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.
The final study cohort comprised less than 50% of those initially contacted. Whilst the cohort had a similar sex distribution than the total population of Nanweng village, it was considerably biased toward older age groups. We screened multiple stool samples for intestinal helminths and randomly assigned the participants to either albendazole or tribendimidine. Treatment outcome was assessed 2 to 4 weeks after dosing using multiple stool samples and a diversity of diagnostic approaches. The prevalence of S. stercoralis
was not significantly reduced by either albendazole or tribendimidine, and no significant drug-specific difference was observed. Among individuals infected with Taenia
spp. at baseline, the observed cure rates of 58.8% for albendazole and 66.7% for tribendimidine showed statistical significance (both p
<0.05). During follow-up, however, additional infections were found, mainly Taenia
spp. among those who had received albendazole, and the difference between the drug-specific overall cure rates was 53.3% (p
0.001). The observed cestocidal effect of tribendimidine, for the time being, should rather be regarded as an indication of a possible activity than as a proof-of-concept. This is due to the obvious diagnostic challenges encountered in field-based clinical studies on large cestodes.
In the current trial, albendazole generally performed slightly better than tribendimidine in curing common soil-transmitted helminth infections. The most notable difference was seen with T. trichiura
, confirming earlier observations that single-dose albendazole is somewhat more efficacious than single-dose tribendimidine against this nematode 
. The observed cure rates against hookworm and T. trichiura
following single-dose albendazole are rather low compared to the results of a recent meta-analysis of this and other WHO-recommended anthelminthics commonly used against common soil-transmitted helminth infections 
. We speculate that this observation is rather reflecting the rigorous diagnostic approach employed than an unusually low susceptibility of local hookworm and T. trichiura
to albendazole. For example, hookworm infections could not only be detected by the widely used Kato-Katz technique, but also by the Koga agar plate method. However, the low cure rates observed in this study should also be seen as a warning sign and call for monitoring of drug efficacy and the potential emergence of drug resistance 
The inclusion of only 123 individuals who met our sample submission requirements into the final study cohort reduced the reported compliance rate but increased the reliability of the results due to the increased overall sensitivity of the employed diagnostic methods 
. Indeed, a lower prevalence was found among those 175 participants who had at least 1 stool sample analyzed, but the drug-specific efficacies were similar (data not shown).
The discovery of notable numbers of infections among those who were deemed negative before treatment can be explained by at least 2 mechanisms, or a combination thereof. First, it is conceivable that the baseline evaluation fell within the prepatent period of recent infections. Second, it is well known that parasitological diagnosis of both S. stercoralis 
lacks sensitivity. For S. stercoralis
, the main remedy for this challenge is screening of multiple stool specimens 
, whilst for Taenia
spp., sensitive coproantigen enzyme-linked immunosorbent assay (ELISA) tests provide valuable alternatives 
. The current diagnostic ‘gold’ standard to confirm treatment success in taeniasis is the recovery of the tapeworm scolex. Alternatively, the absence of proglottids from stools and underwear over a period of 3 months also provides solid proof of cure. However, such extensive observation is usually only feasible in hospital settings. Re-infection after treatment can almost certainly be excluded for Taenia
spp., and it is rather unlikely for S. stercoralis
. We speculate that in our study, the limited sensitivity of the diagnostic tools was more significant since the 3 to 5-week period between baseline and follow-up investigation is rather short for any notable level of re-infections.
We are confident that our results are valid despite the imperfect sensitivity of the employed diagnostic tests, not least due to our rigorous sampling effort. This assumption is supported by the following observations. For S. stercoralis
, the numbers of “new” infections at follow-up was similar in both treatment groups (both n
2), thus reducing the observed cure rate but not affecting the overall conclusion that both drugs exhibit some effect at the employed dosage. A mathematical model 
for the prediction of “true” prevalence further suggested an underestimation of the S. stercoralis
prevalence by the employed procedures within the range actually observed in the present trial 
. After a study involving extensive stool sample collection and analysis by the Baermann technique, Dreyer and co-workers 
suggested that at least 4 stool samples need to be collected to accurately assess the S. stercoralis
infection status, and that only those with at least 2 positive test results should be included in clinical drug trials. In our study, we only included those individuals who had at least 2 stool specimens examined with 2 different diagnostic approaches. Thus, at least 4, and ideally 6, results were available to judge the infection status of the participants both before and after drug administration. Among the 22 S. stercoralis
positives at baseline, 6, 6, 3, 5, 1 and 1 individuals had 1, 2, 3, 4, 5 and 6 positive test results, respectively. The 10 arguably cured individuals had 1 (n
3), 2 (n
3), 3 (n
2) and 4 (n
2) positive baseline test results. Our findings indicate that participants with only 1 or 2 positive tests at baseline were not more likely to be considered cured at treatment evaluation than those with multiple positive tests. However, infections were still found in all participants with 5 or 6 positive tests at baseline. The four individuals who were only found to be infected at treatment evaluation then had 1, 1, 2 and 3 positive test results. Finally, the observed activity of albendazole against Taenia
spp. among those who were found to be infected at baseline has to be put into perspective with the high number of “newly” detected infections at treatment evaluation. Among tribendimidine recipients, only few additional Taenia
spp. infections were found, indeed indicating that single-dose tribendimidine, but not albendazole, might have some effect against Taenia
Unfortunately, the eggs of T. saginata
, T. solium
, and T. asiatica
cannot be readily distinguished microscopically 
. Hence, we are not in a position to determine their relative frequency in our study population. However, the reported and observed diets suggest that the locally dominant species is T. solium
or possibly T. asiatica
since Bulang favor raw pork over raw beef.
As a next step, the efficacy of multiple-dose tribendimidine could be assessed as our results indicate some, albeit currently unsatisfactory effect of this drug against S. stercoralis
spp. In future studies with a focus on these 2 parasites rather than the common soil-transmitted helminths, the reference drug should be praziquantel or niclosamide for Taenia
spp., and ivermectin for S. stercoralis
. Alternatively, triple-dose albendazole might be used as reference treatment 
. When further investigating the efficacy of tribendimidine against large cestodes, including Taenia
spp. in humans, we propose to treat a small group of confirmed taeniasis cases who agreed to submit multiple stool samples and observe proglottids in their stools and underwear over extended time periods.
Infections with A. lumbricoides and hookworm are the main targets for single-dose mass chemotherapy using albendazole or mebendazole. Discussions are underway in the People's Republic of China for the larger-scale use of tribendimidine. Efficacy of the latter drug on other intestinal parasites would be of considerable public health significance, which is explained by the geographic overlap of different helminth infections, including S. stercoralis and Taenia spp. Treatment of individuals with multiple species parasite infections, including S. stercoralis and Taenia spp., is likely to occur. Hence, there is a pressing need to determine the most efficacious tribendimidine treatment regimen for S. stercoralis and Taenia spp. since the exposure of the parasites to sub-curative doses exacerbates the risk of resistance development. Therefore, pharmacovigilance needs to also cover non-target parasites to assure timely detection of emerging resistance.