Machine learning reveals that Mycobacterium tuberculosis genotypes and anatomic disease site impacts drug resistance and disease transmission among patients with proven extra-pulmonary tuberculosis

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.

Cutaneous Manifestations of Mycobacterium tuberculosis: A Literature Review

“…Sibandze et al investigated spoligotypes involved in extrapulmonary tuberculosis infections in South Africa, a region with one of the highest tuberculosis disease burdens [ 23 ]. They cultured isolates and clustered M. tb strains into four lineages: East Asian (1 case), East African (1 case), Euro-American (5 cases), and an orphan lineage (3 cases), which was considered nonclustered due to unmatched genetic strains.…”

“…They found that cutaneous, lymphadenitis, and meningitis cases were significantly more likely to be associated with drug resistance, with 45% of sampled cutaneous TB cases demonstrating pan-resistance and 63% of cases with Rifampin and/or MDR-TB resistance. They also found that there was no association between drug resistance and spoligotypes for any resistance [ 23 ].…”

Molecular investigations of Mycobacterium tuberculosis genotypes among baseline and follow-up strains circulating in four regions of Eswatini

“…In the Kingdom of Eswatini, TB notification and incidence rates have been decreasing steadily in the past decade, from a peak incidence of 1,190 per 100,000 populations in 2009 to a low incidence rate of 329 per 100,000 populations in 2018 [ 2 ]. Notifications of drug resistant TB (DR-TB) mirrored those of drug-susceptible TB for the same period; however, DR-TB has not been adequately tracked by most TB programs in the Sub-Saharan Africa region, until recently [ 3 ]. The proportion of persons developing DR-TB while on treatment, including those with multidrug resistant TB (MDR-TB), increased over the years in Eswatini.…”