Admixed Phylogenetic Distribution of Drug Resistant Mycobacterium tuberculosis in Saudi Arabia

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.

Tuberculosis in Saudi Arabia: the journey across time

“…There was little difference between the distribution of strain lineages in both local and immigrant groups. However, the highest ratio (59.5%) of the shared strain clusters showed the typical social mixing of the resident populations [21].…”

“…The majority of the isolates (81%) were imported strains including the following clades: Central Asian (CAS, 22.5%), ill-defined T clade (19.5%), East African Indian (EAI, 13.5%), Haarlem (7.5%), Latin American Mediterranean (LAM, 7.2%), Beijing (4.4%), Manu (2.7%), X (0.9%), and Mycobacterium bovis (0.9%). In addition, two clonal complexes were identified with unique spoligotyping signatures (octal codes 703777707770371, and 67777377413771), which were specific to Saudi Arabia [21].…”

“…In addition, M. bovis BCG (4.6%), Uganda-I (2.8%), S (2.5%), X (2.2%), New I (1.5%), and TUR (1.5%) were also observed. Interestingly, a higher representation of lineages X, S, Haarlem, and M. bovis BCG were observed among Saudi nationals, whereas EAI, Beijing, Delhi/CAS, and Ghana were well defined among immigrants, even in the highly admixed nature of strain clustering [21].…”

First Insight Into the Fluoroquinolone and Aminoglycoside Resistance of Multidrug-Resistant Mycobacterium tuberculosis in Saudi Arabia

“…20 However, transmission of drugresistant strains to a relatively higher level among the Saudi nationals and immigrants are also recently reported. 24,26 In addition, Varghese and others recently demonstrated a new trend of TB transmission particularly among newly diagnosed immigrant patients, which shows the possibility of reactivation of remote infection immediately followed by a reinfection with drug-resistant strains including MDR-TB. 27 These recent findings clearly justify that the chances of drug-resistant TB in Saudi Arabia is not only limited to acquired resistance but also to recent transmissions.…”

“…This is in concordance with previous studies that showed higher representation rate of Beijing, Delhi/CAS, and EAI clades among MDR isolates particularly XDR-TB. 26,40 This study has few limitations: genome sequencing techniques were not considered to reconfirm the detected mutations or to find unknown or new mutations; the elevated low resistance of moxifloxacin was not tested with higher concentrations; and due to the small size of the study group, phylogenetic analysis on transmission dynamics could not be performed.…”