National Health Laboratory Service, University of the Witwatersrand, Meningeal Pathogens Research Unit, Johannesburg, South Africa; Paediatr. Infect. Dis. Research Unit, Wits Health Consortium, University of the Witwatersrand, Johannesburg, South Africa; Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, United States; Chris Hani-Baragwanath Hospital, Old Nurses Home, West Wing, PO Bertsham, Bertsham, Gauteng, 2013, South Africa
Madhi, S.A., National Health Laboratory Service, University of the Witwatersrand, Meningeal Pathogens Research Unit, Johannesburg, South Africa, Paediatr. Infect. Dis. Research Unit, Wits Health Consortium, University of the Witwatersrand, Johannesburg, South Africa, Chris Hani-Baragwanath Hospital, Old Nurses Home, West Wing, PO Bertsham, Bertsham, Gauteng, 2013, South Africa; Kuwanda, L., National Health Laboratory Service, University of the Witwatersrand, Meningeal Pathogens Research Unit, Johannesburg, South Africa; Cutland, C., National Health Laboratory Service, University of the Witwatersrand, Meningeal Pathogens Research Unit, Johannesburg, South Africa, Paediatr. Infect. Dis. Research Unit, Wits Health Consortium, University of the Witwatersrand, Johannesburg, South Africa; Klugman, K.P., National Health Laboratory Service, University of the Witwatersrand, Meningeal Pathogens Research Unit, Johannesburg, South Africa, Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, United States
Introduction. Pneumococcal conjugate vaccine (PnCV) may be used as a probe to define the burden of pneumococcal disease and better characterize the clinical presentation of pneumococcal pneumonia. Methods. This study used a 9-valent PnCV to define different end points of vaccine efficacy and the preventable burden of pneumococcal pneumonia in 39,836 children who were randomized in a double-blind, placebo-controlled trial in South Africa. Results. Whereas the point-estimate of vaccine efficacy was greatest when measured against the outcome of vaccine-serotype specific pneumococcal bacteremic pneumonia (61%; P = .01), the sensitivity of blood culture to measure the burden of pneumococcal pneumonia prevented by vaccination was only 2.6% in human immunodeficiency virus (HIV)-uninfected children and 18.8% in HIV-infected children. Only 37.8% of cases of pneumococcal pneumonia prevented by PnCV were detected by means of chest radiographs showing alveolar consolidation. A clinical diagnosis of pneumonia provided the best estimate of the burden of pneumococcal pneumonia prevented through vaccination in HIV-uninfected children (267 cases prevented per 100,000 child-years) and HIV-infected children (2573 cases prevented per 100,000 child-years). Conclusion. Although outcome measures with high specificity, such as bacteremic pneumococcal pneumonia, provide a better estimate as to vaccine efficacy, the burden of disease prevented by vaccination is best evaluated using outcome measures with high sensitivity, such as a clinical diagnosis of pneumonia. © 2005 by the Infectious Diseases Society of America. All rights reserved.
Pneumococcus vaccine; article; blood culture; child; clinical trial; controlled clinical trial; controlled study; double blind procedure; drug efficacy; human; Human immunodeficiency virus infection; major clinical study; pneumonia; priority journal; public health; randomized controlled trial; sensitivity and specificity; serotype; Streptococcus pneumoniae; thorax radiography; vaccination; Double-Blind Method; HIV Infections; Humans; Incidence; Infant; Pneumococcal Vaccines; Pneumonia, Pneumococcal; South Africa; Vaccines, Conjugate