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

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  • 1 Barcelona Institute for Global Health (ISGlobal), Hospital Clínic – University of Barcelona, Barcelona, Spain;
  • | 2 Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique;
  • | 3 Mundo Sano Foundation, Buenos Aires, Argentina;
  • | 4 Instituto de Ganadería de Montaña (CSIC-Universidad de León), Grulleros, León, Spain;
  • | 5 Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de León, Campus de Vegazana, León, Spain;
  • | 6 Department of Parasitology, Centre of Infectious Diseases, Leiden University Medical Center (LUMC), Leiden, The Netherlands;
  • | 7 Expanded Special Project for Elimination of NTDs, World Health Organization Regional Office for Africa, Brazzaville, The Republic of the Congo
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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.

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Author Notes

Address correspondence to Berta Grau-Pujol, Barcelona Institute for Global Health (ISGlobal), Hospital Clínic – University of Barcelona, Barcelona 08036, Spain. E-mail: berta.grau@isglobal.org

Disclosure: Data cannot be shared publically because of participants’ consent. But data will be available on a reasonable request from Data Management external unit at ISGlobal (bioesdm@isglobal.es).

Financial support: This work was supported by the British Society for Antimicrobial Chemotherapy (Bsac-2018-0018) and Mundo Sano Foundation (www.mundosano.org). We acknowledge support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the “Generalitat de Catalunya” through the CERCA Program. CISM is supported by the Government of Mozambique and the Spanish Agency for International Development (AECID). M. C. P. was funded by Junta de Castilla y León and Fondo Social Europeo (LE-135-19). J. G. was personally supported at the beginning of the work by the Ramón Areces Foundation and is now funded by the Spanish “Juan de la Cierva” Programme, Ministry of Economy and Competitiveness (FJC-2018-38305). M. M. V. by the “Ramón y Cajal” Programme (RYC-2015-18368), Spanish Ministry of Economy, Industry and Competitiveness (MINECO). This project was in part funded by the EDCTP2 program supported by the European Union (Grant no. RIA2017NCT-1845-STOP; www.stoptheworm.org) Horizon 2020 European Union Funding for Research and Innovation.

Authors’ addresses: Berta Grau-Pujol, Barcelona Institute for Global Health (ISGlobal), Hospital Clínic - University of Barcelona, Barcelona, Spain, Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique, and Mundo Sano Foundation, Buenos Aires, Argentina, E-mail: berta.grau@isglobal.org. Javier Gandasegui, Maria Cambra-Pellejà, and Maria Martinez-Valladares, Instituto de Ganadería de Montaña (CSIC-Universidad de León), Grulleros, León, Spain, and Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de León, Campus de Vegazana, León, Spain, E-mails: javiergandasegui@gmail.com, mcamp@unileon.es, and mmarva@unileon.es. Valdemiro Escola, Jose Carlos Jamine, Osvaldo Muchisse, Anelsio Cossa, and Charfudin Sacoor, Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique, E-mails: valdemiro.escola@manhica.net, jottac34@gmail.com, osvaldo.muchisse@manhica.net, anelsio.cossa@manhica.net, and charfudin.sacoor@manhica.net. Helena Marti-Soler and Jose Muñoz, Barcelona Institute for Global Health (ISGlobal), Hospital Clínic - University of Barcelona, Barcelona, Spain, E-mails: helena.marti@isglobal.org and jose.munoz@isglobal.org. Maria Demontis, Eric A. T. Brienen, and Lisette Van Lieshout, Department of Parasitology, Centre of Infectious Diseases, Leiden University Medical Center (LUMC), Leiden, The Netherlands, E-mails: demontis@rocketmail.com, e.a.t.brienen@lumc.nl, and e.a.van_lieshout@lumc.nl. Jorge Cano, Expanded Special Project for Elimination of NTDs, World Health Organization Regional Office for Africa, Brazzaville, The Republic of the Congo, E-mail: canoj@who.int.

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