit temperature
• Presence of palmar and/or mucosal pallor for early detection of anaemia
• Recent history of convulsion in children
Type of services provided
• Health education and treatment of uncomplicated malaria cases
• Identification of patients with severe disease and non–responsive malaria cases
• Initial supportive treatment and referral to the appropriate level of care
• Where referra l is made (e.g. ADDO, CHW), a referral note should be written
Types of treatment available
• Antimalarials: Artemether-Lumefantrine (ALu) tablets
• Analgesics/antipyretics: Paracetamol, Aspirin (not for children below 12 years of
age)
• Oral fluids
• Exposure and fanning (kupepea)
National Guidelines for Malaria Diagnosis and Treatment 2005
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2.3 Dispensary
At the dispensary a m ore detailed history should be taken and a more extensive
clinical examination should be performed. It is recommended to have laboratory
services for malaria parasites.
Staffing
• Clinical Officers
• Assistant Clinical Officers
• Trained Nurses/Public Health Nurses
• MCH Aides, Pharmaceutical Assistants and Medical attendants (Nurse
Assistants/Auxiliaries, Laboratory Assistants)
All staff, with the exception of Laboratory and Pharmaceutical Assistants, are trained
to administer antimalarial drugs intramuscularly when indicated
Diagnosis is based on
• Clinical history and physical examination
• Blood smear for malaria parasites, Rapid Diagnostic Test (where available)
Type of services provided
• Treatment of uncomplicated malaria cases
• Pre-referral treatment of severe malaria cases with intra-muscular quinine
• Treatment of severe malaria cases where referral is not possible
• Patient education
• Identification of patients with anaemia for the purpose of treatment and/or referral
• Identification of patients with severe disease and treatment failures for referral
with the case summary
• Detection of hypoglycaemia (where available)
• Estimation of haemoglobin (where available)
Type of treatment provided
• Antimalarials:
o Artemether-lumefantrine (ALu) tablets
o Quinine (tablets and injectable)
o SP tablets for Intermittent Preventive Treatment
• Analgesics/antipyretics: Paracetamol and Aspirin
• Anticonvulsant drugs: Diazepam (injectable) and Phenobarbitone
(injectable/tablets)
• Oral Rehydration Therapy (ORT)
• Exposure and Fanning (kupepea)
• Correction of hypoglycaemia: Sugar solution, Dextrose10% or 25% or 50%
solution (where available)
2.4 Health centre
At the health centre, better resources for differential diagnosis and patient monitoring
are available. Therefore, a more detailed history should be taken, more extensive
National Guidelines for Malaria Diagnosis and Treatment 2005
18
clinical examination should be performed and a blood smear for malaria parasites
should be done.
Staffing
• Assistant Medical Officer
• Clinical Officer
• Assistant Clinical Officer
• Public Health Nurse
• Nurse Midwives
• Medical Attendants (Nurse Assistants/auxiliaries)
• Laboratory Technicians/Assistants
• Pharmaceutical Technicians/Assistants
All staff, with the exception of Laboratory/Pharmaceutical A ssistants and
Technicians, are trained to administer antimalarial drugs intramuscularly and/or
intravenously, when indicated.
Diagnosis is based on:
• Clinical history and physical examination
• Blood smear for malaria parasites, Rapid Diagnostic Test (where available)
Type of services provided
• Treatment of uncomplicated and severe malaria cases
• Patient monitoring
• Patient education
• Identification of patients with severe disease and treatment failures for referral
with case summary
• Identification of patients with anaemia for the purpose of treatment and/or referral
• Identification of hypoglycaemia
• Pre-referral treatment
• Detection of hypoglycaemia
• Estimation of haemoglobin (Hb)
Type of treatment available
• Antimalarials:
o Artemether-lumefantrine (ALu) tablets
o Quinine (tablets and injectable)
o SP tablets for Intermittent Preventive Treatment
• Analgesics/anti-pyretics: Paracetamol, Aspirin (not for children under 12 years of
age)
• Anticonvulsants: Diazepam (Injectable) and Phenobarbitone (Injectable/tablet)
• Oral Rehydration Salts (ORS)
• Intravenous fluids: Dextrose 5%, Sodium Chloride 0.9% (Normal Saline), Sodium
Lactate Compound (Ringer Lactate/Hartmann’s solution) and Dextrose Saline
• Correction of hypoglycaemia: dextrose 10%, 25% and 50% solutions
• Exposure and fanning (kupepea)
Blood transfusion services are not usually available at the health centre
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2.5 Hospital
Staffing:
• Specialists
• Medical Officers
• Assistant Medical Officers
• Clinical officers
• Nursing Officers
• Public Health Nurse A and B
• Nurse Midwives
• Medical Attendants (Nursing Assistant/Auxiliaries)
• Laboratory Technicians/Assistants
• Pharmacists and/or Pharmaceutical Technicians/Assistant
• Other Medical Cadres
Diagnosis
At this level there is sufficient clinical expertise for diagnosis of severe malaria and
its complications and adequate differential diagnosis. There should also be greater
efficiency and accuracy in microscopic diagnosis of malaria including identification of
species, sexual and asexual forms and performance of quantitative parasite counts.
Diagnosis is based on:
• Clinical history, physical examination,
• Laboratory tests, radiology and other tests
Laboratory tests available include:
• Blood smear for malaria parasites
• Blood glucose
• Lumbar puncture for CSF examination
• Full blood picture including Hb
• Urinalysis including haemoglobinuria
• Basic biochemical tests
o Liver function tests - including bilirubin, ALT, AST and ALP
o Serum creatinine and blood urea
o Electrolytes including Sodium, Potassium, Chloride, Bicarbonate and
lactate
• Cultures – Blood, urine etc.
Type of services provided
• Treatment of uncomplicated and severe malaria cases
• Health education
• Identification of patients with complicated conditions that cannot be managed at
district/regional hospitals (e.g. renal failure, uncontrollable convulsions, etc.) for
treatment at consultant hospitals
• Identification of patients with anaemia for the purpose of treatment
• Patient monitoring
• Blood transfusion services
• Intensive care
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Type of treatment available
• Antimalarials
o Artemether-lumefantrine (ALu) tablets
o Quinine (tablets and injectable)
o Artemether injectable
o SP tablets for Intermittent Preventive Treatment
o Other antimalarial drugs may be available
• Analgesics/antipyretics: Paracetamol, Aspirin (not for children under 12 years of
age)
• Anticonvulsant drugs: Diazepam Injectable and Phenobarbitone (injectable
/tablet)
• Oral Rehydration Salts (ORS)
• Intravenous fluids: Dextrose 5%, Sodium Chloride 0.9% (Normal Saline), Sodium
Lactate Compound (Ringer Lactate/Hartmann’s solution), Dextrose saline, etc.
• Blood transfusion services
• Correction of hypoglycaemia: Dextrose10%, 25% and 50% solution
• Exposure and fanning (kupepea)
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Chapter 3
Diag nosis of
malaria
National Guidelines for Malaria Diagnosis and Treatment 2005
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CHAPTER 3: DIAGNOSIS OF MALARIA
Describe different methodological options in laboratory diagnosis
3.1 Introduction
In high transmission areas a significant proportion of individuals have parasitaemia
but do not necessarily suffer from malaria disease. An individual with malaria
infection may be completely asymptomatic. It should be noted that the aim of
diagnosis is to assist in the treatment of the disease and not the asymptomatic
infection.
In order to minimize the irrational use of antimalarials, reduce the potential for
developing parasite resistance and provide quality services, it is important to
improve the accuracy of malaria diagnosis.
3.2 Clinical features of malaria
Malaria is an acute disease. Patients usually present with fever, chills and profuse
sweating. The clinical features of malaria vary from mild to severe, according to the
species of the parasite present, the patient's state of immunity, the intensity of the
infection and the presence of accompanying conditions such as malnutrition,
anaemia and other diseases.
Fever is the most common feature of malaria. It may persist for several days,
accompanied by headache, aching joints and general discomfort. The classic
presentation of malaria with high fever chills, shivering and sweating however may
not occur. The onset of malaria symptoms may resemble a flu-like illness. In infants
the early symptoms of malaria may be quite variable and difficult to recognize. They
may be limited to poor appetite, restlessness and loss of normal interest in the
surroundings. Some patients, especially children, may present with a cough and/or
vomiting and diarrhoea.
In P. falciparum infections (which constitutes more than 90% of the cases in
Tanzania), the headache, nausea and vomiting are usually more severe than in
other malarial infections and there is a greater tendency towards the development of
delirium, haemolytic jaundice and anaemia. The mortality is much greater than in
other forms of malaria. Those who survive but who have continuing infection as a
result of inadequate or no treatment may suffer several weeks or months of poor
health. Anaemia, weakness and febrile episodes are characteristic of these cases.
The above signs and symptoms are not specific for malaria and can be found in
other disease conditions. Therefore, it is always necessary to find out other causes
of illness.
3.3 Assessment of the patient
3.3.1 Clinical assessment
A detailed history should be taken and a thorough physical examination made in
order to diagnose diseases other than malaria. A careful assessment of a patient
National Guidelines for Malaria Diagnosis and Treatment 2005
23
with suspected malaria is essential in order to differentiate between uncomplicated
and severe disease. Laboratory investigations are done to complement clinical
diagnosis. In health care facilities without laboratory services, diagnosis is based
only on signs and symptoms.
Table 1 Distinguishing features of uncomplicated malaria in relation to age groups
Features Less than five
years
Older children
and adults
Fever
+ + +
+
Headache
+
+ +
Joint pains
+
+ +
Malaise
+
+ +
Vomiting/diarrhoea
+ + +
+
Body ache
+
+ +
Poor appetite
+ +
+ +
Body weakness
+ +
+ +
Pallor
+ + +
+
Enlarged spleen
+ +
+
Note: + = less common, ++ = common, +++ = Very common
Table 2 Clinical and laboratory features of severe malaria
5
Clinical Manifestations of severe
malaria
Less than five
years
Older children
and adults
Behavioural Changes
+
+++
Prostration/Extreme weakness
+++
+++
Coma
+++
++
Respiratory distress
+++
++
Convulsions
+++
+
Vomiting everything
++
+
Inability to drink or breast feed
++
+
Circulatory collapse/Shock
+
++
Pulmonary oedema
+
+
Bleeding tendency /DIC
+
++
Jaundice
+
+++
Acute Renal Failure
+
++
Haemoglobinuria
+
++
Features and Laboratory Indices
severe malaria
Less than five
years
Older children
and adults
Severe malarial anaemia (Hb <7g/dl or
haematocrit <21%)
+++ +
Hypoglycaemia (< 2.5 mmol/L)
+++
++
Metabolic Acidosis (Arterial pH <7.3,
Bicarbonate <15 mmol/L)
+++ ++
Hyponatraemia (<130 mmol/L)
+
+
Hyperparasitaemia >5000 asexual
parasites per 200 WBC (>200,000
asexual parasites per
µ
L)
++ +
Uraemia (BUN >6.7 mmol/L)
+
+++
Note: + = less common, ++ = common, +++ = Very common
5
Modified from WHO, Severe falciparum malaria. Transaction of the Royal Society of Tropical Medicine and Hygiene, 2000,94 (Suppl. 1)
National Guidelines for Malaria Diagnosis and Treatment 2005
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3.4 Laboratory investigations
Investigations may be done depending on the capacity of the laboratory and the
clinical indications. Laboratory tests should be interpreted in conjunction with clinical
findings.
The role of laboratory tests for malaria management
• As we move towards more expensive antimalarial drugs and in order to preserve
their efficacy, there is an urgent need for improved laboratory services to confirm
clinical diagnosis and support patient care.
• Where microscopy is possible this service should be strengthened through an
efficient quality assurance system, availability of equipment, consumables and
skilled staff.
• Urgent laboratory investigations should be made available for all patients
admitted with severe malaria
• Since parasite-based diagnosis is important, rapid diagnostic tests (RDTs) may
be an alternative or complement to microscopy
Urgent laboratory investigations
• Thick and thin blood smears for malaria parasites (for reporting of results see
Appendix 1)
• Blood glucose estimation in patients with altered consciousness
• Haematocrit and/or haemoglobin estimation
• Lumbar puncture to exclude meningitis at hospital and health center levels (if
facilities for LP are available)
Other laboratory investigations
The following investigations, if available, are also helpful in the management of
severe malaria:
• Serum creatinine or urea. There is no need to measure both, as creatinine is
more useful
• Electrolytes. These may occasionally reveal a correctable abnormality such as
hyponatraemia. Both creatinine and electrolytes are most valuable when acute
renal failure threatens or develops
• Full blood cell count and differential white cell count. Sometimes these may
indicate the possibility of an additional diagnosis
• Blood gases, pH and anion gap. Acidaemia is an indicator of severe disease in
both conscious and unconscious patients
• Chest X-ray. May identify pulmonary oedema or lobar consolidation. It may be of
value in assessing respiratory distress syndrome
• Plasma and cerebrospinal fluid lactate concentrations. These are raised in lactic
acidosis. High levels are associated with a poor prognosis
• Improvements to conventional microscopic techniques for identifying malaria
parasites may be available. These techniques include the Quantitative Buffy
Coat (QBC) and the Acridine Orange (AO) methods.
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Rapid Diagnostic Tests
Rapid diagnostic tests (RDTs) are qualitative techniques based on the detection of
malaria parasite antigens
6
. The tests can be done by minimally trained personnel
and are rapid (can be performed in about 15 minutes) and highly sensitive and
specific with a high diagnostic reliability
7
. The test may remain positive for up to one
month after treatment even though the patient has been cured. Quantification of
parasites is not possible hence the tests cannot be used for evaluation of clinical
outcome.
Rapid diagnostic tests can be used at all levels; however, it will be preferable to
deploy at levels where microscopy is not possible (e.g. dispensary, health centre).
6 The tests detect: P.falciparum histidine rich protein II (HRP-II) produced by trophozoites and young gametocytes; and parasite lactate dehydrogenase
(pLDH) produced by live trophozoites and gametocytes.
7 Mboera et al. Comparison of the Paracheck-Pf ® test to microscopy for confirmation of Plasmodium falciparum malaria in epidemic prone districts of
Tanzania, 2005
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Chapter 4
Management
of
uncomplicated
malaria
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CHAPTER 4: MANAGEMENT OF UNCOMPLICATED
MALARIA
4.1 Introduction
The management of a patient with malaria will be determined by the clinical
presentation and the diagnosis of either uncomplicated or severe disease.
The objectives of treatment of uncomplicated malaria are:
• To provide rapid and long lasting clinical and parasitological cure
• To reduce morbidity including malaria related anaemia
• To halt the progression of simple disease into severe and potentially fatal
disease
In order to achieve these objectives, uncomplicated malaria must be diagnosed early
and the correct treatment administered without delay. Since the progression towards
severe and fatal disease is rapid, especially in children under five years of age, it is
recommended that diagnosis and treatment of uncomplicated malaria should be
done within 24 hours from the onset of symptoms.
4.2 Clinical features of uncomplicated malaria
All health care providers should be able to recognize the following features of
uncomplicated malaria:
• Fever
• Headache
• Joint pains
• Malaise
• Body weakness
• Vomiting
• Diarrhoea
• Chest pains
• Poor appetite
• Anaemia (mild to moderate)
• Hepato-splenomegaly
especially in children
The flow charts in Figure 1 and 2 illustrate the actions for the management of a
patient with suspected malaria (see also appendix 2 and 4 for algorithms).
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Figure 1 Management of a patient with suspected malaria in health facilities without
laboratory services
Take Careful history
Examine the patient
Decide the most likely diagnosis
Decide on severity
Other non severe
disease
Uncomplicated
malaria
Severe malaria or
severe disease
Treat as inpatient
OR
give urgent pre-
referral treatment
Treat as out-patient
and provide health
education on malaria
Treat as out-patient
Refer for
admission
Make a follow up
Make a follow up
(Ask)
(Look and feel)
(Classify)
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Figure 2 Management of a patient with suspected malaria in health facilities with
laboratory services
Take Careful history
Examine the patient
Decide the most likely diagnosis
and severity
Other non severe
disease supected
Uncomplicated Malaria
suspected
Severe malaria or other
severe disease
Treat while waiting lab results
OR
Give pre-referral treatment and
refer urgently
Manage Malaria
according to
severity
Investigate and
manage accordingly
Under five years
treat as uncomplicated
malaria
look for other conditions
and manage
accordingly
Perform malaria test
Negative
Positive
Five years and above
Investigate and manage
accordingly
Close follow up
No
signs and
symptoms of
severe
disease
Signs and symptoms of
severe disea
se
Continue treatment
Review the patient
Perform other investigations
AND/OR
Refer to appropriate health
care facility
Negative blood slide/RDT in a patient without signs and symptoms of severe diseas e
• If under five years of age and still malaria is suspected treat as uncomplicated malaria; also look
for other causes and manage accordingly
• If above five years of age, look for other causes and manage accordingly; close follow up and as k
to come back if condition does not improve
A negative blood slide/RDT in a patient with signs and symptoms of severe d isease
• Treat as severe malaria and add broad spectrum antibiotic(s)
• Review the patient and manage accordingly
• Repeat the blood slide after 4-6 hours and perform other investigations (e.g. lumbar puncture,
blood culture and sensitivity, etc.)
• Eventually, refer to appropriate health care facility
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4.3 Treatment of uncomplicated malaria using combination therapy
Combination therapy refers to the use of two or more antimalarial drugs with
independent mode of action and different biochemical targets in the parasite, which
are synergistic or additive, or complementary in their effect.
Combination therapy can be either:
fixed combination therapy, where all components are co-formulated in a single
tablet/capsule like Artemether-Lumefantrine (ALu)
co-administered therapy, where the components are simultaneously
administered in separate tablets/capsules
The aim of combination therapy is to improve treatment efficacy and also delay the
development of drug resistance.
Artemisinin-based combination therapy (ACT) refers to combinations comprising of
an artemisinin derivative and another antimalarial drug. Examples of artemisinin
derivatives are artemether, artesunate and dihydroartemisinin. Artemisinin
derivatives are efficacious, short acting and generally safe. The partner drug should
be as well efficacious, safe and compatible. Some examples of partner drugs are
Lumefantrine, Amodiaquine, Chlorproguanil-Dapsone and Mefloquine.
4.4 Treatment of uncomplicated malaria with first line drug: Artemether-
Lumefantrine
The first line drug for the treatment of uncomplicated malaria is Artemether -
Lumefantrine (ALu).
Drug description
Artemether-lumefantrine (ALu ) is an oral fixed combination tablet of 20mg
Artemether – a derivative of artemisinin, and 120mg Lumefantrine. Artemether is
effective against all human malaria parasites species. It has a rapid schizonticidal
action against Plasmodium falciparum. Recrudescence is therefore frequent when it
is used as a monotherapy. Lumefantrine is an aryl amino alcohol. It has a longer
elimination half-life of up to 10 days and is associated with a low recrudescence rate,
but has a slower onset of action. ALu therefore combines the benefits of the fast
onset of action of Artemether with the long duration of action and high cure rate of
Lumefantrine in a single oral formulation. It is highly efficacious even against multi
drug resistant malaria parasites with clearance of the parasites from the blood within
2 days.
Available formulations
Tablets: Fixed formulation Artemether 20 mg, Lumefantrine120mg
Indications:
• First line treatment of uncomplicated malaria
Contraindications
• Hypersensitivity to either Artemether or Lumefantrine
National Guidelines for Malaria Diagnosis and Treatment 2005
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Not recommended
• Children below 5kg body weight
• First trimester of pregnancy
• Lactating mothers with child below 5kg of body weight
Use of Artemether-lumefantrine (ALu) in Pregnancy and Lactation
Pregnancy
Presently, Artemisinin compounds cannot be recommended for treatment of malaria
in the first trimester of pregnancy. However, they should not be withheld if treatment
is considered to be life saving for the mother and other anti malarial are considered
to be unsuitable. In the first trimester of pregnancy quinine should be used as first
line treatment. During the first trimester (12 weeks of pregnancy) it is not
recommended to take ALu at all. After the first trimester ALu tablets is first line
medicine.
Lactation
No data is available on the excretion of either of the two compounds in breast milk.
Due to the long elimination half-life of Lumefantrine (up to 10 days), it is not
recommended in mothers breast-feeding children below 5kgs. In this case quinine
should be used. ALu can be used as first line treatment in lactating mothers if no
suitable alternative is available.
Adverse effects of Artemether-lumefantrine (ALu)
While the overall incidence of side effects to ALu is low, the common adverse effects
reported include sleep disorders, headache, dizziness, nausea, anorexia, abdominal
pain, pruritus, rash, cough, palpitation, arthralgia and myalgia. Lumefantrine does
not cause prolongation of QT interval and therefore it is safe in patients with cardiac
illness.
Artemether-lumefantrine administration
• The first dos e of Artemether-lumefantrine should preferably be administered at
the health facility as direct observed treatment (DOT)
• When administering Artemether-lumefantrine, if the drug is vomited or spat out
within 30 minutes, the dose should be repeated
• ALu should be taken with meals to enhance its absorption
Dosage regimen
The dose of artemether-lumefantrine (ALu) is 1.5/12 mg/kg bodyweight twice a day
for three days. For convenience purposes, the dosing schedule for ALu (strength
20/120 mg) is reported in table 3.
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Table 3: Dosage schedule of Artemether 20mg & Lumefantrine 120 mg (ALu)
(number of tablets recommended at approximate timing of dosing)
Day 1 Day 2 Day 3
Kg
Dose
1
st
2
nd
3
rd
4
th
5
th
6
th
Colour
Code
Coartem ®
Hours
0 (*)
8
24
36
48
60
Age
tablets
tablets
tablets
tablets
tablets
tablets
5 up to
15
3 months
up to 3
years
1 1 1 1 1 1
Yellow
15 up
to 25
3 years
up to 8
years
2 2 2 2 2 2
Blue
25 up
to 35
8 years
up to 12
years
3 3 3 3 3 3
Red
35 and
above
12 years
and
above
4 4 4 4 4 4
Green
(*) 0 hours means the time of starting medication (see appendix 5 for time
schedule for 1
st
and 2
nd
dose)
For practical purposes, a simpler dosage regimen is recommended in order to
improve compliance: the first dose should be given as DOT; the second dose
should strictly be given after 8 hours; subsequent doses could be given twice
daily (morning-evening) in the second and third day of treatment until
completion of 6 doses (see illustration below).
WEIGHT
5 - 15 kg
*Strictly after 8 hours
Start
Dose
After
8 hrs*
Day 1
Day 2
Day 3
Mornin
g
Night
Morning
Night
AGE
3 months up
to 3 years
3 years up
to 8 years
8 years up
to 12 years
12 years
and above
15 - 25 kg
25 - 35 kg
35 kg and
above
National Guidelines for Malaria Diagnosis and Treatment 2005
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Non response to ALu may be due to:
• Vomiting the drug
• Poor quality of the drug
• Inadequate dosage
• Fever/symptoms from a cause other than malaria
• Parasite resistance to the drug (rare)
Management of non-response to malaria treatment with ALu
Where a patient returns between 4 to 14 days after treatment with ALu complaining
of continued symptoms of malaria, non-response should be considered and the
following recommendations followed after a full history and examination:
• Where laboratory facilities are not available and malaria is still suspected,
treatment with Quinine should be started immediately with strict follow up
• Where laboratory facilities are available, a blood smear (and not RDT) should be
examined. If parasites are found treatment with Quinine should be started and
treatment failure recorded. If parasites are not found other causes for the
symptoms should be sought and treated accordingly
As far as possible malaria cases should be followed up on the third day if
symptoms persist or immediately if the condition worsens. Health workers
should know where they could refer cases that fail to respond to the
recommended drug regimen for further investigations and appropriate
management
4.5 Management of fever.
Patients with high fever (38.5
0
C and above) should be given an anti-pyretic drug like
paracetamol or aspirin every 4 to 6 hours (maximum 4 doses in 24 hours) until
symptoms resolve, usually after two days. Children below 12 yrs should not be given
aspirin because of the risk of developing Reye's syndrome.
Table 4. Treatment schedule for paracetamol (500mg) tablets
Dosage for children: 10 mg/Kg bw
Age
(years)
Weight
(Kg)
Dose
2 months up to 3 yr
4 up to 14
¼
3 up to 5
14 up to 19
½
5 up to 12
19 up to 35
1
12 up to 14
35 up to 45
1
1
/
2
14 and above
45 and above
2
National Guidelines for Malaria Diagnosis and Treatment 2005
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4.6 Treatment of uncomplicated malaria with second line drug: Quinine
Available formulation
• Tablets 300 mg
• Injection 600 mg in 2 mls
• Quinine hydrochloride syrup 100 mg/5ml
Indications
• Treatment of uncomplicated malaria where ALu is contraindicated
• Treatment of uncomplicated malaria where ALu has failed
• Drug of choice for treatment of uncomplicated malaria
• in first trimester of pregnancy,
• in lactating mothers with children below 5 kg
• in children under weighing below 5 Kg
• Drug of choice for treatment of severe malaria
Contraindications
• Hypersensitivity to quinine
• Optic neuritis
• Myasthenia gravis
Use in pregnancy and lactation
Quinine is safe in pregnancy. In therapeutic doses it does not induce labour. Uterine
contractions and fetal distress associated with the use of quinine, may be
attributable to fever and effects of malaria disease. The risk of quinine induced
hypoglycaemia is however greater in pregnant women than in non-pregnant women.
Adverse effects
• Cinchonism (tinnitus, muffled hearing, sometimes vertigo or dizziness)
• Hypotension especially if injected rapidly by the intravenous route
• Hypoglycaemia, through stimulation of secretion of insulin from pancreatic beta
cells. Hypoglycaemia is particularly likely to develop after intravenous infusion in
pregnancy since beta cells are more susceptible to a variety of stimuli at that time
• Injection sterile abscess
Dosage regimen
Treatment with Quinine tablets (salt) should be given for 7-10 days at a dose of 10
mg/kg every 8 hours. Refer to chapter 5 for details on Quinine use. Preferably the
dose to be given should be calculated for each single patient according to the weight
(not exceeding a maximum dose of 600mg). The table 5 below is given for guidance
when it is impossible to weigh patients.
National Guidelines for Malaria Diagnosis and Treatment 2005
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Table 5: Dosage schedule for malaria treatment using oral Quinine (salt, 300mg
tablet) for different age groups
Dose: 10mg/kg body weight given every 8 hours for 7-10 days
Age
(years)
Weight
(Kg)
Number of tablets
Up to11 months
5 up to 11
¼
1 up to 5
11 up to 19
½
5 up to 8
19 up to 25
¾
8 up to 12
25 up to 35
1
12 up to 14
35 up to 50
1 ½
14 up to 16
50 up to 60
1 ¾
16 and above
60 and above
2
Non-response to Quinine treatment
Refer the patient for thorough investigations and management.
4.7 Health education for uncomplicated malaria patient/caretakers
Focus health education messages on the following:
• Importance of compliance
• Doses and dose schedules
• When to return immediately (worsening conditions especially when fever
remains high, excessive vomiting etc.)
• Continue with feeding and fluid intake
• When to return for follow up to health facility (to ensure good progress)
• Personal protection measures especially use of Insecticide Treated Nets
• Environmental sanitation
National Guidelines for Malaria Diagnosis and Treatment 2005
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Chapter 5
Management
of severe
malaria
National Guidelines for Malaria Diagnosis and Treatment 2005
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CHAPTER 5: MANAGEMENT OF SEVERE MALARIA
5.1 Introduction
Severe Plasmodium falciparum malaria is a medical emergency. Delay in diagnosis
and provision of appropriate treatment may lead to serious complications and even
death. In Tanzania the commonest presentations of severe malaria are severe
anaemia and cerebral malaria.
5.2 Features of severe malaria
One or more of the following features indicate severe malaria
Table 6: Features of severe malaria
Clinical features
Description/criteria
Prostration/extreme weakness
Unable to stand or sit up without support
Impaired consciousness
Altered level of consciousness
Acute confusional state, coma
Change of behaviour
Hallucinations, delusions, agitation
Convulsions
Repetitive abnormal muscular movements
Respiratory distress (due to lactic
acidosis and/or pulmonary
oedema)
Acidotic breathing: deep and laboured breathing
Pulmonary oedema: laboured breathing,
restlessness, blood stained frothy sputum
especially in adults
Bleeding tendency/DIC
Easy/prolonged bleeding
Jaundice
Yellow colouration of mucus membranes
Circulatory collapse/shock
∗
Low systolic BP
∗∗
and fast pulse rate
∗∗∗
Vomiting everything
Throwing up after every feed/drink
Inability to drink or breast feed
Not able to swallow
Condition Corresponding Indices
Severe malarial anaemia
Hb <7g/dl or haematocrit < 21%
Haemoglobinuria
Dark brown or Positive Hb on dipstick urine
Pulmonary oedema
Chest X-ray
Hyperparasitaemia
>5000 asexual parasites per 200 WBC
(>200,000 asexual parasites per μL)
Metabolic acidosis
Arterial pH <7.3, Bicarbonate <15 mmol/L
Acute renal failure
Oliguria urine output <0.3 ml/kg/hr in children
and <17ml/hr in adults
Raised serum creatinine >130 mmol/L and BUN
>6.7 mmol/L
Hypoglycaemia
Glucose <2.5 mmol/L
∗
Shock: cold extremities, capillary refill delayed for ≥ 3 seconds (when a nail of the thumb is pressed);
weak and fast pulse;
** Low systolic BP <50 mmHg in children and <90 mmHg in adults;
*** Fast pulse rate ≥150 per minute in children and ≥100 beats per minute in adults;
National Guidelines for Malaria Diagnosis and Treatment 2005
38
Table 7: Clinical features and laboratory indices of severe malaria in adults and
children and their prognostic values
8
Features Prognostic values
Children Adults
Clinical Manifestations
Behavioural changes
+
+
Prostration
+
+
Coma
+ + +
+ + +
Respiratory distress
+ + +
+ + +
Repeated convulsions
+ + +
+ +
Circulatory collapse/Shock
+ + +
+ + +
Pulmonary oedema
+ + +
+ + +
Bleeding tendency /DIC
+ + +
+ + +
Jaundice
+ +
+
Acute renal failure
+ + +
+ + +
Haemoglobinuria
+
+
Vomiting everything
+ +
+ +
Inability to drink or breast feed
+ + +
+ +
Condition and Laboratory Indices
Severe malarial anaemia (Hb <7 g/dl or
haematocrit <21%)
+ +
+ +
Hypoglycaemia (<2.5 mmol/L)
+ + +
+ + +
Metabolic Acidosis (Arterial pH <7.3,
Bicarbonate <15 mmol/L)
+ + +
+ + +
Hyperparasitaemia >5000 asexual
parasites per 200 WBCs (> 200,000
asexual parasites per
µ
L)
+
+ +
Uraemia (BUN >6.7 mmol/L)
+ +
+ +
Prognosis: + poor, ++ very poor, +++ = worse
5.3 Treatment of severe malaria
The drug of choice for treatment of severe malaria is parenteral Quinine preferably
given by intravenous infusion. Refer to chapter 4 for the pharmacological profile of
Quinine.
5.4 Management of severe malaria at home, shopkeeper and village health
post
Management should include
Early recognition of symptoms and signs defining severe malaria with appropriate
early health care seeking behaviour
• Control of fever by the use of anti-pyretics and fanning (kupepea)
• Administration of oral artemether-lumefantrine (ALu)
• Continued feeding and fluid intake
• Immediate referral to the nearest health care facility
8 Modified from WHO, Severe falciparum malaria. Transaction of the Royal Society of Tropical Medicine and Hygiene, 2000,94 (Suppl. 1):1-90
National Guidelines for Malaria Diagnosis and Treatment 2005
39
5.5 Management of severe malaria at dispensary level
Management should include
• Early diagnosis of severe malaria based upon a complete history, physical
examination and, where possible, blood smear/RDT examination for malaria
parasites. Taking and reporting of blood smear must not be allowed to delay
treatment unduly
• Provision of pre-referral treatment with intra-muscular quinine and
• Immediate referral with clinical summary, to the nearest health care facility where
resources for the continuing care of patients with severe malaria are available
General management
Assessment and resuscitation
• Airway – ensure airway is open with no foreign objects,
• Put the patient in semi prone position
• Breathing – ensure there is adequate respiratory movement
• Circulation – measure pulse rate and blood pressure
• Blood slide for malaria parasites (do not wait for results)
• Blood glucose estimation by glucose strips
• Hb estimation
Pre-referral treatment
• Administration of intra-muscular quinine (refer to table 8)
• In suspected severe malaria where meningitis and septicaemia cannot be ruled
out, a broad-spectrum antibiotic (e.g. Chloramphenicol) should be administered
• Correction of hypoglycaemia by using oral sugar-water
• Control fever with anti-pyretics and fanning (kupepea)
• Control convulsion with diazepam (refer to 5.11)
Dilution of quinine for intra-muscular use
• Quinine Dihydrochloride injection (300 mg/ml) for intra-muscular use
• Dose of 10 mg of sa lt/kg bodyweight (not exceeding a maximum dose of 600mg)
• Dilution: diluted four tim es in water for injection to a concentration of 60 mg/ml.
This dilution will minimize the risk of sterile abscess formation.
• Preferably the dose should be calculated for each single patient according to the
body weight. Table 8 below is given for guidance
National Guidelines for Malaria Diagnosis and Treatment 2005
40
Table 8:Dilution schedule for intra-muscular Quinine administration
(Dose = 10 mg/kg of body weight)
Age
(years)
Weight
(Kg)
Volume of
undiluted
Quinine
(300 mg/ml)
Volume of
diluent (to
add to each
dose)
Total
volume of
diluted
Quinine
(60 mg/ml)
2 up to 4 months
4 up to 6
0.2 ml
0.8 ml
1.0 ml
4 up to 9 months
6 up to 8
0.3 ml
1.2 ml
1.5 ml
9 up to 12 months
8 up to 10
0.4 ml
1.6 ml
2.0 ml
12 months up to 3yrs
10 up to 14
0.5 ml
2.0 ml
2.5 ml
3 up to 5
15 up to 19
0.6 ml
2.4 ml
3.0 ml
5 up to 8
19 up to 25
0.7 ml
2.8 ml
3.5 ml
8 up to 12
25 up to 35
1.0 ml
4.0 ml
5.0 ml
12 up to 14
35 up to 50
1.4 ml
5.6 ml
7.0 ml
14 up to 16
50 up to 60
1.8 ml
7.2 ml
9.0 ml
16 and above
60 and above
2.0 ml
8.0 ml
10.0 ml
The calculated dose should be divided into two halves and then administered by
deep intra-muscular injection preferably into the mid anterolateral aspect of the thigh
(one injection on each side)
5.6 Management of severe malaria at health centre level
Management should include
• Early diagnosis of severe malaria based upon a complete history, physical
examination and blood smear/RDT for malaria parasites. Taking and reporting of
blood smear must not be allowed to delay treatment unduly
• Provision of appropriate treatment with intra-venous Quinine
• Treatment of hypoglycaemia. Hypoglycaemia remains a major problem in the
management of severe malaria especially in young children and pregnant
women. It should be deliberately looked for and treated accordingly.
• Referral with clinical summary to the nearest hospital when clinical need dictates
(e.g. blood transfusion or intensive care)
General management
Assessment and resuscitation
• Airway – ensure airway is open with no foreign objects
• Put the patient in semi prone position
• Breathing – ensure there is adequate respiratory movement
• Circulation – measure Pulse rate and Blood pressure
• Blood slide for malaria parasites (do not wait for results)
• Blood glucose estimation by glucose strips/glucometer
• Hb estimation
Where facilities for intravenous therapy are available
National Guidelines for Malaria Diagnosis and Treatment 2005
41
• Management should follow the guidelines presented for hospital level (see 5.7)
Where facilities for intravenous administration of Quinine are not available:
• Injectable Quinine should be given by the intra-muscular route at a dose of 10
mg/kg bodyweight of salt every 8 hours (refer to table 8 for dilution and dosage),
until the patient is able to take oral medication
• Once oral treatment can be tolerated Quinine tablets should be continued to
complete a 7 days treatment course
OR
• A full course of ALu may be administered to complete treatment (except in
pregnant women during first trimester and children below 5 kg body weight)
5.7 Management of severe malaria at hospital level
Management should include:
Early diagnosis of severe malaria based upon a complete history, physical
examination and blood smear/RDT for malaria parasites. Taking and reporting of
blood smear and other investigations must not be allowed to delay treatment unduly
• Provision of appropriate treatment with intra-venous Quinine
• General management, nursing care and monitoring
• Treatment of complications e.g. blood transfusion where appropriate
• Treatment of hypoglycaemia. Hypoglycaemia remains a major problem in the
management of severe malaria especially in young children and pregnant women. It
should be deliberately looked for and treated accordingly.
• Laboratory investigations for other complications where indicated
General management
Assessment and resuscitation
• Airway – ensure airway is open with no foreign objects
• Put the patient semi prone position
• Breathing – ensure there is adequate respiratory movement
• Circulation – measure Pulse rate and Blood pressure
• Blood slide for malaria parasites (do not wait for results)
• Blood glucose estimation by glucose strips/glucometer
• Hb estimation
Insert intravenous cannula
• Blood samples for random blood glucose (RBG), full blood picture (FBP), serum
creatinine, liver function tests (bilirubin, AST, ALT, ALP) and serum electrolytes
• Start dextrose-saline or dextrose 5% infusion
Insert naso-gastrict tube (if indicated)
• For feeding and medication
Insert urethral catheter (if indicated)
• Urine for dipstick
• Urinary output measurement
Nursing care and monitoring
National Guidelines for Malaria Diagnosis and Treatment 2005
42
• Fluid input and output chart
• Level of consciousness
• Temperature, PR, RR and BP
• Investigations: Hb, Glucose, Creatinine, electrolytes if indicated
Table 9: Investigations
Essential If indicated
Blood glucose estimation
Blood culture and sensitivity
Blood film for malaria parasites/RDT
Chest radiograph
Full blood picture
Cerebrospinal Fluid analysis
Urinalysis (including detection of Hb)
Urine culture and sensitivity
Biochemical tests: serum creatinine, liver
function tests (bilirubin, AST, ALT, ALP)
arterial pH and serum electrolytes
Administration of intravenous quinine
Dose
• Quinine 10 mg/kg body weight of salt
• Diluted in 5-10 ml/kg body weight of 5% Dextrose or dextrose-saline
• Infused over 4 hours and repeated every 8 hours.
• The total volume given will depend on the patient’s overall fluid balance
The drop rate is calculated as follows:
Drop rate per minute =
amount of fluid to be infused (in ml) x 20 (drop factor)
time period to be infused (in minutes)
The table 10 below is given for easier calculation:
Table 10: Dilution schedule and drop rate for intravenous Quinine administration
Age
(years)
Weight(kg)
Quinine
dose
Volume of
undiluted
quinine
solution
(300mg/ml)
Amount of
fluid to be
infused
(in 4
hours)
Drop rate
per
minute
2 up to 4 months
4 up to 6
60 mg
0.2 ml
50 ml
4 drops
4 up to 9 months
6 up to 8
90 mg
0.3 ml
100 ml
8 drops
9 up to 12months
8 up to 10
120 mg
0.4 ml
100 ml
8 drops
12 up to 3yrs
10 up to 14
150 mg
0.5 ml
100 ml
8 drops
3 up to 5
15 up to 19
180 mg
0.6 ml
150 ml
13 drops
5 up to 8
19 up to 25
210 mg
0.7 ml
200 ml
17 drops
8 up to 12
25 up to 36
300 mg
1.0 ml
250 ml
21 drops
12 up to 14
36 up to 50
420 mg
1.4 ml
350 ml
30 drops
14 up to 16
50 up to 60
540 mg
1.8 ml
500 ml
42 drops
16 and above
60 and above
600 mg
2.0 ml
500 ml
42 drops
Infusions should be discontinued as soon as the patient is able to take oral
medication. Patients should be properly instructed to complete the 7-day treatment.
Alternatively, a full course of ALu may be administered to complete treatment
Oral Quinine maintenance doses should be 7 mg/kg body weight in patients with
impaired renal function
National Guidelines for Malaria Diagnosis and Treatment 2005
43
5.8 Monitoring of patients with severe malaria
All patients with severe malaria should be closely monitored as described in table 11 below.
Table 11: Important observations and their implications during treatment of severe malaria
Regularly
observe
Possible observation Appropriate action
A. Clinical
Breathing
Increased respiratory rate:
• < 2 months: 60 or more per minute
• 2 up to 12 months: 50 or more per min
• 1 y r up to 5 yrs: 40 or more per min
• 5 y rs and above: 20 or more per min
Or difficulty in breathing
- Check position of the patient
- Put the patient in semi-prone (Fowler’s) position
- Give oxygen if there is respiratory distress
- Review urine output
- Examine lung, heart and size of the liver
- Chest X ray if available
- If pulmonary oedema is demonstrated, or seems likely treat appropriately.
Axillary
temperature
>38.5
0
C
If temperature remains high or
rises despite 24 hours of quinine
therapy
- Give paracetamol if not given within the past 4 hours
- Fanning (kupepea)
- Reassess and investigate for other possible causes while continuing
treatment
Blood pressure
BP Falls:
• <90 mmHg systolic in an adult
• < 5 0 mmHg in infants and children
(using paediatric cuff)
- Review fluid balance, urine output, quinine infusion rate and haematocrit.
- If hypovolaemic give saline infusion where indicated.
- Look for hemorrhage
- Take blood for bacteriological culture and sensitivity if facilities are
available
- Give broad spectrum antibiotic (for possible bacteraemia)
Urine output
Oliguria:
• <17 ml/hr in an adult or
• <0.3 ml/kg/hr in infants and children
- Review fluid input and status of hydration
- Correct fluid deficit if necessary
- Prevent or manage acute renal failure if suspected
- Catheterize if acute renal failure
Coma score
Deterioration
See appendix 6 for Glasgow and
Blantyre coma scale
- Reassess and investigate for other possible causes while continuing
treatment
- Immediately check blood glucose (correct hypoglycemia if suspected)
- Lumbar puncture
National Guidelines for Malaria Diagnosis and Treatment 2005
44
Convulsions
These can recur, or develop for the
first time during treatment and may
be due to hyperpyrexia, abnormal
blood glucose or electrolyte
imbalance or other causes
- Check axillary temperature if >38.5
0
C , treat as above
- Check blood glucose (correct hypoglycemia if suspected)
- Check fluid balance
- Check electrolytes if possible (to detect hyponatraemia)
- Give anticonvulsant drugs
Bleeding from
venepuncture
sites or
spontaneous
haemorrhage
Prolonged bleeding time
suggesting Disseminated
intravascular coagulopathy (DIC)
- Check bleeding time
- Grouping and cross matching blood
- Give whole fresh blood as needed to correct blood loss and bleeding
tendency (20 ml/kg for children, 2 units in adults)
B. Laboratory
Blood glucose
Falls below 2.5 mmol/L (<45 mg/dl)
OR
<3.0 mmol/L (54mg/dl) in
malnourished children
- Ask when last fed. A child will become hypoglycaemic if deprived of
glucose for more than 12 hours
- Give IV 10 or 25% glucose bolus
- Review infusion
- Maintain feeding
Haematocrit
Falls to 12% or below
- Grouping and cross-matching blood
- Give blood transfusion 10 mls/kg body weight of packed cells
- Repeat haemoglobin and haematocrit at regular intervals
- Consider transfusion if in cardiac failure even if Hb is >4g/dl
Haemoglobin
Falls to 4g/dl or below
Parasitaemia
Remains high 2-3 days or remains
positive for >5 days
Parasitaemia commonly remains
at the initial level for 12-24 hours
even if drugs are fully effective
- Take BS for malaria parasites daily until the results are negative
- Review adequacy of antimalarial dosage
- Consider alternative
45
5.9 Non-response to quinine therapy
Non-response to quinine therapy should be suspected if there is:
• Persistence of clinical features of severe malaria
• Failure of clearance of parasites after 5 days of treatment
• Other possible causes of illness which have not been investigated
Patients with malaria who have not responded to quinine therapy should be given
parenteral Artemether.
Dose:
3.2 mg/kg (loading dose) I.M. followed by 1.6 mg/kg I.M. daily for 6 days
5.10 Emergency management of severe malaria
5.10.1 Convulsions
Convulsions are common in children with severe P. falciparum malaria but are relatively
rare in adults. The general principles for the care of patients with convulsions should be as
follows:
• Maintenance of a clear airway
• Monitoring of vital signs: temperature, pulse rate, respiratory rate and blood pressure
• Nurse the patient in a semi-prone position
• Check blood glucose where possible, or give IV dextrose
Anticonvulsant drug
• Diazepam 0.15 mg/ kg (maximum 10 mg for adults.) slow bolus IV injection In children
diazepam rectal route should be used. Give a dose of 0.5-1.0 mg/ kg. Draw the IV
preparation into a small syringe and remove the needle. Insert 5 cm of a nasogastric
tube into the rectum. Inject the diazepam into the nasogastric tube and flush it with 5 ml
of water. If a nasogastric tube is not available, use a syringe without a needle. Hold
buttocks together for few minutes to ensure retention and absorption of the drug.
If convulsions persist after 10 minutes repeat rectal diazepam treatment as above. Should
convulsions continue despite a second dose, give a further dose of rectal diazepam or
phenobarbitone 20 mg/ kg IM or IV after another 10 minutes
Diazepam should not be used in infants below 1 month of age. Instead use phenobarbitone
20mg/kg IM or IV. If convulsions persist, repeat phenobarbitone 10 mg/ kg after 30 minutes
5.10.2 Hypoglycaemia
• Check blood glucose 4 hourly. If blood glucose falls < 2.5 mmol/l or level of
consciousness deteriorates
• In children
o Give 5 mls/kg of 10% dextrose OR 2.5 mls/kg of 25% dextrose as bolus
46
o If 50% dextrose solution is available, it should be diluted to make 25% by adding
an equal volume of water for injection or normal saline
• In adults
o Give 125 mls of 10% dextrose OR 50 mls of 25% dextrose dextrose as bolus
Where dextrose is not available, sugar water should be prepared by mixing 20 gm of sugar
(4-level tea spoons) with 200 ml of clean water. 50 ml of this solution is given ORALLY or
by naso-gastric tube if unconscious
5.10.3 Hypotension
Give colloid fluids (plasma expander) or blood if haemoglobin is less than 5g/dl
5.10.4 Pulmonary oedema
Check for
• Restlessness
• Frothy sputum
• Basal crepitations
• Low oxygen saturation (< 95%)
Give
• Oxygen
• IV frusemide
• Mechanical ventilation may be needed.
5.10.5 Metabolic Acidosis
In malaria patients metabolic acidosis is attributed to lactic acidosis.
Check for
• Respiratory distress, deep and laboured breathing
Give
• Oxygen
• Correct hypovolaemia
47
•
Chapter 6
Anaemia and
malaria
48
CHAPTER 6: ANAEMIA AND MALARIA
6.1 Introduction
Etiology of anaemia in malaria endemic areas is often multi-factorial, with different causes
interacting in a vicious cycle of nutritional deficiencies, infections and inherited red blood
cell disorders. However, malaria remains one of the main contributors.
Anaemia is a major cause of the high morbidity and mortality associated with malaria. It is
especially serious in young children and pregnant women. In the IMCI evaluation in
Kilombero, Ulanga, Rufiji and Morogoro rural
9
it was found that 87% of children <5 years
had an Hb <11 g/dl, 39% had an Hb <8 g/dl and 3% had an Hb <5 g/dl. About 60% of
anaemia in infants is due to malaria and 30% is due to iron deficiency
10
.
6.2 Definition
Anaemia is defined as reduction of red blood cells or haemoglobin (Hb) concentration or
both below the normal range for the age and sex of the individual (see table 12).
Anaemia due to malaria is usually normocytic and normochromic in nature. During the
course of malaria infection, red blood cells are destroyed. Anaemia can result from
repeated or persistent malaria infections, which may result from inadequate treatment,
parasite resistance or no treatment at all. Anaemia due to malaria may develop rapidly
following an acute malaria attack or insidiously over a period of time.
Table 12: Normal Haemoglobin concentration levels by ages and sex
Category Hb g/dl
Newborn
13.5 - 20
Children less than 6 years
11 - 13
Adult females, not pregnant
12 - 16
Adult females, pregnant
11 - 15
Adult males
13 - 17
The various mechanisms by which malaria may cause anaemia include:
• Haemolysis of parasitised and nonparasitised red blood cells (RBC)
• Enhanced splenic uptake of RBC
• Dyserythr opoiesis or impaired red blood cell production
• Unexplained massive intravascular haemolysis (blackwater fever) may complicate some
infections
9 Schellenberg D, Armstrong Schellenberg JA, Mushi A, de Savigny D, Mgalula L, Mbuya C, Victora C. The Silent Burden of Anaemia in Tanzanian Children: a
Community-based Study. Bull WHO 2003:81(8);581-590
10
Menendez C, Kahigwa E, Hirt R, Vounatsou P, Aponte J, Font F, Acosta C, Galindo C, Kimario J, Urassa H, Brabin B, Smith T, Kitua A, Tanner A, Alonso P.
Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants.
The Lancet 1997; 350: 844-850.
49
For this reason, an understanding of the association between malaria and anaemia is
essential. Effective treatment of both conditions is important in reducing the burden of
morbidity and mortality due to malaria and anaemia.
6.3 Clinical presentation of anaemia
In areas of high malaria endemicity the association between malaria and anaemia is strong.
However, patients presenting with anaemia and malaria are frequently not treated correctly
because their symptoms and signs are often missed. All patients, especially pregnant
women and young children, presenting to health facilities with malaria should be checked
carefully for anaemia.
Ask for (symptoms):
• Easy fatigue/easy tiring
• Inability to feed and drink (Infants and children)
• Dizziness and breathlessness on exertion in pregnant women
• History of eating soil (especially in children or pregnant women)
Look for (signs):
• Pallor (palms, soles, nails beds, conjunctivae and tongue)
• Signs of respiratory distress (nasal flaring, chest indrawing and deep breathing or
grunting)
• Signs of congestive heart failure (dyspnoea, tachycardia, gallop rhythm, basal
crepitations, oedema, puffy eyes, raised jugular venous pressure and enlarged tender
liver)
6.4 Classification of anaemia according to severity
Mild/moderate anaemia, Hb 7-11 g/dl
• Some pallor
Severe anaemia, Hb <7 g/dl
• Severe palmar pallor
• Excessive tiring
• Dyspnoea or breathlessness
• Warm hands
• Peripheral oedema: Pedal pitting
• Tachycardia, collapsing pulse, wide pulse pressure and gallop rhythm.
• Ejection systolic murmur (‘flow’ murmur)
Life threatening anaemia, Hb<5g/dl
• Respiratory distress
o Nasal flaring
o Chest indrawing
o Deep breathing or grunting
• Congestive heart failure
o Pulmonary oedema: basal crepitations
50
o Peripheral oedema: pedal, periorbital, sacral.
o Circulatory congestion: raised jugular venous pressure and enlarged tender liver
o Tachycardia
o Gallop rhythm
6.5 Management of life threatening anaemia (Hb < 5g/dl) associated with malaria
Features
• Respiratory distress
• Congestive heart failure
Treatment
This is a medical emergency.
• Admit the patient
• Treat malaria as severe malaria with parenteral anti malarials (see management of
severe malaria)
• Prop the patient up with pillows or clothing
• Administer oxygen 2.5 L/min to improve oxygen delivery
• Draw blood for grouping and cross matching
Make an effort to have 24 hours access to laboratory estimation of Hb before transfusing –
if not feasible consider rapid tests for Hb estimation (e.g. WHO Haemoglobin colour scale)
to guide decisions on transfusion
Indications for urgent blood transfusion
• Hb equal or less than 4 g/dl and/or
• Signs of heart failure
• Signs of respiratory distress
Administration of blood
• Use packed cell (10 ml/kg in children) or whole blood 20 ml/kg body weight
• Transfuse slowly (4-6 hours per unit)
Drip: drops/min = volume to be transfused in ml x 20(or 15) drop factor_
time of transfusion in hours (4-6 hours) x 60 minutes
1ml whole blood= 20 drops
1ml packed cell= 15 drops
• Where blood is not available, give pre-referral treatment and refer urgently to a health
facility with blood transfusion services.
• Diuretics: Frusemide (IV/IM) for an adult 40 mg or 1 mg/kg bodyweight for children
Children with malarial anaemia are hypovolaemic
Follow-up after discharge
• Start folic acid and ferrous sulphate (do not give ferrous to sickle cell patients)
51
• Review after 14 days to check on haemoglobin or haematocrit level.
• Continue treatment for at least three months
• Encourage patients to protect themselves from being bitten by mosquitoes by sleeping
under an Insecticide Treated Net (ITN)
6.6 Management of severe anaemia (Hb 5 up to 7g/dl) associated with malaria
Features
• Severe palmar pallor, excessive tiring, dyspnoea or breathlessness, warm hands,
peripheral oedema, pedal pitting, tachycardia, collapsing pulse, wide pulse pressure
and gallop rhythm, ejection systolic murmur (‘flow’ murmur)
Management
This condition can be managed as an outpatient with close monitoring OR can be admitted
depending on the severity of the above features
• Treat malaria
• Perform full blood count to investigate morphological type
• Do other investigations to identify other underlying causes of anaemia e.g. stool sample
for hookworm and treat accordingly
• Give oral haematenics for at least three months
• Advise to return immediately if condition worsens
• Follow up after 15 days
6.7 Management of mild/moderate anaemia (7 up to 11 g/dl) associated with malaria
Features
• Some pallor, body weakness
Management
Patients with some pallor or moderate anaemia (Hb >7g/dl) need to be treated for malaria,
as persistent parasitaemia is a cause of anaemia by dyserythropoiesis and haemolysis.
Iron and folic acid speed up haematological recovery after malaria and should be given at
least for three months. It is also important to treat hookworm infestation in children, as this
is a common cause of iron deficiency anaemia.
Folic acid tablets administration
• Start a 3 months treatment course (5 mg daily)
Ferrous sulphate tablets administration
• Start a three months course at dose of 6 mg/kg of elemental iron daily
• Adults need 200mg ferrous sulphate (one tablet) three times daily
6.8 Management of anaemia associated with malaria in pregnancy
• In anaemic pregnant women, even if there are no signs or symptoms of malaria, give an
effective antimalarial appropriate for the gestational age. (see chapter 7)
52
Chapter 7
Management
of malaria in
pregnancy
53
CHAPTER 7: MANAGEMENT OF MALARIA IN PREGNANCY
7.1 Introduction
Pregnant women have a high risk of peripheral parasitaemia and placental malaria. In sub-
Saharan Africa close to 45% of pregnant women have malaria infection during pregnancy
11
and almost half of women who are pregnant for the first time (primigravidae) will be
parasitaemic on their first antenatal visit
12
. They also suffer from a higher number of clinical
malaria attacks than non-pregnant women. Malaria infection during pregnancy is often
asymptomatic. However, in primigravidae malaria tends to be more frequent and the
attacks are more severe. Infection with P. falciparum during pregnancy results in a wide
range of adverse consequences for the pregnant woman, developing foetus and the
newborn. Pregnant women, especially primigravidae, are more susceptible to malarial
infection than non-pregnant women.
7.2 Effects of pregnancy on malaria
During pregnancy the naturally acquired partial immunity to malaria declines. The decline in
immunity is most pronounced during the first and second pregnancy. The reasons for the
decline in immunity is yet undetermined.
7.3 Effects of malaria on pregnancy
Malaria is an important cause of morbidity and mortality for the pregnant woman, the foetus
and the newborn. The effects of malaria in pregnancy are related to the malaria endemicity,
with abortion more common in areas of low endemicity and intrauterine growth retardation
more common in areas of high endemicity.
Table 13: Effects of malaria on morbidity and mortality among pregnant woman, foetus and
newborn
Pregnant Woman
Foetus
Newborn
Morbidity
Severe malaria (*)
Intrauterine growth
retardation
Low birth weight
Anaemia
Congenital Infection
Prematurity
Premature labour
Congenital /neonatal
malaria
Hypoglycaemia
Mortality
Severe malaria (*)
Abortion
Low birth weight
Severe anaemia
Stillbirth
Prematurity
Congenital malaria
Congenital /neonatal
malaria
(*) especially cerebral malaria and pulmonary oedema
11 Steketee (1996), Malaria treatment and prevention in rural Malawi, American Journal of Tropical Medicine and Higyene, 55 (1 Suppl):8-16
12 Menendez C. (1995), Malaria during Pregnancy, Parasitology Today 11(5): 178-183
54
7.4 Management of malaria in pregnancy
Early diagnosis and effective case management of malaria illness in pregnant women is
crucial in preventing the progression of uncomplicated malaria to severe disease and
death.
7.5 Uncomplicated malaria in pregnancy
7.5.1 Clinical features of uncomplicated malaria
The clinical presentation of malaria during pregnancy is often hidden. Some pregnant
women will present with the typical features of uncomplicated and/or severe malaria (see
chapters 4 and 5). However in others, anaemia may be the only recognizable clinical
feature.
7.5.2 Management of uncomplicated malaria
During history taking and physical examination, it is particularly important to elicit signs and
symptoms of severe malaria. Whenever malaria is suspected, laboratory confirmation of
malaria parasites should be performed if possible. If laboratory facilities are not available,
treatment should be started on the basis of clinical presentation. If a laboratory is present, a
negative result does not rule out malaria. RDTs have an added value, as they can be
positive even if parasites are hidden in the placenta.
Quinine is safe in pregnancy. In therapeutic doses it does not induce labour. Uterine
contractions and foetal distress with the use of quinine may be attributable to fever and
effects of malaria disease.
Presently, Artemisinin derivatives cannot be recommended for treatment of malaria in the
first trimester of pregnancy. However, they should not be withheld if treatment is considered
to be life saving for the mother and other antimalarial are considered to be unsuitable.
Artemether-lumefantrine (ALu) is not recommended during pregnancy in the first trimester.
During the first trimester of pregnancy quinine should be used as drug of choice for
treatment of uncomplicated malaria.
During the second and third trimesters of pregnancy Artemether-Lumefantrine should be
used as drug of choice for treatment of uncomplicated malaria
7.6 Severe malaria in pregnancy
7.6.1 Clinical features of severe malaria in pregnancy
Pregnant women infected with malaria are more susceptible to develop severe malaria.
They commonly present with the following features:
55
• high fever
• hyperparasitemia
• low blood sugar
• severe haemolytic anaemia
• cerebral malaria
• pulmonary oedema
7.6.2 Management of severe malaria in pregnancy
The management of severe malaria in pregnant women does not differ from the
management of severe malaria in other adult patients (see chapter 5).
The drug of choice for treatment of severe malaria is intravenous quinine. The dose is
10mg quinine dihydrochloride salt/kg body weight given by infusion in 5% dextrose over
four hours, repeated every eight hours
Infusion should be discontinued as soon as the patient is able to take medication orally.
Give quinine tablets 10mg/kg body weight every 8 hours to complete treatment up to
seven days. N.B. Do not exceed 600mg per dose.
Blood smear for malaria parasites should be taken daily until negative. Review adequacy of
antimalarial dosage. Consider alternative or give additional drug if parasitaemia and/or
clinical signs persist (see chapter 5).
The risk of quinine induced hypoglycaemia is greater in pregnant than non-pregnant
women. Blood sugar should be monitored regularly and if falls below 2.5 mmol/L (< 45
mg/dl) give IV 10% or 25% dextrose.
While the patient is on IV Quinine treatment, pay particular attention to the feeding of the
patient.
7.7 Anaemia associated with malaria in pregnancy
Pregnant woman with haemoglobin level (Hb) <11 g/dl (or haematocrit <33%) is considered
anaemic. In Tanzania, prevalence of anaemia in pregnant women ranges from 23% in
malaria low transmission areas
13
to 82%in malaria high transmission areas
14
. The etiology
of anaemia in pregnancy is multifactorial. In primigravidae, malaria is the major contributor
to anaemia. Malaria infection in pregnancy worsens the pre existing anaemia. Anaemia
increases the risks of maternal mortality, especially in the face of complications such as
abortion and haemorrhage and can be a direct cause of mortality due to cardiac failure.
Anaemia can also contribute to stillbirth and low birth weight.
In Tanzania the major causes of anaemia in pregnancy are:
13 Hinderaker SG et al.: Anaemia in pregnancy in the highlands of Tanzania. Acta Obstet Gynecol Scand 2001, 80:18-26
14 Marchant T et al.: Socially marketed insecticide-treated nets improve malaria and anaemia in pregnancy in southern Tanzania. Trop Med Int Health 2002, 7:149-158
56
• Malaria
• Hookworm and schistosomiasis infection (due to increased blood loss).
• Iron and folate deficiency (due to poor dietary intake and increased demand due to
pregnancy)
• Chronic infection including TB, HIV/AIDS
• Deliveries at short intervals (less than 3 years)
There are three approaches for addressing the maternal anaemia problem:
• Early diagnosis
• Treatment
• Prevention
7.7.1 Management of mild/moderate anaemia (Hb 7 up to 11 g/dl) in pregnancy
• Perform appropriate investigations (BS, peripheral blood film, stool examination, RBC
indices, urinalysis)
• Treat the cause of anaemia if determined
• Give the following drugs
o Full course of oral quinine in the first trimester or ALu in second and third
trimesters
o Iron: Give orally 200mg ferrous sulphate three times a day
o Folic Acid 5 mg daily
o Antihelminthics (e.g. mebendazole from second trimester)
o Treat schistosomiasis if the patient lives in areas with high schistosomia sis
transmission (after delivery)
• Monitor response to treatment
o Clinical response
o Hb measurement is recommended every 2 weeks until Hb reaches 11 g/dl
o Reticulocyte count
For non-responding patients other investigations should be considered e.g. bone marrow
aspiration.
7.7.2 Management of severe anaemia (Hb < 7g/dl) in pregnancy
Severe anaemia has to be aggressively treated before the woman goes into labour. During
labour a patient may go into cardiac failure because of the increased work of the heart.
Likewise, the shunting of the blood to the circulation from the placental bed after delivery,
may overload the circulation and precipitate cardiac failure.
Aims of treatment
• Correct anaemia and improve Hb concentration to a safe level (> 7 g/dl) before the
patient goes into labour
• Avert congestive cardiac failure by increasing the oxygen carrying capacity
Management of severe anaemia
57
Gestational age should determine the appropriate approach for the management of severe
anaemia in pregnancy. Before 36 weeks of gestational age if the patient is not in cardiac
failure the treatment should be as for the moderate anaemia (see section 7.7.1). If in failure
and after 36 weeks of gestational age with or without failure:
• Treat the cause if determined
• Give blood transfusion (preferably packed cells)
• Continue with iron and folic acid up to 3 months after delivery
• Follow up the patient every 2 weeks until Hb reaches 11 gr/dl
7.7.3 Prevention of anaemia
Antenatal Clinic
• Combined ferrous sulphate 200mg + folic acid 0.25mg (FeFo) once or twice daily
• Intermittent Preventive Treatment in the second and third trimester
• Early detection of anaemia
o Hb screening
o Symptom sign surveillance
• De-worming as indicated in the focused antenatal care (FANC)
• Treat any underlying infection
All women should be advised on appropriate diet during pregnancy and on personal
malaria protection using insecticide treated nets (ITN).
7.8 Prevention of malaria during pregnancy
Controlling the effects of malaria infection on the pregnant woman and the foetus requires a
balanced programme of effective case management of malaria illness and prevention of the
consequences of asymptomatic infection. Evidence based effective preventive
interventions are required. These interventions consist of intermittent preventive treatment
and use of insecticide treated nets.
7.8.1 Intermittent preventive treatment (IPT)
Intermittent preventive treatment is the administration of drug therapy in full therapeutic
doses at predetermined intervals during pregnancy even if individuals have no signs of
malaria. IPT should not be considered as chemoprophylaxis; the woman is not protected
from infection and still could be infected after taking SP for IPT.
The drug of choice for IPT is Sulfadoxine/Pyrimethamine (SP).
SP remains the drug of choice for IPT even though it is no longer the first line drug for
malaria treatment. This is because the aim of IPT is to prevent the worst effects of malaria
infection in pregnancy
15
rather than to cure a potentially life-threatening illness. As such, a
15 placental parasitaemia, severe anaemia for the mother and low birth weight for the newborn
58
lower efficacy antimalarial is acceptable for IPT than for curative purposes. It is particularly
important that drugs used in pregnancy are known to be safe. It is also likely that drugs with
a long half-life are the most effective when used as IPT.
The first IPT dose is administered between 20-24 weeks of gestational age. The second
IPT dose should be administered at 28-32 weeks.
IPT should be administered as direct observed treatment (DOT) during an antenatal care
visit
If malaria is diagnosed after administration of IPT with SP a full treatment with antimalarials
should be given according to the guidelines (see section 7.5.2).
IPT is not a contraindication to tetanus toxoid injection and the two can be administered
simultaneously.
Pregnant women who are known to have hypersensitivity to sulfonamides (most commonly
skin rashes) should not receive SP for IPT. Neither Quinine, nor Artemether-lumefantrine
(ALu) should be used for IPT. Currently there is no other recommended alternative drugs
for IPT apart from SP.
7.8.2 Insecticide Treated Net
• Pregnant women should be advised to sleep under Insecticide Treated Nets (ITNs) at
night and to take other personal protective measures to reduce contact with mosquitoes
• Mothers should be encouraged to protect their newborn infants with Insecticide Treated
Nets (ITNs)
59
Chapter 8
Management
of malaria in
the neonate
and infants
below 5 kg
60
CHAPTER 8: MANAGEMENT OF MALARIA IN THE NEONATE
AND INFANTS BELOW 5 KG
8.1 Introduction
Malaria in the neonate (first four weeks of life) is very rare: in Muhimbili Neonatal Unit the
incidence of congenital malaria in hospitalised newborn is 3/100,000
16
. Congenital or
acquired malaria in this age group is life threatening and requires immediate treatment. The
signs and symptoms resemble those seen in the newborn with septicaemia. Quinine
remains the drug of choice for treatment.
8.2 Clinical features
The clinical features of malaria in the newborn include:
• Fever
• Lethargy
• Unable to breastfeed
• Vomiting
• Irritability
• Respiratory distress
• Seizures
• Jaundice
• Pallor
• Hepatosplenomegaly
Laboratory findings will include the presence of malaria parasites, hyperbilirubinaemia,
anaemia (Hb<13.5 g/dl), hypoglycaemia and acidosis.
8.3 Management of neonatal malaria
• Neonates with suspected malaria should be admitted to the hospital immediately as
they can deteriorate quickly and die at home.
• Symptoms and signs of neonatal malaria mimic serious bacterial infection. Therefore,
thorough investigation should be done.
Assessment and resuscitation
• Airway: ensure airway is open
• Breathing: ensure there is adequate respiratory movements, give oxygen if there is
cyanosis
• Circulation: measure pulse rate
16 A.Masawe, personal communication
61
Investigations
The following investigations should be done:
FBP, blood sugar, blood culture and sensitivity, blood slide for malaria parasite, serum
electrolytes.
Treatment
• Broad spectrum antibiotic as provided in the Standard Treatment Guidelines (STG)
• Parenteral quinine 10mg/kg 8 – 12hourly till the baby is able to breast-feed, then oral
quinine is given to complete 7days treatment
• If a neonate is not able to breast feed, give 10% glucose IV 60ml/kg/24hours
• Give blood transfusion if HB is <10g/dl
Nursing care and monitoring
• Monitor vital signs (PR, RR & Temperature)
• Monitor input/output
• Check BS for malaria parasite daily
• Ensure feeding
• Advise on use of ITNs
8.4 Management of malaria in infants below two months and below five
Kg
Malaria is quite uncommon in infants below 2 months of age. Since Artemether-
Lumefantrine is currently not recommended for infants below 5 Kg, quinine is the drug of
choice in this category.
62
Chapter 9
Malaria and
HIV co-
infection
63
CHAPTER 9: MALARIA AND HIV CO-INFECTION
9.1 Introduction
Malaria and HIV infections are both endemic in Tanzania and co–infection is common. The
two diseases are the most important health problems in the country, being the leading
causes of morbidity and mortality.
HIV infection/AIDS reduces immunity to malaria resulting in more frequent and severe
infections. On the other hand, malaria enhances progression of HIV infection to AIDS and
increases its severity. Acute malaria episodes temporarily increase viral replication and
hence viral load. The concentrations of HIV–1 RNA in the blood tend to be higher in HIV–
infected individuals with acute malaria illness than in HIV–infected individuals with no
malaria parasites.
9.2 Clinical features of malaria in HIV/AIDS
HIV infection/AIDS increases the risk and severity of malaria. People with HIV/AIDS are
more likely to have symptoms of malaria and higher parasite densities than those without
HIV infection. Symptoms of malaria may be more severe, persistent and even modified in
the presence of HIV infection/AIDS.
9.2.1 Clinical features of uncomplicated malaria in HIV/AIDS
Fever
Fever is a major symptom of both AIDS and malaria. Patients with AIDS often present with
fever, which may be intermittent or continuous. The acute fever due to malaria could be
masked with the prolonged fever of HIV/AIDS. One should always consider a possibility of
malaria in AIDS patients presenting with fever.
Anaemia
Anaemia may be a feature of both AIDS and malaria.
Headache
Headache may be a feature of both AIDS and malaria. However, the other causes of
headache in AIDS patients such as cerebral toxoplasmosis, meningitis and intracranial
tumours should be ruled out.
Other constitutional symptoms
Diarrhoea, joint aches and general body weakness are found in both, AIDS and malaria.
The symptoms tend to be chronic in AIDS and acute in malaria, hence masked in the
background of AIDS.
64
9.2.2 Clinical features of severe malaria in HIV / AIDS
Severe malaria in HIV/AIDS patients frequently presents as cerebral malaria or severe
anaemia.
Cerebral malaria
AIDS patients with cerebral malaria may present with central nervous system
manifestations (CNS) such as altered level of consciousness, prostration and convulsions.
It is important to note that the manifestation of cerebral malaria resembles the CNS
manifestation of HIV/AIDS e.g. convulsions, prostration and coma
Severe malarial anaemia
A patient with severe anaemia due to malaria may present with severe pallor with or
without heart failure.
The presence of severe anaemia in HIV/AIDS patients may reflect an advanced disease or
co-morbidity with malaria
9.3 Diagnosis
Diagnosis should follow the general principles of diagnosis of malaria based on accurate
history taking, complete physical examination and appropriate laboratory tests as in any
other malaria patient.
Consider the possibility of malaria in HIV/AIDS patients presenting with fever, pallor,
headache and the other constitutional symptoms. More extensive work up should be
performed to exclude other infective causes of fever.
In suspected cerebral malaria in a HIV/AIDS patient, emphasis should be put on
cerebrospinal fluid (CSF) examination to rule out other life threatening conditions such as
bacterial and cryptococcal meningitis. When available, a CT scan should be performed to
rule out cerebral toxoplasmosis.
9.4 Treatment of uncomplicated and severe malaria in HIV /AIDS
Treatment of uncomplicated and severe malaria in HIV/AIDS should follow the same
principles of treating uncomplicated and severe malaria. However it should be noted that,
clearance of parasitaemia may not necessarily be accompanied by clearance of symptoms
(fever) due to the presence of other underlying infections. HIV/AIDS infected adults with low
CD4 cell counts may be more susceptible to treatment failure of anti malaria drugs.
9.5 Malaria and HIV/AIDS in pregnancy
HIV infected pregnant women have an increased risk of infection with malaria parasites and
are more likely to develop clinical malaria. Their malaria parasite density is increased
65
compared to non-HIV infected pregnant women and have reduced response to antimalarial
treatment. HIV and malaria co-infected pregnant women are at very high risk of anaemia
and placental malaria. Pregnant women with dual infection have poorer birth outcomes
(foetal loss, pre-term delivery, low birth weight). A considerable proportion of children born
to women with HIV and malaria has low birth weight and are more likely to die during
infancy. Malaria infection during pregnancy may be associated with increased risk of
mother to child transmission (MTCT) of HIV.
9.6 Effect of malaria on HIV infected children
The effects of malaria on HIV infected children include increased risk of illness and
anaemia.
9.7 Prevention
As people living with HIV/AIDS in areas of high transmission are particularly vulnerable to
malaria, their protection by ITN should be of high priority.
HIV positive pregnant women at risk of malaria should always be protected by ITNs.
They should be referred to PMTCT services
According to the stage of HIV infection, pregnant women at risk of malaria should also
receive either IPT with SP (at least 3 doses), or daily co-trimoxazole prophylaxis
17
HIV infected individuals with advanced immunosuppression (CD4 T-cell count ≤ 200µl)
should receive co-trimoxazole prophylaxis until their CD4 count is above 200µl to prevent
them from infections like respiratory tract infections but also malaria
17 Those women on co-trimoxazole prophylaxis should not be taking SP for IPT at the same time, as this would increase the effects of sulphonamide side effects.
66
Chapter 10:
Therapeutic
efficacy of
antimalarial
drugs
67
CHAPTER 10: THERAPEUTIC EFFICACY OF ANTI MALARIAL
DRUGS
10.1 Introduction
The aim of the national malaria treatment guidelines is to offer antimalarials that are highly
effective. The main determinant of policy change is the therapeutic efficacy and the
consequent effectiveness of the antimalarials in use. The primary objective of monitoring
the therapeutic efficacy is to evaluate the sensitivity of the recommended antimalarial
drugs. One way of monitoring the efficacy of currently used drugs for the treatment of
malaria is a close follow-up of treated cases in the health care facilities. This is a
recommended good routine clinical practice in order to timely detect and manage treatment
failures. The second way to monitor the therapeutic efficacy of antimalarial drugs is in vivo
drug sensitivity tests using elaborated scientific protocols
18
.
10.2 Non response to an antimalarial treatment
Where a patient returns between 4 to 14 days after treatment with recommended
antimalarial drug after ruling out other cause of disease complaining of continued
symptoms of malaria, non-response should be considered.
Causes of non-response to antimalarial treatment include:
• Vomiting the drug
• Inadequate dosage
• Fever/symptoms from a cause other than malaria
• Poor quality of the drug
• Parasite resistance to the drug
The clinician can give an indication of treatment failure if the patient has taken the
antimalarial drug appropriately i.e. according to the correct dosage and duration. The
clinician should change the antimalarial drug to the second line treatment according to
national guidelines. If the clinician observes frequent occurrence of suspected non
response to first line antimalarial therapy, he/she should alert relevant authorities.
18 Assessment and Monitoring of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria, WHO 2003
68
10.3 Parasite Resistance to Antimalarial Drugs (in vivo drug sensitivity tests)
Drug resistance in malaria is defined as the ability of parasite strain to survive and/or
multiply despite the administration and absorption of a drug given in doses equal to or
higher than those usually recommended, but within the limit of tolerance of the subject.
A methodology has been developed by WHO where the therapeutic efficacy of antimalarial
drugs can systematically be monitored. However, prescribers in their routine clinical
practice are not expected to engage themselves in this elaborate protocol. In Tanzania
about 10 sentinel sites in different epidemiological settings are regularly performing drug
sensitivity tests using modified WHO protocol. See Table 14.
Table 14: Classification of treatment failures
Test
Days
Danger
Signs
19
Temperature
(> 37.5 °C)
Parasitaemia Outcome
0 – 3
Present
Yes/No
Any positivity
ETF
2
Absent
Yes/No
Positive > D0
ETF
3
Absent
Yes
Any positivity
ETF
3
Absent
No
≥ 25% of D0
EPF
4 -14
Present
Yes/No
Any positivity
LTF
4 -14
Absent
Yes
Any positivity
LTF
4 -14
Absent
No
Any positivity
LPF
4 -14
Absent
Yes/No
No
ACPR
ETF: Early Treatment Failure
EPF: Early Parasitological Failure
LTF: Late Treatment Failure
LPF: Late Parasitological Failure
ACPR: Adequate Clinical and Parasitological Response
D0: Day 0
19 General Danger signs in children include: Vomiting everything, Inability to drink or breast feed, Recent history and/or observed convulsions, Lethargy/impaired
consciousness. General danger signs in adults: Prostration, Change in behaviour (agitation, violence, hallucination, etc), Impaired consciousness, Jaundice
69
Chapter 11
Malaria
chemo
prophylaxis
70
CHAPTER 11: MALARIA CHEMOPROPHYLAXIS
11.1 Introduction
Chemoprophylaxis is the regular use of antimalarial drugs to prevent development of
malaria parasites following any possible inoculation.
11.2 Indication for malaria chemoprophylaxis
Chemoprophylaxis is recommended for use in the following special groups:
• Patients with sickle cell anaemia
• Non-immune travellers
• Non-immune pregnant women
• Hyper Reactive Malaria Splenomegaly (Tropical Splenomegaly Syndrome)
11.3 Common antimalarial used as prophylactic agents
11.3.1 Chemoprophylaxis in patients with sickle cell anaemia
Chloroquine is still recommended until other alternative drugs are available.
Dose
Adult
300 mg base weekly
Children
5 mg base/kg weekly
11.3.2 Chemoprophylaxis for non-immune travelers
Table 15 Drugs indicated for chemoprophylaxis
Indicati
ons
Adult Children Pregnan
cy
Start Finish
Proguanil
Paludrine®
Non-
Immune
Stay >3
months
200 mg
daily
3mg/kg
daily
Yes
1 week
before
4 weeks
after
Mefloquine
Lariam ®
Non-
Immune
Stay <3
months
250 mg
weekly
5 mg/kg
weekly
Avoid
4 weeks
before
4weeks
after
Proguanil/
Atovaquone
Malarone ®
Up to 28
days
1 tab
daily
See table
15
Avoid
1 day
before
1week
after
Doxycycline
Up to 6
months
100 mg
daily
>12
years
Avoid
1week
before
4weeks
after
71
Refer to chapter 14 of these Guidelines for drug information.
Table 16 Atovaquone/Proguanil paediatric dosage
Weight (kg)
Atovaquone/
Proguanil
(Malarone®)
Total
Daily Dose
Dosage Regimen for Prevention of Malaria in
Paediatric Patients
11 up to 20 62.5 mg/25 mg
1 Atovaquone/Proguanil (Malarone ®) Paediatric (¼
Adult strength) tablet as a single dose daily
20 up to 30 125 mg/50 mg
2 Atovaquone/Proguanil (Malarone ®) Paediatric
(1/2 Adult strength) tablet(s) as a single dose daily
30 up to 40 187.5 mg/75 mg
3 Atovaquone/Proguanil (Malarone ®) Paediatric
(3/4 Adult strength) tablet(s) as a single dose daily
40 and above 250 mg/100 mg
4 Atovaquone/Proguanil (Malarone ®) Paediatric (1
adult strength) tablet(s) as a single dose daily
11.3.3 Chemoprophylaxis for non-immune pregnant women
Non-immune pregnant women should ideally not travel to malarious areas unless
absolutely necessary. Proguanil prophylaxis should be taken during the first three months
(first trimester) of pregnancy; mefloquine prophylaxis may be taken from the fourth month
of pregnancy onwards.
Chemoprophylaxis is currently not recommended for pregnant women living in malaria
endemic areas. Instead, intermittent preventive treatment (IPT) is recommended (see
chapter 7).
11.3.4 Chemoprophylaxis for Hyper Reactive Malaria Splenomegaly
Refer the patient to appropriate level of health care in order to exclude other conditions and
for further management.
72
Chapter 12
Malaria
epidemics
73
CHAPTER 12: MALARIA EPIDEMICS
12.1 Introduction
A malaria epidemic is defined as the occurrence of new cases of malaria clearly exceeding
the number expected at that particular time and place
Generally there is an inverse relationship between the usual intensity of malaria
transmission and the risk of epidemics. Unstable malaria transmission areas, such as fringe
highlands and semi arid zones, are prone to malaria epidemics. Factors associated with
unexpected increases in malaria transmission may be man-made (environmental
modification) or natural (climatic). Furthermore, movements of non-immune population to
areas with sustained malaria transmission (refugees, seasonal labourers) and failure of
malaria control measures (impaired antimalarial drug efficacy) may contribute to the
occurrence of outbreaks. According to the above criteria, in Tanzania about 20% of the
districts are classified as malaria epidemic prone and more than 8 million people are living
in those areas. The epidemic prone district in Tanzania are: Mpwapwa, Dodoma, Kongwa
(central zone), Muleba, Karagwe (Kagera), Ngorongoro, Karatu, Lushoto, Babati, Hanang,
Hai, Same (northern highlands), Njombe, Iringa, Kilolo, Mufindi, Makete, Sumbawanga,
Nkasi, Mbozi, Ileje, Rungwe, Ludewa, Mbinga (southern highlands). The last major
epidemics have been reported in Muleba district following the el nino rains in 1997-1998.
High morbidity and mortality usually occurs during an epidemic. In Tanzania the number of
admissions, blood transfusions and deaths during malaria outbreaks have been found to be
4-5 times higher in epidemic than in non-epidemics years respectively.
12.2 Measures to be considered during malaria epidemics
• Improved malaria case management
• Indoor residual house spraying
• Community mobilization and participation
• Community health education about malaria control in the epidemic area
• Enhance use of ITNs
12.3 Malaria diagnosis in the event of malaria epidemics
General principles
Early diagnosis and treatment is key to reducing malaria morbidity and mortality. However,
in epidemic and complex emergency situations, facilities for laboratory diagnosis may be
either unavailable or so overwhelmed with the case-load that parasite-based diagnosis is
impossible. In such circumstances, it is impractical and unnecessary to demonstrate
parasites before treatment in all cases of fever. Once malaria has been confirmed, and if
74
case numbers are high, treatment based solely on the clinical history is appropriate in most
cases, using a full treatment course.
However, parasite-based diagnosis is essential to:
• diagnose and confirm the cause of an epidemic of febrile illness
• confirm the end of an epidemic and
• follow progress in high-risk cases, e.g. severe malaria.
It would also be useful to diagnose a proportion of cases parasitologically during the
epidemic, to monitor the Slide Positivity Rate (SPR). As the epidemic wanes, the proportion
of fever cases investigated for parasites can be increased. It is important to monitor the
clinical response to treatment wherever possible; bearing in mind that other causes of fever
may be involved.
Use of rapid diagnostic tests in epidemic situations
Rapid diagnostic tests (RDTs) offer the advantage of simplicity and speed in epidemic
situations. Current experience with RDTs indicates that:
• they are useful for confirming the cause and end-point of malaria epidemics;
• they should not be relied on as the sole basis for treatment;
• they should be backed up with adequate quality assurance, including temperature
stability and testing
• negative test results should not preclude treatment.
If RDTs are used, transport and storage should be based on the following principles:
• Avoid heat exposure, e.g. at airports and in vehicles.
• Ensure that stockpiles are stored in central locations that are kept as cool as possible
(e.g. air conditioned areas) in readiness for an outbreak, with quality testing every few
months to ensure that RDTs remain in good condition. Proper storage extends the
shelf-life.
• Seek to maximize the length of time for which RDTs are kept under such conditions
before rapidly deploying them to the field for short-term use.
• Consider simple methods to reduce the temperature at outlying sites (e.g. evaporative
cooling, thatched roofs).
12.4 Disease management in the event of malaria epidemics
12.4.1 Managing uncomplicated malaria cases
Malaria epidemics are emergencies in which populations at risk in epidemic-prone areas
are mainly non-immune or only partially immune. The blood schizonticidal drug to be used
in epidemics (and complex emergencies) must therefore be highly efficacious (> 95% cure),
be safe and offer good patient compliance. Therefore uncomplicated malaria should be
managed with Artemether-lumefantrine (see chapter 4). Complete treatment doses should
always be given in all circumstances.
75
12.4.2 Managing severe malaria
Management of severe malaria in epidemic situations will often take place in temporary
clinics or situations in which staff shortages and high workloads make intensive care
monitoring difficult.
Drug treatment should therefore be as safe as possible, with simple dosing schedules and
a minimum need for monitoring.
The efficacy of intravenous (IV) quinine and intramuscular (IM) artemether are similar under
hospital conditions. However, due to the complicated dosing regimen of IV Quinine, then IM
Artemether is the drug of choice for severe malaria in most epidemic situations.
Dosing schedule for IM Artemether
3.2 mg/kg bodyweight (loading dose) IM followed by 1.6 mg/kg bodyweight IM daily for 6
days
12.5 Preparedness
…
12.5.1 Monitoring drug resistance
In epidemics and complex emergencies there is no opportunity to monitor drug efficacy.
Drug resistance monitoring must be an integral part of preparedness plans and actions.
12.5.2 Central stocks of supplies and equipment
It is essential to ensure that adequate supplies of diagnostics and antimalarial drugs are
available by establishing and maintaining stocks at National and District level to deal with
the eventuality of an epidemic. These stocks will need to be continuously rotated to ensure
that commodity shelf-lives do not expire. Replenishment assumes prompt release,
transport and customs clearance of commodities (if required).
12.5.3 Prevention of malaria during epidemics
During malaria ep idemics there is an increased risk of malaria infection for the whole
population. Therefore, all the population should be protected by ITNs and other personal
protection measures.
76
Chapter 13
Public health
education on
malaria case
management
77
CHAPTER 13: PUBLIC HEALTH EDUCATION ON MALARIA CASE
MANAGEMENT
13.1 Introduction
Health education is the part of health care that is concerned with creating awareness and
promoting appropriate health behaviour. Health education should encourage behaviours
that promote health, prevent illness, cure disease and facilitate rehabilitation. Through
health education, people should gain a better understanding of how their own behaviour
may affect their health.
Health education has an important role to play in bringing about the desired changes in
human behaviour, especially early diagnosis and treatment for children under five years of
age
20
, because:
• What individuals do when they have fever or other symptoms suggestive of malaria will
largely determine the progression of the disease
• What parents/caretakers do to their children when they have features of severe malaria
(e.g. convulsions or anaemia) will largely determine the eventual outcome
• What individuals, families and communities do to protect themselves against mosquito
bites, (e.g. use of ITN and reduction of mosquitoes breeding sites), will influence the risk
of infection
13.2 Health education for malaria diagnosis and treatment
Health education is important to ensure a correct malaria case management. Therefore, all
stakeholders should consider the following:
• Education on early recognition of symptoms and signs of malaria
• Education for demand of better services at health facility level
• Education on signs and symptoms of severe malaria
• Promotion of early and appropriate health care seeking behaviour
• Promotion of prompt and effective action for treatment and care of suspected cases of
malaria
• Promotion of appropriate referral system for severe cases of malaria and treatment
failures
20 Since the progression towards severe and fatal disease is rapid, especially in children under five years of age, it is recommended that diagnosis and treatment of
uncomplicated malaria should be done within 24 hours from the onset of symptoms.
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13.3 The role of health service providers in promoting appropriate malaria case
management and preventive measures
Health workers at all levels of care should ensure that health education is given to all
patients/caretakers using the following measures:
• Education on continued feeding and fluid intake during illness, especially in children
under five years old
• Education on compliance with medical treatment
• Education on side effects of the drugs if any
• Education on when the patient should return for follow-up
• Education on when the patient should return immediately
• Promotion of personal protective measures such as the use of insecticide treated nets,
repellants and environmental manipulation and management.
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Chapter 14
Other
antimalarial
drugs available
in Tanzania
80
CHAPTER 14: OTHER ANTIMALARIAL DRUGS AVAILABLE IN
TANZANIA
14.1 Introduction
The Ministry of Health, public and private health care providers and the community have a
collective responsibility to apply standardized treatment protocols to maximize the
usefulness of the few antimalarial drugs that are available and retard the development of
parasite drug resistance. Therefore, this chapter provides information on antimalarial drugs
already registered in Tanzania as of 2005.
It is necessary that health care providers should make themselves aware of the range,
rational use and safety of the antimalarial drugs registered and available and limit their use
accordingly.
Some of the drug formulations described in this chapter are monotherapies. Their
use is discouraged to minimize the risk of developing parasite resistance. However
they have been retained during the transition period from mono to combination
therapy. They will be withdrawn from use when the supply of combination drugs will
be optimal.
14.2 Antimalarial mono-therapies or single component of combination therapies
14.2.1 Artemisinin and its derivatives
These are potent and rapidly acting blood schizonticides and gametocides. They are
effective against malaria parasites including multi-resistant strains of P.falciparum. They
are generally very safe drugs and are well tolerated.
Indications
• All forms of malaria including severe P.falciparum malaria resistant to quinine
• Malaria due to multi-drug resistant strains of P.falciparum
Contraindications
• They should not be used with drugs which cause QT interval prolongation e.g.
quinidine, halofantrin etc
• They should not be used with neuroleptics, and erythromycin
Use in pregnancy and lactation
Artemisinin and its derivatives can be used during the second and third trimester of
pregnancy in areas of multi-drug resistance if there is no other effective treatment available.
Their use in the first trimester of pregnancy is not recommended.
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Adverse effects
They are generally well tolerated but there have been documented cases of nausea,
vomiting, itching and fever. In addition abnormal bleeding and dark urine have occasionally
been documented as well as minor cardiac changes (non specific S-T changes and first
degree A-V block). These return to normal after improvement of malaria symptoms.
Available formulations
• Dihydroartemisinin: available as tablets of 50 mg and 60 mg and powder for
suspension 160 mg/80 mls. Dose: 4 mg/kg divided in two doses administered on the
first day followed by 2 mg/kg once a day for 5 days
• Artesunate: available as tablets/capsules (50 mg, 100 mg and 200 mg). Dose: 4 mg/kg
divided in two doses administered on the first day followed by 2 mg/kg once a day for 5
days
• Artemether: available as capsules (40 mg), powder for suspension (300 mg/100 mls)
and injectable (80 mg/ml). Oral dose: first day, 4mg/kg bodyweight twice, day 2 to day 5
2mg/kg bodyweight daily. Injectable 3.2 mg/kg bodyweight loading dose IM, 1.6 mg/kg
IM daily for 6 days
•
β
-Artemether: available as capsules (20 mg, 40 mg, 50 mg), and injectable (20 mg/ml
and 80 mg/ml)
14.2.2 Sulfadoxine/Pyrimethamine,
This is a synergistic combination of antifolate drugs. The combination is a highly active
blood schizonticide against P.falciparum. It is rapidly absorbed from the gut following oral
administration. The plasma half-life of pyrimethamine is about 4 days and that of
sulfadoxine is about 8 days.
Available formulations
• Tablets: Sulfadoxine 500 mg with pyrimethamine 25 mg.
• Injectable Sulfadoxine/Pyrimethamine (There are no clear therapeutic benefits of using
parenteral over oral formulations of SP)
Indications
Intermittent Preventive Treatment in pregnancy (IPT)
Contraindications:
History of Sulfonamide hypersensitivity
Adverse effects of Sulfadoxine/pyrimethamine (SP)
These may include skin reactions, which in some cases may be severe in the form of
Steven-Johnson syndrome (erythema multiforme major) or toxic epidermal necrolysis. This
is quite rare but can be fatal. Very rarely bone marrow suppression can occur and
haemolysis in G6PD–deficient individuals may be seen.
Steven-Johnson syndrome
