In 2017, 1.6 million people died of tuberculosis. This disease is curable but has also developed drug resistance. Yet even multidrug-resistant tuberculosis (MDR-TB) can often still be cured with alternative antibiotics, provided that the disease is diagnosed quickly.

Inadequate diagnostic tests

An international team of researchers has now shown that MDR-TB strains have developed ways to fool even the latest diagnostic tests, endorsed by the World Health Organization. And, due to the wide use of these tests, a recent outbreak in South Africa has remained undetected for five years.

"We found two different strains circulating in the North-East of South Africa," explains senior author Emmanuel André (KU Leuven / University Hospitals Leuven), who led the study together with Dr Ndivhuho Makhado (Dr George Mukhari Tertiary Laboratory, South Africa). "These strains both have a specific DNA mutation that is associated with resistance against the antibiotic Rifampicin. The problem is that this particular mutation, which was previously known but thought to be very infrequent, is not detected by commercial tests claiming to detect Rifampicin resistance."

Detrimental effects

As a result, a substantial number of patients infected with MDR-TB strains were misdiagnosed and inadequately treated in South Africa. "These misdiagnoses have contributed to the dissemination of the outbreak and the development of additional drug resistance," Dr André continues.

"We need to act now and rethink how we diagnose multidrug-resistant tuberculosis to prevent further damage. Most patients were diagnosed in Rustenburg, a city located at 100 km from the capital Pretoria, which hosts major international mining companies and drives very large numbers of international workers. Many people living in these communities are migrant workers exposed to poverty and poor sanitary conditions. The risks are legion."

Alternative diagnostic test

For the purposes of this study, the researchers developed alternative diagnostic tests.

In order to screen the rpoB Ile491Phe mutation from a collection of as much as 37,644 cases of tuberculosis diagnosed at the Dr George Mukhari Tertiary Laboratory in Pretoria between 2013 and 2016, the researchers randomly selected a subset of isoniazid mono-resistant strains. A subset of 249 strains was screened using a rapid MAS-PCR test newly developed by Dr Emmanuel André and colleagues in Belgium.

The rpoB Ile491Phe positive cases were then further evaluated for extensive drug-resistance testing and refined phylogenetic analysis using whole genome sequencing and the Deeplex© MycTB assay, a commercial assay co-developed by Dr Philip Supply (CNRS and Institut Pasteur de Lille, France) and Genoscreen (France).

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