title: Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomised controlled trial.
abstract: BACKGROUND
  Cryptosporidiosis in children in developing countries causes persistent diarrhoea and malnutrition and is associated with increased mortality, but there is no effective treatment. We aimed to assess the effect of nitazoxanide-a new broad-spectrum antiparasitic drug-on morbidity and mortality in Zambian children with diarrhoea due to Cryptosporidium parvum.
  
  
  METHODS
  Children with cryptosporidial diarrhoea who were admitted to the University Teaching Hospital, Lusaka, Zambia, between November, 2000, and July, 2001, and whose parents consented to their having an HIV test were randomly assigned nitazoxanide (100 mg twice daily orally for 3 days) or placebo. The primary endpoint was clinical response on day 7 after the start of treatment. Secondary endpoints included parasitological response by day 10 and mortality at day 8. Analysis was by intention to treat, with exclusion of patients subsequently found to be negative for C parvum or co-infected at baseline. The trial was stratified by HIV serology.
  
  
  RESULTS
  50 HIV-seropositive and 50 HIV-seronegative children were recruited for the study, four of whom were subsequently excluded. In HIV-seronegative children, diarrhoea resolved in 14 (56%) of 25 receiving nitazoxanide and 5 (23%) of 22 receiving placebo (difference 33%, 95% CI 7-59; p=0.037). C parvum was eradicated from stool in 13 (52%) of 25 receiving nitazoxanide and three (14%) of 22 receiving placebo (38%, 95% CI 14-63; p=0.007). Four children (18%) of 22 in the placebo group had died by day 8, compared with none of 25 in the nitazoxanide group (-18%, -34 to 2; p=0.041). HIV-seropositive children did not benefit from nitazoxanide. Nitazoxanide was not significantly associated with adverse events in either stratum.
  
  
  CONCLUSIONS
  A 3-day course of nitazoxanide significantly improved the resolution of diarrhoea, parasitological eradication, and mortality in HIV-seronegative, but not HIV-seropositive, children.
authors.affiliation: Department of Paediatrics, University of Zambia School of Medicine, Lusaka, Zambia.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Amadi
authors.forename: Mwiya
authors.initials: M
authors.lastname: Mwiya
authors.forename: John
authors.initials: J
authors.lastname: Musuku
authors.forename: Angela
authors.initials: A
authors.lastname: Watuka
authors.forename: Sandie
authors.initials: S
authors.lastname: Sianongo
authors.forename: Ayman
authors.initials: A
authors.lastname: Ayoub
authors.forename: Paul
authors.initials: P
authors.lastname: Kelly
mesh_terms: D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D002675:Child, Preschool; D003457:Cryptosporidiosis / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D003967:Diarrhea / Q000188:drug therapy* / Q000469:parasitology; D005260:Female; D018023:HIV Seronegativity; D006679:HIV Seropositivity; D006801:Humans; D007223:Infant; D008297:Male; D009574:Nitro Compounds; D009752:Nutritional Status; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D015024:Zambia / Q000453:epidemiology
chemical_list: D000981:Antiprotozoal Agents; D009574:Nitro Compounds; D013844:Thiazoles; C041747:nitazoxanide