Acute lower respiratory tract infections and respiratory syncytial virus in infants in Guinea-Bissau: a beneficial effect of BCG vaccination for girls: Community based case–control study
Introduction
Globally, acute lower respiratory tract infections (ALRI) cause 20% of the 10 million deaths in children younger than 5 years of age in low- and middle-income countries. In developed countries, acute respiratory infections are the leading cause of morbidity [1]. Respiratory syncytial virus (RSV), a pneumovirus in the family Paramyxoviridae, is a major respiratory pathogen of infants and young children worldwide [2], [3], [4]. In most children, RSV causes upper respiratory tract infection, but 25–40% of primary infections descend to the lower airways causing pneumonia, bronchiolitis, and bronchitis [5]. The most severe infections occur in infants below 6 months of age [6] among whom up to 4% of primary infections lead to hospitalisation [8], [9]. Despite nearly 50 years of research, no safe and effective therapy or vaccine is available. The normal cellular immune response to RSV infections in humans and mice seems to be mostly Th1-like including CD8+ CTL activity. This response may be altered in accordance with the pre-existent immunological profile of the host, and studies suggest that severe RSV infection is associated with an exaggerated Th2 response [10], [11], [12].
M. bovis Bacillus Calmette Guérin (BCG) is the world's most widely used vaccine. BCG immunisation in early life induces a potent immune response [13]. Several studies suggest that BCG vaccination may have non-targeted effects that may be mediated by a modulation of the immune response to unrelated antigens. BCG vaccination was shown to be associated with a reduced risk of atopic disorders and childhood mortality [14], [15], [16]. A cellular immune response to BCG as measured by the presence of a scar or a positive tuberculin reaction is associated with a reduced childhood mortality which cannot merely be explained by prevention of tuberculosis [17]. We therefore hypothesised that BCG vaccination might influence the incidence of symptomatic infections affecting young children. In this study, we investigated whether BCG vaccination may be associated with a reduced risk of developing ALRI, caused by RSV or not.
Section snippets
Bandim Health Project and the ALRI study
Since 1978, the Bandim Health Project has implemented demographic and epidemiological surveillance in several districts in the capital of Guinea-Bissau, including the districts Bandim 1, Bandim 2, and Belem [18]. In July 1994, we initiated a matched case–control study of lower respiratory tract infections in children below 5 years of age from the three study districts. The diagnosis of ALRI was based on an age-adjusted standard for respiratory frequency and chest in-drawings as recommended by
Distribution of background factors among case- and control-infants
The distribution of various background factors is presented in Table 1 where it can be seen that case infants were more often living in a house with straw roof indicating lower socio-economic status. However, none of the other socio-economic factors (electricity, television) indicated an important difference.
BCG vaccination among ALRI case infants compared to control infants
As presented in Table 2, most BCG-unvaccinated infants were from 1996. During 1996, there was a lack of BCG vaccine in Bissau, and the median age of BCG vaccination was therefore higher in
BCG vaccine, ALRI, and RSV–ALRI
This study investigated whether infants with ALRI or RSV–ALRI were more likely to be BCG-unvaccinated, or to have no scar after BCG vaccination than were control infants without symptoms of ALRI. Our study suggested that BCG vaccination and the presence of a scar among BCG infants reduced the risk of ALRI. Moreover, we observed a trend towards a reduced risk of RSV–ALRI among BCG vaccinated infants. The association was significant only among girls. These findings are consistent with earlier
Conclusion
In this study in infants in Guinea-Bissau, BCG vaccination was associated with a reduced risk of ALRI.
Acknowledgements
The studies of RSV received support from Danish Development Research Council, Danish Medical Research Council, WHO, and Novo Nordisk Foundation. Contributors: P.-E.K. and P.A. initiated the RSV studies. L.G.S., E.N., A.P., and P.-E.K. implemented the field studies. I.P.J. was responsible for testing of RSV antigen and antibodies. M.N., A.M., and P.A. developed the plan for the present study. L.G.S., H.J., and P.A. carried out the analyses. L.G.S. and P.A. wrote the first draft of the paper, and
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