Decreased Pneumococcal Meningitis after PCV7 Implementation: Another Vaccine Success Story
Decreased Pneumococcal Meningitis after PCV7 Implementation: Another Vaccine Success Story
Abstract & Commentary
Brian G. Blackburn, MD
Clinical Assistant Professor of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine
Dr. Blackburn reports no financial relationships relevant to this field of study. This article originally appeared in the June 2008 issue of Infectious Disease Alert. It was peer reviewed by Connie Price, MD. Dr. Price Reports no financial relationships relevant to this field of study.
Source: Tsai CJ, et al. Changing epidemiology of pneumococcal meningitis after the introduction of pneumococcal conjugate vaccine in the United States. Clin Infect Dis. 2008;46:1664-1672.
Synopsis: After implementation of universal childhood vaccination with the seven-valent pneumococcal conjugate vaccine (PCV7), the incidence of pneumococcal meningitis decreased not only among children, but also among adults.
Pneumococcal meningitis remains a deadly disease, with a case fatality rate among adults that is still above 20%, and also with permanent neurological sequelae in a substantial minority of survivors.1 Prevention of this disease, thus, remains an important element of public health policy. Although the 23-valent pneumococcal polysaccharide vaccine (PPV23) has been available for over 25 years, it has proven only adequate in preventing invasive pneumococcal disease in adults, with a protective efficacy of about 55-60%.2 Furthermore, because children under two years of age do not mount a reliable immunologic response to polysaccharide vaccines, protection of this high-risk group is not achieved with PPV23.
In 2000, a seven-valent pneumococcal conjugate vaccine (PCV7) was licensed in the United States, and recommendations followed shortly thereafter for universal vaccination of children 2-23 months of age.3 Conjugate vaccines offer several advantages over polysaccharide vaccines, including immunogenicity in young children, better stimulation of the memory T-cell response, and eradication of the carrier state, offering better herd immunity.
Although several studies have subsequently demonstrated sharp declines in invasive pneumococcal disease among the target population of this vaccine (children under two years of age), the data have not convincingly demonstrated a decrease in pneumococcal meningitis among adults.4 Because this conjugate vaccine would be expected to decrease pneumococcal colonization among children under two, one might expect the overall burden of disease due to the vaccine serotypes to decrease in the population.
Tsai and colleagues undertook a retrospective review of the Nationwide Inpatient Sample (NIS), a large database with patient level information from about 1000 hospitals (a 20% sample of community hospitals) in the United States. Using discharge diagnosis ICD-9 codes, they ascertained the incidence of pneumococcal and other forms of meningitis from 1994-2004, using population-based hospitalization and mortality rates. Universal PCV7 vaccination of children under two was recommended beginning in 2000; although they did not have access to individual patient vaccination status, they used year of illness as a proxy for vaccination status, with 1994-1999 regarded as the baseline (pre-vaccination) period, 2000 as the transitional year, and 2001-2004 as the post-vaccination period.
Hospitalization rates for pneumococcal meningitis decreased 33% among all ages in 2001-2004 compared to 1994-1999. Subgroup analysis showed that the decrease in pneumococcal meningitis hospitalization rates in the post-vaccination period was 66% among children under two and 33% among adults over 65, compared to the pre-vaccination period. In addition, deaths due to pneumococcal meningitis decreased 51% and 44% in these groups, respectively. Significant decreases in pneumococcal meningitis hospitalization rates were also seen in the 2-4 and 18-39 year age groups, and strong trends toward fewer hospitalizations were seen in the other age groups. Overall, Tsai et al estimated that PCV7 prevented 3330 pneumococcal meningitis hospitalizations and 394 deaths in 2001-2004. The median age of patients with pneumococcal meningitis increased from 37 to 46 years in the post-vaccination period due to the more robust impact on younger children. Interestingly, decreases in hospitalization rates for meningococcal, Haemophilus influenzae, and other types of meningitis were seen in the post-vaccination period as well.
Commentary
PCV7 has been one of the major public health success stories of the past decade. Not only has it resulted in a significant decrease in the incidence of invasive pneumococcal disease among young children (the target population of this vaccine, and the group at highest risk for bacterial meningitis), it has also resulted in significantly lower rates of invasive pneumococcal disease among adults, including pneumococcal meningitis. Probably related, in large part, to decreased colonization rates in vaccinated children, this is a prime example of the advantage of conjugate vaccines over polysaccharide vaccines.
Although Tsai et al did not have access to individual patient vaccination status, and could not control for the possibility of increased PPV23 vaccination rates among adults in 2001-2004, the declines in pneumococcal meningitis incidence occurred in sharp drops centered around the 2000-2001 period, lending weight to the hypothesis that the decreases described in the article were indeed due to PCV7, which came into widespread use in 2000. Although most other types of meningitis decreased over the study period as well, these seemed to be part of longer trends, dating back years prior to the implementation of PCV7; this renders an uncontrolled, confounding effect occurring in 2000 that decreased all causes of meningitis less likely.
Along with enthusiasm for the decrease in the seven PCV7 serotypes circulating in the community, and the resultant salutary effect on invasive pneumococcal disease, there has been concern that the increase in non-vaccine serotypes might negate the benefit of the vaccine.5 The data presented by Tsai et al suggest that despite this potential for serotype replacement, this has not affected the vaccine's impact on overall morbidity and mortality to date. This, however, does remain an issue that will require close monitoring in the years to come.
References
- van de Beek D, et al. Community-acquired bacterial meningitis in adults. N Engl J Med. 2006;354:44-53.
- Musher DM, et al. Effect of pneumococcal vaccination: a comparison of vaccination rates in patients with bacteremic and nonbacteremic pneumococcal pneumonia. Clin Infect Dis. 2006;43:1004-1008.
- Advisory Committee on Immunization Practices. Preventing pneumococcal disease among infants and young children. MMWR. 2000;49:1-35.
- Lexau CA, et al. Changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine. JAMA. 2005;294:2043-2051.
- Hicks LA, et al. Incidence of pneumococcal disease due to non-pneumococcal conjugate vaccine (PCV7) serotypes in the United States during the era of widespread PCV7 vaccination, 1998-2004. J Infect Dis. 2007;196:1346-1354.
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