Double-blind, randomized, placebo-controlled study of nitazoxanide in the treatment of fascioliasis in adults and children from northern Peru L. FAVENNEC*, J. JAVE ORTIZ  , G. GARGALA*, N. LOPEZ CHEGNE  , A. AYOUB à & J. F. ROSSIGNOL à *ADEN, EA 3234, Laboratoire de Parasitologie, Faculte ´ de Me ´decine et de Pharmacie, Universite ´ de Rouen, Rouen, France;  Hospital General de Cajamarca, Cajamarca, Peru; àDepartment of Infectious and Parasitic Diseases, London School of Hygiene and Tropical Medicine, London, UK Accepted for publication 17 September 2002 SUMMARY Background: Human fascioliasis is a significant world- wide health problem, and massive or repeated infections by Fasciola hepatica can lead to considerable morbidity. Aim: To evaluate the safety and efficacy of nitazoxa- nide, when compared with placebo, in the treatment of fascioliasis in adults and children from northern Peru. Methods: A double-blind, placebo-controlled study was carried out in 50 adults and 50 children infected with F. hepatica. The diagnosis of infection was based on the presence of F. hepatica eggs in one stool sample obtained before inclusion in the study. Patients were randomized to receive treatment with either a 7-day course of nitazoxanide (100 mg b.d., age range 2–3 years; 200 mg b.d., age range 4–11 years; 500 mg b.d., age > 12 years) or matching placebo. Three post-treat- ment stool examinations were carried out between 30 and 90 days after initiation of treatment. Results: The parasite was eliminated in 18 of 30 (60%) adults completing the study who received nitazoxanide vs. one of eight adults in the placebo group (P ¼ 0.042), and similarly in 14 of 35 (40%) children completing the treatment vs. none of eight in the placebo group (P ¼ 0.038). Only mild, transient adverse events were reported. Conclusions: A 7-day course of nitazoxanide was effect- ive in adults and children in the treatment of F. hepatica, when compared with placebo. INTRODUCTION Human fascioliasis caused by Fasciola hepatica is a significant world-wide health problem. 1 Recent studies indicate that 2.4–17 million people are infected world- wide. Although the mortality due to fascioliasis is generally low, massive or repeated infections can lead to considerable morbidity. Many drugs have been used to treat human fascioliasis. Older drugs (tetrachloride, tetrachlorethylene, bithionol) are nowadays considered either not especially effective, too toxic or both. A possible replacement (triclabendazole) is experiencing problems of resistance in veterinary use for which it was developed. This situation justifies the search for new effective drugs. Nitazoxanide, or 2-acetolyloxy-N-(5- nitro-2-thiazolyl)benzamide, is a potent inhibitor of the pyruvate:ferredoxin oxidoreductase enzyme, effective against a broad range of protozoa, nematodes, cestodes, trematodes and anaerobic bacteria. 2–7 Nitazoxanide and its first blood metabolite, desacetyl- nitazoxanide or tizoxanide, are effective in vitro against F. hepatica, with minimum inhibitory concentrations between 1 and 5 lg ⁄ mL. In F. gigantica experimentally infected rabbits, nitazoxanide at a daily dose of Correspondence to: Dr L. Favennec, ADEN, EA 3234, Laboratoire de Parasitologie, Faculte ´ de Me ´decine et de Pharmacie, Universite ´ de Rouen, Rouen, France. E-mail: loic.favennec@chu_rouen.fr Aliment Pharmacol Ther 2003; 17: 265–270. doi: 10.1046/j.0269-2813.2003.01419.x Ó 2003 Blackwell Publishing Ltd 265