A novel approach - the propensity to propagate (PTP) method for controlling for host factors in studying the transmission of Mycobacterium tuberculosis.

Olivier Neyrolles,Hanna Nebenzahl-Guimaraes,Megan B Murray,Martien W Borgdorff,Dick Van Soolingen

doi:10.1371/journal.pone.0097816

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.

Highlights

Transmission of Mycobacterium tuberculosis (MTB) occurs through aerosol droplets
Our finding that the distribution of cluster’s propensity to propagate (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
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

Summary

Introduction

Transmission of Mycobacterium tuberculosis (MTB) occurs through aerosol droplets. Subsequent cases in transmission chains result in ‘‘clusters’’ of patients who share Mtb strains of the same genotype or molecular fingerprint [1]. There is substantial evidence to suggest that bacterial factors contribute to variability in cluster size and the extent of transmission of TB. Verhagen and colleagues showed that newly diagnosed index cases in a larger cluster infected more people than did newly diagnosed cases in smaller clusters [8]. This implies that clusters grow over time because of well-known patient risk factors for TB transmission, and because the strain itself generates an increased number of tuberculin skin test-positive contacts, and spreads more effectively than other strains

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