Reduction of malaria transmission to Anopheles mosquitoes with a six-dose regimen of co-artemether

Abstract

Background: Resistance of malaria parasites to chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) is increasing in prevalence in Africa. Combination therapy can both improve treatment and provide important public health benefits if it curbs the spread of parasites harbouring resistance genes. Thus, drug combinations must be identified which minimise gametocyte emergence in treated cases, and so prevent selective transmission of parasites resistant to any of the partner drugs.

Methods and findings: In a randomised controlled trial, 497 children with uncomplicated falciparum malaria were treated with CQ and SP (three doses and one dose respectively; n = 91), or six doses of artemether in fixed combination with lumefantrine (co-artemether [Coartem, Riamet]) (n = 406). Carriage rates of Plasmodium falciparum gametocytes and trophozoites were measured 7, 14, and 28 d after treatment. The infectiousness of venous blood from 29 children carrying P. falciparum gametocytes 7 d after treatment was tested by membrane-feeding of Anopheles mosquitoes. Children treated with co-artemether were significantly less likely to carry gametocytes within the 4 weeks following treatment than those receiving CQ/SP (30 of 378 [7.94%] versus 42 of 86 [48.8%]; p < 0.0001). Carriers in the co-artemether group harboured gametocytes at significantly lower densities, for shorter periods (0.3 d versus 4.2 d; p < 0.0001) and were less infectious to mosquitoes at day 7 (p < 0.001) than carriers who had received CQ/SP.

Conclusions: Co-artemether is highly effective at preventing post-treatment transmission of P. falciparum. Our results suggest that co-artemether has specific activity against immature sequestered gametocytes, and has the capacity to minimise transmission of drug-resistant parasites.

Figure 1. Profile of the Study

Ten and 38 children in the CQ/SP and co-artemether groups, respectively, who were not seen on day 7 were seen on day 14. Two and four children, respectively, who were not seen on day 7 or day 14 were seen on day 28. Ten children in the co-artemether group not seen on day 14 were seen on day 28.

Figure 2. Gametocyte Carriage after Treatment with CQ/SP or Co-Artemether

Point-prevalence of gametocyte-positive thick films in both treatment groups at 7, 14, and 28 d post-treatment (limit of detection: five gametocytes per μl of peripheral blood). Error bars represent 95% CI calculated from the binomial distribution. Denominators for CQ/SP and co-artemether (CoArt) groups are, respectively, 74 and 336 (day 7), 79 and 356 (day 14), and 72 and 355 (day 28).

Figure 3. Crude Parasitological Failure after Treatment with CQ/SP or Co-Artemether

Point-prevalence of trophozoite-positive thick films in both treatment groups at 7, 14, and 28 d post-treatment (limit of detection: five trophozoites per μl of peripheral blood). Error bars represent 95% CI calculated from the binomial distribution. Denominators for CQ/SP and co-artemether (CoArt) groups are, respectively, 74 and 336 (day 7), 79 and 356 (day 14), and 72 and 355 (day 28).