Browsing by Author "Evans, Thomas G."

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    Phase 2b controlled trial of M72/AS01E vaccine to prevent tuberculosis
    (Massachusetts Medical Society, 2018-10-25) Van der Meeren, Olivier; Hatherill, Mark; Nduba, Videlis; Wilkinson, Robert J.; Muyoyeta, Monde; Van Brakel, Elana; Ayles, Helen M.; Henostroza, German; Thienemann, Friedrich; Scriba, Thomas J.; Diacon, Andreas; Blatner, Gretta L.; Demoitie, Marie-Ange; Tameris, Michele; Malahleha, Mookho; Innes, James C.; Hellstrom, Elizabeth; Martinson, Neil; Singh, Tina; Akite, Elaine J.; Khatoon Azam, Aisha; Bollaerts, Anne; Ginsberg, Ann M.; Evans, Thomas G.; Gillard, Paul; Tait, Dereck R.
    BACKGROUND: A vaccine to interrupt the transmission of tuberculosis is needed. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 2b trial of the M72/AS01E tuberculosis vaccine in Kenya, South Africa, and Zambia. Human immunodeficiency virus (HIV)–negative adults 18 to 50 years of age with latent M. tuberculosis infection (by interferon-γ release assay) were randomly assigned (in a 1:1 ratio) to receive two doses of either M72/AS01E or placebo intramuscularly 1 month apart. Most participants had previously received the bacille Calmette–Guérin vaccine. We assessed the safety of M72/AS01E and its efficacy against progression to bacteriologically confirmed active pulmonary tuberculosis disease. Clinical suspicion of tuberculosis was confirmed with sputum by means of a polymerase-chain-reaction test, mycobacterial culture, or both. RESULTS: We report the primary analysis (conducted after a mean of 2.3 years of follow-up) of the ongoing trial. A total of 1786 participants received M72/AS01E and 1787 received placebo, and 1623 and 1660 participants in the respective groups were included in the according-to-protocol efficacy cohort. A total of 10 participants in the M72/AS01E group met the primary case definition (bacteriologically confirmed active pulmonary tuberculosis, with confirmation before treatment), as compared with 22 participants in the placebo group (incidence, 0.3 cases vs. 0.6 cases per 100 person-years). The vaccine efficacy was 54.0% (90% confidence interval [CI], 13.9 to 75.4; 95% CI, 2.9 to 78.2; P=0.04). Results for the total vaccinated efficacy cohort were similar (vaccine efficacy, 57.0%; 90% CI, 19.9 to 76.9; 95% CI, 9.7 to 79.5; P=0.03). There were more unsolicited reports of adverse events in the M72/AS01E group (67.4%) than in the placebo group (45.4%) within 30 days after injection, with the difference attributed mainly to injection-site reactions and influenza-like symptoms. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups. CONCLUSIONS: M72/AS01E provided 54.0% protection for M. tuberculosis–infected adults against active pulmonary tuberculosis disease, without evident safety concerns. (Funded by GlaxoSmithKline Biologicals and Aeras; ClinicalTrials.gov number, NCT01755598. opens in new tab.)
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    Translational research for tuberculosis elimination : priorities, challenges, and actions
    (Public Library of Science, 2016) Lienhardt, Christian; Lonnroth, Knut; Menzies, Dick; Balasegaram, Manica; Chakaya, Jeremiah; Cobelens, Frank; Cohn, Jennifer; Denkinger, Claudia M.; Evans, Thomas G.; Kallenius, Gunilla; Kaplan, Gilla; Kumar, Ajay M. V.; Matthiessen, Line; Mgone, Charles S.; Mizrahi, Valerie; Mukadi, Ya-diul; Nguyen, Viet Nhung; Nordstrom, Anders; Sizemore, Christine F.; Spigelman, Melvin; Squire, S. Bertel; Swaminathan, Soumya; Van Helden, Paul D.; Zumla, Alimuddin; Weyer, Karin; Weil, Diana; Raviglione, Mario
    Summary Points: • The WHO End TB Strategy, endorsed by the World Health Assembly in May 2014, has the ambitious goal of ending the global tuberculosis (TB) epidemic by 2035, with targets of a 95% decline in deaths due to TB (compared with 2015) and a 90% reduction in incidence of TB to ten cases/100,000 or less and no TB-affected household experiencing catastrophic costs due to TB. • Achieving this goal will only be possible through the development and rapid uptake of new tools, including rapid point-of-care diagnostics, safe and shorter treatment of latent TB infection and disease, and an efficacious TB vaccine, combined with efficient health systems and care provision, and actions on the social determinants of TB. • Research for TB elimination requires an intensification of efforts across a continuum from fundamental research to clinical, epidemiological, implementation, health system, and social science research. • Enhancing research along the full spectrum, from basic to implementation, and strengthening research capacity, particularly in low- and middle-income countries severely affected by the TB epidemics, is crucial for TB elimination. • The creation of a research-enabling environment that fosters and rewards high-quality research requires a broad-based, concerted effort by national governments and international donors to develop and promote TB research and research capacity at the country level and the effective engagement of all stakeholders.