Molecular techniques to isolate soil-transmitted helminth β-tubulin genes to enhance global surveillance of benzimidazole resistance Open Access
Kobokovich, Amanda (Spring 2018)
Abstract
Background: Soil-transmitted helminths (STH) are highly endemic among resource-poor populations and result in serious health consequences, particularly among pre-school and school-aged children. Mass drug administration (MDA) with benzimidazoles is a highly utilized method to treat populations in these endemic areas. There is increasing concern of anthelmintic resistance to benzimidazoles, heralded by the devastating consequences of overuse in the veterinary field. There is evidence that single-nucleotide polymorphisms (SNPs) in the β-tubulin genes of the STH can confer resistance to benzimidazoles. We assessed the prevalence of these SNPs in two different study populations with different exposure to preventative chemotherapy campaigns.
Methods: Samples selected from surveillance efforts in the Solomon Islands and Guatemala to optimize PCR and Next Generation sequencing to isolate the β-tubulin genes of Ascaris lumbricoides and Necator americanus in order to evaluate the prevalence of SNPs conferring benzimidazole resistance. Statistical analysis was performed on all three STH of interest to evaluate the associations between infection and demographic characteristics.
Findings: Despite the use of a highly specific and valid sequencing technique, we found no evidence of benzimidazole resistance via β-tubulin SNPs in these populations. Regardless of lifestyle similarities, Kwai village had lower odds of infection compared to Ngongosila village across all three STH (A. lumbricoides: OR=0.50, 95% CI=0.36, 0.68) (Hookworms: OR=0.59, 95% CI=0.40, 0.86) (T. trichiura: OR=0.83, 95% CI=0.02, 0.37). Age was associated with both STH prevalence and low STH infection intensity for A. lumbricoides and hookworms. In Guatemala, odds of infection with A. lumbricoides was lower among hospital patients (OR=0.28, 95% CI=0.11, 0.73), while odds of infection with T. trichiura was higher among hospital patients (OR=4.20, 95% CI=1.81, 9.73), both compared to health center patients.
Conclusions: This is the first study of its kind to use this novel molecular technique to identify benzimidazole resistance in STH. Our analysis of infection prevalence and demographic data revealed several interesting associations between age and village, in the Solomon Islands, and site of admission, in Guatemala. More attention must be given to stopping the chain of transmission in endemic locations such that preventative chemotherapy with benzimidazoles is no longer so heavily relied upon.
Table of Contents
Background/Literature Review………………………………………………….
1
Introduction ………………………………………………………………………
23
Materials and Methods…………………………………………………………...
26
Results……………………………………………………………………………..
33
Discussion …………………………………………………………………………
39
Future Directions………………………………………………………….
43
Public Health Implications……………………………………………….
43
References…………………………………………………………………………
45
Tables………………………………………………………………………………
49
Figures………………………………………………………………...…………...
53
Appendix A………………………………………………..………………………
57
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Molecular techniques to isolate soil-transmitted helminth β-tubulin genes to enhance global surveillance of benzimidazole resistance () | 2018-04-25 12:00:59 -0400 |
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