Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness
Abstract
Background BCG vaccine has shown consistently high efficacy against childhood tuberculous meningitis and miliary tuberculosis, but variable efficacy against adult pulmonary tuberculosis and other mycobacterial diseases. We assess and compare the costs and effects of BCG as an intervention against severe childhood tuberculosis in different regions of the world.Methods We calculated the number of tuberculous meningitis and miliary tuberculosis cases that have been and will be prevented in all children born in 2002, by combining estimates of the annual risk of tuberculosis infection, the proportion of infections that lead to either of these diseases in unvaccinated children, the number of children vaccinated, and BCG efficacy.Findings We estimated that the 100.5 million BCG vaccinations given to infants in 2002 will have prevented 29,729 cases of tuberculous meningitis (5th-95th centiles, 24,063-36,192) in children during their first 5 years of life, or one case for every 3435 vaccinations (2771-4177), and 11,486 cases of miliary tuberculosis (7304-16,280), or one case for every 9314 vaccinations (6172-13,729). The numbers of cases prevented would be highest in South East Asia (46%), sub-Saharan Africa (27%), the western Pacific region (15%), and where the risk of tuberculosis infection and vaccine coverage are also highest. At US2-3 dollars per dose, BCG vaccination costs US206 dollars (150-272) per year of healthy life gained.Interpretation BCG vaccination is a highly cost-effective intervention against severe childhood tuberculosis; it should be retained in high-incidence countries as a strategy to supplement the chemotherapy of active tuberculosis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
BCG vaccination prevents severe disease manifestations such as tuberculous meningitis and miliary TB in children.
“BCG vaccination prevents severe disease manifestations such as tuberculous meningitis and miliary TB in children61”
From A guide to vaccinology: from basic principles to new developments (2021) · cites this paper as [61]
Cites
Disease Control Priorities in Developing Countries
Jamison, D., Mosley, W. H., Measham, A., & Bobadilla, J. L. (1993) · World Bank, Washington, DC eBooks · doi:10.1596/0-1952-0990-7 · Cited by 3,714 · see citing works
Dye, C., Scheele, S., >Dolin, P., Pathania, V. S., Raviglione, M. C., & for the WHO Global Surveillance and Monitoring Project (1999) · JAMA · doi:10.1001/jama.282.7.677 · Cited by 2,955 · see citing works
Self-citationON ESTIMATING THE RELATION BETWEEN BLOOD GROUP AND DISEASE
Woolf, B. (1955) · Annals of Human Genetics · doi:10.1111/j.1469-1809.1955.tb01348.x · Cited by 2,739 · see citing works
The Growing Burden of Tuberculosis: <b>Global Trends and Interactions With the HIV Epidemic</b>
Corbett, E. L., Watt, C. J., Walker, N., Maher, D., Williams, B. G., Raviglione, M. C., & Dye, C. (2003) · Archives of Internal Medicine · doi:10.1001/archinte.163.9.1009 · Cited by 2,553 · see citing works
Self-citationEfficacy of BCG Vaccine in the Prevention of Tuberculosis
Colditz, G. A. (1994) · JAMA · doi:10.1001/jama.1994.03510330076038 · Cited by 2,001 · see citing works
Economic foundations of cost-effectiveness analysis
Garber, A. M., & Phelps, C. E. (1997) · Journal of Health Economics · doi:10.1016/s0167-6296(96)00506-1 · Cited by 768 · see citing works
Colditz, G. A., Berkey, C. S., Mosteller, F. C., Brewer, T. F., Wilson, M. E., Burdick, E., & Fineberg, H. V. (1995) · PEDIATRICS · doi:10.1542/peds.96.1.29 · Cited by 759 · see citing works
Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli
Behr, M. A., Warren, S., Salamon, H., Hopewell, P. C., Ponce‐de‐León, A., Daley, C. L., & Small, P. M. (1999) · The Lancet · doi:10.1016/s0140-6736(98)03406-0 · Cited by 751 · see citing works
Protective Effect of BCG against Tuberculous Meningitis and Miliary Tuberculosis: A Meta-Analysis
Rodrigues, L. C., Diwan, V. K., & Wheeler, J. G. (1993) · International Journal of Epidemiology · doi:10.1093/ije/22.6.1154 · Cited by 654 · see citing works
Tuberculosis; a comprehensive international approach
(1994) · International Journal of Biochemistry · doi:10.1016/0020-711x(94)90047-7 · Cited by 344 · see citing works
BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa
Garly, M., Martins, C. L., Balé, C., Baldé, M. A., Hedegaard, K. L., Gustafson, P., Lisse, I. M., Whittle, H. C., & Aaby, P. (2003) · Vaccine · doi:10.1016/s0264-410x(03)00181-6 · Cited by 339 · see citing works
Long-term Efficacy of BCG Vaccine in American Indians and Alaska Natives
Aronson, N., Santosham, M., Comstock, G. W., et al. (2004) · JAMA · doi:10.1001/jama.291.17.2086 · Cited by 338 · see citing works
Efficacy of BCG vaccine against leprosy and tuberculosis in northern Malawi
Pönnighaus, J. M., Msosa, E., Gruer, P. J. K., et al. (1992) · The Lancet · doi:10.1016/0140-6736(92)90794-4 · Cited by 208 · see citing works
Cost effectiveness of chemotherapy for pulmonary tuberculosis in three sub-Saharan African countries
Murray, C., DeJonghe, E., Chum, H. J., Nyangulu, D. S., Salomão, A. L. S. J., & Styblo, K. (1991) · The Lancet · doi:10.1016/0140-6736(91)92600-7 · Cited by 190 · see citing works
The seventh nationwide tuberculosis prevalence survey in Korea, 1995.
Hong, Y. P., Kim, S. J., Wj, L., Lee, E. K., & Han, Y. C. (1998) · PubMed · Cited by 162 · see citing works
The effect of tuberculosis control in China
(2004) · The Lancet · doi:10.1016/s0140-6736(04)16764-0 · Cited by 156 · see citing works
Romanus, V., Hallander, H. O., Wåhlén, P., Olinder-Nielsen, A. M., Magnusson, P. H. W., & Juhlin, I. (1995) · Tubercle and Lung Disease · doi:10.1016/s0962-8479(05)80028-0 · Cited by 140 · see citing works
Methodological issues in the estimation of the tuberculosis problem from tuberculin surveys
Rieder, H. L. (1995) · Tubercle and Lung Disease · doi:10.1016/0962-8479(95)90552-9 · Cited by 137 · see citing works
Snider, D. E., Rieder, H. L., Combs, D. L., et al. (1988) · The Pediatric Infectious Disease Journal · doi:10.1097/00006454-198804000-00008 · Cited by 118 · see citing works
Miliary tuberculosis in children
HUSSEY, G., MBCHB, CHISHOLM, T., et al. (1991) · The Pediatric Infectious Disease Journal · doi:10.1097/00006454-199111000-00008 · Cited by 114 · see citing works
Low Birth Weight Infants and Calmette-Guérin Bacillus Vaccination at Birth
Roth, A., Jensen, H., Garly, M., et al. (2004) · The Pediatric Infectious Disease Journal · doi:10.1097/01.inf.0000129693.81082.a0 · Cited by 112 · see citing works
Espinal, M., Pérez-Then, E. N., Baéz, J., Hénriquez, L., Fernández, K., Lopez, M. J., Olivo, P., & Reingold, A. L. (2000) · The Lancet · doi:10.1016/s0140-6736(99)04402-5 · Cited by 105 · see citing works
Field trials of tuberculosis vaccines: How could we have done them better?
Comstock, G. W. (1994) · Controlled Clinical Trials · doi:10.1016/0197-2456(94)90042-6 · Cited by 100 · see citing works
[Epidemiology of tuberculosis].
Durieux, P. (1990) · PubMed · Cited by 95 · see citing works
(1994) · Tubercle and Lung Disease · doi:10.1016/0962-8479(94)90003-5 · Cited by 87 · see citing works
Romanus, V., Svensson, Å., & Hallander, H. O. (1992) · Tubercle and Lung Disease · doi:10.1016/0962-8479(92)90149-e · Cited by 86 · see citing works
Six years' experience with the discontinuation of BCG vaccination
Trnka, L., Dănkovã, D., & Svandova, E. (1994) · Tubercle and Lung Disease · doi:10.1016/0962-8479(94)90080-9 · Cited by 82 · see citing works
Odhiambo, J. A., Borgdorff, M. W., Kiambih, F. M., Kibuga, D., Kwamanga, D., Nganga, L., Agwanda, R., Kalisvaart, N. A., Misljenovic, O., Nagelkerke, N. J. D., et al. (1999) · American Journal of Public Health · doi:10.2105/ajph.89.7.1078 · Cited by 76 · see citing works
Filho, V. W., de Castilho, E. A., Rodrigues, L. C., et al. (1990) · PubMed · Cited by 69 · see citing works
[Epidemiology of tuberculosis].
Bermejo, M. A. M., Clavera, I., Michel de la Rosa, F., et al. (2007) · PubMed · Cited by 66 · see citing works
The 1997 Nationwide Tuberculosis Prevalence Survey in the Philippines.
Tupasi, T. E., Radhakrishna, S., Rivera, A. B., et al. (1999) · PubMed · Cited by 65 · see citing works
Barker, R. D. (2012) · Medicine · doi:10.1016/j.mpmed.2012.03.002 · Cited by 58 · see citing works
Miceli, I. N. P., Kantor, I. N., COLAIÁCOVO, D., et al. (1988) · International Journal of Epidemiology · doi:10.1093/ije/17.3.629 · Cited by 54 · see citing works
Does BCG vaccine prevent tuberculous meningitis?
Thilothammal, N., Krishnamurthy, P. V., Runyan, D. K., et al. (1996) · Archives of Disease in Childhood · doi:10.1136/adc.74.2.144 · Cited by 53 · see citing works
Tuberculosis in children and adolescents: California, 1985 to 1995
Lobato, M. N., Cummings, K., WILL, D., et al. (1998) · The Pediatric Infectious Disease Journal · doi:10.1097/00006454-199805000-00012 · Cited by 52 · see citing works
Cost savings from alternative treatments for tuberculosis
Barnum, H. N. (1986) · Social Science & Medicine · doi:10.1016/0277-9536(86)90212-1 · Cited by 48 · see citing works
Epidemiology of tuberculosis in children.
Chaulet, P. (1992) · PubMed · Cited by 46 · see citing works
Camargos, P. A. M., Guimarães, M. D. C., & Antunes, C. (1988) · International Journal of Epidemiology · doi:10.1093/ije/17.1.193 · Cited by 45 · see citing works
Garly, M., Balé, C., Martins, C. L., et al. (2001) · Vaccine · doi:10.1016/s0264-410x(01)00339-5 · Cited by 39 · see citing works
Effectiveness of BCG vaccination against tuberculous meningitis.
Awasthi, S., & Moin, S. (1999) · PubMed · Cited by 38 · see citing works
Does B.C.G. vaccination prevent or postpone the occurrence of tuberculous meningitis?
Mittal, S. K., Aggarwal, V., Rastogi, A., et al. (1996) · The Indian Journal of Pediatrics · doi:10.1007/bf02730815 · Cited by 36 · see citing works
Case-control study on evaluation of BCG vaccination of newborn in Rangoon, Burma
Myint, T.-T., Win, H., Aye, H. H., et al. (1987) · Annals of Tropical Paediatrics · doi:10.1080/02724936.1987.11748499 · Cited by 32 · see citing works
Tupasi, T. E., Radhakrishna, S., Pascual, M. L., et al. (2000) · PubMed · Cited by 31 · see citing works
Stopping routine vaccination for tuberculosis in schools
Fine, P. (2005) · BMJ · doi:10.1136/bmj.331.7518.647 · Cited by 31 · see citing works
Self-citationAnnual risk of tuberculous infection in four defined zones of India: a comparative picture.
Chadha, V. K., Agarwal, S., Kumar, P., et al. (2005) · PubMed · Cited by 25 · see citing works
de March-Ayuela, P. (1994) · Tubercle and Lung Disease · doi:10.1016/0962-8479(94)90115-5 · Cited by 23 · see citing works
Transmission of tubercle bacilli
van Geuns, H. A. (1969) · Tubercle · doi:10.1016/0041-3879(69)90011-7 · Cited by 23 · see citing works
Trend in the annual risk of tuberculous infection in Egypt, 1950-1996.
Ibiary, S. E., Coster, E. J. M. D., Tolba, F. M., et al. (1999) · PubMed · Cited by 21 · see citing works
Risk of infection with Mycobacterium tuberculosis in Malawi: national tuberculin survey 1994.
Salaniponi, F. M. L., Kwanjana, J. H., ten Veen, J. H., et al. (2004) · PubMed · Cited by 21 · see citing works
(2001) · PubMed · Cited by 20 · see citing works
A cost–benefit analysis of BCG revaccination in the Czech Republic
Pathania, V. S. (1999) · Vaccine · doi:10.1016/s0264-410x(98)00462-9 · Cited by 17 · see citing works
Prevalence and annual risk of tuberculosis infection in Laos.
Arnadottir, T., Soukaseum, H., Vangvichit, P., et al. (2001) · PubMed · Cited by 16 · see citing works
Epidemiological evaluation of BCG vaccine efficacy in Delhi--1989.
Rs, S., Srivastava, D. K., Aa, S., et al. (1989) · PubMed · Cited by 15 · see citing works
Methodological Considerations in Case-Control Studies to Evaluate BCG Vaccine Effectiveness
Wünsch‐Filho, V., Moncau, J. E. C., & Nakao, N. (1993) · International Journal of Epidemiology · doi:10.1093/ije/22.1.149 · Cited by 13 · see citing works
The Epidemiology of Tuberculosis in Children
Marais, B. J., & Khatami, A. (2017) · Journal of Pediatric Infectious Diseases · doi:10.1055/s-0037-1606601 · Cited by 13 · see citing works
Murtagh, K. (1980) · The Lancet · doi:10.1016/s0140-6736(80)90973-3 · Cited by 12 · see citing works
Paula, A. D. (1958) · PubMed · Cited by 11 · see citing works
Spyridis, P., Tsolia, M. N., Gelesme, A., et al. (2003) · PubMed · Cited by 7 · see citing works
Case series evaluation of BCG vaccine efficacy against tubercular meningitis in children in Delhi.
Bhattacharjee, J., Sharma, R., Singh, J., et al. (1993) · PubMed · Cited by 6 · see citing works
[Annual risk of tuberculosis infection in Madagascar: study from 1991 to 1994].
Champetier de Ribes, G., Ranaivoson, G., Rakotoherisoa, E., et al. (1997) · PubMed · Cited by 6 · see citing works
Sp, Z., Maldhure, B. R., Ag, D., et al. (1996) · PubMed · Cited by 4 · see citing works
[Protective effect of intradermal BCG on tuberculous meningitis].
Costa, M. D. C., El, M., & Ll, P. (1991) · PubMed · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Global Burden of Latent Tuberculosis Infection: A Re-estimation Using Mathematical Modelling
Houben, R. M. G. J., & Dodd, P. J. (2016) · PLOS Medicine · doi:10.1371/journal.pmed.1002152 · Cited by 2,054 · see citing works
Kleinnijenhuis, J., Quintin, J., Preijers, F., Joosten, L. A. B., Ifrim, D. C., Saeed, S., Jacobs, C., van Loenhout, J., de Jong, D., Stunnenberg, H. G., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1202870109 · Cited by 1,728 · see citing works
A guide to vaccinology: from basic principles to new developments
Pollard, A. J., & Bijker, E. M. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-020-00479-7 · Cited by 1,593 · see citing works
Pai, M., Behr, M. A., Dowdy, D., Dheda, K., Divangahi, M., Boehme, C. C., Ginsberg, A., Swaminathan, S., Spigelman, M., Getahun, H., et al. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.76 · Cited by 1,270 · see citing works
Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials
Mangtani, P., Abubakar, I., Ariti, C., Beynon, R., Pimpin, L., Fine, P. E. M., Rodrigues, L. C., Smith, P. G., Lipman, M., Whiting, P. F., et al. (2014) · Clinical Infectious Diseases · doi:10.1093/cid/cit790 · Cited by 995 · see citing works
Self-citationPerez-Velez, C. M., & Marais, B. J. (2012) · New England Journal of Medicine · doi:10.1056/nejmra1008049 · Cited by 572 · see citing works
Tuberculous meningitis: more questions, still too few answers
Thwaites, G. E., van Toorn, R., & Schoeman, J. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70168-6 · Cited by 482 · see citing works
Newton, S. M., Brent, A. J., Anderson, S., Whittaker, E., & Kampmann, B. (2008) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(08)70182-8 · Cited by 480 · see citing works
Nguipdop-Djomo, P., Heldal, E., Rodrigues, L. C., Abubakar, I., & Mangtani, P. (2016) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(15)00400-4 · Cited by 202 · see citing works
Eisenhut, M., Paranjothy, S., Abubakar, I., Bracebridge, S., Lilley, M., Mulla, R., Lack, K., Chalkley, D., & McEvoy, M. (2009) · Vaccine · doi:10.1016/j.vaccine.2009.08.031 · Cited by 85 · see citing works
Strain-specific differences in the genetic control of two closely related mycobacteria
Di Pietrantonio, T., Hernandez, C., Girard, M., Verville, A., Orlova, M., Belley, A., Behr, M. A., Loredo-Osti, J. C., & Schurr, E. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1001169 · Cited by 21 · see citing works
- Authors
- Trunz, B. B., Fine, P., & Dye, C.
- Affiliations
- London School of Hygiene & Tropical Medicine (GB)
- World Health Organization (CH)
- ORCID
- Dye, C
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2006-04
- Volume
- 367
- Issue
- 9517
- Pages
- 1173-1180
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2106682613
- Cited by
- 1,114
- References
- 62
- Citations by year
- 2026: 33 · 2025: 51 · 2024: 48 · 2023: 58 · 2022: 49 · 2021: 66 · 2020: 67 · 2019: 54 · 2018: 43 · 2017: 60 · 2016: 64 · 2015: 62 · 2014: 68 · 2013: 64 · 2012: 58
- FWCI
- 6.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- BCG vaccine, pediatric tuberculosis, tuberculous meningitis, miliary tuberculosis, vaccine efficacy, cost-effectiveness, vaccination coverage, tuberculosis incidence, infant immunization, global tuberculosis burden
- MeSH terms
- BCG Vaccine, Child, Preschool, Cost-Benefit Analysis, Female, Humans, Infant, Male, Risk Factors, Tuberculosis, Meningeal, Tuberculosis, Miliary, Global Health
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
