High level of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine in children in Tanzania

Abstract

In many areas of tropical Africa affected by chloroquine-resistant Plasmodium falciparum, a combination of sulfadoxine and pyrimethamine (S-P) is used for alternative medication, especially in young children. In Magoda village in Muheza District, north-eastern Tanzania, 38 children 1-10 years of age were enrolled in a therapeutic study of S-P in July 1994. All had monoinfections of P. falciparum and an asexual parasite count of 1000-80,000/microL of blood. S-P was given as a single dose corresponding to 0.8-1.4 mg pyrimethamine/kg body weight. Of the 38 children followed up to day 7, 10 showed an S/RI response, 26 an RII response, and 2 an RIII response. Older children had lower pre-treatment parasitaemia and a better therapeutic response than younger children. Among the various contributory factors responsible for the poor therapeutic result, drug pressure from a prophylactic intervention with weekly dapsone-pyrimethamine between May 1993 and May 1994 seems to have been the most important.

The safety and efficacy of sulfadoxine-pyrimethamine, amodiaquine, and their combination in the treatment of uncomplicated Plasmodium falciparum malaria.

“…An R-I resistance level of 26% and an R-II level of 15% are bad news at a time when SP drug pressure is likely to increase dramatically as a result of the change in the national malaria treatment policy. Based on experience from elsewhere, [10][11][12] it is likely that clinical resistance to SP will develop rapidly. This is of particular concern because several studies of CT include SP as a constituent drug; consequently, it may be that by the time SPcontaining CT regimens are available, their effectiveness will have been undermined by increased levels of SP resistance.…”

“…Tanzania has joined Malawi and Kenya 6,7 in replacing CQ with SP as firstline treatment of malaria. However, concerns that the long half-life of the drug may lead to a relatively rapid increase in the rate at which resistance develops, 8 especially in situations in which the drug pressure is high, have been borne out by molecular 9 and in vivo studies 10,11 and by the short duration of its efficacy in Thailand. 12 If SP is to be a useful component of CT, it needs to be protected until combinations with artemether are shown to be safe, effective, and available.…”

Comparative Efficacy of Aminoquinoline-Antifolate Combinations for the Treatment of Uncomplicated Falciparum Malaria in Kampala, Uganda

“…Indeed, evidence for increasing SP resistance in East Africa has begun to emerge. [3][4][5][6] Countries faced with a high prevalence of CQ-resistant malaria are increasingly considering the use of combination therapy to treat uncomplicated malaria. Combination therapy has been advocated to improve efficacy and delay the development and spread of drug resistance.…”

Genome comparison of progressively drug resistant Plasmodium falciparum lines derived from drug sensitive clone

“…Emergence of strains resistant to pyrimethamine appeared in the field rapidly soon after introduction of the pyrimethamine-sulfadoxine combination as an alternate to chloroquine in all countries where this combination was deployed. The resistance to pyrimethamine-sulfadoxine combination is fast increasing (Ronn et al 1996). Proguanil, unlike pyrimethamine, still plays a useful role in prophylaxis and treatment in combination with other drugs (Peters 1998).…”