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Epidemiology of pneumococcal disease in children/Cocuklarda pnomokokal hastalik epidemiyolojisi.


The 2004 World Health Organization report on 'what are children dying from' identified pneumococcal disease as the cause of death in 17% of the world's children, second only to malaria. Estimates of 1 million annual deaths in children from pneumococcal disease demonstrate its significance as a major cause of childhood morbidity and mortality despite the availability of effective antimicrobial therapy. Understanding the epidemiology and serotype distribution of pneumococcal disease is vital to reducing the burden of disease and its associated morbidity and mortality. The epidemiology identifies how large the burden of disease is and which age cohort(s) to target for prevention, how much disease can be prevented with a specific vaccine and how the costs of a vaccine program compare to the savings accrued in medical and societal costs as a result of a reduction in disease.

Variation in Incidence Rates of Invasive Pneumococcal Disease

Nasopharynge al colonization with Streptococcus pneumoniae is nearly universal, yet only a small proportion of children develop invasive disease, primarily those under three years of age or those with co-morbid illnesses. However, great variation in incidence rates for IPD among children across the globe exists. Greenwood reported that the incidence of IPD in children under 2 years of age varies from less than 100 cases/100,000 in Finland to more than 1000 per 100,000 in Australian Aboriginal children; a 10 fold difference (1) (Fig. 1). In part, these differences in rates of infection are due to co-morbid features, such as HIV and malnutrition, which occur more frequently in many industrializing countries (1-3). The frequency of invasive pneumococcal disease as well as presumed pneumococcal pneumonia are also greater in indigenous populations, both in industrialized countries such as the US, Canada and Australia as well as developing countries such as Papa New Guinea and American Samoa. Additionally, the incidence of disease may vary greatly among populations within a country; for example in the United States, Native American and African American children suffered IPD at a substantially greater rate than Caucasian children (4,5). Still, it is critically important to recognize that, in virtually all countries, the majority of cases occur in healthy infants and toddlers, as they represent an immunologically na've population lacking both specific antibody and strong innate immunity.


Epidemiology of Specific Clinical Syndromes

The age distribution of the three most common clinical manifestations of invasive pneumococcal disease, meningitis, pneumonia and bacteremia from the Calgary area Streptococcus pneumoniae Research Study (CASPER) are depicted in Figure 2. Evident in the figure is that pneumococcal meningitis, although the least common of the syndromes, occurs primarily in young infants (6). The incidence of pneumococcal meningitis reported in Western Europe and the USA (8-9 per 100 000 child years) was similar prior to introduction of PCV7 (163) However, studies of pneumococcal meningitis from Africa demonstrate incidence rates among children <2 years of age that are much higher (40-43 per 100 000 child years) (8). In a review of 50 publications by Peltola et al, S. pneumoniae was reported to be the leading non-epidemic cause of meningitis in Africa and selected studies from Asia, Middle-Eastern countries, and South America (9). The proportion of bacterial meningitis cases attributable to S. pneumoniae is even higher in children with HIV infection (10). During the time period 1998-2007 (PCV7 was introduced in 2002), the CASPER study reported an incidence of pneumococcal meningitis of ~2 per 100,000 in infants under 5 months of age, 5 per 100,000 in infants 6 through 23 months of age and 3 per 1000,000 in toddlers 2 through 4 years of age (6). In addition to the higher incidence rates of pneumococcal meningitis in industrializing countries, greater case fatality rates and neurological sequelae have been observed in these children compared to those from industrialized countries. Case fatality rates in excess of 50% have been reported from some African and Asian countries. S. pneumoniae is believed to contribute significantly to the 100 000-500 000 annual deaths from meningitis among children in industrializing countries (1).

Epidemiology of Bacteremia

Onset early in life, high rates of severe clinical infections, substantial morbidity and mortality characterize bacteremia in the developing world. In contrast, in developed countries the incidence peaks between 6 and 18 months of age, and bacteremia without focal infection is the most common clinical syndrome. Overall mortality is low in developed compared to developing countries.

Unsuspected or 'occult' bacteremia in children 3 to 36 months of age has been reported in up to 4% of febrile infants and toddlers without evidence of toxicity or focal infection. In countries where blood cultures are performed on febrile children with mild or moderate toxicity, bacteremia has been identified in studies from emergency or walk-in clinics as well as office practice settings (10). Age less than 24 months and temperature greater than 39[degrees]C characterize the clinical presentation of children with 'occult' pneumococcal bacteremia. Disease is less frequent in children younger than 3 months of age. Laboratory studies reveal that elevated white blood cells or absolute neutrophil counts, and elevated erythrocyte sedimentation rate or C reactive protein are clues to identifying children with pneumococcal bacteremia, but are most valuable as negative predictors (negative predictive value is 99.5%). Spontaneous clearance is found in approximately one third of cases, with persistent signs or symptoms, though not necessarily persistent bacteremia, in two thirds (11). Whether a comparable syndrome exists in developing countries is unclear largely because of differences in clinical practices due to resource limitations in performing blood cultures in ambulant febrile children. Differences in the severity of illness among cases of bacteremia without a focus are highlighted in a report from Bangkok. In a hospital-based study in Bangkok, IPD without a focus was associated with 23% mortality primarily in children with co-morbid conditions (12). These reports suggest that IPD without a focus is different in severity and associated complications in Thailand compared to the US. The large proportion of cases with pneumonia or meningitis, the high death rates during the initial few days of hospitalization and the earlier age of onset for IPD in developing countries may suggest that host factors such as nutritional status, co-morbid conditions or genetic factors result in rapid progression when pneumococcal bacteremia occurs, rather than the relatively slower progression and relatively high rate of spontaneous resolution described in US children.

Epidemiology of S. pneumoniae pneumonia

Lower respiratory tract infection remains the leading cause of childhood mortality in industrializing countries and data on the epidemiology of LRTI in many of these countries are limited (13,14). Rudan and colleagues recently reviewed the published literature between 1966 and 2000 on incidence of LRTI. They reported a median incidence of LRTI in developing countries at 29 episodes per 100 child-years, estimating 154.5 million new cases each year, of which 7 to 13 percent warrant hospitalization (13). Rudan et al. estimated that Asia and sub-Saharan Africa have the highest burden of disease. The burden of LRTI was also found to be greatest among children under one year old. Countries with a high burden of HIV infection in children are likely to have even higher incidence of LRTI, as data from South Africa found such children have an 6.6 fold greater incidence than HIV uninfected children. The proportion of cases of LRTI attributable to pneumococcus remains a challenge as only a minority of cases are bacteremic (3-30%) (15-17), few lung puncture studies are performed on healthy children and the specificity of other diagnostic studies has not been established. One method of estimating the proportion of pneumonia due to the pneumococcus is to determine the reduction in LRTI in clinical trials or following introduction of PCV (18). These studies have revealed that pneumococci cause a spectrum of LRTI that includes lobar pneumonia and empyema, 'viral' pneumonia and possibly some proportion of bronchitis/bronchiolitis (19). In South Africa, a 9 valent PCV reduced chest X-ray proven alveolar pneumonia by 20% in healthy children (17). In Northern California in the US, the clinical trials of PCV7 reduced WHO defined first episode of X-ray proven pneumonia in children under 2 years of age 25.5% (intent to treat) (20). PCV9 protected against 'viral pneumonia' as defined as a child with hospitalized pneumonia in whom a virus was identified in the respiratory tract; a 31 to 50% decline was observed in children under 2 years. The concept of pneumococcal lower respiratory tract infection may even extend to bronchitis/bronchiolitis, as Dagan demonstrated a 23% decline in these diagnoses in a randomized trial of PCV9 in a day care center (21). These studies help clarify the spectrum of pneumococcal lower respiratory tract disease and suggest that PCV can reduce a substantial number of cases of childhood pneumonia in both industrialized and industrializing countries.


Invasive pneumococcal infection and pneumococcal pneumonia are global causes of morbidity and mortality in children. In both industrialized and industrializing countries, infants and toddlers and children with high risk medical conditions (SS disease, HIV, cancer, high dose steroids, etc) are at greatest risk of disease. A peak incidence in industrialized countries is usually observed between 1 and 2 years of age and younger in industrializing countries. Even with the availability of effective antibiotics, mortality remains high, supporting the need for prevention.

Gelis Tarihi: 20.12.2009

Kabul Tarihi: 05.01.2010


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(2.) Madhi SA, Petersen K, Madhi A, Wasas A, Klugman KP. Impact of human immunodeficiency virus type 1 on the disease spectrum of Streptococcus pneumoniae in South African children. Pediatr Infect Dis J 2000; 19: 1141-7.

(3.) Molyneux EF, Riordan FA, Walsh A. Acute bacterial meningitis in children presenting to the Royal Liverpool Children's Hospital, Liverpool, UK and the Queen Elizabeth Central Hospital in Blantyre, Malawi: a world of difference. Ann Trop Paediatr 2006; 26: 29-37.

(4.) MMWR. Preventing pneumococcal disease among infants and young children. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morb.Mortal.Wkly.Rep 2000; 49: 135.

(5.) Davidson M, Parkinson AJ, Bulkow LR, Fitzgerald MA, Peters HV, Parks DJ. The epidemiology of invasive pneumococcal disease in Alaska, 1986-1990-ethnic differences and opportunities for prevention. J Infect Dis 1994; 170: 368-76.

(6.) Kellner JD, Vanderkooi OG, MacDonald J, Church DL, Tyrrell GJ, Scheifele DW. Changing epidemiology of invasive pneumococcal disease in Canada, 1998-2007: update from the Calgary-area Streptococcus pneumoniae research (CASPER) study. Clin Infect Dis 2009; 49: 205-12.

(7.) Zangwill KM, Vadheim CM, Vannier AM, Hemenway LS, Greenberg DP, Ward JI. Epidemiology of invasive pneumococcal disease in southern California: implications for the design and conduct of a pneumococcal conjugate vaccine efficacy trial. J Infect Dis 1996; 174: 752-9.

(8.) O'Dempsey TJ, McArdle TF, Lloyd-Evans N, et al. Pneumococcal disease among children in a rural area of west Africa. Pediatr Infect Dis J 1996; 15: 431-7.

(9.) Peltola H. Burden of meningitis and other severe bacterial infections of children in africa: implications for prevention. Clin Infect Dis 2001; 32: 64-75.

(10.) Molyneux EM, Tembo M, Kayira K, et al. The effect of HIV infection on paediatric bacterial meningitis in Blantyre, Malawi. Arch Dis Child 2003; 88: 1112-8.

(11.) Breiman RF, Spika JS, Navarro VJ, Darden PM, Darby CP. Pneumococcal bacteremia in Charleston County, South Carolina. A decade later. Arch.Intern.Med. 1990; 150: 1401-5.

(12.) Klein JO. 1981. The epidemiology of pneumococcal disease in infants and children. Rev Infect Dis 1981; 3: 246-53.

(13.) Sirinavin S, Vorachit M, Thakkinstian A, Hongsanguensri S, PWittayawongsruji P.Pediatric invasive pneumococcal disease in a teaching hospital in Bangkok. Int J Infect Dis 2003; 7: 183-9.

(14.) Rudan I, Tomaskovic L, Boschi-Pinto C, Campbell H. Global estimate of the incidence of clinical pneumonia among children under five years of age. Bull World Health Organ 2004; 82: 895-903.

(15.) Williams BG, Gouws E, Boschi-Pinto C, Bryce J, Dye C. Estimates of worldwide distribution of child deaths from acute respiratory infections. Lancet Infect Dis 2002; 2: 25-32.

(16.) No authors mentioned. Pneumonia in childhood. Lancet 1988; 1: 741-3.

(17.) Madhi SA, Kuwanda L, Cutland C, Klugman KP. The impact of a 9-valent pneumococcal conjugate vaccine on the public health burden of pneumonia in HIV-infected and -uninfected children. Clin Infect Dis 2005; 40: 1511-8.

(18.) Dagan R. Pneumococcal conjugate vaccines probe studies: the solution points to the problem. Adv Exp Med Biol 2009; 634: 69-77.

(19.) Madhi SA, Klugman KP. A role for Streptococcus pneumoniae in virus-associated pneumonia. Nat Med 2004; 10: 811-3.

(20.) Hansen J, Black S, Shinefield H, et al. Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than 5 years of age for prevention of pneumonia: updated analysis using World Health Organization standardized interpretation of chest radiographs. Pediatr Infect Dis J 2006; 25: 779-81.

(21.) Dagan R, Sikuler-Cohen M, Zamir O, Janco J, Givon-Lavi N, Fraser D. Effect of a conjugate pneumococcal vaccine on the occurrence of respiratory infections and antibiotic use in daycare center attendees. Pediatr Infect Dis J 2001; 20: 951-8.

Stephen I. Pelton

Boston University, Schools of Medicine and Public Health, Departments of Pediatric Infectious Diseases and Epidemiology, Boston Medical Center, Boston, MA, USA

Correspondence Address:

Yazisma Adresi:

Stephen I. Pelton, M.D

Professor of Pediatrics and Epidemiology

Boston University Schools of Medicine and Public Health

Chief, Division of Pediatric

Infectious Diseases Maxwell

Finland Laboratory for Infectious Diseases

Boston Medical Center

670 Albany Street, 6th

Floor, Boston, MA 02118

Phone: 1 617 414 7407

Fax: 1 617 414 5806

Figure 1. What Are Children Dying From: WHO REPORT 2004


YF, Diphteria, Polio, Hepatitis B    0%
Tetanus                              5%
Pertussis                            7%
Measles                             13%
Hib                                  9%
Rotavirus                           10%
Pneumococcus                        17%
Meningococcus A/C JE                 1%
TB                                   9%
HIV                                  9%
Malaria                             28%

(Source: World Health Report 2004)

Note: Table made from pie chart.
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Article Details
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Author:Pelton, Stephen I.
Publication:Journal of Pediatric Infection
Article Type:Report
Geographic Code:1USA
Date:Mar 1, 2010
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