Combination of probenecid-sulphadoxine-pyrimethamine for intermittent preventive treatment in pregnancy

Abstract

The antifolate sulphadoxine-pyrimethamine (SP) has been used in the intermittent prevention of malaria in pregnancy (IPTp). SP is an ideal choice for IPTp, however, as resistance of Plasmodium falciparum to SP increases, data are accumulating that SP may no longer provide benefit in areas of high-level resistance. Probenecid was initially used as an adjunctive therapy to increase the blood concentration of penicillin; it has since been used to augment concentrations of other drugs, including antifolates. The addition of probenecid has been shown to increase the treatment efficacy of SP against malaria, suggesting that the combination of probenecid plus SP may prolong the useful lifespan of SP as an effective agent for IPTp. Here, the literature on the pharmacokinetics, adverse reactions, interactions and available data on the use of these drugs in pregnancy is reviewed, and the possible utility of an SP-probenecid combination is discussed. This article concludes by calling for further research into this potentially useful combination.

Figure 1

Hypothetical parasite burden profiles during pregnancy with SP IPT in a high-transmission setting. Entomological inoculation rate is about 50 infectious bites per person per year. Note that many infections self-cure (each infection is depicted as a green line). The hatched bars represent the duration of "suppressive prophylactic activity", and the solid bars represent the period during which parasite multiplication is suppressed (i.e. levels exceed the in vivo MIC). The horizontal dotted line at 10⁸ parasites represents the level at which malaria can be detected on a blood film. (A) represents a drug-sensitive area; (B) represents a moderately resistant area. Reproduced from: White NJ (2005) Intermittent Presumptive Treatment for Malaria. PLoS Med 2(1): e3. doi:10.1371/journal.pmed.0020003