Prevalence and factors associated with multidrug-resistant tuberculosis in South India

Abstract

India accounts for about one-fourth of the global burden of MDR-TB. This study aims to assess the prevalence and factors associated with tuberculosis drug resistance among patients from South India. MTBDRplus assay and MGIT liquid culture performed on 20,245 sputum specimens obtained from presumptive MDR-TB cases during a six-year period from 2013 to 2018 were analyzed retrospectively. Univariate and multivariate logistic regression analysis was carried out to evaluate factors associated with MDR, Rifampicin mono-resistance, and Isoniazid mono-resistance. MDR, Rifampicin mono- resistant and Isoniazid mono-resistant TB were found in 5.4%, 2.5%, and 11.4% cases of presumptive MDR-TB, respectively. Based on the rpoB gene, true resistance, hetero-resistance, and inferred resistance to Rifampicin was found in 38%, 29.3%, and 32.7% of the 1582 MDR cases, respectively. S450L (MUT3) was the most common rpoB mutation present in 59.4% of the Rifampicin resistant cases. Of the 3390 Isoniazid resistant cases, 72.5% had mutations in the katG gene, and 27.5% had mutations in the inhA gene. True resistance, heteroresistance, and inferred resistance accounted for 42.9%, 22.2%, and 17.3% of the 2459 katG resistant cases, respectively. True resistance, heteroresistance, and inferred resistance for the inhA gene were found in 54.5%, 40.7%, and 4.7% cases, respectively. MDR-contact (AOR 3.171 95% CI: 1.747-5.754, p-0.000) treatment failure (AOR 2.17595% CI: 1.703-2.777, p-0.000) and female gender (AOR 1.315 95% CI: 1.117-1.548, p-0.001), were positively associated with MDR-TB. Previous TB treatment did not show a significant positive association with MDR (AOR 1.113 95% CI: 0.801-1.546, p-0.523). Old age (AOR 0.994 95% CI: 0.990-0.999, p-0.023) and HIV seropositivity (AOR 0.580 95% CI: 0.369-0.911, p-0.018) were negatively associated with MDR-TB. Although Rifampicin mono-resistance had a positive association with treatment failure (AOR 2.509 95% CI: 1.804-3.490, p < .001), it did not show any association with previous TB treatment (AOR 1.286 95% CI: 0.765-2.164, p-0.342) or with history of contact with MDR-TB (AOR 1.813 95% CI: 0.591-5.560, p-0.298). However, INH mono-resistance showed a small positive association with the previous history of treatment for TB (AOR 1.303 95% CI: 1.021-1.662, p-0.033). It was also positively associated (AOR 2.094 95% CI: 1.236-3.548, p-0.006) with MDR-TB contacts. Thus INH resistance may develop during treatment if compliance has not adhered too and may be easily passed on to the contacts while Rifampicin resistance is probably due to factors other than treatment compliance. MDR-TB, i.e. resistance to both Rifampicin and Isoniazid, is strongly correlated with treatment failure, spread through contact, and not to treatment compliance. The temporal trend in this region shows a decrease in MDR prevalence from 8.4% in 2015 to 1.3% in 2018. A similar trend is observed for Rifampicin mono-resistance and Isoniazid mono-resistance, pointing to the effectiveness of the TB control program. The higher proportion of inferred resistance observed for Rifampicin compared with INH may indicate a surfeit of mechanisms that enable rifampicin resistance. Association of MDR-TB with age, gender, and HIV status suggest the role of the immune system in the emergence of the MDR phenotype.

Figure 1

Geographic distribution of samples across different districts of Tamil Nadu and Puducherry (PD) states. (Courtesy: www.d-maps.com, webmaster@d-maps.com).

Figure 2

Flow Chart describing the workflow for the study.

Figure 3

Temporal profile of TB drug resistance in presumptive MDR-TB patients during 2013 to 2018.

Figure 4

Comparison of Resistance detection by direct and indirect LPA.