Gerald Friedland, MD, FIDSA, painted a frightening picture of the emergence of the epidemics of extensively drug resistant (XDR) tuberculosis (TB) and HIV co-infection at the 48^th Annual Meeting of IDSA, highlighting the experience in Tugela Ferry, a small, rural site about two and a half hours from the Indian Ocean in South Africa. “Epidemics such as these are not accidents or random events, but predictable consequences of complex biological, behavioral, and social and economic interactions,” said Dr. Friedland, professor of medicine and epidemiology at Yale University in New Haven, Conn., who gave the Maxwell Finland Lecture.

More than 50 percent of those newly infected with HIV in sub-Saharan Africa are also TB infected. In Tugela Ferry, located in one of the poorest areas of South Africa, with a high HIV burden and a historically low completion rate for TB treatment, 90 percent of HIV-infected patients are co-infected with TB, said Dr. Friedland, a member of the Center for Global Health Policy’s Scientific Advisory Committee. The TB case rate is more than 1,000 per 100,000 people. Care is provided by a rural district hospital with 350 beds, with open congregate male and female medical and TB wards with 40 beds.

Integrating the care and treatment of TB and HIV in high prevalence areas is a necessary but infrequently employed strategy globally, as TB and HIV programs have developed separately. The recently completed Starting Antiretroviral Therapy at Three Points in Tuberculosis Therapy (SAPIT) trial showed that integrated treatment of HIV and TB in an urban African setting  improves outcomes, reduces mortality, and is more effective than sequential treatment, noted Dr. Friedland, whose team worked to integrate HIV and TB treatment in the rural setting of Tugela Ferry.

A similar study performed by this team, the Sizonq'oba study, also showed mortality was significantly reduced with rapid initiation of integrated, community-based HIV and TB treatment, but found multi-drug resistant (MDR) and XDR-TB were the major causes of death among study participants. “That was a shock and a non-anticipated one, but in retrospect, one that could have been anticipated, given the collision of the TB and HIV epidemics,” Dr. Friedland said.

Of 53 cases of XDR-TB later identified in Tugela Ferry, all also tested HIV positive. Ninety-eight percent died within 16 days of a TB culture being taken. For most of these patients, the XDR-TB diagnosis was not made until after death, increasing the possibility of transmission to others while the infected patients received treatment in hospitals before their deaths. Other evidence for nosocomial transmission existed: no previous exposure to TB drugs through prior treatment of TB in the majority of the patients (51 percent); two-thirds hospitalized in the last two years; eight health care workers died with XDR-TB; and genotyping revealing a similar strain of TB in the vast majority of cases.

By the end of 2009, nearly 1,000 cases of XDR and MDR-TB had been diagnosed, with more than half being XDR-TB. During the past 24 months in Tugela Ferry, new cases of drug-resistant TB have continued to be diagnosed but the numbers have decreased. Some improvement in survival among those with drug resistant TB has now been documented, from 98 to 82 percent, but mortality from more readily treated MDR-TB also remains unacceptably high at 67 percent.

There are thought to be 25,000 global cases of XDR-TB emerging every year, but the true global extent is unknown. Despite the troubling trend, it is not impossible to improve the face of TB program performance, Dr. Friedland said. Receiving ART is one predictor of survival in XDR-TB patients with HIV infection, but reducing transmission is key and can be achieved by earlier identification and diagnosis, airborne infection control strategies, and decreased reliance on hospital care. Modeling shows 48 percent of transmitted cases of XDR-TB could be averted using many feasible preventive methods, even in resource-constrained settings, including wearing masks, decreased hospital stays, and better natural ventilation, among others.

“We have to go into the community, and not wait until cases appear in the hospital, to interrupt community transmission and get to cases earlier in their natural history,” said Dr. Friedland, who also highlighted longer-term needs: new diagnostics (with the ability to diagnose MDR and XDR-TB within one to two hours), new drugs and treatment regimens, new vaccines, basic and translational research and operational implementation science, and a new commitment to address the health disparities and social inequities, which underlie the convergent global epidemics of TB and HIV.

Audio and synchronized speaker slides from the 2010 IDSA Annual Meeting are available for purchase online.

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