Pneumococcal Vaccination Program Research Articles

Change in Bacterial Causes of Community-Acquired Parapneumonic Effusion and Pleural Empyema in Children 6 Years After 13-Valent Pneumococcal Conjugate Vaccine Implementation.

We describe here changes in the bacterial causes of pleural empyema before and after implementation of the 13-valent pneumococcal conjugate vaccine (PCV13) program in France (2009-2017). For 220 (39.3%) of 560 children, a bacterial cause was found. The frequency of pneumococcal infection decreased during the study from 79.1% in 2009 to 36.4% in 2017 (P < .001). Group A streptococcus is now the leading cause of documented empyema (45.5%).

The choice of analytical methodology can alter conclusions regarding herd effects of paediatric pneumococcal vaccination programmes

BackgroundEstimation 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. MethodsTo 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. ResultsThe 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. ConclusionsThe 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.

PIN82 - IN SMALL DOSES: MISSING THE BOOSTER DOSE IN A REDUCED PNEUMOCOCCAL CONJUGATE VACCINATION SCHEDULE

Policymakers in the UK are considering modifying the pneumococcal conjugate vaccination (PCV) program from a 2+1 to a 1+1 schedule. Our dynamic transmission model estimated an increase in invasive pneumococcal disease (IPD) in <2 year-olds due to the proposed schedule. This study builds upon previous work by investigating differential risk of IPD in those who do not receive the booster dose in the two schedules. An established transmission dynamic model was parameterized using UK serotype-specific IPD data and published literature to predict 5-year cumulative IPD incidence per 100,000. For children ages 1 - <2, IPD incidence risk ratios (IRR) were calculated as the risk of IPD without a booster dose compared to no booster dose. These IRR were then compared between 2+1 and 1+1 schedules. Scenario analyses examined the impact of modeling assumptions and parameter uncertainty. For a 2+1 schedule, the model predicted a 5-year cumulative IRR of vaccine-type IPD in 1 - <2 year-olds of 1.08 for those who miss the booster dose versus those receiving the booster dose. In a 1+1 schedule, this IRR was 1.37, a 27.3% relative increase compared to a 2+1 schedule. Scenario analyses found that effectiveness of a priming dose was the main driver of increased disease when individuals miss a booster, with relative increases ranging from 16.7% to 45.6%. Results demonstrate continued use of a 2+1 schedule would provide greater IPD protection to younger populations than the proposed 1+1 schedule. This outcome is magnified if single priming dose effectiveness is lower than hypothesized. Policymakers should consider the decreased protection afforded to children who may be more likely to miss their booster dose.

Modeling the sustained use of the 13-valent pneumococcal conjugate vaccine compared to switching to the 10-valent vaccine in Mexico

ABSTRACTIntroduction: Pneumococcal diseases caused by Streptococcus pneumoniae represent a significant health and economic burden. Mexico has benefited from the inclusion of the 7-valent (PCV7) and 13-valent pneumococcal conjugate vaccines (PCV13) since their inclusion in the National Immunization Program (NIP) in 2006 and 2010, respectively. The objective of this study is to estimate the impact of the existing program and predict future implications of a change in the current program.Methods: A previously published model was updated to estimate the historic impact of the PCV programs relative to pre-PCV implementation. Future disease trends were forecasted based on historical serotype behaviors for each PCV13 serotype and non-vaccine serotypes across different age groups. Costs and outcomes were estimated over a 10-year period based on continued use of PCV13 compared to a switch to PCV10.Results: The PCV7 and subsequent PCV13 NIP were estimated to prevent over 1.5 million cases of pneumococcal disease and 1,854 deaths, corresponding to a net savings of $34.50 Billion MXN. Continued use of PCV13 was estimated to save over 300 thousand cases of pneumococcal disease and 373 deaths compared to switching to PCV10 over a 10-year period. Despite a higher vaccine cost, maintaining PCV13 was cost-saving compared to PCV10, saving $6.71 billion MXN over 10 years.Conclusion: The PCV program in Mexico has provided a significant return on investment. Sustained PCV13 use was estimated to provide the greatest healthcare and economic impact in Mexico. Changes to the pneumococcal vaccination program could result in serotype replacement and reduction in herd effects.

Retrospective cost-effectiveness of the 23-valent pneumococcal polysaccharide vaccination program in Australia

BackgroundThe Australian infant pneumococcal vaccination program was funded in 2005 using the 7-valent pneumococcal conjugate vaccine (PCV7) and the 13-valent conjugate vaccine (PCV13) in 2011. The PCV7 and PCV13 programs resulted in herd immunity effects across all age-groups, including older adults. Coincident with the introduction of the PCV7 program in 2005, 23-valent pneumococcal polysaccharide vaccine (PPV23) was funded for all Australian adults aged over 65 years. MethodsA multi-cohort Markov model with a cycle length of one year was developed to retrospectively evaluate the cost-effectiveness of the PPV23 immunisation program from 2005 to 2015. The analysis was performed from the healthcare system perspective with costs and quality-adjusted life years discounted at 5% annually. The incremental cost-effectiveness ratio (ICER) for PPV23 doses provided from 2005 to 2015 was calculated separately for each year when compared to no vaccination. Parameter uncertainty was explored using deterministic and probabilistic sensitivity analysis. ResultsIt was estimated that PPV23 doses given out over the 11-year period from 2005 to 2015 prevented 771 hospitalisations and 99 deaths from invasive pneumococcal disease (IPD). However, the estimated IPD cases and deaths prevented by PPV23 declined by more than 50% over this period (e.g. from 12.9 deaths for doses given out in 2005 to 6.1 in 2015), likely driven by herd effects from infant PCV programs. The estimated ICER over the period 2005 to 2015 was approximately A$224,000/QALY gained compared to no vaccination. When examined per year, the ICER for each individual year worsened from $140,000/QALY in 2005 to $238,000/QALY in 2011 to $286,000/QALY in 2015. ConclusionThe cost-effectiveness of the PPV23 program in older Australians was estimated to have worsened over time. It is unlikely to have been cost-effective, unless PPV23 provided protection against non-invasive pneumococcal pneumonia and/or a low vaccine price was negotiated. A key policy priority should be to review of the future use of PPV23 in Australia, which is likely to be more cost-effective in certain high-risk groups.

Exploring the costs of a 13-valent pneumococcal conjugate vaccination program for home care patients

Objective: The city of Joensuu in Finland vaccinated 409 elderly home care patients with the 13-valent pneumococcal conjugate vaccine (PCV13) in autumn 2012. All home care patients were also eligible for a seasonal influenza vaccine. The objective of this retrospective real-world data cohort study was to evaluate whether the immunization intervention with PCV13 for home care patients was cost saving from the payer’s (municipality’s) perspective in terms of a return on investment (ROI).Methods: This was a retrospective observational registry study. We used registry data from the regional Mediatri patient information system covering all North Karelian municipalities, including individual-level data for all health and social care service utilization, diagnoses and procedures. Home care patients and their use of services were followed for 2 years. Cost comparisons were based on two specifications: (1) pneumonia-related health care costs; and (2) total health care costs. We compared patients who had received both influenza and PCV13 vaccinations to patients only vaccinated against influenza.Result: The pneumonia-related costs in the PCV13-vaccinated group were 434 EUR lower and the total health care costs 3800 EUR lower per person, compared to the non-PCV13-vaccinated group (bootstrapped 95% CIs -1682–527 EUR and -8233–621 EUR, respectively). PCV13 vaccination was associated with a return on investment of 7 EUR per 1 EUR spent during the 2 year follow-up period when pneumonia-related costs were used as baseline. Probability of the positive return on investment was .715.Conclusion: The results suggest that vaccinating home care patients could potentially be cost saving from the health care and service producer’s perspectives. The uncertainty from the decision-making perspective was due to the large variation in individual costs.

The impact on vaccination coverage following introduction of a routine pneumococcal vaccination programme for the elderly in Japan

In October 2014, a routine pneumococcal vaccination programme in the elderly aged 65–100 years old was initiated in Japan. Currently, this programme is within a transitional period. Eligibility for subsidy under the programme is granted for target ages in 5-year increments, over a 5-year roll-out period. We assessed the impact of the routine vaccination programme on vaccination coverage and explored the factors relating to pneumococcal vaccine uptake. We conducted a cross-sectional web-based survey in 2015 for respondents aged 65–79 years. A total of 3889 respondents answered the survey. The vaccination coverage in this study was estimated as 33.5%. Of the total respondents, 3327 were not vaccinated at initiation of the routine vaccination programme. The uptake of vaccination after implementation of the programme among them was 22.3%. There was a significant relationship between vaccination and eligibility for subsidy under the routine vaccination programme (adjusted odds ratio: 16.7). While there are some limitations to this study, introduction of the routine vaccination programme might affect pneumococcal vaccination coverage in the elderly.

Evolution of Pneumococcal Vaccine introduction in Childhood and Older Adult National Immunization Programs in Latin America and the Caribbean

Background: In Latin America and the Caribbean (LAC), Streptococcus pneumoniae is associated with an important burden of disease and mortality. The highest incidence of invasive disease and fatality occur at the extremes of life (the first 12 months of life and 65 years or older). In 2007, WHO recommended that all countries should include pneumococcal conjugate vaccine (PCV) as part of their childhood national immunization program (NIP). Since then, PCV uptake globally has occurred rapidly. In 2015, PAHO launched the 2015-2020 Regional Immunization Action Plan which promotes universal and equitable access to immunization services throughout the life cycle. The objective of this review is to describe the evolution of the incorporation of publicly funded pneumococcal immunization in childhood and older adults in LAC NIPs since their recommendation by WHO or PAHO. Methods & Materials: A comprehensive search was done of official national government websites and the country profiles in the WHO immunization monitoring system. Results: Currently, 36 LAC countries/territories have introduced PCV10 or PCV13 in their routine childhood NIP representing 98% of the region's birth cohort (10.8 million). The majority of the countries/territories use PCV13, with the exception of Brazil, Colombia and Ecuador, which use PCV10. All NIPs have a 3-dose schedule (either 2+1 or 3+0). A total of 8 countries have a universal funded program for older adults for 60 or 65 years and older, representing 30% of the region's cohort population (22 and 15 million, respectively). Six countries have pneumococcal polysaccharide vaccine (PPV23) (Chile, Costa Rica, Mexico, Nicaragua, Paraguay, and Uruguay) and two countries fund a sequential regimen with PCV13+PPV23 (Argentina and Panamá). Some countries have implemented or extended funding of pneumococcal immunization to high risk patients. Conclusion: Fast and efficient PCV introduction in infants has occurred since 2007 following WHO/PAHO recommendations. Unlike the introduction of pneumococcal vaccine in childhood in LAC NIPs, only a few countries in LAC have introduced a universal pneumococcal vaccination program for older adults in their NIPs. Infant and older adult cohorts that could potentially benefit from a publicly funded pneumococcal vaccination NIP represent around 98% and 30% of the referenced populations, respectively.

Prevalence of middle ear abnormalities from otitis media in relation with pneumococcal vaccine use in the Inuit population of Nunavik, province of Quebec, Canada

BackgroundOtitis media (OM) constitutes an important public health problem in the Inuit population of Nunavik, Northern Quebec. One of the objectives of the childhood pneumococcal vaccination program is to reduce OM burden. The program was implemented in 2002, and 7-, 10-, and 13-valent conjugate vaccines were used sequentially, with doses offered at 2, 4, 6 and 12–18 months, respectively. ObjectiveTo assess the prevalence of middle ear abnormalities at age 5 years in relation with exposure to different pneumococcal conjugate vaccines. MethodsImmunization cards and audiology screening tests at age 5 years of children born in 1994–2010 were reviewed. Children were classified according to the vaccine schedule recommended for their birth cohort or to the vaccines they actually received. Log-linked binomial regression models were used to assess the relative abnormalities risk according to different vaccination schedules. ResultsAmong 3517 children with complete documentation, the prevalences of minor and major abnormalities were 29% and 18%, respectively. Minor abnormalities frequency was higher in unvaccinated children (34%) and lower in children vaccinated with PCV7 (22%), PCV7 + PCV10 (17%), PCV10 (15%) and PCV10 + PCV13 (18%). No substantial differences among vaccine schedules were observed for major abnormalities. ConclusionsPneumococcal conjugate vaccination was associated with a decreased frequency of middle ear abnormalities although no effect was seen for major abnormalities which may be trigger by OM with early onset.Clinicaltrials.gov registration number: NCT01694329

Serotype distribution of invasive Streptococcus pneumoniae in adults 65 years of age and over after the introduction of childhood 13-valent pneumococcal conjugate vaccination programs in Canada, 2010–2016

The 13-valent conjugate vaccine (PCV13) was recommended for childhood immunization programs in 2010 in Canada and has decreased the incidence of invasive pneumococcal disease (IPD) in children and changed the epidemiology of IPD in adults. This study investigated the epidemiology of IPD in adults 65 years of age and older in Canada. A total of 7282 invasive S. pneumoniae isolated from adults ≥65 years old were serotyped from 2010 to 2016 and antimicrobial susceptibility was performed on 2527 isolates. Serotyping was performed by Quellung reaction using commercial antisera and antimicrobial susceptibilities were determined by broth microdilution. PCV7 serotypes decreased non-significantly from 2010 to 2016 from 9.1% (n = 96) to 6.7% (n = 72) while the additional six PCV13 serotypes declined significantly from 39.5% (n = 418) to 18.6% (n = 201) (p < 0.05). The 23-valent pneumococcal polysaccharide vaccine (PPV23) and non-vaccine (NVT) serotypes increased from 26.3% (n = 278) to 36.2% (n = 393) (p < 0.05), and from 25.1% (n = 266) to 38.4% (n = 416) (p < 0.05), respectively. There were no significant changes in antimicrobial resistance rates from 2011 to 2016: 24.1% of the IPD from adults ≥65 years were resistant to clarithromycin (n = 609), 10.0% to doxycycline (n = 254), 11.8% to penicillin (n = 299), 5.2% to cefuroxime (n = 131), 6.6% to clindamycin (n = 168), 6.0% to trimethoprim-sulfamethoxazole (n = 152), and 0.5% (n = 12) to ceftriaxone. Although overall incidence of IPD in adults ≥65 years has remained relatively constant from 2010 to 2016, childhood PCV13 vaccination programs have been successful in indirectly reducing IPD caused by PCV13 serotypes in adults through herd immunity effects.

Predicting the impact of pneumococcal conjugate vaccine programme options in Vietnam

ABSTRACTAlthough catch-up campaigns (CCs) at the introduction of pneumococcal conjugate vaccines (PCVs) may accelerate their impact, supply constraints may limit their benefit if the need for additional PCV doses results in introduction delay. We studied the impact of PCV13 introduction with and without CC in Nha Trang, Vietnam – a country that has not yet introduced PCV – through a dynamic transmission model. We modelled the impact on carriage and invasive pneumococcal disease (IPD) of routine vaccination (RV) only and that of RV with CCs targeting <1y olds (CC1), <2y olds (CC2) and <5y olds (CC5). The model was fitted to nasopharyngeal carriage data, and post-PCV predictions were based on best estimates of parameters governing post-PCV dynamics. With RV only, elimination in carriage of vaccine-type (VT) serotypes is predicted to occur across all age groups within 10 years after introduction, with near-complete replacement by non-VT. Most of the benefit of CCs is predicted to occur within the first 3 years with the highest impact at one year, when IPD incidence is predicted to be 11% (95%CrI 9 – 14%) lower than RV with CC1, 25% (21 – 30 %) lower with CC2 and 38% (32 – 46%) lower with CC5. However, CCs would only prevent more cases of IPD insofar as such campaigns do not delay introduction by more than about 6, 12 and 18 months for CC1, CC2 and CC5. Those findings are important to help guide vaccine introduction in countries that have not yet introduced PCV, particularly in Asia.

Estimating the cost-effectiveness of a sequential pneumococcal vaccination program for adults in Germany.

IntroductionIn Germany, a 23-valent polysaccharide pneumococcal vaccine (PPSV23) is recommended for elderly (60+) and patients 16+ with chronic diseases not associated with immune suppression. For all other patients at risk, sequential immunization with a 13-valent pneumococcal conjugate vaccine (PCV13) first, followed by PPSV23 is recommended. Repeated vaccination with PPSV23 is recommended every 6 years after individual assessment by the physician. This was adopted into the vaccination directive with binding reimbursement and funding. However, additional voluntary services allow statutory health insurances to differentiate from each other. Aim of this study is to estimate the cost-effectiveness of voluntary service scenarios compared to the strategy in place to support informed decision making.MethodsA microsimulation framework with Markov-type process of a population susceptible to pneumococcal disease over a lifetime horizon was developed to compare effectiveness and cost-effectiveness of different vaccination strategies. We simulated 1,000 iterations for seven scenarios. Assumptions were derived from published literature and probabilistic sensitivity analysis was run to show the robustness of the model.ResultsOur study indicates that all voluntary service strategies could prevent further clinical cases compared to the existing policy. Depending on the scenario, 48–142 invasive pneumococcal disease (IPD), 24,000–45,000 hospitalized all-cause nonbacteremic pneumonia (NBP), 15,000–45,000 outpatient NBP cases, and 4,000–8,000 deaths could be avoided on average. This refers to potential savings of €115 Mio. - €187 Mio. for medical and non-medical costs. Additional costs per patient for the payer are €2.48 to €7.13 and for the society €2.20 to €6.85. The ICER per LYG ranged from €3,662 to €23,061 (payer) and €3,258 to €29,617 (societal). All but one scenario was cost-effective in ≥60% of the generated 1,000 simulations.ConclusionCompared to the vaccination strategy in place, the different hypothetical scenarios can be considered cost-effective and suitable as additional voluntary services.

Pneumococcal vaccination for HIV-infected individuals in Singapore

Susceptibility to infections with pneumococcal bacteria ( Streptococcus pneumoniae) is substantially higher among human immunodeficiency virus (HIV)-infected individuals, and accounts for a significant burden of morbidity and healthcare costs. Pneumococcal vaccination is recommended in most countries for HIV-infected adults. Current policy in Singapore and Australia recommends the use of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) as a booster dose following the use of 13-valent pneumococcal conjugate vaccine (PCV13). Despite this, adherence to this policy has been suboptimal in Singapore. This may be related to the fact that PPSV23 has not been shown to have any impact on pneumococcal carriage (the necessary prerequisite for disease development). PPSV23 has also been associated with immune hyporesponsiveness, raising concerns over the use of this vaccine globally and, in particular, in high-risk populations. The lack of data from studies comparing PCV13 and PPSV23 has also contributed to the suboptimal uptake of pneumococcal vaccines by healthcare professionals for HIV-infected individuals. This review article discusses the key issues and importance of rigorous pneumococcal vaccination programmes for HIV-infected individuals. Current recommendations for pneumococcal vaccination of HIV-infected individuals in Singapore should be adopted more readily to reduce the burden of pneumococcal disease in this high-risk group.

A pneumococcal conjugate vaccination programme reduced clinically suspected invasive disease in unvaccinated children.

The 10-valent pneumococcal conjugate vaccine was introduced to the Finnish national vaccination programme for children born since June 2010. We evaluated the changes in the rates of clinically suspected invasive pneumococcal disease (IPD) in unvaccinated children to estimate the indirect herd protection impact of the programme. The target cohort for this ecological before and after comparison were unvaccinated children born from January 2008 to May 2010 and ineligible for the vaccination programme, who were followed up from 2011 to 2014. The reference cohort was age and season-matched children born in January 2003 to 2005 and followed up from 2006 to 2009. National data on hospital discharge codes compatible with IPD or unspecified sepsis were collected. We compared the follow-up periods of 2007-2009 in the reference cohort and 2012-2014 in the target cohort. The incidence of non-laboratory-confirmed IPD in unvaccinated children fell by 68%, from 47 to 15/100 000 person-years. When unspecified sepsis was added, the decrease was 39%, from 171 to 104/100 000 person-years. Laboratory confirmed IPD fell by 44%, from 15 to 8/100 000 person-years. The pneumococcal vaccination programme provided herd protection against clinically suspected IPD. The absolute reduction was almost 10-times higher than for just laboratory-confirmed disease.

Modeling Possible Inclusion of Pneumococcal Conjugate Vaccine into the National Immunization Program for Infants in India

BackgroundIndia is home to up to 28 million infants born annually, and yet to a large extent these children do not benefit from the protection provided by a pneumococcal conjugate vaccine (PCV) immunization program. The Government of India, with support from Gavi, The Vaccine Alliance (in short, Gavi), has committed to a pilot implementation of PCV. There are few public health impact evaluations available for India, and equally limited epidemiologic data. ObjectivesTo estimate the potential impact of an infant pneumococcal vaccination program in India. MethodsUsing a well-established pneumococcal disease impact model parameterized with local data to the extent possible, we calculated the potential impact of introducing an infant PCV program in India. The model considered direct vaccine protection by PCV10 or PCV13, focusing on children younger than 5 years, while varying vaccine uptake according to the implementation method (i.e., state-level programs [Gavi funding] or a government-supported national immunization program [NIP]). ResultsWith state-level PCV13 programs comprising 25% uptake across the country, approximately 1.9 million cases of pneumococcal disease and approximately 77,000 deaths could be prevented annually. An NIP with PCV13 could prevent approximately 7.6 million cases of pneumococcal disease and approximately 0.3 million pneumococcal deaths annually, compared with no vaccination, considering 100% vaccine uptake. These results are likely to have underestimated the additional potential benefits of herd effects in unvaccinated children and adults. ConclusionsIncorporation of PCV into an Indian vaccination program for infants is predicted to have a substantially positive health impact. Gavi funding of state-level programs is an important step toward achieving the full benefits of an NIP in India.

Evolution over time in the cost-effectiveness of pneumococcal conjugate vaccine (PCV13) in older Australians due to herd protection from infant vaccination

In many settings, serotype changes as a result of infant 13-valent pneumococcal conjugate vaccine (PCV13) programs are likely to continue after the introduction of adult PCV13 programs. We applied a multi-cohort model to explore how potential serotype changes may impact on the cost-effectiveness of PCV13 use in Australian adults aged over 65 years. We found assumptions around continued herd protection from infant PCV13 programs to be critical when assessing the cost-effectiveness of adult PCV13 vaccination in Australia. Future cost-effectiveness analyses of adult PCV13 programs need to carefully consider how to predict these future changes in serotypes, with Australian data suggesting that the changes post-PCV13 use in infants may be different than post-PCV7.

Elucidating the impact of the pneumococcal conjugate vaccine programme on pneumonia, sepsis and otitis media hospital admissions in England using a composite control

BackgroundThe seven-valent pneumococcal conjugate vaccine (PCV) was introduced in England in September 2006, changing to the 13-valent vaccine in April 2010. PCV impact on invasive pneumococcal disease (IPD) has been extensively reported, but less described is its impact on the burden of pneumonia, sepsis and otitis media in the hospital.MethodsUsing details on all admissions to hospitals in England, we compared the incidence of pneumococcal-specific and syndromic disease endpoints in a 24-month pre-PCV period beginning April 2004 to the 24-month period ending March 2015 to derive incidence rate ratios (IRRs). To adjust for possible secular trends in admission practice, IRRs were compared to the IRRs for five control conditions over the same period and the relative change assessed using the geometric mean of the five control IRRs as a composite, and individually for each control condition to give the min-max range. Relative changes were also compared with IRRs for IPD from the national laboratory database. The effect of stratifying cases into those with and without clinical risk factors for pneumococcal infection was explored.ResultsRelative reductions in pneumococcal pneumonia were seen in all age groups and in those with and without risk factors; in children under 15 years old reductions were similar in magnitude to reductions in IPD. For pneumonia of unspecified cause, relative reductions were seen in those under 15 years old (maximum reduction in children under 2 years of 34%, min-max: 11–49%) with a relative increase in 65+ year olds most marked in those with underlying risk conditions (41%, min-max: 0–82%). Reductions in pneumococcal sepsis were seen in all age groups, with the largest reduction in children younger than 2 years (67%, min-max 56–75%). Reductions in empyema and lung abscess were also seen in under 15 year olds. Results for other disease endpoints were varied. For disease endpoints showing an increase in raw IRR, the increase was generally reduced when expressed as a relative change.ConclusionsUse of a composite control and stratification by risk group status can help elucidate the impact of PCV on non-IPD disease endpoints and in vulnerable population groups. We estimate a substantial reduction in the hospitalised burden of pneumococcal pneumonia in all age groups and pneumonia of unspecified cause, empyema and lung abscess in children under 15 years of age since PCV introduction. The increase in unspecified pneumonia in high-risk 65+ year olds may in part reflect their greater susceptibility to develop pneumonia from less pathogenic serotypes that are replacing vaccine types in the nasopharynx.

Changes in the Nature and Severity of Invasive Pneumococcal Disease in Children Before and After the Seven-valent and Thirteen-valent Pneumococcal Conjugate Vaccine Programs in Calgary, Canada.

Since the introduction of childhood pneumococcal conjugate vaccines, invasive pneumococcal disease (IPD) incidence has decreased in children and the predominant serotypes causing disease have changed. This study describes changes in the clinical features of IPD in children (<18 years) before and after the conjugate vaccine introduction. The Calgary Area Streptococcus pneumoniae Epidemiology Research study collects information on all IPD cases in Calgary, Alberta, Canada. Descriptive and regression analyses were used to compare IPD in the pre-vaccine (January 2000 to August 2002), post-7-valent protein-polysaccharide conjugate vaccine (September 2002 to June 2010) and post-13-valent protein-polysaccharide conjugate vaccine (PCV13) (July 2010 to December 2015) periods; intensive care unit and inpatient admissions were outcome measures. The incidence of IPD in children (<18 years) decreased from an average of 17 cases/100,000/yr in 2000-2001 to 4 cases/100,000/yr in 2015. The median age of children presenting with IPD shifted from 2.0 years (interquartile range: 2.5) in the pre-vaccine period to 3.9 years (interquartile range: 6.2) in the post-PCV13 period. The proportion of children with a comorbidity that is an indication for pneumococcal vaccination did not change. Invasive disease with focus (meningitis, pneumonia, empyema, peritonitis) compared with invasive disease with bacteremia only increased from 44.6% in pre-vaccine to 64.0% and 61.4% in the post-7-valent protein-polysaccharide conjugate vaccine and post-PCV13 periods, respectively (P = 0.017). Having IPD in the post-PCV13 period compared with the pre-vaccine period was associated with an increased odds of hospitalization [Odds ratio (OR): 2.9; 95% Confidence Interval (CI): 1.4-6.2]. Clinical features of IPD have changed since pneumococcal conjugate vaccines were introduced, with a shift toward more focal infections requiring hospitalization. Although overall IPD cases have declined, disease that does occur appears to be more severe.

Decision-Tree Model for Support of Health Policy Choices Based on Pneumococcal Conjugate Vaccine (PCV) Program Outcomes.

Pneumococcal Conjugate Vaccine (PCV) has the potential to save lives in low-income countries. We have developed a computational model and web-based decision support software for comparing cost-benefit tradeoffs from alternative PCV program designs, considering their direct and indirect effects on early childhood populations in resource-poor settings. This supports policy-makers in estimating potential health outcomes and cost-effectiveness of different vaccination program strategies for a wide range of population coverage and vaccine effectiveness assumptions.

Radiographically Confirmed Community-Acquired Pneumonia in Pediatric Patients Prior to Pneumococcal Vaccination in Nepal

Background The massive burden of pediatric pneumonia is associated with high morbidity and mortality, particularly in developing countries where immunization programs are absent or recently been implemented. The objective of this study was to describe the number of hospitalizations and outcomes of children aged 1 month to 10 years with community-acquired pneumonia (CAP) between January 1, 2014, and June 30, 2015, in semi-rural Nepal. Methods This retrospective study was undertaken prior to the implementation of the pneumococcal conjugate vaccination (PCV) program in Bhaktapur district of Nepal. Chart review of children with CAP, defined as the presence of symptoms, physical examination findings compatible with bacterial pneumonia together with lobar consolidation on chest X-ray (CXR), was performed. Data extracted included laboratory parameters and blood cultures on admission, antibiotic treatment, and length of hospital stay, as well as complications, such as death, intensive care unit admission, pleural effusion, and empyema. Outcomes assessed were clinical improvement accompanied by radiological improvement of consolidation. Results During the study period, 367 patients were admitted with pneumonia, of which, 74 (20%) had definite CXR evidence of lobar pneumonia. A total of 86.5% of the cases were children &lt; 5 years of age. Admission blood cultures from all patients were negative. More than 80% of patients had white blood cell (WBC) counts &gt;11,000/mm3 and ≥ 75% neutrophils. The highest number of cases presented between February and July. Forty-three of 45 patients responded to crystalline penicillin (CP), and 25/27 patients treated with cefotaxime also responded; the mean duration of treatment was 10 ± 2.3 days. There were no deaths. None of the patients developed empyema, sepsis, or pleural effusion or required intensive care unit admission. Conclusions CAP in pre-PCV semi-rural Nepal mostly affects male children &lt; 5 years old and peaks between March and May. In-hospital treatment with CP or cefotaxime is effective.