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.

Keywords:tuberculosis, BCG vaccines, prevention, vaccine effectiveness, vaccine efficacy, cohort study

Funding. The study had no sponsor support.

Conflict of interests. The authors declare no conflict of interests.

For citation: Favorov M.O., Belilovsky E.M., Tursynbaeva A.S., Ismailov Sh.Sh. The effectiveness of three commercially available Bacillus Calmette-Guerin vaccines for the prevention of tuberculosis among children: results of a cohort, controlled, retrospective analysis. Infektsionnye bolezni: novosti, mneniya, obuchenie [Infectious Diseases: News, Opinions, Training]. 2020; 9 (1): 8-18. doi: 10.33029/2305-3496-2020-9-1-8-18 (in Russian)

References

1. Favorov M., Ali M., Tursunbayeva A., Aitmagambetova I., Kilgore P., Ismailov S., Chorba T. Comparative tuberculosis (TB) prevention effectiveness of Bacillus Calmette-Guerin (BCG) vaccines from different producers among children. PLOSONE 2012. URL:https://doi.org/10.1371/journal.pone.0032567

2. Belilovskiy E., Borisov S., Dadu A., Favorov M. Implementation of the Computerized TB Surveillance in National Tuberculosis program. Int J Tuberc Lung Dis. The 3rd Congress of IUATLD. European Regionю 14th National Congress on Lung Diseases. June, 2004. Moscow, Abstract book. Abstract #222.

3. Colditz G., Brewer T., Berkey C., Wilson M., Burdick E., Fineberg H. Efficacy of BCG Vaccine in the Prevention of Tuberculosis. Meta-analysis of published literature. JAMA. 1994. 271: 698-702.

4. URL: https://www.who.int/immunization/BCG_8May2008_RU.pdf ("BCG vaccine. WHO Position") (in Russian), date of reference 09.08.2019

5. Comstock G.W. Simple, practical ways to assess the protective efficacy of a new tuberculosis vaccine. Clin Infect Dis. 2000; 30 (Suppl 3): S250-3.

6. Romanus V. Tuberculosis in bacillus Calmette-Guerin immunized and non-immunized children in Sweden: a ten years evaluation following cessation of general bacillus Calmette-Guerin immunization of the newborn in 1975. Pediatr Infect Dis J. 1987; 6: 272-80.

7. Mackenzie R., Dixon A.K. Measuring the effects of imaging: an evaluative framework. Clin Radiol. 1995; 50 (8): 513-8.

8. https://www.healthcare-economist.com/2016/01/25/efficacy-vs-effectiveness-vs-efficiency/ (date of reference 09.08.2019)

9. Padungchan S., Konjanart S., Kasiratta S., Daramas S., ten Dam H.G. The effectiveness of BCG vaccination of the newborn against childhood tuberculosis in Bangkok. Bull World Health Organ. 1986; 64: 247-58.

10. Tidjani O., Amedome A., ten Dam H.G. The protective effect of BCG vaccination of the newborn against childhood tuberculosis in an African community. Tubercle. 1986; 67: 269-81.

11. Knowledge heals. 60 years of useless TB vaccination. https://glagolas.livejournal.com/126884.html (date of reference 09.08.2019) (in Russian)

12. WHO/UNICEF Review of National Immunization Coverage 19802007, Kazakhstan, 2008.

13. Statistical TB review for the Republic of Kazakhstan / Ed. Sh.Sh. Ismailova. Almaty; 2009: 65 p. (in Russian)

14. Agency on Statistics of Republic of Kazakhstan. http://www.stat.kz (in Russian)

15. Smith P.G., Morrow R.H. (eds.). Field trials of health interventions in developing countries. A Toolbox. 2nd ed. London: Macmillan Education Limited; 1996.

16. Belilovsky E.M., Borisov S.E., Rybka L.N. TB surveillance in the city of Moscow and prospects for its development. Tuberkulez i sotsial’no znachimye zabolevaniya [Tuberculosis and Socially Significant Diseases]. 2017; (1): 4-13. (in Russian)

17. Shapiro C., Cook N., Evans D., et al. A case-control study of BCG and childhood tuberculosis in Cali, Colombia. Int J Epidemiol. 1985; 14: 441-6.

18. Sirinavin S., Chotpitayasunondh T., Suwanjutha S., Sunakorn P., Chantarojanasiri T. Protective efficacy of neonatal Bacillus Calmette-Guerin vaccination against tuberculosis. Pediatr Infect Dis J. 1991; 10: 359-65.

19. Comstock G.W. Field trials of tuberculosis vaccines: how could we have done them better? Control Clin Trials. 1994; 15: 247-76.

20. von Reyn C.F. Routine childhood Bacillus Calmette-Guerin immunization and HIV infection. Clin Infect Dis. 2006; 42: 559-61.

21. Favorov M., Belilovsky E., Aitmagambetova I., Ismailov S., White M. E., Chorba T. Tuberculosis deaths averted by implementation of the DOTS strategy in Kazakhstan. Int J Tuberc Lung Dis. 2010; 14 (12): 1582-8.

22. Aksenova V.A., Baryshnikova L.A., Sevostyanova T.A., Klevno N.I. Tuberculosis in children in Russia and the objectives of the TB service and general pediatric service for the prevention and early detection of disease. Tuberkulez i bolezni legkikh [Tuberculosis and Lung Disease]. 2014; (3): 40-6. (in Russian)

23. Fine PE. BCG vaccination against tuberculosis and leprosy. Br Med Bull. 1988; 44: 691-703.

24. Rodrigues L.C., Diwan V.K., Wheeler J.G. Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis. Int J Epidemiol. 1993; 22 (6): 1154-8.

25. Mangtani P., Abubakar I., Ariti C., Beynon R., Pimpin L., Fine P.E.M., et al. Protection by BCG vaccine against tuberculosis: A systematic review of randomized controlled trials. Clin Infect Dis. 2014;58 (4): 470-80.

26. Belilovsky E.M., Kochetkova E.Ya., Seltsovsky P.P., Kotova E.A., Rybka L.N., Rostovtsev S.A., et al. TB incidence in Moscow. In: TB control in the city of Moscow. Analytical review of statistical indicators for tuberculosis. 2017, ed. by Bogorodskaya E.M., Litvinov V.I., Belilovsky E.M. Moscow: MNPTSBT; 2018: 33-66. (in Russian)

27. Ilchenko A.D., Bogorodskaya E.M., Mokhireva L.V. Organization of TB care for the homeless, foreign and nonresident citizens in the city of Moscow. In: TB control in the city of Moscow. Analytical review of statistical indicators for tuberculosis. 2017, ed. by Bogorodskaya E.M., Litvinov V.I., Belilovsky E.M. Moscow: MNPTSBT; 2018: 207-52. (in Russian)

28. Fine P.E. BCG: the challenge continues. Scand J Infect Dis. 2001; 33: 243-5.

29. Delogu G., Fadda G. The quest for a new vaccine against tuberculosis. J Infect Dev Ctries. 2009; 3: 5-15.

30. Behr M.A., Wilson M.A., Gill W.P., et al. Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science. 1999; 284: 1520-3.

31. Brosch R., Gordon S.V., Garnier T., et al. Genome plasticity of BCG and impact on vaccine efficacy. Proc Natl Acad Sci. USA. 2007; 104: 5596-601.

32. Svenson S., Kallenius G., Pawlowski A., Hamasur B. Towards new tuberculosis vaccines. Hum Vaccin. 2010; 6: 309-17.

33. Russell D.G., Barry C.E. 3rd, Flynn J.L. Tuberculosis: What we don’t know can, and does, hurt us. Science. 2010; 328: 852-6.

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)

CHIEF EDITOR
Aleksandr V. Gorelov
Academician of the Russian Academy of Sciences, MD, Head of Infection Diseases and Epidemiology Department of the Scientific and Educational Institute of Clinical Medicine named after N.A. Semashko ofRussian University of Medicine, Ministry of Health of the Russian Federation, Professor of the Department of Childhood Diseases, Clinical Institute of Children's Health named after N.F. Filatov, Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Deputy Director for Research, Central Research Institute of Epidemiology, Rospotrebnadzor (Moscow, Russian Federation)

Journals of «GEOTAR-Media»