Date Published: October 15, 2008
Publisher: Public Library of Science
Author(s): Peter Steinmann, Xiao-Nong Zhou, Zun-Wei Du, Jin-Yong Jiang, Shu-Hua Xiao, Zhong-Xing Wu, Hui Zhou, Jürg Utzinger, Photini Sinnis
Abstract: BackgroundTribendimidine 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 FindingsIn 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/SignificanceOur 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.
Partial Text: There is a growing awareness of the intolerable burden due to the so-called neglected tropical diseases . Hence, new initiatives are underway for their control . For helminth infections, the mainstay of control in high-burden areas rests on regular administration of anthelminthic drugs –. However, only a handful of drugs that have been developed many years ago are available , and there is considerable concern that resistance might develop, e.g., following repeated exposure of helminths to sub-curative doses. Reduced efficacy of common anthelminthic drugs is a major problem in veterinary medicine already, but for humans, it is of no clinical relevance thus far . Another issue is that in a world where intestinal polyparasitism is common, yet neglected –, and frequently used treatment regimens are only effective against a limited number of helminths , some species which are not effectively controlled by common drugs might increase in relative frequency, e.g., Strongyloides stercoralis and Taenia spp.
To our knowledge, this is the first investigation assessing the safety and efficacy of single-dose tribendimidine for treating S. stercoralis and Taenia spp. infections, and the first clinically-monitored use of tribendimidine in a setting with high rates of intestinal multiparasitism. Indeed, infections with one of the three main soil-transmitted helminths were found in 72.4–87.8% of the study participants, and only 4 of the 123 individuals in our final cohort (3.3%) harbored none of these helminths. The prevalence of S. stercoralis and Taenia spp. at baseline was 17.9% and 26.0%, respectively. Our study was an open-label trial, comparing a single oral dose of albendazole with that of tribendimidine, with both drugs administered at either 200 mg or 400 mg according to participants’ age.