Cough Aerosol Cultures of Mycobacterium tuberculosis: Insights on TST / IGRA Discordance and Transmission Dynamics

Abstract

RationaleThe diagnosis of latent tuberculosis (TB) infection (LTBI) is complicated by the absence of a gold standard. Discordance between tuberculin skin tests (TST) and interferon gamma release assays (IGRA) occurs in 10–20% of individuals, but the underlying mechanisms are poorly understood.MethodsWe analyzed data from a prospective household contact study that included cough aerosol culture results from index cases, environmental and contact factors. We assessed contacts for LTBI using TST and IGRA at baseline and six weeks. We examined TST/IGRA discordance in qualitative and quantitative analyses, and used multivariable logistic regression analysis with generalized estimating equations to analyze predictors of discordance.Measurements and ResultsWe included 96 TB patients and 384 contacts. Discordance decreased from 15% at baseline to 8% by six weeks. In adjusted analyses, discordance was related to less crowding (p = 0.004), non-cavitary disease (OR 1.41, 95% CI: 1.02–1.96; p = 0.03), and marginally with BCG vaccination in contacts (OR 1.40, 95% CI: 0.99–1.98, p = 0.06).ConclusionsWe observed significant individual variability and temporal dynamism in TST and IGRA results in household contacts of pulmonary TB cases. Discordance was associated with a less intense infectious exposure, and marginally associated with a BCG-mediated delay in IGRA conversion. Cough aerosols provide an additional dimension to the assessment of infectiousness and risk of infection in contacts.

Incident Mycobacterium tuberculosis infection in household contacts of infectious tuberculosis patients in Brazil

“…Conversely, in high prevalence settings, the expected proportion of contacts with TST conversion would be lower as a result of the opposite epidemiologic scenario. Interestingly, the proportion of contacts with TST conversion in the present study is consistent with the 4–10% reported in most other studies in both low and high TB burden settings [ 15 , 27 – 29 ]. The narrow variation in TST conversion across vastly different epidemiologic settings is striking in itself and unlikely to be explained by chance alone.…”

“…Recently, there has been great interest in studying household contacts that remain uninfected despite close contact with a TB patient, as they are thought to represent a phenotype of innate or acquired resistance to M. tuberculosis infection [ 3 , 10 ]. In meta-analyses of household contact studies ~50% of contacts are found to be TST-negative [ 4 , 5 ], but this may be due to multiple factors such as exposure misclassification [ 29 ], missing TST converters, and limited sensitivity of TST and IGRA [ 3 ]. Our findings are in agreement with previous studies that found an association between TST conversion and socioeconomic status, [ 30 ] and lower rates of infection in females [ 27 ] –possibly as a result of family behavior patterns.…”

“…The absence of community controls did not permit estimating the secondary attack rate of TB infection within households [ 12 ]. We did not obtain cough generated M. tuberculosis aerosols in index patients, which may have led to exposure misclassification [ 29 ]. We used the visualization of a scar as a surrogate for BCG vaccination although it is estimated that up to 10% of BCG vaccinated infants may not develop a scar [ 13 ].…”

Epidemiological and genomic determinants of tuberculosis outbreaks in First Nations communities in Canada

“…A high rate of disease progression among contacts could also result from a particularly aggressive MTB strain but, as noted above, our results do not support this. An alternative explanation is that the source cases had an intense cough and an unusually high bacterial burden and produced aerosols that delivered a large or repeated inoculum to their contacts [ 37 ]. It is also plausible that environmental conditions contributed to these outbreaks.…”

Mycobacterium tuberculosis Sulfolipid-1 Activates Nociceptive Neurons and Induces Cough

“…A hallmark symptom of active pulmonary tuberculosis and a major mechanism of disease transmission is a persistent, sometimes bloody cough. The vast majority of de novo Mycobacterium tuberculosis (Mtb) infections are acquired from contact with actively infected, coughing individuals (Fennelly et al, 2004;Jones-Ló pez et al, 2015). Previous hypotheses regarding the mechanism of cough in pulmonary tuberculosis emphasized the role of infection-induced lung irritation and production of inflammatory mediators (Turner, 2019;Turner and Bothamley, 2015).…”