Page 73 - University of Pretoria Research Review 2017

Foreword
Introductory Messages
DEVELOPMENT AND CHANGE
Communicable Diseases
Anti-microbial resistance complicates TB pandemic
Nontuthuko Maningi, Department of Medical Microbiology
The treatment of TB is made more complex as a result of the ability of different Mycobacterium tuberculosis strains to mutate and develop resistance to existing treatments. Researchers need to be one step ahead, if we are to win the fight against TB.
In collaboration with Professor Bernard Fourie,
Dr Nontuthuko Maningi from the Department of Medical Microbiology has been working to describe the genomes of antimicrobial-resistant organisms, as well as testing the effectiveness of different diagnostic techniques to identify susceptibility to antibiotics.
The susceptibility of Mycobacterium tuberculosis, the organism responsible for TB disease, to antimicrobial drugs, has been linked to specific mutations in the DNA of the bacteria. Interestingly, different mutations are responsible for resistance to different drugs. These mutations also occur at different frequencies within different populations, necessitating the profiling of
M. tuberculosis at a regional level.
M. tuberculosis can contain various mutations coding for resistance to a suite of drugs, often with multiple
mutations causing resistance to a single drug. These mutations and subsequent resistance to antimicrobial agents complicate the treatment of TB, often delaying early diagnosis and treatment, and lengthening the time needed for treatment.
Dr Maningi has been working to assess the frequency of the mutation Arg463Leu in the katG gene in multidrug-resistant TB (MDR-TB). These mutations
lead to isoniazid (INH) resistance, and the frequency of these mutations varies within individual organisms and geographical areas. The current, commercially available assay used to identify INH resistance, does not target the Arg463Leu mutation, potentially missing 20 to 40% of INH-resistant organisms. At the moment, the assay only targets codon 315 and InhA mutations. Including the Arg463Leu mutation in the assay will improve the ability to detect INH resistance.
In 2017, Dr Maningi completed a study profiling a historical sample of M. tuberculosis isolates. Using line probe assay and whole genome sequencing,
Dr Maningi and co-authors found that almost 71% of isolates were resistant to multiple antimicrobial drugs. Of the isolates that were susceptible to antimicrobial agents, only 26% were wild-type, or occurring naturally in host populations. Alarmingly, many of the M. tuberculosis isolates contained novel mutations, not tested for using standard assay techniques. Three of their multidrug-resistant M. tuberculosis (MDR-
TB) isolates showed mutations in the gyrA and rrs genes, indicating that extensively drug-resistant M. tuberculosis was present in South Africa, long before
it was first formally recognised in 2006. Dr Maningi
and co-authors also completed a study testing the efficacy of different drug susceptibility assays to detect susceptibility to different antimicrobial agents. They concluded that in South African populations, assays available for rapid diagnosis of MDR-TB and extremely drug-resistant TB (XDR-TB) perform with high specificity and sensitivity. The widespread use of these assays
in high-burden settings is integral for speeding up diagnosis, creating appropriate treatment plans and improving outcomes.
PEOPLE AND CONTEXTS
HEALTH AND WELL-BEING
PLANET AND SUSTAINABILITY
Awards
Lead Researchers
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