“These are not accidents or random events, but predictable consequences of complex interactions,” said Gerald Freidland, MD, as he painted a frightening picture of the emergence of extensively drug resistant (XDR) tuberculosis in Tugela Ferry, KwaZulu Natal, South Africa. He spoke to a packed audience at the 48th annual meeting of the Infectious Diseases Society of America Friday evening.
“The confluence of HIV and TB is in southern Africa,” Friedland said, adding that more than fifty percent of those newly infected with HIV in sub-Saharan Africa are also TB infected. He started his talk describing the emergence of co-infected men and women injection drug users (IDU) in the Bronx in the 1980s. In a ten year period, the prevalence of HIV in IDU rose from ten to 40 percent; and although TB notification rates in the U.S. were falling from 1920-1980, there was an unexpected rise in the ‘80s coincident with the arrival of HIV. This gave New York an opportunity to understand the complex interaction between the two diseases.
In South Africa, Friedland described the underlying causes of the explosive HIV epidemic including: the poverty and destruction of traditional societies brought about by colonialism and apartheid; gender inequality; the transportation system allowing for rapid migration; and denial, stigma and an ineffective response to the epidemic.
Tugela Ferry is a small, rural site about two and a half hours inland from the Indian Ocean, in the Msinga District of rural KwaZulu Natal, South Africa. The TB case rate is more than 1,000 per 100,000. It is one of the poorest areas in South Africa, with a high HIV burden and a historically low completion rate for TB treatment. Ninety percent of HIV-infected persons are co-infected with tuberculosis. Care is provided by a rural district hospital with 350 beds, with male and female medical and TB wards with forty beds.
In South Africa, antenatal seroprevalence is greater than 25 percent, there are more than 12,000 new TB cases per year. The SAPIT trial, which stands for Starting Antiretroviral Therapy at Three Points in Tuberculosis Therapy, showed that integrated treatment of HIV and TB improves outcomes and reduces mortality, and is more effective than sequential treatment. While the trial showed mortality was significantly reduced with rapid initiation of HIV and TB treatment, multi-drug resistant (MDR) and XDR-TB were major causes of death. “That was a shock and a non-anticipated one,” Friedland said.
In the ensuing year (2009), 53 cases of XDR-TB were accumulated in Tugela Ferry, all tested were HIV positive, and there was 98 percent rapid mortality within 16days of taking a TB culture. The diagnosis was made for most people post-mortem, increasing the possible transmission to others while getting treatment in hospitals. Other evidence for nosocomial transmission included: no prior treatment of TB in the majority of patients (51 percent); two-thirds were hospitalized in the last two years; eight health care workers died with XDR TB; and genotyping showed that the vast majority of organisms showed similar strain.
In the past 48 months in Tugela Ferry, emergence of drug-resistant TB has gone down but it has not gone away. By the end of 2009 nearly 1,000 cases of XDR and MDR-TB have been diagnosed, and more than half are XDR-TB. Successful treatment of drug-resistant TB in Tugela Ferry has improved. Mortality from XDR-TB is now 82 percent instead of 98 percent; mortality from MDR_TB stands at 67 percent.
There are thought to be 25,000 cases of XDR TB emerging every year, but the true global extent is unknown, said Friedland, adding “we are looking at the ears of a hippo.” But, in the face of all of this, it is not impossible to improve the face of TB program performance, he said.
Receiving ART is one of the predictors of survival in XDR TB patients, but reducing transmission is key, and that will be achieved by earlier diagnosis, airborne infection control strategies, and decreased reliance on hospital care, Friedland said.
Modeling shows we can avert 48 percent of transmitted cases of XDR TB using many preventive methods – including wearing masks, decreased hospital stay, and better ventilation among others. In South Africa, you can open all windows and put mixer fans on for nine out of 12 months of the year, Friedland said, improving natural ventilation, which is a big help in reducing transmission.
“We have to go into the community to interrupt community transmission and get to cases earlier in their natural history,” Friedland said. And in the longer term we need new diagnostics (ability to diagnose MDR and XDR-TB within one to two hours), new drugs and treatment regimens, new vaccines, basic and translational operational implementation science, and a new commitment to address issues of health disparities and social inequities.