Global variation in bacterial strains that cause tuberculosis disease: a systematic review and meta-analysis

Abstract

BackgroundThe host, microbial, and environmental factors that contribute to variation in tuberculosis (TB) disease are incompletely understood. Accumulating evidence suggests that one driver of geographic variation in TB disease is the local ecology of mycobacterial genotypes or strains, and there is a need for a comprehensive and systematic synthesis of these data. The objectives of this study were to (1) map the global distribution of genotypes that cause TB disease and (2) examine whether any epidemiologically relevant clinical characteristics were associated with those genotypes.MethodsWe performed a systematic review of PubMed and Scopus to create a comprehensive dataset of human TB molecular epidemiology studies that used representative sampling techniques. The methods were developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We extracted and synthesized data from studies that reported prevalence of bacterial genotypes and from studies that reported clinical characteristics associated with those genotypes.ResultsThe results of this study are twofold. First, we identified 206 studies for inclusion in the study, representing over 200,000 bacterial isolates collected over 27 years in 85 countries. We mapped the genotypes and found that, consistent with previously published maps, Euro-American lineage 4 and East Asian lineage 2 strains are widespread, and West African lineages 5 and 6 strains are geographically restricted. Second, 30 studies also reported transmission chains and 4 reported treatment failure associated with genotypes. We performed a meta-analysis and found substantial heterogeneity across studies. However, based on the data available, we found that lineage 2 strains may be associated with increased risk of transmission chains, while lineages 5 and 6 strains may be associated with reduced risk, compared with lineage 4 strains.ConclusionsThis study provides the most comprehensive systematic analysis of the evidence for diversity in bacterial strains that cause TB disease. The results show both geographic and epidemiological differences between strains, which could inform our understanding of the global burden of TB. Our findings also highlight the challenges of collecting the clinical data required to inform TB diagnosis and treatment. We urge future national TB programs and research efforts to prioritize and reinforce clinical data collection in study designs and results dissemination.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1180-x) contains supplementary material, which is available to authorized users.

Zoonotic tuberculosis in India: looking beyondMycobacterium bovis

“…M. tuberculosis sensu stricto isolates from South Asia were dispersed across lineages 1-4 with an enrichment of lineages 1 and 3, which is concordant with previous reports ( 26 ). Cattle origin MTBC sequences deposited from South Asia were distributed among M. tuberculosis lineage 1 and M. orygis lineages, highlighting the need to understand pathogenicity and transmission dynamics of these pathogens in cattle.…”

“…Alternatively, Rahim et al suggested that the global distribution of these subspecies indicates the emergence of M. orygis prior to M. bovis from a common MTBC ancestor, wherein M. orygis may have been dispersed to South Asia with the migration of humans and become established before the arrival of M. bovis ( 14 ). However, prior establishment of an MTBC lineage does not negate the introduction of another at a later point in time, as is demonstrated by the wide dispersal of M. tuberculosis lineages 2 and 4 ( 26 ).…”

Origin of tuberculosis in the Paleolithic predicts unprecedented population growth and female resistance

“…Our work also has incorporated other assumptions regarding the different virulence mechanisms between "ancient" and "modern" MtbC lineages in the knowledge that this is a question open to discussion. What is clear is the evidence for the higher dissemination ability of "modern" lineages compared with "ancient" ones 21 . The fact that the latter are restricted to specific geographical regions also points to some sort of genetic susceptibility linked to race/ethnic groups, as proposed by several authors 7,17,66 .…”

“…Thus, the trade-off for "ancient" MtbC lineages is the higher probability of progression to active TB at a cost of being less able to disseminate through the population explaining why "ancient" lineages can only be found in certain geographical locations 21 . The fact that the appearance of "modern" lineages (46,000 BCE) coincided with a significant increase in the population (from 10 4 to 10 6 individuals) in Asia, while remaining constant in Africa (around 10 6 people) 22,23 , indicates that some sort of population explosion occurred in Asia before the Neolithic, as proposed by several authors [24][25][26] , giving support to its dissemination.…”

The geno-spatio analysis of Mycobacterium tuberculosis complex in hot and cold spots of Guangxi, China

“…It is widely recognized that Mycobacterium tuberculosis (Mtb) of different molecular types have different transmission capacities, pathogenicity and drug resistance rates [1,2]. Therefore, Mtb genotypes may be associated with the tuberculosis (TB) endemicity [3,4].…”