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LOW EFFICACY OF MEBENDAZOLE AGAINST HOOKWORM IN VIETNAM: TWO RANDOMIZED CONTROLLED TRIALS

Vietnam is participating in a global de-worming effort that aims to treat 650 million school children regularly by 2010. The treatment used in Vietnam is single dose oral mebendazole (Phardazone®) 500 mg. We tested the efficacy of single dose mebendazole 500 mg in the therapy of hookworm infection in a randomized double-blind placebo-controlled trial among 271 Vietnamese schoolchildren. The treatment efficacy of single dose mebendazole in children did not differ significantly from placebo, with a reduction in mean eggs per gram of feces relative to placebo of 31% (95% CI -9 to 56%, P = 0.1). In light of these findings we then carried out a similar randomized trial comparing triple dose mebendazole, single dose albendazole, and triple dose albendazole against placebo in 209 adults in the same area. The estimated reduction in mean post-treatment eggs per gram of feces relative to placebo was 63% (95% CI 30–81%) for triple mebendazole, 75% (47–88%) for single albendazole, and 88% (58–97%) for triple albendazole. Our results suggest that single dose oral mebendazole has low efficacy against hookworm infection in Vietnam, and that it should be replaced by albendazole. These findings are of major public health relevance given the opportunity costs of treating entire populations with ineffective therapies. We recommend that efficacy of anti-helminth therapies is pilot tested before implementation of national gut worm control programs.

Received April 25, 2006. Accepted for publication November 22, 2006.

Acknowledgments: We are grateful to Dr. Antonio Montresor (WHO) for scientific advice given and for his help in establishing the initial contact to Pharbaco Hanoi. We also thank Dr. Nguyen Quoc Hung and Dr. Phung Duc Thuan (Institute of Malariology, Parasitology & Entomology, Ho Chi Minh City) for their assistance in conducting the stool analysis validation study, and Prof. David Pritchard and Dr. Alan Brown (University of Nottingham) for scientific advice. Ms. Nguyen Thi Thu Tam, Ms. Nguyen Thi Thu Nga, Ms. Tran Thi Hoang Chau, and Dr. Mary Chambers (all Oxford University Clinical Research Unit Ho Chi Minh City) helped with the randomization and packaging of tablets.

Financial support: CF is funded through a Radcliffe Research Fellowship from University College, University of Oxford. The study was supported through a research grant from Asthma UK, and the Bastow Award from the Special Trustees for Nottingham University Hospitals.

^* Address correspondence to R. J. Quinnell, Institute of Integrative and Comparative Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK. E-mail: r.j.quinnell{at}leeds.ac.uk

Authors’ addresses: Carsten Flohr, MRCPCH, Radcliffe Research Fellow, Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam and Centre for Population Studies, Institute of Clinical Research, University of Nottingham, Nottingham, NG7 3RD, UK, E-mail: flohr{at}dng.vnn. Luc Nguyen Tuyen, PhD, Director, Khanh Hoa Provincial Center for Malaria and Filariasis Control, Nha Trang City, Vietnam, E-mail: luctuyen{at}dng.vnn.vn. Sarah Lewis, PhD, Reader in Medical Statistics, University of Nottingham, Division of Respiratory Medicine, City Hospital, Nottingham, NG5 1PB, UK, E-mail: sarah.lewis{at}nottingham.ac.uk. Truong Tan Minh, PhD, Director, Khanh Hoa Provincial Health Service, Nha Trang, Vietnam, E-mail: soyte-kh{at}dng.vnn.vn. Jim Campbell, Research Microbiologist, AIBMS, Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, E-mail: jcampbell{at}hcm.fpt.vn. Professor John Britton, MD, Professor of Epidemiology and Head of Division of Epidemiology and Public Health, University of Nottingham, NG7 2RD, E-mail: j.britton{at}virgin.net. Professor Hywel Wiliams, PhD, Professor of Dermato-Epidemiology, Centre for Evidence-Based Dermatology, University of Nottingham, Nottingham, NG7 2RD, UK, E-mail: hywel.williams{at}nottingham.ac.uk. Tran Tinh Hien, PhD, Vice-Director, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, E-mail: tthien{at}hcm.vnn.vn. Professor Jeremy Farrar, DPhil, Director, Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, E-mail: jeremyjf{at}hcm.vnn.vn. Rupert Quinnell, DPhil, Lecturer, Institute of Integrative and Comparative Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK, E-mail: r.j.quinnell{at}leeds.ac.uk.