Thiamin supplementation does not reduce the frequency of adverse events after anti-malarial therapy among patients with falciparum malaria in southern Laos

Abstract

BackgroundIn 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.MethodsAn 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.ResultsAfter 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.ConclusionThiamin 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.Trial registrationISRCTN 85411059

Comparison of Thiamin Diphosphate High-Performance Liquid Chromatography and Erythrocyte Transketolase Assays for Evaluating Thiamin Status in Malaria Patients without Beriberi

“…We compared admission TDP concentration with ETKA (α) and basal ETK activity in erythrocytes in 230 patients infected with Plasmodium falciparum, as demonstrated by positive admission Giemsa-stained peripheral blood slides, in southern Laos; see ref. 18 for details. Samples were collected during the rainy season, when malaria transmission is high, from June to November 2008 to 2010.…”

“…Data for this study come from a trial of malaria supplementation in southern Laos. 18 Malaria is a common cause of morbidity in southern Laos, and one third of patients present with biochemical thiamin deficiency. 18 It was postulated thiamin supplementation may improve neurological side effects and adverse outcomes.…”

“…18 Malaria is a common cause of morbidity in southern Laos, and one third of patients present with biochemical thiamin deficiency. 18 It was postulated thiamin supplementation may improve neurological side effects and adverse outcomes. 5,18 The trial demonstrated that thiamin levels increased following supplementation, but there was no reduction in adverse events.…”

“…18 It was postulated thiamin supplementation may improve neurological side effects and adverse outcomes. 5,18 The trial demonstrated that thiamin levels increased following supplementation, but there was no reduction in adverse events. Here, we compare the assessment of thiamin status by direct measurement of TDP using HPLC against erythrocyte transketolase assays in these malaria patients.…”

“…Here, we compare the assessment of thiamin status by direct measurement of TDP using HPLC against erythrocyte transketolase assays in these malaria patients. 18…”