Media Alert
10 December 2018

For Immediate Release

Ms Ndivhuho Makhado, the Senior Medical Scientist, Microbiological Pathology Department

A ground breaking international research team discovered two different Multi Drug Resistant Tuberculosis (MDR-TB) strains which escape detection by standard routine methods of TB detection. These findings were published in the prestigious “Lancet Infectious Disease” Journal in Oct 2018. Visit https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30496-1/ for full text.

The research showed that isoniazid monoresistant Mycobacterium tuberculosis (a causative agent of TB) isolates, carry a specific mutation, Ile491Phe mutation from two different strains, which is associated with Rifampicin (RIF) resistance, a surrogate marker for MDR-TB. This mutation is not detected by conventional laboratory tests endorsed by the World Health Organization (WHO) that are used to detect 95% of known RIF resistance within the RIF Resistance Determining Region (RRDR) of the rpoB gene.

The laboratory work, which ultimately resulted in the discovery of the MDR-TB strain began in 2015, in the National Health Laboratory Service (NHLS) – Dr George Mukhari Tertiary Laboratory (NHLS –DGMTL, at SMU), in which Ms Ndivhuho Makhado, the Senior Medical Scientist, in the Microbiological Pathology (MP) Department and team, identified isolates with probable mutation that cause resistance to first line drugs for TB treatment.

The intensive research project involved a collaborative team of Microbiologists from SMU, University of Antwerp (AU) in Belgium and University of Lille, in France, who worked over the months to uncover this new TB strain. A total of 277 Isoniazid (INH) monoresistant isolates were randomly selected from 37 644 positive cultures of TB cases referred to the NHLS – DGMTL from four provinces; Gauteng, North West, Limpopo and Mpumalanga, between 2013 and 2016. The researchers identified the Ile491Phe mutation in 37 (15%) of 249 samples, and reclassified them as MDR-TB, as these are genotypically resistant to all first-line drugs by Deeplex-MycTB sequencing method. Six isolates harboured four distinct mutations potentially associated with decreased bedaquiline sensitivity.

A substantial number of MDR-TB cases harbouring the Ile491Phe mutation in the rpoB gene that are missed by current diagnostic methods, may result in ineffective first-line treatment, continued amplification of drug resistance and concurrent silent spread in the community.

The study highlights a potential challenge in the currently used WHO-endorsed methods in identifying all MDR-TB cases which may result in: amplification of drug resistance, ineffective patient management and adverse treatment outcomes. The researchers further highlight the importance of a continued monitoring of the prevalence of drug resistant TB as well as potentially increased mutations outside the RRDR. The results of this research work will give guidance towards implementing better diagnostic tools such as rapid MAS-PCR and whole-genome sequencing, which can help to improve diagnosis on these clinically significant mutations, and therefore improve TB treatment outcomes in South Africa.

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