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      Tribendimidine and Albendazole for Treating Soil-Transmitted Helminths, Strongyloides stercoralis and Taenia spp.: Open-Label Randomized Trial

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          Abstract

          Background

          Tribendimidine is an anthelminthic drug with a broad spectrum of activity. In 2004 the drug was approved by Chinese authorities for human use. The efficacy of tribendimidine against soil-transmitted helminths ( Ascaris lumbricoides, hookworm, and Trichuris trichiura) has been established, and new laboratory investigations point to activity against cestodes and Strongyloides ratti.

          Methodology/Principal Findings

          In an open-label randomized trial, the safety and efficacy of a single oral dose of albendazole or tribendimidine (both drugs administered at 200 mg for 5- to 14-year-old children, and 400 mg for individuals ≥15 years) against soil-transmitted helminths, Strongyloides stercoralis, and Taenia spp. were assessed in a village in Yunnan province, People's Republic of China. The analysis was on a per-protocol basis and the trial is registered with controlled-trials.com (number ISRCTN01779485). Both albendazole and tribendimidine were highly efficacious against A. lumbricoides and, moderately, against hookworm. The efficacy against T. trichiura was low. Among 57 individuals who received tribendimidine, the prevalence of S. stercoralis was reduced from 19.3% to 8.8% (observed cure rate 54.5%, p = 0.107), and that of Taenia spp. from 26.3% to 8.8% (observed cure rate 66.7%, p = 0.014). Similar prevalence reductions were noted among the 66 albendazole recipients. Taking into account “new” infections discovered at treatment evaluation, which were most likely missed pre-treatment due to the lack of sensitivity of available diagnostic approaches, the difference between the drug-specific net Taenia spp. cure rates was highly significant in favor of tribendimidine ( p = 0.001). No significant adverse events of either drug were observed.

          Conclusions/Significance

          Our results suggest that single-dose oral tribendimidine can be employed in settings with extensive intestinal polyparasitism, and its efficacy against A. lumbricoides and hookworm was confirmed. The promising results obtained with tribendimidine against S. stercoralis and Taenia spp. warrant further investigations. In a next step, multiple-dose schedules should be evaluated.

          Author Summary

          More than a billion people are infected with intestinal worms and, in the developing world, many individuals harbor several kinds of worms concurrently. There are only a handful of drugs available for treatment, and drug efficacy varies according to the worm species. We compared the efficacy of a single oral dose of tribendimidine, a new broad-spectrum worm drug from China, with the standard drug albendazole for the treatment of hookworm, large roundworm ( Ascaris lumbricoides), whipworm ( Trichuris trichiura) and, for the first time, Strongyloides stercoralis and tapeworm ( Taenia spp.). Our single-blind randomized trial was conducted in a village in Yunnan province, southwest China. Both drugs showed high efficacy against A. lumbricoides and a moderate efficacy against hookworm. Among 57 tribendimidine recipients, the prevalence of S. stercoralis was reduced from 19.3% to 8.8%, and that of Taenia spp. from 26.3% to 8.8%. Similar prevalence reductions were noted among the 66 albendazole recipients. Taking into account additional infections only discovered at treatment evaluation, the difference between the drug-specific Taenia spp. net cure rates was highly significant in favor of tribendimidine. In view of our promising results, multiple-dose schedules with tribendimidine against S. stercoralis and Taenia spp. should be evaluated next.

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          Most cited references49

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          Control of neglected tropical diseases.

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            Taenia solium cysticercosis.

            The larval stage of the pork tapeworm (Taenia solium) infects the human nervous system, causing neurocysticercosis. This disease is one of the main causes of epileptic seizures in many less developed countries and is also increasingly seen in more developed countries because of immigration from endemic areas. Little information is available on the natural evolution of taeniasis or cysticercosis. Available therapeutic measures include steroids, treatments for symptoms, surgery, and, more controversially, antiparasitic drugs to kill brain parasites. Efforts to control and eliminate this disease are underway through antiparasitic treatment of endemic populations, development of pig vaccines, and other measures.
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              Multiparasite communities in animals and humans: frequency, structure and pathogenic significance.

              Individual humans and animals are subject to infection by a variety of parasites (broadly defined to include viruses, bacteria and other non-protozoan microparasites) at any one time. Multiple parasite infections occur frequently in populations of wild animals as well as in humans from developing countries. In some species and regions, hosts with multiple infections are more common than hosts with either no infection or a single infection. Studies, predominantly on animals, show that a wide variety of environmental and host-dependent factors can influence the structure and dynamics of the communities of parasites that make up these multiple infections. In addition, synergistic and competitive interactions can occur between parasite species, which can influence the likelihood of their successful transmission to other hosts and increase or decrease their overall pathogenic impact. This review summarises aspects of our current knowledge on the frequency of multiparasite infections, the factors which influence them, and their pathogenic significance.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, USA )
                1935-2727
                1935-2735
                October 2008
                15 October 2008
                : 2
                : 10
                Affiliations
                [1 ]Department of Public Health and Epidemiology, Swiss Tropical Institute, Basel, Switzerland
                [2 ]National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, People's Republic of China
                [3 ]Helminthiasis Division, Yunnan Institute of Parasitic Diseases, Simao, People's Republic of China
                [4 ]Jiangsu Institute of Parasitic Diseases, Wuxi, People's Republic of China
                New York University School of Medicine, United States of America
                Author notes

                Conceived and designed the experiments: PS XNZ ZWD SHX ZXW JU. Performed the experiments: PS ZWD JYJ HZ. Analyzed the data: PS. Wrote the paper: PS XNZ SHX JU. Designed and implemented the study, managed and analyzed the data and prepared the manuscript: PS. Designed the study, facilitated and supervised part of the study implementation and revised the manuscript draft: XNZ. Assisted in the design and implementation of the study: ZWD JYJ HZ. Designed the study, supervised part of the study implementation and revised the manuscript draft: SHX and ZXW. Designed the study, supervised PS and revised the manuscript draft: JU.

                Article
                07-PNTD-RA-0291R3
                10.1371/journal.pntd.0000322
                2561005
                18923706
                98ede670-1c90-4efe-8da6-6d8764642277
                Steinmann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                Page count
                Pages: 10
                Categories
                Research Article
                Infectious Diseases/Epidemiology and Control of Infectious Diseases
                Infectious Diseases/Helminth Infections
                Infectious Diseases/Neglected Tropical Diseases
                Public Health and Epidemiology
                Public Health and Epidemiology/Infectious Diseases

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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