Clinical and genetic risk factors for the development of multi-drug resistant tuberculosis in non-HIV infected patients at a tertiary care center in India: a case-control study

Abstract

Genetic susceptibility of the host to multi-drug resistant tuberculosis (MDR-TB) is not fully understood. We undertook a case-control study at a tertiary care center at New Delhi, India to identify the clinical and genetic predictors of MDR-TB as compared to the drug sensitive TB cases. Patients with multi-drug resistant tuberculosis were identified on the basis of drug sensitivity testing by the proportion method. Treatment was initiated according to standard norms and all patients were followed up during the period. Genomic DNA extracted from the peripheral blood mononuclear cell pellet was used for amplification of HLA class II region (second exon) with a set of forward (5') and reverse (3') primers. A sequence specific 5' biotinylated probes were used to determine 12 DRB1, 8 DQA1 and 13 DQB1 alleles by the PCR-SSOP method. Past history of disease, higher severity of illness, inadequacy of drug treatment and presence of HLA-DRB1*14, DQB1*0503 and DQB1*0502 alleles were found to be significant risk factors for MDR-TB. Multivariate analysis identified poor past compliance to treatment (odds ratio, OR=6.6; 95% confidence interval, CI [2.0-21.5]), higher number of cavities (OR=6; 95% CI [2.1-17.3]) in chest radiographs and the presence of the HLA-DRB1*14 allele (OR=8.2; 95% CI [2.1-31.3]) as independent predictors of MDR-TB. Our results suggest that a combination of clinical and immunogenetic parameters could provide better information on drug resistance in tuberculosis with implications in therapy.