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The World Health Organization (WHO) estimates that Streptococcus pneumoniae is responsible for up to one million deaths annually among children less than five years of age.1 Pneumococcus is a leading cause of bacterial pneumonia, meningitis, and sepsis. However, due to diagnostic challenges, the burden of pneumococcal disease is largely invisible. In this issue of the journal, Abdullah Brooks and others uncover the substantial disease burden affecting children living in an impoverished urban community in Dhaka, Bangladesh.2 This is the most rigorous study of the pneumococcal disease burden in an Asian setting. The overall incidence of invasive pneumococcal disease among children less than five 5 years of age was 447 episodes per 100,000 child years, which is comparable to incidence rates found among children coming to hospitals in rural African settings3,4 and more than five times higher than rates seen prior to widespread vaccination in the United States, a setting in which blood cultures are frequently performed on febrile children.5 Before this study, direct evidence for the high pneumococcal disease burden in Asia lagged behind that for Africa, despite the importance of pneumonia as a leading cause of childhood mortality in both regions.
To reveal the pneumococcal disease burden, the authors established active surveillance for acute respiratory illness among children living in 5,000 selected households visited weekly by trained staff. Children with fever or signs and symptoms of respiratory illness were referred to a nearby study clinic where blood cultures were performed for children meeting clinical criteria.
Key features of this study were the systematic use of blood cultures and the evaluation of both hospitalized and non-hospitalized children. Pneumococcus is consistently a leading cause of severe pneumonia, invasive disease, and death among hospitalized children.6,7 However, limiting surveillance to hospital admissions can underestimate the pneumococcal disease burden. A study in Kenya found four times the burden of pneumococcal disease among children presenting to a hospital compared with children admitted to a hospital.3 Moreover, some children with pneumococcal infection may not come to hospitals. In many urban areas, ill children can receive care from a variety of providers. Antibiotics received prior to hospitalization decrease the sensitivity of blood cultures. For these reasons, the authors implemented active community-based surveillance to identify children with acute respiratory illnesses. The results give us the most accurate picture to date of the disease burden. The study also provides new information about the serotype distribution and antimicrobial resistance of pneumococci causing invasive disease in Bangladeshi children, although based on a small number of isolates.
The finding that a higher percentage of pneumococcal serotypes are included in current pneumococcal vaccines than previously estimated by hospital-based studies is encouraging for the potential use of these vaccines in Asia. In addition, the prevalence of resistance to antibiotics among pneumococcal isolates means that preventing these infections may be more important than ever.
The major limitation of blood cultures is their insensitivity. Clinical trials have shown that a small fraction of vaccine-preventable pneumococcal disease is microbiologically confirmed. In The Gambia for example, pneumococcal vaccination decreased the incidence of clinical pneumonia (defined according to WHO Integrated Management of Childhood Illness criteria) by 15 episodes per 1,000 child-years and radiologically confirmed pneumonia by 13 episodes per 1,000 child-years compared with 1.9 episodes per 1,000 child-years for culture-confirmed invasive pneumococcal disease.8 The trial also demonstrated a 16% reduction in all-cause mortality, which is equivalent to 5 deaths averted per 1,000 child-years of observation.8 In Bangladesh, the authors estimate that a pneumococcal vaccine that was 25% effective against clinically diagnosed pneumonia could prevent an incredible one million episodes each year among young children. Although the currently licensed seven-valent pneumococcal conjugate vaccine provides lower coverage of invasive serotypes found in Bangladesh, the vaccine-preventable disease burden is substantial. Pneumococcal vaccines awaiting licensure that include 10 and 13 serotypes would provide greater coverage. Surveillance for invasive disease is important not only for the information it provides about pneumococcal serotypes and antimicrobial resistance, but for establishing links to vaccine trials from which we can make inferences about the vaccine-preventable burden of disease.
Estimates of the preventable disease burden can help decision makers prioritize the introduction of pneumococcal vaccines. In 2007, the WHO and collaborators will complete estimates of the burden of pneumonia and meningitis caused by S. pneumoniae and Haemophilus influenzae type b for every country in the world as part of the Global Burden of Disease project.9 Regional serotype distribution can then be used to determine the number of pneumococcal cases and deaths that could be prevented with pneumococcal conjugate vaccines. There is a compelling case for the introduction of currently available pneumococcal vaccines, especially in countries with high childhood mortality.1 An unprecedented amount of financial support is available through the Global Alliance for Vaccines and Immunization and innovative funding initiatives to help countries introduce pneumococcal vaccines.10 Thirty Global Alliance for Vaccines and Immunization–eligible countries, mostly in the African region, have already expressed their desire to introduce pneumococcal vaccines by 2010 (Pneumococcal Vaccines Accelerated Development and Introduction Plan, www.preventpneumo.org). These new data from Bangladesh should spark enthusiasm about the potential benefits of pneumococcal vaccination throughout Asia.
Finally, given the complex etiology of pneumonia, it is important to see the introduction of pneumococcal conjugate vaccines as part of a comprehensive strategy to reduce pneumonia mortality. As shown by the study in Bangladesh, multiple bacterial pathogens cause invasive disease among children with respiratory symptoms and fever, and slum conditions underlie the high burden of disease. Together with introduction of new vaccines, strengthening case management with effective antibiotics, improving nutrition, and reducing indoor air pollution should be components of a strategy to improve child survival.11 Reducing pneumonia mortality is critical if countries are to achieve the fourth Millennium Development Goal of a two-thirds reduction in childhood mortality.
Received August 15, 2007. Accepted for publication August 16, 2007.
Disclosure: None of the authors has any conflicts of interest.
* Address correspondence to Brendan Flannery, Global Immunization Division, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop E-05, Atlanta, GA 30333. E-mail bflannery{at}cdc.gov 
Authors’ addresses: Brendan Flannery, Global Immunization Division, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop E-05, Atlanta, GA 30333, Telephone: 404-639-8224, E-mail: bflannery{at}cdc.gov. Cynthia G. Whitney, Respiratory Diseases Branch, Division of Bacterial Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop C-23, Atlanta, GA 30333, Telephone: 404-639-2215, E-mail: cwhitney{at}cdc.gov.
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