True Resistance of Ascaris to Albendazole in Rwanda?

Last year, Kr├╝cken et al. published an interesting paper titled: "Reduced efficacy of albendazole against Ascaris lumbricoides in Rwandan schoolchildren." in the international journal for Parasitology: Drugs and Drug Resistance. (original article Here). The article mentions the results of a drug efficacy trial with a single dose of 400mg Albendazole (ALB) in 12 schools in Rwanda where Ascaris is the predominant STH infection. An overall reduced cure rate (70%) and fecal egg count reduction rate (75%) was reported. Nevertheless, no putative benzimidazole-resistance associated polymorphisms were detected in 4 of the Ascaris B-tubulin isotype genes examined. Given these results, the authors claimed suspicion of ALB resistance in these Ascaris populations.

Upon deeper evaluation of the data collected and provided in this paper an important methodological issue came to light that could provide a more straightforward explanation as to why a reduction in effecacy and cure rates were observed. The authors namely reported that the post-treatment examination was performed between 7 and 10 days after the treatment with ALB. At that time, complete expulsion of adult worms and/or parasite eggs can however not be ensured and would likely lead to misleading conclusions regarding drug efficacy.

Although the time point at which post-treatment samples are collected is crucial to readily interpret the drug efficacy, empirical evidence for the optimal timing of post-treatment sampling remains scarce for all STHs. In this light, Levecke et al. followed with the publication of the results of an expulsion study performed by Easton and colleagues in 19 Kenyan individuals treated with ALB. (Find paper HERE) There it was apparant that it takes up to 10 days for all infected individuals to clear the adult worm load and that approximately 20% of all worms is being expelled between day 7 and 10 post treatment.

The barplot represents the number of adult Ascaris worms recovered from 21 Kenyan patients treated on day 0 with 400mg Albendazole over a time span of 10 days post treatment  (white: female; black:male and grey: unknown sex)

Based on these findings, it is recommended to wait at least 14 days after an ALB treatment before conducting follow-up egg counts.Any sampling performed before this time point may result in biased ERR estimates, due to release of residual eggs from moridund or degenerating worms.

 

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