Discordant Rifampicin Sequencing

The Centre for Tuberculosis offers a national service to resolve phenotypic and genotypic discordance.  South Africa is among the top worse afflicted countries for both HIV infection and tuberculosis (TB) with co-infection rates at 78% in TB cases. TB-HIV co-infection exacerbates both diagnostic and therapeutic challenges, causing a massive burden on the current health care system.  HIV co-infected patients, have a 2-fold higher prevalence of Multidrug Resistant TB (MDR), therefore quick and accurate detection of drug resistance is essential for adequate management, which would ensure that patients are put on the correct drug regime sooner. HIV patients are at a higher risk of reinfection, and mixed infection, especially in South Africa where the infection pressure is high and multiple exposure prominent.

Mixed MTB infection (multiple strains of Mtb) continue to cause an increase in the rate of false-negative drug resistance testing, obtained by both drug susceptibility testing and GeneXpert. Heteroresistance, however, can arise, as a result of within-host diversification following a single infection. Both types of infection could influence the diagnosis of drug resistance especially if patients are infected with isolates that differ in drug susceptibility.  South Africa implemented the GeneXpert as the first line test for TB suspects is able rapidly diagnose TB and predict genotypic susceptibilit of Rifampicin, a marker for multiple drug resistance.  Therefore accurate detection of drug-resistance is essential as it influences treatment regimen. As part of the TB-HIV surveillance activities at the TB Supranational Reference Laboratory, sputum samples from HIV positive patients, in high burdened districts, with rifampicin sensitive GeneXpert results to confirm the result phenotypically.