Abstract
Uncontrolled transmission of Mycobacterium tuberculosis (M. tuberculosis, MTB) drug resistant strains is a challenge to control efforts of the global tuberculosis program. Due to increasing multi-drug resistant (MDR) cases in Arunachal Pradesh, a northeastern state of India, the tracking and tracing of these resistant MTB strains is crucial for infection control and spread of drug resistance. This study aims to correlate the phenotypic DST, genomic DST (gDST) and phylogenetic analysis of MDR-MTB strains in the region. Of the total 200 samples 22 (11%) patients suspected of MDR-TB and 160 (80%) previously treated MDR-TB cases, 125 (62.5%) were identified as MTB. MGIT-960 SIRE DST detected 71/125 (56.8%) isolates as MDR/RR-MTB of which 22 (30.9%) were detected resistant to second-line drugs. Whole-genome sequencing of 65 isolates and their gDST found Ser315Thr mutation in katG (35/45; 77.8%) and Ser531Leu mutation in rpoB (21/41; 51.2%) associated with drug resistance. SNP barcoding categorized the dataset with Lineage2 (41; 63.1%) being predominant followed by Lineage3 (10; 15.4%), Lineage1 (8; 12.3%) and Lineage4 (6; 9.2%) respectively. Phylogenetic assignment by cgMLST gave insights of two Beijing sub-lineages viz; 2.2.1 (SNP difference < 19) and 2.2.1.2 (SNP difference < 9) associated with recent ongoing transmission in Arunachal Pradesh. This study provides insights in identifying two virulent Beijing sub-lineages (sub-lineage 2.2.1 and 2.2.1.2) with ongoing transmission of TB drug resistance in Arunachal Pradesh.
Highlights
India is leading in the highest rates of tuberculosis (TB) incidence and mortality globally, with an estimate of 2.69 million cases [1,2]
Drug-resistant tuberculosis (DR-TB) is a major public health concern globally, it represents an alarming situation in India, with 135,000 multi-drug resistant (MDR)-TB cases contributing to 27% of global drug-resistant tuberculosis (DR-TB) cases [1]
Of the total 200 cultures inoculated in Bactec MGIT 960 145 (72.5%) were flagged positive with an average turnaround time (TAT) of 18 days
Summary
India is leading in the highest rates of tuberculosis (TB) incidence and mortality globally, with an estimate of 2.69 million cases [1,2]. In India, the paucity of rapid diagnosis in locations having low resources and high endemicity areas where access to health care centers is difficult, remains a major constraint in treating DR-TB cases. It is estimated that around 56% of MDR-TB cases in India remain undiagnosed [4]. Arunachal Pradesh, one of the states in the northeastern region of India bordering China with 80% area covered with forest, mostly with hilly terrains, has awakened consciousness of NTEPs due to the high prevalence of around 78.8% MDR-TB cases [5]. The reason for undiagnosed drug-resistant cases is the location of most villages in impoverished forest zones, poor connectivity of roads to health centers leading to inadequate access to health services
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