title: Protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children in rural Uganda: a randomised clinical trial.
abstract: OBJECTIVE
  To evaluate the protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children (uninfected children born to HIV infected mothers) in Africa.
  
  
  METHODS
  Non-blinded randomised control trial
  
  
  METHODS
  Tororo district, rural Uganda, an area of high malaria transmission intensity
  
  
  METHODS
  203 breastfeeding HIV exposed infants enrolled between 6 weeks and 9 months of age
  
  
  METHODS
  Co-trimoxazole prophylaxis from enrollment until cessation of breast feeding and confirmation of negative HIV status. All children who remained HIV uninfected (n = 185) were then randomised to stop co-trimoxazole prophylaxis immediately or continue co-trimoxazole until 2 years old.
  
  
  METHODS
  Incidence of malaria, calculated as the number of antimalarial treatments per person year.
  
  
  RESULTS
  The incidence of malaria and prevalence of genotypic mutations associated with antifolate resistance were high throughout the study. Among the 98 infants randomised to continue co-trimoxazole, 299 malaria cases occurred in 92.28 person years (incidence 3.24 cases/person year). Among the 87 infants randomised to stop co-trimoxazole, 400 malaria cases occurred in 71.81 person years (5.57 cases/person year). Co-trimoxazole prophylaxis yielded a 39% reduction in malaria incidence, after adjustment for age at randomisation (incidence rate ratio 0.61 (95% CI 0.46 to 0.81), P = 0.001). There were no significant differences in the incidence of complicated malaria, diarrhoea, pneumonia, hospitalisations, or deaths between the two treatment arms.
  
  
  CONCLUSIONS
  Co-trimoxazole prophylaxis was moderately protective against malaria in HIV exposed infants when continued beyond the period of HIV exposure despite the high prevalence of Plasmodium genotypes associated with antifolate resistance. Trial registration Clinical Trials NCT00527800.
authors: Department of Medicine, University of Washington, UW/FHCRC Clinical Research, Box 358080, Seattle, WA 98195-8080, USA. tgsand@u.washington.edu
authors: Taylor G
authors: TG
authors: Sandison
authors: Jaco
authors: J
authors: Homsy
authors: Emmanuel
authors: E
authors: Arinaitwe
authors: Humphrey
authors: H
authors: Wanzira
authors: Abel
authors: A
authors: Kakuru
authors: Victor
authors: V
authors: Bigira
authors: Julius
authors: J
authors: Kalamya
authors: Neil
authors: N
authors: Vora
authors: James
authors: J
authors: Kublin
authors: Moses R
authors: MR
authors: Kamya
authors: Grant
authors: G
authors: Dorsey
authors: Jordan W
authors: JW
authors: Tappero
mesh_terms: D000962:Antimalarials / Q000627:therapeutic use*; D001942:Breast Feeding / Q000453:epidemiology; D003968:Diarrhea, Infantile / Q000517:prevention & control; D005260:Female; D015658:HIV Infections; D018023:HIV Seronegativity; D006801:Humans; D015994:Incidence; D007223:Infant; D008288:Malaria / Q000453:epidemiology / Q000517:prevention & control*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D012141:Respiratory Tract Infections / Q000517:prevention & control; D012423:Rural Health; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*; D014454:Uganda / Q000453:epidemiology
chemical_list: D000962:Antimalarials; D015662:Trimethoprim, Sulfamethoxazole Drug Combination