Remarkable early declines in hospitalizations for pneumonia among young children9 were sustained during the past decade of PCV7 use, alleviating concerns that disease caused by pneumococcal serotype replacement would erode the benefits of vaccination.11 Hospitalizations also declined in other age groups, most notably in older adults, an age group in which the disease burden from pneumonia is substantial and in-hospital mortality ranges from 7 to 12%. Overall, in 2009, there were about 168,000 fewer hospitalizations for pneumonia than would have been expected on the basis of hospitalization rates in the 3 years preceding the introduction of PCV7. This estimated annual reduction in hospitalizations is five times as high as the annual reduction in cases of invasive pneumococcal disease.1

Although 20 to 60% of cases of community-acquired pneumonia are thought to be pneumococcal, only a small proportion of pneumonias are diagnosed as pneumococcal (Table 1), and serotype information is usually unavailable.7 The attribution of trends in rates of disease to the PCV7 vaccination program requires an understanding of expected changes in rates among young children that are based on the results of randomized vaccine trials performed before licensure and on changes in pneumococcal nasopharyngeal carriage, which account for the indirect effects of vaccination.

The 43.2% decline in annual hospitalizations for pneumonia among children younger than 2 years of age is consistent with clinical trial results. In a prelicensure trial of PCV7 in children enrolled in Northern California by Kaiser Permanente,8 rates of radiographically defined pneumonia fell by 30% (95% CI, 11 to 46). Randomized trials conducted in South Africa, the Philippines, and Gambia showed declines of 17 to 37% in rates of pneumonia.16

PCV7 also had a major effect on pneumococcal carriage. The carriage of PCV7 serotypes was markedly reduced by 2009, and nonvaccine serotypes became the predominant colonizers.5,17,18 Indirect protection against invasive pneumococcal disease in unvaccinated groups has also been reported.19

Before the introduction of PCV7, vaccine serotypes caused 80% of invasive pneumococcal disease in young children. The proportion of invasive pneumococcal disease caused by vaccine serotypes was considerably lower in adults, but it increased with increasing age, reaching 51% in those 85 years of age or older.20 Seven years after the introduction of PCV7, invasive pneumococcal disease caused by vaccine serotypes was almost eliminated in children younger than 5 years of age and declined by more than 85% in all unvaccinated age groups. Total cases of invasive pneumococcal disease, which include cases caused by vaccine serotypes and cases caused by nonvaccine serotypes, declined by 76% among children younger than 5 years of age and by 43%, 40%, 18%, and 37% among persons 5 to 17 years of age, 18 to 49 years of age, 50 to 64 years of age, and 65 years of age or older, respectively.1 These total reductions in invasive pneumococcal disease encompass the decline in vaccine-serotype disease and the increase in nonvaccine serotype disease.11

The reduction in hospitalizations for pneumonia among unvaccinated persons is perhaps more remarkable than the decline among young children, who were targeted for vaccination. Indeed, older adults accounted for more than half the decline in overall hospitalizations for pneumonia. The patterns of decline in hospitalizations for pneumonia are similar to those observed for all cases of invasive pneumococcal disease, with the largest relative and absolute reductions at the extremes of age.1,2 For both invasive pneumococcal disease and pneumonia, the potential for disease reduction was highest at the extremes of age, because the rates of vaccine-serotype disease were highest in these age groups before PCV7 was introduced.20

Substantial reductions in rates of childhood pneumonia have been reported in other countries where PCV7 has been introduced. In Australia, a time-series analysis showed reductions of 38% and 29% in pneumonia among children younger than 2 years of age and those 2 to 4 years of age, respectively, within 2 years after the introduction of the vaccine in 2005.21 In the United Kingdom, hospitalizations for pneumonia among children younger than 15 years of age, which had increased through 2006, when PCV7 was introduced there, fell by 19% by 2008.22 The association of declines in rates of pneumonia with the timing of vaccine introduction in multiple countries supports a causal association.

The attribution of changes in pneumonia to the PCV7 vaccination program also requires consideration of changes in coding practices, hospital admission thresholds, and other factors. Despite stable overall hospitalization rates among older adults in the years 2000 through 2009, there were major declines in hospitalizations for which the diagnostic codes were pneumonia, congestive heart failure, and coronary atherosclerosis.14 Lindenauer et al. explored changes in hospital coding for pneumonia in the years 2003 through 2009 and found increasing use of sepsis as the first listed diagnosis and of pneumonia as a secondary rather than primary (first-listed) diagnosis.23 Our definition of hospitalization for pneumonia included hospitalizations for which sepsis was the primary diagnosis, so our reported rates were not influenced by such coding changes.

Pneumonia is the only common childhood condition for which hospitalizations declined during the study period,14 and the decline was temporally associated with the introduction of PCV7.9 Among children, the decline in hospitalizations for pneumonia was not accompanied by a “compensatory” increase in outpatient visits for pneumonia24; in fact, decreases in outpatient visits for pneumonia were reported.25-28 In addition, the decline in the length of stay and the stability of in-hospital rates of death from pneumonia (Table 1) suggest no major increases in admission thresholds.

It seems unlikely that influenza vaccination was a major contributor to these declines in childhood pneumonia, since influenza vaccination of healthy young children was uncommon before the initial (2004) and expanded (2006) recommendations for it were made by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices. By 2009, only 30% of healthy children were being vaccinated for influenza.29 Among adults, the major increases in pneumococcal and influenza vaccination predate the introduction of PCV7. Among adults 65 years of age or older, the rates of both pneumococcal polysaccharide vaccination and influenza vaccination had more than doubled between 1989 and 1999 (from 14% to 50% and from 30% to 66%, respectively).30 Similarly, the rate of smoking fell from 40% of the adult population in the 1970s to 26% in the 1990s.31 During this period in which major changes in immunization practices and smoking behavior occurred, hospitalizations for pneumonia in adults actually increased.32 Since the introduction of PCV7 in 2000, there have been much more modest changes, with the percentage of adults 65 years of age or older who received pneumococcal polysaccharide vaccine increasing to 60% and the percentage who received influenza vaccine increasing to 67% by 2008.30 During this same period, the percentage of adults who smoked fell to 24%.31

Notwithstanding the substantial reductions in pneumonia observed after the introduction of PCV7, unvaccinated age groups have a residual burden of pneumococcal disease due to serotypes covered by the vaccine.13 In the United Kingdom, a novel urinary immunoassay was used to diagnose serotype-specific pneumococcal pneumonia in hospitalized adults 2 years after PCV7 was introduced. Investigators estimated that 40% of cases of pneumonia were pneumococcal, that at least 20% of these cases were caused by PCV7 serotypes, and that this portion increased with increasing age.33 Thus, even 2 years after the introduction of the vaccine and despite a rapid decline in cases of childhood invasive pneumococcal disease, a substantial portion of cases of pneumonia in adults were still due to vaccine serotypes. This finding is consistent with the slower rate of decline in cases of invasive pneumococcal disease caused by PCV7 serotypes in U.S. adults1 and with the modest decline in all cases of pneumonia in adults during the early PCV7 period.

It is not known whether the direct vaccination of adults with PCV13 would prevent pneumonia in adults and whether such efforts would add substantially to the indirect benefits generated by the ongoing PCV13 vaccination program in infants, which may now be reducing the transmission of the additional six vaccine serotypes.34,35 PCV13 has recently been recommended for immunocompromised adults in the United States,36 a group for which efficacy data are already available,37 and indirect benefits are likely to be modest.13,38

In summary, the reduction initially observed in hospitalizations for childhood pneumonia was sustained in the decade after 2000, when PCV7 was introduced. More modest relative declines in hospitalizations for pneumonia among older adults emerged more slowly and resulted in large absolute overall reductions in hospitalizations for pneumonia.