Identification of a predominant genotype of Mycobacterium tuberculosis in Brazilian indigenous population

S A Hadi,E A T Cunha,D A M Villela,E P Brenner,P C Basta,J Ravi,V Simonsen,R S Santos,S Sreevatsan,I V Kolte,L Ferrazoli

doi:10.1038/s41598-020-79621-3

S A Hadi, E A T Cunha + Show 9 more

Open Access

https://doi.org/10.1038/s41598-020-79621-3

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Abstract

After nearly a century of vaccination and six decades of drug therapy, tuberculosis (TB) kills more people annually than any other infectious disease. Substantial challenges to disease eradication remain among vulnerable and underserved populations. The Guarani-Kaiowá people are an indigenous population in Paraguay and the Brazilian state of Mato Grosso do Sul. This community, marginalized in Brazilian society, experiences severe poverty. Like other South American indigenous populations, their TB prevalence is high, but the disease has remained largely unstudied in their communities. Herein, Mycobacterium tuberculosis isolates from local clinics were whole genome sequenced, and a population genetic framework was generated. Phylogenetics show M. tuberculosis isolates in the Guarani-Kaiowá people cluster away from selected reference strains, suggesting divergence. Most cluster in a single group, further characterized as M. tuberculosis sublineage 4.3.3. Closer analysis of SNPs showed numerous variants across the genome, including in drug resistance-associated genes, and with many unique changes fixed in each group. We report that local M. tuberculosis strains have acquired unique polymorphisms in the Guarani-Kaiowá people, and drug resistance characterization is urgently needed to inform public health to ensure proper care and avoid further evolution and spread of drug-resistant TB.

Highlights

After nearly a century of vaccination and six decades of drug therapy, tuberculosis (TB) kills more people annually than any other infectious disease
TB is hyperendemic among indigenous populations like the Guarani-Kaiowá in Brazil, there has been a lack of investigation into TB transmission in these settings, a red flag for public health policy
Our phylogenomic study indicates that, cases were diagnosed across six different territories over a study period of six years, a majority of the sequenced cases are caused by M. tuberculosis clustered into sublineage 4.3.3 (Fig. 1, blue clades)

Summary

Introduction

After nearly a century of vaccination and six decades of drug therapy, tuberculosis (TB) kills more people annually than any other infectious disease. The existing evidence indicates that incidence of active TB and prevalence of latent TB infection (LTBI) are significantly higher in indigenous groups compared to non-indigenous populations g lobally[1]. This is a result of socioeconomic inequalities, including limited access to education, lack of employment opportunities and marginalization[2]. The aim of this study was to characterize the genomic patterns of diversification of drug resistance, and explore whether hyperendemic, locally circulating Mycobacterium tuberculosis in the indigenous population of the Guarani-Kaiowá may be a product of regular introductions from outside the community, or unchecked transmission within

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