A Randomized Open-Label Trial of Artesunate- Sulfadoxine-Pyrimethamine with or without Primaquine for Elimination of Sub-Microscopic P. falciparum Parasitaemia and Gametocyte Carriage in Eastern Sudan

Abstract

BackgroundIn areas of seasonal malaria transmission, treatment of asymptomatic carriers of malaria parasites, whose parasitaemia persists at low densities throughout the dry season, could be a useful strategy for malaria control. We carried out a randomized trial to compare two drug regimens for clearance of parasitaemia in order to identify the optimum regimen for use in mass drug administration in the dry season.Methodology and Principal FindingsA two-arm open-label randomized controlled trial was conducted during the dry season in an area of distinct seasonal malaria in two villages in Gedarif State in eastern Sudan. Participants were asymptomatic adults and children aged over 6 months, with low-density P. falciparum infection detected by PCR. Participants were randomized to receive artesunate/sulfadoxine-pyrimethamine (AS+SP) combination for three days with or without a dose of primaquine (PQ) on the fourth day. Parasitaemia detected by PCR on days 3, 7 and 14 after the start of treatment and gametocytes detected by RT-PCR on days 7 and 14 were then recorded. 104 individuals who had low density parasitaemia at screening were randomized and treated during the dry season. On day 7, 8.3% were positive by PCR in the AS+SP+PQ group and 6.5% in the AS+SP group (risk difference 1.8%, 95%CI −10.3% to +13.8%). At enrolment, 12% (12/100) were carrying gametocytes. This was reduced to 6.4% and 4.4% by day 14 (Risk difference 1.9% (95%CI −9.3% to +13.2%) in AS+SP+PQ and AS+SP groups, respectively.ConclusionAddition of primaquine to artemisinin combination treatment did not improve elimination of parasitaemia and prevention of gametocyte carriage in carriers with low-density parasitaemia in the dry season.Trial RegistrationClinicalTrials.gov NCT00330902

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“…This addition reduced gametocyte prevalence during treatment and the risk of transmission to another host. These results are in contrast to those reported by El-Sayed and others 19 who concluded that adding PQ did not reduce sexual and asexual parasitemias. These results may be partly explained by the fact that PQ was added to treatment with AS + SP on the fourth day after starting treatment, and treatment was evaluated for asymptomatic patients who had been diagnosed as having submicroscopic parasitemia by polymerase chain reaction.…”

Effect of Primaquine on Gametocyte Carriage in the Case-Management of Uncomplicated Falciparum Malaria with Acts: Nigerian Perspective

“…On the contrary, studies from Sudan and India showed reduced or no effect of PQ [29] [30]. These studies agree with Okell et al, who in a randomized controlled study also showed conclusively that a six-dose course of Artemether-Lumefantrine (co-artemether) given to children with P. falciparum malaria in Gambia reduces gametocyte prevalence, duration of gametocyte carriage, and infectiousness to mosquitoes [31].…”

“…Additionally, most studies attest to the considerable contribution of sub-microscopic gametocytaemia to mosquito infection [30] [32]. Measuring the effects of the different treatments on submicroscopic gametocytaemia using molecular methods of gametocyte detection such as the PCR would have increased the power of the study since microscopy notoriously underestimates gametocytes counts [30].…”

The role of submicroscopic parasitemia in malaria transmission: what is the evidence?

“…Finally, with lower levels of transmission, acquired immunity is expected to be lower. So at any given time point, an individual may be more likely to be asymptomatic because he/she is either in the process of resolving parasitemia due to treatment or might be in the process of developing a symptomatic infection [7,4,24,25]. Each of these major differences means that the asymptomatic reservoir may vary in different settings with regards to persistence, gametocyte carriage, and hence mosquito infectivity and transmission potential.…”