Direct transmission seems to drive XDR-TB

Time in hospitals and social contacts provide epidemiological links

In a cross-sectional study in KwaZulu-Natal state of South Africa -- the epicenter of extensively drug-resistant TB in the country -- 15% of the epidemiological links to extensively drug resistant TB were person-to-person transmission and another 18% were hospital-based links, according to Sara Auld, MD, of Emory University School of Medicine in Atlanta, and colleagues.

The researchers were able to find links to 122 patients with extensively drug-resistant TB, or about 30% of the study population, Auld reported at the Conference on Retroviruses and Opportunistic Infections.

She noted that South Africa has the largest burden of extensively drug-resistant TB in the world and that is compounded by HIV co-infection.

"XDR-TB is widespread in South Africa despite effective HIV treatment programs, and is resistant to most first-line and second-line tuberculosis drugs," she said. "Clinical and genotypic data indicate transmission is the primary driver of the epidemic. The epidemic driven by transmission highlights the need for prevention focused on improving infection control."

Previous studies, Auld noted, have shown that while there may have been some increase of extensively drug-resistant TB by mistreatment of multidrug-resistant disease, most of the patients in the study found to have extensively drug-resistant TB had never been treated for TB. Their resistant strain of TB most likely came from close contacts in a hospital setting, a work setting, or even at the home.

"We showed that 70% of XDR-TB cases could be related to direct transmission of resistant strains," she said.

The study, conducted from 2011 to 2014, involved interviews with 404 people with confirmed extensively drug-resistant TB in KwaZulu-Natal. The study participants were asked to name all contacts at home, work, or other locations where they spent more than 2 hours each week, as well as all hospitalizations in the previous 5 years.

"We then performed a social network analysis to connect participants maintained with one another," she explained, She said 77% of the the patients in the study were HIV-co-infected; about 75% were on antiretroviral therapy, and half of the patients had viral suppression.

The participants named about 2,900 contacts, and about 25 of those individuals were believed by the participants to have some form of TB. The authors determined that 1% of these patients had extensively drug-resistant TB, Auld told MedPage Today.

For hospital-based epidemiological links, the authors reported that 39% of participants were hospitalized prior to collection of extensively drug-resistant TB diagnostic sample during "vulnerable period." In addition, 61% overlapped in the hospital with other participants while vulnerable.

The group were unable to determine if there were specific risk factors for transmission, such as age or gender. "Everyone is at risk for transmission," Auld said. "The situation in KwaZulu-Natal is a cautionary tale of how that might relate to other communities in sub-Saharan Africa. If XDR-TB is introduced into another community, transmission is possible there as well."

Given the direct person-to-person transmission, multiple methods will have to be employed to address the problem, she stated.

"Specifically, this means diagnosing patients earlier; separating patients suspected of having drug resistant disease; and re-designing health care facilities to provide more effective isolation," Auld explained at a CROI press conference. "Contact investigation must also be implemented to try to find and diagnose cases in the community. Our study underscores the urgent need for effective treatment for XDR-TB to help prevent future cases."

Study limitations included missing transmission links, death prior to diagnosis, and the reliance on patient recall for social networks and hospital admissions.

Conventional wisdom holds that drug-resistant TB is a byproduct of improper treatment, or because patients neglected to take their medications, pointed out Richard Chaisson, MD, director of the Johns Hopkins Center for TB Research in Baltimore.

"But it is very clear now that multidrug-resistant tuberculosis and XDR TB are largely the result of people who have been transmitting it to others rather than people acquiring it through bad treatment," he told MedPage Today. "People are transmitting it in households, and in hospitals, and probably in other places such as on buses. It is probably being spread in places where people with XDR-TB hang out and cough on others."

Auld and some co-authors disclosed support from the NIH, the National Institute of Allergy and Infectious Diseases, the Einstein Center for AIDS Research, the Emory Center for AIDS Research, the Atlanta Clinical and Translational Science Institute, and the CDC.

Auld and co-authors disclosed no relevant relationships with industry.

disclosed no relevant relationships with industry.

Primary Source
Conference on Retroviruses and Opportunistic Infections

Source Reference: Auld S, et al "HIV-Associated XDR TB is transmitted in households and hospitals in South Africa" CROI 2016; Abstract 157.

Source: MedPage Today