Background

The serotype distribution of invasive pneumococcal disease (IPD) informs the coverage of next generation pneumococcal conjugate vaccines (PCVs). This analysis describes IPD coverage by the current PCVs (PCV10/PCV13) and next generation, PCV15 and PCV20.

Methods

Serotype counts for children <5 years were obtained from national or regionally-representative IPD surveillance systems from high-income countries. Up to the three most recent years of data were included. Excluded countries reported <20 cases overall or only reported data prior to pediatric PCV introduction into the National Immunization Program (NIP). Coverage was calculated for PCV10 (1,4,5,6B,7F,9V,14,18C,19F,23F), PCV13 (PCV10-types, 3,6A,19A, plus 6C, which is highly-related to 6A), PCV15 (PCV13-types, 22F,33F), and PCV20 (PCV15-types, 8,10A,11A,12F,15B, plus 15C, which is highly-related to 15B) as the number of cases in PCVs divided by the total number of cases (excluding missing and non-typeable cases) reported for each country.

Results

Twenty-seven of 80 (34%) high-income countries met inclusion criteria, reporting >5,000 cases that were included in the analysis. Coverage by current and next generation PCVs varied by country and World Health Organization (WHO) region (Table).

Conclusions

PCV20 offers substantial coverage above current PCVs and next generation PCV15 and could address the considerable remaining IPD burden among children in high-income countries globally.

Background

While regulatory endpoints for pneumococcal conjugate vaccines (PCVs) routinely include radiologically- or vaccine serotype (VST) confirmed disease, public health decision-making benefits from consideration of all disease prevented regardless of diagnostic or etiological confirmation.

Methods

We followed PRISMA guidelines to perform a systematic literature review for Phase III/IV efficacy trials of PCVs from 1997 through 2019. We estimated study-specific vaccine-preventable disease incidence (VPDI) (control group minus intervention group incidences) for all-cause disease versus radiologically- and/or etiologically-confirmed outcomes. VPDI ratios between the broadest clinical and most narrowly defined outcomes were calculated [PROSPERO registration, CRD42019145268].

Results

Ten studies met the criteria. In children < 5 years, VPDI ratios ranged from 0.6 to 3.7 for otitis media (clinical versus VST etiologically-confirmed); from 1.3 to 1.8 for pneumonia (clinical versus radiologically-confirmed); 3.1 and 19.0 for pneumonia (clinical versus bacterial or VST); and 3.8 in one study of invasive pneumococcal disease (non-laboratory to laboratory-confirmed). In adults, VPDI ratios ranged from 2.2 to 2.9 for pneumonia (clinical to pneumococcal or VST).

Conclusions

Relying on only radiologically-confirmed or etiologically-confirmed outcomes substantially underestimated PCVs’ public health benefits. Broader clinical outcomes should be considered by vaccine technical committees when making decisions for pediatric and adult PCV use.

Background

The United States experienced a substantial reduction in the incidence of invasive pneumococcal disease (IPD) following the introduction of pneumococcal conjugate vaccines (PCVs), PCV7 in 2000 and PCV13 in 2010, yet, disease remains. Expanded valency PCVs, PCV15 and PCV20 that contain two and seven additional serotypes compared to PCV13, are in advanced development.

Methods

We used the CDC Active Bacterial Core surveillance (ABCs) data from 2017 to quantify the incidence and to assess PCV coverage of IPD. ABC is an active laboratory and population-based surveillance system in 10 geographically diverse sites in the United States. Analyses were limited to the serotypes covered by PCV13 (1,3,4,5,6A,6B, 7F,9V,14,18C,19A,19F,23F, plus 6C, which is highly-related to 6A), PCV15 (PCV13-types, 22F,33F), and PCV20 (PCV15-types, 8,10A,11A,12F, plus 15C, which is highly-related to 15B).

Results

In 2017, non-PCV13 and PCV13 serotypes accounted for 63.1-75.0% and 25.0-36.9% of IPD cases across different age groups. The additional two serotypes in PCV15 and the seven serotypes in PCV20 accounted for 8.3-17.0% and 23.8-37.1% of the remaining IPD cases, respectively (Table).

Conclusions

PCV20 could address a substantial remaining burden of IPD, covering an estimated 55.1-66.1% of cases across all age groups.

Background

Despite the indirect effects of routine pediatric pneumococcal conjugate vaccine (PCV) use, invasive pneumococcal disease (IPD) persists in older adults. This analysis describes IPD coverage of current PCVs (PCV10/PCV13) and next generation, PCV15 and PCV20.

Methods

Serotype counts for adults ≥60/≥65 years were obtained from national or regionally-representative IPD surveillance systems in high-income countries. Up to the three most recent years of data were included. Excluded countries reported <20 cases overall or only reported data prior to pediatric PCV introduction into the National Immunization Program (NIP). Coverage was calculated for PCV10 (1,4,5,6B,7F,9V,14,18C,19F,23F), PCV13 (PCV10-types,3,6A,19A, plus 6C, which is highly-related to 6A), PCV15 (PCV13-types, 22F,33F), and PCV20 (PCV13-types, 8,10A,11A,12F,15B, plus 15C, which is highly-related to 15B) as the number of cases in PCVs divided by total number of cases (excluding missing and non-typeable) reported for each country.

Results

Twenty-eight of 80 (35%) high-income countries met inclusion criteria, reporting >25,000 cases that were included in the analysis. Coverage by current and next generation PCVs varied by country and World Health Organization (WHO) region (Table).

Conclusions

PCV20 offers substantial coverage above current PCVs and next generation PCV15 and could address the considerable remaining IPD burden among older adults in high-income countries globally.

Background

In Canadian adults aged ≥65, routine pneumococcal-polysaccharide-vaccine (PPV23) use has been recommended for several decades, and 13-valent pneumococcal conjugate vaccine (PCV13) on an individual basis - since 2016. When PCV13 is administered, sequential PPV23 is recommended to broaden serotype coverage.

We aimed to assess the proportion of PCV13-, PPV23/non13-, PCV15-, and PCV20-type IPD among Canadian older adults.

Methods

Proportions of IPD due to PCV13, PPV23/non13, PCV15 and PCV20 serotypes were calculated from case counts reported, by serotype and age group, from the National Microbiology Laboratory between 2010 and 2017.

Results

Among all IPD, the contribution of PCV13-type declined from 50% (487/967) to 23% (287/1,238). PPV23/non13-type IPD increased from 25% (240/967) to 39% (487/1,238). In 2017, IPD proportions due to PCV15- and PCV20-types were 36% (447/1,238) and 52% (646/1,238) (Figure 1).

Conclusions

Despite routine PPV23 program, increasing trend in cases and proportions of PPV23/non13-type IPD was noted during the observation period. Initial decline in PCV13-type IPD, likely an indirect effect of pediatric program, leveled off in recent years supporting the need for broad PCV13 use in older adults. PCV20, which shares 19 serotypes with PPV23, could address limitations of the PPV23 program in the ability to control vaccine-type IPD.

Background

Despite more than 6 years of routine pediatric PCV13 implementation in Canada, PCV13 serotypes still contributed to roughly 25% of invasive pneumococcal disease in older adults in 2017. One of the elements that can affect disease transmission and immunization program effectiveness is vaccine schedule completion. With transition to PCV13 in 2010/2011, a reduced, 2+1 routine immunization schedule was adopted across Canadian provinces, with the third dose recommended at 12 months of age.

Methods

We estimated the cumulative number of children with incomplete routine PCV13 vaccination series from 2011 to 2017, measured at 2 years of age. National Immunization Survey Coverage rates (available for 2011, 2013, 2015 and 2017; averaged for 2012, 2014 and 2016) along with Canadian census data were used to derive the number of children with incomplete PCV13 series.

Results

There were ~609,000 children with incomplete PCV13 series at 2 years of age in Canada in 2011-2017 (Table 1).

Conclusions

The substantial estimated number of children with incomplete PCV13 series by 2 years of age over the study period, coupled with reduced-dose schedule may have undermined achievement of optimal public health impact. Potential role of these factors in PCV13 program effectiveness in Canada requires better understanding.

Background

In the Netherlands randomized controlled trial (RCT) of 13-valent pneumococcal conjugate vaccine (PCV13) among persons age 65+ years, the primary outcome was chest x-ray (CXR) confirmed, vaccine-type (VT) primarily non-bacteremic Community Acquired Pneumonia (CAP), the latter determined almost entirely by serotype-specific urinary antigen detection (SSUAD). The sensitivity and specificity of SSUAD and CXR for identifying primarily non-bacteremic pneumonia preventable by PCV13 is unknown.

Methods

In the Netherlands RCT, we compared vaccine-preventable-disease-incidence (VPDI) for all episodes of clinically defined CAP to that for CXR-confirmed VT-CAP. VPDI was calculated as the incidence rate difference between controls and vaccinated persons.

Results

VPDI per 100,000 person-years of follow-up for all episodes of clinical CAP vs. VT-CAP were: total population, 72.2/25.1 (2.9-fold); at-risk condition for pneumococcus other than immunosuppression, 121.4/34.3 (3.5-fold); and not at-risk, 35.5/17.6 (2.0-fold) (Table).

Conclusions

PCV13 prevented 2.0 to 3.5 more episodes of clinical CAP than CXR-confirmed VT-CAP, reflecting that SSUAD was designed for the regulatory outcome of vaccine efficacy, which relies on test specificity, and that CXR may have imperfect sensitivity for CAP in elderly persons. Assessing PCV13’s true public health value will require use of rate reductions or adjustment factors to account for clinically defined CAP.

Background

In Canada, age-based recommendation for adult pneumococcal vaccination starts at 65 years (routine for PPV23, on an individual basis for PCV13). Recent literature reports large additional pneumococcal pneumonia and non-pneumonia IPD burden in Canadian adults aged 50-64 years.

Methods

Case counts of IPD by serotype and age group were obtained from published annual National Microbiology Laboratory (NML) reports of passive laboratory-based surveillance. We calculated the proportion of all IPD cases occurring in adults 50-64, ≥65, and ≥50 years of age and trends in the proportion of PCV13-type IPD in these age groups, for 2010-2017.

Results

Between 2010 and 2017, adults aged 50-64 and ≥65 contributed 27% and 38% of 21, 610 reported IPD cases, respectively. The proportion of PCV13-type IPD declined from 52% to 34% in 50-64 cohort, and 50% to 23% in ≥65 cohort, showing a plateau since 2014 in all three age groups (Figure 1).

Conclusions

Adults ≥65 years contributed 38%, and those 50-64 years an incremental 27% of all IPD in Canada over the study period. In 2017, 23% and 34% of IPD in these two cohorts, respectively, was of PCV13-type. These findings support the rationale for intensified PCV13 immunization efforts in both age groups.