Determining the risk-factors for molecular clustering of drug-resistant tuberculosis in South Africa.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) epidemic is driven mainly by the effect of ongoing transmission. In high-burden settings such as South Africa (SA), considerable demographic and geographic heterogeneity in DR-TB transmission exists. Thus, a better understanding of risk-factors for clustering can help to prioritise resources to specifically targeted high-risk groups as well as areas that contribute disproportionately to transmission. METHODS: The study analyzed potential risk-factors for recent transmission in SA, using data collected from a sentinel molecular surveillance of DR-TB, by comparing demographic, clinical and epidemiologic characteristics with clustering and cluster sizes. A genotypic cluster was defined as two or more patients having identical patterns by the two genotyping methods used. Clustering was used as a proxy for recent transmission. Descriptive statistics and multinomial logistic regression were used. RESULT: The study identified 277 clusters, with cluster size ranging between 2 and 259 cases. The majority (81.6%) of the clusters were small (2-5 cases) with few large (11-25 cases) and very large (≥ 26 cases) clusters identified mainly in Western Cape (WC), Eastern Cape (EC) and Mpumalanga (MP). In a multivariable model, patients in clusters including 11-25 and ≥ 26 individuals were more likely to be infected by Beijing family, have XDR-TB, living in Nelson Mandela Metro in EC or Umgungunglovo in Kwa-Zulu Natal (KZN) provinces, and having history of imprisonment. Individuals belonging in a small genotypic cluster were more likely to infected with Rifampicin resistant TB (RR-TB) and more likely to reside in Frances Baard in Northern Cape (NC). CONCLUSION: Sociodemographic, clinical and bacterial risk-factors influenced rate of Mycobacterium tuberculosis (M. tuberculosis) genotypic clustering. Hence, high-risk groups and hotspot areas for clustering in EC, WC, KZN and MP should be prioritized for targeted intervention to prevent ongoing DR-TB transmission.

Distribution and Clonality of drug-resistant tuberculosis in South Africa.

BACKGROUND: Studies have shown that drug-resistant tuberculosis (DR-TB) in South Africa (SA) is clonal and is caused mostly by transmission. Identifying transmission chains is important in controlling DR-TB. This study reports on the sentinel molecular surveillance data of Rifampicin-Resistant (RR) TB in SA, aiming to describe the RR-TB strain population and the estimated transmission of RR-TB cases. METHOD: RR-TB isolates collected between 2014 and 2018 from eight provinces were genotyped using combination of spoligotyping and 24-loci mycobacterial interspersed repetitive-units-variable-number tandem repeats (MIRU-VNTR) typing. RESULTS: Of the 3007 isolates genotyped, 301 clusters were identified. Cluster size ranged between 2 and 270 cases. Most of the clusters (247/301; 82.0%) were small in size (< 5 cases), 12.0% (37/301) were medium sized (5-10 cases), 3.3% (10/301) were large (11-25 cases) and 2.3% (7/301) were very large with 26-270 cases. The Beijing genotype was responsible for majority of RR-TB cases in Western and Eastern Cape, while the East-African-Indian-Somalian (EAI1_SOM) genotype accounted for a third of RR-TB cases in Mpumalanga. The overall proportion of RR-TB cases estimated to be due to transmission was 42%, with the highest transmission-rate in Western Cape (64%) and the lowest in Northern Cape (9%). CONCLUSION: Large clusters contribute to the burden of RR-TB in specific geographic areas such as Western Cape, Eastern Cape and Mpumalanga, highlighting the need for community-wide interventions. Most of the clusters identified in the study were small, suggesting close contact transmission events, emphasizing the importance of contact investigations and infection control as the primary interventions in SA.