Resistance to Latent Mycobacterium tuberculosis Infection in South Africa: Immunologic Profiling

Despite significant exposure to Mycobacterium tuberculosis (Mtb), some humans remain uninfected, as defined by persistently negative immune sensitization tests (tuberculin skin test, TST; interferon gamma release assays, IGRA). To explore mechanisms of natural resistance to Mtb infection, we profiled tissues from highly-exposed Mtb contacts from South Africa. The cohort in this submission were gold miners in South Africa who had worked in the mining industry ≥ 15 years with presumed high Mtb exposure, based on extreme tuberculosis incidence rates and high prevalence of latent Mtb infection (Chihota et al. 2022, PMID: 35302992; Ntshiqa et al. 2021, doi: 10.12688/gatesopenres.13191.1). TST and IGRA testing were performed at enrollment of gold miners, some of whom remained available for repeat testing at 12 months. ]]>
For each immune profiling assay, we defined Mtb ‘resister' (RSTR) cases as those that maintained negative TST and IGRA testing at all sampling times. Controls with latent Mtb infection (LTBI) were those with concordant, positive TST and IGRA testing at all sampling dates, and who showed no clinical evidence of tuberculosis disease.Inclusion Criteria:Gold miners from South Africa, aged 33-60, who had worked in the mining industry for ≥ 15 years were eligible. Exclusion Criteria:Participants were excluded if they had any history of TB (or treatment for TB), silicosis, or HIV (Chihota et al. 2022, PMID: 35302992). ]]>
Gold miner subjects were recruited as part of the Highly Exposed TB Uninfected (HETU) study in North West Province, South Africa between August 2015 and December 2016 (Chihota et al. 2022, PMID: 35302992), the majority of whom were followed over 12 months.]]>