Abstract:
BACKGROUND: There is a general dearth of information on extrapulmonary tuberculosis (EPTB). Here, we investigated
Mycobacterium tuberculosis (Mtb) drug resistance and transmission patterns in EPTB patients treated in the Tshwane
metropolitan area, in South Africa.
METHODS: Consecutive Mtb culture-positive non-pulmonary samples from unique EPTB patients underwent
mycobacterial genotyping and were assigned to phylogenetic lineages and transmission clusters based on
spoligotypes. MTBDRplus assay was used to search mutations for isoniazid and rifampin resistance. Machine learning
algorithms were used to identify clinically meaningful patterns in data. We computed odds ratio (OR), attributable
risk (AR) and corresponding 95% confidence intervals (CI).
RESULTS: Of the 70 isolates examined, the largest cluster comprised 25 (36%) Mtb strains that belonged to the East
Asian lineage. East Asian lineage was significantly more likely to occur within chains of transmission when
compared to the Euro-American and East-African Indian lineages: OR = 10.11 (95% CI: 1.56–116). Lymphadenitis,
meningitis and cutaneous TB, were significantly more likely to be associated with drug resistance: OR = 12.69 (95%
CI: 1.82–141.60) and AR = 0.25 (95% CI: 0.06–0.43) when compared with other EPTB sites, which suggests that poor
rifampin penetration might be a contributing factor.
CONCLUSIONS: The majority of Mtb strains circulating in the Tshwane metropolis belongs to East Asian, EuroAmerican and East-African Indian lineages. Each of these are likely to be clustered, suggesting on-going EPTB
transmission. Since 25% of the drug resistance was attributable to sanctuary EPTB sites notorious for poor rifampin
penetration, we hypothesize that poor anti-tuberculosis drug dosing might have a role in the development of
resistance.
