Reduced efficacy of albendazole against Ascaris lumbricoides in Rwandan schoolchildren

Abstract

Control of human soil-transmitted helminths (STHs) relies on preventive chemotherapy of schoolchildren applying the benzimidazoles (BZ) albendazole or mebendazole. Anthelmintic resistance (AR) is a common problem in nematodes of veterinary importance but for human STHs, information on drug efficacy is limited and routine monitoring is rarely implemented. Herein, the efficacy of single dose albendazole (400 mg) was evaluated in 12 schools in the Huye district of Rwanda where Ascaris is the predominant STH. Ascaris eggs were detected by wet mount microscopy and the Mini-FLOTAC method to assess cure rate (CR) and faecal egg count reduction (FECR). Blood and faecal samples were analysed for co-infections with Plasmodium sp. and Giardia duodenalis, respectively. Ascaris positive samples collected before and after treatment were analysed for putatively BZ-resistance associated β-tubulin gene single nucleotide polymorphisms. The overall CR was 69.9% by Mini-FLOTAC and 88.6% by wet mount microscopy. The FECR was 75.4% and the 95% calculated confidence intervals were 50.4–87.8% using sample variance, 55.4–88.8% by bootstrapping, and 75.0–75.7% applying a Markov Chain Monte Carlo Bayesian approach. FECR varied widely between 0 and 96.8% for individual schools. No putative BZ-resistance associated polymorphisms were found in the four Ascaris β-tubulin isotype genes examined. Since FECRs <95% indicate reduced efficacy, these findings raise the suspicion of BZ resistance. In the absence of respective molecular evidence, heritable AR in the local Ascaris populations cannot be formally proven. However, since FECRs <95% indicate reduced efficacy, BZ resistance may be suspected which would be alarming and calls for further analyses and routine monitoring in preventive chemotherapy programs.

Molecular monitoring of the therapeutic effect of Albendazole on Ascaris lumbricoides and Ancylostoma duodenale infected children using conventional multiplex PCR

“…in Timor-Leste Susana. Exceeding our results for A. lumricoides Krücken et al, [28] reported a pre-ADZ treatment prevalence of 33.3% for Ascaris in Rwandan schoolchildren, and Augusto et al, [29] detected 65.8% rate in children and young adults in Mozambique.…”

New codon 198 β-tubulin polymorphisms in highly benzimidazole resistant Haemonchus contortus from goats in three different states in Sudan

“…Anthelmintic resistance is already a significant problem in veterinary medicine [7], and currently is suspected to be developing in nematodes that infect humans [8]. The economic impact of AR in farm animals is caused by direct production losses such as losses due to clinical and subclinical disease despite treatment, costs for testing of anthelmintic efficacy and the use of new, more expensive classes of anthelmintics [9].…”

Plant-Based Natural Products for the Discovery and Development of Novel Anthelmintics against Nematodes

“…Resistance against one particular anthelmintic drug is typically accompanied by resistance against other members belonging to the same class (i.e., side-resistance, as opposed to cross-and multidrug-resistance, which refers to resistance against two or multiple drugs belonging to different anthelmintic drug classes) [31]. Anthelmintic resistance has been claimed to occur occasionally also in human intestinal nematodes [35,36], but this is controversial [10,37,38]. It may only be a matter of time before this phenomenon becomes common in helminths of humans [23,39].…”

“…The authors concluded that plants from the Leguminosae family may offer an alternative source for the control of gastrointestinal nematodes of small ruminants. (5,6,7,17,19,26,27,28,31,32,33,34,36), saponin (4,25), terpenoids (12,13,15,16,18,37), alkaloids (1,2,3,8,9), coumaric acid (14,29,30), miscellaneous (10,11,20,21,22,24).…”