Outbreak of multidrug-resistant tuberculosis not detected by standard tests – ScienceDaily



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On September 26, the United Nations announced a plan to raise $ 13 billion a year to fight TB by 2030. With 10 million new cases and 1.6 million deaths in 2017, it is expected that Is the most prevalent infectious disease in the world, in front of HIV. . Of the more than 450,000 new cases of antibiotic-resistant TB that have probably occurred, only 25% have been detected. A study conducted by an international research team * co-directed by Philip Supply, a CNRS researcher at the Lille Infection and Immunity Center (CNRS / Inserm / Pasteur Institute of Lille / University of Lille), highlighted this serious problem of detection, particularly in South Africa.

The results, published in The Lancet Infectious Diseases, show that some South African isolates of Mycobacterium tuberculosis (the bacteria that causes the disease) carry a specific combination of mutations that make them resistant to the two prescribed first-line antibiotics: rifampicin and isoniazid. This combined resistance is not detected by standard tests approved by the World Health Organization: the region of the gene carrying a particular mutation causing resistance to rifampicin is not included in the DNA test and resistance to treatment due to this mutation is not detected in crops.

This omission results in the failure of first-line treatment in patients, increased mortality and contagion, and the development of additional antibiotic resistance. In particular, the researchers detected the presence of mutations that probably led to a decrease in sensitivity to bedaquiline, the last molecule used to treat cases of multidrug-resistant tuberculosis. These mutations appeared immediately after its launch in the country from 2013.

This was discovered thanks to a new test for the reactivity of optical discs developed by Genoscreen ** and P. Supply. Unlike standard DNA testing, this one analyzes a wide panel of target genes in the bacteria and can identify resistance to more than a dozen antibiotics simultaneously. These results are obtained in one to three days, compared to the weeks required for the cultures. The test will help solve the problem of under-detection of MDR-TB.

It will benefit from a new algorithm for detecting resistance mutations, whose effectiveness has been detailed in an article published in the New England Journal of Medicine by another consortium (CRyPTIC) ***, in which participated Dr. Supply and Genoscreen. This study was based on an analysis of 10,000 genomes, making it one of the largest microbial genome sequencing projects conducted to date.

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