The effectiveness of three commercially available Bacillus Calmette-Guerin vaccines for the prevention of tuberculosis among children: Results of a cohort, controlled, retrospective analysis

Abstract

The study analyzed aggregated national data on Bacillus Calmette-Guerin (BCG) vaccination of newborns against tuberculosis (TB) and information obtained by case-based computer surveillance data for TB in the Republic of Kazakhstan. Over nearly two decades, coverage of newborns vaccinated against TB ranged from 86 to 99%, except for a 7-month period from September 2004 to March 2005, when the BCG vaccine was not administered. Beginning in September 2002, newborns received a BCG preparation produced by one of three different manufacturers (NPO “Mikrogen” Russia; Institute of Immunology and Virology, Torlak, Serbia; and BCG Laboratory, Japan) or no BCG vaccine. The presence of an “unvaccinated” cohort of newborns and the availability of data from a computerized system for registering and managing TB cases in the country made it possible to conduct a retrospective comparative cohort analysis of the effectiveness of BCG vaccination for preventing TB in children. Aim. The interpretation and analysis of epidemiological information obtained in the study of measures to prevent the spread of TB through BCG vaccination. Material and methods. This retrospective analysis compared the efficacy of BCG vaccination of newborns for preventing childhood TB over four 7-month time periods (n=618 658 observations). Three cohorts received vaccine produced by one of three manufacturers; another cohort was unvaccinated. The TB surveillance system made it possible to monitor the children within each cohort for 3 years. The surveillance system registered all new cases of TB, including cases where the diagnosis was established by clinical and radiological methods, patients with laboratory-confirmed TB, and patients with TB meningitis. For each vaccinated cohort, prophylactic efficacy was calculated based on the relative risk of the incidence of new TB cases compared to the unvaccinated cohort. Results. Data on the efficacy and effectiveness of BCG vaccination of newborns were compared with findings in the unvaccinated group. All vaccines showed a protective effect, but there were differences in the degrees of effectiveness and efficacy of the tested BCG vaccines. The Japanese, Serbian, and Russian vaccines were effective in preventing clinically radiologically confirmed cases of TB in 69, 43, and 22% respectively. The same vaccines have been shown to prevent laboratory-confirmed TB cases, with efficacy of 92, 82, and 51% respectively. Discussion. The results obtained help to justify the feasibility of the existing BCG immunization program in countries with a continuing high and average incidence of tuberculosis, as well as in territories with a significant level of migration. The level of immunogenicity and effectiveness of BCG vaccines from different manufacturers may differ significantly. When determining the national immunization policy, the effectiveness of BCG products from different manufacturers must be taken into account.