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[afro-nets] Treating severe and complicated malaria

Treating severe and complicated malaria

BMJ 2004;328:155 (17 January), doi:10.1136/bmj.328.7432.155

Umberto D'Alessandro, head of epidemiology unit
Department of Parasitology, Prince Leopold Institute of Tropical
Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium

Clinical attacks are usually uncomplicated and can be managed
with an effective oral drug. Most occur in sub-Saharan Africa.
Of the 200 million episodes of clinical malaria that occur each
year among African children, 4-6 million are severe and life
threatening, and most of the 1 million deaths from malaria
worldwide are in Africa.1 Although some risk factors for severe
malaria have been identified-for example, human leucocyte anti-
gens (HLA Bw 53 is associated with protection from severe ma-
laria), it is still unclear why only some children develop se-
vere disease.

The clinical manifestations of severe malaria are complex and
may vary between age groups and according to the intensity of
transmission that determines the speed at which partial immunity
is acquired. Case management is also complex and is not limited
to giving efficacious antimalarial drugs-it includes proper man-
agement of complications such as hypoglycaemia and metabolic

Quinine remains the most widely used antimalarial drug in the
treatment of severe malaria,1 but decreased sensitivity has been
detected in areas of South East Asia.2 Nowadays, drug resistance
is probably the major problem for malaria control countries
where malaria is endemic. This extract from Clinical Evidence
defined chloroquine and sulfadoxine-pyrimethamine as drugs of
"unknown effectiveness"; in the light of the widespread resis-
tance to chloroquine and the emerging resistance to sulfadoxine-
pyrimethamine, these two drugs should not be considered in se-
vere cases.

Slow, constant intravenous infusion is the preferred route for
giving quinine.3 This is not always possible and quinine can
also be given by deep intramuscular injection into the anterior
thigh. Intragluteal injection should be avoided because of the
risk of sciatic nerve damage, and the absorption is slow and un-
certain.4 A few studies have shown good efficacy and tolerabil-
ity for rectal administration, without the problems of the in-
tramuscular route or the complexity of intravenous administra-

In children able to attend a health facility that is well
staffed and with adequate supplies, most deaths occur within 24
hours after admission,5 underscoring the importance of early
treatment for preventing deaths.6 It is therefore important to
improve access to appropriate care. One way of tackling this
problem is to simplify the treatment by using rectal quinine or
rectal artemisinin or artesunate, which could be given promptly
even at basic health facilities. A trial on prompt administra-
tion of rectal artesunate is ongoing and should provide some
data on its usefulness in early treatment.

Artemether is rightly classified among the interventions likely
to be beneficial and has a marginal advantage over quinine. It
is easier to use (intramuscularly) and is less likely to cause
hypoglycaemia, but the cost of injections for treating an adult
is about three times that of quinine.2 In settings with poor re-
sources, cost has to be taken into account when drug policies
are formulated. Nevertheless, the drug accounts for only a frac-
tion of the total cost of managing cases of severe malaria. A
careful evaluation is needed.

Another message comes from the small sample size of most of the
reviewed studies, which underlines the difficulties of carrying
out research on treatment of severe malaria.


[1] World Health Organization. Severe falciparum malaria. Trans
R Soc Trop Med Hyg 2000;94(suppl 1): 1-74.[ISI:

[2] World Health Organization. The use of antimalarial drugs:
report of a WHO informal consultation. Geneva: WHO, 2001.

[3] Winstanley P. Modern chemotherapeutic options for malaria.
Lancet Infectious Diseases 2001;1: 242-50.[CrossRef:

[4] Barennes H, Kailou D, Pussard E, Munjakazi JM, Fernan M,
Sherouat H, et al. Administration intrarectale de la quinine: un
traitement précoce du paludisme grave de l'enfant? Cahiers
d'études et de recherche francophones/Santé 2001;11: 145-53.

[5] Marsh K, Forster D, Waruiru C, Mwangi I, Winstanley M, Marsh
V, et al. Indicators of life-threatening malaria in African
children. N Engl J Med 1995;332: 1399-404.[Abstract:

/Free Full Text:

[6] D'Alessandro U, Olaleye B, Langerock P, Bennett S, Cham K,
Cham B, et al. The Gambian national impregnated bednet pro-
gramme: evaluation of effectiveness by means of case-control
studies. Trans R Soc Hyg Trop Med 1997;91: 638-42. 

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