Molecular epidemiology and transmission dynamics of multi-drug resistant tuberculosis strains using whole genome sequencing in the Amhara region, Ethiopia.

BACKGROUND: Drug resistant Mycobacterium tuberculosis prevention and care is a major challenge in Ethiopia. The World health organization has designated Ethiopia as one of the 30 high burden multi-drug resistant tuberculosis (MDR-TB) countries. There is limited information regarding genetic diversity and transmission dynamics of MDR-TB in Ethiopia. OBJECTIVE: To investigate the molecular epidemiology and transmission dynamics of MDR-TB strains using whole genome sequence (WGS) in the Amhara region. METHODS: Forty-five MDR-TB clinical isolates from Amhara region were collected between 2016 and 2018, and characterized using WGS and 24-loci Mycobacterium Interspersed Repetitive Units Variable Number of Tandem Repeats (MIRU-VNTR) typing. Clusters were defined based on the maximum distance of 12 single nucleotide polymorphisms (SNPs) or alleles as the upper threshold of genomic relatedness. Five or less SNPs or alleles distance or identical 24-loci VNTR typing is denoted as surrogate marker for recent transmission. RESULTS: Forty-one of the 45 isolates were analyzed by WGS and 44% (18/41) of the isolates were distributed into 4 clusters. Of the 41 MDR-TB isolates, 58.5% were classified as lineage 4, 36.5% lineage 3 and 5% lineage 1. Overall, TUR genotype (54%) was the predominant in MDR-TB strains. 41% (17/41) of the isolates were clustered into four WGS groups and the remaining isolates were unique strains. The predominant cluster (Cluster 1) was composed of nine isolates belonging to lineage 4 and of these, four isolates were in the recent transmission links. CONCLUSIONS: Majority of MDR-TB strain cluster and predominance of TUR lineage in the Amhara region give rise to concerns for possible ongoing transmission. Efforts to strengthen TB laboratory to advance diagnosis, intensified active case finding, and expanded contact tracing activities are needed in order to improve rapid diagnosis and initiate early treatment. This would lead to the interruption of the transmission chain and stop the spread of MDR-TB in the Amhara region.

Disease management at the wildlife-livestock interface: Using whole-genome sequencing to study the role of elk in Mycobacterium bovis transmission in Michigan, USA.

The role of wildlife in the persistence and spread of livestock diseases is difficult to quantify and control. These difficulties are exacerbated when several wildlife species are potentially involved. Bovine tuberculosis (bTB), caused by Mycobacterium bovis, has experienced an ecological shift in Michigan, with spillover from cattle leading to an endemically infected white-tailed deer (deer) population. It has potentially substantial implications for the health and well-being of both wildlife and livestock and incurs a significant economic cost to industry and government. Deer are known to act as a reservoir of infection, with evidence of M. bovis transmission to sympatric elk and cattle populations. However, the role of elk in the circulation of M. bovis is uncertain; they are few in number, but range further than deer, so may enable long distance spread. Combining Whole Genome Sequences (WGS) for M. bovis isolates from exceptionally well-observed populations of elk, deer and cattle with spatiotemporal locations, we use spatial and Bayesian phylogenetic analyses to show strong spatiotemporal admixture of M. bovis isolates. Clustering of bTB in elk and cattle suggests either intraspecies transmission within the two populations, or exposure to a common source. However, there is no support for significant pathogen transfer amongst elk and cattle, and our data are in accordance with existing evidence that interspecies transmission in Michigan is likely only maintained by deer. This study demonstrates the value of whole genome population studies of M. bovis transmission at the wildlife-livestock interface, providing insights into bTB management in an endemic system.

Antimicrobial Susceptibility Testing of Mycobacterium bovis Isolates from Michigan White-Tailed Deer during the 2009 Hunting Season.

Michigan has had an ongoing outbreak of endemic Mycobacterium bovis which has been recognized within and sustained by its free-ranging white-tailed deer population since 1994. Worldwide, organisms within the Mycobacterium tuberculosis complex have exhibited the ability to develop resistance to antimicrobial agents, resulting in both the multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of human tuberculosis. Michigan's Bovine Tuberculosis Working Group has conducted active antimicrobial susceptibility testing on wildlife isolates of the endemic M. bovis organism at five-year intervals to detect any emerging drug resistance patterns. The results of 33 white-tailed deer origin isolates collected from the 2009 hunting season are reported here. There continues to be no evidence of any drug resistance except for pyrazinamide resistance. These results are likely due to the lack of antibacterial treatment applied to either wildlife or domestic animals which would provide selection pressure for the development of drug resistance.