Abstract

BackgroundThe phylogeographical structure of Mycobacterium tuberculosis is generally bimodal in low tuberculosis (TB) incidence countries, where genetic lineages of the isolates generally differ with little strain clustering between autochthonous and foreign-born TB patients. However, less is known on this structure in Saudi Arabia—the most important hub of human migration as it hosts a total population of expatriates and pilgrims from all over the world which is equal to that of its citizens.MethodologyWe explored the mycobacterial phylogenetic structure and strain molecular clustering in Saudi Arabia by genotyping 322 drug-resistant clinical isolates collected over a 12-month period in a national drug surveillance survey, using 24 locus-based MIRU-VNTR typing and spoligotyping.Principal FindingsIn contrast to the cosmopolitan population of the country, almost all the known phylogeographic lineages of M. tuberculosis complex (with noticeable exception of Mycobacterium africanum/West-African 1 and 2) were detected, with Delhi/CAS (21.1%), EAI (11.2%), Beijing (11.2%) and main branches of the Euro-American super-lineage such as Ghana (14.9%), Haarlem (10.6%) and Cameroon (7.8%) being represented. Statistically significant associations of strain lineages were observed with poly-drug resistance and multi drug resistance especially among previously treated cases (p value of < = 0.001 for both types of resistance), with relative over-representation of Beijing strains in the latter category. However, there was no significant difference among Saudi and non-Saudi TB patients regarding distribution of phylogenetic lineages (p = 0.311). Moreover, 59.5% (22/37) of the strain molecular clusters were shared between the Saudi born and immigrant TB patients.ConclusionsSpecific distribution of M. tuberculosis phylogeographic lineages is not observed between the autochthonous and foreign-born populations. These observations might reflect both socially favored ongoing TB transmission between the two population groups, and historically deep-rooted, prolonged contacts and trade relations of the peninsula with other world regions. More vigorous surveillance and strict adherence to tuberculosis control policies are urgently needed in the country.

Highlights

  • Tuberculosis (TB) still remains as a major, global public health problem

  • Recent studies have shown an association between strain genetic lineages and TB patient geographic origin [2,5,6,7,8,] revealing a strong phylogeographical structuring of the pathogen

  • Six isolates were excluded from the study dataset based on the detection of double alleles in two or more MIRU-VNTR loci, indicating the simultaneous presence of two independent strains potentially due to mixed infection or contamination

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Summary

Introduction

Tuberculosis (TB) still remains as a major, global public health problem. Worldwide, 10 million new cases of active TB and 1.8 million associated deaths are estimated to occur annually [1]. Recent studies have shown an association between strain genetic lineages and TB patient geographic origin [2,5,6,7,8,] revealing a strong phylogeographical structuring of the pathogen This association has been hypothesized to reflect the potential contribution of social factors limiting contacts between host population groups in some settings and/or potential adaptation of specific M. tuberculosis lineages to particular host populations, which have important implications, e.g. for new vaccine development [7,9]. These associations have been detected when studying large immigration urban centers in the Western world, such as San Francisco [7]; Brussels region [10]; and Montreal [8]; or Western countries such as Switzerland [11]. Less is known on this structure in Saudi Arabia—the most important hub of human migration as it hosts a total population of expatriates and pilgrims from all over the world which is equal to that of its citizens

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