Consequences of rpoB mutations missed by the GenoType MTBDRplus assay in a programmatic setting in South Africa.

Background: Rifampicin resistance missed by commercial rapid molecular assays but detected by phenotypic assays may lead to discordant susceptibility results and affect patient management. Objective: This study was conducted to evaluate the causes of rifampicin resistance missed by the GenoType MTBDRplus and its impact on the programmatic management of tuberculosis in KwaZulu-Natal, South Africa. Methods: We analysed routine tuberculosis programme data from January 2014 to December 2014 on isolates showing rifampicin susceptibility on the GenoType MTBDRplus assay but resistance on the phenotypic agar proportion method. Whole-genome sequencing was performed on a subset of these isolates. Results: Out of 505 patients with isoniazid mono-resistant tuberculosis on the MTBDRplus, 145 (28.7%) isolates showed both isoniazid and rifampicin resistance on the phenotypic assay. The mean time from MTBDRplus results to initiation of drug-resistant tuberculosis therapy was 93.7 days. 65.7% of the patients had received previous tuberculosis treatment. The most common mutations detected in the 36 sequenced isolates were I491F (16; 44.4%) and L452P (12; 33.3%). Among the 36 isolates, resistance to other anti-tuberculosis drugs was 69.4% for pyrazinamide, 83.3% for ethambutol, 69.4% for streptomycin, and 50% for ethionamide. Conclusion: Missed rifampicin resistance was mostly due to the I491F mutation located outside the MTBDRplus detection area and the L452P mutation, which was not included in the initial version 2 of the MTBDRplus. This led to substantial delays in the initiation of appropriate therapy. The previous tuberculosis treatment history and the high level of resistance to other anti-tuberculosis drugs suggest an accumulation of resistance.

Pre-Diagnosis Health Seeking Behaviors and Experiences Post-Diagnosis, among Men Diagnosed with Tuberculosis in a District of Gauteng Metropolitan City, South Africa: In-Depth Interviews.

BACKGROUND: Tuberculosis remains the number one killer among infectious diseases in South Africa. The TB disease burden is said to be higher among males, 1.6 times more than females in 2018. Moreover, men are reported to have poor healthcare-seeking behaviors. Loss in social and physical functioning, including reduced sexual desires and changes in family life, have been reported following a TB diagnosis. This study explored the meaning that male TB patients attach to their TB diagnosis and impact of TB infection in their lives and those of the people living with them. METHODS: This exploratory qualitative study was conducted among 25 participants recruited among male patients seeking TB care from two clinics in informal settlements of the city of Johannesburg. In-depth interviews with open-ended questions were conducted using an audio recorder for the collection of data. Data analysis was conducted on the NVivo version 12 software following an inductive thematic approach. RESULTS: The ages of the participants ranged between 18 and 61 years. Most were unemployed, and only a few were married or in steady relationships. From the two emerging themes, pre-TB diagnosis health-seeking behaviors and post TB-diagnosis experiences, several subthemes were identified. For the former theme, the subthemes include, seeking help from community-based healers and self-medicating, waiting for some period to see if the alternative medicine or treatment worked, taking time to visit a healthcare facility, triggers to seek healthcare, and symptoms reported on presentation to the healthcare facility. The post-TB diagnosis subthemes include making sense of the TB diagnosis, context of disclosing the TB status, fear of social exclusion and experiences of stigma, support received during illness, life changes after TB infection and diagnosis, and lessons learned from the TB experience and future healthcare-seeking behavior. CONCLUSION: Secrecy about the TB diagnosis indicates fear of social exclusion, and this could be due to the highly stigmatized nature of TB. Waiting to see if alternative medication worked, delayed the TB diagnosis, with consequent late initiation of the anti-TB treatment. The life changes experienced post-TB diagnosis affect the quality of life of the participants and their families. The study recommends that these issues be addressed as a priority.

Effects of introducing Xpert MTB/RIF test on multi-drug resistant tuberculosis diagnosis in KwaZulu-Natal South Africa.

BACKGROUND: An algorithm instituted following Xpert MTB/RIF (Xpert) introduction in South Africa advocates for treating all Xpert rifampicin resistant patients as MDR-TB cases while awaiting confirmation by phenotypic or genotypic drug susceptibility testing. This study evaluates how the Xpert has influenced the diagnosis and management of drug resistant TB in the highest burdened district of KwaZulu-Natal Province. METHODS: Data was retrospectively collected from all patients with rifampicin resistance on Xpert performed between March 2011 and April 2012. Xpert results were compared with those of phenotypic and/genotypic drug susceptibility testing. Patients' records were used to determine the time to treatment initiation. RESULTS: Out of 637 patients tested by Xpert, 50% had confirmatory results, of which a third were sent on the same day as Xpert test. The rate of rifampicin discordance and monoresistance was 8.8% and 13.4% respectively and there was no difference between phenotypic and genotypic confirmation. Among those who had been initiated on treatment, 28%, 40%, 21% and 8% of patients commenced within 2 weeks, 1 month, 2 months and 3 months of Xpert testing respectively, while the remaining 3% were observed without treatment. CONCLUSION: This study emphasizes the importance of complying with the algorithm in confirming all Xpert rif resistant cases so as to ensure proper management of these patients. Despite the rapidity of the Xpert results, only about 70% of patients had been initiated treatment at one month. Therefore there is a definite need to improve the health systems in order to improve on these delays.