Admixed Phylogenetic Distribution of Drug Resistant <em>Mycobacterium tuberculosis</em> in Saudi Arabia

<div><h3>Background</h3><p>The phylogeographical structure of <em>Mycobacterium tuberculosis</em> 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.</p> <h3>Methodology</h3><p>We 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.</p> <h3>Principal Findings</h3><p>In contrast to the cosmopolitan population of the country, almost all the known phylogeographic lineages of <em>M. tuberculosis</em> complex (with noticeable exception of <em>Mycobacterium africanum</em>/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.</p> <h3>Conclusions</h3><p>Specific distribution of <em>M. tuberculosis</em> 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.</p> </div

Distributions of <i>M. tuberculosis</i> complex strain lineages among Saudi and non-Saudi cases.

<p>Lineages identified as described in text were segregated as per “Saudi” and “Non-Saudi” nationalities. Bar diagrams show the proportion (in percentage) of each lineage in each of these two groups. The lineages TUR, NEW-I and URAL were clubbed under the label “Others” as the corresponding isolates are very few in number.</p

Association between drug-resistance and strain lineages.

1<p>Mono drug resistance was used as the closest reference to a pan-sensitive status.</p>2<p>Uganda-I (N = 9), S (8), X (7), New I (n = 5),), TUR (n = 5), Unknown (n = 2).</p

Distribution of strain clusters among the study groups.

<p>A) Saudi patients-only, B) non-Saudi patients-only and C) mixed strain molecular clusters. The distribution of strain clusters detected among the three categories is indicated above each diagram. Strain phylogenetic distribution with percentages of different lineages found within each cluster category is also shown. Strain molecular clusters were identified based on isolates sharing identical MIRU-VNTR types and spoligotypes.</p

Molecular clusters found among the 322 study isolates.

1<p>Molecular clustering identified based on MIRUVNTR and spoligo profiles.</p

Demographical summary of the study samples.

1<p>Eastern Saudi Arabia.</p>2<p>Central Saudi Arabia.</p>3<p>Western Saudi Arabia.</p>4<p>Southern Saudi Arabia.</p>5<p>Bangladesh, India, Nepal, Pakistan, Sri Lanka,</p>6<p>China, Indonesia, Malaysia, Philippines.</p>7<p>Yemen.</p>8<p>Algeria, Chad, Egypt, Eritrea, Ethiopia, Nigeria, Senegal, Somalia, Sudan.</p

Drug resistant pattern of the enrolled isolates.

1<p>Newly diagnosed cases.</p>2<p>Patient received >1 month of anti TB drug therapy.</p>3<p>Multidrug resistant tuberculosis; resistant to at least isoniazid and rifampicin.</p>4<p>Pan-resistance was defined here as resistance to all four first-line drugs.</p