Public health and economic impact of 13-valent pneumococcal conjugate vaccine in US adults aged ≥50 years

Background

A 13-valent pneumococcal conjugate vaccine (PCV13) was recently developed for use in older adults, and may be effective not only against invasive pneumococcal disease (IPD) but also nonbacteremic pneumococcal pneumonia. The potential public health and economic impact of PCV13 in this population is unknown.

Methods

A microsimulation model depicting risk and costs of IPD and all-cause nonbacteremic pneumonia (NBP) in US adults aged ≥50 years (n = 96.1 million), as well as expected impact of vaccination, was developed. Effectiveness of PPSV23 was based on published literature, and for all-cause NBP, was zero; effectiveness of PCV13 was based on PCV7 data in children, and for all-cause NBP, was varied across a reasonable range. Lifetime outcomes and costs were projected assuming: (1) use of PCV13 in all subjects at model entry, with and without periodic revaccination; and (2) use of PPSV23 per current ACIP recommendations.

Results

Use of PCV13 in all subjects at model entry without revaccination – in lieu of PPSV23 use per recommendations – reduced cases of IPD by 15,000 (95% CI 9000–21,000); cases of NBP by 1.2 million (0.9–1.5); total healthcare costs by $3.5 billion (1.9–5.2); and total societal costs by $7.4 billion (5.3–9.8). Use of PCV13 with revaccination every 5–10 years resulted in fewest cases of disease and lowest total costs. Findings were largely unchanged in sensitivity analyses.

Conclusions

Assuming that the effectiveness of PCV13 in adults is comparable to that observed for PCV7 in children and under reasonable assumptions regarding the underlying risks and costs of IPD and NBP, model projections suggest that routine use of PCV13 – in lieu of PPSV23 – would result in a greater reduction in the overall burden of pneumococcal disease in older US adults.     

Pneumococcal epidemiology among us adults hospitalized for community-acquired pneumonia

BackgroundFew studies have measured the burden of adult pneumococcal disease after the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the US infant vaccination schedule. Further, most data regarding pneumococcal serotypes are derived from invasive pneumococcal disease (IPD), which represents only a fraction of all adult pneumococcal disease burden. Understanding which pneumococcal serotypes cause pneumonia in adults is critical for informing current immunization policy. The objective of this study was to measure the proportion of radiographically-confirmed (CXR+) community-acquired pneumonia (CAP) caused by PCV13 serotypes in hospitalized US adults.MethodsThis observational, prospective surveillance study recruited hospitalized adults aged ≥18 years from 21 acute care hospitals across 10 geographically-dispersed cities in the United States between October 2013 and September 2016. Clinical and demographic data were collected during hospitalization. Vital status was ascertained 30 days after enrollment. Pneumococcal serotypes were detected via culture from the respiratory tract and normally-sterile sites (including blood and pleural fluid). Additionally, a novel, Luminex-based serotype-specific urinary antigen detection (UAD) assay was used to detect serotypes included in PCV13.ResultsOf 15,572 enrolled participants, 12,055 eligible patients with CXR+CAP were included in the final analysis population. Mean age was 64.1 years and 52.7% were aged ≥65 years. Common comorbidities included chronic obstructive pulmonary disease (43.0%) and diabetes mellitus (28.6%). PCV13 serotypes were detected in 552/12,055 (4.6%) of all patients and 265/6347 (4.2%) of those aged ≥65 years. Among patients aged 18–64 years PCV13 serotypes were detected in 3.8–5.3% of patients depending on their risk status.ConclusionsAfter implementation of a pneumococcal conjugate vaccination program in US children, and despite the herd protection observed in US adults, a persistent burden of PCV13-type CAP remains in this population.     

Burden of vaccine-preventable pneumococcal disease in hospitalized adults: A Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) network study

BackgroundPneumococcal community acquired pneumonia (CAP_Spn) and invasive pneumococcal disease (IPD) cause significant morbidity and mortality worldwide. Although childhood immunization programs have reduced the overall burden of pneumococcal disease, there is insufficient data in Canada to inform immunization policy in immunocompetent adults. This study aimed to describe clinical outcomes of pneumococcal disease in hospitalized Canadian adults, and determine the proportion of cases caused by vaccine-preventable serotypes.MethodsActive surveillance for CAP_Spn and IPD in hospitalized adults was performed in hospitals across five Canadian provinces from December 2010 to 2013. CAP_Spn were identified using sputum culture, blood culture, a commercial pan-pneumococcal urine antigen detection (UAD), or a serotype-specific UAD. The serotype distribution was characterized using Quellung reaction, and PCR-based serotyping on cultured isolates, or using a 13-valent pneumococcal conjugate vaccine (PCV13) serotype-specific UAD assay.Results and conclusionsIn total, 4769 all-cause CAP cases and 81 cases of IPD (non-CAP) were identified. Of the 4769 all-cause CAP cases, a laboratory test for S. pneumoniae was performed in 3851, identifying 14.3% as CAP_Spn. Of CAP cases among whom all four diagnostic test were performed, S. pneumoniae was identified in 23.2% (144/621). CAP_Spn cases increased with age and the disease burden of illness was evident in terms of requirement for mechanical ventilation, intensive care unit admission, and 30-day mortality. Of serotypeable CAP_Spn or IPD results, predominance for serotypes 3, 7F, 19A, and 22F was observed. The proportion of hospitalized CAP cases caused by a PCV13-type S. pneumoniae ranged between 7.0% and 14.8% among cases with at least one test for S. pneumoniae performed or in whom all four diagnostic tests were performed, respectively. Overall, vaccine-preventable pneumococcal CAP and IPD were shown to be significant causes of morbidity and mortality in hospitalized Canadian adults in the three years following infant PCV13 immunization programs in Canada.     

Changes in pathogens and pneumococcal serotypes causing community-acquired pneumonia in The Netherlands

BackgroundIn 2006 a 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in the immunisation programme for infants in The Netherlands and replaced by PCV10 in 2011. Limited data exist about the impact of PCV on the aetiology of CAP as a whole. The aim of the present study is to describe the overall changes in microbial aetiology, pneumococcal burden (including non-bacteraemic pneumococcal pneumonia) and its serotypes in adult community-acquired pneumonia (CAP) after the introduction of these PCVs.MethodsHospitalised adult CAP patients who participated in three consecutive trials were studied (2004–2006 (n = 201), 2007–2009 (n = 304) and 2012–2016 (n = 300) and considered as pre-PCV7, PCV7 and PCV10 period). Extensive conventional microbiological testing was applied for all patients. In addition, patients with a serotype-specific pneumococcal antibody response were diagnosed with pneumococcal CAP. Changes in proportions of causative pathogens and distributions of pneumococcal serotypes were calculated.ResultsThe proportion of pneumococcal CAP decreased from 37% (n = 74/201) to 26% (n = 77/300) comparing the pre-PCV7 period with the PCV10 period (p = 0.01). For other pathogens, including Legionella spp., Mycoplasma pneumoniae, S. aureus, H. influenzae, and respiratory viruses, no sustained shifts were observed in their relative contribution to the aetiology of CAP. Within the pneumococcal CAP patients, we observed a decrease in PCV7 and an increase in non-PCV10 serotype disease. PCV10-extra type disease did not decrease significantly comparing the PCV10 period with the pre-PCV7 and PCV7 period, respectively. Notably, PCV7 type disease decreased both in bacteraemic and non-bacteraemic patients.ConclusionsOur findings confirm that PCV introduction in infants impact the microbial aetiology of adult CAP and suggest herd effects in adults with CAP after introduction of PCVs in children.     

Exploratory efficacy endpoints in the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA)

BackgroundThe Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) assessed vaccine-type community-acquired pneumonia (VT-CAP) and vaccine-type invasive pneumococcal disease (VT-IPD) prevention with 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ⩾65 years. We report vaccine efficacy (VE) of PCV13 for the remaining 23 exploratory endpoints and serotype distributions for pneumococcal CAP and IPD.MethodsThis was a parallel-group, randomised, placebo-controlled, double-blind trial comparing single-dose PCV13 with placebo. Exploratory CAP endpoints included first episode of confirmed non-VT (NVT) pneumococcal CAP; all confirmed episodes of NVT pneumococcal CAP, pneumococcal CAP, nonbacteraemic/noninvasive (NB/NI) VT pneumococcal CAP, and NB/NI pneumococcal CAP; and first and all episodes of culture-confirmed VT pneumococcal CAP, culture-confirmed pneumococcal CAP, culture-confirmed NVT pneumococcal CAP, probable VT pneumococcal CAP, probable NVT pneumococcal CAP, and probable and possible pneumococcal CAP. Exploratory IPD endpoints included all episodes of VT-IPD and IPD, and first and all episodes of NVT-IPD. The per-protocol and modified intent-to-treat (mITT) populations were evaluated.ResultsIn total, 84,496 participants were enrolled. Eight of 23 exploratory CAP and IPD endpoints were statistically significant in both populations. In the per-protocol population, these included VE of 29% for all episodes of confirmed pneumococcal CAP, 43% for all NB/NI episodes of VT pneumococcal CAP, 52% for all episodes of culture-confirmed pneumococcal CAP, and 53% for all episodes of IPD. Comparable VE estimates were observed in the mITT population. The most common VT serotypes were 1 (10 first episodes of confirmed pneumococcal CAP; 2 first episodes of IPD) and 7F (22; 7) among PCV13 and placebo recipients, respectively.ConclusionsThe results of this analysis yielded statistically significant PCV13 VE for all episodes of confirmed pneumococcal CAP (including NB/NI and culture-confirmed episodes) and for all episodes of IPD in adults aged ⩾65 years. These findings are consistent with the primary efficacy analysis. ClinicalTrials.gov identifier: NCT00744263.     

Pneumococcal conjugate vaccine herd effects on non-invasive pneumococcal pneumonia in elderly

BackgroundHerd protection from infant pneumococcal conjugate vaccination is well established for invasive pneumococcal disease (IPD) but not for non-IPD pneumococcal community-acquired pneumonia (PCAP). We assessed the contribution of vaccine-serotypes in non-IPD PCAP in adults 65 years and older in the period 2008–2013.MethodsThis is a post hoc analysis of two prospective studies from the Netherlands. Serotype specific urinary antigen detection and routine microbiological testing were used to categorize episodes as IPD or non-IPD PCAP caused by 7-valent pneumococcal conjugate vaccine (PCV7), PCV10-7 (three additional PCV10 serotypes), PCV13-10 (three additional PCV13 serotypes), and non-PCV13 serotypes. Proportions per vaccine-serotype group were assessed per year from June 1st to May 31st. Time trends were compared to national IPD data.ResultsOf 270 non-IPD PCAP episodes with known serotype, PCV7 serotypes decreased from 28% in 2008/2009 to 7% in 2012/2013 (p-value for trend <0.001). No change in PCV10-7 (19% overall) and PCV13-10 (29% overall) serotypes was observed. Non-PCV13 serotypes increased from 30% in 2008/2009 to 37% in 2012/2013 (p-value for trend 0.048). Trends corresponded with national IPD data.ConclusionPCV7 serotypes declined in non-IPD PCAP among elderly between 2008 and 2013, comparable to IPD data. No reduction in the additional PCV10 serotypes could be demonstrated within the first two years after PCV10 introduction.     

Pneumococcal serotypes and antibiotic resistance in healthy carriage children after introduction of PCV13 in Lima,Peru

ObjectiveTo determinate the frequency of Streptococcus pneumoniae nasopharyngeal carriers, serotypes and antimicrobial resistance in healthy children in Lima, Peru, post-PCV13 introduction and to compare the results with a similar study conducted between 2006 and 2008 before PCV7 introduction (pre-PCV7).MethodsA cross-sectional multicenter study was conducted between January 2018 and August 2019 in 1000 healthy children under two years of age. We use standard microbiological methods to determinate S. pneumoniae from nasopharyngeal swab, Kirby Bauer and minimum inhibitory concentration methods to determinate antimicrobial susceptibility and whole genomic sequencing to determinate pneumococcal serotypes.ResultsThe pneumococcal carriage rate was 20.8 % vs. 31.1 % in pre-PCV7 (p < 0.001). The most frequent serotypes were 15C, 19A and 6C (12.4 %, 10.9 % and 10.9 % respectively). The carriage of PCV13 serotypes after PCV13 introduction decreased from 59.1 % (before PCV7 introduction) to 18.7 % (p < 0.001). Penicillin resistance was 75.5 %, TMP/SMX 75.5 % and azithromycin 50.0 %, using disk diffusion. Penicillin resistance rates using MIC breakpoint for meningitis (MIC ≥ 0.12) increased from 60.4 % to 74.5 % (p = 0.001).ConclusionThe introduction of PCV13 in the immunization program in Peru has decreased the pneumococcal nasopharyngeal carriage and the frequency of PCV13 serotypes; however, there has been an increase in non-PCV13 serotypes and antimicrobial resistance.     

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.     

Invasive disease potential of Streptococcus pneumoniae serotypes before and after 10-valent pneumococcal conjugate vaccine introduction in a rural area,southern Mozambique

BackgroundInvasive pneumococcal disease (IPD) is a significant cause of morbidity and mortality among children worldwide. In April 2013, Mozambique introduced 10-valent PCV (PCV10) into the National Expanded Program on immunization using a three-dose schedule at 2, 3, and 4 months of age. We aimed to evaluate the invasive disease potential of pneumococcal serotypes among children in our region before and after PCV10 introduction.MethodsWe used data from ongoing population-based surveillance for IPD and cross-sectional pneumococcal carriage surveys among children aged <5 years in Manhiҫa, Mozambique. To determine the invasive disease potential for each serotype pre- and post-PCV10 introduction, odds ratios (OR) and 95% confidence intervals (95% CI) were calculated comparing serotype-specific prevalence in IPD and in carriage. For each serotype, OR and 95% CI > 1 indicated high invasive disease potential and OR and 95% CI < 1 indicated low invasive disease potential.ResultsIn the pre-PCV10 period, 524 pneumococcal isolates were obtained from 411 colonized children and IPD cases were detected in 40 children. In the post-PCV10 period, 540 pneumococcal isolates were obtained from 507 colonized children and IPD cases were detected in 30 children. The most prevalent serotypes causing IPD pre-PCV10 were 6A (17.5%), 6B (15.0%), 14 (12.5%), 23F (10.0%) and 19F (7.5%), and post-PCV10 were 6A (36.7%), 13 (10%), 1 (10.0%), 6B (6.7%) and 19A (6.7%). Serotypes associated with high invasive disease potential pre-PCV10 included 1 (OR:22.3 [95% CI 2.0; 251.2]), 6B (OR:3.1 [95% CI 1.2; 8.1]), 14 (OR: 3.4 [95% CI 1.2; 9.8]) and post-PCV10 included serotype 6A (OR:6.1[95% CI 2.7; 13.5]).ConclusionThe number of serotypes with high invasive disease potential decreased after PCV10 introduction. Serotype 6A, which is not included in PCV10, was the most common cause of IPD throughout the study and showed a high invasive potential in the post-PCV10 period.     

Economic evaluation of second generation pneumococcal conjugate vaccines in Norway

Background

A seven valent pneumococcal conjugate vaccine (PCV7) was introduced in the Norwegian childhood immunization programme in 2006, and since then the incidence of invasive pneumococcal disease has declined substantially. Recently, two new second generation pneumococcal conjugate vaccines have become available, and an update of the economic evidence is needed. The aim of this study was to estimate incremental costs, health effects and cost-effectiveness of the pneumococcal conjugate vaccines PCV7, PCV13 and PHiD-CV in Norway.

Methods

We used a Markov model to estimate costs and epidemiological burden of pneumococcal- and NTHi-related diseases (invasive pneumococcal disease (IPD), Community Acquired Pneumonia (CAP) and acute otitis media (AOM)) for a specific birth cohort. Using the most relevant evidence and assumptions for a Norwegian setting, we calculated incremental costs, health effects and cost-effectiveness for different vaccination strategies. In addition we performed sensitivity analyses for key parameters, tested key assumptions in scenario analyses and explored overall model uncertainty using probabilistic sensitivity analysis.

Results

The model predicts that both PCV13 and PHiD-CV provide more health gains at a lower cost than PCV7. Differences in health gains between the two second generation vaccines are small for invasive pneumococcal disease but larger for acute otitis media and myringotomy procedures. Consequently, PHiD-CV saves more disease treatment costs and indirect costs than PCV13.

Conclusion

This study predicts that, compared to PVC13, PHiD-CV entails lower costs and greater benefits if the latter is measured in terms of quality adjusted life years. PVC13 entails more life years gained than PHiD-CV, but those come at a cost of NOK 3.1 million (∼€0.4 million) per life year. The results indicate that PHiD-CV is cost-effective compared to PCV13 in the Norwegian setting.     

Streptococcus pneumoniae serotype 3 is masking PCV13-mediated herd immunity in Canadian adults hospitalized with community acquired pneumonia: A study from the Serious Outcomes Surveillance (SOS) Network of the Canadian immunization research Network (CIRN)

BackgroundThe 13-valent pneumococcal conjugate vaccine (PCV13) was recently shown to be effective against PCV13-type invasive pneumococcal disease (IPD) and pneumococcal community acquired pneumonia (CAP_Spn) in healthy adults aged ≥65 years, prompting many countries to re-assess adult immunization. In Canada, the potential benefits of adult PCV13 immunization were unclear given anticipated herd immunity from PCV13 childhood immunization introduced since 2010. This study describes the serotype distribution and clinical outcomes of Canadian adults aged ≥16 years, who were hospitalized with CAP_Spn and IPD from 2010 to 2015.MethodsActive surveillance for CAP and IPD was performed in adult hospitals across five Canadian provinces. IPD was identified when Streptococcus pneumoniae was isolated from sterile sites. Bacteremic and non-bacteremic CAP_Spn were identified using blood culture, and sputum culture or PCV13-specific urine antigen detection (UAD_PCV13), respectively. Serotype was assigned using Quellung reaction, PCR, or UAD_PCV13.ResultsOf 6687 CAP cases where a test was performed, S. pneumoniae positivity decreased from 15.9% in 2011 to 8.8% in 2014, but increased to 12.9% in 2015. CAP_Spn attributed to PCV13 serotypes followed a similar trend, dropping from 8.3% in 2010 to 4.6% in 2014, but increasing to 6.3% in 2015. The decline was primarily attributed to serotypes 7F and 19A, and the proportional increase to serotype 3. Similar trends were noted for bacteremic and non-bacteremic CAP_Spn. Serious outcomes such as 30-day mortality, intensive care unit admission, and requirement for mechanical ventilation were prominent in CAP_Spn and IPD cases, but remained unchanged over the study years.ConclusionHerd immunity afforded primarily by serotypes 7F and 19A appears to be partly masked by a concomitant proportional increase of serotype 3. Despite evidence of herd immunity, these PCV13 serotypes remain persistent in Canadian adults hospitalized with CAP_Spn, and represent between 5 and 10% of all CAP in this patient population.     

Impact of the 13-valent pneumococcal conjugate vaccine (pcv13) on invasive pneumococcal disease and carriage in Alaska

BackgroundAlaska Native (AN) children have experienced high rates of invasive pneumococcal disease (IPD). In March 2010, PCV13 was introduced statewide in Alaska. We evaluated the impact of PCV13 on IPD in children and adults, 45 months after introduction.MethodsPneumococcal sterile site isolates, reported through state-wide surveillance, were serotyped using standard methods. We defined a pre-PCV13 time period 2005–2008 and post-PCV13 time period April 2010–December 2013; excluding Jan 2009–March 2010 because PCV13 was introduced pre-licensure in one high-risk region in 2009.ResultsAmong Alaska children <5 years, PCV13 serotypes comprised 65% of IPD in the pre-PCV13 period and 26% in the PCV13 period. Among all Alaska children <5 years, IPD rates decreased from 60.9 (pre) to 25.4 (post) per 100,000/year (P<0.001); PCV13 serotype IPD decreased from 37.7 to 6.4 (P<0.001). Among AN children <5 years, IPD rates decreased from 149.2 to 60.8 (P<0.001); PCV13 serotype IPD decreased from 87.0 to 17.4 (P<0.001); non-PCV13 serotype IPD did not change significantly. Among persons 5–17 and ≥45 years, the post-vaccine IPD rate was similar to the baseline period, but declined in persons 18–44 years (39%, P < 0.001); this decline was similar in AN and non-AN persons (38%, P = 0.016, 43%, P = 0.014, respectively).ConclusionsForty-five months after PCV13 introduction, overall IPD and PCV13-serotype IPD rates had decreased 58% and 83%, respectively, in Alaska children <5 years of age when compared with 2005–2008. We observed evidence of indirect effect among adults with a 39% reduction in IPD among persons 18–44 years.     

Public health impact and cost-effectiveness of 15-valent pneumococcal conjugate vaccine use among the pediatric population of the United States

BackgroundAlthough use of the 13-valent pneumococcal conjugate vaccine (PCV13) among children has reduced incidence of pneumococcal disease, a considerable burden of disease remains. PCV15 is a new vaccine that contains pneumococcal serotypes 22F and 33F in addition to serotypes contained in PCV13. To inform deliberations by the Advisory Committee on Immunization Practices on recommendations for PCV15 use among U.S. children, we estimated the health impact and cost-effectiveness of replacing PCV13 with PCV15 within the routine infant immunization program in the United States. We also assessed the impact and cost-effectiveness of a supplementary PCV15 dose among children aged 2–5 years who have already received a full PCV13 series.MethodsWe estimated the incremental number of pneumococcal disease events and deaths averted, costs per quality adjusted life-year (QALY) gained, and costs per life-year gained under different vaccination strategies using a probabilistic model following a single birth cohort of 3.9 million individuals (based on 2020 U.S. birth cohort). We assumed that vaccine effectiveness (VE) of PCV15 against the two additional serotypes was the same as the VE of PCV13. The cost of PCV15 use among children was informed from costs of PCV15 use among adults and from discussions with the manufacturer.ResultsOur base case results found that replacing PCV13 with PCV15 prevented 92,290 additional pneumococcal disease events and 22 associated deaths, while also saving $147 million in costs. A supplementary PCV15 dose among children aged 2–5 years who were fully vaccinated with PCV13 prevented further pneumococcal disease events and associated deaths but at a cost of more than $2.5 million per QALY gained.ConclusionsA further decrease in pneumococcal disease in conjunction with considerable societal cost savings could be expected from replacing PCV13 with PCV15 within the routine infant immunization program in the United States.     

Cost-effectiveness analysis of a universal mass vaccination program with a PHiD-CV 2+1 schedule in Malaysia

Background

Currently, two pediatric pneumococcal conjugate vaccines are available in the private market of Malaysia—13-valent pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide and non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). This study aimed to evaluate the cost-effectiveness of a universal mass vaccination program with a PHiD-CV 2+1 schedule versus no vaccination or with a PCV13 2+1 schedule in Malaysia.

Methods

A published Markov cohort model was adapted to evaluate the epidemiological and economic consequences of programs with no vaccination, a PHiD-CV 2+1 schedule or a PCV13 2+1 schedule over a 10-year time horizon. Disease cases, deaths, direct medical costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were estimated. Locally published epidemiology and cost data were used whenever possible. Vaccine effectiveness and disutility data were based on the best available published data. All data inputs and assumptions were validated by local clinical and health economics experts. Analyses were conducted from the perspective of the Malaysian government for a birth cohort of 508,774. Costs and QALYs were discounted at 3% per annum. One-way and probabilistic sensitivity analyses were performed.

Results

Compared with no vaccination, a PHiD-CV 2+1 program was projected to prevent 1109 invasive pneumococcal disease (IPD), 24,679 pneumonia and 72,940 acute otitis media (AOM) cases and 103 IPD/pneumonia deaths over 10 years, with additional costs and QALYs of United States dollars (USD) 30.9 million and 1084 QALYs, respectively, at an ICER of USD 28,497/QALY. Compared with a PCV13 2+1 program, PHiD-CV 2+1 was projected to result in similar reductions in IPD cases (40 cases more) but significantly fewer AOM cases (30,001 cases less), with cost savings and additional QALYs gained of USD 5.2 million and 116 QALYs, respectively, demonstrating dominance over PCV13. Results were robust to variations in one-way and probabilistic sensitivity analyses.

Conclusions

A PHiD-CV 2+1 universal mass vaccination program could substantially reduce pneumococcal disease burden versus no vaccination, and was expected to be cost-effective in Malaysia. A PHiD-CV 2+1 program was also expected to be a dominant choice over a PCV13 2+1 program in Malaysia.

     

Recalibrated estimates of non-bacteremic and bacteremic pneumococcal community acquired pneumonia in hospitalized Canadian adults from 2010 to 2017 with addition of an extended spectrum serotype-specific urine antigen detection assay

Objective(s)In the context of age- and risk-based pneumococcal vaccine recommendations in Canada, this study presents updated data from active surveillance of pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) in hospitalized adults from 2010 to 2017.MethodsS. pneumoniae was detected using culture (blood and sputum), and urine antigen detection (UAD). Serotyping was performed with Quellung, PCR, or using the PCV13- and PPV23 (non-PCV13)-specific UADs. Laboratory results, demographic, and outcome data were categorized by age (16–49, 50–64, and 65 + ) and by disease [non-bacteremic pCAP, bacteremic pCAP, and IPD(non-CAP)].Results11,129 CAP cases and 216 cases of IPD (non-CAP) were identified. Laboratory testing for S. pneumoniae was performed in 8912 CAP cases, identifying 1264 (14.2%) as pCAP. Of pCAP cases, 811 (64.1%) were non-bacteremic and 455 (35.9%) were bacteremic. Adults 65 + years represented 54.5% of non-bacteremic pCAP, 41.4% of bacteremic pCAP, and 48.6% of IPD cases. Adults 50–64 years contributed 30.3%, 33.1%, and 29.9%, respectively. In pCAP, PCV13 serotypes declined between 2010 and 2014 due to declines in serotypes 7F and 19A, then plateaued from 2015 to 2017 with persistence of serotype 3. In later study years, non-bacteremic pCAP was predominant, and PPV23 (non-PCV13) serotypes increased from 2015 to 2017, with serotypes 22F, 11A, and 9 N being most frequently identified. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These outcomes and mortality were more common in bacteremic pCAP and IPD, versus non-bacteremic pCAP.Conclusion(s)Along with IPD, pCAP surveillance (bacteremic and non-bacteremic) is important as their trends may differ over time. With insufficient herd protection from PCV13 childhood immunization, or use of PPV23 in adults, this study supports direct adult immunization with PCV13 or higher valency conjugate vaccines to reduce the residual burden of pCAP and IPD.     

Population-based incidence of invasive pneumococcal disease in children and adults in Ontario and British Columbia, 2002–2018: A Canadian Immunization Research Network (CIRN) study

BackgroundInvasive pneumococcal disease (IPD) burden, evaluated in Canada using reported confirmed cases in surveillance systems, is likely underestimated due to underreporting. We estimated the burden of IPD in Ontario and British Columbia (BC) by combining surveillance data with health administrative databases.MethodsWe established a cohort of 27,525 individuals in Ontario and BC. Laboratory-confirmed IPD cases were identified from Ontario’s integrated Public Health Information System and the BC Centre for Disease Control Public Health Laboratory. Possible IPD cases were identified from hospitalization data in both provinces, and from emergency department visit data in Ontario. We estimated the age and sex adjusted annual incidence of IPD and pneumococcal conjugate/polysaccharide vaccine (PCV/PPV) serotype-specific IPD using Poisson regression models.ResultsIn Ontario, 20,205 overall IPD cases, including 15,299 laboratory-confirmed cases, were identified with relatively stable age- and sex-adjusted annual incidence rates ranging from 13.7/100,000 (2005) to 13.6/100,000 (2018). In BC, 7,320 overall IPD cases, including 5,932 laboratory-confirmed cases were identified; annual incidence rates increased from 10.9/100,000 (2002) to 13.2/100,000 (2018). Older adults aged ≥ 85 years had the highest incidence rates. During 2007–2018 the incidence of PCV7 serotypes and additional PCV13 serotypes decreased while the incidence of unique PPV23 and non-vaccine serotypes increased in both provinces.ConclusionsIPD continues to cause a substantial public health burden in Canada despite publicly funded pneumococcal vaccination programs, resulting in part from an increase in unique PPV23 and non-vaccine serotypes.     

Long-term population impact of infant 10-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in adults in Finland

BackgroundLimited data are available on long-term indirect effects of ten-valent pneumococcal conjugate vaccine (PCV10) programmes. We evaluated changes in invasive pneumococcal disease (IPD) incidence, mortality, and serotype distribution in adults up to 9 years after infant PCV10 introduction.MethodsCulture-confirmed IPD cases ≥18 years (n = 5610; 85% were pneumonia) were identified through national, population-based laboratory surveillance; data were linked with population registry to conduct nationwide follow-up study. In a time-series model, we compared serotype-specific IPD incidence and associated 30-day mortality rates before and after PCV10 by using negative binomial regression models.ResultsDuring pre-PCV10 period (7/2004–6/2010), overall IPD incidence in adults ≥18 years increased yearly by 4.8%. After adjusting for trend and seasonality, the observed PCV10 serotype IPD incidence in 7/2018–6/2019 was 90% (12/100,000 person-years) lower than the expected rate without PCV10 program. Non-PCV10 serotype incidence was 40% (4.4/100,000 person-years) higher than expected; serotypes 3, 19A, 22F, and 6C accounted for most of the rate increase. However, incidence of non-PCV10 IPD levelled off by end of follow-up. The observed-expected incidence rate-ratio (IRR) was 0·7 (95 %CI 0·5–0.8) for all IPD and 0·7 (95 %CI 0·3–1·3) for IPD-associated 30-day mortality. Case-fatality proportion decreased from 11·9% to 10.0% (p < 0.01). In persons ≥65 years, the IRR was 0·7 (95 %CI 0·5–0.95).ConclusionsSignificant indirect effects were seen for vaccine-serotype IPD and for overall IPD in all adult age groups. For non-vaccine IPD, the incidence stabilized 5 years after infant PVC10 program introduction, resulting in a steady state in which non-vaccine IPD accounted for nearly 90% of overall IPD. Substantial pneumococcal disease burden remains in older adults.     

Early impact of sequential introduction of 7-valent and 13-valent pneumococcal conjugate vaccine on IPD in Israeli children <5 years: An active prospective nationwide surveillance

BackgroundThe 7-valent pneumococcal conjugated vaccine (PCV7) was introduced to the Israeli national immunization plan (NIP) in July 2009 (administered at age 2, 4 and 12 months), with a fast reduction of invasive pneumococcal disease (IPD) caused by PCV7 serotypes. Starting in November 2010, PCV13 gradually replaced PCV7.AimTo report the impact of PCV7/PCV13 sequential introduction on IPD in Israeli children <5 years.MethodsAn ongoing nationwide, prospective, population-based, active surveillance. All IPD episodes (Streptococcus pneumoniae isolated from blood and/or cerebrospinal fluid) from July 2004 through June 2013 were included.ResultsOverall, 2670 IPD episodes were recorded. Incidence of IPD caused by PCV7 + 6A serotypes during the PCV13 period vs. pre-PCV period decreased by 95% (Incidence Rate Ratio [IRR] = 0.05; 95% CI = 0.03–0.09). This reduction was observed in a two-step manner: 90% in the PCV7-period and further 5% in the PCV13-period. The rates of IPD caused by the 5 additional PCV13-serotypes (1, 3, 5, 7F, 19A; 5VT) increased initially by 47%, but subsequently decreased by 79%, resulting in an overall 70% reduction during the entire study period (IRR = 0.30; 0.21–0.44). A two-fold increase in non-PCV13 serotypes IPD was observed (IRR = 2.43; 1.73–3.66). In total, a 63% reduction of all-serotype IPD episodes was observed in children <5 years (69% and 48% in children <2 and 2–4 years old, respectively).ConclusionsAfter initiation of PCV NIP, a rapid and substantial 2-step IPD reduction was observed in children <5 years. The serotype-specific rate reduction reflected the sequential introduction of PCV7/PCV13.     

Pneumococcal conjugate serotype distribution and predominating role of serotype 3 in German adults with community-acquired pneumonia

IntroductionImplementation of the 7-valent pneumococcal conjugate vaccine (PCV7) in infant vaccination programs has substantially reduced the burden of PCV7 serotypes also in adult community-acquired pneumonia (CAP). Currently, it is unclear, if this extensive herd protection effect can be extrapolated to the additional 6 serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13), which replaced PCV7 in Germany in 2010.ObjectivesWe investigated changing trends for PCV13 serotypes in adult CAP patients between three to seven years after implementation of PCV13 infant immunization in Germany.MethodsBetween December 2012 and January 2017, urine samples from German adult patients with radiologically confirmed CAP were prospectively collected by the multi-center cohort study CAPNETZ and analyzed by the serotype-specific multiplex urinary antigen detection assay (SSUAD) allowing for the detection of PCV13 serotypes.ResultsPCV13 serotypes were found in 59 of 796 (7.4%) patients with all-cause CAP, most prevalent was serotype 3 (30 of 59 patients, 50.8%). All patients with serotype 3-CAP were admitted to hospital and the majority required oxygen at admission (83.3% of patients with serotype 3-CAP versus 50.9% of patients with pneumococcal CAP by other serotypes, p = 0.005). Compared to SSUAD testing, conventional microbiological workup missed 27 of 30 (90.0%) serotype 3-CAP cases. We could not observe a time trend in the proportions of PCV13 serotypes and serotype 3 in all-cause CAP between 2013 and 2016 (OR trend per year 0.84, 95% CI 0.64–1.11 for PCV13 serotypes and OR trend per year 0.95, 95% CI 0.70–1.28 for serotype 3). Conclusions: Conventional methods underestimate serotype 3-CAP that can cause severe disease. Changes in overall PCV13 coverage were not detected during the years 2013 to 2016, mostly driven by a high proportion of serotype 3.