A first assessment of the genetic diversity of Mycobacterium tuberculosis complex in Cambodia

Abstract

BackgroundCambodia is among the 22 high-burden TB countries, and has one of the highest rates of TB in South-East Asia. This study aimed to describe the genetic diversity among clinical Mycobacterium tuberculosis complex (MTC) isolates collected in Cambodia and to relate these findings to genetic diversity data from neighboring countries.MethodsWe characterized by 24 VNTR loci genotyping and spoligotyping 105 Mycobacterium tuberculosis clinical isolates collected between 2007 and 2008 in the region of Phnom-Penh, Cambodia, enriched in multidrug-resistant (MDR) isolates (n = 33).ResultsClassical spoligotyping confirmed that the East-African Indian (EAI) lineage is highly prevalent in this area (60%-68% respectively in whole sample and among non-MDR isolates). Beijing lineage is also largely represented (30% in whole sample, 21% among non-MDR isolates, OR = 4.51, CI95% [1.77, 11.51]) whereas CAS lineage was absent. The 24 loci MIRU-VNTR typing scheme distinguished 90 patterns with only 13 multi-isolates clusters covering 28 isolates. The clustering of EAI strains could be achieved with only 8 VNTR combined with spoligotyping, which could serve as a performing, easy and cheap genotyping standard for this family. Extended spoligotyping suggested relatedness of some unclassified "T1 ancestors" or "Manu" isolates with modern strains and provided finer resolution.ConclusionsThe genetic diversity of MTC in Cambodia is driven by the EAI and the Beijing families. We validate the usefulness of the extended spoligotyping format in combination with 8 VNTR for EAI isolates in this region.

Molecular epidemiology of tuberculosis in Cambodian children

“…In the Mekong river delta in Viet Nam, overall a lower transmissibility [18]. Among adults, a genotype analysis of strains from Phnom Penh has shown that among non-multidrugresistant strains, Beijing genotypes accounted for 21% of the total [7] comparable to our 19% from roughly the same area.…”

Development and application of single-tube multiplex real-time PCR for lineage classification of Mycobacterium tuberculosis based on large sequence polymorphism in Northeast Thailand

“…We confirm that the IO lineage predominates in the region, as it does in other Southeast Asian countries. For example, in Northern Vietnam, this lineage accounts for 41.7% of cases, and in Cambodia, 68% of cases [5,30,31]. Based on LSPs, only the Beijing, IO and EuA lineages were identified from pulmonary TB patients in Northeast Thailand.…”

“…Large RDs contain genes that can affect the phenotype whereas small RDs interfere with gene expression around the indel site. Different lineages of Mtb were suggested to exhibit different degrees of virulence, of association with drug resistance and response to BCG vaccination [5]. These mycobacterial lineages associated with particular geographical regions and human ethnic groups suggest adaptation to regional human populations and host-pathogen co-evolution [1].…”

Draft Genome Sequence of a Clinical Isolate of Multidrug-Resistant Mycobacterium tuberculosis East African Indian Strain OSDD271

“…CAS and EAI genotypes, along with the Beijing genotypes, contribute to the major proportion of clinical strains in India (5–8). EAI strains have also been reported as one of the major genotypes in many countries of Southeast Asia and Africa (9). EAI strains have been shown previously to be associated with slow transmissibility in human populations/patients in some parts of the world (10) and along with CAS strains have been suggested to be involved in extrapulmonary tuberculosis in some regions of the world (11, 12).…”