Nitazoxanide in the treatment of viral gastroenteritis: a randomized double-blind placebo-controlled clinical trial.

BACKGROUND: Enteric viruses including noroviruses and rotavirus are leading causes of diarrhoeal disease and gastroenteritis worldwide, and there is no effective treatment. AIM: To evaluate nitazoxanide, a thiazolide anti-infective agent, in treating viral gastroenteritis in adults and adolescents. METHODS: 50 out-patients at least 12 years of age (mean 33.5 years) presenting with diarrhoea and stool-positive by enzyme-linked immunosorbent assay for norovirus, rotavirus or adenovirus were enrolled in a double-blind, placebo-controlled clinical trial. Patients were randomly assigned either nitazoxanide 500 mg or placebo twice daily for 3 days. The primary end point was time from first dose to resolution of symptoms. Analysis was modified intent-to-treat for 45 patients, excluding five patients with other identified enteropathogens at baseline. RESULTS: The median time from first dose to resolution of symptoms was 1.5 days (IQR: 0.5-2.5) for nitazoxanide-treated patients and 2.5 days (IQR: 1.5-4.5) for the placebo group. Significant reductions in time to resolution of symptoms were observed for all patients analysed (P < 0.0001) and for subsets of patients with rotavirus (P = 0.0052) and norovirus (P = 0.0295). The number of patients with adenovirus (n = 5) was too small to draw any conclusion. No significant adverse events were reported. CONCLUSIONS: Nitazoxanide may play an important role in managing viral gastroenteritis in adults.

Inhibitory activities of epidermal growth factor receptor tyrosine kinase-targeted dihydroxyisoflavone and trihydroxydeoxybenzoin derivatives on Sarcocystis neurona, Neospora caninum, and Cryptosporidium parvum development.

Several gene sequences of parasitic protozoa belonging to protein kinase gene families and epidermal growth factor (EGF)-like peptides, which act via binding to receptor tyrosine kinases of the EGF receptor (EGFR) family, appear to mediate host-protozoan interactions. As a clue to EGFR protein tyrosine kinase (PTK) mediation and a novel approach for identifying anticoccidial agents, activities against Sarcocystis neurona, Neospora caninum, and Cryptosporidium parvum grown in BM and HCT-8 cell cultures of 52 EGFR PTK inhibitor isoflavone analogs (dihydroxyisoflavone and trihydroxydeoxybenzoine derivatives) were investigated. Their cytotoxicities against host cells were either absent, mild, or moderate by a nitroblue tetrazolium test. At concentrations ranging from 5 to 10 microg/ml, 20 and 5 analogs, including RM-6427 and RM-6428, exhibited an in vitro inhibitory effect of > or = 95% against at least one parasite or against all three, respectively. In immunosuppressed Cryptosporidium parvum-infected Mongolian gerbils orally treated with either 200 or 400 mg of agent RM-6427/kg of body weight/day for 8 days, fecal microscopic oocyst shedding was abolished in 6/10 animals (P of <0.001 versus untreated controls) and mean shedding was reduced by 90.5% (P of <0.0001) and 92.0% (P of <0.0001), respectively, higher levels of inhibition than after nitazoxanide (200 mg/kg/day for 8 days) or paromomycin (100 mg/kg/day for 8 days) treatment (55.0%, P of <0.001, and 17.5%, P of >0.05, respectively). After RM-6427 therapy (200 mg/kg/day for 8 days), the reduction in the ratio of animals with intracellular parasites was nearly significant in ileum (P = 0.067) and more marked in the biliary tract (P < 0.0013) than after nitazoxanide or paromomycin treatment (0.05 < P < 0.004). RM-6428 treatment at a regimen of 400 mg/kg/day for 12 days inhibited oocyst shedding, measured using flow cytometry from day 4 (P < 0.05) to day 12 (P < 0.02) of therapy, when 2/15 animals had no shedding (P < 0.0001) and 11/15 were free of gut and/or biliary tract parasites (P < 0.01). No mucosal alteration was microscopically observed for treated or untreated infected gerbils. To our knowledge, this report is the first to suggest that the isoflavone class of agents has the potential for anticoccidial therapy.

Nitroimidazoles in the treatment of trichomoniasis, giardiasis, and amebiasis.

Nitroimidazoles have been extensively evaluated in the treatment of trichomoniasis, giardiasis, liver and intestinal amebiasis. The most widely used are metronidazole, tinidazole, ornidazole, and secnidazole. Tinidazole, ornidazole, and secnidazole have a much longer half-life than metronidazole, allowing single-dose or once daily administration. Nitro-5-imidazoles remain extremely effective drugs for treating protozoans, Trichomonas vaginalis, Entamoeba histolytica, and Giardia intestinalis. Although all are suspected of potential carcinogenicity, they are the drugs of choice for treating protozoal infections.