Treating severe and complicated malaria
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《英国医生杂志》
1 Department of Parasitology, Prince Leopold Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium udalessandro@itg.be
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 antigens (HLA Bw 53 is associated with protection from severe malaria), it is still unclear why only some children develop severe 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 management of complications such as hypoglycaemia and metabolic acidosis.
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 resistance to chloroquine and the emerging resistance to sulfadoxine-pyrimethamine, these two drugs should not be considered in severe 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 uncertain.4 A few studies have shown good efficacy and tolerability for rectal administration, without the problems of the intramuscular route or the complexity of intravenous administration.4
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 administration 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 resources, cost has to be taken into account when drug policies are formulated. Nevertheless, the drug accounts for only a fraction 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.
Search date October 2002
Competing interests: None declared.
References
World Health Organization. Severe falciparum malaria. Trans R Soc Trop Med Hyg 2000;94(suppl 1): 1-74.
World Health Organization. The use of antimalarial drugs: report of a WHO informal consultation. Geneva: WHO, 2001.
Winstanley P. Modern chemotherapeutic options for malaria. Lancet Infectious Diseases 2001;1: 242-50.
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.
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.
D'Alessandro U, Olaleye B, Langerock P, Bennett S, Cham K, Cham B, et al. The Gambian national impregnated bednet programme: evaluation of effectiveness by means of case-control studies. Trans R Soc Hyg Trop Med 1997;91: 638-42.(Umberto D'Alessandro, hea)
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 antigens (HLA Bw 53 is associated with protection from severe malaria), it is still unclear why only some children develop severe 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 management of complications such as hypoglycaemia and metabolic acidosis.
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 resistance to chloroquine and the emerging resistance to sulfadoxine-pyrimethamine, these two drugs should not be considered in severe 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 uncertain.4 A few studies have shown good efficacy and tolerability for rectal administration, without the problems of the intramuscular route or the complexity of intravenous administration.4
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 administration 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 resources, cost has to be taken into account when drug policies are formulated. Nevertheless, the drug accounts for only a fraction 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.
Search date October 2002
Competing interests: None declared.
References
World Health Organization. Severe falciparum malaria. Trans R Soc Trop Med Hyg 2000;94(suppl 1): 1-74.
World Health Organization. The use of antimalarial drugs: report of a WHO informal consultation. Geneva: WHO, 2001.
Winstanley P. Modern chemotherapeutic options for malaria. Lancet Infectious Diseases 2001;1: 242-50.
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.
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.
D'Alessandro U, Olaleye B, Langerock P, Bennett S, Cham K, Cham B, et al. The Gambian national impregnated bednet programme: evaluation of effectiveness by means of case-control studies. Trans R Soc Hyg Trop Med 1997;91: 638-42.(Umberto D'Alessandro, hea)