Pneumococcal Disease In Infants Research Articles

Dynamics of invasive pneumococcal disease in infants < 2 years old following PCV7/13 implementation using two infant and a booster dose schedule: evidence for indirect protection of young infants, Israel, 2004 to 2019.

BackgroundPneumococcal conjugated vaccine (PCV)7 and PCV13 programmes started in Israel from July 2009 and November 2010 respectively, with a 2+1 schedule (one dose at 2 months old, one at 4 months old, and a booster dose at 12 months old). Thereafter, invasive pneumococcal disease (IPD) rates substantially declined in children. Uptake of all three doses in < 2-year-olds since 2012 is > 90%. For still incompletely vaccinated infants (≤ 12 months old), how well the PCV 2+1 programme shields from IPD is not fully resolved.AimTo assess the adequacy of protection conferred by the 2+1 schedule PCV vaccination programme, particularly among incompletely-vaccinated infants.MethodsThis was a population-based, prospective, nationwide active IPD surveillance study in Israel, 2004-2019, in children < 24 months old. We estimated annual incidence rates (IR) of overall IPD, IPD caused by PCV13 serotypes (VT13), and non-PCV13 serotypes (NVT13). Annual IPD IRs were stratified by age: < 4 months (receiving ≤ 1 dose), 4-6 months (immediately post dose 2), 7-12 months (a few months post dose 2), and 13-23 months (post dose 3). Late-PCV (2004-2008) to pre-PCV13 (2016-2019) mean annual IR ratios (IRRs) were calculated.Results2,569 IPD episodes were recorded. VT13 decreased > 90% in all age groups, while NVT13 seemed to increase. All-IPD rates declined in all age groups by 56-70%. The 2+1 schedule impact on 7-12-month-old infants (pre-booster) was similar to that on 13-23-month-old children (post booster), with PCV13 IPD reductions of 97% and 98%, respectively.ConclusionsIndirect (herd) protection of infants, including < 4 month-olds with ≤ 1 PCV dose, was achieved by the 2+1 PCV schedule programme which thus seems adequate.

Changing Incidence of Invasive Pneumococcal Disease in Infants Less Than 90 Days of Age Before and After Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Blantyre, Malawi: A 14-Year Hospital Based Surveillance Study.

Background:Invasive pneumococcal disease (IPD) in young infants is uncommon but associated with high morbidity and mortality. Accurate data on the burden of IPD in young infants in low-income countries are lacking. We examined the burden of IPD in infants <90 days old in Blantyre, Malawi over a 14-year period and evaluated the indirect impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on vaccine-serotype IPD (VT-IPD) in this population.Methods:We conducted laboratory-based prospective IPD surveillance in infants <90 days of age admitted to Queen Elizabeth Central Hospital in Blantyre between 2005 and 2018, including 7 years pre-PCV13 and 7 years post-PCV13 introduction. IPD was defined as Streptococcus pneumoniae identified by culture from blood or cerebrospinal fluid. Serotypes were determined by multiplex polymerase chain reaction and latex agglutination testing.Results:We identified 130 cases of culture-confirmed IPD in infants <90 days old between 2005 and 2018. Total IPD incidence was declining before PCV13 introduction. The mean incidence of IPD was significantly lower in the post-PCV13 era. Serotypes 5 (27.8%) and 1 (15.6%) were most prevalent. Even after PCV13 introduction, VTs remained the primary cause of IPD, with serotype 5 accounting for 17.4% and serotype 1 for 13.0% of cases in young infants.Conclusion:Vaccine serotypes 1 and 5 were the main cause of IPD in neonates and young infants, both before and after PCV13 introduction. This suggests incomplete indirect protection with persisting VT carriage across the population despite vaccination in this setting. Alternative vaccine schedules and other vaccine introduction approaches need to be considered to protect this vulnerable population.

Effects of 13-Valent Pneumococcal Conjugate Vaccine on Invasive Pneumococcal Disease in Infants Aged 0 to 90 Days in Madrid, Spain

Effects of 13-Valent Pneumococcal Conjugate Vaccine on Invasive Pneumococcal Disease in Infants Aged 0 to 90 Days in Madrid, Spain

Invasive Pneumococcal Disease in Infants Aged 0-60 Days in the United States in the 13-Valent Pneumococcal Conjugate Vaccine Era.

We identified 53 infants aged 0-60 days with invasive pneumococcal disease (IPD) at 8 children's hospitals in the United States (2005-2015). After the introduction of 13-valent pneumococcal conjugate vaccine (PCV13), IPD caused by PCV13 serotypes decreased ~30% providing some evidence of indirect protection. However, approximately 60% of IPD was still caused by PCV13 serotypes.

Polysaccharide Conjugate Vaccine against Pneumococcal Pneumonia in Adults

BackgroundPneumococcal polysaccharide conjugate vaccines prevent pneumococcal disease in infants, but their efficacy against pneumococcal community-acquired pneumonia in adults 65 years of age or older is unknown.MethodsIn a randomized, double-blind, placebo-controlled trial involving 84,496 adults 65 years of age or older, we evaluated the efficacy of 13-valent polysaccharide conjugate vaccine (PCV13) in preventing first episodes of vaccine-type strains of pneumococcal community-acquired pneumonia, nonbacteremic and noninvasive pneumococcal community-acquired pneumonia, and invasive pneumococcal disease. Standard laboratory methods and a serotype-specific urinary antigen detection assay were used to identify community-acquired pneumonia and invasive pneumococcal disease.ResultsIn the per-protocol analysis of first episodes of infections due to vaccine-type strains, community-acquired pneumonia occurred in 49 persons in the PCV13 group and 90 persons in the placebo group (vaccine efficacy, 45.6%; 95.2% confidence interval [CI], 21.8 to 62.5), nonbacteremic and noninvasive community-acquired pneumonia occurred in 33 persons in the PCV13 group and 60 persons in the placebo group (vaccine efficacy, 45.0%; 95.2% CI, 14.2 to 65.3), and invasive pneumococcal disease occurred in 7 persons in the PCV13 group and 28 persons in the placebo group (vaccine efficacy, 75.0%; 95% CI, 41.4 to 90.8). Efficacy persisted throughout the trial (mean follow-up, 3.97 years). In the modified intention-to-treat analysis, similar efficacy was observed (vaccine efficacy, 37.7%, 41.1%, and 75.8%, respectively), and community-acquired pneumonia occurred in 747 persons in the PCV13 group and 787 persons in placebo group (vaccine efficacy, 5.1%; 95% CI, −5.1 to 14.2). Numbers of serious adverse events and deaths were similar in the two groups, but there were more local reactions in the PCV13 group.ConclusionsAmong older adults, PCV13 was effective in preventing vaccine-type pneumococcal, bacteremic, and nonbacteremic community-acquired pneumonia and vaccine-type invasive pneumococcal disease but not in preventing community-acquired pneumonia from any cause. (Funded by Pfizer; CAPITA ClinicalTrials.gov number NCT00744263.)

Association between respiratory syncytial virus activity and pneumococcal disease in infants: a time series analysis of US hospitalization data.

The importance of bacterial infections following respiratory syncytial virus (RSV) remains unclear. We evaluated whether variations in RSV epidemic timing and magnitude are associated with variations in pneumococcal disease epidemics and whether changes in pneumococcal disease following the introduction of seven-valent pneumococcal conjugate vaccine (PCV7) were associated with changes in the rate of hospitalizations coded as RSV. We used data from the State Inpatient Databases (Agency for Healthcare Research and Quality), including >700,000 RSV hospitalizations and >16,000 pneumococcal pneumonia hospitalizations in 36 states (1992/1993-2008/2009). Harmonic regression was used to estimate the timing of the average seasonal peak of RSV, pneumococcal pneumonia, and pneumococcal septicemia. We then estimated the association between the incidence of pneumococcal disease in children and the activity of RSV and influenza (where there is a well-established association) using Poisson regression models that controlled for shared seasonal variations. Finally, we estimated changes in the rate of hospitalizations coded as RSV following the introduction of PCV7. RSV and pneumococcal pneumonia shared a distinctive spatiotemporal pattern (correlation of peak timing: ρ = 0.70, 95% CI: 0.45, 0.84). RSV was associated with a significant increase in the incidence of pneumococcal pneumonia in children aged <1 y (attributable percent [AP]: 20.3%, 95% CI: 17.4%, 25.1%) and among children aged 1-2 y (AP: 10.1%, 95% CI: 7.6%, 13.9%). Influenza was also associated with an increase in pneumococcal pneumonia among children aged 1-2 y (AP: 3.2%, 95% CI: 1.7%, 4.7%). Finally, we observed a significant decline in RSV-coded hospitalizations in children aged <1 y following PCV7 introduction (-18.0%, 95% CI: -22.6%, -13.1%, for 2004/2005-2008/2009 versus 1997/1998-1999/2000). This study used aggregated hospitalization data, and studies with individual-level, laboratory-confirmed data could help to confirm these findings. These analyses provide evidence for an interaction between RSV and pneumococcal pneumonia. Future work should evaluate whether treatment for secondary bacterial infections could be considered for pneumonia cases even if a child tests positive for RSV. Please see later in the article for the Editors' Summary.

Why do we need a systematic review of pneumococcal conjugate vaccine dosing schedules?

It is well known that Streptococcus pneumoniae remains a leading cause of childhood mortality; in 2008, it was estimated to be responsible for over 500,000 deaths in children aged 1–59 months.1 It is also known that the pneumococcus is a cause of significant morbidity and mortality among those younger and older than the 1- to 59-month age group,2,3 although prevention of disease in these age groups has not been the target of global efforts to date. Serious diseases caused by the pneumococcus across all age groups include pneumonia, meningitis and sepsis. Developing countries, mostly in Africa and Asia, carry the highest burden of both pneumococcal disease incidence and mortality in children; this burden is measured both in terms of rates and absolute numbers of cases and deaths.1

Impact of the 7-Valent Pneumococcal Conjugate Vaccine on Invasive Pneumococcal Disease in Infants Younger Than 90 Days in England and Wales

Streptococcus pneumoniae is an uncommon but well-recognized cause of invasive bacterial disease in young infants. This study aimed to determine the impact of the 7-valent pneumococcal conjugate vaccine (PCV7) on invasive pneumococcal disease (IPD) in infants aged <90 days in England and Wales and describe their clinical characteristics following PCV7 introduction. Trends in IPD among infants aged <90 days during 1998-1999 through 2009-2010 were analyzed using enhanced national surveillance data. Following PCV7 introduction, clinical information was also obtained for IPD cases in the birth cohorts eligible for vaccination. Prior to PCV7 introduction, IPD incidence in infants aged <90 days was 13.0 (95% confidence interval [CI], 12.0-14.0) per 100 000 live births and PCV7 serotypes accounted for 44% (154/349) of serotyped isolates. PCV7 introduction resulted in 83% (95% CI, 66%-91%, P < .001) reduction in PCV7 IPD and a declining trend in overall IPD by 2009-2010. Of the 256 cases diagnosed after PCV7 introduction, 23% (n = 60) had been born before 37 weeks' gestation. A third of cases (84/256, 33%) developed IPD in the first 48 hours of life, where 42% (35/84) were premature. Meningitis was diagnosed in 94 infants (37%) and its prevalence increased with age. Case fatality was 7% (18/256) and was higher for meningitis than nonmeningitis cases (adjusted odds ratio, 3.8 [95% CI, 1.2-12.0], P = .024). Young infants have benefited from PCV7 through indirect (herd) protection. Given that a third of cases occurred within 48 hours of birth, further studies should focus on risk factors for IPD in pregnancy and strategies to prevent mother-to-child transmission.

Cost-effectiveness of 2 + 1 dosing of 13-valent and 10-valent pneumococcal conjugate vaccines in Canada

BackgroundThirteen-valent pneumococcal conjugate vaccine (PCV13) and 10-valent pneumococcal conjugate vaccine (PCV10) are two recently approved vaccines for the active immunization against Streptococcus pneumoniae causing invasive pneumococcal disease in infants and children. PCV13 offers broader protection against Streptococcus pneumoniae; however, PCV10 offers potential protection against non-typeable Haemophilus influenza (NTHi). We examined public health and economic impacts of a PCV10 and PCV13 pediatric national immunization programs (NIPs) in Canada.MethodsA decision-analytic model was developed to examine the costs and outcomes associated with PCV10 and PCV13 pediatric NIPs. The model followed individuals over the remainder of their lifetime. Recent disease incidence, serotype coverage, population data, percent vaccinated, costs, and utilities were obtained from the published literature. Direct and indirect effects were derived from 7-valent pneumococcal vaccine. Additional direct effect of 4% was attributed to PCV10 for moderate to severe acute otitis media to account for potential NTHi benefit. Annual number of disease cases and costs (2010 Canadian dollars) were presented.ResultsIn Canada, PCV13 was estimated to prevent more cases of disease (49,340 when considering both direct and indirect effects and 7,466 when considering direct effects only) than PCV10. This translated to population gains of 258 to 13,828 more quality-adjusted life-years when vaccinating with PCV13 versus PCV10. Annual direct medical costs (including the cost of vaccination) were estimated to be reduced by $5.7 million to $132.8 million when vaccinating with PCV13. Thus, PCV13 dominated PCV10, and sensitivity analyses showed PCV13 to always be dominant or cost-effective versus PCV10.ConclusionsConsidering the epidemiology of pneumococcal disease in Canada, PCV13 is shown to be a cost-saving immunization program because it provides substantial public health and economic benefits relative to PCV10.

Contribution of vaccines to our understanding of pneumococcal disease

Pneumonia is the leading cause of mortality in children in developing countries and is also the leading infectious cause of death in adults. The most important cause of pneumonia is the Gram-positive bacterial pathogen, Streptococcus pneumoniae, also known as the pneumococcus. It has thus become the leading vaccine-preventable cause of death and is a successful and diverse human pathogen. The development of conjugate pneumococcal vaccines has made possible the prevention of pneumococcal disease in infants, but has also elucidated aspects of pneumococcal biology in a number of ways. Use of the vaccine as a probe has increased our understanding of the burden of pneumococcal disease in children globally. Vaccination has also elucidated the clinical spectrum of vaccine-preventable pneumococcal infections; the identification of a biological niche for multiple pneumococcal serotypes in carriage and the differential invasiveness of pneumococcal serotypes; the impact of pneumococcal transmission among children on disease burden in adults; the role of carriage as a precursor to pneumonia; the plasticity of a naturally transformable pathogen to respond to selective pressure through capsular switching and the accumulation of antibiotic-resistance determinants; and the role of pneumococcal infections in hospitalization and mortality associated with respiratory viral infections, including both seasonal and pandemic influenza. Finally, there has been a recent demonstration that pneumococcal pneumonia in children may be an important cause of hospitalization for those with underlying tuberculosis.

Potential Impact of Accelerating the Primary Dose of Pneumococcal Conjugate Vaccine in Infants

To estimate the potential effect of the acceleration of administration of the first dose of pneumococcal conjugate vaccine from 2 months to 6 weeks of age. Prediction model using data from a retrospective cohort study. Published data from 8 states that participated in Active Bacterial Core Surveillance of the Emerging Infections Program Network for pneumococcus before pneumococcal conjugate vaccine introduction (July 1, 1997- June 30, 2000). A total of 759 739 live births under surveillance. Intervention Estimating the potential benefit of administration of the first dose of the pneumococcal conjugate vaccine at 6 weeks of age instead of 2 months of age. Estimation of reduction in the rate of invasive pneumococcal disease in infants 61 to 90 days of age. The estimated direct effect of the acceleration of administration of the first dose of pneumococcal conjugate vaccine from 2 months to 6 weeks of age when this vaccine was first introduced could have reduced the burden of invasive pneumococcal disease in infants 61 to 90 days of age by 39.9%, 56.0%, and 72.1% for respective vaccine efficacies of 50%, 70%, and 90%. This translates into preventing an estimated 73, 103, and 133 cases of invasive pneumococcal disease per year among approximately 4 112 052 live births in the United States. The acceleration of administration of the pneumococcal conjugate vaccine from 2 months to 6 weeks of age could reduce the burden of invasive pneumococcal disease among infants. This observation may be important when a new conjugate vaccine becomes available, particularly among populations with prevalent invasive pneumococcal disease from a serotype included in the new vaccine.

Perinatal and Crowding-Related Risk Factors for Invasive Pneumococcal Disease in Infants and Young Children: A Population-Based Case-Control Study

Denmark's systems of registry-based data offer a unique opportunity to examine, on a population basis, risk factors for invasive pneumococcal disease (IPD) relating to perinatal and crowding exposures among children. The main objective of this study was to identify the role of familial and day care factors in the risk of IPD among unvaccinated infants and children. A total of 1381 children aged 0-5 years old who experienced IPD were identified from a national surveillance program of IPD in Denmark. Risk factors were assessed in a matched, nested, case-control study that assigned 10 population control subjects to every case patient. Exposure information was obtained from several population-based, person-identifiable Danish registries. Preterm birth and low birth weight significantly increased the risk of IPD among infants. In infants 0-5 months of age, the risk of IPD was high among infants who had older siblings, compared with infants of the same age who had no older siblings (adjusted rate ratio [aRR], 3.38; 95% confidence interval, 2.11-5.42), whereas the aRR was low (aRR, 0.56; 95% confidence interval, 0.47-0.65) in children aged 6-23 months. Day care attendance, compared with home care, increased the aRR of IPD 0-2 months after enrollment in a day care program (aRR, 2.28; 95% confidence interval, 1.73-3.00), whereas the aRR was 0.70; (95% confidence interval, 0.46-1.06) > or = 6 months after enrollment in children aged 6-23 months. During infancy (age, 0-6 months), risk of IPD is associated with low birth weight, presumably because of lower levels of passively acquired maternal antibody. During early childhood, exposure to other young children (either siblings or through day care attendance) is clearly associated with IPD, but natural exposure appears to occur rapidly and confer durable immunity.

Indikationen und Nutzen der Pneumokokken-Konjugat-Vakzine

Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, sinusitis, and acute otitis media in children and adults worldwide. Especially in the age group of < 2 years the incidence of invasive pneumococcal is high. The vulnerability of children to S. pneumoniae can also be demonstrated by the high rate of sequelae (> 20 % in Germany) and the high mortality (7.5 %) in pneumococcal meningitis. A 7-valent pneumococcal conjugate vaccine that was shown to be highly efficacious in preventing invasive pneumococcal disease in infants in the USA was licensed in Europe in 2001. It is expected that broad usage of the vaccine would reduce the incidence of invasive pneumococcal disease and the levels of pneumococcal resistance significantly.

Vaccination Reduces Invasive Pneumococcal Infection Among the Unvaccinated, Too

A heptavalent pneumococcal conjugate vaccine (PCV7) was licensed in 2000 for administration to children aged 2 months to 23 months. These authors compared rates of invasive pneumococcal disease in infants younger than 90 days during the 3 years …

Impact of the Conjugate Pneumococcal Vaccine in Arkansas

On the basis of the success of the early trials in the prevention of invasive pneumococcal disease in infants and children using a heptavalent conjugate pneumococcal vaccine, the American Academy of Pediatrics recommended in August 2000 that the vaccine be given concurrently with other childhood immunizations. Data concerning invasive pneumococcal infections from 1998-2000 were compared with 2001-2003 to assess the impact of the heptavalent pneumococcal conjugate vaccine in Arkansas. Basic demographic data were gathered as well as history of vaccination with the pneumococcal vaccine, underlying medical conditions, site of infection and morbidity and mortality. Pneumococcal isolates were serogrouped or serotyped and penicillin susceptibilities were obtained. The incidence of invasive disease decreased from a high of 5.78/100,000 population to 3.02/100,000 population (P = 0.002). Although the percentage of White patients increased from 2001-2003, the overall incidence of disease did not change. The incidence of disease among Blacks fell from 20.5/100,000 population to 4.9/100,000 population. The greatest decrease of disease occurred in children 24 months of age or younger with the incidence rate falling from 44.2/100,00 population to 8.30/100,000 population (P < 0.02). The incidence among White children 24 months of age or younger fell from 19/100,000 population to 1.8/100,000 population, whereas that of Black children 24 months of age or younger declined from 164/100,000 to 35/100,000. From 1998 to 2000, 3.7/100 cases were from nonvaccine serogroups compared with 44/100 cases from 2001 to 2003 (P < 0.001). In children 24 months of age or younger, the number of nonvaccine isolates increased from 1.3/100 cases to 30.5/100 cases (P < 0.001). Overall 56 (44%) were nonsusceptible to penicillin from 1998 to 2000; that was not significantly different from 2001-2003 when 37 (46%) of 81 isolates were nonsusceptible to penicillin. A significant decrease of invasive pneumococcal disease has been documented in Arkansas. Of concern, however, is the increasing number of invasive isolates not included in the current vaccine.

Induction of functional secretory IgA responses in breast milk, by pneumococcal capsular polysaccharides.

Capsule-specific secretory IgA (s-IgA) in breast milk may enhance protection against pneumococcal disease in infants. After immunization of 3 lactating mothers with 23-valent polysaccharide vaccine, specific s-IgA, but not IgG, increased by >2-fold in milk of at least 1 subject for 6 of 7 serotypes. The s-IgA was predominantly IgA1, in secretory form, and highly specific with avidity distinct from serum IgA and IgG. Milk whey from 2 immunized women supported dose- and complement-dependent killing of Streptococcus pneumoniae serotypes 19F and 14 by human neutrophils, as did purified s-IgA to serotype 19F. These data reveal that capsule-specific human s-IgA in breast milk can initiate killing of S. pneumoniae, providing proof of concept that vaccine-induced human mucosal s-IgA can support functional bactericidal activity. Determining the biologic role for s-IgA in killing and inhibiting adherence of S. pneumoniae in vivo will contribute to the development of mucosal vaccines against S. pneumoniae.

The future of pneumococcal conjugate vaccines for prevention of pneumococcal diseases in infants and children.

Seven-valent pneumococcal conjugate vaccine (PCV7) was licensed in February 2000. In June 2000, the Advisory Committee on Immunization Practices and the American Academy of Pediatrics recommended the universal administration of pneumococcal conjugate vaccine for all children 23 months of age and younger and for children 24 to 59 months of age who are at high risk for serious pneumococcal disease. Since then, >23 million doses have been administered in the United States. Postlicensure surveillance of invasive pneumococcal disease (IPD) in the United States from the Active Bacterial Core Surveillance program at the Centers for Disease Control and Prevention and the Northern California Kaiser Permanente Vaccine Study Center has reported a decline in IPD and in pneumococcal disease incidence as a result of vaccine serotypes, respectively. During this period, issues critical to the long-term success of PCV7 have become more relevant: Will PCV7 be as effective in groups of children who are at high risk for IPD as in healthy children? Will nonvaccine types replace vaccine serotypes in the nasopharynx and in disease? Why are the results of the clinical trials different for IPD and for acute otitis media? How many doses of PCV7 and what concentrations of antibody are necessary for protection? Will universal administration of PCV7 to children younger than 2 years reduce antimicrobial drug resistance and alter prescribing patterns of physicians for febrile infants? Have there been unanticipated adverse events or benefits observed? The purpose of this report is to review the current data available to address these questions and to identify gaps that will require additional knowledge to determine the ultimate value of pneumococcal conjugate vaccines in reducing the burden of pneumococcal disease in infants and children.

A Conjugate Vaccine for the Prevention of Pediatric Pneumococcal Disease

The use of the pneumococcal 7-valent conjugate vaccine (PCV7 [Prevnar], Wyeth Lederle Vaccines), and the impact it is likely to have on pneumococcal disease are reviewed. Pneumococcal disease in infants and young children is a major health care burden, and the increase in antibiotic resistance among pneumococci has complicated disease management. The 23-valent polysaccharide pneumococcal vaccines do not protect infants and children younger than 2 years of age. PCV7 is effective in this population and should dramatically reduce the incidence of invasive pneumococcal disease and have an impact on the incidence of infections caused by Streptococcus pneumoniae serotypes present in the vaccine. Research has shown that pneumococcal conjugate vaccines reduce nasopharyngeal carriage of vaccine serotype S. pneumoniae, including antibiotic-resistant strains. Routine immunization is expected to substantially reduce the morbidity and mortality associated with invasive pneumococcal disease in children, and coupled with expected herd immunity and decreased antibiotic selective pressure, it should have a positive impact beyond the immunized population.

A new conjugate vaccine against pneumococcal disease.

Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity and mortality, particularly among infants and children. Pneumococcal 7-valent conjugate vaccine (PNCRM7) is the first conjugate vaccine known to prevent most invasive pneumococcal disease in infants and children. PNCRM7, which has a favorable safety profile, provides protection against invasive disease caused by antibiotic-resistant strains of S. pneumoniae, and the vaccine has demonstrated a significant impact on otitis media recurrence. Routine immunization with this vaccine should substantially reduce morbidity and mortality and improve the quality of life for infants, children, and their families.

The epidemiology of pneumococcal infection in children in the developing world.

Pneumonia causes about three million deaths a year in young children, nearly all of which are in developing countries. Streptococcus pneumoniae (the pneumococcus) is the most important bacterial cause of pneumonia in young children and so is likely to be responsible for a high proportion of these deaths. The pneumococcus is also responsible for a substantial proportion of the 100,000-500,000 deaths that occur from meningitis in children each year. The incidence of invasive pneumococcal disease in children in the developing world is several times higher than in industrialized countries. This discrepancy may, in part, be due to socio-economic differences but genetic factors may also play a role. Children with sickle cell disease have a substantially increased risk of invasive pneumococcal infection and a search is being made for other possible genetic risk factors. Infection with human immunodeficiency virus (HIV) also predisposes to invasive pneumococcal disease and so the incidence of this disease in young children is expected to rise as increasing numbers of African and Asian children are born with a perinatally acquired HIV infection. Until recently, pneumococcal infections could be treated effectively with penicillin, a cheap and safe antibiotic. However, pneumococci that are resistant to penicillin are becoming prevalent in many countries, necessitating a change to more costly antibiotics which may be beyond the reach of the health services of poor, developing countries. The spread of antibiotic resistance has provided an added stimulus to the development of vaccines that might be able to prevent pneumococcal disease in infants. Recently developed polysaccharide-protein conjugate vaccines show promise and are now undergoing field trials. How deployment of these vaccines will influence the balance between invasive pneumococcal infections and asymptomatic nasopharyngeal carriage of pneumococci is uncertain.