title: Thiamin supplementation does not reduce the frequency of adverse events after anti-malarial therapy among patients with falciparum malaria in southern Laos.
abstract: 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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ISRCTN 85411059.
authors.affiliation: Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao People's Democratic Republic. mayfong@tropmedres.ac.
authors.forename: Mayfong
authors.initials: M
authors.lastname: Mayxay
authors.forename: Maniphone
authors.initials: M
authors.lastname: Khanthavong
authors.forename: Lorna
authors.initials: L
authors.lastname: Cox
authors.forename: Odai
authors.initials: O
authors.lastname: Sichanthongthip
authors.forename: Mallika
authors.initials: M
authors.lastname: Imwong
authors.forename: Tiengkham
authors.initials: T
authors.lastname: Pongvongsa
authors.forename: Bouasy
authors.initials: B
authors.lastname: Hongvanthong
authors.forename: Samlane
authors.initials: S
authors.lastname: Phompida
authors.forename: Viengxay
authors.initials: V
authors.lastname: Vanisaveth
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Paul N
authors.initials: PN
authors.lastname: Newton
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000962:Antimalarials / Q000009:adverse effects* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007812:Laos; D016778:Malaria, Falciparum / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000627:therapeutic use; D013831:Thiamine / Q000627:therapeutic use*; D013832:Thiamine Deficiency / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000962:Antimalarials; D010919:Placebos; D013831:Thiamine