The optimal timing of post-treatment sampling for the assessment of anthelminthic drug efficacy against Ascaris infections in humans

Abstract

The egg reduction rate (ERR) is the current standard mean to assess the efficacy of drugs against human soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura and hookworm). Although the timing of post-treatment sampling is pivotal for a readily interpretation of drug efficacy, there is lack empirical data that allows recommending the optimal time point for a follow-up egg counting. In the present study, we re-analyzed both the kinetics of worm expulsion and egg output for Ascaris lumbricoides following a single oral dose of albendazole in a series of studies previously conducted in Kenyan communities. The results indicate that it takes up to 10 days post-treatment before the expulsion of both adult male and female Ascaris worms is completed, approximately 20% of the worms being expelled between day 7 and 10 post-treatment. The sequential analysis of the egg out put, indicated a poor ERR (89.4%) at day 7 post-treatment, but a 100% ERR at day 14 and 21 post-treatment. Based on our findings we recommend to wait at least 14 days after an albendazole treatment before conducting the follow-up egg count. Any sampling before this time point may result in biased ERR estimates, due the release of residual eggs from moribund or degenerating worms.

Efficacy and safety of co-administered ivermectin plus albendazole for treating soil-transmitted helminths: A systematic review, meta-analysis and individual patient data analysis

“…Of the four studies selected to summarize overall efficacy, two [ 20 , 24 ] presented low risk of bias as per the Cochrane risk of bias tool but the remaining two studies [ 18 , 19 ] were not double-blinded and did not report on several procedures. Moreover, two of the included studies [ 18 , 20 ] did not adhere to the recommended follow up time point 2–3 weeks post-treatment [ 66 ]. Finally, within the five safety-related studies eligible for the meta-analysis, three reached acceptable quality levels with at least five out of the six bias indicators considered as “low risk”.…”

Comment on “The optimal timing of post-treatment sampling for the assessment of anthelminthic drug efficacy against Ascaris infections in humans”

“…A recent publication by Levecke et al (2018) provided interesting information on the kinetics of expulsion of Ascaris lumbricoides in humans following benzimidazole treatment. They show that expulsion of Ascaris worms can occur as late as 10 days post treatment with 400 mg albendazole and that this late worm expulsion affects faecal egg count reduction (FECR = egg reduction rate, ERR), which was only 89.4% on day 7 post treatment in their dataset but reached 100% at day 10 post treatment.…”

“…emerging benzimidazole resistance. This interpretation is now criticized by Levecke and colleagues based on their findings that a FECR of 89% on day 7 can still reach 100% on days 14 and 21 ( Levecke et al (2018) ). We fully agree with Levecke and colleagues that future study designs should take this delayed clearance in humans into account.…”

“…In contrast, other schools had FECRs higher than 90% or even 95%. This variation has not been equally considered and weighted by Levecke et al (2018) with respect to the overall conclusion of suspected emerging BZ resistance ( Krücken et al, 2017 ). While the school showing 0% FECR was indeed revisited on day 7 post treatment, the three schools with 52–56% FECR were all resampled on day 10.…”

“…In the veterinary field, there is plenty of data available showing that interpretation of FECRs require host-specific modifications. Studies such as ours and that by Levecke et al (2018) are important to evaluate how criteria applied in veterinary medicine should be adapted for human infections. The logistic challenges to obtain such data are considerable including the daily collection of complete faecal matter over two weeks and the quantification of worms in these samples under field conditions.…”