BACKGROUND Drug-resistant tuberculosis threatens recent gains in the treatment of tuberculosis and human immunodeficiency virus (HIV) infection worldwide. A widespread epidemic of extensively drug-resistant (XDR) tuberculosis is occurring in South Africa, where cases have increased substantially since 2002. The factors driving this rapid increase have not been fully elucidated, but such knowledge is needed to guide public health interventions. METHODS We conducted a prospective study involving 404 participants in KwaZulu-Natal Province, South Africa, with a diagnosis of XDR tuberculosis between 2011 and 2014. Interviews and medical-record reviews were used to elicit information on the participants’ history of tuberculosis and HIV infection, hospitalizations, and social networks. Mycobacterium tuberculosis isolates underwent insertion sequence (IS)6110 restriction-fragment– length polymorphism analysis, targeted gene sequencing, and whole-genome sequencing. We used clinical and genotypic case definitions to calculate the proportion of cases of XDR tuberculosis that were due to inadequate treatment of multidrug-resistant (MDR) tuberculosis (i.e., acquired resistance) versus those that were due to transmission (i.e., transmitted resistance). We used social-network analysis to identify community and hospital locations of transmission. RESULTS Of the 404 participants, 311 (77%) had HIV infection; the median CD4+ count was 340 cells per cubic millimeter (interquartile range, 117 to 431). A total of 280 participants (69%) had never received treatment for MDR tuberculosis. Genotypic analysis in 386 participants revealed that 323 (84%) belonged to 1 of 31 clusters. Clusters ranged from 2 to 14 participants, except for 1 large cluster of 212 participants (55%) with a LAM4/KZN strain. Person-to-person or hospital-based epidemiologic links were identified in 123 of 404 participants (30%). CONCLUSIONS The majority of cases of XDR tuberculosis in KwaZulu-Natal, South Africa, an area with a high tuberculosis burden, were probably due to transmission rather than to inadequate treatment of MDR tuberculosis. These data suggest that control of the epidemic of drug-resistant tuberculosis requires an increased focus on interrupting transmission. (Funded by the National Institute of Allergy and Infectious Diseases and others.)

Background-Extensively drug-resistant (XDR) tuberculosis has spread among hospitalized patients in South Africa, but the epidemic-level impact of hospital-based infection control strategies remains unknown.

The XDR-tuberculosis epidemic in Tugela Ferry, South Africa, has been highly clonal. However, the epidemic is not the result of a point-source outbreak; rather, a high degree of interconnectedness allowed multiple generations of nosocomial transmission. Similar to the outbreaks of multidrug-resistant tuberculosis in the 1990s, poor infection control, delayed diagnosis, and a high HIV prevalence facilitated transmission. Important lessons from those outbreaks must be applied to stem further expansion of this epidemic.

We assessed the association between the causative agents of vaginal discharge and pelvic inflammatory disease (PID) among women attending a rural sexually transmitted disease clinic in South Africa; the role played by coinfection with human immunodeficiency virus type 1 (HIV-1) was studied. Vaginal and cervical specimens were obtained to detect Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, and bacterial vaginosis. HIV-1 infection was established by use of serum antibody tests. A total of 696 women with vaginal discharge were recruited, 119 of whom had clinical PID. Patients with trichomoniasis had a significantly higher risk of PID than did women without trichomoniasis (P=.03). PID was not associated with any of the other pathogens. When the patients were stratified according to HIV-1 status, the risk of PID in HIV-1-infected patients with T. vaginalis increased significantly (P=.002); no association was found in patients without HIV-1. T. vaginalis infection of the lower genital tract is associated with a clinical diagnosis of PID in HIV-1-infected women.

Mycobacterium tuberculosis remains a leading cause of death worldwide, especially among individuals infected with HIV1. While phylogenetic analysis has revealed M. tuberculosis spread throughout history2–5 and in local outbreaks6–8, much less is understood about its dissemination within the body. Here, we report genomic analysis of 2693 samples collected postmortem from lung and extrapulmonary biopsies of 44 subjects in KwaZulu-Natal, South Africa who received minimal antitubercular treatment and most of whom were HIV seropositive. We found that purifying selection acted within individual patients, without the need for patient-to-patient transmission. Despite negative selection, mycobacteria diversified within individuals to form sub-lineages that co-existed for years. These sub-lineages, as well as distinct strains from mixed infections, were differentially distributed throughout the lung, suggesting temporary barriers to pathogen migration. As a consequence, samples taken from the upper airway often captured only a fraction of the population diversity, challenging current methods of outbreak tracing and resistance diagnostics. Phylogenetic analysis indicated that dissemination from the lungs to extrapulmonary sites was as frequent as between lung sites—supporting similar migration routes within and between organs, at least in subjects with HIV. Genomic diversity therefore provides a record of pathogen diversification and repeated dissemination across the body.

The high prevalence of asymptomatic STIs in pregnancy is compelling evidence that demands the development and validation of point-of-care tests for STIs be expedited. In addition, the high incidence of STIs 3 months postpartum suggests that women in this study setting resume unprotected sexual intercourse soon after delivery.

CD2 agreed well with expert opinion, with additional clinical events, such as arthropathy and inflammatory dermatoses, being classified as IRIS and added to CD2. We propose revised case definitions for both paradoxical and unmasking IRIS.

Exogenous reinfection is an important mechanism for the development of MDR and XDR TB. In addition to strengthening TB treatment programs, effective infection control strategies are urgently needed to reduce the transmission of MDR and XDR TB.