Abstract

Mycobacterium bovis is the main pathogen of bovine, zoonotic, and wildlife tuberculosis. Despite the existence of programs for bovine tuberculosis (bTB) control in many regions, the disease remains a challenge for the veterinary and public health sectors, especially in developing countries and in high-income nations with wildlife reservoirs. Current bTB control programs are mostly based on test-and-slaughter, movement restrictions, and post-mortem inspection measures. In certain settings, contact tracing and surveillance has benefited from M. bovis genotyping techniques. More recently, whole-genome sequencing (WGS) has become the preferential technique to inform outbreak response through contact tracing and source identification for many infectious diseases. As the cost per genome decreases, the application of WGS to bTB control programs is inevitable moving forward. However, there are technical challenges in data analyses and interpretation that hinder the implementation of M. bovis WGS as a molecular epidemiology tool. Therefore, the aim of this review is to describe M. bovis genotyping techniques and discuss current standards and challenges of the use of M. bovis WGS for transmission investigation, surveillance, and global lineages distribution. We compiled a series of associated research gaps to be explored with the ultimate goal of implementing M. bovis WGS in a standardized manner in bTB control programs.

Highlights

  • Tuberculosis (TB) is a transmissible disease of humans and animals accompanying societies for thousands of years [1]

  • variable number tandem repeats (VNTR) is a locus in which a nucleotide sequence is arranged as tandem repeats, i.e., repeats clustered together and oriented in the same direction

  • The size of this locus varies according to the number of times the nucleotide sequence is repeated

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Summary

Introduction

Tuberculosis (TB) is a transmissible disease of humans and animals accompanying societies for thousands of years [1]. Despite progress in its control and prevention, TB is a top cause of mortality by a single infectious agent in the world and has devastating effects on bovine livestock and wildlife populations. Ten million new cases and 1.2 million human deaths were reported in 2018, and the increasing incidence of multidrug resistant strains is a threat to public health [2]. Bovine TB (bTB) is an OIE (World Organisation for Animal Health) notifiable disease and, of the 179 countries reporting disease status in 2015–2016, approximately 50% declared the presence of TB in animals, with higher prevalence in Africa and parts of Asia and the Americas [3]. Despite an effective global notification system, the actual impact of bTB in animals is not fairly quantified, especially in wildlife and in countries where disease control programs are not well-established [4]. TB in cattle has important socioeconomic consequences, as the loss of livestock severely affects producers in developing countries with poorly implemented disease control programs and in certain developed nations where specific wildlife reservoirs create pockets of infection [4,5,6,7,8,9,10]

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