Single-Nucleotide Polymorphisms in the Beta-Tubulin Gene and Its Relationship with Treatment Response to Albendazole in Human Soil-Transmitted Helminths in Southern Mozambique

Abstract

Soil-transmitted helminth (STH) cornerstone control strategy is mass drug administration (MDA) with benzimidazoles. However, MDA might contribute to selection pressure for anthelmintic resistance, as occurred in livestock. The aim of this study is to evaluate the treatment response to albendazole and the relationship with the presence of putative benzimidazole resistance single-nucleotide polymorphisms (SNPs) in the β-tubulin gene of STH in Southern Mozambique. After screening 819 participants, we conducted a cohort study with 184 participants infected with STH in Manhiça district, Southern Mozambique. A pretreatment and a posttreatment stool samples were collected and the STH infection was identified by duplicate Kato-Katz and quantitative polymerase chain reaction (qPCR). Cure rate and egg reduction rates were calculated. Putative benzimidazole resistance SNPs (F167Y, F200T, and E198A) in Trichuris trichiura and Necator americanus were assessed by pyrosequencing. Cure rates by duplicate Kato-Katz and by qPCR were 95.8% and 93.6% for Ascaris lumbricoides, 28% and 7.8% for T. trichiura, and 88.9% and 56.7% for N. americanus. Egg reduction rate by duplicate Kato-Katz was 85.4% for A. lumbricoides, 34.9% for T. trichiura, and 40.5% for N. americanus. Putative benzimidazole resistance SNPs in the β-tubulin gene were detected in T. trichiura (23%) and N. americanus (21%) infected participants at pretreatment. No statistical difference was observed between pretreatment and posttreatment frequencies for none of the SNPs. Although treatment response to albendazole was low, particularly in T. trichiura, the putative benzimidazole resistance SNPs were not higher after treatment in the population studied. New insights are needed for a better understanding and monitoring of human anthelmintic resistance.

Anthelmintic resistance in soil-transmitted helminths: One-Health considerations

“…The presence of the common resistance markers in human STHs further provides compelling evidence for how patterns of resistance in veterinary parasites can emerge in related human parasites (O'Halloran 2021 ). What is currently uncertain is whether any of these SNPs are influencing BZ efficacy against human STHs (Furtado et al 2019 ; Grau-Pujol et al 2022 ; Matamoros et al 2019 ; Orr et al 2019 ; Zuccherato et al 2018 ). However, Diawara et al ( 2013 ) concluded that ALB exerts selection pressure on the β-tubulin gene at position 200 in T. trichiura , which could explain the moderate ALB efficacy against human trichuriasis.…”

“…F167Y, F200Y, E198A PCR and sequencing N. americanus Low Ghana (Orr et al 2019 ) 6. F167Y, F200Y, E198A PCR and pyrosequencing T. trichiura , N. americanus x Mozambique (Grau-Pujol et al 2022 ) 7. F167Y, E198A, E198L, F200Y Deep amplicon sequencing A. lumbricoides , A. suum x Ethiopia, Tanzania, Belgium (Roose et al 2021 ) 8.…”

“…Furthermore, the resistance patterns in veterinary species provide compelling evidence of the possibility of widespread resistance in related human species, especially with the current community-wide MDA programs. Although there is no conclusive evidence of AH resistance in human STH species, many questions still linger as to whether there is any link between the isotype-1 β-tubulin SNPs and the possible emergence of BZ resistance in human STHs (Furtado et al 2019 ; Grau-Pujol et al 2022 ; Matamoros et al 2019 ; Orr et al 2019 ; Zuccherato et al 2018 ). However, since some of the parasites are zoonotic and capable of producing patent infections in people, the prospect of AR developing in clinical settings cannot be disregarded any longer.…”

A drug repurposing screen for whipworms informed by comparative genomics

“…Indeed, of the three major soil-transmitted helminthiases, current drugs have the lowest efficacy for trichuriasis [4,5]. Furthermore, there is worrying evidence of resistance to mebendazole and albendazole in Trichuris in humans [6,7].…”