Treatment of cryptosporidiosis with short-course nitazoxanide is not effective in children with HIV infection, according to a Zambian study published online by The Lancet.
Cryptosporidiosis is a major cause of death among children and adults with HIV in Africa, because the infection causes massive diarrhoea and subsequent wasting due to malabsorption of food. Nitazoxanide has been shown to be effective in cases of adult HIV-negative cryptosporidiosis, but this study, carried out by researchers in Lusaka with colleagues from St Bartholemew’s and Royal London School of Medicine in the United Kingdom, is the first published report of the use of the drug in HIV-positive individuals.
Fifty HIV-positive and 50 HIV-negative children with cryptosporidiosis were randomised to receive 100mg of nitazanoxide twice daily for three days or placebo. Cryptospordial infections was established by the presence of cryptosporidial oocysts in stool samples, and children with giardia and/or Entamoeba histolytica were excluded.
After seven days diarrhoea had stopped in 56% of HIV-negative children who received nitazoxanide compared to 23% of the HIV-negative placebo group (p=0.037), and at day 10 cryptosporidium was not present in the stools of 52% of the HIV-negative treated group, compared with 38% of the placebo group. Seventeen per cent of the HIV-negative placebo group had died by day 8.
However, only 8% of the HIV-positive children treated with nitazoxanide experienced resolution of diarrhoea by day 7, compared to 25% of the placebo group (a non-significant difference). No benefit in terms of parasitological clearance or mortality was observed in HIV-positive children; 20% had died by day 8 of the study, compared to none of the HIV-negative children treated with nitazoxanide. Eradication of cryptosporidium was associated with a higher CD4 cell count 1387 cells/mm3 versus 554 cells/mm3.
After the initial 10 day randomisation phase, mothers were offered the option of a further three day course of open-label nitazozanide treatment. Twenty four HIV-positive children entered this phase of the study; four days after ceasing treatment, 16 had no evidence of diarrhoea. Ten out of 13 of the HIV-positive children on their second course of nitazoxanide treatment had a clinical response at this stage. However, only three of 12 achieved eradication of cryptosporidium after a second phase of treatment.
The authors suggest that HIV-positive children with cryptosporidiosis may require an extended course of treatment.
Amadi B et al. Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomised trial. The Lancet (online advance publication), October 8 2002.