Stephenson LS , Holland CV , Cooper ES , 2000. The public health significance of Trichuris trichiura .Parasitology 121 (Suppl): S73–S95.
Crowe AL , Smith P , Ward L , Currie BJ , Baird R , 2014. Decreasing prevalence of Trichuris trichiura (whipworm) in the Northern Territory from 2002 to 2012. Med J Aust 200: 286–289.
Diawara A , Drake LJ , Suswillo RR , Kihara J , Bundy DA , Scott ME , Halpenny C , Stothard JR , Prichard RK , 2009. Assays to detect beta-tubulin codon 200 polymorphism in Trichuris trichiura and Ascaris lumbricoides. PLoS Negl Trop Dis 3: e397.
Campbell SJ , Nery SV , McCarthy JS , Gray DJ , Soares Magalhães RJ , Clements A , 2016. A critical appraisal of control strategies for soil-transmitted helminths. Trends Parasitol 32: 97–107.
Jourdan PM , Lamberton P , Fenwick A , Addiss DG , 2018. Soil-transmitted helminth infections. Lancet 391: 252–265.
Kwa MS , Veenstra JG , Roos MH , 1994. Benzimidazole resistance in Haemonchus contortus is correlated with a conserved mutation at amino acid 200 in beta-tubulin isotype 1. Mol Biochem Parasitol 63: 299–303.
Prichard R , 2001. Genetic variability following selection of Haemonchus contortus with anthelmintics. Trends Parasitol 17: 445–453.
Ghisi M , Kaminsky R , Mäser P , 2007. Phenotyping and genotyping of Haemonchus contortus isolates reveals a new putative candidate mutation for benzimidazole resistance in nematodes. Vet Parasitol 144: 313–320.
McKay GJ , Cooke LR , 1997. A PCR-based method to characterize and identify benzimidazole resistance in Helminthosporium solani. FEMS Microbiol Lett 152: 371–378.
Atanásio-Nhacumbe A , Lambert SM , da Silva Souza B , Ayres M , 2019. Molecular detection of benzimidazole resistance levels associated with F167Y and F200Y polymorphisms in Haemonchus contortus of goats from Mozambique. Parasitol Res 118: 245–253.
Rashwan N , Scott M , Prichard R , 2017. Rapid Genotyping of β-tubulin Polymorphisms in Trichuris trichiura and Ascaris lumbricoides. PLoS Negl Trop Dis 11: e0005205.
Zuccherato LW , Furtado LF , Medeiros C , Pinheiro C , Rabelo ÉM , 2018. PCR-RFLP screening of polymorphisms associated with benzimidazole resistance in Necator americanus and Ascaris lumbricoides from different geographical regions in Brazil. PLoS Negl Trop Dis 12: e0006766.
Martínez-Valladares M , Valderas-García E , Gandasegui J , Skuce P , Morrison A , Castilla Gómez de Agüero V , Cambra-Pellejà M , Balaña-Fouce R , Rojo-Vázquez FA , 2020. Teladorsagia circumcincta beta tubulin: the presence of the E198L polymorphism on its own is associated with benzimidazole resistance. Parasit Vectors 13: 453.
Avramenko RW , Redman EM , Melville L , Bartley Y , Wit J , Queiroz C , Bartley DJ , Gilleard JS , 2019. Deep amplicon sequencing as a powerful new tool to screen for sequence polymorphisms associated with anthelmintic resistance in parasitic nematode populations. Int J Parasitol 49: 13–26.
Furtado LF , Magalhães JG , Rabelo É , 2018. Standardization and application of a modified RFLP-PCR methodology for analysis of polymorphisms linked to treatment resistance in Ancylostoma braziliense. Parasit Vectors 11: 540.
Furtado LF , Bello AC , dos Santos HA , Carvalho MR , Rabelo ÉM , 2014. First identification of the F200Y SNP in the β-tubulin gene linked to benzimidazole resistance in Ancylostoma caninum. Vet Parasitol 206: 313–316.
Furtado LF , Alves WP , Moreira TB , Costa LM Jr. , Miranda R , Rabelo É , 2016. Standardization and application of the tetraprimer ARMS-PCR technique for screening of the E198A SNP in the β-tubulin gene of hookworm populations in Brazil. Vet Parasitol 224: 65–67.
Furtado LF , Medeiros C , Zuccherato LW , Alves WP , de Oliveira V , da Silva VJ , Miranda GS , Fujiwara RT , Rabelo É , 2019. First identification of the benzimidazole resistance-associated F200Y SNP in the beta-tubulin gene in Ascaris lumbricoides. PLoS One 14: e0224108.
Furtado L , Dos Santos TR , de Oliveira V , Rabelo É , 2020. Genotypic profile of benzimidazole resistance associated with SNP F167Y in the beta-tubulin gene of Necator americanus helminths obtained from Brazilian populations. Infect Genet Evol 86: 104594.
Silvestre A , Cabaret J , 2002. Mutation in position 167 of isotype 1 beta-tubulin gene of Trichostrongylid nematodes: role in benzimidazole resistance? Mol Biochem Parasitol 120: 297–300.
Rashwan N , Bourguinat C , Keller K , Gunawardena NK , de Silva N , Prichard R , 2016. Isothermal diagnostic assays for monitoring single nucleotide polymorphisms in Necator americanus associated with benzimidazole drug resistance. PLoS Negl Trop Dis 10: e0005113.
Diawara A et al.2013. Association between response to albendazole treatment and β-tubulin genotype frequencies in soil-transmitted helminths. PLoS Negl Trop Dis 7: e2247.
Olsen A , 2007. Efficacy and safety of drug combinations in the treatment of schistosomiasis, soil-transmitted helminthiasis, lymphatic filariasis and onchocerciasis. Trans R Soc Trop Med Hyg 101: 747–758.
Geary TG et al.2010. Unresolved issues in anthelmintic pharmacology for helminthiases of humans. Int J Parasitol 40: 1–13.
Ritchie LS , 1948. An ether sedimentation technique for routine stool examinations. Bull US Army Med Dep 8: 326.
Lake SL , Matthews JB , Kaplan RM , Hodgkinson JE , 2009. Determination of genomic DNA sequences for beta-tubulin isotype 1 from multiple species of cyathostomin and detection of resistance alleles in third-stage larvae from horses with naturally acquired infections. Parasit Vectors 2 (Suppl 2): S6.
Diawara A , Schwenkenbecher JM , Kaplan RM , Prichard RK , 2013. Molecular and biological diagnostic tests for monitoring benzimidazole resistance in human soil-transmitted helminths. Am J Trop Med Hyg 88: 1052–1061.
Furtado L , de Aguiar P , Zuccherato LW , Teixeira T , Alves WP , da Silva VJ , Gasser RB , Rabelo É , 2019. Albendazole resistance induced in Ancylostoma ceylanicum is not due to single-nucleotide polymorphisms (SNPs) at codons 167, 198, or 200 of the beta-tubulin gene, indicating another resistance mechanism. Parasitol Res 118: 837–849.
Sanger F , Nicklen S , Coulson AR , 1977. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74(12): 5463–5467.
Hansen TV , Thamsborg SM , Olsen A , Prichard RK , Nejsum P , 2013. Genetic variations in the beta-tubulin gene and the internal transcribed spacer 2 region of Trichuris species from man and baboons. Parasit Vectors 6: 236.
Matamoros G , Rueda MM , Rodríguez C , Gabrie JA , Canales M , Fontecha G , Sanchez A , 2019. High endemicity of soil-transmitted helminths in a population frequently exposed to albendazole but no evidence of antiparasitic resistance. Trop Med Infect Dis 4: 73.
Blackhall WJ , Kuzmina T , von Samson-Himmelstjerna G , 2011. β-Tubulin genotypes in six species of cyathostomins from anthelmintic-naive Przewalski and benzimidazole-resistant brood horses in Ukraine. Parasitol Res 109: 1199–1203.
Ademola IO , Krücken J , Ramünke S , Demeler J , von Samson-Himmelstjerna G , 2015. Absence of detectable benzimidazole-resistance associated alleles in Haemonchus placei in cattle in Nigeria revealed by pyrosequencing of β-tubulin isotype 1. Parasitol Res 114: 1997–2001.
Redman E , Whitelaw F , Tait A , Burgess C , Bartley Y , Skuce PJ , Jackson F , Gilleard JS , 2015. The emergence of resistance to the benzimidazole anthelmintics in parasitic nematodes of livestock is characterised by multiple independent hard and soft selective sweeps. PLoS Negl Trop Dis 9: e0003494.
Schwenkenbecher JM , Kaplan RM , 2009. Real-time PCR assays for monitoring benzimidazole resistance-associated mutations in Ancylostoma caninum. Exp Parasitol 122: 6–10.
Dixit AK , Das G , Dixit P , Singh AP , Kumbhakar NK , Sankar M , Sharma RL , 2017. An assessment of benzimidazole resistance against caprine nematodes in central India. Trop Anim Health Prod 49: 1471–1478.
Mohanraj K , Subhadra S , Kalyanasundaram A , Ilangopathy M , Raman M , 2017. Genotyping of benzimidazole resistant and susceptible isolates of Haemonchus contortus from sheep by allele specific PCR. J Parasit Dis 41: 282–288.
Furtado LFV , de Paiva Bello ACP , Rabelo ÉML , 2016. Benzimidazole resistance in helminths: from problem to diagnosis. Acta Trop 162: 95–102.
Zhang H , Brankovics B , van der Lee TA , Waalwijk C , van Diepeningen AA , Xu J , Xu J , Chen W , Feng J , 2016. A single-nucleotide-polymorphism-based genotyping assay for simultaneous detection of different carbendazim-resistant genotypes in the Fusarium graminearum species complex. PeerJ 4: e2609.
Barrère V , Alvarez L , Suarez G , Ceballos L , Moreno L , Lanusse C , Prichard RK , 2012. Relationship between increased albendazole systemic exposure and changes in single nucleotide polymorphisms on the β-tubulin isotype 1 encoding gene in Haemonchus contortus. Vet Parasitol 186: 344–349.
Bennett A , Guyatt H , 2000. Reducing intestinal nematode infection: efficacy of albendazole and mebendazole. Parasitol Today 16: 71–74.
Keiser J , Utzinger J , 2010. The drugs we have and the drugs we need against major helminth infections. Adv Parasitol 73: 197–230.
Vercruysse J , Albonico M , Behnke JM , Kotze AC , Prichard RK , McCarthy JS , Montresor A , Levecke B , 2011. Is anthelmintic resistance a concern for the control of human soil-transmitted helminths? Int J Parasitol Drugs Drug Resist 1: 14–27.
Niciura SC et al.2012. F200Y polymorphism in the β-tubulin gene in field isolates of Haemonchus contortus and risk factors of sheep flock management practices related to anthelmintic resistance. Vet Parasitol 190: 608–612.
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Preventive chemotherapy is recommended by the WHO as the main strategy for controlling infections caused by nematodes in humans, aiming to eliminate the morbidity associated with these infections. This strategy consists of routine periodic administration of benzimidazoles, among other drugs. Although these drugs decrease the intensity of infections, they have the potential to exert selection pressure for genotypes bearing mutations associated with drug resistance, which may result in the establishment of resistant worm populations. There is evidence in the literature of resistance to these drugs in nematodes that infect humans, including in the species Trichuris trichiura. Single-nucleotide polymorphisms (SNPs) in the beta-tubulin gene located at codons 167, 198, and 200 are associated with the mechanism of resistance to benzimidazoles in nematodes. Here, we standardized a molecular technique based on an amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) to analyze codons 167, 198, and 200 of T. trichiura. The ARMS-PCR methodology was successfully established to evaluate the codons of interest. A total of 420 samples of individual eggs were analyzed from populations obtained from five Brazilian states. A mutation in codon 198 was observed at a frequency of 4.8% (20/420), while for the other two codons, no polymorphism was observed. This is the first report of the presence of this mutation in populations of T. trichiura in Brazil. This fact and the emergence of the problem already observed in other species reinforces the need for regular monitoring of SNPs related to benzimidazole resistance using techniques that are highly sensitive and specific.
Financial support: This work was supported by the Fundação de Amparo à Pesquisa do Estado de Minas Gerais – FAPEMIG (Grant nos. APQ-01289-21 and APQ-02273-21).
Authors’ addresses: Valéria Nayara Gomes Mendes de Oliveira, Luciana Werneck Zuccherato, Talita Rodrigues dos Santos, and Élida Mara Leite Rabelo, Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Belo Horizonte, Minas Gerais, Brazil, E-mails: nayaragmo@gmail.com, lucianawerneck@yahoo.com.br, talitarodrigues779@gmail.com, and elidam.rabelo@gmail.com. Luis Fernando Viana Furtado, Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Belo Horizonte, Minas Gerais, Brazil, and Universidade do Estado de Minas Gerais, Unidade Passos, Minas Gerais, Brazil, E-mail: lfvfurtado@gmail.com.