Browsing by Author "Doherty, T. M."

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    Identification of subclinical tuberculosis in household contacts using exposure scores and contact investigations
    (BMC (part of Springer Nature), 2020-01-31) Bekken, Gry K.; Ritz, Christian; Selvam, Sumithra; Jesuraj, Nelson; Hesseling, Anneke C.; Doherty, T. M.; Grewal, Harleen M. S.; Vaz, Mario; Jenum, Synne
    Background: The goal of tuberculosis elimination put forward in the End TB Strategy prioritizes diagnosis and treatment of incipient and subclinical TB, recently defined by key stakeholders as “asymptomatic, early pre-clinical disease during which pathology evolves”. Regarded as indicative of a high risk of TB progression, considerable efforts have been made to identify these cases through exploration of biomarkers. The present study aimed to evaluate simple scoring systems for TB exposure as screening tools for subclinical TB, the only identifiable of the incipient and subclinical disease states, in a contact investigation (CI) setting of low HIV-prevalence. Methods: Nested within a large prospective study in household contacts (HHCs) of smear positive pulmonary TB cases in South-India conducted 2010–2012, we assessed 1) the association between the Tuberculosis Contact Score (TCS) and the Infectivity Score, with established tools for Mycobacterium tuberculosis (Mtb) infection, corrected for established TB risk factors, and 2) the capability of the TB exposure scores to identify subclinical TB defined by Mtbculture positivity in sputum or gastric aspirate (subjects < 5 years) specimen. Results: Of 525 HHCs, 29 were Mtb-culture positive and 96.6% of these asymptomatic. The TCS and the Infectivity Score associated with positive Tuberculin Skin Test and QuantiFeron TB-Gold In-tube assay (QFT) results in multivariate analyses (TCS: ORTST 1.16, 95% CI: 1.01, 1.33; ORQFT 1.33 95% CI: 1.16, 1.51. Infectivity Score: ORTST 1.39, 95% CI: 1.10, 1.76; ORQFT 1.41 95% CI: 1.16, 1.71). The Infectivity Score showed a moderate capability to identify subclinical TB (AUC of 0.61, 95% CI: 0.52, 0.70). Conclusions: Although our results did not identify an easily applicable screening tool for subclinical TB, the present study indicates that focusing on TB-related symptoms in CI settings may be of limited value for early identification of HHCs with high risk for TB progression.
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    Impact of age and sex on mycobacterial immunity in an area of high tuberculosis incidence
    (2010) Gallant, C. J.; Cobat, A.; Simkin, L.; Black, G. F.; Stanley, K.; Hughes, J.; Doherty, T. M.; Hanekom, W. A.; Eley, B.; Beyers, Nulda; Jais, J-P.; Van Helden, Paul D.; Abel, L.; Alcais, A.; Hoal, E. G.; Schurr, E.
    SETTING: The extent of immune reactivity measured by the tuberculin skin test (TST) and interferon-gamma (IFN-γ) T-cell assays is usually not analysed. OBJECTIVE: To determine the impact of age and sex on assay positivity and on the extent of reactivity of both TST and T-cell assays in young persons in an area of South Africa with high TB transmission. RESULTS: Age had a strong impact on assay positivity for all seven immune phenotypes tested (P < 0.0007). Among positive responders, the extent of purified protein derivative (PPD) triggered IFN-γ release (P < 0.003) was sensitive to age. ESAT-6 triggered IFN-γ release (day 7, P = 0.03) and the frequency of PPD-specific IFN-γ+CD4+ (P = 0.03) and IFN-γ+CD8+ cells (P = 0.04) were weakly dependent on age. By contrast, the extent of TST induration was insensitive to age (P > 0.05), and sex had no significant impact on any phenotype measured (P > 0.05). The high proportion of positive responders in the 1-10 year age-group observed with long-term whole blood assays, but not with 3-day assays and TST, suggests that long-term whole blood assays may be confounded by bacille Calmette-Guérin vaccination in this age group. CONCLUSION: There is a significant impact of age, but not sex, on different assays of immune reactivity in this high TB transmission setting. © 2010 The Union.