2009 Malaria Guideline

GUIDELINES FOR THE
TREATMENT OF MALARIA
IN
SOUTH AFRICA
2009
TABLE OF CONTENTS
Preface
iii
Acknowledgem ents
iv
Abbreviations
Summary
vi
Treatment of Malaria in South Africa - Summ ary Flowchart 2007
vii
1. Introduction
2. Objectives
3. Parasite species
4. Risk groups
5. Clinical presentation and diagnosis

5.1 Sym ptoms and s igns
5.2 Laboratory diagnosis
5.2 Referral criteria
3
3
5
6
6. Treatment
6.1 Uncomplicated Plasmodium falciparum m alaria
6.1.1 Chemotherapy
6.1.2 General m anagement
6.1.3 Drugs us ed in the treatment of Plasm odium falciparum m alaria
6.1.3.1 Artem is inin-bas ed com bination therapy
6.1.3.2 Quinine
6.1.4 Treatm ents not recomm ended for falciparum malaria
6.2 Treatment of non-Plasm odium falciparum infections
6.3 Treatment of mixed Plasmodium s pecies infections
6.4 Treatment during pregnancy
6.4.1 Diagnos is of m alaria in pregnancy
6.4.2 Managem ent of uncomplicated malaria in pregnancy
6.4.3 Managem ent of severe malaria in pregnancy
6.5 Treatm ent of infants and young children
6.5.1 Managing uncom plicated (non-severe) m alaria in young children
6.5.2 Managing severe malaria in young children
6.6 Malaria and HIV
8
8
8
9
11
11
12
13
14
15
15
16
16
17
18
18
19
20
ii
7. Severe malaria
7.1 Features indicating severe m alaria
7.2 Treatm ent
7.3 Chemotherapy
7.4 Loading doses
7.5 Maintenance dos es
7.6 Other chemotherapeutic options
7.7 General m anagement pf severe m alaria
7.8 Complications
7.8.1 Anaem ia
7.8.2 Hypoglycaemia
7.8.3 Cerebral m alaria
7.8.4 Renal failure
7.8.5 Circulatory collapse
7.8.6 Metabolic acidos is
7.8.7 Res piratory com plications
7.8.8 Hepatic dysfunction
7.8.9 Diss em inated intravas cular coagulation (DIC)
7.8.10 Secondary infections
7.8.11 Hyperparasitaem ia
7.8.12 Malarial haem oglobinuria
7.8.13 Exchange trans fusion
7.8.14 Splenic rupture
22
22
24
24
25
25
26
26
28
28
28
29
30
30
31
32
33
33
33
34
35
35
35
8. References
37
9. Dosage guidelines for the treatment of malaria
42
10. Summary of malaria treatment guidelines
45
11. Malaria risk map for South Africa
47
iii
PREFACE
Cons iderable s uccess has been achieved in the control and m anagement of malaria in South
Africa in recent years . This is des pite the ongoing development of paras ite and vector
resis tance to drugs and insecticides , res pectively.
It gives me great pleas ure to introduce these guidelines on the treatm ent of m alaria in South
Africa.
The objectives of thes e publications are to provide all those involved in the m anagement of
m alaria with clear and practical guidelines for the diagnosis and appropriate treatment of
m alaria.
The intended treatment outcomes are the prevention of m alaria morbidity and mortality. In
addition the recommendations are intended to contribute to a reduced malaria transmiss ion
and to lim it res is tance to anti-m alarial drugs .
These guidelines are bas ed on the World Health Organizations guidelines for the treatment
of m alaria. Additional literature surveys have been undertaken. Factors that were cons id ered
in the choice of therapeutic options included: effectiveness, s afety, and im pact on malaria
transmiss ion and on the emergence and s pread of anti-m alarial res is tance.
The previous guidelines were compiled in Augus t 2002. Advances in the availability of antim alarial drugs and changes in res pect of transm iss ion, intens ity, drug resis tance and health
care delivery in South Africa have prom pted revis ion of thes e guidelines .
It is hoped thes e guidelines will facilitate effective, appropriate and timeous treatm ent of
m alaria, thereby reducing the burden of this diseas e in our communities and in South Africa.
--------------------------------------Ms B Hogan, MP
Minis ter of Health
Date:
iv
ACKNOWLEDGEMENTS
The National Departm ent of Health (DOH) and the National Malaria Advis ory Group (MAG)
initiated these revised treatment guidelines . Without the contribution of the key pers ons
m entioned below, thes e updated guidelines would not have become a reality. Thes e pers ons
include:
Dr Lucille Blum berg, National Ins titute for Communicable Dis eases, National Health
Laboratory Services; Prof Karen Barnes, Departm ent of Clinical Pharm acology, University of
Cape Town, Dr Cornelia Duvenage, Departm ent of Internal Medicine, 1 Military Hos pital;
Dr Jan van den Ende (MAG Chairperson), Drs Martin and Sim Inc and Toga Laboratories ;
Dr Etienne Immelm an, Department of Health, KwaZulu Natal, Dr Gerhard Swart, Department
of Health and Social Services , Mpum alanga Province, Dr Frank Hans ford, Department of
Health (SCAT Chairpers on); Mrs Lee Baker, Medicines Inform ation Cons ultant, Am aye za
Information Centre.
DOH officials: Dr Bonnie Maloba, Communicable Diseas e Control (CDC), Mr Devanand

Moonasar (CDC), Ms Tsakani Furum ele (CDC), Dr. Eunice Mis iani (CDC), Dr. Frew Bens on
(CDC), Ms Helecine Zeeman (Pharm acy Programm es and Planning),
Mrs Nerine Willers (CDC) and Ms Mary Anne Groepe (WHO, South Africa)
Furthermore, I would like to express m y gratitude to those persons who reviewed the
guidelin es . Thes e pers ons include: Associate Professor John Frean, National Ins titute for
Communicable Dis eas es , National Health Laboratory Services and Profess or Gary Maartens ,
Departm ent of Clinical Pharmacolo gy, Univers ity of Cape Town.
---------------------------------------------------Mr T Ms eleku
Director-General: Departm ent of Health
ABBREVIATIONS
ACT
Artem isinin-based com bination therapy
ARDS
Acute res piratory distress syndrome
CDC
Communicable Diseas e Control
CNS
Central nervous s ystem
CVP
Central venous press ure
DIC
Diss eminated intravas cular coagulation
KZN
KwaZulu-Natal
NSAIDS
Non-s teroidal anti-inflamm atory drugs
RDT
Rapid diagnos tic tests
SP
Sulphadoxine-pyrimetham ine
vi
SUMMARY
Plasmodium falciparum accounts for the m ajority of m alaria cas es in Southern Africa and
m ay be ass ociated with severe and fatal disease. Almos t all South Africans are nonimmune, including res idents of seas onal m alaria transm ission areas, and are therefore at ris k
for developing severe m alaria.
The diagnosis and management of malaria is urgent. Delayed diagnosis and
inappropriate treatment are associated with significantly increased morbidity and
mortality. Classically, malaria presents with fever, rigors, headache and body pains,
but the clinical features are non-specific and may be confused with many other
diseases, especially influenza. A definitive diagnosis should be made promptly by
demonstrating the parasite on microscopy of a blood smear or by using a rapid malaria
antigen test.
The choice of anti-malarial agents is dependent on the severity of illness and the
pattern of drug resistance of the parasite in the geographical area where malaria was
acquired. In keeping with the WHO recommendations, using anti-malarial drugs in
combination is essential, and artemisinin-based combinations are preferred. For
uncomplicated malaria acquired in South Africa, artem ether-lumefantrine (Coartem) or
alternatively quinine plus either doxyc ycline or clindam ycin is recommended. High-level
resis tance precludes the us e of chloroquine for falciparum m alaria.
Sulfadoxinepyrim ethamine (SP) is no longer recommended.
For s evere malaria, quinine (with the addition of doxyc ycline or clindam ycin) is currently
recommended. Patients with s evere m alaria will require hospital adm iss ion. All patients with
m alaria require careful clin ical and parasitological follow-up. The m ajor complications of
m alaria include: cerebral malaria, hypoglycaemia, anaemia, renal failure, acute res piratory
dis tress s yndrom e (ARDS) and m etabolic acidos is , and thes e carry high m ortality rates
especia lly in children, pregnant woman and in those living with HIV and AIDS. These
complications require specific m anagem ent.
DIS CLAIM ER
This material is intended for us e by healthcare professionals . It has been com piled from
inform ation currently available, and although the greates t care has been taken the
Departm ent of Health and its Malaria Advis ory Group do not accept res pons ibility for errors or
omiss ions . Readers are referred to the reference articles for further inform ation and should
exercise their own professional judgem ent in confirm ing and interpreting the findings
pres ented in the publication. Thes e guidelines were iss ued in 2008 by the National
Departm ent of Health, and replace all previous guidelines .
vii
Treatment of Malaria in South Africa- Summary Flowchart 2006

Confirm Diagnosis
& assess sev erity
Quinine plus eith er

dox y cy cline or clindamy cin*
Or
OR
Uncomplicated P. falciparum malaria

- mild sy mptoms
- ambulant
- normal mental function
- v omiting not persis tent
- no organ dy sfunction
Artemether-lumefantrine (Coartem)
IV Quinine plus either

dox y cy cline or clindamy cin
Severe P. falciparum malaria

(See definition pg 22)
P. ovale or P. vivax:
chloroquine plus primaquine
P. malariae:
chloroquine
Other Plasmodium s pecies**
Clinical foll ow up and repeat blood

smear
Add clindamy cin or dox y cycline as soon as can be tolerated after quinine is started. Clindamycin is
preferred in children <8 y ears and pregnant women.
** If uns ure of species, treat as for P. falciparum. If mixed infection of P. falciparum plus P. vivax / ovale,
treat as for P. falciparum plus follow with primaquine
viii
Malaria treatment guidelines Final Draft 23 June 2009

1.
INTRODUCTION
The relentless development of drug resistance in malaria parasites (notably

P. falciparum), has necessitated ongoing updates of chemoprophylaxis and
treatment policies globally.
In South Africa, chloroquine resistance was first demonstrated in KwaZulu-Natal
(KZN), and later in Mpumalanga.
This prompted a policy change from
chloroquine to sulphadoxine-pyrimethamine (SP) as first line treatment for

uncomplicated malaria in KZN in 1988 and in Mpumalanga and Limpopo
provinces in 1997.
The development of significant SP resistance in KZN led to a further policy

change in 2001, with artemether-lumefantrine replacing SP as first line treatment
for uncomplicated P. falciparum infections. Subsequently, in December 2004,
Limpopo Province also replaced SP with artemether-lumefantrine. Mpumalanga
Province used SP-artesunate in the public sector from 2001 to end of 2005, but
moved to an artemether-lumefantrine policy in January 2006.
In order to combat the pattern of continued drug resistance of sequential single
drug therapy, combination chemotherapy, preferably using an artemisinin
derivative, is the decided policy. Additional benefits include improved treatment
outcomes and a decrease in malaria transmission, resulting in greater costeffectiveness.
These guidelines have been compiled using both international and local
information. In South Africa there is ongoing monitoring of malaria prevalence
and distribution, and the therapeutic efficacy of anti-malarial drugs.
New
information arising from such monitoring activities will inform future guidelines.

2.
OBJ ECTIVES
The objectives of malaria treatment are:
3.
To prevent mortality
To prevent disease progression and development of severe malaria
To reduce morbidity
To eliminate parasitaemia to minimise transmission, and
To limit the emergence and spread of drug resistance
PARASITE SPECIES
More than 90% of human malaria infections in sub-Saharan Africa are due to
Plasmodium falciparum while the rest are due to Plasmodium ovale,
Plasmodium vivax, or Plasmodium malariae.
Occasionally mixed infections
occur. Infections due to P. falciparum may be severe and complicated. These

complications occur almost invariably as a result of delay in diagnosis and/or
treatment of an uncomplicated infection, the use of ineffective therapy or under
dosing with effective drugs.
4.
RISK GROUPS
South Africans are non-immune, including residents in areas where malaria

transmission occurs. Partial immunity may be acquired after long-term, repeated
exposure to P. falciparum infection, a situation that occurs in residents of high
transmission areas, such as parts of Mozambique, Malawi, Tanzania and some
other southern African countries.
Particular high-risk groups for the development of severe P. falciparum malaria in
South Africa include: non-immune travellers to malaria areas and residents (of
all age groups) in malaria areas. Pregnant women, young children, the elderly,
splenectomised
and
immuno-compromised
vulnerable.
individuals
are
particularly

There is increasing data on the interaction between HIV and malaria, showing
increased clinical attacks of malaria and higher parasite densities in semiimmune adults who are HIV infected. There is also evidence that non-immune
patients co-infected with HIV have a higher risk of severe malaria and malariarelated mortality.
5.
CLINICAL PRESENTATION AND DIAGNOSIS
A high index of suspicion is the most important element in the diagnosis of

malaria. Malaria areas in South Africa include north-eastern KwaZulu-Natal, and
low altitude areas of Mpumalanga and Limpopo provinces, particularly those
bordering Zimbabwe, Mozambique and Swaziland (see map).
Very rarely,
malaria is contracted in the North-West and Northern Cape provinces adjacent to

the Molopo and Orange rivers respectively.
Malaria transmission occurs in almost all countries in sub-Saharan Africa with the
exception of Lesotho. Within each country, geographical distribution of malaria
will vary, and year-round transmission with seasonal disease peaks is usual. In
southern Africa these peaks are typically from September to May.
5.1 SYMPTOMS AND SIGNS
Symptoms and signs of malaria may present as early as 7 days after exposure,
with an average of 10 - 21 days elapsing after being bitten by an infected
mosquito. Longer incubation periods may occur in patients who have been on
chemoprophylaxis or selected antibiotics
e.g. cotrimoxazole, tetracycline,
macrolides, chloramphenicol and quinolones. Very rarely, incubation periods for

P. falciparum of 6 - 18 months have been recorded. Malaria due to infections
with P. vivax, P. ovale or P. malariae can take up to 12 months to first manifest
clinically.
As signs and symptoms of malaria are very non-specific, a high index of
suspicion is critical.

Signs and symptoms could include the following:
Symptoms in Adults
Fever
Headache
Rigors (cold shivers and hot sweats)
Myalgia
Weakness
Dizziness
Loss of appetite
Diarrhoea
Nausea and vomiting
Sore throat
Symptoms in children
Fever
Vomiting
Weakness
Lethargy
Diarrhoea
Cough
Poor feeding
Clinical signs in adults and children

Uncomplicated Malaria
Severe Malaria
Fever
Fever
Splenomegaly and/or
Severe prostration
hepatomegaly
Splenomegaly and/or hepatomegaly
Pallor
Jaundice
Increased respiratory rate
Change in the level of consciousness
Reduced urine output
Bleeding
Shock
Presentation of P. falciparum malaria is very variable and may mimic many
other diseases (and vice versa) including influenza, viral hepatitis, meningitis,
septicaemia, typhoid, tick bite fever, gastroenteritis, viral haemorrhagic fever,
trypanosomiasis, HIV seroconversion illness, urinary tract infection and relapsing
fever.

Non-immune patients with uncomplicated malaria are at increased risk of
disease progression to severe P. falciparum malaria. Life-threatening
complications can develop rapidly in these patients. Malaria should be
suspected in any person presenting with any of the above symptoms who
has a history of travel to, or residence in, a malaria transmission area (See
malaria risk map).
In a febrile patient in South Africa where there is no other obvious cause of fever
and a recent history of visiting or living in a malaria area is not forthcoming,
malaria should still be considered as infected mosquitoes have been occasionally
documented to travel long distances by road, rail and air transport.
5.2
LABORATORY DIAGNOSIS
A diagnosis of malaria cannot be confirmed or excluded clinically. Since

the clinical presentation is non-specific and may mimic many other
diseases, patients blood should be examined immediately to confirm or
exclude the diagnosis. A blood test for parasites should be done
irrespective of the time of the year or whether the patient has or has not
taken chemoprophylaxis.
In the majority of malaria cases, examination of correctly stained blood smears
will reveal malaria parasites. However, a negative smear does not exclude the
diagnosis; repeat specimens should be examined regularly and urgently without
waiting for fever peaks, until the diagnosis is confirmed, the patient has
recovered or another definitive diagnosis is made. Examination of the peripheral
blood smear will give an indication of the species of parasite as well as the
*
parasite density. High levels of parasitaemia (>4% or 3+) should be treated as
severe malaria in non-immune patients. Importantly, the converse may not be

true, with severe disease also occurring with low parasitaemias in the peripheral
blood. The interpretation of a low parasite count must always be considered in
conjunction with the patients clinical condition and other laboratory results (See
7.1: Severe malaria).
A number of commercial rapid diagnostic tests (RDTs) are available for early
diagnosis in health facilities where microscopy is not immediately available.
These kits detect parasite antigen namely histidine-rich protein 2 (or lactate
The parasite density refers to the parasite load in the peripheral blood expressed semi-quantitatively
(1 to 5+) or as a percentage of infected red blood cells. Quantification is often inaccurat e and does not
necess arily reflect the total parasite load in the patient.

dehydrogenase or aldolase).
The majority of the tests will only detect P.
falciparum; while a few will detect the other malaria species but are less sensitive
for these.
The rapid tests for P. falciparum are generally highly sensitive.
Performance is, however, dependent on the correct storage, usage and

interpretation of results and the quality of the particular test used. These tests
should be used only for diagnosis of acute malaria infections, and not for followup, as they may remain positive for several weeks even after successful
treatment. The test may be negative early in the disease, and false positives
may be encountered rarely.
If the diagnosis of malaria cannot be confirmed (unavailability of laboratory tests,
or negative tests), the decision to commence malaria therapy should be made on
clinical grounds, based on whether exposure to malaria parasites was possible
and the severity of the clinical features. In cases of severe malaria a blood
smear or rapid malaria test is likely to be positive. However, some patients with
severe malaria may rarely have a negative smear due to sequestration of
parasitized red blood cells. In patients who are treated empirically for malaria, it
is imperative to continue to look for alternative diagnoses and to follow-up
patients very carefully.
Thrombocytopenia is a common finding in patients with malaria. A blood smear
should be checked for malaria parasites or an RDT performed whenever this
laboratory finding is made unexpectedly. A malaria smear is indicated in patients
with recurrent symptoms and a negative RDT, to exclude non-falciparum malaria.
5.3 REFERRAL CRITERIA
NOTE: Clinical judgement must be applied
Ideally all patients with malaria should be treated in hospital. Definite indications
for hospital admission:
o
All children 1 year (and consider admitting children up to 5 years

where possible)
All pregnant patients
All patients 65 years
Immuno-compromised patients where possible

o
All patients with features of severe malaria or danger signs:
Confusion
Decreased level of consciousness
Convulsions
Extreme weakness (prostration)
Jaundice
Decreased urine output
Haemoglobinuria
Severe anaemia (Hb 6 g/dl)/ HCT 20%)
Persistent vomiting (unable to tolerate oral medication)
Respiratory distress
Shock
Suspected treatment failure (including reappearance of parasites

within 6 weeks of treatment).
Malaria is a notifiable disease

The notification of all malaria cases is mandatory. The procedure to follow for
notifiable medical conditions:
1.
Healthcare worker (not necessarily a medical doctor):
Diagnose
(preferably a definitive diagnosis) and notify the malaria case using GW17/5
or applicable notification form, immediately, as some of the important
information required on the notification form may not be a vailable after the
patient has left the healthcare facility.
If possible, the malaria species
should be specified in the notification form.

2.
Local authority/hospital/district (whoever is responsible for disease

containment) submits the GW17/3 summary of cases and GW17/4
summary of deaths forms weekly.
3.
Regional/district office health information unit will collate and use this
information to plan and monitor the impact of malaria control and case
management interventions.
NOTE: As thousands of malaria cases present in non-malaria areas in South

Africa each year, it is critical that these cases also get notified to the local

authority to facilitate adequate provision of malaria diagnosis and management
resources to healthcare facilities in these areas.
6.
TREATMENT
Patients should receive prompt treatment with the most effective regimen
available. Where patients present in non-malaria areas, treatment should ideally
be initiated in hospital.
In malaria areas the majority of patients with
uncomplicated malaria can be treated at primary health care level.

The choice of chemotherapy for malaria is dependent on the severity of disease,
the known or suspected resistance pattern of the parasite in the area where the
malaria infection was acquired, the species of parasite, patient characteristics
(age, pregnancy, co-morbidity, allergies, concomitant medications) and the
presence or absence of vomiting.
Drug choices may change over time with the development of parasite resistance
or the availability of new anti-malarial treatments.
6.1. UNCOMPLICATED PLASMODIUM FALCIPARUM MALARIA
6.1.1
Chemotherapy
It is important to attempt to differentiate between uncomplicated and severe

malaria.
Patients with uncomplicated malaria include: those who have mild
symptoms, are ambulant and have no evidence of organ dysfunction either

clinically or on laboratory tests and in whom the parasite count is less than 5%
(see section 7: Severe malaria, for details). However, uncomplicated malaria
may rapidly progress to severe malaria if the patient is not treated appropriately.
For patients with uncomplicated malaria, the recommended chemotherapy is the
fixed dose artemisinin-based combination, artemether-lumefantrine (Coartem)
in all patients over 1 year of age and non-pregnant patients. In children 1 year
and all pregnant patients, the recommended chemotherapy is quinine plus
clindamycin.

When artemether-lumefantrine (Coartem) is not available, uncomplicated
malaria can also be treated with quinine plus either doxycycline or clindamycin.
It is advisable that quinine only be used as observed treatment of inpatients, due
to the possibility of adverse drug reactions and the poor tolerability of this 7-day
regimen.
All first doses of drugs must be given under supervision and patients must
be observed for at least an hour as vomiting is common in patients with
malaria and treatment must be repeated if the patient vomits within the first hour.
Vomiting oral treatment is one of the commonest reasons for treatment failure.
6.1.2
General management
It is easy to underestimate the severity of disease and complications may

arise despite apparent appropriate chemotherapy. Patients with malaria
should be carefully assessed and closely monitored.
The clinical and
parasitological response of patients to treatment should be monitored regularly;

in particular, the mental state, respiratory rate and urine output. Adequate fluids
should be given, and antipyretics (paracetamol) administered when needed.
Ibuprofen has been used but there is less experience with this compound. Other
non-steroidal anti-inflammatory drugs (NSAIDS) should be avoided as they may
increase the risk of renal failure in patients with malaria.
If patients with uncomplicated malaria cannot be admitted to hospital for

treatment, they (or their caregivers) should be warned of the symptoms and signs
of severe malaria and advised of the urgency of then returning for hospitalisation
and appropriate treatment.
Patients should experience a clinical response to therapy within 24 - 48 hours. A
repeat peripheral blood smear should be performed where possible after 72
hours of treatment: a decrease of at least 75% of the initial parasite count is
expected with effective treatment.

Treatment failure in malaria may manifest as:
Early treatment failure:
Failure to respond clinically and/or achieve 75% decrease in parasite

count by 72 hours
No decrease or an increase in asexual/erythrocytic forms of the

parasites in peripheral blood 48 hours after starting treatment
Late treatment failure
Recurrence of parasitaemia within 6 weeks of treatment (which could

be either from recrudescence of the original infection or, if in a malaria
transmission area, a new infection)
Presence of parasites 7 days after treatment (excluding presence of

gametocytes)
Treatment failure may be due to:
Parasite resistance to the anti-malarial drug used
Vomiting of oral medication
Non-compliance with medication
Failure to take fat/food with artemether-lumefantrine leading to poor

absorption of lumefantrine component
Re-infection (apparent treatment failure)
Relapse due to P. ovale or P. vivax due to failure to treat hypnozoites
NOTE: On a malaria peripheral blood smear, the presence of gametocytes,

the stage of malaria parasites lifecycle responsible for malaria transmission,
does not indicate treatment failure, as these may be present for several
weeks after successful treatment.
Treatment failures after completing a full course current first-line therapy of either
7-days of quinine (plus doxycycline or clindamycin) or a 3-day artemetherlumefantrine regimen are rare, as both these treatments have very high cure
rates. Patients who have failed first-line treatment with artemether-lumefantrine
should then be given a course of quinine with either doxycycline or clindamycin.
Treatment failures following quinine treatment of uncomplicated malaria could be
10

treated with artemether-lumefantrine, provided malaria complications are
carefully excluded.
6.1.3
Drugs used in the treatment of Plasmodium falciparum malaria
6.1.3.1 Artemisinin-based combination therapy

Artemisinin-based combination therapies (ACTs) are now generally considered
as the best current treatment for uncomplicated falciparum malaria (WHO 2006).
ACTs have the advantages of rapid clinical and parasitological response,
improved cure rate, decreased malaria transmission and the potential to delay
anti-malarial resistance. A number of artemisinin derivatives have been used
successfully in the treatment of P. falciparum malaria including multi-drug
resistant malaria and for the blood stages of P. vivax infections. The most
evidence of efficacy and safety is currently available for the derivatives
artemether and artesunate. This class of anti-malarial has a favourable safety
profile. When used as single-drug therapy (monotherapy) for less than 7 days
recrudescence is common.
Therefore the artemisinin derivatives should
always be used in combination with an effective, longer-acting antimalarial.
Combination therapy is essential for delaying development of
resistance to this crucial class of drugs. The choice of the second drug will
depend on resistance, cost, side effect profile and efficacy. The only artemisinin
derivative currently registered in South Africa is the combination of artemether
with lumefantrine (Coartem).
In patients with severe malaria, parenteral
artemisinins are effective and intravenous artesunate reduced malaria related

deaths by 32%.
Artemether-lumefantrine (Coartem)
This fixed dose combination containing 20mg artemether plus lumefantrine
120mg is the recommended first line treatment for uncomplicated malaria in all
malaria transmission areas in South Africa. It has the advantages of a shorter
treatment course (6 doses over 3 days) and far better tolerability than the only
effective alternative, quinine. However, its indication is limited to the treatment of
uncomplicated malaria as there is no evidence of its efficacy in more severe
disease. Artemether-lumefantrine is contra-indicated in pregnancy and in those
patients who have a history of allergy to artemether or lumefantrine. Data in
11

children less than 1 year of age is limited.
Adequate absorption of the
lumefantrine component is critically dependent on co-administration with

food or drink containing 1.3 g of fat (e.g. 100 ml milk). This drug has been
best studied in patients weighing less than 65 kg and thus is not yet registered
for use in patients weighing greater than 65 kg, although initial results in this
group are encouraging. As this is a relatively new drug, no drug interactions or
contra-indications other than pregnancy and allergy have been identified.
Ad verse effects identified include: sleep disturbances, headaches, dizziness,
palpitations, abdominal pain, anorexia, cough, arthralgia, myalgia, asthma and
fatigue. Rarely, hypersensitivity reactions have been reported. Ad verse events
or potential drug interactions should be reported to the National Adverse Drug
Event Monitoring Centre [021- 4486181 (fax) or 021- 4066234 (tel)].
Intravenous artesunate
Parenteral artemisinin derivatives, notably artemether and artesunate, have been
successfully used for treating severe malaria. In a randomized controlled trial of
severe malaria in adults living in areas of low malaria transmission in Asia, the
death rate was one-third lower among the adults who received intravenous
artesunate compared to those who received quinine. Patients treated with IV
artesunate have a 1/20 to 1/11 better survival rate than those getting IV
quinine. This is the first published study on severe malaria, which showed a
clear difference in mortality between the two treatments. Artesunate is also
easier to use and is not associated with hypoglycemia, which can be
caused or exacerbated by quinine. Similar studies are now being conducted in
children in Africa. Until these results are available, and an intravenous parenteral
artesunate is registered in South Africa, quinine remains the recommended
treatment for severe malaria in South Africa.
6.1.3.2 Quinine
Quinine is a rapidly acting, effective anti-malarial drug used for both
uncomplicated and severe malaria acquired in sub-Saharan Africa.
Quinine
resistance is rare in this area, although increasing slowly in Southeast Asia. Oral
quinine therapy is an alternative option recommended in uncomplicated malaria
but the initial doses of quinine should be administered intravenously if the patient
12

is vomiting repeatedly. Quinine therapy should be continued for 7-10 days. The
addition of a second, effective, anti-malarial drug, i.e. doxycycline or clindamycin,
is indicated to ensure complete parasite clearance and improve cure rates. One
of these agents should be added as soon as can be tolerated (usually 2 - 3 days
after commencement of the quinine), to ensure that possible adverse effects from
the quinine are not confused with those of the second agent. In patients less
than 8 years old or during pregnancy, clindamycin should be used rather than
doxycycline or other tetracyclines. Shortened courses of quinine (3 days) cannot
be recommended for treatment. Patients initially treated for severe malaria with
quinine should complete the course of treatment with the same drug, as
completion of therapy initiated with quinine with a course of artemetherlumefantrine has not been adequately evaluated.
It is most important that patients (or caregivers) understand that it is essential to
complete the course of 7-10 days of quinine (with doxycycline or clindamycin) as
adherence with this poorly tolerated treatment is generally low. Minor adverse
effects, causing a syndrome known as cinchonism, are frequent during the
treatment of malaria with quinine. Mild hearing impairment (notably high tone
deafness), tinnitus, headache, nausea and slight visual disturbances occur in up
to 70% of patients during quinine therapy and are not an indication to discontinue
therapy.
Major
side
effects
include
arrhythmias, hypersensitivity and
hypoglycaemia. Hypoglycaemia is the most frequent serious adverse reaction.

Quinine toxicity presents with central nervous system (CNS) disturbances
(primarily visual and auditory) and cardiovascular abnormalities (hypo tension,
heart block, ventricular arrhythmias), and can be confused with severe malaria.
Cardio toxicity is particularly related to rapid infusion of quinine.
6.1.4
Treatments not recommended for falciparum malaria
Monotherapies (anti-malarial agents used on their own) are no longer

recommended for the treatment of falciparum malaria. Artemisinin derivatives
should never be used as monotherapy as this could select for resistance and
compromise the value of artemisinin-based combination treatments (ACTs);
taking artemisinin monotherapies for less than 7 days is strongly associated with
treatment failure (recrudescence of infection). Chloroquine is not recommended
13

following the emergence of high-level resistance in most parts of the world
including
South
Africa.
Sulphadoxine-pyrimethamine
is
no
longer
recommended in South Africa, due to the availability of more effective

combination therapy, coupled with high-level resistance in some parts of the
country.
Mefloquine is registered only for prophylaxis but not treatment, given the higher
incidence of severe psychiatric adverse effects associated with treatment doses.
Halofantrine treatment is not advisable given the associated cardio toxicity,
variable bioavailability and drug interactions in patients who have taken
mefloquine prophylaxis. Clindamycin and doxycycline are slow acting antimalarials and should never be used as monotherapy, but are added to quinine
treatment regimens to improve cure rates.
6.2 TREATMENT OF NON-PLASMODIUM FALCIPARUM INFECTIONS
In sub-Saharan Africa, a minority of the malaria infections are due to one of the
other Plasmodium species, namely P. vivax, P. ovale or P. malariae. Infections
contracted in the Caribbean and some countries in Central America and the
Middle East are mostly due to P. vivax. Generally, disease due to infection with
the non-falciparum malarias is uncomplicated, although P. vivax has rarely
caused severe malaria and P malariae may be associated with the nephrotic
syndrome in children.
microscopically.
The parasite species should be reliably confirmed
If unsure of the species, standard treatment for
P. falciparum should be administered. P. ovale and P. malariae are currently

chloroquine-sensitive, but rare cases of chloroquine-resistant P. vivax have been
documented in Oceania, Brazil, and Indonesia.
In South Africa P. ovale is the most common of the non-falciparum malarias.
Anaemia may complicate chronic P. ovale infection.
Pure infections of
P. malariae can be treated with chloroquine monotherapy, while the extra-hepatic

phases of infections with P. vivax or P. ovale can be treated with chloroquine (or
quinine or artemether-lumefantrine).
For P. vivax or P. ovale a follow-up
course of primaquine is essential to eradicate the residual hepatic phase to

prevent relapse.
14

Primaquine must be given for 14 days at the recommended dosages.
Primaquine is contra-indicated in children less than 1 year of age and during
pregnancy. In pregnant women eradication of the hepatic stage must be delayed
until after delivery. Patients with severe glucose-6-phosphate dehydrogenase
(G-6-PD) deficiency (<10 % residual enzyme activity) should not receive
primaquine due to the risk of severe haemolytic anaemia. There is no proven
alternative
for
these
patients, although
continuing
weekly prophylactic
chloroquine (usually for 3 years) may be effective. Primaquine may be taken by

patients with mild deficiency of G-6-PD (10 - 60% residual enzyme activity) at a
reduced dose of 0.5 - 0.7 mg/kg body weight once every 7 days for 8 weeks.
Such patients should be evaluated for anaemia and haemoglobinuria at 3, 7, and
10 days after the start of primaquine.
6.3
TREATMENT OF MIXED PLASMODIUM INFECTIONS
In patients with confirmed or suspected mixed infections i.e. P. falciparum with

either P. vivax or P. ovale, the standard therapy for uncomplicated or severe
P. falciparum malaria (either quinine or artemether-lumefantrine) plus a follow-up
course of primaquine is recommended. A mixed infection of P. falciparum and
P. malariae should be managed as for P. falciparum malaria. The severity of the
P. falciparum infection should dictate choice of initial therapy. Doubt frequently
exists about the presence of P. falciparum in addition to other Plasmodium
species. The patient should then be treated for P. falciparum, as this is the
species most frequently associated with severe infections and complications.
6.4 TREATMENT DURING PREGNANCY
Pregnant women, particularly in the second and third trimesters of pregnancy,
are more likely to develop severe malaria than other adults and have a higher
malaria-related mortality rate. Malaria in pregnancy is particularly associated
with complications such as cerebral malaria, hypoglycaemia, and pulmonary
oedema/ARDS. In addition, maternal malaria increases the risk of spontaneous
abortion, stillbirth, premature delivery, low birth weight (a leading cause of child
mortality) and rarely, congenital malaria. Foetal distress may occur peripartum.
The risk of severe malaria extends into the early postpartum period.
It is
important to carefully follow up pregnant women treated for malaria, and their
15

infants, to promptly diagnose and adequately manage the known complications
of malaria in pregnancy.
6.4.1
Diagnosis of malaria in pregnancy
A high index of suspicion is the most important element in the diagnosis of

malaria. Malaria is frequently missed or misdiagnosed in pregnancy and needs
to be differentiated from complications of pregnancy e.g. intrauterine sepsis,
eclampsia, or pyelonephritis, as signs and symptoms may be similar.
Suspect malaria if the patient is resident in or has travelled to a malaria
transmission area. A history of visiting a malaria transmission area should be
explored in all pregnant women with fever. A malaria smear (repeated if initially
negative) or malaria antigen test is mandatory for any pregnant patient with fever
and a history of malaria exposure.
Fever is common, but may be absent in some cases.
It is important to attempt to differentiate between uncomplicated and severe
malaria.
However, uncomplicated malaria may progress rapidly to severe
malaria in pregnancy if the patient is not treated urgently and appropriately.

All pregnant women with malaria must be admitted to hospital and those
with severe malaria should be transferred to the highest level of care
available (either a le vel 2 or level 3 hospital)
6.4.2
Management of uncomplicated malaria in pregnancy
The treatment of choice for uncomplicated malaria is quinine followed by a

course of clindamycin. Do xycycline is contraindicated. Quinine has proved to
be safe when used in normal therapeutic doses, and since the risks of malaria
are great, there is no debate about using a less effective therapy. Quinines main
adverse effect in pregnancy is hypoglycaemia and patients should be closely
monitored for this. Quinine may be oxytocic, but this effect may also be due to
the malaria itself.
The incidence of teratogenesis is unknown, although
congenital abnormalities, notably CNS anomalies and limb defects have been
occasionally reported with quinine use in the first trimester. With the doses used
to treat malaria, the benefits of quinine therapy outweigh the risks.
16

Currently, the artemisinins are only recommended when no effective alternative
anti-malarial is available.
derivatives in the 2
nd
There is increasing experience with artemesinin
and 3rd trimesters of pregnancy, and no adverse effects on
the mother or human foetus have been documented to date. However, some
animal studies have shown teratogenicity, particularly with high doses. Suboptimal absorption of lumefantrine (as in artemether-lumefantrine) in pregnancy
has been suggested in one study. In lactating women, uncomplicated malaria
should be treated with artemether-lumefantrine, and quinine and clindamycin
used for severe malaria.
6.4.3
Management of severe malaria in pregnancy
In severe malaria parenteral quinine in full dosages should be given
Obstetric advice should be sought early
The role of early Caesarean section for the viable live fetus is
unproven
Termination of pregnancy is not generally indicated
Hypoglycemia should be expected and is often recurrent if the patient

is receiving quinine, and may be refractory to glucose administration.
Hypoglycemia must be considered urgently in any pregnant woman
with malaria who presents with convulsions, confusion or a depressed
level of consciousness
It may be difficult to differentiate cerebral malaria from eclampsia. If a

pregnant woman living in a malaria area has fever, headaches or
convulsions and malaria cannot be excluded, it is essential to treat the
woman for both malaria and eclampsia
Respiratory failure due to ARDS is a particular problem of malaria in

pregnancy and is difficult to manage and carries a high mortality rate
It is critical therefore to monitor fluid balance very carefully. Fluid

overload may potentiate the development of ARDS. Hypovolaemia
however, may potentiate renal failure, metabolic acidosis
and
circulatory collapse. Accurate recording of fluid input and output is

essential (CVP < 5 cm H2O). ARDS commonly occurs several days
after treatment is initiated
17
The risk of severe malaria extends into the early post partum period.
Postpartum bacterial infection is a common complication in these
patients
6.5 TREATMENT OF INFANTS AND YOUNG CHILDREN

Infants and young children (especially those <5 years) are particularly at risk for
severe malaria and complications can develop very rapidly without warning. The
symptoms of malaria in children may differ from those in adults, and therefore
malaria should be suspected if a child who has been in a malaria transmission
area develops a febrile illness. Poor feeding, lethargy, irritability, coughing and
convulsions
(frequently
subtle),
are
important
presenting
features.
Hypoglycaemia, cerebral malaria, anaemia, and metabolic acidosis are

important complications.
Agitation and respiratory distress (as a result of
metabolic acidosis) are ominous signs. Secondary bacterial infections, including

septicaemia, are common and broad-spectrum antibiotics should be given to
children with severe malaria.
Renal failure and acute respiratory distress
syndrome are rare in young children. Meningitis is important in the differential

diagnosis of malaria.
6.5.1
Managing uncomplicated (non-severe) malaria in young children
In children over 1 year of age with uncomplicated malaria, recommended

treatment is artemether-lumefantrine or quinine plus clindamycin.
However,
children have a higher risk of developing complicated malaria so should ideally

be admitted for treatment under close supervision.
For children 1 year of age with uncomplicated malaria the treatment of choice
is quinine plus clindamycin. This is because of the risk of rapid development
of complications. As there is no quinine syrup available, it can be difficult to
administer to children. Crushed tablets mixed in mashed bananas, chocolate
syrup or jam can be used to make the quinine more palatable. Pharmacists may
be able to specially prepare quinine syrup.
Children who are vomiting but who have no other indications of severe malaria
should be given parenteral quinine in the recommended doses (see Section 9,
18

Dosage Guidelines) until the child can take medication orally. Particular care
must be taken to ensure that the correct dosage is administered. Once oral
intake is confirmed then switch to any of the 2 regimens above (depending on the
childs age).
Suspect severe malaria in any child at risk of malaria with any of the following
signs:
Unable to drink or breastfeed
Vomits everything
Has had convulsions
Lethargic or unconscious
Stiff neck or bulging fontanelle

Children with severe malaria need to be managed differently to children with
uncomplicated/non-severe malaria. Section 6.5.2 explains the management of
severe malaria in children.
6.5.2 Managing severe malaria in young children

Intravenous (parenteral) quinine is indicated for severe malaria in children and
the usual loading dose of 20mg/kg is used. Particular care must be taken to
ensure that the correct dosage is administered. Where intravenous quinine is not
promptly available, or cannot be given safely, initial administration of quinine by
deep intra-muscular injection using scrupulous aseptic technique, should be
considered prior to referral. When given intramuscularly, quinine dihydrochloride
should be diluted to reduce pain and prevent sterile abscess formation. Dilutions
to between 60 and 100 mg/ml should be made.
19
Management of severe malaria in young children
Check airway, breathing, circulation (ABC)

Agitation and respiratory distress (as a result of metabolic acidosis) are
ominous signs
Children who present with shock and acidosis should be given a bolus
(20 mg/kg) of fluid, either colloid (plasma) OR crystalloid (Ringers
lactate, or normal saline if this is unavailable)
Secondary bacterial infections, including septicaemia, are common
and broad-spectrum antibiotics e.g. third generation cephalosporins
should be given to children with severe malaria
Renal failure and acute respiratory distress syndrome are rare in
young children
Meningitis is important in the differential diagnosis of malaria with a
change depressed level in the level of consciousness or convulsions
Convulsions in children with malaria may be due to hypoglycaemia,
cerebral malaria or pyrexia
Artemisinin derivatives have been shown to be safe and highly effective in

children, including cases of severe malaria and multi-drug resistant malaria.
Rectal artesunate is being developed to provide anti-malarial cover while a
patient is being transferred to a hospital from a primary healthcare facility where
parenteral treatment is not safely available.
Intra-muscular artemether and
intravenous artesunate have been shown to be safe and effective in the

treatment of severe malaria in children. None of rectal artesunate, intra-muscular
artemether or intravenous artesunate is registered for use in South Africa,
although when these products become available they are expected to provide a
safer and possibly more effective alternative to quinine.
6.6 MALARIA AND HIV
A large number of HIV-infected patients either live in areas where malaria
transmission occurs, or travel to these areas. Overlap of symptoms of the two
diseases, especially fever, may result in HIV-positive patients with malaria
presenting late to health facilities and the diagnosis of malaria being missed.
Although acute malaria causes a temporary increase in replication of HIV and
hence in plasma viral load, there is no evidence that malaria has a substantial
effect on the clinical progression of HIV infection, HIV transmission or response
to antiretroviral treatment. HIV-infected individuals who live in areas of stable
malaria transmission and are thus expected to be malaria semi-immune, are at
20

increased risk of symptomatic parasitaemia and/or may exhibit higher levels of
peripheral parasitaemia than semi-immune adults who are HIV-negative. HIVinfected patients who are malaria non-immune are at higher risk of severe
malaria and of dying from malaria. As HIV progresses and immuno-suppression
worsens, the risks of severe malaria increase. Renal failure has been identified
as a particular complication in this group of patients.
Secondary bacterial
infection is common and empiric antibiotic treatment should be given, e.g. a third
generation cephalosporin.
Electrolyte disturbances are common and close
monitoring is essential. Thus, patients co-infected with HIV/AIDS and malaria

should be admitted for treatment and close monitoring at the highest level of care
available, preferably a level 2 or level 3 hospitals.
It is unclear how HIV infection modifies the therapeutic response to antimalarials. Increased parasite burdens and reduced host immunity, both of which
occur with HIV infection, may be associated with delayed parasite clearance and
increased failure rates. Patients with HIV infection who develop malaria should
receive the recommended anti-malarial regimens, although more closely
monitored, to ensure an adequate response. There are limited data regarding
interaction
of anti-malarials
with
antiretroviral
drugs.
Pharmacological
interactions between certain anti-retrovirals (ARVs) and anti-malarial drugs are

theoretically possible and might lead to toxicity or sub-therapeutic drug levels.
However there are no documented interactions. WHO suggests that patients
receiving protease inhibitors and the NNRTI delavirdine should avoid halofantrine
(Note: this drug is not recommended for malaria treatment in South Africa).
Since lumefantrine is related to halofantrine, the combination artemetherlumefantrine may therefore have the potential to interact with ARVs.
21

7.
SEVERE MALARIA
Unless P. falciparum malaria is promptly diagnosed and treated, the clinical

picture may deteriorate rapidly. Severe malaria carries a significant morbidity
and mortality.
Young children, pregnant women, immuno-suppressed patients and any nonimmune persons are at risk for the development of complications. One can
assume that all South Africans living in the malaria areas in this country and all
South African travellers are non-immune.
7.1 FEATURES INDICATING SEVERE MALARIA
Clinical Features
Prostration
Impaired consciousness (Glasgow & Blantyre coma scales)
Multiple convulsions
Respiratory distress (acidotic breathing)
Circulatory collapse
Pulmonary oedema (radiological)
Acute respiratory distress syndrome (ARDS)
Abnormal bleeding
Jaundice
Haemoglobinuria
Biochemical Features
Renal impairment serum creatinine >265 mol/litre or rapidly rising

creatinine (>2.5 mol/kg/day) or urine output <400 ml/day (adult)
Acidosis (plasma bicarbonate <15 mmol/litre) (serum lactate > 5
mmol/liter)
Hepatic impairment (transaminases > 3 times normal)
Hypoglycaemia (blood glucose <2.2 mmol/liter)
Hypoxia (PO 2 - < 8 Kpa in room air)
Haematological Features
Parasitaemia 5% or 3+
Anaemia: haemoglobin < 6 g/dL or haematocrit <20%
5% neutrophils contain malaria pigment
Presence of schizonts of P. falciparum in peripheral blood smear
Evidence of DIC
22

The Glasgow Coma Scale
Best motor response
Carrying out request (obeying command)
Localising response to pain
Withdraws to pain
Flexor response to pain
Extensor posturing to pain
No response to pain
Best verbal response
Orientated
Confused conversation
Inappropriate speech
Incomprehensible speech
None
Eye opening
Spontaneous eye opening
Eye opening in response to speech
Eye opening to response to pain
No eye opening
Score
6
5
4
3
2
1
5
4
3
2
1
4
3
2
1
An overall scale is made by adding the score in the three areas assessed,
e.g.:
No response to pain + no verbalisation + no eye opening = 3
Severe injury, GCS < 8
Moderate injury GCS 9-12
Minor injur y GCS 13-15
Blantyre paediatric coma scale
Motor Response
Localises to pain
Withdraws from pain stimuli
No response
2
1
0
Verbal Response
Appropriate cry
Inappropriate cry/moan
No cry
2
1
0
Eye Response
Directed
Not Directed
1
0
4-5 normal
2-3 mild impairment
0- severe impairment
23

7.2 TREATMENT
The patient should be treated in the highest level of care available. Management
of severe malaria comprises 4 main areas: clinical assessment of the patient,
specific anti-malarial treatment, adjunctive therapy and supportive care.
SEVERE MALARIA IS A MEDICAL EMERGENCY
Initial Assessment:
o
The airway should be secured in unconscious patients and breathing and
circulation assessed
o
The patient should be weighed or body weight estimated so that drugs,

including anti-malarials, and fluids can be given on a body weight basis
An intravenous cannula should be inserted and an immediate measurement

of blood glucose (rapid test) done
A detailed clinical examination should be conducted, with particular note of

the level of consciousness and record of the coma score
A lumbar puncture for cerebrospinal fluid analysis to exclude bacterial

meningitis should be considered in unconscious patients
The degree of acidosis is an important determinant of outcome; the plasma

bicarbonate or venous lactate level should therefore be measured if
possible. If facilities are available, arterial or capillary blood pH and gases
should be measured in patients who are unconscious, hyperventilating or in
shock
Submit blood urgently for full blood count, platelet count, and measurement
of urea, creatinine and electrolytes and obtain results urgently
The assessment of fluid balance is critical in severe malaria. Respiratory

distress, with acidotic breathing, in severely anaemic children, often
indicates hypovolaemia and requires prompt rehydration and, where
indicated, blood transfusion.
7.3 CHEMOTHERAPY
Quinine is the drug of choice for the treatment of severe malaria in South Africa.
Intravenous quinine is the preferred route of administration, especially where the
patient is comatose, vomiting or severely ill. Quinine administration is always by
slow, rate-controlled intravenous administration, never by bolus injection.
24

Where intravenous quinine administration is not feasible, not available or
considered unsafe, the intra-muscular route may be used initially.
7.4 LOADING DOSES
In severe malaria an initial loading dose must be given, by slow intravenous
infusion over 4 hours. The rationale for the loading dose is to rapidly reach a
therapeutic level.
The loading dose is quinine dihydrochloride salt, 20 mg/kg body weight diluted in
5-10 ml/kg body weight of 5% dextrose water over 4 hours. The loading dose is
given strictly according to body weight. The disposition of quinine in very
obese patients is not known. It has been suggested that there is a ceiling dose
above which quinine should not be given, but there is no evidence to support
this.
The loading dose should be omitted if the patient has received quinine, or
mefloquine prophylaxis, in the preceding 24 hours.
In these cases, ECG
monitoring is necessary.
7.5 MAINTENANCE DOSES
Six to eight hours after starting the loading dose, a maintenance dose of quinine
dihydrochloride salt, 10 mg/kg diluted in 5-10 ml/kg body weight of a dextrosecontaining solution should be commenced and infused over 4-6 hours.
Intravenous quinine should be administered every 8 hours until the patient can
take oral medication (usually by 48 hours). For obese patients, the maintenance
dose should be calculated according to ideal body weight. Ideal body weight can
be calculated for adults by a formula as follows:
Males: IBW (Kg) = 0.9 x height in cm - 88

Females: IBW (Kg) = 0.9 x height in cm - 92
The total duration of therapy is 7-10 days.
25

The use of additional doxycycline or clindamycin does not add initial therapeutic
benefit for severe malaria and may contribute to drug side effects. They should
be added once the patient is improving.
Once the patient is improving, oral treatment should be continued as per the
recommendations for uncomplicated malaria. The dose of quinine should be
reduced in renal failure (See 7.8.4).
Quinine has a narrow therapeutic window, although serious side effects

(cardiovascular or nervous system) during anti-malarial treatment are unusual.
The most frequent side effect during intravenous therapy is hypoglycaemia,
especially in pregnant women and children. Hypotension, heart block, ventricular
arrhythmias, tinnitus and neurological problems, including convulsions and visual
disturbances, occur rarely.
7.6 OTHER CHEMOTHERAPEUTIC OPTIONS
In cases of suspected quinine resistance, where there has been a poor
parasitological response to quinine, an artemisinin derivative (not yet registered
in SA) may be considered, when available. Parenteral artemisinin derivatives,
notably artemether and artesunate, have been successfully used for treating
severe malaria. See Section 6.1.3.1.
7.7 GENERAL MANAGEMENT OF SEVERE MALARIA
The following measures should be applied in the management of all patients with
clinically diagnosed or suspected severe malaria:
Patient should be admitted to the highest level of care, ideally an

intensive care unit. Good nursing care is vital
Appropriate anti-malarial chemotherapy must be commenced

urgently. Ideally the drug should initially be given intravenously
If parasitological confirmation of malaria is not readily available, a

blood film should be made and treatment started on the basis of the
26

clinical presentation, in very ill patients with febrile disease with no
other obvious cause
Doses must be calculated on a mg/kg of body weight basis. A loading

dose of drug should be administered immediately on diagnosis. It
is therefore important, whenever possible, to weigh the patient (see 7.5
on ideal IBW).
This is particularly important for children.
confuse the doses of salt and base.
Do not
Quinine doses are usually
prescribed as salt (10 mg of salt = 8.3 mg of base)
Other treatable causes of coma (e.g. meningitis, hypoglycaemia and

severe anaemia) should be excluded
A rapid initial check of the blood glucose level and frequent monitoring
for hypoglycaemia are important. Where this is not possible and the
patient has a depressed level of consciousness and/or convulsions,
glucose should be given as 50% dextrose solution intravenously. See
section 7.8.2
Regular monitoring of the core temperature, respiratory rate, blood

pressure, level of consciousness and other vital signs is mandatory
Laboratory
measurements
should
include:
regular
checks
of
haemoglobin, glucose, urea and creatinine, electrolytes and liver

functions, acid-base status where possible and parasite density
Monitor fluid balance carefully.
Avoid over- and under-hydration.
Fluid overload is extremely dangerous as it may precipitate potentially

fatal respiratory failure. Hypovolaemia however, may potentiate renal
failure, metabolic acidosis and circulatory collapse. Accurate recording
of fluid input and output is essential as fluid balance should be
according to urine output and normal and excess fluid loss. Frequent
central venous pressure (CVP) monitoring is recommended; maintain
27

the CVP at between 0-5 cm of water. Consider risk of bleeding due to
thrombocytopenia when inserting CVP line
Monitor urine output constantly and carefully observe for the

appearance of haemoglobinuria
o
Reduce high body temperatures (> 39 C) by vigorous tepid sponging
and fanning. Antipyretics may also be given. Avoid aspirin-containing

compounds and non-steroidal anti-inflammatory drugs
Look for and manage any complicating or associated infections. A

broad-spectrum antibiotic is recommended e.g. a 3
rd
generation
cephalosporin
7.8 COMPLICATIONS
7.8.1
Anaemia
Definition
A haemoglobin level 6 g/dL or a haematocrit 20%.
Anaemia is a common complication of malaria, especially in young children and
pregnant women.
It occurs as a result of haemolysis and/or bone marrow
dysfunction. Severe anaemia may manifest as cardiac failure, shock, hypoxia or

confusion. There may be other causes contributing to anaemia in some patients.
Management
Blood transfusion should be considered in patients in whom the Hb is 6 g/dL or
less, or the haematocrit is less than 20%, especially those with cardiovascular
decompensation and shock. Caution should be exercised and fluid overload
should be avoided. If no fresh blood is available packed red cell concentrate
may be used.
7.8.2
Hypoglycaemia
Definition
A blood glucose level <2.2 mmol/l.
28

Hypoglycaemia is common in severe malaria, particularly in pregnancy, in
children, and in patients on intravenous quinine.
Blood glucose should be
monitored 4-6 hourly. H ypoglycaemia may not always present with classical
symptoms of sweating, anxiety, dilatation of pupils or tachycardia.
It must
always be excluded in patients with malaria who present with depressed

levels of consciousness, including coma and convulsions.
Management
Adults: 50 ml of 50% dextrose water given intravenously as a bolus.
Children: 1 ml of 50% dextrose water/kg body weight. This should be followed
by continuous intravenous infusion of 5 or 10% dextrose solution. Avoid fluid
overload.
7.8.3
Cerebral malaria
Definition
An y patient with a depressed level of consciousness, ranging from agitation or
confusion, to coma.
Cerebral malaria can resemble bacterial or viral infections of the central nervous
system, or any cause of raised intra-cranial pressure. The clinical features are
not specific; the patient may be flaccid, spastic, exhibit meningism, photophobia
or symmetrical upper motor neurone signs. Papilloedema or cerebral oedema is
not usually found. It is very important to exclude hypoglycaemia. If meningitis
is suspected, a lumbar puncture should be performed. Cerebral malaria may
occur as an isolated complication, or as part of multi-organ failure.
Convulsions may occur as a result of cerebral malaria, accompanying fever or in
association with hypoglycaemia.
Management
Prophylactic anticonvulsants are currently not recommended.
Treatment of
convulsions is with standard anticonvulsant drugs and supportive measures.
29

Supportive treatment should include: treatment of convulsions, monitoring of
level of consciousness and effective protection of the airway when the GCS <9.
Dexamethasone and mannitol are not recommended.
7.8.4 Renal failure
Definition
A serum creatinine greater than 265 mol/l, or a rapidly rising creatinine of more
than 2.5 mol/kg/day, and/or a urine output of less than 0.5 ml/kg/hr or less than
400 ml/day in an adult should be regarded as renal failure. When patients
present in a polyuric phase it is critical to replace fluid losses adequately.
Renal failure is generally an early complication of malaria in adults, and occurs
rarely in children. Hypo volaemia, sequestration of parasitized red cells in the
renal
vasculature,
intravascular
haemolysis
and
haemoglobinuria
are
incriminated in the development of renal dysfunction in malaria. This may lead to

acute tubular necrosis and renal failure. Acute renal failure is usually reversible
with appropriate management.
Management
Dehydration, if present, must be corrected carefully. Excessive administration of
fluids should be avoided to minimise the risk of pulmonary oedema. A central
venous catheter should be inserted where possible and maintained between 0-5
cm of water. Meticulous attention to fluid intake and output is essential to avoid
fluid overload.
Early dialysis is recommended, where available, as renal failure in malaria occurs
against a background of a hypercatabolic state. Early referral for dialysis is
recommended if the serum creatinine is rising by more than 2.5 mol/kg/day.
Veno-venous hemofiltration is the most effective mode of dialysis in malaria.
Patients with impaired renal function require a reduction in maintenance quinine
dihydrochloride salt to 5-7 mg/kg every 8 hours, after 48 hours of treatment with
the full dose. Quinine is not removed by dialysis.
30

7.8.5
Circulatory collapse
Definition
Systolic blood pressure less than 80 mmHg in adults and children >13 years. In
younger children (<13 years) clinical assessment can be a more reliable
indication of circulatory collapse than blood pressure measurement because,
firstly, the correct cuff size is often unavailable and secondly, children are able to
maintain normal blood pressure in the face of severe circulatory collapse more
efficiently than adults. Use the following signs to indicate circulatory collapse in
children:
Tachycardia
Cool/cold and clammy extremities e.g. limbs
Mottled/pale skin indicating poor perfusion
An exact cut-off point for systolic blood pressure in children is difficult as blood
systolic blood pressure increases with age from approximately 75 mmHg (at
birth) to 124 mmHg at 13 years. However a systolic blood pressure <50 mmHg
at any age indicates severe circulatory collapse.
Circulatory collapse may be seen in patients with metabolic acidosis, severe
anaemia, dehydration, ARDS, a ruptured spleen or septicaemia.
Management
Ideally, a central venous catheter should be inserted and hypovolaemia corrected
with an appropriate volume expander (blood or plasma) or isotonic saline. Start
inotropes if the CVP is >5 cm of water and the patient is still shocked, and start
rd
broad-spectrum antibiotics e.g.3 generation cephalosporin.
7.8.6
Metabolic acidosis
Measurement of acid-base status is a very useful tool in assessing a patient with

malaria. Metabolic acidosis, especially lactic acidosis, is an important indicator of
severe malaria, even if no other complications are present, and is a poor
prognostic sign.
Metabolic acidosis may present as shock and/or
respiratory distress; in children severe anaemia may present with metabolic

acidosis.
31

Management
Correct any reversible cause of acidosis, in particular dehydration,

convulsions and severe anaemia. Take care not to give excessive
fluid. The routine use of bicarbonate is not recommended. Anaemia
contributes to metabolic acidosis in children and should be managed
as follows:
Hb 6/dl
Packed cells 10-20 ml/kg over 4-6 hours ivi.
If deep breathing, reduced skin turgor, cool peripheries or

disturbed consciousness
10 ml/kg ivi over 1 hour,

Then
10 ml/kg ivi over 1-4 hours
Hb > 6g/dl
Crystalloid (0,9% saline) or Ringers lactate 10-20 ml/kg ivi over 4

hours. (rate of infusion based on clinical judgment)
Exclude metabolic acidosis with a blood gas.
Other causes for increased
respiratory rate may be excluded with a chest X-ray.

7.8.7 Respiratory complications
Acute respiratory distress syndrome (ARDS) is an uncommon, but often-fatal
complication of severe malaria, and is a particularly severe problem in
pregnancy.
ARDS may appear several days after chemotherapy has been
started, and the general condition of the patient appears to have improved.
An increase in the respiratory rate, bilateral crepitations, clinical and laboratory
evidence of cyanosis, confusion, agitation, or an arterial oxygen saturation of less
than 90%, should alert the clinician to the possibility of ARDS.
Pulmonary
oedema as a result of iatrogenic fluid overload, or pneumonia, should also be

considered.
32

Management
Treatment depends on the severity of the respiratory complications. Fluids must
be restricted. Diuretics should be given where indicated. Oxygen should be
administered, and in some patients ventilatory support may be required.
7.8.8 Hepatic dysfunction
Although a raised indirect bilirubin due to haemolysis is a frequent finding in

malaria, the clinical presence of jaundice or the finding of raised hepatic
transaminases ( 3 x normal) should alert the clinician of the probability of severe
malaria. The presence of jaundice combined with renal failure and acidosis
is cause for great concern.
7.8.9
DIC is
Disseminated intravascular coagulation (DIC)

rare in patients
with severe malaria.
Moderate degrees
of
thrombocytopenia are noted in the majority of cases of uncomplicated malaria,

but bleeding is not common. However severe degrees of thrombocytopenia may
be an indication of severe malaria and may be associated with bleeding. With
effective malaria treatment, platelet counts return to normal within a few days.
DIC is mostly associated with multi-organ failure, or hyperparasitaemia, and may
in some cases be due to secondary bacterial infection or septicaemia.
Management
Fresh whole blood if indicated, and available; and platelet transfusions if the
platelet count is very low or there is evidence of bleeding; alternatively red cell
concentrate plus fresh dried plasma and vitamin K.
7.8.10 Secondary infections
Secondary bacterial infections may complicate malaria: aspiration pneumonia,
urinary tract infections in catheterised patients, and nosocomial infections in
hospitalised patients. Secondary bacterial infections are a particular problem in
HIV co-infected patients. In a significant number of patients with severe malaria,
especially in children, bacteraemia and septicaemia have been noted, and Gram-
33

negative and Gram-positive bacteria have been cultured.
This syndrome is
associated with high mortality, and is a particular problem in children.

Management
Antibiotics (3
rd
generation cephalosporin) should be administered to all children
with severe malaria, HIV-positive patients and to any patient in whom

septicaemia is suspected. Although this is a bigger problem in children, most
guidelines recommend antibiotics for adults too as the features of bacterial and
malarial sepsis overlap. A broad-spectrum antibiotic should be administered to
cover both Gram-positive and Gram-negative bacteria e.g. a 3
rd
generation
cephalosporin.
7.8.11 Hyperparasitaemia
In general, peripheral parasite counts above 5% should be regarded as severe
malaria as this is associated with increased morbidity. Low parasite counts do
not exclude severe malaria or complications, and a parasite count must always
be interpreted together with the clinical picture and other laboratory findings.
Parasite counts are not always accurate, and counts can vary cyclically,
depending on when the smear is taken.
The peripheral parasite count does not accurately reflect the parasite load. In
highly endemic malarious areas, semi-immune persons may tolerate high
parasite densities, without clinical symptoms and complications. The presence of
schizonts of P. falciparum in a peripheral blood smear is an important indicator of
severe malaria.
Management
The patient should be managed with a rapidly acting effective anti-malarial drug.
The use of artemether-lumefantrine in hyperparasitaemia has not yet been
studied and it is possible that the course of artemisinsin-derivative would be too
short to see the same benefits of 7 days of artesunate. As hyperparasitaemia
increases the risk of malaria complications (which are often underdiagnosed) and
of malaria mortality, initial intravenous quinine therapy should be considered.
The patient should be especially closely monitored for complications, even if
34

these are not present initially. Exchange transfusion possibly has a role to play
in patients with hyperparasitaemia whose parasite counts increase or fail to
decrease significantly despite appropriate therapy.
7.8.12 Malarial haemoglobinuria
The pathogenesis is unknown. The condition is seen in patients with G-6-PD
deficiencies, which are treated with anti-malarial drugs, notably oxidant drugs like
primaquine. The condition occasionally occurs in patients with severe malaria
and in those with malaria treated with quinine. Intravascular haemolysis leads to
anaemia, passage of haemoglobin in the urine, and varying degrees of renal
failure.
Management
Continue appropriate malaria chemotherapy: quinine may be continued
(primaquine must be avoided in patients with G-6-PD deficiency). Supportive
therapy should include blood transfusions for severe anaemia, adequate fluids
and renal dialysis where indicated.
7.8.13 Exchange transfusion
The role of exchange transfusion in severe malaria is controversial and there are
no controlled studies to support its use.
Exchange transfusion may be considered for use in selected patients e.g.
patients with hyperparasitaemia in whom the parasite count increases despite
appropriate chemotherapy, and patients who develop multi-organ dysfunction
despite appropriate chemotherapy.
The requirements for exchange transfusion include a safe blood supply, a skilled
operator and a haemodynamically stable patient. The exchange volume should
be 4-10 litres of blood for an adult.
7.8.14 Splenic rupture
Splenic rupture is a rare complication of malaria, and is more common in P. vivax
infections.
35

(Page 52 WHO TREA TMENT GUIDELINES 2006)
36

8.
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Baird JK, Hoffman SL. Primaquine therapy for malaria.
Clinical Infectious
Diseases 2004; 39: 1336 1346
Barnes KI et al. Efficacy of rectal artesunate compared to parenteral quinine in

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Cohen C, Karstaedt A, Frean J, et al. Increased prevalence of severe malaria in
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Falade C, Makanga M, Premij Z, et.al.
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of Tropical Medicine and Hygiene 2005; 99(6): 459-67
Gaye O et al. Diagnosis of Plasmodium falciparum malaria using ParaSight F,
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Grimwade K et al. HIV infection as a cofactor for severe falciparum malaria in
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Grimwade K et al. Childhood malaria in a region of unstable transmission and

high humans immunodeficiency virus prevalence. Pediatric Infectious Disease
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Hien TT et al. Comparative pharmacokinetics of intramuscular artesunate and

artemether in patients with severe falciparum malaria. Anti-microbial Agents and
Chemotherapy 2004; 48: 4234 4239
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microscopy for confirmation of symptomatically diagnosed malaria. Journal of
Clinical Microb iology 2002; 40: 4675 4678
Krishna S, White N J. Pharmokinetics of quinine, chloroquine and amodiaquine.
Clinical implications. Clinical Pharmokinetics 1996; 30: 263-299
Marsh K et al. Clinical Algorithm for malaria in Africa. Lancet 1996; 34: 1327
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McGready R, Cho T, Keo N K et al. Artemisinin anti-malarials in pregnancy: a
prospective treatment study of 539 episodes of multi-drug resistant Plasmodium
falciparum. Clinical Infectious Diseases 2001; 33(12): 2009-16
Newton PN et al. Randomized comparison of artesunate and quinine in the
treatment of severe falciparum malaria. Clinical Infectious Diseases 2003; 37: 7
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Pasvol G et al.
Quinine treatment of severe falciparum malaria in African
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American Journal of

Phan GT et al. Artemesinin or chloroquine for blood stage Plasmodium vivax
malaria in Vietnam. Tropical Medicine and International Health 2002; 7: 858
864
Riddle MS, Jackson JL et al. Exchange transfusion as an adjunct therapy in

severe Plasmodium falciparum malaria: a meta-analysis.
Clinical Infectious
Diseases 2002; 34: 1192-1198
Ringwald P. Monitoring anti-malarial drug efficacy. Clinical Infectious Diseases

2004, 38: 1192 1193
Ter Kuile F et al. The burden of co-infection with human immunodeficiency virus
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Taylor WR. Anti-malarial drug toxicity: a re view. Drug Safety 2004; 27: 25 61
Toovey S, Jamieson A. Co-artemether has been used in ambulatory treatment

of falciparum malaria. British Medical Journal 2002; 324: 1585A
van Hensbroek M B et al. Quinine pharmacokinetics in young children with
severe malaria American Journal of Tropical Medicine and Hygiene 1996; 54:
237 242
van Hensbroek M B, On yiorah E, Jaffar S. et al. A trial of artemether versus

quinine in children with cerebral malaria. New England Journal of Medicine
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von Seidlein L et al. A randomized controlled trial of artemether/benflumetol, a

new anti-malarial, and pyrimethamine/sulphadoxine in the
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van Vugt M, Wilairatana P, Gemperli B, et al.
artemether-lumefantrine
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multidrug-resistant
Plasmodium
falciparum malaria. American Journal of Tropical Medicine and Hygiene 1999;

60(6): 936-942
van Vugt M, Looareesuwan S, Wilairatana P, et al. Artemether-lumefantrine for
the treatment of multidrug-resistant falciparum malaria.
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Royal Society of Tropical Medicine and Hygiene 2000; 94: 545-548

van Vugt M et al. A case-control auditory evaluation of patients treated with
artemisinin derivatives for multi-drug resistant Plasmodium falciparum malaria.
American Journal of Tropical Medicine and Hygiene 2000; 62: 65-69
van Vugt MV et al. Efficacy of six doses of artemether-lumefantrine (benflumetol)
in multidrug-resistant Plasmodium falciparum malaria.
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White NJ. Optimal regimes for parenteral quinine. Transactions of the Royal
Society of Tropical Medicine and Hygiene 1995; 89: 462 464
White NJ. The treatment of malaria. New England Journal of Medicine 1996;
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White NJ. The assessment of anti-malarial drug efficacy. Trends in Parasitology
2002; 18: 458 464
White NJ, Olliaro PL.
Strategies for the prevention of anti-malarial drug
resistance: rationale for combination chemotherapy for malaria. Parasitology

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40

WHO Expert Committee on Malaria. Twentieth Report. Geneva, World Health
Organization 2000; (WHO Technical Report, Series No. 892)
41

DOSAGE GUIDELINES FOR THE TREATMENT OF MALARIA (JUNE 2009)
DRUG
QUININE (parenteral)
1 ampoule (1 ml)
usually contains 300
mg quinine
dihydrochloride
QUININE (oral)
1 tablet usually
contains 300 mg
quinine sulphate
DOXYCYCLINE
(Use in combination
with quinine)
CLINDAMYCIN
(Use in combination
with quinine in
pregnancy and
children <8 years)
ADULT DOSAGE
PAEDIATRIC DOSAGE
Loading dose: Quinine dihydrochloride salt 20 mg/kg by IV
infusion over 4 hours in 5% dextrose saline:
[Important Note: No loading dose to be given if the patient has
definitely received treatment doses of mefloquine, quinine (more
than 40 mg/kg in the previous 2 days), or quinidine or halofantrine
(in the last 24 hours). If in doubt the loading dose should be
given.]
Maintenance dose: Eight hours after the start of the loading
dose, give 10 mg/kg quinine dihydrochloride salt infused over 4-6
hours, repeated every 8 hours until the patient can take oral
quinine.
Important Note : If a treatment dose of mefloquine has been
taken in the 12 hours before severe malaria treatment starts, ECG
monitoring would be advisable.]
The required dose, diluted preferably in 5% dextrose to
counteract hypoglycaemia, is given in a total volume of 5-10 ml/kg
(depending on patients fluid balance) by infusion into a large
vein.
Where facilities for IV infusion do not exist, quinine can be
given IM in the same dosage. The required dose, diluted to
between 60 mg and 100 mg/ml, should be given as half the
dose in each anterior thigh.
Total quinine (parenteral and/or oral) duration at least 7-10
days, or until smears are negative.
Paediatric dose: Same as adult dose.
All patients should ideally have cardiac monitoring.
The dose of IV quinine should be reduced by 1/3-1/2 (to 5-7
mg/kg) on the third day of treatment if parenteral therapy is
required for more than 48 hours because there has been no
significant improvement in the clinical condition of the patient,
or acute renal failure has developed.
600 mg (i.e. usually 2 tablets) 10 mg salt/kg body weight every
every 8 hours for 7 days or 10 8 hours for 7 days. The tablets
mg salt/kg (maximum usually may be crushed with banana,
600 mg) 8 hourly for 7 days
jam or chocolate syrup.
Commence as soon as can be Do not use in children under 8
tolerated after starting quinine. years old.
200 mg stat; followed by 100- 4 mg/kg stat, then 2 mg/kg daily
200 mg daily for 7 da ys. Avoid for at least 7 days or until
in pregnancy.
negative smears.
Commence as soon as can be 10 mg/kg bd for 7 days or 5
tolerated after starting quinine mg/kg tds for 7 days.
10 mg/kg bd for 7 days or 5
mg/kg tds for 7 days.
42

DOSAGE GUIDELINES FOR THE TREATMENT OF MALARIA (continued)
DRUG
ARTEMETHER
LUMEFANTRINE
1 tablet contains
artemether 20 mg plus
lumefantrine 120 mg.
ADULT DOSAGE
PAEDIATRIC DOSAGE
10 - <15 kg: One tablet stat, followed by one after 8 hours and
then one twice daily on each of the following two days (total
course = 6 tablets)
15-<25 kg: Two tablets stat, followed by two after 8 hours and
then two twice daily on each of the following two days (total
course = 12 tablets)
25-<35 kg: Three tablets stat, followed by three after 8 hours and
then three twice daily on each of the following two days (total
course = 18 tablets)
35-<65 kg: Four tablets stat, followed by four after 8 hours and
then four twice daily on each of the following two days (total
course = 24 tablets).
>65 kg: Dose as for > 35 kg above, although inadequate
experience in this weight group justifies closer monitoring of
treatment response.
CHLOROQUINE
(non-falciparum
malaria only)
1 tablet contains 150
mg chloroquine base
PRIMAQUINE
1 tablet usually
contains 26.3 mg
primaquine phosphate
= 15 mg primaquine
base.
MEFLOQUINE (not
registered for
treatment of malaria in
South Africa)
1 tablet contains 250
mg base
Administer with food/milk containing at least 1.3g fat to ensure

adequate ab sorption.
Orally: 1.5g over 3 da ys, as Initial dose: 10 mg base/kg
follows: initially 600
mg, then 5 mg base/kg at the same
followed by 300 mg 6-8 hours dosage intervals as the adult
later, and 300 mg once daily on regimen.
second and third days.
Contra-indicated in children
Orally: 15 mg base daily for 14
days following standard
under 1 year old.
0.250.3 mg base/kg daily for
treatment or 0.25 mg base/kg
daily for 14 days.
14 days following standard
treatment.
In mild G-6-PD Deficiency (1060% residual G-6-PD activity):
In mild G-6-PD Deficiency: 0.545 mg base weekly/0.5-0.8 mg 0.8 mg base/kg weekly for
base/kg body weight once a
8 weeks.
week for six to eight weeks.
Oral, 25 mg/kg base (maximum Oral, 25 mg/kg base as a single
total dose 1.5 g) in 23 divided dose or 2 divided doses.
doses 68 hours apart as
follows: loading dose, 750 mg;
then 500 mg after 68 hours
and 250 mg after a further 6-8
hours.
Adapted with permission from the Malaria Update, edited b y A. Swart of the Medicines
Information Centre, UCT.
43

Important Notes:
Patients, who vomit less than 30 minutes after receiving the drug orally,
should be given a second full dose. If they vomit 30-60 minutes after the
dose, an additional half-dose should be given.
When treating severe malaria, oral treatment should be substituted as soon

as the patient can take tablets by mouth and at least 3 doses of parenteral
quinine have been given.
For P. vivax malaria acquired in Oceania and southeast Asia the dose of
primaquine should be increased to 0.33-0.5 mg base/kg daily for 14 days.
44

Summary of Malaria Treatment Guidelines
Early diagnosis and prompt correct treatment are crucial
Malaria is a progressive and unpredictable disease.
Complications may develop despite treatment.
Severity of disease is frequently underestimated, so careful monitoring of all
patients is mandatory.
Uncomplicated malaria
Only patients with malaria who are ambulant, with normal mental state, adequate
urine output, able to take oral medication, and not vomiting excessively can be
considered as uncomplicated. Note: All pregnant women and children < 1 year
should b e regarded as high-risk patients and treated with quinine at the highest
level of care availab le.
Indicators of severe malaria
Decreased level
of consciousness
(prostration, extreme weakness,
restlessness, confusion, convulsions, coma)
Severe vomiting, diarrhoea or dehydration, decreased urine output

(<0.5 ml/kg/hr), or impaired renal function
Unable to take oral medication
Respiratory distress (respiratory rate > 30 per minute)
Circulatory compromise (low BP, cold peripheries)
Spontaneous bleeding (disseminated intravascular coagulation)
Jaundice
Parasitaemias of 5% or greater
General Management of Se vere Malaria

Manage patients in highest level of care available
1.
Monitor fluid balance carefully.
Avoid over- OR under-hydration. Fluid
overload is extremely dangerous as it may precipitate potentially fatal

respiratory failure. Hypovolaemia is also dangerous and may potentiate
renal failure, metabolic acidosis and circulatory collapse.
Accurate
recording of fluid input and output is essential. Frequent central venous

pressure monitoring is recommended; maintain between 0 and 5 cm H2O.
45

2.
A rapid initial measurement of blood glucose level and 4-6 hourly monitoring
for hypoglycaemia are essential.
3.
Regular monitoring of temperature, respiratory rate, blood pressure, and

level of consciousness is mandatory.
4.
Look for and manage any associated infections. Where indicated, bacterial
meningitis should be excluded by lumbar puncture, or covered by
appropriate empiric antibiotic treatment.
5.
Reduce fever > 39 C b y tepid sponging, and paracetamol.
6.
Transfuse if haemoglobin 6 g/dl (haematocrit < 20%) or anaemia

associated with haemodynamic compromise.
7.
Laboratory tests: Regular monitoring of haemoglobin, urea and electrolytes,

acid-base status, and an initial assessment of liver function.
8.
Level of parasitaemia should be assessed daily; at 72 hours, level of

parasitaemia should be less than 25% of baseline.
9.
Early dialysis (haemo- or peritoneal dialysis) is recommended and may be

life-saving.
Indications
for
dialysis
include
metabolic
acidosis,
hyperkalaemia, fluid overload, rapidly rising creatinine or patients who

remain anuric after adequate re-hydration.
10. Treat seizures promptly with intravenous benzodiazepines (check for
hypoxia and hypoglycaemia).
11. Respiratory
failure
(ARDS/pulmonary
oedema):
Administer
oxygen,
furosemide, assisted ventilation (PEEP) if required.

As malaria complications develop rapidly, regular monitoring and urgent
interventions may be lifesaving.
46

MALARIA RISK MAP FOR SOUTH AFRICA
47
Department of Health
Private Bag X 828
PRETORIA
0001
FAX: (012) 312-3113
GUIDELINES FOR THE TREATMENT OF MALARIA

Directorate: Communicable Disease Control (Hallmark R 1411)
NAME:
ADDRESS: PH YSIC AL AND POSTAL
CODE:
TEL. NO:
NUMBER OF COPIES:
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GUIDELINES FOR THE

Treatment of Malaria in South Africa - Summ ary Flowchart 2007

5. Clinical presentation and diagnosis

9. Dosage guidelines for the treatment of malaria

10. Summary of malaria treatment guidelines

11. Malaria risk map for South Africa

DOH officials: Dr Bonnie Maloba, Communicable Diseas e Control (CDC), Mr Devanand

Artem isinin-based com bination therapy

Acute res piratory distress syndrome

Communicable Diseas e Control

Central nervous s ystem

Central venous press ure

Diss eminated intravas cular coagulation

Non-s teroidal anti-inflamm atory drugs

Rapid diagnos tic tests

Treatment of Malaria in South Africa- Summary Flowchart 2006

Quinine plus eith er

Uncomplicated P. falciparum malaria

IV Quinine plus either

Severe P. falciparum malaria

Other Plasmodium s pecies**

Clinical foll ow up and repeat blood

Malaria treatment guidelines Final Draft 23 June 2009

The relentless development of drug resistance in malaria parasites (notably

This prompted a policy change from

chloroquine to sulphadoxine-pyrimethamine (SP) as first line treatment for

The development of significant SP resistance in KZN led to a further policy

Malaria treatment guidelines Final Draft 23 June 2009

The objectives of malaria treatment are:

To prevent disease progression and development of severe malaria

To eliminate parasitaemia to minimise transmission, and

To limit the emergence and spread of drug resistance

Occasionally mixed infections

occur. Infections due to P. falciparum may be severe and complicated. These

South Africans are non-immune, including residents in areas where malaria

Malaria treatment guidelines Final Draft 23 June 2009

CLINICAL PRESENTATION AND DIAGNOSIS

A high index of suspicion is the most important element in the diagnosis of

malaria is contracted in the North-West and Northern Cape provinces adjacent to

e.g. cotrimoxazole, tetracycline,

macrolides, chloramphenicol and quinolones. Very rarely, incubation periods for

Malaria treatment guidelines Final Draft 23 June 2009

Clinical signs in adults and children

Malaria treatment guidelines Final Draft 23 June 2009

A diagnosis of malaria cannot be confirmed or excluded clinically. Since

severe malaria in non-immune patients. Importantly, the converse may not be

Malaria treatment guidelines Final Draft 23 June 2009

The majority of the tests will only detect P.

The rapid tests for P. falciparum are generally highly sensitive.

Performance is, however, dependent on the correct storage, usage and

All children 1 year (and consider admitting children up to 5 years

All pregnant patients

All patients 65 years

Immuno-compromised patients where possible

Malaria treatment guidelines Final Draft 23 June 2009

All patients with features of severe malaria or danger signs:

Decreased level of consciousness

Extreme weakness (prostration)

Decreased urine output