High dose prolonged treatment with nitazoxanide is not effective for cryptosporidiosis in HIV positive Zambian children: a randomised controlled trial

Abstract

BackgroundTreatment of cryptosporidiosis in HIV infected children has proved difficult and unsatisfactory with no drugs having demonstrable efficacy in controlled trials except nitazoxanide. We hypothesised that a prolonged course of treatment with high dose nitazoxanide would be effective in treating cryptosporidiosis in HIV positive Zambian children.MethodsWe performed a double-blind, randomised, placebo controlled trial in paediatric patients in the UTH in Lusaka. The study included HIV positive children between one and eleven years of age if 2 out of 3 stool samples were positive for oocysts of Cryptosporidium spp. Children were given nitazoxanide suspension in a dose of 200 mg twice daily (bid) for 28 days (if 1-3 years old) or 400 mg bid for 28 days (if 4-11 years old), or matching placebo.ResultsSixty children were randomised and 52 were fully evaluated. Only five children were 4 years of age or over and received the higher dose. In the primary efficacy analysis, 11 out of 26 (42%) in the active treatment group achieved a 'Well' clinical response compared to 8 out of 26 (35%) in the placebo group. Parasitological response was declared as 'Eradicated' in 27% in the active group and 35% in the placebo group. Mortality (16/52, 31%) did not differ by treatment allocation.ConclusionWe found no significant benefit in children with cryptosporidiosis despite high dose and longer treatment duration. This is the second randomised controlled trial to suggest that in Zambian children with HIV-related immunosuppression nitazoxanide does not eradicate this infection nor provide clinical symptom reduction.Trial RegistrationThe trial was registered as ISRCTN41089957.

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“…Likewise, nitazoxanide, which is the only FDA-approved drug for the treatment of cryptosporidiosis in immunocompetent patients older than 1 year (16), is not approved for HIV-infected patients (17). Also, clinical trials demonstrated that there were no differences in mortality or parasitological responses between the patients who received nitazoxanide and placebo (18)(19)(20). New drugs are clearly needed.…”

Novel Bumped Kinase Inhibitors Are Safe and Effective Therapeutics in the Calf Clinical Model for Cryptosporidiosis

“…In malnourished children, a survival advantage was shown with nitazoxanide treatment, but the response rate was poor [7,8]. Furthermore, randomized trials show no benefit with nitazoxanide treatment in patients with AIDS [8,17]. More-effective parasite-specific drugs are clearly needed for treating cryptosporidiosis.…”

“…Further, the mechanism of action of nitazoxanide against Cryptosporidium is unknown, and it is speculated that it may act via a nonspecific immunomodulatory effect [7,16]. In malnourished children, a survival advantage was shown with nitazoxanide treatment, but the response rate was poor [7,8]. Furthermore, randomized trials show no benefit with nitazoxanide treatment in patients with AIDS [8,17].…”

“…Infection in humans may be anthroponotic, as occurs with C. hominis, or zoonotic, as occurs for some C. parvum infections acquired from calves [6]. In immunocompromised individuals, such as those with AIDS, cryptosporidial diarrhea may become persistent and life threatening [7,8]. In immunocompetent individuals, Cryptosporidium infection causes watery diarrhea, often continuing beyond 10 days from the onset [7].…”

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“…Currently, the only available drug for human infections (nitazoxanide -Romark Laboratories, Florida, USA), has variable efficacy (Abubakar et al, 2007;Amadi et al, 2009) and an effective vaccine has yet to be developed (Mead, 2014;Ryan et al, 2016). Halofuginone lactate (Halocur; Intervet, New Zealand) is commercially available against cryptosporidiosis in dairy calves, with variable efficacy (Trotz-Williams et al, 2011;Almawly et al, 2013).…”