A Novel Approach - The Propensity to Propagate (PTP) Method for Controlling for Host Factors in Studying the Transmission of Mycobacterium Tuberculosis

Abstract

RationaleUnderstanding the genetic variations among Mycobacterium tuberculosis (MTB) strains with differential ability to transmit would be a major step forward in preventing transmission.ObjectivesTo describe a method to extend conventional proxy measures of transmissibility by adjusting for patient-related factors, thus strengthening the causal association found with bacterial factors.MethodsClinical, demographic and molecular fingerprinting data were obtained during routine surveillance of verified MTB cases reported in the Netherlands between 1993 and 2011, and the phylogenetic lineages of the isolates were inferred. Odds ratios for host risk factors for clustering were used to obtain a measure of each patient's and cluster's propensity to propagate (CPP). Mean and median cluster sizes across different categories of CPP were compared amongst four different phylogenetic lineages.ResultsBoth mean and median cluster size grew with increasing CPP category. On average, CPP values from Euro-American lineage strains were higher than Beijing and EAI strains. There were no significant differences between the mean and median cluster sizes among the four phylogenetic lineages within each CPP category.ConclusionsOur finding that the distribution of CPP scores was unequal across four different phylogenetic lineages supports the notion that host-related factors should be controlled for to attain comparability in measuring the different phylogenetic lineages' ability to propagate. Although Euro-American strains were more likely to be in clusters in an unadjusted analysis, no significant differences among the four lineages persisted after we controlled for host factors.

Transmission and Progression to Disease of Mycobacterium tuberculosis Phylogenetic Lineages in The Netherlands

“…In The Netherlands, for example, one study showed that the number of positive contacts around a case increases with growing cluster size (7). In a subsequent study in the same setting, cluster size growth was not different between phylogenetic lineages after controlling for host risk factors (8). However, this study could not distinguish between transmission rates and progression to disease.…”

“…The phylogenetic lineages of isolates were determined using a combination of spoligotyping, the MIRU (mycobacterial interspersed repetitive unit) best match analysis offered by the MIRU-VNTRplus online tool, and RFLP similarity, as described in a previous study using the same data set (8,14). Three species (M. africanum, Mycobacterium bovis, and M. tuberculosis) and four major phylogenetic lineages of M. tuberculosis were identified: the Euro-American, Central Asian strain (CAS), East African Indian (EAI), and Beijing genotypes.…”

PhyResSE: a Web Tool Delineating Mycobacterium tuberculosis Antibiotic Resistance and Lineage from Whole-Genome Sequencing Data

“…This allows assessment of the evidence for the impact of each variant. To simplify this process, variants for which strong experimental evidence is available (e.g., from allelic-exchange experiments [30]) are highlighted in bold as high-confidence SNPs (e.g., katG315, rpoB445, rpoB450). The nomenclature used in the plain-language report is based on the M. tuberculosis H37Rv reference genome.…”

Genotypic clustering does not imply recent tuberculosis transmission in a high prevalence setting: A genomic epidemiology study in Lima, Peru

“…We quantified the host predilection to transmit TB with the PTP measure and found the cluster to have a higher score than the median PTP measure reported by a study in Netherlands. 35 Our study had five patients with a particularly high PTP above the highest reported value of 3·9, 35 potentially contributing to transmission in the population we studied. A few prior studies have characterized bacterial genetic factors that contributed to increased transmissibility.…”

“…We measured host infectiousness in the cluster using the ‘propensity to propagate’ 35 (PTP) method and identified five patients as having the highest possible score (PTP> 4). This was related to patients being younger (20-29y) males with smear positive PTB and a history of substance use (Supplementary Figure 4).…”