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Publication Open Access Thiamin supplementation does not reduce the frequency of adverse events after anti-malarial therapy among patients with falciparum malaria in southern Laos(2014-07-15) Mayxay, Mayfong; Khanthavong, Maniphone; Cox, Lorna; Sichanthongthip, Odai; Mallika Imwong; มัลลิกา อิ่มวงศ์; Pongvongsa, Tiengkham; Hongvanthong, Bouasy; Phompida, Samlane; Vanisaveth, Viengxay; White, Nicholas J; Newton, Paul N; Mayxay, Mayfong; Mahidol University. Faculty of Tropical Medicine. Department of Molecular Tropical Medicine and Genetics.Background: In a recent study one third of Lao patients presenting with uncomplicated Plasmodium falciparum malaria had biochemical evidence of thiamin deficiency, which was associated with a higher incidence of adverse events. Thiamin supplementation might, therefore, reduce adverse events in this population. Methods: An exploratory, double-blind, parallel group, placebo-controlled, superiority trial of thiamin supplementation in patients of all ages with uncomplicated and severe falciparum malaria was conducted in Xepon District, Savannakhet Province, southern Laos. Patients were randomly assigned to either oral thiamin 10 mg/day for 7 days immediately after standard anti-malarial treatment then 5 mg daily until day 42, or identical oral placebo. Results: After interim analyses when 630 patients (314 in thiamin and 316 in placebo groups) had been recruited, the trial was discontinued on the grounds of futility. On admission biochemical thiamin deficiency (alpha ≥ 25%) was present in 27% of patients and 9% had severe deficiency (alpha > 31%). After 42 days of treatment, the frequency of thiamin deficiency was lower in the thiamin (2%, 1% severe) compared to the placebo (11%, 3% severe) groups (p < 0.001 and p = 0.05), respectively. Except for diarrhoea, 7% in the placebo compared to 3% in the thiamin group (p = 0.04), and dizziness on day 1 (33% vs 25%, p = 0.045), all adverse events were not significantly different between the groups (p > 0.05). Clinical, haematological, and parasitological responses to treatment did not differ significantly between the two groups. Conclusion: Thiamin supplementation reduced biochemical thiamin deficiency among Lao malaria patients following anti-malarial drug treatment, but it did not reduce the frequency of adverse events after anti-malarial therapy or have any detected clinical or parasitological impact.Publication Open Access The neurological assessment in young children treated with artesunate monotherapy or artesunate-mefloquine combination therapy for uncomplicated Plasmodium falciparum malaria(2009) Ambler, Michael T.; Dubowitz, Lilly M.; Ratree Arunjerdja; Hla, Eh Paw; Thwai, Kyaw Lay; Viladpainguen, Jacher; Pratap Singhasivanon; ประตาป สิงหศิวานนท์; uxemburger, Christine; Nosten, François; McGready, Rose; McGready, Rose; Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit (MORU)Background: Mefloquine and artesunate combination therapy is the recommended first-line treatment for uncomplicated malaria throughout much of south-east Asia. Concerns have been raised about the potential central nervous system (CNS) effects of both drug components and there are no detailed reports in very young children. Methods: Children, aged between three months and five years, with acute uncomplicated Plasmodium falciparum malaria were randomized to either 7 days of artesunate monotherapy or the same schedule of artesunate plus mefloquine on day 7 and 8. Neurological testing targeting coordination and behaviour was carried out at day 0, 7, 9, 10, 14 and 28. Nonfebrile healthy control children from the same population were tested on days 0, 7, 14 and 28. Results: From December 1994 to July 1997, 91 children with uncomplicated P. falciparum, 45 treated with artesunate monotherapy, 46 treated with mefloquine and artesunate combination therapy and 36 non-febrile controls, underwent neurological testing. Malaria and fever had a significant negative impact on testing performance. By contrast, the antimalarial treatments were not associated with worsening performances in the various components of the test. Artesunate and mefloquine do not appear to have a significant influence on coordination and behaviour. Children treated with mefloquine were significantly less likely to suffer recurrent malaria infection during follow-up compared to those treated with artesunate alone (P = 0.033). Conclusion: In keeping with the results of randomized controlled trials in adults, mefloquine was not associated with a decrease in specific items of neurological performance. Likewise, children treated with artesunate did not perform significantly differently to control children. This study does not exclude subtle or rare treatment CNS effects of artesunate or mefloquine. Treatment of acute uncomplicated malaria results in a significant improvement on items of neurological performance.Publication Open Access The impact of human reservoir of malaria at a community-level on individual malaria occurrence in a low malaria transmission setting along the Thai-Myanmar border(2010-05) Saranath Lawpoolsri; สารนาถ ล้อพูลศรี; Chavez, Irwin F.; Surapon Yimsamran; สุรพล ยิ้มสำราญ; Supalap Puangsa-art; สุภลาภ พวงสอาด; Nipon Thanyavanich; นิพนธ์ ธัญญวานิช; Wanchai Maneeboonyang; Wuthichai Chaimungkun; Pratap Singhasivanon; ประตาป สิงหศิวานนท์; Maguire, James H.; Hungerford, Laura L.; Saranath Lawpoolsri; Mahidol University. Faculty of Tropical Medicine. Department of Tropical HygieneBACKGROUND: The probability of contracting malaria in a given individual is determined not only by the individual's characteristics, but also the ecological factors that characterize the level of human-vector contact in the population. Examination of the relationship between "individual" and "supra-individual" variables over time is important for understanding the local malaria epidemiology. This is essential for planning effective intervention strategies specifically for each location. METHODS: A retrospective cohort study was conducted, which followed a community-cohort of about 3,500 residents in seven hamlets along the Thai-Myanmar border between 1999 and 2006. Potential malaria determinants measured at different levels (temporal variables, individual variables, and hamlet variables) were incorporated into multilevel models to estimate their effects on an individual's risk of malaria attack. RESULTS: The monthly minimum temperature was significantly associated with the seasonal variation of malaria risk. An individual risk of malaria attack decreased by about 50% during the period that active surveillance was conducted; an additional 15% and 25% reduction of Plasmodium falciparum and Plasmodium vivax incidence, respectively, was observed after the use of artesunate-mefloquine combination therapy (ACT) for treatment of P. falciparum. Male children (age < 16 years old) were at highest risk of both P. falciparum and P. vivax attack. An increase in the hamlet's incidence of P. falciparum and P. vivax by 1 per 100 persons in a previous month resulted in 1.14 and 1.34 times increase in the risk of P. falciparum and P. vivax, respectively, among individuals in a particular hamlet. CONCLUSION: In a small area with low malaria transmission intensity, the variation in mosquito abundance is relatively similar across the residential areas; incidence of malaria between hamlets, which reflects the community level of human infectious reservoirs, is an important predictor for the malaria risk among individuals within these hamlets. Therefore, local malaria control strategies should focus on interventions that aim to reduce the gametocyte carriage in the population, such as early detection and treatment programmes and the use of ACT for P. falciparum.