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Person-to-person transmission drives epidemic of XDR-TB in South African province
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Person-to-person transmission may be the primary driver of an epidemic of extensively drug-resistant tuberculosis in South Africa that has exploded over the past 15 years, the scale of which matches the incidence rate of all forms of TB in the United States, according to researchers.
A prospective study of hundreds of patients in one hard-hit South African province showed that inadequate treatment accounted for — at most — 31% of the cases of extensively drug-resistant TB (XDR-TB), the deadliest form of the disease.
According to Neel R. Gandhi, MD, associate professor of epidemiology in the Rollins School of Public Health at Emory University, and colleagues, the remaining XDR-TB cases in KwaZulu-Natal, a province on South Africa’s east coast, were the result of transmission in either the hospital or community setting.
Gandhi and colleagues said the results suggest controlling the South African epidemic starts with interrupting transmission.
“In the interval since XDR tuberculosis was first described globally and in South Africa, the XDR tuberculosis epidemic in South Africa has continued unabated,” they wrote in The New England Journal of Medicine.
Transmission occurring in hospitals, community
According to the CDC, there was a 10-fold increase in XDR-TB cases in South Africa from 2002 to 2015 — an increase that has not been fully explained, Gandhi and colleagues said. To explore what is driving the epidemic, they enrolled 39% (n = 404) of the patients who were diagnosed with XDR-TB in KwaZulu-Natal between May 2011 and August 2014.
Among the enrollees, 58% were women, the median age was 34 years and 50% lived in rural areas, according to Gandhi and colleagues. Seventy-seven percent were co-infected with HIV, including a majority (76%) who were on ART, and 17% had cavitary disease, they found.
Just 31% of the participants had been previously treated for multidrug-resistant TB (MDR-TB), including 84% who experienced treatment failure. According to Gandhi and colleagues, XDR-TB in patients previously treated for MDR-TB was presumed to have developed through acquired resistance based on the clinical case definition.
Transmission led to XDR-TB in the remaining patients (n = 280), Gandhi and colleagues said. Overall, they identified a person-to-person or hospital-based epidemiologic links between 30% of the 404 patients.
Targeted gene sequencing of TB isolates from 386 participants showed that 84% matched another isolate in the study, including 84% (n = 323) that belonged to one of 31 clusters. The largest cluster included 212 patients; the remaining 30 ranged in size from two to 14 patients.
Gandhi and colleagues said a comprehensive strategy to stop the epidemic of XDR-TB in South Africa should include the continued use of hospital-based interventions such as infection-control programs and outpatient treatment.
“Methods for controlling transmission in community settings are less well-studied,” they wrote. “Since nearly half the epidemiologic links in our study occurred in households, interventions that decrease transmission in community settings are needed. Early identification of patients with drug-resistant tuberculosis, screening of household contacts, and universal drug-susceptibility testing for all patients who are suspected of having tuberculosis are recommended.”
Transmission also driving MDR-TB epidemic in China
Gandhi and colleagues noted that XDR-TB, which is lethal and hard to treat, is increasingly recognized as a threat to global health and that a lack of preventive therapy for contacts of patients “further underscores the need to control the current epidemic.”
“As the global tuberculosis community mobilizes around the goal of no new tuberculosis infections, the age-old approach of turning off the tap by stopping transmission is all the more critical for halting epidemics of drug-resistant tuberculosis,” they concluded.
CDC Director Thomas R. Frieden, MD, MPH, said the findings by Gandhi and colleagues “are further proof that we need to better detect, prevent, diagnose, and treat drug-resistant TB.”
“TB resistant to last-resort drugs is spreading through hospitals and homes, at work, and in other places in this high-burden community,” Frieden said in a statement. “The only way to stop this disease is by improving infection control and rapidly finding and effectively treating people with TB.”
Person-to-person transmission also has been identified as a driver of MDR-TB infection, including in China, where researchers said recently that person-to-person transmission was fueling an epidemic.
Chongguang Yang, PhD, postdoctoral associate of epidemiology of microbial diseases at Yale School of Medicine, and colleagues analyzed MDR-TB isolates from 324 patients in Shanghai aged 15 years and older who were diagnosed with the infection between Jan. 1, 2009, and Dec. 31, 2012, and discovered that 59% of them were treatment-naive.
Yang and colleagues combined treatment-naive cases with cases included in genomic clusters and estimated that up to 73% of all MDR-TB cases were likely caused by transmission of MDR strains.
They drew the same conclusion as Gandhi and colleagues.
“Our findings suggest that strategies and interventions to halt ongoing transmission of MDR strains should be a priority for [TB] control programs in China and other settings with a high burden of [MDR-TB],” Yang and colleagues wrote. – by Gerard Gallagher
Disclosure: Please see the full studies for a list of all authors’ relevant financial disclosures.
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