Background:  Drug-resistant TB has emerged as a major global clinical and public health challenge, particularly in high HIV prevalence settings of Sub-Saharan Africa.  The recent discovery of large numbers of cases of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB in HIV-co-infected patients in rural South Africa likely represents a previously unrecognized and rapidly evolving epidemic rather than a localized outbreak. New cases, with extremely high mortality, continue to appear; now involving all South African provinces and likely beyond. Primary infection with resistant organisms acquired in health care settings is central to recent M/XDR TB spread, but increased community transmission is expected. The combination of a large population of HIV-infected susceptible hosts, overburdened TB and MDR TB programs with poor TB treatment success rates, lack of microbiologic monitoring, and absent airborne infection control, have provided ideal conditions for this MDR and XDR TB epidemic of unparalleled magnitude. Continued epidemic growth of MDR and XDR TB threatens both existing TB and newly developed HIV antiretroviral roll out programs in areas with high TB and HIV prevalences.

Conclusions:  Controlling MDR and XDR TB in this context, requires more complete definition of epidemiology and transmission patterns, increased laboratory capacity for culture and drug-susceptibility testing and the rapid implementation of epidemic control measures that reduce aerosolization of and exposure to resistant organisms, particularly among those with HIV co-infection. These include earlier identification of cases in hospital and community settings, provision of treatment and facilities and strategies for humane separation of infectious patients from susceptible persons in congregated settings, decreased reliance on hospitalization with accompanying increased decentralization of care and treatment, implementation of already available effective airborne control policies and practices, protection of health care workers, and further integration of TB and HIV care, including universal provision of indicated ART. Recent studies indicate that these measures, in concert, could avert a significant number and proportion of anticipated new infections. A fully successful response to the emergence of MDR and XDR TB requires dramatic and sustained increase in motivation and resources to address the many long-neglected issues in TB research, prevention, and care.