Drug-resistant TB mostly being spread person-to-person in SA

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The worst form of drug-resistant tuberculosis in SA isn’t just arising from inadequate treatment, it’s mostly being spread from person to person. Researchers tracked TB that is resistant to at least four key drugs and found that 69 percent of the victims had never received treatment.

Reuters Health reports that this is according to a new study of hundreds of cases in South Africa that has important implications for how the deadly disease is treated.

Researchers tracked TB that is resistant to at least four key drugs and found that 69 percent of the victims had never received treatment, an indication that they had acquired it from others with extensively drug-resistant TB.

TB develops resistance to drugs when it is attacked with lacklustre therapy, allowing the slow-growing bacterium to become insensitive to well-established therapies. Strains that are simultaneously resistant to at least four drugs have been reported in 105 countries.

“For many years, there was this thought that maybe drug-resistant TB strains might not be able to be transmitted as efficiently a regular TB strains,” co-author Dr Neel R Gandhi of Emory University’s Rollins School of Public Health in Atlanta said in the report.

The results “turn this idea on its head,” said Dr William Schaffner, professor of infectious disease at Vanderbilt University Medical Centre in Atlanta who was not involved in the research.

The study team’s estimate that two thirds of the cases are surfacing because the disease is spreading by person-to-person contact “is mostly likely a minimum estimate,” Gandhi said.

“This is an epidemic we’ve known about for 10 years and we don’t seem to be making a dent in it,” he said. “And that may be because the driver isn’t what we thought it was.” “It raises the possibility of turning the clock back to the 1930s and 1940s” and requiring infected people to live in sanatoriums so patients can’t inadvertently spread the disease, Schaffner said. “You also have to do better at diagnosing them earlier. We’re going to have to be a lot more aggressive in finding the infected people early. These are substantial public health challenges.”

Drug resistance has gotten so bad, the rate of successful treatment can be less than 40% if a person acquires an extensively drug-resistant strain. It can be particularly deadly in people who also harbour HIV, the Aids virus. In South Africa, where the new study was done, there has been a 10-fold increase in the number of extensively drug-resistant cases in the past decade. One in 36,000 are now infected.

The team of researchers used contact tracing to find where the TB patients were spending at least two hours per week, trying to uncover any links. They found 31 clusters of the disease, the largest of which accounted for 84% of the 404 patients they studied.

Living with someone with TB accounted for most of the acquired cases, although the disease was also spread in the workplace (representing 13% of cases) or in other community settings such as a church, bar, beauty salon or prison (accounting for 8% of cases). “Certain networks spanned multiple homes, family generations, and community settings,” the study team writes.

Complicating control is that people can be infectious before they know they have drug-resistant TB. “We know people transmit (the disease) for weeks or months before they come for a diagnosis,” said Gandhi, an associate professor of epidemiology, global health and infectious diseases at Emory. “You have to focus on stopping the chain of transmission,” he said. “You have to identify early and intervene early. When you diagnose, drug susceptibility should be part of that diagnosis. And we have to do a better job creating facilities where transmission doesn’t take place, particularly in healthcare settings, hospitals, homeless shelters in the US and in schools and workplaces.”

The other researchers involved in the study were from the US Centres for Disease Control and Prevention in Atlanta, the Albert Einstein College of Medicine in New York and the University of KwaZulu-Natal in KZN South Africa, the province of 10.3m people where the study was done.

Abstract
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.)

Authors
N Sarita Shah, Sara C Auld, James CM Brust, Barun Mathema, Nazir Ismail, Pravi Moodley, Koleka Mlisana, Salim Allana, Angela Campbell, Thuli Mthiyane, Natashia Morris, Primrose Mpangase, Hermina van der Meulen, Shaheed V Omar, Tyler S Brown, Apurva Narechania, Elena Shaskina, Thandi Kapwata, Barry Kreiswirth, Neel R Gandhi

Reuters Health report
New England Journal of Medicine abstract


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