Tuberculosis Disease In Adults Research Articles

Parallel use of low-complexity automated nucleic acid amplification tests and lateral flow urine lipoarabinomannan assays to detect tuberculosis disease in adults and adolescents living with HIV

Parallel use of low-complexity automated nucleic acid amplification tests and lateral flow urine lipoarabinomannan assays to detect tuberculosis disease in adults and adolescents living with HIV

120. A Randomized Double-blind Trial Assessing the Efficacy of M72/AS01E Vaccine Against Pulmonary Tuberculosis Disease in Adults With Latent Mycobacterium tuberculosis Infection

BackgroundAn effective tuberculosis (TB) vaccine is urgently needed to support the End TB Strategy to reduce the number of new TB cases by 80% by 2030. M72/AS01E candidate vaccine is an adjuvanted recombinant fusion protein derived from Mycobacterium tuberculosis Mtb32A and Mtb39A proteins.MethodsWe conducted a randomized, double-blind, placebo-controlled phase 2b trial (NCT01755598) in Southern and Eastern Africa to assess M72/AS01E’s efficacy against bacteriologically confirmed pulmonary TB disease in HIV-seronegative (HIV–) adults aged 18–50 years infected with Mtb (defined by a positive IFN-γ release assay). Participants were randomized 1:1 to receive M72/AS01E or placebo at day D0 and D30. Reactogenicity, safety, immunogenicity were assessed, and incident TB disease measured from D30 postdose 2 up to ≥24 months for this analysis (follow-up ongoing up to 37 months). Efficacy against various TB disease case definitions (Figure 1) was estimated. Primary objective: efficacy against culture- or PCR-confirmed pulmonary TB disease in HIV– adults (case definition 1; success criterion: lower limit of 90% 2-sided CI >0%, power: 80%).ResultsDemographic characteristics were similar between M72/AS01E (1786) and placebo (1787) recipients. Efficacy against pulmonary TB disease case definition 1 was 54.0% (90% CI: 13.9, 75.4; P = 0.042); efficacy against other case definitions and a sensitivity analysis are shown in Figure 1. Leading solicited symptoms were pain, fatigue, and headache (Figure 2). In all recipients, unsolicited symptoms (D0–29) were more frequent after M72/AS01E (67.4%) than placebo (45.4%), mainly attributable to increased injection site reactions and flu-like symptoms. Serious adverse events (D0–month 7) incidences were similar between groups (M72/AS01E: 1.6%; placebo: 1.8%). During the study, 24 adults died (14 due to traumatic events); all deaths were unrelated to the trial.ConclusionM72/AS01E presents a clinically acceptable safety profile and significantly reduces bacteriologically confirmed pulmonary TB disease incidence in HIV– adults with latent Mtb infection. Funding. BMGF; Aeras; DFID UK; DGIS; AusAID; GlaxoSmithKline Biologicals SA.Disclosures O. Van Der Meeren, GSK: Employee and Shareholder, Salary. M. Hatherill, Aeras: Investigator, Research grant. R. J. Wilkinson, GSK: Grant Investigator, indirect funding. H. M. Ayles, GSK: Grant Investigator, Research grant. G. Henostroza, Aeras: Investigator, Grant recipient. M. A. Demoitié, GSK: owns stocks and is named inventor on patent applications relating to certain uses of M72/AS01E, Salary. T. Singh, GSK: Employee and Shareholder, Salary. E. J. Akite, GSK: Employee, Salary. A. K. Azam, GSK: Employee, Salary. A. Bollaerts, GSK: Employee, Salary. A. M. Ginsberg, GSK: Collaborator, Research support. BMGF: Grant Investigator, Grant recipient. UK DFID: Grant Investigator, Grant recipient. P. Gillard, GSK: Employee and Shareholder, Salary and stock. D. R. Tait, Aeras: Employee, Salary. GSK: Shareholder, Salary.

Age- and Sex-Specific Social Contact Patterns and Incidence of Mycobacterium tuberculosis Infection.

We aimed to model the incidence of infection with Mycobacterium tuberculosis among adults using data on infection incidence in children, disease prevalence in adults, and social contact patterns. We conducted a cross-sectional face-to-face survey of adults in 2011, enumerating “close” (shared conversation) and “casual” (shared indoor space) social contacts in 16 Zambian communities and 8 South African communities. We modeled the incidence of M. tuberculosis infection in all age groups using these contact patterns, as well as the observed incidence of M. tuberculosis infection in children and the prevalence of tuberculosis disease in adults. A total of 3,528 adults participated in the study. The reported rates of close and casual contact were 4.9 per adult per day (95% confidence interval: 4.6, 5.2) and 10.4 per adult per day (95% confidence interval: 9.3, 11.6), respectively. Rates of close contact were higher for adults in larger households and rural areas. There was preferential mixing of close contacts within age groups and within sexes. The estimated incidence of M. tuberculosis infection in adults was 1.5–6 times higher (2.5%–10% per year) than that in children. More than 50% of infections in men, women, and children were estimated to be due to contact with adult men. We conclude that estimates of infection incidence based on surveys in children might underestimate incidence in adults. Most infections may be due to contact with adult men. Treatment and control of tuberculosis in men is critical to protecting men, women, and children from tuberculosis.

Performance of the Interferon Gamma Release Assays in Tuberculosis Disease in Children Five Years Old or Less.

Interferon Gamma Release Assays (IGRAs) were developed for the indirect or immunologic diagnosis of tuberculosis infection; however, they have also been used to assist in difficult to diagnose cases of tuberculosis disease in adults, and to a lesser extent, in children, especially in those under 5 years old. We evaluated the utility of using an IGRA in pediatric tuberculosis in younger children in a hospital setting. The diagnostic accuracy of T-SPOT.TB and TST was assessed in 117 children with active tuberculosis and 413 children with respiratory tract infection. Sensitivity and specificity were calculated for the tests used individually and together. Concordance was also calculated. Sensitivity of T-SPOT.TB (82.9%) was higher than TST (78.6% using a 5mm cut-off), especially in children confirmed to have TB. T-SPOT.TB was more specific than TST using a 5mm cut-off (96.1% vs. 70.9%). Combining T-SPOT.TB and TST results improved the sensitivity to 96.6%. In conclusion, the results of the current study indicate that T-SPOT.TB has good sensitivity and specificity, supporting its use among patients of this age. A combination of IGRA and TST would be useful additions to assist in the diagnosis of childhood TB.