ArticlesEffect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness
Introduction
Randomised controlled trials and case-control studies have shown consistently high efficacy of BCG vaccination against severe forms of childhood tuberculosis, principally miliary disease and meningitis, but variable efficacy against pulmonary tuberculosis in adults.1, 2, 3, 4, 5 Increases in tuberculous meningitis and mycobacterial glandular disease were reported after BCG vaccination was discontinued in Sweden and the former Czechoslovakia.6, 7, 8 BCG also prevents leprosy.9 More controversially, it might reduce childhood mortality from other causes, perhaps because BCG promotes a T-helper-1 immune response.10, 11 The studies whose results showed high efficacy against severe childhood tuberculosis have lent support to the view that BCG should continue to be used in countries where the disease remains a substantial public-health problem, and roughly 100 million doses are given to infants every year.
However, the evidence for efficacy from trials is not, on its own, sufficient to justify BCG vaccination on its present large scale. That argument needs an assessment of the number of cases and deaths prevented in relation to effort and cost. We have used information about efficacy together with data for risk of severe childhood tuberculosis to assess, for all countries and territories where BCG vaccine is routinely administered to infants, the number of cases of tuberculous meningitis and miliary tuberculosis expected, with and without BCG vaccination, in children born in 2002. This analysis leads to estimates of the numbers of cases prevented by country, by region, and for the whole world.
Section snippets
Methods
We assessed the annual risk of infection for tuberculosis by country and the risk of tuberculous meningitis and miliary tuberculosis in children after infection, and we have updated earlier meta-analyses of BCG efficacy. To see whether BCG vaccination is good value for money in comparison with other health programmes, we have calculated the cost of vaccination per case and death prevented, and the cost per year of healthy life gained.
Results
According to the methods described, the BCG vaccinations given to 100·5 million of the 132·8 million children born in 2002 would have prevented almost 30 000 cases of tuberculous meningitis, or one case for roughly every 3500 inoculations (table 4). These vaccinations will also have prevented nearly 11 500 cases of miliary tuberculosis, or one case for roughly every 9300 inoculations. Most of the cases would have been prevented in southeast Asia (46%), Africa (27%, both African regions
Discussion
The 100 million doses of BCG vaccine given to children every year prevent about 40 000 cases of tuberculous meningitis and miliary tuberculosis before these children reach their fifth birthdays, or roughly one case prevented for every 2500 inoculations. Worldwide, the cost of vaccination is US$200 or less per year of healthy life gained. The cost per DALY gained in every region of the world is much less than the average annual income per head (eg, gross national income ⩽US$735 in low income
References (74)
- et al.
Protective effect of BCG against TB meningitis and miliary TB: a meta-analysis
Int J Epidemiol
(1993) - et al.
Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature
JAMA
(1994) Field trials of tuberculosis vaccines: how could we have done them better?
Control Clin Trials
(1994)BCG vaccines and vaccination
- et al.
The efficacy of Bacillus Calmette-Guérin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature
Pediatrics
(1995) - et al.
The impact of changing BCG coverage on tuberculosis incidence in Swedish-born children between 1969 and 1989
Tuber Lung Dis
(1992) - et al.
Atypical mycobacteria in extrapulmonary disease among children. Incidence in Sweden from 1969 to 1990, related to changing BCG- vaccination coverage
Tuber Lung Dis
(1995) - et al.
Six years' experience with the discontinuation of BCG vaccination. 4. Protective effect of BCG vaccination against the Mycobacterium avium intracellulare complex
Tuber Lung Dis
(1994) - et al.
Efficacy of BCG vaccine against leprosy and tuberculosis in northern Malawi
Lancet
(1992) - et al.
BCG vaccination among West African infants is associated with less anergy to tuberculin and diphtheria-tetanus antigens
Vaccine
(2001)
Low birth weight infants and Calmette-Guérin bacillus vaccination at birth: community study from Guinea-Bissau
Pediatr Infect Dis J
World population prospects: the 2002 Revision
National tuberculosis prevalence survey, 2002, Cambodia
Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country
JAMA
The growing burden of tuberculosis: global trends and interactions with the HIV epidemic
Arch Intern Med
The relationship between the risk of tuberculous infection and the risk of developing infectious tuberculosis
Bull Int Union Tuberc Lung Dis
Infectiousness of Mycobacterium tuberculosis in HIV-1-infected patients with tuberculosis: a prospective study
Lancet
Nationwide random survey for the epidemiology of tuberculosis in 1990
Report on Nationwide Random Survey for the Epidemiology of Tuberculosis in 2000
The 1997 Nationwide Tuberculosis Prevalence Survey in the Philippines
Int J Tuberc Lung Dis
BCG coverage and the annual risk of tuberculosis infection over a 14-year period in the Philippines assessed from the Nationwide Prevalence Surveys
Int J Tuberc Lung Dis
The seventh nationwide tuberculosis prevalence survey in Korea, 1995
Int J Tuberc Lung Dis
Tuberculosis and the HIV epidemic: increasing annual risk of tuberculous infection in Kenya, 1986–1996
Am J Public Health
Tuberculosis control in the era of the HIV epidemic: risk of tuberculosis infection in Tanzania, 1983–1998
Int J Tuberc Lung Dis
Tanzanian National Tuberculin Survey, 4th Round Results of Interim Analysis of 12 Regions. Tuberculosis Surveillance Research Unit Progress Report 2003-Volume II
The Hague: KNCV Tubercuclosis Foundation
Risk of infection with Mycobacterium tuberculosis in Malawi: national tuberculin survey 1994
Int J Tuberc Lung Dis
[Annual risk of tuberculosis infection in Madagascar: study from 1991 to 1994]
Bull Soc Pathol Exot
Trend in the annual risk of tuberculous infection in Egypt, 1950–1996
Int J Tuberc Lung Dis
Prevalence and annual risk of tuberculosis infection in Laos
Int J Tuberc Lung Dis
Annual risk of tuberculous infection in four defined zones of India: a comparative picture
Int J Tuberc Lung Dis
Methodological issues in the estimation of the tuberculosis problem from tuberculin surveys
Tuber Lung Dis
The effect of tuberculosis control in China
Lancet
Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli
Lancet
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