Serological markers were able to detect spatial variation in malaria transmission at the microepidemiological level, and they have the potential to form an effective method for spatial targeting of malaria control efforts.

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Background P. falciparum gametocytes may persist after treatment with sulphadoxine-pyrimethamine (SP) plus artesunate (AS) and contribute considerably to malaria transmission. We determined the efficacy of SP+AS plus a single dose of primaquine (PQ, 0.75 mg/kg) on clearing gametocytaemia measured by molecular methods.MethodologyThe study was conducted in Mnyuzi, an area of hyperendemic malaria in north-eastern Tanzania. Children aged 3–15 years with uncomplicated P. falciparum malaria with an asexual parasite density between 500–100,000 parasites/µL were randomized to receive treatment with either SP+AS or SP+AS+PQ. P. falciparum gametocyte prevalence and density during the 42-day follow-up period were determined by real-time nucleic acid sequence-based amplification (QT-NASBA). Haemoglobin levels (Hb) were determined to address concerns about haemolysis in G6PD-deficient individuals.Results108 individuals were randomized. Pfs25 QT-NASBA gametocyte prevalence was 88–91% at enrolment and decreased afterwards for both treatment arms. Gametocyte prevalence and density were significantly lower in children treated with SP+AS+PQ. On day 14 after treatment 3.9% (2/51) of the SP+AS+PQ treated children harboured gametocytes compared to 62.7% (32/51) of those treated with SP+AS (p<0.001). Hb levels were reduced in the week following treatment with SP+AS+PQ and this reduction was related to G6PD deficiency. The Hb levels of all patients recovered to pre-treatment levels or greater within one month after treatment.ConclusionsPQ clears submicroscopic gametocytes after treatment with SP+AS and the persisting gametocytes circulated at densities that are unlikely to contribute to malaria transmission. For individuals without severe anaemia, addition of a single dose of PQ to an efficacious antimalarial drug combination is a safe approach to reduce malaria transmission following treatment.Trial RegistrationControlled-Trials.com ISRCTN61534963

The antimalarial combination of sulfadoxine and pyrimethamine (SP) was introduced as first-line treatment for uncomplicated malaria in Tanzania during 2001 following 18 years of second-line use. The genetic determinants of in vitro resistance to the two drugs individually are shown to be point mutations at seven sites in the dihydrofolate reductase gene (dhfr) conferring resistance to pyrimethamine and five sites in the dihydropteroate synthase (dhps) gene conferring resistance to sulfadoxine. Different combinations of mutations within each gene confer differing degrees of insensitivity, but information about the frequency with which allelic haplotypes occur has been lacking because of the complicating effects of multiple infection. Here we used a novel highthroughput sequence-specific oligonucleotide probe-based approach to examine the present resistance status of three Plasmodium falciparum populations in northern Tanzania. By using surveys of asymptomatic infections and screening for the presence of all known point mutations in dhfr and dhps genes, we showed that just five dhfr and three dhps allelic haplotypes are present. High frequencies of both triple-mutant dhfr and doublemutant dhps mutant alleles were found in addition to significant interregional heterogeneity in allele frequency. In vivo studies have shown that the cooccurrence of three dhfr mutations and two dhps mutations in an infection prior to treatment is statistically predictive of treatment failure. We have combined data for both loci to determine the frequency of two-locus genotypes. The triple-dhfr/double-dhps genotype is present in all three regions with frequencies ranging between 30 and 63%, indicating that treatment failure rates are likely to be high.Sulfadoxine-pyrimethamine (SP) has now replaced chloroquine as the first-line curative antimalarial in much of East Africa. The earliest reports of emerging SP resistance in Africa were from Muheza district in Tanzania during 1994 and 1995 (32, 37). SP remains in use throughout Tanzania and was recently officially adopted as the national first-line treatment for nonsevere Plasmodium falciparum malaria. It is now a priority to learn how widespread genetic determinants of SP resistance currently are in the larger regions of northern Tanzania.To investigate this issue, we have carried out a populationbased genetic analysis of P. falciparum in the North and South Pare Mountains and Hai district, which are distinct geographical areas with their own microclimates and tribes. There had been no malaria research in these districts since 1965 until recent work showed relatively low levels of transmission, with an estimated entomological inoculation rate of 24 infective bites/person/year in Hai district (C. Drakeley and D. Chandramohan, unpublished data) compared with an entomological inoculation rate in the range of 34 to 405 infective bites/person/ year in Muheza district (14).It is widely understood that people self-treat with antimalarial drugs, which can be freely purchased (24); as a consequen...