Cinthya Ruiz-Tagle

Trials guidance: The Abstract should not exceed 350 words. Please minimize the use of abbreviations and do not cite references in the The abstract must include the following separate sections: Background : Mycobacterium tuberculosis acquisition after exposure is common but difficult to diagnose and frequently requires serial testing given that immunological evidence of infection can take several weeks to develop. Even though tuberculosis infection (TBI) is asymptomatic, its long-term effects remain unclear due to poorly understood host-pathogen interactions and delayed disease development, and research has shown that active mycobacterial replication and inflammation occur during TBI. Although the main purpose of antituberculosis prophylaxis has been to prevent people with established TBI from progressing to active tuberculosis disease, a few studies have suggested that this prophylaxis, when administered during the window period after exposure, can prevent the acquisition of TBI in very young children. Considering that newer preventive regimens are shorter and safer, this study aims to assess whether tuberculosis prophylaxis —when given in the window period after exposure— can prevent new infections in older children and adolescents who have been recently exposed. Methods : A multicentre cluster-randomized controlled clinical trial will be performed in Chile. A total of 360 households (clusters) with children aged ≥5 to <18 years, who have been recently exposed to a new case of pulmonary tuberculosis will be randomized to intervention or control arm. In the intervention arm, contacts will receive immediate tuberculosis prophylaxis, regardless of the interferon-gamma release assay (IGRA) result. In the control arm, participants will receive tuberculosis prophylaxis only if the IGRA test results positive, as per standard of care. In both arms, the prophylaxis scheme will be the usual weekly isoniazid plus rifapentine for 12 weeks regimen. The primary outcome will be assessed at the individual level by IGRA conversions from negative at baseline to positive at the 12-week follow-up. Discussion : This trial will establish the effectiveness of a window prophylaxis strategy in reducing the risk of TBI acquisition after exposure in a community setting, a strategy that can potentially contribute to global tuberculosis elimination by reducing M. tuberculosis reservoirs. Trial registration : ClinicalTrials.gov, NCT07086820. Registered 17 July 2025, https://clinicaltrials.gov/study/NCT07086820.

Background: The duration of infectiousness following pulmonary tuberculosis treatment initiation remains uncertain. We aimed to assess whether a bundled intervention designed to decrease respiratory exposure was feasible and would reduce new tuberculosis infections in household contacts (HHCs). Methods: We conducted a pilot cluster-randomized controlled trial with a hybrid type 1 effectiveness-implementation design in Santiago, Chile. Random allocation was performed, and 2 healthcare districts were assigned to the intervention (n = 180 HHCs) and 1 to standard of care (n = 149 HHCs). Eligible participants were people newly diagnosed with pulmonary tuberculosis and their HHCs. The intervention included education, mask use, household ventilation, and nightly separation of tuberculosis patients, for 2 weeks. Intervention adherence was evaluated weekly. Effectiveness was assessed at the individual level with QuantiFERON®-TB Gold Plus (QFT) test conversions in HHCs at 12-week follow-up. Results: Between October 2021 and December 2023, 384 HHCs and 157 people with tuberculosis were enrolled. Overall, 56.3% of contacts were women, with a mean age of 34.6 years and a baseline QFT positivity of 32.3%. A total of 216 contacts had negative QFT result at baseline, with 179 (82.9%) completing follow-up. QuantiFERON®-TB Gold Plus conversions occurred in 11 (12.8%) and 10 (10.8%) HHCs from the intervention and control arms, respectively (incidence risk ratio 1.10, 95% CI .71–1.71, P = .849). Good adherence to the respiratory bundle was reported by 53% of participants on day 7 and 54% on day 14. Conclusions: Isolation and restrictive measures after tuberculosis treatment initiation proved challenging and did not reduce tuberculosis infections in HHCs, suggesting limited benefit for transmission control.

Interferon-gamma (IFN-γ) release assays play a pivotal role in tuberculosis infection (TBI) diagnosis, with QuantiFERON-TB Gold Plus—an enzyme-linked immunosorbent assay (ELISA)—among the most widely utilized. Newer QuantiFERON-TB platforms with shorter turnaround times were recently released. We aimed to evaluate these platforms’ agreement in the diagnosis of TBI. Blood samples from a prospective cohort of tuberculosis household contacts were collected at baseline and after 12 weeks of follow-up, and tested with LIAISON, an automated chemiluminescence immunoassay (CLIA) system, QIAreach, a lateral flow (QFT-LF) semi-automated immunoassay, and the ELISA QuantiFERON-TB Gold Plus platform. Test concordances were analyzed. ELISA vs CLIA overall agreement was 83.3% for all tested samples (120/144) [Cohen’s kappa coefficient (κ): 0.66 (95% CI: 0.54–0.77)]. Samples positive with CLIA provided consistently higher IFN-γ levels than with ELISA ( P < 0.001). Twenty-four (16.7%) discordant pairs were obtained, all CLIA-positive/ELISA-negative: 15 (62.5%) had CLIA IFN-γ levels within borderline values (0.35–0.99 IU/mL) and 9 (37.5%) >0.99 IU/mL. QFT-LF showed only 76.4% (68/89) overall agreement with ELISA [κ: 0.53 (95% CI: 0.37–0.68)] with 21 (23.6%) discordant results obtained, all QFT-LF-positive/ELISA-negative. Overall concordance between ELISA and CLIA platforms was substantial, and only moderate between ELISA and QFT-LF. The CLIA platform yielded higher IFN-γ levels than ELISA, leading to an almost 17% higher positivity rate. The techniques do not seem interchangeable, and validation against other gold standards, such as microbiologically-confirmed tuberculosis disease, is required to determine whether these cases represent true new infections or whether CLIA necessitates a higher cutoff. IMPORTANCE: Tuberculosis is an airborne infectious disease caused by Mycobacterium tuberculosis that affects over 10 million people annually, with over 2 billion people carrying an asymptomatic tuberculosis infection (TBI) worldwide. Currently, TBI diagnosis includes tuberculin skin test and the blood-based interferon-gamma (IFN-γ) release assays, with Qiagen QuantiFERON-TB Gold Plus (QFT) being among those most widely utilized. We evaluated Qiagen's newer QFT platforms commercially available in a prospective cohort of tuberculosis contacts. A substantial agreement was obtained between the current QFT-enzyme-linked immunosorbent assay (ELISA) and the new QFT-chemiluminescence immunoassay (CLIA) platform, although QFT-CLIA provided higher concentrations of IFN-γ, leading to a 16.6% higher positivity rate. We highlight that both platforms may not be directly interchangeable and that further validation is required.

Cancer patients on chemotherapy have a lower immune response to SARS-CoV-2 vaccines. Therefore, through a prospective cohort study of patients with solid tumors receiving chemotherapy, we aimed to determine the immunogenicity of an mRNA vaccine booster (BNT162b2) among patients previously immunized with an inactivated (CoronaVac) or homologous (BNT162b2) SARS-CoV-2 vaccine. The primary outcome was the proportion of patients with anti-SARS-CoV-2 neutralizing antibody (NAb) seropositivity at 8–12 weeks post-booster. The secondary end points included IgG antibody (TAb) seropositivity and specific T-cell responses. A total of 109 patients were included. Eighty-four (77%) had heterologous vaccine schedules (two doses of CoronaVac followed by the BNT162b2 booster) and twenty-five had (23%) homologous vaccine schedules (three doses of BNT162b2). IgG antibody positivity for the homologous and heterologous regimen were 100% and 96% (p = 0.338), whereas NAb positivity reached 100% and 92% (p = 0.13), respectively. Absolute NAb positivity and Tab levels were associated with the homologous schedule (with a beta coefficient of 0.26 with p = 0.027 and a geometric mean ratio 1.41 with p = 0.044, respectively). Both the homologous and heterologous vaccine regimens elicited a strong humoral and cellular response after the BNT162b2 booster. The homologous regimen was associated with higher NAb positivity and Tab levels after adjusting for relevant covariates.

Tuberculosis (TB) is an infectious disease of extremely high epidemiological burden worldwide that is easily acquired through the inhalation of infected respiratory droplets. The complex pathogenesis of this infection spans from subjects never developing this disease despite intense exposure, to others in which immune containment fails catastrophically and severe or disseminated forms of disease ensue.