Search

Background: Estimation of the magnitude of the herd effect on invasive pneumococcal disease (IPD) is important when evaluating health benefits and cost-effectiveness of paediatric pneumococcal conjugate vaccine (PCV) programmes and may influence policy makers' decisions on PCV use. Several epidemiological, programmatic, and immunological factors can affect the magnitude of the PCV herd effect. We investigated to what extent the choice of analytical methodology may also influence herd effect estimates., Methods: To estimate the magnitude of the herd effect from paediatric PCV programmes, we examined overall IPD incidence rates in ≥65-year-olds from Finland, Australia, England/Wales, and the United States under different analytical scenarios. We used two different statistical methods: before/after comparison of average IPD incidence rates and interrupted time series (ITS) analysis accounting for underlying time trends. We also investigated how varying the length of the pre- and post-PCV analysis periods influenced the outcomes., Results: The estimated impact of paediatric PCV programmes on IPD incidence rates in adults ≥65 years varied substantially across the different scenarios within each country. The choice of statistical method and analysis periods contributed to this variation, and their influence varied by setting. For the datasets from England/Wales and the United States, the different scenarios produced relatively minor variation in estimated impact. For the Australian and Finnish datasets, differences were more prominent. In particular, for Finland, opposite conclusions could be drawn depending on the methodology: while no estimated herd effect was seen with the before/after method, a herd effect was evident with the ITS method., Conclusions: The choice of statistical method and analysis periods can substantially influence the magnitude of estimated herd effects from paediatric PCV programmes. It is important to consider the reliability and presence of pre-PCV patterns in the IPD surveillance data used for analysis, the methodology and associated assumptions used to estimate herd effects., (Copyright © 2018 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.)

Universal infant vaccination with the 7-valent pneumococcal conjugate vaccine (PCV7) has nearly eliminated PCV7-serotype invasive pneumococcal disease (IPD) in young U.S. children, but has been accompanied by increases in the incidence of serotype 19A IPD. Because antibiotic-non-susceptible 19A has increased more than antibiotic-susceptible 19A, antibiotic selection pressure could be contributing to this trend. We developed a dynamic compartmental transmission model of pneumococcus to better understand the causes of this rise and to estimate the impact of vaccines or changes in antibiotic use on future IPD incidence in the U.S. in <2 year-olds. The model predicted that with current practices, serotype 19A IPD incidence will plateau at about the 2007 level over the next few years. The model suggests that antibiotic usage played a major role in the rise in antibiotic-non-susceptible 19A IPD, with a lesser contribution from PCV7 vaccination. However, hypothetical large decreases in antibiotic use starting in 2008 are predicted to yield only gradual decreases in antibiotic-non-susceptible 19A IPD. On the other hand, vaccines with modest (20%) effectiveness against 19A (or 6A or PCV7-serotypes) carriage are predicted to substantially (by 80%) decrease the incidence of IPD caused by those serotypes within 10 years of implementation. Our findings highlight that vaccine effects on colonization are key to their overall benefits. In addition, serotype changes following vaccine introduction may have multifactorial origins, with antibiotic use an important factor for resistant strains such as 19A.

Background: Introduction of the 7-valent pneumococcal conjugate vaccine (7vCRM) in several countries has led to a rapid, significant drop in vaccine-type invasive pneumococcal disease (IPD) in immunized children. In the United States and some other countries with high antibiotic use, a subsequent rise in serotype 19A IPD has been taken to indicate that the 19F conjugate in the vaccine provides no cross-protection against the immunologically related 19A., Discussion: We systematically assessed the clinical efficacy and effectiveness of 19F-containing vaccines against 19A disease or nasopharyngeal carriage by searching English-language articles in the electronic databases PubMed, Current contents, Scopus, and Embase from 1985 to 2008. The vaccine efficacy and effectiveness point estimates were consistently positive for modest protection against 19A IPD and acute otitis media (AOM). However, statistical significance was not reached in any individual study. No consistent impact of 7vCRM on 19A nasopharyngeal colonization could be detected. These findings are discussed in context of immunogenicity analyses indicating that 7vCRM induces functionally active anti-19A antibodies after the booster dose, and that other 19F-containing vaccine formulations may elicit higher levels of such antibodies after both primary and booster doses., Summary: Taken together, these results suggest that 19F-conjugates can provide some protection against 19A disease. The magnitude of this protection in a given setting will likely depend on several factors. These include the anti-19A immunogenicity of the specific vaccine formulation, the number of doses of that formulation needed to elicit the response, and the burden of 19A disease that occurs after those doses. It is possible that a modest protective effect may be obscured by the presence of countervailing selection pressures (such as high antibiotic use) that favor an increase in colonization with antibiotic-non-susceptible strains of 19A.

Background: US recommendations issued in 1999 for hepatitis A (HA) childhood immunization varied according to regional HA incidences prior to vaccination. Mathematical models of HA transmission, especially those accounting for herd protection, can be useful in formulating new, highly effective recommendations that could lead to disease elimination., Methods: A mathematical model of HA transmission was designed to assess the impact of different vaccination strategies on the evolution of HA infection over time in the United States. The model represents HA transmission dynamics and is stratified by age and regions defined in the Advisory Committee for Immunization Practices 1999 recommendations. The model accounts for herd protection and HA importation, using an age-dependent "force of infection" varying over time as a function of the prevalence of subjects with infectious HA., Results: The model predicts a clear benefit of vaccinating all US children at as young an age as possible. Nationwide routine immunization at 1 year of age with 70% coverage would prevent 57% of additional cases during the period 1995-2029, compared with the continuation of the regional strategy of vaccinating children at 2 years of age, as recommended by the Advisory Committee for Immunization Practices in 1999. In contrast, the model also predicts that nationwide routine immunization for children 12 years of age only would result in a 14% increase of HA cases during the period 1995-2029, compared with the number of cases predicted with the regional strategy of the immunization of 2-year-olds., Conclusions: These findings highlight the importance of accounting for herd protection induced by early childhood HA vaccination. They also support the very recent Advisory Committee for Immunization Practices recommendations for universal HA immunization of 1-year-olds.

The development of glycoconjugate vaccines for Streptococcus pneumoniae that are effective in very young children has renewed interest in identification of which among the more than 90 pneumococcal serotypes are most likely to cause invasive pneumococcal disease (IPD). Serotype distribution is thought to vary geographically, even between regions as socioeconomically similar as western Europe and North America. To explain these variations, we note the considerable variation that exists between reported rates of IPD in young children in the USA and west European countries. We postulate that this variation is attributable to different blood-culture rates and practices, and that mild IPD is probably underdiagnosed and under-reported in western Europe. On the basis of a comparison of serotype distributions between the two regions, we also postulate that those serotypes found at similar frequencies in both regions are virulent and rarely cause mild disease. As a result, reported distributions of IPD serotypes, especially when expressed as percentages, might be strongly skewed by the distribution of clinical presentations in a particular study population.