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Question clinique
In HIV-negative adults, aged 18-50years, who are infected with latent tuberculosis, does a novel vaccine prevent the development of active disease?
L’Essentiel
In patients with latent tuberculosis (TB), a TB vaccine (M72/AS01E) reduces the likelihood that they will develop active TB (number needed to treat [NNT] = 333 over 3 years) with no effect on mortality. It is unclear whether this vaccine would be cost-effective at the population level. 1b
Référence
Plan de l'etude: Randomized controlled trial (double-blinded)
Financement: Industry
Cadre: Population-based
Sommaire
M. tuberculosis infection remains an important public health threat, particularly in low-income countries. In this study, set in Kenya, South Africa, and Zambia, 3289 adults aged 18 to 50 years who were HIV-negative, had a positive interferon-gamma release result for infection with M. tuberculosis, and no signs of active disease were randomized to receive either 2 doses of the M72/AS01E vaccine given 1 month apart or matching placebo. All but 2 patients randomized to the vaccine group received the first injection, but 243 failed to get the second injection. Groups were balanced at the beginning of the study, and approximately two-thirds of participants were 30 years or younger. The primary analysis included only the patients who received both injections, a per-protocol analysis that inflates benefit compared with the preferred intention-to-treat analysis. The authors describe a 50% vaccine efficacy rate, which is, of course, a relative measure and also inflates the apparent benefit. More clinically meaningful are the absolute risks of developing TB, which were 0.3% in the vaccine group and 0.6% in the placebo group during the 3 years after immunization (P < .05; NNT = 333 to prevent one case of active TB over 3 years). There was odd clustering by age, with 3 cases in the vaccine group and 16 in the placebo group among patients 25 years or younger, 6 vs 2 among those 26 to 30 years, and 4 vs 8 among patients older than 30 years. Thus, using a cutoff of 25 years, the vaccine appears to be highly effective in young patients and totally ineffective in the older group, but using a cutoff of 30 years, the efficacy is similar between older and younger patients. Analyzing age as a continuous variable, though, found no association with vaccine effectiveness. The vaccine was generally safe, and there was no significant difference in mortality between groups. Immunogenicity persisted throughout the 3-year study in the subset of patients in whom it was studied. The study was not powered to detect an effect on mortality.
Reviewer
Mark H. Ebell, MD, MS
Professor
University of Georgia
Athens, GA