Non-specific effects of vaccination on child survival: prospective cohort study in Burkina Faso
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《英国医生杂志》
1 Institut de Recherche pour le Développement, Laboratoire Population, Environnement et Développement, BP 64501, 34394 Montpellier Cedex 5, France, 2 Biostatem, Parc Scientifique G Besse, F 30035 N?mes, France, 3 Unité d'Etudes et de Recherche en Démographie, 03 BP 7118, Ouagadougou 03, Burkina Faso
Correspondence to: J Vaugelade vaugelad@ird.fr
Abstract
Vaccination of children, particularly with measles vaccine, has been associated with reduced child mortality.1-4 In Guinea-Bissau, recipients of one dose of diphtheria, tetanus, and pertussis vaccine had a higher mortality than those who received none of the childhood vaccines.5 We examined the association between vaccination and child mortality in Burkina Faso.
Materials and methods
During 1985-96, 9412 births were registered in the Pissila and Yako regions of Burkina Faso. We excluded 204 stillbirths and 123 infants with no recorded month of birth, leaving 9085 infants.
The death rate of these children was high: 90 per thousand in the first year, and 70 per thousand in the second year. By five years, the cumulative rate was 220 per thousand.
Most of the vaccinated children received either BCG (mean age 4.8 months for BCG before 24 months) followed by diphtheria, tetanus, and pertussis (mean age 6.3 months), or the vaccines simultaneously. Some children were vaccinated with BCG only, more rarely with diphtheria, tetanus, and pertussis only. Before 6 months of age, 45% (4049 of 9085) of the children received BCG or diphtheria, tetanus, and pertussis; 21% (1941 of 9085) were vaccinated between six and 24 months (table 1). Overall, 19% (583 of 3050) of the children aged 6 months and 70% (3892 of 5584) of those aged 24 months who had had one dose of diphtheria, tetanus, and pertussis, received a second dose (mean age 12.8 months); 39% (1531 of 3892) of them received measles vaccine simultaneously. Measles vaccine (mean age 12.7 months) was usually given with yellow fever vaccine.
Table 1 Numbers (percentages) of children vaccinated with BCG or diphtheria, tetanus, and pertussis by 6 and 24 months of age (or end of observation, if occurred before these ages) and numbers (percentages) of deaths analysed (measles censored)
All significant associations between mortality or vaccination and covariates were as expected—for example, the presence of a dispensary in the village was associated with reduced mortality and increased the likelihood of vaccination (table 2).
Table 2 Risk ratios for mortality (6-24 months) and odds ratios for vaccination by selected covariates in children in two regions of Burkina Faso
Vaccination and mortality
The survival curves for vaccinated children from six to 24 months were significantly different to the survival curve for unvaccinated children (figure).
Kaplan-Meier survival curves of children by vaccination status at 6 months of age
Vaccination with BCG was associated with lower mortality when data were analysed by vaccination status (risk ratio 0.37) and vaccination status recorded at the first visit (risk ratio 0.46). Risk ratios for diphtheria, tetanus, and pertussis were similar to BCG (table 3). Adjusted relative risks were also similar (table 3). Results for boys and girls were similar to those for both sexes (table 4). Table 5 shows that the second dose of diphtheria, tetanus, and pertussis was not associated with lower mortality.
Table 3 Non-adjusted and adjusted risk ratios (95% confidence intervals) for mortality for BCG and diphtheria, tetanus, and pertussis vaccines analysed by vaccination status before age 2 years and vaccination status at first visit
Table 4 Non-adjusted and adjusted risk ratios (95% confidence intervals) for mortality by sex for BCG and diphtheria, tetanus and pertussis vaccines analysed by vaccination status at less than 2 years of age and vaccination status at first visit
Table 5 Risk ratios (95% confidence intervals) for mortality for second dose of diphtheria, tetanus, and pertussis vaccine among children vaccinated with BCG
Discussion
Hull HF, Williams PJ, Oldfield F. Measles mortality and vaccine efficacity in rural west Africa. Lancet 1983;1: 972-5.
Koenig MA, Khan MA, Wojtyniak B, Clemens JD, Chakraborty J, Fauveau V. The impact of measles vaccination upon childhood mortality in Matlab, Bandgladesh. Bull WHO 1990;68: 441-7.
Garenne M, Leroy O, Beau JP, Sene I. Efficacity of measles vaccines after controlling for exposure. Am J Epidmiol 1991;338: 183-94.
Vaugelade J. Demographic evaluation of a child health program in Burkina Faso in demographic evaluation of health programmes. Paris: Committee for International Co-operation in National Research in Demography, 1997: 123-30.
Kristensen I, Aaby P, Jensen H. Routine vaccinations and child survival: follow up study in Guinea-Bissau, West Africa. BMJ 2000;321: 1435-9.
Vaugelade J, Poirier J, Guiella G, Ouedrago R. Problématique et méthodologie des observatoires démographiques dans trois zones du Burkina Faso: Pissila, Niangoloko et Yako-Gourcy (1986-1996). Ouagadougou, Burkina Faso: IRD-UERD, 2000.
Jensen H. Analysis of multivariate survival data from longitudinal epidemiological studies: with special reference to the impact of routine immunisation in infancy. PhD Thesis. Denmark: University of Copenhagen, 2002.
Cox. Regression models and life-tables. J Roy Stat Soc Series B, 1972: 187-202.
Fine P. Commentary: an unexpected finding that needs confirmation or rejection. BMJ 2000;321: 1440.
Aaby P, Jensen H, Samb B, Cisse B, Sodeman M, Jakobsen M, et al. Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactived poliovirus: reanalysis of the West Afican studies. Lancet 2003;361: 2183-8.
Vaugelade J. Variations de la mortalité saisonnière avant 5 ans selon le biotope en Afrique intertropicale. African population conference, Dakar, Senegal, International Union for the Scientific Study of the Population. Liège, Belgium: IUSSP, 1988: 3.4.51-61.
Aaby P, Samb B, Simondon F, Seck AM, Knudsen K, Whittle H. Non-specific beneficial effects of measles immunization: analysis of mortality studies from developing countries. BMJ 1995;311: 481-5.(J Vaugelade, demographer1)
Correspondence to: J Vaugelade vaugelad@ird.fr
Abstract
Vaccination of children, particularly with measles vaccine, has been associated with reduced child mortality.1-4 In Guinea-Bissau, recipients of one dose of diphtheria, tetanus, and pertussis vaccine had a higher mortality than those who received none of the childhood vaccines.5 We examined the association between vaccination and child mortality in Burkina Faso.
Materials and methods
During 1985-96, 9412 births were registered in the Pissila and Yako regions of Burkina Faso. We excluded 204 stillbirths and 123 infants with no recorded month of birth, leaving 9085 infants.
The death rate of these children was high: 90 per thousand in the first year, and 70 per thousand in the second year. By five years, the cumulative rate was 220 per thousand.
Most of the vaccinated children received either BCG (mean age 4.8 months for BCG before 24 months) followed by diphtheria, tetanus, and pertussis (mean age 6.3 months), or the vaccines simultaneously. Some children were vaccinated with BCG only, more rarely with diphtheria, tetanus, and pertussis only. Before 6 months of age, 45% (4049 of 9085) of the children received BCG or diphtheria, tetanus, and pertussis; 21% (1941 of 9085) were vaccinated between six and 24 months (table 1). Overall, 19% (583 of 3050) of the children aged 6 months and 70% (3892 of 5584) of those aged 24 months who had had one dose of diphtheria, tetanus, and pertussis, received a second dose (mean age 12.8 months); 39% (1531 of 3892) of them received measles vaccine simultaneously. Measles vaccine (mean age 12.7 months) was usually given with yellow fever vaccine.
Table 1 Numbers (percentages) of children vaccinated with BCG or diphtheria, tetanus, and pertussis by 6 and 24 months of age (or end of observation, if occurred before these ages) and numbers (percentages) of deaths analysed (measles censored)
All significant associations between mortality or vaccination and covariates were as expected—for example, the presence of a dispensary in the village was associated with reduced mortality and increased the likelihood of vaccination (table 2).
Table 2 Risk ratios for mortality (6-24 months) and odds ratios for vaccination by selected covariates in children in two regions of Burkina Faso
Vaccination and mortality
The survival curves for vaccinated children from six to 24 months were significantly different to the survival curve for unvaccinated children (figure).
Kaplan-Meier survival curves of children by vaccination status at 6 months of age
Vaccination with BCG was associated with lower mortality when data were analysed by vaccination status (risk ratio 0.37) and vaccination status recorded at the first visit (risk ratio 0.46). Risk ratios for diphtheria, tetanus, and pertussis were similar to BCG (table 3). Adjusted relative risks were also similar (table 3). Results for boys and girls were similar to those for both sexes (table 4). Table 5 shows that the second dose of diphtheria, tetanus, and pertussis was not associated with lower mortality.
Table 3 Non-adjusted and adjusted risk ratios (95% confidence intervals) for mortality for BCG and diphtheria, tetanus, and pertussis vaccines analysed by vaccination status before age 2 years and vaccination status at first visit
Table 4 Non-adjusted and adjusted risk ratios (95% confidence intervals) for mortality by sex for BCG and diphtheria, tetanus and pertussis vaccines analysed by vaccination status at less than 2 years of age and vaccination status at first visit
Table 5 Risk ratios (95% confidence intervals) for mortality for second dose of diphtheria, tetanus, and pertussis vaccine among children vaccinated with BCG
Discussion
Hull HF, Williams PJ, Oldfield F. Measles mortality and vaccine efficacity in rural west Africa. Lancet 1983;1: 972-5.
Koenig MA, Khan MA, Wojtyniak B, Clemens JD, Chakraborty J, Fauveau V. The impact of measles vaccination upon childhood mortality in Matlab, Bandgladesh. Bull WHO 1990;68: 441-7.
Garenne M, Leroy O, Beau JP, Sene I. Efficacity of measles vaccines after controlling for exposure. Am J Epidmiol 1991;338: 183-94.
Vaugelade J. Demographic evaluation of a child health program in Burkina Faso in demographic evaluation of health programmes. Paris: Committee for International Co-operation in National Research in Demography, 1997: 123-30.
Kristensen I, Aaby P, Jensen H. Routine vaccinations and child survival: follow up study in Guinea-Bissau, West Africa. BMJ 2000;321: 1435-9.
Vaugelade J, Poirier J, Guiella G, Ouedrago R. Problématique et méthodologie des observatoires démographiques dans trois zones du Burkina Faso: Pissila, Niangoloko et Yako-Gourcy (1986-1996). Ouagadougou, Burkina Faso: IRD-UERD, 2000.
Jensen H. Analysis of multivariate survival data from longitudinal epidemiological studies: with special reference to the impact of routine immunisation in infancy. PhD Thesis. Denmark: University of Copenhagen, 2002.
Cox. Regression models and life-tables. J Roy Stat Soc Series B, 1972: 187-202.
Fine P. Commentary: an unexpected finding that needs confirmation or rejection. BMJ 2000;321: 1440.
Aaby P, Jensen H, Samb B, Cisse B, Sodeman M, Jakobsen M, et al. Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactived poliovirus: reanalysis of the West Afican studies. Lancet 2003;361: 2183-8.
Vaugelade J. Variations de la mortalité saisonnière avant 5 ans selon le biotope en Afrique intertropicale. African population conference, Dakar, Senegal, International Union for the Scientific Study of the Population. Liège, Belgium: IUSSP, 1988: 3.4.51-61.
Aaby P, Samb B, Simondon F, Seck AM, Knudsen K, Whittle H. Non-specific beneficial effects of measles immunization: analysis of mortality studies from developing countries. BMJ 1995;311: 481-5.(J Vaugelade, demographer1)