ena-STUDY-LSHTM-20-07-2021-14:03:43:317-406
MOLECULAR CHARACTERIZATION OF DRUG-RESISTANT Mycobacterium tuberculosis AMONG FILIPINO PATIENTS DERIVED FROM THE NATIONAL TUBERCULOSIS PREVALENCE SURVEY PHILIPPINES 2016
Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a high burden disease and leading cause of mortality in the Philippines. Disease control is being compromised by circulating drug-resistant strains, where resistance is caused by genetic mutations in M. tuberculosis genes coding for drug-targets or -converting enzymes. Understanding the genetic diversity of M. tuberculosis strains in the population, including those that are multi-drug resistant (MDR), will aid in formulating strategies for effective control and prevention of TB. By whole genome sequencing of M. tuberculosis isolates (n=100) from patients derived from the Philippine National Tuberculosis Prevalence Survey in 2016, we sought to provide a baseline assessment of the genotypic and phylogenetic characteristics of drug-susceptible and MDR-TB isolates. The majority (96/100) of the isolates were the EAI2-Manila strain-type (lineage 1), with one (1/100) Lineage 2 (Beijing), one (1/100) Lineage 3 (CAS1), and two (2/100) Lineage 4 (LAM9) strains. The EAI2-Manila clade was not significantly associated with patient's age, sex, TB severity, bacillary load and phenotypic and in silico drug resistance profile. Five of the six MDR-TB isolates predicted by in silico profiling were concordant with phenotypic drug resistance profile. The EAI2-Manila isolates were found to have high SNP variability, and genetically similar to those isolated from other countries. Twenty-one mutations were identified in nine drug resistance-related genes, all of which have been reported in previous studies. Overall, the results from this study contribute to the growing data on the molecular characteristics of Philippine M. tuberculosis isolates, which can help in developing tools for rapid diagnosis of TB in the country, and thereby reducing the high burden of disease.
Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a high burden disease and leading cause of mortality in the Philippines. Disease control is being compromised by circulating drug-resistant strains, where resistance is caused by genetic mutations in M. tuberculosis genes coding for drug-targets or -converting enzymes. Understanding the genetic diversity of M. tuberculosis strains in the population, including those that are multi-drug resistant (MDR), will aid in formulating strategies for effective control and prevention of TB. By whole genome sequencing of M. tuberculosis isolates (n=100) from patients derived from the Philippine National Tuberculosis Prevalence Survey in 2016, we sought to provide a baseline assessment of the genotypic and phylogenetic characteristics of drug-susceptible and MDR-TB isolates. The majority (96/100) of the isolates were the EAI2-Manila strain-type (lineage 1), with one (1/100) Lineage 2 (Beijing), one (1/100) Lineage 3 (CAS1), and two (2/100) Lineage 4 (LAM9) strains. The EAI2-Manila clade was not significantly associated with patient's age, sex, TB severity, bacillary load and phenotypic and in silico drug resistance profile. Five of the six MDR-TB isolates predicted by in silico profiling were concordant with phenotypic drug resistance profile. The EAI2-Manila isolates were found to have high SNP variability, and genetically similar to those isolated from other countries. Twenty-one mutations were identified in nine drug resistance-related genes, all of which have been reported in previous studies. Overall, the results from this study contribute to the growing data on the molecular characteristics of Philippine M. tuberculosis isolates, which can help in developing tools for rapid diagnosis of TB in the country, and thereby reducing the high burden of disease.