Lexau, C. et al. Changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine. JAMA 294, 2043-2051

Department of International Health, Johns Hopkins University, Baltimore, Maryland, United States
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 10/2005; 294(16):2043-51. DOI: 10.1001/jama.294.16.2043
Source: PubMed


A conjugate vaccine targeting 7 pneumococcal serotypes was licensed for young children in 2000. In contrast to the 23-valent polysaccharide vaccine used in adults, the 7-valent conjugate vaccine affects pneumococcal carriage and transmission. Early after its introduction, incidence of invasive pneumococcal disease declined among older adults, a group at high risk for pneumococcal disease.
To determine among adults aged 50 years or older whether incidence of invasive pneumococcal disease, disease characteristics, or the spectrum of patients acquiring these illnesses have changed over the 4 years since pneumococcal conjugate vaccine licensure.
Population-based surveillance of invasive pneumococcal disease in 8 US geographic areas (total population, 18,813,000), 1998-2003.
Incidence of invasive pneumococcal disease by pneumococcal serotype and other characteristics; frequency among case patients of comorbid conditions and other factors influencing mortality.
Incidence of invasive pneumococcal disease among adults aged 50 years or older declined 28% (95% confidence interval [CI], -31% to -24%), from 40.8 cases/100,000 in 1998-1999 to 29.4 in 2002-2003. Among those aged 65 years or older, the 2002-2003 rate (41.7 cases/100,000) was lower than the Healthy People 2010 goal (42 cases/100,000). Among adults aged 50 years or older, incidence of disease caused by the 7 conjugate vaccine serotypes declined 55% (95% CI, -58% to -51%) from 22.4 to 10.2 cases/100,000. In contrast, disease caused by any of the 16 serotypes only in polysaccharide vaccine did not change, and disease caused by serotypes not in either vaccine increased somewhat, from 6.0 to 6.8 cases/100,000 (13%; 95% CI, 1% to 27%). Between 1998-1999 and 2002-2003, the proportion of case-patients with human immunodeficiency virus infection increased from 1.7% (47/2737) to 5.6% (124/2231) (P<.001), and those with any comorbid condition that is an indication for pneumococcal polysaccharide vaccination increased from 62.3% (1842/2955) to 72.0% (1721/2390) (P<.001).
Our findings indicate that use of conjugate vaccine in children has substantially benefited older adults. However, persons with certain comorbid conditions may benefit less than healthier persons from the indirect effects of the new vaccine.

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    • "The potential of a vaccine to prevent disease depends on the incidence of disease caused by serotypes that are covered by the vaccine, the vaccine effectiveness (VE) and the vaccine uptake. Like in other settings where PCV has been implemented in childhood immunisation programmes (Lexau et al. 2005;Miller et al. 2011;Harboe et al. 2014), the epidemiology of IPD in Norway has substantially changed, both by direct protection of immunised children, and by indirect protection due to decreased transmission of vaccine serotype pneumococci to non-vaccinated age-groups (Steens et al. 2013). Simultaneously, the incidence of IPD caused by non-vaccine serotypes (NVT) has slightly increased as a result of serotype replacement (Weinberger et al. 2011;Hicks et al. 2007;Miller et al. 2011;Steens et al. 2013). "
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    ABSTRACT: Two different vaccines, a 23-valent polysaccharide vaccine (PPV23) and a 13-valent conjugate vaccine (PCV13), are available for prevention of invasive pneumococcal disease (IPD) in the population aged 65 years and older (65+). The IPD epidemiology in the 65+ is undergoing change due to indirect effects of childhood immunisation. Vaccine recommendations for the 65+ must take into account these trends in epidemiology. We therefore explored the preventive potential of vaccination strategies to prevent IPD in the 65+, including PPV23, PCV13 or PCV13+PPV23 in 2014-2019. Quasi-Poisson regression models were fitted to 2004-2014 population-wide surveillance data and used to predict incidences for vaccine-type and non-vaccine type IPD. We determined the number of people needed to be vaccinated to prevent one case per season (NNV) for each strategy and estimated the public health impact on the IPD case counts from increasing the vaccine uptake to 28-45%. Our results indicate that PCV13-IPD will decrease by 71% from 58 (95% prediction interval 55-61) cases in 2014/15 to 17 (6-52) in 2018/19 and PPV23-IPD by 32% from 168 (162-175) to 115 (49-313) cases. The NNV will increase over time for all strategies because of a decreasing vaccine-type IPD incidence. In 2018/19, the PCV13-NNV will be 5.3 times higher than the PPV23-NNV. Increasing the vaccine uptake will lead to a larger public health impact for all scenarios. Combining PCV13 and PPV23 is most effective, but the additional effect of PCV13 will decrease and is only marginal in 2018/19. Our study demonstrates the importance of increasing PPV23 uptake and of developing vaccines that confer broader immunity. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
    Epidemics 01/2015; 30. DOI:10.1016/j.epidem.2015.01.001 · 1.87 Impact Factor
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    • "Finally, the multivariable logistic regression analyses we performed allow to adjust for possible confounding by age, sex and comorbidities of the association of serotype/serogroup with the analyzed outcomes, but are not capturing the more complex biological interactions between host and bacterial factors in shaping the likelihood of the analyzed outcomes. However, our results are comparable with similar studies from different settings [2] [4] [6] [20] "
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    ABSTRACT: Background: In Switzerland, the heptavalent (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) were recommended for all infants aged <2 years in 2007 and 2011, respectively. Due to herd effects, a protective impact on the invasive pneumococcal disease (IPD) rates in adults had been expected. Methods: Within this study, data from the nationwide mandatory surveillance was analyzed for all adult patients ≥16 years with IPD of known serotype/serogroup during 2003-2012. Trend (for IPD cases from 2003 to 2012) and logistic regression analyses (2007-2010) were performed to identify changes in serotype distribution and to identify the association of serotypes with age, clinical manifestations, comorbidities and case fatality, respectively. Findings: The proportion of PCV7 serotypes among all IPD cases (n=7678) significantly declined in adults from 44.7% (2003) before to 16.7% (2012) after the recommendation of PCV7 (P<0.001). In contrast, the proportion of non-PCV7 serogroup/serotypes increased for non-PCV13 but also PCV13 serotypes (not included in PCV7) at the same time. Serotype distribution varied significantly across ages, clinical manifestations and comorbidities. Serotype was furthermore associated with case fatality (P=0.001). In a multivariable logistic regression model, analyzing single serotypes showed that case-fatality was increased for the serotypes 3 (P=0.008), 19A (P=0.03) and 19F (P=0.005), compared to serotype 1 and 7F. Conclusion: There was a significant decline in PCV7 serotypes among adults with IPD in Switzerland after introduction of childhood vaccination with PCV7. Pneumococcal serotypes were associated with case fatality, age, clinical manifestation and comorbidities of IPD in adults. These results may prove useful for future vaccine recommendations for adults in Switzerland.
    Vaccine 07/2014; 32(40). DOI:10.1016/j.vaccine.2014.07.060 · 3.62 Impact Factor
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    • "The fact that only 38% of isolates identified were PCV7 serotypes (plus serotype 6A) suggests that these serotypes represent a smaller proportion of potential IPD-causing serotypes and that vaccination with the PCV13 may increase protection against IPD. The low percentage of PCV7-related serotypes could be due to the herd immunity effect, as reported in the United States31,32 and United Kingdom,33 however, considering that the uptake of PCV7 is low in Singapore.15 Also, minimal changes were reported in the incidences of IPD in children in Singapore after early stages of PCV7 implementation during 2005–2010 by Thoon et al.34 "
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    ABSTRACT: Streptococcus pneumoniae is a major cause of sepsis, meningitis and respiratory disease worldwide. Pneumococcal conjugate vaccines (PCVs) have now been implemented in many countries worldwide, including Singapore. To evaluate the effectiveness of these vaccines, pneumococcal surveillance studies are required. Detailed and unified pneumococcal epidemiology data are currently scarce in South East Asia. Thus, we present data on invasive pneumococcal (IPD) isolates from Singapore that could assist in evaluating the effectiveness of pneumococcal vaccine in Singapore. One hundred and fifty-nine invasive pneumococcal disease isolates were received by the National Public Health Laboratory in Singapore between June 2009 and August 2010. Isolates were characterized using serotyping and multilocus sequence typing. Twenty-four different serotypes were found, the most common of which were 19A, 3, 7F, 23F, 6B, 14, 8 and 19F (in rank order). One hundred and two sequence types were observed, of which 38 were novel due to new alleles or new combinations of already existing alleles. Based on the Simpson’s Index of Diversity, serotypes 3, 6B and 19A were the most genetically diverse. Novel sequence types were more prevalent among conjugate vaccine serotypes 3, 19F and 23F and non-conjugate vaccine serotype 8, serogroup 15 and in non-typable isolates. We have demonstrated considerable genetic diversity among invasive pneumococci before and during the widespread use of conjugate vaccines in Singapore. Approximately half of all novel IPD clones identified in this study were non-conjugate vaccine serotypes. Although PCVs would target the most common serotypes, the high genetic diversity in non-vaccine serotypes would require further surveillance studies.
    Emerging Microbes and Infections 06/2014; DOI:10.1038/emi.2014.37 · 2.26 Impact Factor
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