A trial of proguanil-dapsone in comparison with sulfadoxine-pyrimethamine for the clearance of Plasmodium falciparum infections in Tanzania

Considerable levels of resistance to sulfadoxine-pyrimethamine (SP) have be en reported in Plasmodium falciparum in north-eastern Tanzania, and the ide ntification of a suitable antimalarial to replace SP is now a high priority . We conducted a trial in July 2000 to determine the efficacy of proguanil (PG) plus dapsone (DS), compared with that of SP, for the treatment of asym ptomatic falciparum infection. A total of 220 children with parasitaemia gr eater than or equal to 2000 per muL completed the study; 112 had received a single dose of SP (dosage calculated for pyrimethamine 1.25 mg/kg and sulf adoxine 25 mg/kg) and 108 had taken PG 10 mg/kg with DS 2.5 mg/kg each day for 3 days. Clearance of asexual parasites at day 7 was 14.3% with SP, but 93.5% with PG-DS. The remarkably high failure rate with SP was not associat ed with occurrence of leucine substitution at position 164 of the dhfr gene . Both treatment regimens were well tolerated. Compared with available data on another antifolate combination, chlorproguanil-dapsone ('Lapdap'), PG-D S was slightly but significantly inferior in achieving parasite clearance ( 99.5% versus 93.5%). The estimated cost of a 3-day course of PG-DS treatmen t for a child weighing 18 kg is US $0.15. With the rising incidence of SP-r esistant P. falciparum infection, PG-DS could provide an effective, afforda ble and already available therapeutic alternative for malaria in East Afric a at least until chlorproguanil-dapsone is registered.