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In a first of its kind study into the population and spread of tuberculosis-causing (TB) bacteria in Ho Chi Minh City, Thuong Thuong Nguyn and collegues at OUCRU Vietnam, Australia, UK and Singapore have found that more than half of cases can be attributed to one particular strain of the bacteria.

Diagram showing the geographical distribution of TB, MDR-TB and TB/HIV, with their intersections

Using state-of-the-art genomics technology, a Melbourne-led international collaboration, including researchers from OUCRU in Vietnam and Singapore, sequenced the DNA from bacteria isolated from the lungs of 1635 TB patients located in outpatient clinics in eight districts of Ho Chi Minh City. The findings, published in Nature Genetics this week, concluded that the strain of TB-causing bacteria known as the Beijing lineage, was responsible for 59 per cent of infections, and even more (75%) of those diagnosed in younger people.

TB is the leading cause of death globally from a single infectious agent – Mycobacterium tuberculosis – that typically affects the lungs, but can also infect other sites of the body. Multiple antibiotics are used to treat TB, however treatment is long (six months), and the emergence of drug-resistant bacteria is a considerable threat to global health.

Vietnam is one of the WHO High Burden Countries for TB and multi drug-resistant TB, and in 2016 there were an estimated 126,000 cases and 13,850 deaths in the South East Asian country. Co-lead Investigator of the study and a Senior Research Fellow, Dr Sarah Dunstan from the Peter Doherty Institute for Infection and Immunity (a joint venture of The University of Melbourne and The Royal Melbourne Hospital), said within the Beijing lineage they found a mutation, which likely bolsters the bacteria’s ability to spread. “Combating and managing TB spread requires new strategies to diagnose, treat and protect against emerging and evolving strains of the bacteria,” said Dr Dunstan. “Armed with an understanding of how the disease is spread in Ho Chi Minh City could allow more targeted local TB control, and this knowledge could potentially be applied to other settings given the Beijing lineage is found worldwide, predominantly in Asia.”

First author on the paper describing the study, Associate Professor Kathryn Holt from the University of Melbourne’s Bio21 Molecular Science and Biotechnology Institute, said the study shows the Beijing lineage of TB bacteria spreads more easily from person-to-person than other strains of the bacteria. “Contact tracing – looking for early signs of TB infection in people who have been in close contact with TB patients, and treating them before they can spread the disease further – is an important part of TB control, but it takes a lot of resources,” said Associate Professor Holt. “All TB patients have the potential to transmit the TB bacteria to others when they cough, but our data indicates this is more likely to result in new disease cases if the infection is caused by the Beijing lineage. So if resources are limited, it would make sense to prioritise contact tracing for Beijing lineage TB cases.”

Co-author Dr Nguyen T. T. Thuong, head of OUCRU’s TB group in Ho Chi Minh City, comments: “TB treatment fails in many patients infected with multidrug resistant strains, which are then passed on, increasing the number of resistant cases in the community. My team in Vietnam now is running a pilot study in early diagnosis of drug resistant TB cases using whole genome sequencing. The findings from this publication can be applied concurrently to identify those carrying the easily-spread-mutation. If this test becomes a bedside diagnostic tool, it will allow not only early diagnosis of drug resistance and more precise treatment but also better management against disease transmission.”

The study was funded by the National Health and Medical Research Council in Australia, Wellcome Trust UK and A*STAR Biomedical Research Council Singapore.

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