Vaccine-type Disease Research Articles

Estimating the economic burden of pneumococcal meningitis and pneumonia in northern Ghana in the African meningitis belt post-PCV13 introduction

BackgroundGhana introduced 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant immunization program in 2012, using a three-dose primary series without a booster. Despite ≥ 88% reported three-dose vaccination coverage since 2013, PCV13-type pneumococcal meningitis outbreaks have occurred. We estimated the ongoing economic burden of PCV13-type pneumococcal meningitis and pneumonia in northern Ghana, an area within the African meningitis belt with seasonal increases of pneumococcal meningitis post-PCV13 introduction, to inform PCV13 vaccination policy. MethodsWe performed a cross-sectional survey among patients with pneumonia or meningitis at three hospitals in northern Ghana to determine patient-level costs (direct medical and nonmedical, indirect patient and caregiver costs) incurred in household, outpatient, and inpatient settings. Pneumonia burden was estimated using 2017–2018 administrative records. Pneumococcal meningitis burden was estimated using 2017–2018 case-based surveillance data. Economic burden was reported in 2019 U.S. dollars ($) from the societal perspective. ResultsFor an area with a total population of 5,068,521, our model estimated 6,441 PCV13-type pneumonia cases and 286 PCV13-type meningitis cases occurred in a typical year post-PCV13. In the base case scenario, the total economic burden was $5,230,035 per year ($777 per case). By age group, cost per PCV13-type pneumonia case was $423 (<5 years), $911 (5–14 years), and $784 (≥15 years); cost per PCV13-type meningitis case was $2,128 (<5 years), $3,247 (5–14 years), and $2,883 (≥15 years). Most (78.0–93.4%) of the total societal cost was due to indirect costs related to deaths from PCV13-type diseases. ConclusionsThe estimated economic burden of PCV13-type disease in northern Ghana remains substantial, especially in older children and adults who were expected to have benefited from indirect effects from infant immunization. Additional interventions such as changes in the infant immunization schedule, reactive vaccination, or catch-up PCV13 vaccination may be needed to control remaining vaccine-type disease.

Pneumococcal serotype trends, surveillance and risk factors in UK adult pneumonia, 2013–18

BackgroundChanges over the last 5 years (2013–18) in the serotypes implicated in adult pneumococcal pneumonia and the patient groups associated with vaccine-type disease are largely unknown.MethodsWe conducted a population-based prospective...

Preferences for Adult Pneumococcal Vaccine Recommendations Among United States Health Care Providers.

IntroductionIn 2014, the Advisory Committee on Immunization Practices (ACIP) of the US Centers for Disease Control and Prevention (CDC) recommended 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) for all adults aged ≥ 65 years, with a commitment to revisit the recommendation for PCV13 because of declining vaccine-type disease. The Evidence-to-Recommendation framework used by the ACIP includes review of evidence regarding feasibility and stakeholder acceptability, but no surveys of vaccinator preferences have been published in the literature.MethodsPhysicians (N = 700), physician assistants (N = 100), pharmacists (N = 100), and nurse practitioners (N = 100) who recently prescribed, administered, or recommended adult pneumococcal vaccine were surveyed in March 2018. Object-case best–worst scaling was used to assess preferences among potential recommendation scenarios: retaining the then-current 2014 recommendation without a scheduled re-evaluation, retaining with a scheduled re-evaluation, revising PCV13 to Category B (retaining PPSV23 as Category A), removing PCV13 (retaining PPSV23 as Category A), and removing both PCV13 and PPSV23.ResultsProviders’ most preferred recommendations were retaining the 2014 recommendation with another planned re-evaluation (52.6%) and retaining the then-current recommendation without planned re-evaluation (40.0%). Few preferred changing PCV13 to Category B (3.2%), removing PCV13 (3.7%), or removing both pneumococcal vaccines (0.5%).ConclusionsThe majority of vaccinators surveyed preferred to retain the 2014 recommendation, either with another scheduled reassessment or indefinitely.FundingPfizer, Inc.Electronic Supplementary MaterialThe online version of this article (10.1007/s40121-019-00266-5) contains supplementary material, which is available to authorized users.

1440. Potential Impact of Routine Use of 13-Valent Pneumococcal Conjugate Vaccine on Hospitalizations for Pneumonia among Older Adults in Canada

BackgroundIn Canada, 13-valent pneumococcal conjugate vaccine (PCV13) was licensed for the prevention of vaccine-type (VT) pneumonia in adults in July 2015. Herd effects stemming from the routine pediatric PCV13 program have historically led to reductions in VT disease in older adults, and there is currently no recommendation for a routine age-based PCV13 program for this age group. However, recent data suggest these indirect effects may have plateaued, leaving a persistent and substantial burden of potentially preventable pneumococcal disease in older adults. We evaluated the potential impact of PCV13 immunization program for Canadian adults aged ≥65 years on hospitalizations for community-acquired pneumonia (CAP).MethodsWe constructed a mathematical model based on Canada-specific burden of disease estimates and published estimates of PCV13 effectiveness and durability. We estimated the number of hospitalizations averted as the product of (i) the size of the Canadian population aged ≥65 years, (ii) the incidence of all-cause CAP, (iii) the proportion of CAP that is VT, (iv) PCV13 effectiveness, and (v) the duration of protection for PCV13 over a 5-year time horizon. We assumed that rates of all-cause CAP, the proportion of VT CAP, and PCV13 effectiveness remained constant over the 5-year assessment period. We assumed a 5% annual all-cause mortality rate in the overall population. We estimated hospital days averted as the product of hospitalizations averted and median length of stay. Model assumptions are summarized in Table 1.ResultsBased on model assumptions, PCV13 use in Canadian adults aged ≥65 years would lead to an annual rate reduction of 62 (11–77) hospitalizations per 100,000 persons, per year. This reduction, applied to the entire Canadian population of older adults, would avert an estimated 17,274 (3,037–21,711) hospitalizations and 138,192 (24,298–173,690) hospital days over a 5-year period.ConclusionDespite herd effects from the routine pediatric program, direct PCV13 immunization of older adults in Canada could result in considerable additional reduction in hospitalizations for pneumonia. Disclosures J. Vojicic, S. Dion, R. E. Isturiz, C. Laferriere, M. Major, R. M. Nepal, and J. A. Suaya: Pfizer: Employee and Shareholder, Benefits and stock and Salary; J. M. McLaughlin, Pfizer: Employee, Salary.

Pneumococcal vaccine impacts on the population genomics of non-typeable Haemophilus influenzae.

The implementation of pneumococcal conjugate vaccines (PCVs) has led to a decline in vaccine-type disease. However, there is evidence that the epidemiology of non-typeable Haemophilus influenzae (NTHi) carriage and disease can be altered as a consequence of PCV introduction. We explored the epidemiological shifts in NTHi carriage using whole genome sequencing over a 5-year period that included PCV13 replacement of PCV7 in the UK’s National Immunization Programme in 2010. Between 2008/09 and 2012/13 (October to March), nasopharyngeal swabs were taken from children <5 years of age. Significantly increased carriage post-PCV13 was observed and lineage-specific associations with Streptococcus pneumoniae were seen before but not after PCV13 introduction. NTHi were characterized into 11 discrete, temporally stable lineages, congruent with current knowledge regarding the clonality of NTHi. The increased carriage could not be linked to the expansion of a particular clone and different co-carriage dynamics were seen before PCV13 implementation when NTHi co-carried with vaccine serotype pneumococci. In summary, PCV13 introduction has been shown to have an indirect effect on NTHi epidemiology and there exists both negative and positive, distinct associations between pneumococci and NTHi. This should be considered when evaluating the impacts of pneumococcal vaccine design and policy.

Long-term impact of 10-valent pneumococcal conjugate vaccination on invasive pneumococcal disease among children in Finland

BackgroundThe ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Finnish National Vaccination Programme (NVP) in September 2010. The impact of PCV10 vaccination against invasive pneumococcal disease (IPD) in vaccine-eligible children has been high. We evaluated the long-term impact of PCV10 vaccination against IPD in vaccine-eligible and older, unvaccinated children six years after PCV10 introduction with a special focus on cross-protection against PCV10-related serotypes (serotypes in the same serogroups as the PCV10 types). MethodsWe used data on IPD from the national, population-based surveillance. A target cohort of vaccine-eligible children (born June 2010 or later) was followed from 3 months of age until the end of 2016. For the indirect effect, another cohort of older PCV10-ineligible children was followed from 2012 through 2016. IPD rates were compared with those of season- and age-matched reference cohorts before NVP introduction. ResultsAmong vaccine-eligible children, the incidence of all IPD decreased by 79% (95% CI 74–83%). There was a statistically significant reduction in the incidence of 6A IPD, but for 19A, the reduction was non-significant and the incidence of 19A increased towards the end of the study period in the older vaccine-eligible children. The increase in non-PCV10 related serotypes was non-significant.In the unvaccinated older children, the incidence of all IPD decreased by 33% (95% CI 8–52%) compared to the reference cohort, and there was no impact on serotype 6A or 19A IPD. ConclusionOverall, the impact of PCV10 vaccination on IPD was high in vaccine-eligible children, with a major reduction in vaccine-type disease, and without notable replacement by other serotype groups. Our data suggest that PCV10 results in long-lasting direct cross-protection against 6A IPD. For 19A, no net reduction was observed six years after NVP introduction in the vaccine-eligible cohort. The indirect impact on IPD in unvaccinated children sustained.

Cost-Effectiveness of Vaccinating Immunocompetent ≥65 Year Olds with the 13-Valent Pneumococcal Conjugate Vaccine in England.

BackgroundRecently a large clinical trial showed that the use of 13-valent pneumococcal conjugate vaccine (PCV13) among immunocompetent individuals aged 65 years and over was safe and efficacious. The aim of this study was to assess the cost-effectiveness of vaccinating immunocompetent 65 year olds with PCV13 vaccine in England. England is a country with universal childhood pneumococcal conjugate vaccination programme in place (7-valent (PCV7) since 2006 and PCV13 since 2010), as well as a 23-valent pneumococcal polysaccharide (PPV23) vaccination programme targeting clinical risk-groups and those ≥65 years.MethodA static cohort cost-effectiveness model was developed to follow a cohort of 65 year olds until death, which will be vaccinated in the autumn of 2016 with PCV13. Sensitivity analysis was performed to test the robustness of the results.ResultsThe childhood vaccination programme with PCV7 has induced herd protection among older unvaccinated age groups, with a resultant low residual disease burden caused by PCV7 vaccine types. We show similar herd protection effects for the 6 additional serotypes included in PCV13, and project a new low post-introduction equilibrium of vaccine-type disease in 2018/19. Applying these incidence projections for both invasive disease and community-acquired pneumonia (CAP), and using recent measures of vaccine efficacy against these endpoints for ≥65 year olds, we estimate that vaccination of a cohort of immunocompetent 65 year olds with PCV13 would directly prevent 26 cases of IPD, 69 cases of CAP and 15 deaths. The associated cost-effectiveness ratio is £257,771 per QALY gained (using list price of £49.10 per dose and £7.51 administration costs) and is therefore considered not cost-effective. To obtain a cost-effective programme the price per dose would need to be negative. The results were sensitive to disease incidence, waning vaccine protection and case fatality rate; despite this, the overall conclusion was robust.ConclusionsVaccinating immunocompetent individuals aged ≥65 years with PCV13 is efficacious. However the absolute incidence of vaccine-type disease will likely become very low due to wider benefits of the childhood PCV13 vaccination programme, such that a specific PCV13 vaccination programme targeting the immunocompetent elderly would not be cost-effective.

Effectiveness of ten-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in Brazil: a matched case-control study

In March 2010, Brazil introduced the ten-valent pneumococcal conjugate vaccine (PCV10), which was licensed based on non-inferiority of immunological correlates of protection compared with the seven-valent vaccine. The schedule comprised three primary doses at ages 2 months, 4 months, and 6 months, and a booster dose at age 12 months. A single catch-up dose was offered for children aged 12-23 months at the time of introduction. We assessed PCV10 effectiveness against invasive pneumococcal disease in Brazilian children. Invasive pneumococcal disease, defined as isolation of Streptococcus pneumoniae from blood, cerebrospinal fluid, or another normally sterile site, was identified in children age-eligible for at least one PCV10 dose through laboratory-based and hospital-based surveillance in ten states in Brazil from March 1, 2010, until Dec 31, 2012. We aimed to identify four age-matched and neighbourhood-matched controls for each case. We used conditional logistic regression and calculated PCV10 effectiveness as (1-adjusted matched odds ratio) × 100% for vaccine-type and vaccine-related serotypes (ie, in the same serogroup as a vaccine serotype). In 316 cases (median age 13·2 months, range 2·6-53·1) and 1219 controls (13·3 months, 2·6-53·1), the adjusted effectiveness of an age-appropriate PCV10 schedule was 83·8% (95% CI 65·9-92·3) against vaccine serotypes, and 77·9% (41·0-91·7) against vaccine-related serotypes. Serotype-specific effectiveness was shown for the two most common vaccine serotypes-14 (87·7%, 60·8-96·1) and 6B (82·8%, 23·8-96·1)-and serotype 19A (82·2%, 10·7-96·4), a serotype related to vaccine serotype 19F. A single catch-up dose in children aged 12-23 months was effective against vaccine-type disease (68·0%, 17·6-87·6). No significant effectiveness was shown against non-vaccine serotypes for age-appropriate or catch-up schedules. In the routine immunisation programme in Brazil, PCV10 prevents invasive disease caused by vaccine serotypes. PCV10 might provide cross-protection against some vaccine-related serotypes. Brazilian Ministry of Health, Pan-American Health Organization, and US Centers for Disease Control and Prevention.

Why do we need a systematic review of pneumococcal conjugate vaccine dosing schedules?

It is well known that Streptococcus pneumoniae remains a leading cause of childhood mortality; in 2008, it was estimated to be responsible for over 500,000 deaths in children aged 1–59 months.1 It is also known that the pneumococcus is a cause of significant morbidity and mortality among those younger and older than the 1- to 59-month age group,2,3 although prevention of disease in these age groups has not been the target of global efforts to date. Serious diseases caused by the pneumococcus across all age groups include pneumonia, meningitis and sepsis. Developing countries, mostly in Africa and Asia, carry the highest burden of both pneumococcal disease incidence and mortality in children; this burden is measured both in terms of rates and absolute numbers of cases and deaths.1

Pneumococcal serotypes in adult non-invasive and invasive pneumonia in relation to child contact and child vaccination status

BackgroundOn a population level, pneumococcal conjugate vaccination in children has reduced the incidence of vaccine-type disease in all age groups, including older adults. Few individual level studies have been performed...

Impact of pneumococcal conjugate vaccines on nasopharyngeal carriage and invasive disease among unvaccinated people: Review of evidence on indirect effects

BackgroundInvasive disease due to Streptococcus pneumoniae remains an important worldwide cause of morbidity and mortality, particularly in young children and the elderly. The development and use of pneumococcal conjugate vaccines (PCVs) have had a dramatic impact on rates of vaccine-type invasive pneumococcal disease (IPD) not only in the pediatric population targeted for vaccination but in non-vaccinated age-groups as well. This indirect effect is directly mediated by a reduction of vaccine-type nasopharyngeal carriage and thus transmission by vaccinated children. Current PCV licensing procedures do not take into consideration nasopharyngeal carriage impact, and thus the indirect effect. This review summarizes the evidence for the indirect effect of PCV on vaccine-type disease and its correlation with changes in carriage among unvaccinated populations, to assess the basis for inclusion of carriage in the PCV licensing process. MethodsRandomized controlled trials, surveillance and other observational studies published between 1994 and 2013 were systematically identified from global, regional and review databases and conference abstracts. We included as primary evidence, studies in non-vaccinated groups addressing changes in both vaccine-type IPD and carriage between pre- and post-PCV introduction periods; studies missing one of these four components were included as supporting rather than primary evidence. ResultsWe identified studies from 14 countries, nearly all developed countries. Vaccine-type IPD and carriage in non-targeted populations consistently decreased after PCV introduction, with the magnitude of decrease growing over time. Where IPD and carriage were observed in the same population, VT-decreases occurred contemporaneously. These relationships held true across age-groups and between indigenous and non-indigenous populations in the US and Australia. ConclusionsIndirect PCV impact on VT-IPD and VT-carriage has been significant. Impact on carriage should be considered for inclusion in the PCV licensure process as a predictor of indirect effects.

Impact of human papillomavirus (HPV) vaccination on HPV 16/18-related prevalence in precancerous cervical lesions

BackgroundVaccination against human papillomavirus (HPV) types 16 and 18 is recommended for girls aged 11 or 12 years with catch-up vaccination through age 26 in the U.S. Cervical intraepithelial neoplasia (CIN) grade 2 or 3 and adenocarcinoma in situ (CIN2+) are used to monitor HPV vaccine impact on cervical disease. This report describes vaccination status in women diagnosed with CIN2+ and examines HPV vaccine impact on HPV 16/18-related CIN2+. MethodsAs part of a vaccine impact monitoring project (HPV-IMPACT), females 18–31 years with CIN2+ were reported from pathology laboratories in CA, CT, NY, OR, TN from 2008 to 2011. One diagnostic block was selected for HPV DNA typing with Roche Linear Array. Demographic, abnormal Papanicolaou (Pap) test dates and vaccine status information were collected. The abnormal Pap test immediately preceding the CIN2+ diagnosis was defined as the ‘trigger Pap’. ResultsAmong 5083 CIN2+ cases reported to date, 3855 had vaccination history investigated; 1900 had vaccine history documented (vaccinated, with trigger Pap dates, or unvaccinated). Among women who initiated vaccination >24 months before their trigger Pap, there was a significantly lower proportion of CIN2+ lesions due to 16/18 compared to women who were not vaccinated (aPR=.67, 95% CI: .48–.94). Among the 1900 with known vaccination status, 20% initiated vaccination on/after their trigger screening. Women aged 21–23 years were more likely to initiate vaccination on/after the trigger Pap compared to 24–26 year olds (29.0% vs. 19.6%, p=.001), as were non-Hispanic blacks compared to non-Hispanic whites (27.3% vs. 19.0%, p=.001) and publicly compared to privately insured women (38.1% vs. 17.4%, p<.0001). ConclusionWe found a significant reduction in HPV 16/18-related lesions in women with CIN2+ who initiated vaccination at least 24 months prior to their trigger Pap. These preliminary results suggest early impact of the HPV vaccine on vaccine-type disease, but further evaluation is warranted.

Pneumococcal conjugated vaccines: impact of PCV-7 and new achievements in the postvaccine era

Pneumococcal disease is a major health problem worldwide. Large, rapid declines in overall invasive pneumococcal disease and mucosal disease in children, reductions in vaccine-type disease in unvaccinated children and adults (indirect effects) and significant drops in antibiotic-resistant infections were observed after the introduction of a safe, available and immunogenic seven-valent pneumococcal vaccine. The determination of vaccine efficacy is a complex process, which includes efficacy, immunogenicity, safety, cross-reactivity, indirect effects and substantial geographic variation in serotype coverage. In this report, we perform an overview of the literature on current, investigational and potential candidate pneumococcal conjugated vaccines (PCVs). Every country should have its own strong and sustained surveillance system implemented to monitor the effects of vaccination on the frequency of vaccine and nonvaccine serotypes for invasive or mucosal disease, nasopharyngeal carriage and the indirect effects before and after introduction of PCV. New PCVs (PHiD-CV and PCV-13) may provide even greater coverage worldwide, especially in developing countries. Vaccine experts’ efforts are currently focused on developing alternative vaccine strategies against pneumococcal infections, especially the development of vaccines based on pneumococcal proteins.

Impact of the Pneumococcal Conjugate Vaccine on Serotype Distribution and Antimicrobial Resistance of Invasive Streptococcus pneumoniae Isolates in Dallas, TX, Children From 1999 Through 2005

Because the heptavalent pneumococcal conjugate vaccine has reduced vaccine-type invasive pneumococcal disease (IPD) in children, a greater proportion of IPD is now caused by nonvaccine (NVT) serotypes. We analyzed the serotypes, antimicrobial resistance profiles and genetic relatedness of Streptococcus pneumoniae responsible for IPD at Children's Medical Center of Dallas. S. pneumoniae isolates were collected from January 1, 1999 through December 31, 2005. Incidence of IPD was calculated using inpatient and emergency center admissions to Children's Medical Center of Dallas as the denominator. Isolates were serotyped, and their penicillin and cefotaxime susceptibility determined. The 19A isolates were further characterized by pulsed-field gel electrophoresis, multilocus sequence typing and determination of penicillin-binding proteins and mef and erm genes. The incidence of IPD decreased from 93.6 cases/100,000 patients in 1999 to a nadir of 41 cases/100,000 patients in 2003 (P < 0.001). The number of IPD cases caused by serotype 19A increased, accounting for 40% of the cases of IPD in 2005. Penicillin and cefotaxime susceptibility of IPD isolates did not change from 1999 through 2005 (P = 0.687). There was a decrease in penicillin (P < 0.001) and cefotaxime (P = 0.034) susceptibility in NVT serotypes from 1999 to 2005. Molecular characterization of 19A isolates revealed a predominance of ST-199 (62%). Several highly penicillin-resistant and intermediately cefotaxime-resistant strains emerged in 2004 and 2005. In Dallas, heptavalent pneumococcal conjugate vaccine reduced the incidence of IPD from 1999 to 2005 by reducing the incidence of vaccine-type disease. NVT serotypes, particularly 19A, were prevalent and more resistant to antimicrobials in 2004 and 2005.

Effectiveness of seven-valent pneumococcal conjugate vaccine against invasive pneumococcal disease: a matched case-control study

When seven-valent pneumococcal conjugate vaccine was introduced in the USA, many children were vaccinated on schedules that differed from those tested in clinical trials. Our aim was to assess the effectiveness of the vaccine against various pneumococcal serotypes, and to measure the effectiveness of the recommended dose schedule and of catch-up and incomplete schedules. Invasive disease, defined as isolation of pneumococcus from a sterile site, was identified in children aged 3-59 months through the US Centers for Disease Control and Prevention's Active Bacterial Core surveillance. We tested isolates for serotype and antimicrobial susceptibility. Three controls, matched for age and zip code were selected for each case. We calculated the matched odds ratio for vaccination using conditional logistic regression, controlling for underlying conditions. Vaccine effectiveness was calculated as one minus the adjusted matched odds ratio times 100%. We enrolled 782 cases and 2512 controls. Effectiveness of one or more doses against vaccine serotypes was 96% (95% CI 93-98) in healthy children and 81% (57-92) in those with coexisting disorders. It was 76% (63-85) against infections that were not susceptible to penicillin. Vaccination prevented disease caused by all seven vaccine serotypes, and by vaccine-related serotype 6A. Several schedules were more protective than no vaccination; three infant doses with a booster were more protective against vaccine-type disease than were three infant doses alone (p=0.0323). The seven-valent pneumococcal conjugate vaccine prevents invasive disease in both healthy and chronically ill children. The vaccine is effective when used with various non-standard schedules.