Clinical and epidemiological characteristics of individuals resistant to M. tuberculosis infection in a longitudinal TB household contact study in Kampala, Uganda

Abstract

BackgroundDespite sustained exposure to a person with pulmonary tuberculosis (TB), some M. tuberculosis (Mtb) exposed individuals maintain a negative tuberculin skin test (TST). Our objective was to characterize these persistently negative TST (PTST-) individuals and compare them to TST converters (TSTC) and individuals who are TST positive at study enrollment.MethodsDuring a TB household contact study in Kampala, Uganda, PTST-, TSTC, and TST + individuals were identified. PTST- individuals maintained a negative TST over a 2 year observation period despite prolonged exposure to an infectious tuberculosis (TB) case. Epidemiological and clinical characteristics were compared, a risk score developed by another group to capture risk for Mtb infection was computed, and an ordinal regression was performed.ResultsWhen analyzed independently, epidemiological risk factors increased in prevalence from PTST- to TSTC to TST+. An ordinal regression model suggested age (p < 0.01), number of windows (p < 0.01) and people (p = 0.07) in the home, and sleeping in the same room (p < 0.01) were associated with PTST- and TSTC. As these factors do not exist in isolation, we examined a risk score, which reflects an accumulation of risk factors. This compound exposure score did not differ significantly between PTST-, TSTC, and TST+, except for the 5–15 age group (p = 0.009).ConclusionsThough many individual factors differed across all three groups, an exposure risk score reflecting a collection of risk factors did not differ for PTST-, TSTC and TST + young children and adults. This is the first study to rigorously characterize the epidemiologic risk profile of individuals with persistently negative TSTs despite close exposure to a person with TB. Additional studies are needed to characterize possible epidemiologic and host factors associated with this phenotype.

Advancing host-directed therapy for tuberculosis

“…Neutrophils also participate through the transfer of granuleswhich contain antimicrobial agents that traffic to early endosomes containing mycobacteria -to macrophages and through the production of S100 proteins 9, 10 . In some individuals who remain tuberculin skin test-negative despite prolonged and repeated exposure to M. tuberculosis, these innate immune responses may be sufficient to prevent infection 11 . Further genetic studies of these resistant individuals may identify new HDT targets 12 .…”

Understanding the Tuberculosis Disease Progression and Future Directions of Research in Tuberculosis: A Mini Review

“…The risk of progression to active TB disease in LTBI child is influenced by the virulence of the mycobacteria, bacillary load, age and patient's immune response (Seddon et al 2013;Ma et al 2014). HIV co-infection is the strongest known risk factor for progression of LTBI to active TB disease (Lai et al 2016).…”

“…Indeed, attempts were made to improve the reliability of diagnostic tool as well as to know the factors that contribute to false positive or false negative results. For instance, a prospective study by Ma et al (2014) among household contact of smear positive TB on standard TB regimen in Uganda found that 5-15 years old age group had tendency to have persistently negative TST (Ma et al 2014). Furthermore, Oberhelman et al (2015) compared the used of culture and/or microscopic evaluation against PCR method for bacteriological confirmation of TB.…”

Genomics of Human Pulmonary Tuberculosis: from Genes to Pathways

“…Some studies have been family-based, while others used a traditional case-control design. The advantage of family-based studies of TB is that exposure is more certain even if variable [34, 35]. …”