Academic journal article Bulletin of the World Health Organization

Therapeutic Efficacy of Sulfadoxine-Pyrimethamine, Amodiaquine and the Sulfadoxine-Pyrimethamine-Amodiaquine Combination against Uncomplicated Plasmodium Falciparum Malaria in Young Children in Cameroon. (Research)

Academic journal article Bulletin of the World Health Organization

Therapeutic Efficacy of Sulfadoxine-Pyrimethamine, Amodiaquine and the Sulfadoxine-Pyrimethamine-Amodiaquine Combination against Uncomplicated Plasmodium Falciparum Malaria in Young Children in Cameroon. (Research)

Article excerpt

Introduction

The spread of chloroquine-resistant Plasmodium falciparum malaria in Africa poses a serious challenge to the management of malaria infections, which is based on rapid diagnosis and treatment with suitable drugs. Chloroquine is no longer effective in Cameroon except in the northern provinces, i.e. there is a clinical and/or parasitological failure rate exceeding 25% on day 14 (1-3). Similar observations on the declining clinical efficacy of chloroquine have been reported with increasing frequency from other African countries, notably in Central and East Africa (4-6).

Current options for the treatment of acute uncomplicated ehloroquine-resistant P. falciparum infections in Africa include the use of amodiaquine (AQ) and sulfadoxine-pyfimethamine (SP). The choice of these drugs is based not only on their clinical efficacy but also on their affordability to the great majority of African patients, good tolerance, safety for young children, and low toxicity risk. Their high but not total clinical efficacy when used separately has been demonstrated in recent clinical trials conducted in chloroquine-resistant zones of Africa (7-10). The side-effects are well known and documented. Toxic reactions occur with each of them but are rarely associated with the standard therapeutic doses, and the clinical benefit derived from SP and AQ outweighs the risk of toxicity. Orally administered quinine is an alternative option and is generally reserved for patients who have failed to respond to chloroquine, AQ, and/or SP. Other available antimalarial drugs, such as mefioquine, halofantrine, artemisinin derivatives, lumefantrine, and atovaquone, are highly effective against chloroquine-resistant P. falciparum but do not satisfy all the above criteria and are not, therefore, indicated at present for the treatment of most malarial infections in Africa.

Because of the high prevalence of chloroquine-resistant P. falciparum malaria, several East African countries have adopted SP for the first-line treatment of uncomplicated malaria (11). Although this drug remains highly effective, some studies conducted recently in East Africa have reported treatment failures (12-14). In Yaounde, Cameroon, a failure rate of 12% was observed in children aged over 5 years and in adults treated with SP and followed up for at least 14 days (7). These observations are in agreement with previous experience in South-East Asia, where SP is no longer effective (15, 16). The rapid development of resistance to SP when the drug is employed on the national or regional scale is attributable to the requirement of few point mutations in the parasite's dihydropteroate synthase gene (for sulfadoxine) and dihydrofolate reductase gene (for pyrimethamine) (17).

Most malaria experts believe that AQ is still useful and effective in areas of low-grade chloroquine resistance (18). Cameroon has officially adopted the use of AQ in its antimalarial drug policy. Recent therapeutic monitoring at various sentinel sites in the country indicates that AQ has high efficacy in the treatment of falciparum malaria in children under 5 years of age (3). In fact, there is some evidence that AQ is less effective in areas where chloroquine resistance has attained a high level, essentially in Asia, and this has led to concerns about potential cross-resistance between chloroquine and AQ (19-23). In Yaounde studies indicate that there was no treatment failure with AQ in children aged over 5 years or in adults, but parasitological failure was evident in 9 of 67 (13.4%) children aged under 5 years on day 14 (7, 24). These observations raise the question as to how long SP and AQ, used alone, can remain effective in Africa.

One of the possible therapeutic strategies for prolonging the clinical efficacy of an antimalarial drug and reducing the risk of selecting drug-resistant malaria parasites is to use drug combinations (25-27). This strategy has been adopted in multidrug-resistant areas in South-East Asia, where mefloquine-sulfadoxine-pyrimethamine, which is no longer used, quinine-tetracycline, and mefloquine-artemisinin derivatives have been employed for tint-line treatment. …

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