SummaryBackgroundArtemisinin-combination therapy (ACT) is recommended as first-line treatment of falciparum malaria throughout the world, and fixed-dose combinations are preferred by WHO; whether a single gametocytocidal dose of primaquine should be added is unknown. We aimed to compare effectiveness of four fixed-dose ACTs and a loose tablet combination of artesunate and mefloquine, and assess the addition of a single gametocytocidal dose of primaquine.MethodsIn an open-label randomised trial in clinics in Rakhine state, Kachin state, and Shan state in Myanmar (Burma) between Dec 30, 2008, and March 20, 2009, we compared the effectiveness of all four WHO-recommended fixed-dose ACTs (artesunate–mefloquine, artesunate–amodiaquine, dihydroartemisinin–piperaquine, artemether–lumefantrine) and loose artesunate–mefloquine in Burmese adults and children. Eligible patients were those who presented to the clinics with acute uncomplicated Plasmodium falciparum malaria or mixed infection, who were older than 6 months, and who weighed more than 5 kg. Treatments were randomised in equal numbers within blocks of 50 and allocation was in sealed envelopes. All patients were also randomly assigned to receive either a single dose of primaquine 0·75 mg base/kg or not. Patients were followed up for 63 days. Treatment groups were compared by analysis of variance and multiple logistic regression. The primary outcome was the 63 day recrudescence rate. This study is registered with clinicaltrials.gov, number NCT00902811.Findings155 patients received artesunate–amodiaquine, 162 artemether–lumefantrine, 169 artesunate–mefloquine, 161 loose artesunate–mefloquine, and 161 dihydroartemisinin–piperaquine. By day 63 of follow-up, 14 patients (9·4%; 95% CI 5·7–15·3%) on artesunate–amodiaquine had recrudescent P falciparum infections, a rate significantly higher than for artemether–lumefantrine (two patients; 1·4%; 0·3–5·3; p=0·0013), fixed-dose artesunate–mefloquine (0 patients; 0–2·3; p<0·0001), loose artesunate–mefloquine (two patients; 1·3%; 0·3–5·3; p=0·0018), and dihydroartemisinin–piperaquine (two patients 1·3%; 0·3–5·2%; p=0·0012). Hazard ratios for re-infection (95% CI) after artesunate–amodiaquine were 3·2 (1·3–8·0) compared with the two artesunate–mefloquine groups (p=0·01), 2·6 (1·0–6–0) compared with artemether–lumefantrine (p=0·04), and 2·3 (0·9–6·0) compared with dihydroartemisinin–piperaquine (p=0·08). Mixed falciparum and vivax infections were common: 129 (16%) had a mixed infection at presentation and 330 (41%) patients had one or more episodes of Plasmodium vivax infection during follow-up. The addition of a single dose of primaquine (0·75 mg/kg) reduced P falciparum gametocyte carriage substantially: rate ratio 11·9 (95% CI 7·4–20·5). All regimens were well tolerated. Adverse events were reported by 599 patients, most commonly vomiting and dizziness. Other side-effects were less common and were not related to a specific treatment.InterpretationArtesunate–amodiaquine should not be used in Myanmar, because the other ACTs are s...

CitationEfficacy SummaryBackground Artemisinin-based combinations are judged the best treatments for multidrug-resistant Plasmodium falciparum malaria. Artesunate-mefl oquine is widely recommended in southeast Asia, but its high cost and tolerability profi le remain obstacles to widespread deployment. To assess whether dihydroartemisinin-piperaquine is a suitable alternative to artesunate-mefl oquine, we compared the safety, tolerability, effi cacy, and eff ectiveness of the two regimens for the treatment of uncomplicated falciparum in western Myanmar (Burma).

BackgroundInsecticide-treated bed nets (ITN) reduce malaria morbidity and mortality consistently in Africa, but their benefits have been less consistent in Asia. This study’s objective was to evaluate the malaria protective efficacy of village-wide usage of ITN in Western Myanmar and estimate the cost-effectiveness of ITN compared with extending early diagnosis and treatment services.MethodsA cluster-randomized controlled trial was conducted in Rakhine State to assess the efficacy of ITNs in preventing malaria and anaemia in children and their secondary effects on nutrition and development. The data were aggregated for each village to obtain cluster-level infection rates. In total 8,175 children under 10 years of age were followed up for 10 months, which included the main malaria transmission period. The incidence and prevalence of Plasmodium falciparum and Plasmodium vivax infections, and the biting behaviour of Anopheles mosquitoes in the area were studied concurrently. The trial data along with costs for current recommended treatment practices were modelled to estimate the cost-effectiveness of ITNs compared with, or in addition to extending the coverage of early diagnosis and treatment services.ResultsIn aggregate, malaria infections, spleen rates, haemoglobin concentrations, and weight for height, did not differ significantly during the study period between villages with and without ITNs, with a weighted mean difference of −2.6 P. falciparum episodes per 1,000 weeks at risk (95% Confidence Interval −7 to 1.8). In areas with a higher incidence of malaria there was some evidence ITN protective efficacy. The economic analysis indicated that, despite the uncertainty and variability in their protective efficacy in the different study sites, ITN could still be cost-effective, but not if they displaced funding for early diagnosis and effective treatment which is substantially more cost-effective.ConclusionIn Western Myanmar deployment of ITNs did not provide consistent protection against malaria in children living in malaria endemic villages. Early diagnosis and effective treatment is a more cost effective malaria control strategy than deployment of ITNs in this area where the main vector bites early in the evening, often before people are protected by an ITN.

BackgroundIn a large cluster randomized control trial of insecticide-treated bed nets (ITN) in Western Myanmar the malaria protective effect of ITN was found to be highly variable and, in aggregate, the effect was not statistically significant. A coincident entomological investigation measured malaria vector abundance and biting behaviour and the human population sleeping habits, factors relevant to ITN effectiveness.MethodsEntomological surveys were carried out using different catching methods to identify potential malaria vector species and characterise their biting habits. The salivary glands were dissected from all female anophelines caught to identify sporozoites by microscopy.FindingsBetween 1995 and 2000 a total of 4,824 female anopheline mosquitoes were caught with various catching methods. A total of 916 person nights yielded 3,009 female anopheline mosquitoes between 6 pm and 6 am. Except for Anopheles annularis, which showed no apparent preference (51% outdoor biting), all major species showed a strong preference for outdoor biting; Anopheles epiroticus (79%), Anopheles subpictus (72%), Anopheles maculatus (92%), Anopheles aconitus (85%) and Anopheles vagus (72%). Most human biting occurred in the early evening with the peak biting time between 6 pm and 7 pm (35%). Overall 51% (1447/2837) of all bites recorded were between 6 pm and 8 pm. A large proportion of children were not sleeping under an ITN during peak biting times. Only one An. annularis mosquito (0.02%) had malaria sporozoites identified in the salivary glands.ConclusionsPeak vector biting occurred early in the evening and mainly occurred outdoors. The limited efficacy of ITN in this area of Western Myanmar may be explained by the biting behaviour of the prevalent Anopheles mosquito vectors in this area.

The excellent retention over >6 years in this large cohort demonstrates that ART delivery at the primary care level in Myanmar is feasible and should encourage support for further ART expansion in the country.