Transmission, prevention and management of drug resistant tuberculosis

Abstract

The rise of drug-resistant tuberculosis threatens the very fabric of traditional tuberculosis control efforts, particularly in South Africa, Eastern Europe and parts of Asia. Initial complacency was guided by laboratory observations which suggested that drug-resistant strains of Mycobacterium tuberculosis are less transmissible than drug-susceptible “wild-type” strains. However, the fact that young children in close contact with adult drug-resistant tuberculosis patients frequently became infected and/or diseased, usually with the same strain, provided clear evidence of transmissibility. Advanced genomic analysis has since provided novel insight into the evolution and spread of drug-resistant strains, highlighting unique epidemiological features related to programmatic management in specific geographic areas. Young children and immune compromised individuals are at high risk to develop active tuberculosis following close contact with a drug-resistant source case. Although observational data demonstrate clear benefit from contextualized post-exposure prophylaxis, formal guidance remains limited pending more robust information from large field trials. Wide scale roll-out of the MTB/RIF Xpert® test has facilitated early diagnosis of cases with drug-resistant tuberculosis. Multiple challenges such as high cost, technical and maintenance issues, result interpretation, false positive read-outs and misassignment of multi-drug resistant (MDR) status in cases with rifampicin mono-resistance remain, especially in resource-limited settings. In addition, MDR treatment programs are inadequate and heavily dependent on external donor funding in most settings, this restricts treatment access and threatens the sustainability of programs.