Evaluation of the Epidemiological Relevance of Variable-Number Tandem-Repeat Genotyping ofMycobacterium bovisand Comparison of the Method with IS6110Restriction Fragment Length Polymorphism Analysis and Spoligotyping

Abstract

Sources ofMycobacterium bovis is the causative agent of tuberculosis in bovines. In addition to cattle, this pathogen has an exceptionally wide host range, extending to goats, cats, dogs, pigs, lions, deer, nonhuman primates, and humans. Many susceptible species, including humans, are putative spillover hosts, in which infection is not confined. Some countries, such as Great Britain and Ireland, are currently experiencing an exponential increase in the incidence of bovine tuberculosis. Moreover, M. bovis

Genotyping North American Animal Mycobacterium Bovis Isolates Using Multilocus Variable Number Tandem Repeat Analysis

“…Other research groups have experienced similar difficulties and have eliminated 1 or both of these markers from consideration. 1,12,18 Allowing 1 locus to remain polymorphic within each of the MLVA types did not affect the phylogenetic analysis when using the subset of 6 loci for types K, L, and M because the polymorphism within these types was observed at loci not included in the subset. In addition, each of these polymorphisms involved only a 1-step change in the TR copy number.…”

“…1,9,12,[16][17][18] A previous study, 18 based on a worldwide collection of M. tuberculosis isolates, proposed an optimized set of 24 VNTR loci, which included a subset of 15 discriminatory loci, for use as a first-line typing method. However, the determination of which markers and groups of markers will prove to be the most useful for local application should be determined empirically.…”

“…9,15 In a recent study of M. bovis isolates found in Belgium, MLVA was highly consistent among isolates with known epidemiological links, and it discriminated better than both IS6110 RFLP and spoligotyping among isolates with no known epidemiologic links. 1 Assessment of MLVA of M. bovis isolates found in North America is limited. The MLVA loci that prove to be the most useful for genotyping isolates may vary from region to region and should be chosen experimentally for the target region.…”

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

“…First, on a population basis, strain typing identifies strain relatedness, thus identifying chains of transmission (a cluster of isolates with identical genotypes according to IS6110 DNA fingerprinting, 44 mycobacterial inter spersed repetitive units-variable numbers of tandem repeat [MIRU-VNTR] typing, 45 or whole-genome sequencing; 46 figure 2) and providing an indication of how well a tuberculosis control programme functions with respect to transmission control. 47,48 High clustering of drug-resistant tuberculosis strains is indicative of high levels of transmission, which might be because of the absence of appropriate case detection and diagnosis-associated delays (and hence treatment delays).…”

“…45,50 This definition of a cluster can be flexible to allow for minor variation in the IS6110 RFLP or MIRU-VNTR patterns and evolutionary events. 51,52 Within the context of drug-resistant tuberculosis, supporting the definition of a cluster with resistance-conferring SNP data is crucial.…”