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Abstract
BackgroundDifferent combinations of variable number of tandem repeat (VNTR) loci have been proposed for genotyping Mycobacterium tuberculosis complex (MTBC). Existing VNTR schemes show different discriminatory capacity among the six human MTBC lineages. Here, we evaluated the discriminatory power of a “customized MIRU12” loci format proposed previously by Comas et al. based on the standard 24 loci defined by Supply et al. for VNTR-typing of MTBC in Ghana.MethodOne hundred and fifty-eight MTBC isolates classified into Lineage 4 and Lineage 5 were used to compare a customized lineage-specific panel of 12 MIRU-VNTR loci (“customized MIRU-12″) to the standard MIRU-15 genotyping scheme. The resolution power of each typing method was determined based on the Hunter-Gaston- Discriminatory Index (HGDI). A minimal set of customized MIRU-VNTR loci for typing Lineages 4 (Euro-American) and 5 (M. africanum West African 1) strains from Ghana was defined based on the cumulative HGDI.Results and ConclusionAmong the 106 Lineage 4 strains, the customized MIRU-12 identified a total of 104 distinct genotypes consisting of 2 clusters of 2 isolates each (clustering rate 1.8%), and 102 unique strains while standard MIRU-15 yielded a total of 105 different genotypes, including 1 cluster of 2 isolates (clustering rate: 0.9%) and 104 singletons. Among, 52 Lineage 5 isolates, customized MIRU-12 genotyping defined 51 patterns with 1 cluster of 2 isolates (clustering rate: 0.9%) and 50 unique strains whereas MIRU-15 classified all 52 strains as unique. Cumulative HGDI values for customized MIRU-12 for Lineages 4 and 5 were 0.98 respectively whilst that of standard MIRU-15 was 0.99. A union of loci from the customised MIRU-12 and standard MIRU-15 revealed a set of customized eight highly discriminatory loci: 4052, 2163B, 40, 4165, 2165, 10,16 and 26 with a cumulative HGDI of 0.99 for genotyping Lineage 4 and 5 strains from Ghana.
Highlights
Tuberculosis (TB) is a major public health problem worldwide, causing 8.8 million new cases and more than 1.4 million deaths each year [1]
Among the 106 Lineage 4 strains, the customized MIRU-12 identified a total of 104 distinct genotypes consisting of 2 clusters of 2 isolates each, and 102 unique strains while standard MIRU-15 yielded a total of 105 different genotypes, including 1 cluster of 2 isolates and 104 singletons
Different combinations of MIRU and other variable number of tandem repeat (VNTR) loci have been proposed to complement the standard MIRU-15 scheme to achieve higher discrimination. Results accumulated from such studies clearly revealed that due to the strong phylogeographic structure exhibited by Mycobacterium tuberculosis complex (MTBC), the most relevant MIRU-VNTR
Summary
Tuberculosis (TB) is a major public health problem worldwide, causing 8.8 million new cases and more than 1.4 million deaths each year [1]. The conventional indicators used for assessing TB control programmes focuses on the proportion of patients with new sputum smear positive pulmonary disease that are cured by the end of treatment or whose sputum microscopy becomes negative after the first 2 months of treatment [3]. Such indicators ignore important aspects of TB control such as the duration of infectivity, the frequency of reactivation, and the risk of progression among the infected contacts, or the risk of transmission. We evaluated the discriminatory power of a ‘‘customized MIRU12’’ loci format proposed previously by Comas et al based on the standard 24 loci defined by Supply et al for VNTR-typing of MTBC in Ghana
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