Pneumococcal conjugate vaccines (PCV7/10/13/15/20) and PPSV23

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disease risks

post-acute and long-term sequelae

vaccine efficacy and effectiveness

vaccine safety and adverse events

sources

Invasive pneumococcal disease (bacteraemia, meningitis, bacteraemic pneumonia) Streptococcus pneumoniae

Disease risks

Acute risks of the infection itself: complications, hospitalisation, ICU, death.

Outcome (O)	Population (P)	Estimate	Design (S)	Source
Death from pneumococcal meningitis in children under 5, Latin America and the Caribbean severity: death case definition: Culture-confirmed pneumococcal meningitis in studies published 2000-2010	children under 5 years vaccination status: mixed country: Latin America and the Caribbean setting: mostly hospital-based studies period: 2000-2010 Infant <1y1-4y	33.2 (21.3–46.2) CFR (%) per pneumococcal meningitis case	meta-analysis	Ciapponi et al. 2014 Pediatr Infect Dis J quote The case fatality ratio was 33.2% (95% CI: 21.3-46.2) for meningitis and 29.0% (95% CI: 21.9-36.8) for sepsis. abstract, RESULTS Pooled from 39 studies; the same sentence gives 29.0% for pneumococcal sepsis. Mostly pre-PCV era for the region.
In-hospital death from pneumococcal meningitis in African children severity: death case definition: Laboratory-confirmed bacterial meningitis in children aged 1 month to 15 years, 37 African studies	children aged 1 month to 15 years vaccination status: unvaccinated country: multiple (21 African countries) setting: hospital Infant <1y1-4y5-11y12-17y	35 in-hospital CFR (%), median across studies per pneumococcal meningitis case admitted	systematic review	Ramakrishnan et al. 2009 BMC Med quote The highest in-hospital case fatality ratios observed were for pneumococcal meningitis (median = 35%) and Hib meningitis (median = 25%) compared to meningococcal meningitis (median = 4%). abstract, RESULTS A median across studies, not a pooled estimate, so no interval. Pre-PCV era. Hib meningitis was 25% and meningococcal 4% in the same sentence.
Invasive pneumococcal disease, estimated annual cases in children under 5 severity: any invasive disease case definition: Invasive disease (bacteremia and meningitis) as estimated by CDC for the pre-conjugate-vaccine era	children younger than age 5 years vaccination status: unvaccinated country: United States setting: national estimate period: before routine PCV use (pre-2000) Infant <1y1-4y	17,000 estimated annual cases (count) per year, all US children under 5	expert body	cdc.gov quote An estimated 17,000 cases of invasive disease occurred each year, of which 13,000 were bacteremia without a known site of infection and about 700 were meningitis. Pink Book chapter 17, Secular Trends in the United States Pre-vaccine era national estimate from CDC. Of these, most were bacteremia without a known site and about 700 were meningitis, per the same sentence group.
Deaths from invasive pneumococcal disease in children under 5, annual estimate severity: death case definition: Deaths attributed to invasive pneumococcal disease in CDC's pre-vaccine estimate	children younger than age 5 years vaccination status: unvaccinated country: United States setting: national estimate period: before routine PCV use (pre-2000) Infant <1y1-4y	200 estimated annual deaths (count) per year, all US children under 5	expert body	cdc.gov quote An estimated 200 children died every year as a result of invasive pneumococcal disease. Pink Book chapter 17, Secular Trends in the United States Pair with pcv-bur-001 (17,000 cases) for the pre-vaccine picture; do not divide one by the other to make a CFR, since both are rounded estimates.
Deaths from invasive pneumococcal disease, all ages, annual estimate severity: death case definition: Invasive pneumococcal disease (bacteremia and meningitis), CDC estimate for 2017	all ages, more than half in adults with an indication for pneumococcal vaccine vaccination status: mixed country: United States setting: national estimate period: 2017 All ages	3,500 estimated annual deaths (count) per year, US population	expert body	cdc.gov quote More than 31,000 cases and more than 3,500 deaths from invasive pneumococcal disease (bacteremia and meningitis) are estimated to have occurred in the United States in 2017. Pink Book chapter 17, Secular Trends in the United States Current-era figure in a population with routine infant PCV since 2000. The same sentence gives more than 31,000 cases.
Death from bacteremic pneumococcal pneumonia severity: death case definition: Pneumococcal pneumonia with bacteremia	not specified (predominantly adults) vaccination status: not reported country: United States All ages	10 CFR (%) per case of bacteremic pneumonia	expert body	cdc.gov quote The case fatality ratio of pneumonia with bacteremia is around 10%. Pink Book chapter 17, Clinical Features Rounded CDC summary figure without an interval or period.
Death from pneumococcal bacteremia severity: death case definition: Pneumococcal bacteremia with or without pneumonia	not specified vaccination status: not reported country: United States All ages	12 CFR (%) per case of pneumococcal bacteremia	expert body	cdc.gov quote The overall case fatality ratio for bacteremia is about 12%. Pink Book chapter 17, Clinical Features Rounded CDC summary figure. The same paragraph notes a fulminant course in patients with asplenia.
Death from pneumococcal meningitis in adults severity: death case definition: Pneumococcal meningitis	adults vaccination status: not reported country: United States 18-49y50-64y65+	14 CFR (%) per case of pneumococcal meningitis	expert body	cdc.gov quote The case fatality ratio of pneumococcal meningitis is about 14% among adults. Pink Book chapter 17, Clinical Features CDC summary figure for adults; neurologic sequelae among survivors are described as common in the same passage but not quantified there (see post_acute records).
Pneumococcal meningitis incidence in infants before PCV severity: meningitis case definition: Pneumococcal meningitis	children younger than 1 year vaccination status: unvaccinated country: United States period: before routine PCV use Infant <1y	10 incidence per 100,000 population per year per 100,000 infants per year	expert body	cdc.gov quote Before routine use of pneumococcal conjugate vaccine, children younger than 1 year had the highest rates of pneumococcal meningitis, approximately 10 cases per 100,000 population. Pink Book chapter 17, Pneumococcal Disease in Children Infants had the highest pneumococcal meningitis rate of any age group before PCV7.
Invasive pneumococcal disease incidence in children with asplenia or immunocompromise severity: any invasive disease case definition: Invasive pneumococcal disease in children with functional or anatomic asplenia (particularly sickle cell disease) or immunocompromising conditions	children risk group: sickle cell disease, asplenia, immunocompromising conditions immune status: immunocompromised or asplenic vaccination status: not reported country: United States Infant <1y1-4y5-11y	5,000 to 9,000 incidence per 100,000 population per year per 100,000 children with these conditions per year	expert body	cdc.gov quote Children with functional or anatomic asplenia, particularly those with sickle cell disease, and children with immunocompromising conditions are at very high risk for invasive disease, with rates in some studies more than 50 times higher than those among children of the same age without these conditions (i.e., incidence rates of 5,000 to 9,000 per 100,000 population). Pink Book chapter 17, Pneumococcal Disease in Children A range quoted from some studies, described as more than 50 times the rate in children without these conditions. No interval or era given.
Invasive pneumococcal disease incidence in adults with hematologic cancer severity: any invasive disease case definition: Invasive pneumococcal disease in adults age 18 through 64 years with hematologic cancer	adults 18 through 64 years risk group: hematologic cancer immune status: immunocompromised vaccination status: not reported country: United States period: 2013-2014 18-49y50-64y	129 incidence per 100,000 population per year per 100,000 adults with hematologic cancer per year	expert body	cdc.gov quote For adults age 18 through 64 years with hematologic cancer, the rate of invasive pneumococcal disease in 2013–2014 was 129 per 100,000 population. Pink Book chapter 17, Clinical Features Current-era (post-PCV13) figure in the highest-risk adult group named by CDC.
Invasive pneumococcal disease incidence in commercially insured children under 2, pre-PCV7 severity: any invasive disease case definition: IPD episodes identified by ICD-9/10-CM claims codes in the MarketScan Commercial database	children under 2 years vaccination status: unvaccinated country: United States setting: commercially insured population period: pre-PCV7 (1998-1999) Infant <1y1-4y	65.6 incidence per 100,000 person-years per 100,000 person-years	cohort	Hu et al. 2022 BMC Public Health quote RESULTS: In commercially insured children, IPD IRs decreased from 9.4 to 2.8 episodes/100,000 PY between the pre-PCV7 (1998-1999) and late PCV13 period (2014-2018) overall, and from 65.6 to 11.6 episodes/100,000 PY in children < 2 years. abstract, RESULTS Claims-based ascertainment, lower than the laboratory-based ABCs rate for the same era (pcv-bur-010). The same sentence gives the late-PCV13 rate (pcv-bur-014).
Invasive pneumococcal disease incidence in commercially insured children under 2, late PCV13 era severity: any invasive disease case definition: IPD episodes identified by ICD-9/10-CM claims codes in the MarketScan Commercial database	children under 2 years vaccination status: mixed country: United States setting: commercially insured population period: late PCV13 period (2014-2018) Infant <1y1-4y	11.6 incidence per 100,000 person-years per 100,000 person-years	cohort	Hu et al. 2022 BMC Public Health quote RESULTS: In commercially insured children, IPD IRs decreased from 9.4 to 2.8 episodes/100,000 PY between the pre-PCV7 (1998-1999) and late PCV13 period (2014-2018) overall, and from 65.6 to 11.6 episodes/100,000 PY in children < 2 years. abstract, RESULTS Residual burden after two decades of PCV; the abstract notes rates rose again in the late PCV13 period in this age group and that the share of cases with underlying risk factors increased.
Invasive pneumococcal disease incidence in children under 2, pre-PCV7 baseline severity: any invasive disease case definition: Isolation of Streptococcus pneumoniae from a normally sterile site, Active Bacterial Core surveillance	children under two years of age vaccination status: unvaccinated country: United States setting: population-based surveillance, seven areas (population 16 million) period: 1998-1999 baseline Infant <1y1-4y	188.0 incidence per 100,000 population per year per 100,000 children under 2 per year	surveillance	Whitney et al. 2003 N Engl J Med quote 59.0 cases per 100,000 vs. 188.0 per 100,000, P<0. abstract, RESULTS Baseline rate before PCV7; the same sentence gives the 2001 rate (pcv-bur-011) and the 69 percent decline.
Invasive pneumococcal disease incidence in children under 2, one year after PCV7 severity: any invasive disease case definition: Isolation of Streptococcus pneumoniae from a normally sterile site, Active Bacterial Core surveillance	children under two years of age vaccination status: mixed country: United States setting: population-based surveillance, seven areas period: 2001 Infant <1y1-4y	59.0 incidence per 100,000 population per year per 100,000 children under 2 per year	surveillance	Whitney et al. 2003 N Engl J Med quote 59.0 cases per 100,000 vs. 188.0 per 100,000, P<0. abstract, RESULTS First full year after PCV7 introduction; vaccination coverage was still rising, so the population is mixed.
Invasive pneumococcal disease incidence in adults 65 and older, pre-PCV7 baseline severity: any invasive disease case definition: Isolation of Streptococcus pneumoniae from a normally sterile site, Active Bacterial Core surveillance	adults 65 years of age or more vaccination status: not reported country: United States setting: population-based surveillance, seven areas period: 1998-1999 baseline 65+	60.1 incidence per 100,000 population per year per 100,000 adults 65+ per year	surveillance	Whitney et al. 2003 N Engl J Med quote 49.5 per 100,000 vs. 60.1 per 100,000, P<0. abstract, RESULTS Adults were not the PCV7 target; the 18 percent fall to 49.5 by 2001 in the same sentence is the earliest US signal of indirect (herd) protection.
Invasive pneumococcal disease incidence in infants aged 0 to 90 days, before PCV7 severity: any invasive disease case definition: Laboratory-confirmed IPD in infants aged 0 to 90 days, active surveillance in 8 US states	infants aged 0 to 90 days vaccination status: unvaccinated country: United States setting: population-based surveillance period: July 1997 to June 2000 NeonateInfant <1y	11.8 (9.6–14.5) incidence per 100,000 live births per 100,000 live births	surveillance	Poehling et al. 2006 JAMA quote Mean rates of IPD for infants aged 0 to 90 days decreased 40% from 11.8 (95% confidence interval [CI], 9.6-14.5) to 7.2 (95% CI, 5.6-9.4; P = .004) per 100 000 live births following PCV7 introduction. abstract, RESULTS Infants too young to be vaccinated; the fall to 7.2 after PCV7 (same sentence) is an indirect effect of vaccinating older children.
Death from invasive pneumococcal disease, all ages, Europe severity: death case definition: IPD cases reported by 17 European countries to the European surveillance system in 2010	all ages, 38.2% over 65 years vaccination status: mixed country: multiple (17 European countries) setting: national surveillance period: 2010 n: 2,921 patients All ages	9.0 CFR (%) per reported IPD case	surveillance	Navarro-Torné et al. 2015 Emerg Infect Dis quote Death was reported in 264 (9.0%) cases. abstract Older age, meningitis and penicillin non-susceptibility were associated with death. Death reporting completeness varies by country, so this is a lower-bound CFR.
Death from invasive pneumococcal disease, all ages, pre-PCV Netherlands severity: death case definition: Hospitalised IPD patients with isolates from nine sentinel laboratories covering 25% of the Dutch population	all ages vaccination status: unvaccinated country: Netherlands setting: hospital, sentinel laboratory surveillance period: before PCV7 introduction (June 2004 to 2006) All ages	16.2 CFR (%) per hospitalised IPD case	surveillance	Vestjens et al. 2019 Vaccine quote While the case fatality rate (CFR) decreased from 16.2% pre-PCV to 13.4% post-PCV10 (RR:0.83, 95%CI:0.70-0.99), the switch to PCV10 had no further impact on CFR (RR:1.14, 95%CI:0.96-1.36). abstract, RESULTS The same sentence gives the post-PCV10 CFR of 13.4% (RR 0.83); the switch from PCV7 to PCV10 did not change CFR further.
Death from invasive pneumococcal disease in children under 5, pre-PCV7 severity: death case definition: Hospitalised IPD patients, nine Dutch sentinel laboratories	children under 5 years vaccination status: unvaccinated country: Netherlands setting: hospital, sentinel surveillance period: pre-PCV7 (2004-2006) Infant <1y1-4y	5 CFR (%) per hospitalised IPD case	surveillance	Wagenvoort et al. 2016 Vaccine quote IPD case-fatality decreased in children <5 years from 5% to 3%, in 5-64 years old from 9% to 7% and in elderly ≥65 years significantly from 22% to 17%, due to lower case-fatality rates for most emerging non-PCV7 serotypes. abstract, RESULTS Fell to 3% in 2008-2012 (same sentence). High-income child IPD CFR is an order of magnitude below the LMIC meningitis CFRs in pcv-bur-020 and pcv-bur-021.
Death from invasive pneumococcal disease in adults 65 and older, pre-PCV7 severity: death case definition: Hospitalised IPD patients, nine Dutch sentinel laboratories	elderly 65 years and older vaccination status: not reported country: Netherlands setting: hospital, sentinel surveillance period: pre-PCV7 (2004-2006) 65+	22 CFR (%) per hospitalised IPD case	surveillance	Wagenvoort et al. 2016 Vaccine quote IPD case-fatality decreased in children <5 years from 5% to 3%, in 5-64 years old from 9% to 7% and in elderly ≥65 years significantly from 22% to 17%, due to lower case-fatality rates for most emerging non-PCV7 serotypes. abstract, RESULTS Fell significantly to 17% in 2008-2012 (same sentence) because emerging non-PCV7 serotypes carried lower case-fatality.
In-hospital death within 30 days from invasive pneumococcal disease in adults severity: death case definition: Nationwide IPD surveillance in adults, Israel	adults, 54% aged 65 years or older vaccination status: mixed country: Israel setting: hospital, national surveillance period: 2009-2018 n: 3,864 IPD episodes 18-49y50-64y65+	22 CFR (%) per adult IPD episode with outcome data	surveillance	Wieder-Finesod et al. 2025 Clin Microbiol Infect quote In-hospital CFR was 22% (698/3140). abstract, RESULTS Post-PCV13 era (Israel introduced infant PCV in 2009). CFR varied by serotype: 21.1% for PCV13 serotypes, 16.2% for PCV20-non-PCV13, 28.5% for non-PCV20 serotypes.
30-day death from invasive pneumococcal disease in adults, pre-PCV10 Finland severity: death case definition: Culture-confirmed IPD in adults 18 years or older, national laboratory surveillance linked to population registry	adults 18 years and older vaccination status: not reported country: Finland setting: national surveillance period: pre-PCV10 (July 2004 to June 2010) n: 5,610 adult IPD cases over the whole study 18-49y50-64y65+	11.9 CFR (%) per adult IPD case	surveillance	Nuorti et al. 2022 Vaccine quote Case-fatality proportion decreased from 11·9% to 10.0% (p < 0.01). abstract, RESULTS Fell to 10.0% after infant PCV10 (same sentence, p < 0.01). 85% of adult IPD was pneumonia.
Death from invasive pneumococcal disease in adults 65 and older, Barcelona severity: death case definition: Culture-proven IPD in adults, active hospital surveillance	adults 65 years and older vaccination status: not reported country: Spain setting: hospital period: baseline 1994-2001 (unchanged through 2013) 65+	24 CFR (%) per adult IPD case	surveillance	Grau et al. 2016 J Infect quote case fatality rate did not change (24 vs. 22 vs. 24 percent); however, there was a decline in PCV7 serotypes-specific death (4. abstract, RESULTS Unchanged across the PCV7 and PCV13 periods in this age group even as vaccine-serotype deaths fell, because non-vaccine-serotype deaths rose. In adults 18-64 the CFR fell from 22 to 12 percent over the same periods.
Death among children with sickle cell disease (HbSS) and invasive pneumococcal disease severity: death case definition: IPD episodes in children with HbSS aged under 10 years, Georgia Emerging Infections Program / ABCs, metropolitan Atlanta	children under 10 years risk group: sickle cell disease (HbSS) immune status: functional asplenia vaccination status: mixed country: United States setting: population-based surveillance period: before 2002 (pre-PCV7 era) vs after Infant <1y1-4y5-11y	14 CFR (%) per IPD episode in a child with HbSS	surveillance	Adamkiewicz et al. 2023 Blood Adv quote Among children with HbSS and IPD, death declined from 14% to 3% after 2002, and meningitis declined from 16% to 8%. abstract Pre-2002 figure; the same sentence gives 3% afterwards. IPD incidence in these children fell 87% but remained 20 to 29 times the reference population.
Serotype replacement: increase in non-PCV13-type IPD six years after PCV10/PCV13 in children under 5 severity: any invasive disease case definition: Serotype-specific IPD from surveillance sites using PCV10 or PCV13 with at least 50% primary-series uptake, PSERENADE project	children younger than 5 years vaccination status: mixed country: multiple (30 countries, primarily high income) setting: national or regional surveillance period: 6 years after PCV10 or PCV13 introduction vs pre-PCV n: 32 PCV13 sites (488 758 cases) and 15 PCV10 sites (46 386 cases) Infant <1y1-4y	2.3-3.3 fold increase in incidence relative to pre-PCV baseline relative to pre-PCV incidence	surveillance	Bennett et al. 2025 Lancet Infect Dis quote Non-PCV13-type IPD increased similarly for both products (age <5 years: 2·3-3·3-fold; age ≥65 years: 1·7-2·3-fold). abstract, FINDINGS Range across product and prior-PCV7 strata, not a confidence interval. In adults 65 and older the increase was 1.7-2.3-fold (same sentence). Despite replacement, all-serotype IPD in under-5s still fell 58-74% (pcv-eff-074).
Serotype 19A IPD increase at PCV10 sites in children under 5 severity: any invasive disease strain: serotype 19A case definition: Serotype 19A IPD at sites using PCV10 (which lacks 19A), PSERENADE project	children younger than 5 years vaccination status: mixed country: multiple setting: surveillance sites using PCV10 period: 6 years after PCV10 introduction vs before any PCV Infant <1y1-4y	1.6-2.3 fold increase in incidence relative to pre-PCV baseline relative to pre-PCV incidence	surveillance	Bennett et al. 2025 Lancet Infect Dis quote PCV7-related serotype 19A increases before PCV10 or PCV13 introduction were reversed at PCV13 sites (age <5 years: 61-79% decline relative to before any PCV; age ≥65 years: 7-26% decline) but increased at PCV10 sites (age <5 years: 1·6-2·3-fold; age ≥65 years: 3·6-4·9-fold). abstract, FINDINGS Range across strata, not a CI. At PCV13 sites 19A instead declined 61-79% in the same age group (same sentence), the clearest product difference in the analysis.
Share of remaining IPD in children under 5 caused by PCV13 serotypes at mature PCV13 sites severity: any invasive disease case definition: Serotyped IPD cases 5 or more years after PCV13 introduction, sites with at least 70% primary-series uptake	children younger than 5 years vaccination status: mixed country: multiple (41 countries) setting: surveillance period: mainly 2015-2018 n: 42 PCV13 sites (63 362 cases) Infant <1y1-4y	26.4 (21.3–30.0) proportion of IPD cases (%) per IPD case in children under 5	surveillance	Garcia et al. 2025 Lancet Infect Dis quote At PCV13 sites, PCV13 serotypes caused 26·4% (21·3-30·0) of IPD cases in children younger than 5 years and 29·5% (27·5-33·0) of cases in adults aged 50 years or older. abstract, FINDINGS Three quarters of residual child IPD at mature PCV13 sites is due to non-vaccine serotypes. Serotype 3 alone caused about 9% of child cases and 14% of cases in adults 50+ at both PCV10 and PCV13 sites.
Global deaths from pneumococcal disease in children aged 1-59 months, year 2000 severity: death case definition: Modelled pneumococcal pneumonia, meningitis and other invasive disease deaths, WHO country estimates with vaccine-probe attributable fractions	children aged 1-59 months vaccination status: unvaccinated country: global period: 2000 Infant <1y1-4y	826,000 (582,000–926,000) estimated annual deaths (count) per year, global children aged 1-59 months	modelling	O'Brien et al. 2009 Lancet quote Pneumococcal disease caused about 826,000 deaths (582,000-926,000) in children aged 1-59 months, of which 91,000 (63,000-102,000) were in HIV-positive and 735,000 (519,000-825,000) in HIV-negative children. abstract, FINDINGS Uncertainty range, not a 95% CI. Pre-PCV baseline for the global burden; 91,000 of these deaths were in HIV-positive children.
Global deaths from pneumococcal disease in HIV-uninfected children aged 1-59 months, 2015 severity: death case definition: Modelled pneumococcal pneumonia, meningitis and other invasive disease deaths using WHO/MCEE mortality envelopes and vaccine-probe attributable fractions	children aged 1-59 months immune status: HIV-uninfected vaccination status: mixed country: global period: 2015 Infant <1y1-4y	294 000 (192 000–366 000) estimated annual deaths (count) per year, global HIV-uninfected children aged 1-59 months	modelling	Wahl et al. 2018 Lancet Glob Health quote FINDINGS: We estimated that there were 294 000 pneumococcal deaths (uncertainty range [UR] 192 000-366 000) and 29 500 Hib deaths (18 400-40 700) in HIV-uninfected children aged 1-59 months in 2015. abstract, FINDINGS Uncertainty range, not a 95% CI. The same abstract notes less conservative assumptions give up to 515 000 deaths, and that 81% of pneumococcal deaths presented as pneumonia.
Decline in global child pneumococcal deaths from 2000 to 2015 severity: death case definition: Modelled pneumococcal deaths in children aged 1-59 months	children aged 1-59 months vaccination status: mixed country: global period: 2000 to 2015 Infant <1y1-4y	51 (7–74) percentage decline in annual deaths (%) relative to modelled deaths in 2000	modelling	Wahl et al. 2018 Lancet Glob Health quote We estimate that pneumococcal deaths declined by 51% (7-74) and Hib deaths by 90% (78-96) from 2000 to 2015. abstract, FINDINGS Uncertainty range, not a 95% CI; very wide because the pneumonia-attributable fraction is itself uncertain. Hib deaths fell 90% in the same period.

Vaccine efficacy and effectiveness

Every estimate compiled, annotated by population (P), intervention (I), comparator (C), outcome (O) and study design (S).

Outcome (O)	Population (P)	Intervention / comparator	Estimate	Design (S)	Source
Vaccine-serotype invasive pneumococcal disease severity: any invasive disease case definition: Culture-confirmed IPD caused by serotypes in the vaccine, intent-to-treat, HIV-1 negative children	children under two years at enrolment immune status: HIV-1 negative country: multiple (Africa, United States, Philippines, Finland) n: 57,015 PCV and 56,029 control children across six RCTs Infant <1y1-4y	PCV7, PCV9 and PCV11 (CRM197 and other carriers) as used in the trials platform: protein-polysaccharide conjugate doses: 3 or more primary doses as per trial vs placebo or another vaccine	80 (58–90) VE (%)	meta-analysis GRADE: high 6 RCTs (11 publications)	Lucero et al. 2009 Cochrane Database Syst Rev quote Only two trials have data on all-cause admissions.The main analysis for this review involved HIV-1 negative children and used the pooled results of random-effects model, intent-to-treat analysis (ITT).Pooled vaccine efficacy (VE) for VT-IPD was 80% (95% confidence interval (CI) 58% to 90%, P < 0.0001); all serotypes-IPD, 58% (95% CI 29% to 75%, P = 0.001); World Health Organization X-ray defined pneumonia was 27% (95% CI 15% to 36%, P < 0.0001); clinical pneumonia, 6% (95% CI 2% to 9%, P = 0.0006); and all-cause mortality, 11% (95% CI -1% to 21%, P = 0.08). abstract, MAIN RESULTS Random-effects pooled efficacy; the review rated the IPD evidence high quality. Analyses in HIV-1 positive children had similar findings but no separate pooled number is given in the abstract.
Invasive pneumococcal disease caused by any serotype severity: any invasive disease case definition: Culture-confirmed IPD, all serotypes, intent-to-treat, HIV-1 negative children	children under two years at enrolment immune status: HIV-1 negative country: multiple Infant <1y1-4y	PCV7, PCV9 and PCV11 as used in the trials platform: protein-polysaccharide conjugate doses: 3 or more primary doses as per trial vs placebo or another vaccine	58 (29–75) VE (%)	meta-analysis GRADE: high 6 RCTs	Lucero et al. 2009 Cochrane Database Syst Rev quote Only two trials have data on all-cause admissions.The main analysis for this review involved HIV-1 negative children and used the pooled results of random-effects model, intent-to-treat analysis (ITT).Pooled vaccine efficacy (VE) for VT-IPD was 80% (95% confidence interval (CI) 58% to 90%, P < 0.0001); all serotypes-IPD, 58% (95% CI 29% to 75%, P = 0.001); World Health Organization X-ray defined pneumonia was 27% (95% CI 15% to 36%, P < 0.0001); clinical pneumonia, 6% (95% CI 2% to 9%, P = 0.0006); and all-cause mortality, 11% (95% CI -1% to 21%, P = 0.08). abstract, MAIN RESULTS Lower than vaccine-type efficacy because non-vaccine serotypes are untouched; the gap between 80% and 58% is the room for serotype replacement.
All-cause mortality severity: death case definition: Death from any cause during trial follow-up, HIV-1 negative children	children under two years at enrolment immune status: HIV-1 negative country: multiple Infant <1y1-4y	PCV7, PCV9 and PCV11 as used in the trials platform: protein-polysaccharide conjugate doses: 3 or more primary doses as per trial vs placebo or another vaccine	11 (-1–21) VE (%)	meta-analysis 5 trials with mortality data, none powered for it	Lucero et al. 2009 Cochrane Database Syst Rev quote Only two trials have data on all-cause admissions.The main analysis for this review involved HIV-1 negative children and used the pooled results of random-effects model, intent-to-treat analysis (ITT).Pooled vaccine efficacy (VE) for VT-IPD was 80% (95% confidence interval (CI) 58% to 90%, P < 0.0001); all serotypes-IPD, 58% (95% CI 29% to 75%, P = 0.001); World Health Organization X-ray defined pneumonia was 27% (95% CI 15% to 36%, P < 0.0001); clinical pneumonia, 6% (95% CI 2% to 9%, P = 0.0006); and all-cause mortality, 11% (95% CI -1% to 21%, P = 0.08). abstract, MAIN RESULTS Interval crosses zero (P = 0.08). The review calls it compatible with a mortality reduction but not proof of one.
Invasive pneumococcal disease caused by serotype 3 severity: any invasive disease strain: serotype 3 case definition: Serotype 3 IPD in observational PCV13 effectiveness studies stratified by serotype, published before 14 August 2017	children country: multiple Infant <1y1-4y5-11y	PCV13 platform: protein-polysaccharide conjugate doses: as per included studies vs unvaccinated or non-vaccine-type controls as per included studies	63.5 (37.3–89.7) VE (%)	meta-analysis 4 published studies	Sings et al. 2019 Clin Infect Dis quote The pooled PCV13 VE against serotype 3 IPD from the random-effects meta-analysis was 63.5% (95% confidence interval [CI], 37.3%-89.7%). abstract Pfizer-authored meta-analysis. Including two conference posters gave 72.4% (56.7-88.0). Conflicts with UK indirect-cohort findings of no serotype 3 protection; see flag.
Invasive pneumococcal disease severity: any invasive disease case definition: IPD as defined in the included randomised trials	adults country: multiple n: 64,852 participants in 18 RCTs 18-49y50-64y65+	pneumococcal polysaccharide vaccine (PPV, mostly 14- and 23-valent) platform: plain polysaccharide doses: 1 vs placebo or no vaccine	0.26 (0.14–0.45) OR (vaccinated vs unvaccinated)	meta-analysis 18 RCTs (random-effects, I2 = 0%)	Moberley et al. 2013 Cochrane Database Syst Rev quote Meta-analysis of the RCTs found strong evidence of PPV efficacy against IPD with no statistical heterogeneity (OR 0.26, 95% CI 0.14 to 0.45; random-effects model, I(2) statistic = 0%). abstract, MAIN RESULTS Cochrane 2013. Reported as an odds ratio, not VE; the review found no heterogeneity for this outcome.
All-cause mortality severity: death case definition: Death from any cause in the included RCTs	adults country: multiple 18-49y50-64y65+	pneumococcal polysaccharide vaccine (PPV) platform: plain polysaccharide doses: 1 vs placebo or no vaccine	0.90 (0.74–1.09) OR (vaccinated vs unvaccinated)	meta-analysis RCTs (random-effects, I2 = 69%)	Moberley et al. 2013 Cochrane Database Syst Rev quote PPV was not associated with substantial reductions in all-cause mortality (OR 0.90, 95% CI 0.74 to 1.09; random-effects model, I(2) statistic = 69%). abstract, MAIN RESULTS No substantial reduction in all-cause mortality; the review does not support PPV for preventing death or all-cause pneumonia, only IPD.
Invasive pneumococcal disease in populations currently targeted for vaccination severity: any invasive disease case definition: Culture-confirmed IPD in non-randomised studies that controlled for important confounders	adults in groups for whom the vaccine is currently utilised country: multiple n: 62,294 participants in seven non-RCTs 18-49y50-64y65+	PPSV23 platform: plain polysaccharide doses: 1 vs unvaccinated, adjusted for confounders	0.48 (0.37–0.61) OR (vaccinated vs unvaccinated)	meta-analysis 7 non-randomised studies (I2 = 31%)	Moberley et al. 2013 Cochrane Database Syst Rev quote Non-RCTs provided evidence for protection against IPD in populations for whom the vaccine is currently utilised (OR 0.48, 95% CI 0.37 to 0.61; random-effects model, I(2) statistic = 31%). abstract, MAIN RESULTS Observational effectiveness is weaker than the RCT efficacy (pcv-eff-043), consistent with older and sicker real-world recipients and waning.
Invasive pneumococcal disease by any serotype, clinical trials severity: any invasive disease case definition: IPD in randomised trials of adults aged 60 years and over in industrialised countries	adults aged 60 years and over country: industrialised countries 50-64y65+	PPSV23 platform: plain polysaccharide doses: 1 vs placebo or no vaccine	73 (10–92) VE (%)	meta-analysis 4 clinical trials	Falkenhorst et al. 2017 PLoS One quote Pooled VE against IPD (by any serotype) was 73% (95%CI: 10-92%) in four clinical trials, 45% (95%CI: 15-65%) in three cohort studies, and 59% (95%CI: 35-74%) in three case-control studies. abstract, RESULTS The same sentence gives 45% (15-65) from three cohort studies and 59% (35-74) from three case-control studies. Higher trial estimates (follow-up about 2.5 years) than observational ones (about 5 years) may reflect waning.
Invasive pneumococcal disease by any serotype, cohort studies severity: any invasive disease case definition: IPD in cohort studies of adults aged 60 years and over	adults aged 60 years and over country: industrialised countries 50-64y65+	PPSV23 platform: plain polysaccharide doses: 1 vs unvaccinated	45 (15–65) VE (%)	meta-analysis 3 cohort studies	Falkenhorst et al. 2017 PLoS One quote Pooled VE against IPD (by any serotype) was 73% (95%CI: 10-92%) in four clinical trials, 45% (95%CI: 15-65%) in three cohort studies, and 59% (95%CI: 35-74%) in three case-control studies. abstract, RESULTS Observational, longer follow-up than the trials in pcv-eff-048.
Vaccine-type invasive pneumococcal disease, 3+0 schedule (no booster) severity: any invasive disease case definition: VT-IPD in randomised controlled trials of three-dose primary series without booster	young children country: multiple Infant <1y1-4y	PCV (7-, 9- or 11-valent as per trial) platform: protein-polysaccharide conjugate doses: 3 schedule: 3+0 vs placebo or control vaccine	65 to 71 VE (%), range across trials	systematic review	Conklin et al. 2014 Pediatr Infect Dis J quote In clinical trials, vaccine efficacy ranged from 65% to 71% with 3+0 and 83% to 94% with 3+1. abstract, RESULTS Range across trials, not a pooled estimate or CI. The same sentence gives 83% to 94% with 3+1 (pcv-eff-059). Only one observational study directly compared schedules and supported a booster.
Vaccine-type invasive pneumococcal disease, 3+1 schedule severity: any invasive disease case definition: VT-IPD in randomised controlled trials of three-dose primary series with booster	young children country: multiple (mostly North America and Europe) Infant <1y1-4y	PCV (7-, 9- or 11-valent as per trial) platform: protein-polysaccharide conjugate doses: 4 schedule: 3+1 vs placebo or control vaccine	83 to 94 VE (%), range across trials	systematic review	Conklin et al. 2014 Pediatr Infect Dis J quote In clinical trials, vaccine efficacy ranged from 65% to 71% with 3+0 and 83% to 94% with 3+1. abstract, RESULTS Range across trials, not a CI. Observational data showed reductions up to 100% with 2+1 or 3+1 and up to 90% with 3+0, but the review concluded differences between schedules are hard to discern.
Invasive pneumococcal disease caused by serotype 19A (cross-protection from PCV10) severity: any invasive disease strain: serotype 19A (not in PCV10) case definition: Serotype 19A IPD in observational studies of PCV10, children with at least one dose	children 5 years and under country: multiple Infant <1y1-4y	PCV10 (PHiD-CV) platform: protein-polysaccharide conjugate doses: 1 or more vs unvaccinated or non-vaccine-type controls as per included studies	82.2 VE (%)	systematic review	Berman-Rosa et al. 2020 Pediatrics quote PCV-10 crossprotection against 19A was significant in children ≤5 years with ≥1 dose (82.2% and 71%). abstract, RESULTS Two study estimates (82.2% and 71%) are given in the same sentence; no pooled estimate because of heterogeneity. Cross-protection against 19A was not verified in children under 12 months, and the population-level 19A increase at PCV10 sites (pcv-bur-037) argues it is incomplete.
Acute otitis media severity: otitis media case definition: Acute otitis media in studies of PCV13 in healthy children under 5	children under 5 years country: multiple Infant <1y1-4y	PCV13 platform: protein-polysaccharide conjugate doses: 1 or more vs unvaccinated or pre-vaccine controls as per included study	86 (61–94) VE (%)	systematic review	Berman-Rosa et al. 2020 Pediatrics quote PCV-13 was effective against AOM (86%; 95% confidence interval [CI]: 61 to 94). abstract, RESULTS Otitis media is not invasive disease but is the commonest pneumococcal illness; PCV10 estimates in the same sentence were 26.9% (5.9-43.3) clinically defined and 43.3% (1.7-67.3) bacteriologically confirmed.
PCV13-serotype invasive disease in adults 65 and older, indirect effect of infant PCV13 severity: any invasive disease strain: PCV13 serotypes case definition: Invasive disease caused by PCV13 serotypes, CDC surveillance	adults age 65 years or older country: United States period: since 2010 65+	PCV13 in children (indirect effect) platform: protein-polysaccharide conjugate doses: routine infant schedule vs pre-PCV13 incidence	over 60 percentage decline (%)	expert body	cdc.gov quote Since introduction of PCV13 in children in 2010, invasive disease caused by PCV13 serotypes has declined over 60% among adults age 65 years or older through PCV13 indirect effects. Pink Book chapter 17, Immunogenicity and Vaccine Efficacy CDC summary statement; no interval. The CDC surveillance page (cdc-gov-ebc9c01b7d) gives 95% overall and 99% PCV13-type declines in under-5s from 1998 through 2021.
Invasive disease caused by vaccine serotypes severity: any invasive disease case definition: Invasive pneumococcal disease due to the seven vaccine serotypes in fully vaccinated children	infants vaccinated at 2, 4, 6 and 12 to 15 months risk group: healthy children in a managed-care population country: United States setting: Northern California Kaiser Permanente period: 1995-1999 n: 37,868 children randomised Infant <1y1-4y	PCV7 (heptavalent CRM197 conjugate, Wyeth Lederle) platform: protein-polysaccharide conjugate doses: 4 schedule: 2, 4, 6 and 12-15 months vs meningococcal type C CRM197 conjugate vaccine	97.4 (82.7–99.9) VE (%)	RCT	Black et al. 2000 Pediatr Infect Dis J quote As of that time 40 fully vaccinated cases of invasive disease caused by vaccine serotype had been identified, all but 1 in controls for an efficacy of 97.4% (95% confidence interval, 82.7 to 99.9%), and 52 cases, all but 3 in controls in the intent-to-treat analysis for an efficacy of 93.9% (95% confidence interval, 79.6 to 98.5%). abstract, RESULTS Per-protocol (fully vaccinated) analysis as of April 1999; 40 cases, all but one in controls. The licensing trial for the first PCV.
Invasive disease caused by vaccine serotypes, intent-to-treat severity: any invasive disease case definition: Invasive pneumococcal disease due to the seven vaccine serotypes, all randomised children	infants vaccinated at 2, 4, 6 and 12 to 15 months risk group: healthy children in a managed-care population country: United States setting: Northern California Kaiser Permanente period: 1995-1999 n: 37,868 children randomised Infant <1y1-4y	PCV7 (heptavalent CRM197 conjugate) platform: protein-polysaccharide conjugate doses: 1 or more (intent-to-treat) schedule: 2, 4, 6 and 12-15 months vs meningococcal type C CRM197 conjugate vaccine	93.9 (79.6–98.5) VE (%)	RCT	Black et al. 2000 Pediatr Infect Dis J quote As of that time 40 fully vaccinated cases of invasive disease caused by vaccine serotype had been identified, all but 1 in controls for an efficacy of 97.4% (95% confidence interval, 82.7 to 99.9%), and 52 cases, all but 3 in controls in the intent-to-treat analysis for an efficacy of 93.9% (95% confidence interval, 79.6 to 98.5%). abstract, RESULTS Intent-to-treat analysis including partially vaccinated children; 52 cases, all but three in controls. No evidence of replacement by non-vaccine serotypes within the trial.
Vaccine-type invasive pneumococcal disease, 3+1 schedule severity: any invasive disease case definition: Culture-confirmed IPD due to any of the ten vaccine serotypes, national infectious diseases register	infants under 7 months at first vaccination country: Finland setting: nationwide cluster-randomised trial (FinIP) period: February 2009 to January 2012 n: 30,528 participants assessed for the primary objective Infant <1y1-4y	PCV10 (PHiD-CV10, Synflorix) platform: protein-polysaccharide conjugate (protein D, tetanus and diphtheria toxoid carriers) doses: 4 schedule: 3+1 vs hepatitis A or B vaccine control clusters	100 (83–100) VE (%)	cluster RCT	Palmu et al. 2013 Lancet quote The estimates for vaccine effectiveness were 100% (95% CI 83-100) for PHiD-CV10 3+1 and 92% (58-100) for PHiD-CV10 2+1 groups. abstract, FINDINGS No vaccine-type cases in the 3+1 group versus 12 in controls. Double-blind cluster design; follow-up to January 2012.
Vaccine-type invasive pneumococcal disease, 2+1 schedule severity: any invasive disease case definition: Culture-confirmed IPD due to any of the ten vaccine serotypes, national register	infants under 7 months at first vaccination country: Finland setting: nationwide cluster-randomised trial (FinIP) period: February 2009 to January 2012 Infant <1y1-4y	PCV10 (PHiD-CV10, Synflorix) platform: protein-polysaccharide conjugate doses: 3 schedule: 2+1 vs hepatitis A or B vaccine control clusters	92 (58–100) VE (%)	cluster RCT	Palmu et al. 2013 Lancet quote The estimates for vaccine effectiveness were 100% (95% CI 83-100) for PHiD-CV10 3+1 and 92% (58-100) for PHiD-CV10 2+1 groups. abstract, FINDINGS One vaccine-type case in the 2+1 group. First trial confirmation that a reduced 2+1 infant schedule protects; the interval overlaps the 3+1 estimate entirely.
Invasive pneumococcal disease of any serotype severity: any invasive disease case definition: Any culture-confirmed invasive pneumococcal disease irrespective of serotype, combined infant cohorts	infants under 7 months at first vaccination (3+1 and 2+1 cohorts combined) country: Finland setting: FinIP cluster-randomised trial period: 2009-2012 Infant <1y1-4y	PCV10 (PHiD-CV10) platform: protein-polysaccharide conjugate doses: 3 or 4 schedule: 2+1 or 3+1 vs hepatitis vaccine control clusters	93 (75–99) VE (%)	cluster RCT	Palmu et al. 2013 Lancet quote Two cases of any culture-confirmed invasive disease irrespective of serotype were detected in combined PHiD-CV10 infant cohorts compared with 14 in the corresponding control cohorts (vaccine effectiveness 93%, 75-99). abstract, FINDINGS Two cases in vaccinated infant cohorts versus 14 in controls. All-serotype effectiveness this close to vaccine-type effectiveness reflects a short follow-up before replacement serotypes emerge.
Invasive pneumococcal disease in catch-up cohorts vaccinated at 7-18 months severity: any invasive disease case definition: Any invasive pneumococcal disease in children enrolled at 7-11 months (2+1) or 12-18 months (two doses)	children aged 7-18 months at first dose country: Finland setting: FinIP cluster-randomised trial period: 2009-2012 Infant <1y1-4y	PCV10 (PHiD-CV10) platform: protein-polysaccharide conjugate doses: 2 or 3 schedule: catch-up: 2+1 at 7-11 months or two doses at 12-18 months vs hepatitis vaccine control clusters	100 (79–100) VE (%)	cluster RCT	Palmu et al. 2013 Lancet quote In catch-up cohorts, seven cases of invasive disease were reported, all in the control group: two cases in the children enrolled at 7-11 months of age; and five cases in children enrolled at 12-18 months of age (vaccine effectiveness 100%, 79-100). abstract, FINDINGS Seven cases, all in controls. Supports catch-up vaccination of older infants and toddlers.
Vaccine-serotype invasive pneumococcal disease severity: any invasive disease case definition: Culture-confirmed IPD due to vaccine serotypes, end-of-study per-protocol	infants vaccinated at 2, 4, 6 and 15-18 months country: Argentina, Panama and Colombia period: 2007-2011 n: 10,211 PHiD-CV and 10,140 control (end-of-study per-protocol) Infant <1y1-4y	PCV10 (PHiD-CV, Synflorix) platform: protein-polysaccharide conjugate doses: 4 schedule: 2, 4, 6 and 15-18 months vs hepatitis B / hepatitis A control vaccines	100 (74.3–100) VE (%) follow-up: mean 28-30 months	RCT	Tregnaghi et al. 2014 PLoS Med quote Per-protocol VE was 16.1% (95% CI: -1.1%, 30.4%; one-sided p = 0.032) against clinically confirmed AOM, 67.1% (95% CI: 17.0%, 86.9%) against vaccine serotype clinically confirmed AOM, 100% (95% CI: 74.3%, 100%) against vaccine serotype IPD, and 65.0% (95% CI: 11.1%, 86.2%) against any IPD. abstract, METHODS AND FINDINGS The same sentence gives any-serotype IPD VE 65.0% (11.1-86.2) and clinically confirmed AOM VE 16.1% (-1.1 to 30.4), which crosses zero.
Invasive pneumococcal disease of any serotype severity: any invasive disease case definition: Culture-confirmed IPD, any serotype, end-of-study per-protocol	infants vaccinated at 2, 4, 6 and 15-18 months country: Argentina, Panama and Colombia period: 2007-2011 Infant <1y1-4y	PCV10 (PHiD-CV, Synflorix) platform: protein-polysaccharide conjugate doses: 4 schedule: 2, 4, 6 and 15-18 months vs hepatitis B / hepatitis A control vaccines	65.0 (11.1–86.2) VE (%) follow-up: mean 28-30 months	RCT	Tregnaghi et al. 2014 PLoS Med quote Per-protocol VE was 16.1% (95% CI: -1.1%, 30.4%; one-sided p = 0.032) against clinically confirmed AOM, 67.1% (95% CI: 17.0%, 86.9%) against vaccine serotype clinically confirmed AOM, 100% (95% CI: 74.3%, 100%) against vaccine serotype IPD, and 65.0% (95% CI: 11.1%, 86.2%) against any IPD. abstract, METHODS AND FINDINGS Any-serotype IPD; wide interval because IPD was rare in these well-served populations.
Invasive pneumococcal disease caused by vaccine serotypes severity: any invasive disease case definition: Culture-confirmed IPD due to vaccine serotypes, per-protocol	children aged 6-51 weeks at enrolment country: The Gambia setting: rural, LMIC period: 2000-2004 Infant <1y1-4y	PCV9 platform: protein-polysaccharide conjugate doses: 3 schedule: 3+0 (no booster) vs placebo	77 (51–90) VE (%)	RCT	Cutts et al. 2005 Lancet quote Efficacy of the conjugate vaccine was 77% (51-90) against invasive pneumococcal disease caused by vaccine serotypes, 50% (21-69) against disease caused by all serotypes, and 15% (7-21) against all-cause admissions. abstract, FINDINGS A three-dose no-booster schedule; the same sentence gives 50% (21-69) against all-serotype IPD and 15% (7-21) against all-cause hospital admissions.
All-cause hospital admissions severity: hospitalisation case definition: Any hospital admission, per-protocol	children aged 6-51 weeks at enrolment country: The Gambia setting: rural, LMIC period: 2000-2004 Infant <1y1-4y	PCV9 platform: protein-polysaccharide conjugate doses: 3 schedule: 3+0 vs placebo	15 (7–21) VE (%)	RCT	Cutts et al. 2005 Lancet quote Efficacy of the conjugate vaccine was 77% (51-90) against invasive pneumococcal disease caused by vaccine serotypes, 50% (21-69) against disease caused by all serotypes, and 15% (7-21) against all-cause admissions. abstract, FINDINGS A reduction in admissions for any cause is a probe of total pneumococcal burden beyond confirmed IPD.
All-cause mortality severity: death case definition: Death from any cause during follow-up	children aged 6-51 weeks at enrolment country: The Gambia setting: rural, LMIC with high child mortality period: 2000-2004 n: 17,437 children randomised Infant <1y1-4y	PCV9 platform: protein-polysaccharide conjugate doses: 3 schedule: 3+0 vs placebo	16 (3–28) VE (%)	RCT	Cutts et al. 2005 Lancet quote We also found an efficacy of 16% (3-28) against mortality. abstract, FINDINGS The only individual PCV trial to show a statistically significant reduction in all-cause child mortality; it drives the lower bound of the Cochrane pooled mortality estimate (pcv-eff-005).
First episode of vaccine-serotype invasive pneumococcal disease in HIV-uninfected children severity: any invasive disease case definition: IPD due to serotypes in the vaccine, intention-to-treat	infants vaccinated at 6, 10 and 14 weeks immune status: HIV-uninfected country: South Africa setting: Soweto, high-HIV-prevalence urban LMIC setting period: 1998-2001 n: 39,836 children randomised Infant <1y1-4y	PCV9 (CRM197 conjugate) platform: protein-polysaccharide conjugate doses: 3 schedule: 6, 10 and 14 weeks (3+0) vs placebo	83 (39–97) VE (%)	RCT	Klugman et al. 2003 N Engl J Med quote RESULTS: Among children without human immunodeficiency virus (HIV) infection, the vaccine reduced the incidence of a first episode of invasive pneumococcal disease due to serotypes included in the vaccine by 83 percent (95 percent confidence interval, 39 to 97; 17 cases among controls and 3 among vaccine recipients). abstract, RESULTS 17 cases among controls and 3 among vaccine recipients.
First episode of vaccine-serotype invasive pneumococcal disease in HIV-infected children severity: any invasive disease case definition: IPD due to serotypes in the vaccine, intention-to-treat, HIV-infected children	infants vaccinated at 6, 10 and 14 weeks immune status: HIV-infected country: South Africa setting: Soweto period: 1998-2001 Infant <1y1-4y	PCV9 (CRM197 conjugate) platform: protein-polysaccharide conjugate doses: 3 schedule: 6, 10 and 14 weeks (3+0) vs placebo	65 (24–86) VE (%)	RCT	Klugman et al. 2003 N Engl J Med quote Among HIV-infected children, the efficacy was 65 percent (95 percent confidence interval, 24 to 86; 26 and 9 cases, respectively). abstract, RESULTS 26 and 9 cases respectively. Lower than in HIV-uninfected children (pcv-eff-022) but still significant; the absolute number of cases prevented was larger because baseline risk is far higher with HIV.
Vaccine-type invasive pneumococcal disease severity: any invasive disease case definition: IPD due to PCV13 serotypes, per-protocol	adults 65 years of age or older country: Netherlands period: 2008-2013 65+	PCV13 platform: protein-polysaccharide conjugate doses: 1 vs placebo	75.0 (41.4–90.8) VE (%) follow-up: mean 3.97 years	RCT	Bonten et al. 2015 N Engl J Med quote RESULTS: In the per-protocol analysis of first episodes of infections due to vaccine-type strains, community-acquired pneumonia occurred in 49 persons in the PCV13 group and 90 persons in the placebo group (vaccine efficacy, 45.6%; 95.2% confidence interval [CI], 21.8 to 62.5), nonbacteremic and noninvasive community-acquired pneumonia occurred in 33 persons in the PCV13 group and 60 persons in the placebo group (vaccine efficacy, 45.0%; 95.2% CI, 14.2 to 65.3), and invasive pneumococcal disease occurred in 7 persons in the PCV13 group and 28 persons in the placebo group (vaccine efficacy, 75.0%; 95% CI, 41.4 to 90.8). abstract, RESULTS 7 versus 28 episodes. Modified intention-to-treat VE 75.8%.
Recurrent pneumococcal disease caused by vaccine serotypes or serotype 6A severity: any pneumococcal disease case definition: Further episode of pneumococcal infection due to PCV7 serotypes or 6A in adolescents and adults who had recovered from documented IPD	adolescents and adults immune status: 88% HIV-seropositive prior infection: all had recovered from documented invasive pneumococcal disease country: Malawi setting: LMIC, pre-widespread antiretroviral therapy period: February 2003 to October 2007 n: 496 patients, 798 person-years 12-17y18-49y50-64y	PCV7 platform: protein-polysaccharide conjugate doses: 2 schedule: two doses 4 weeks apart vs placebo	74 (30–90) VE (%)	RCT	French et al. 2010 N Engl J Med quote Of these episodes, 5 occurred in the vaccine group and 19 in the placebo group, for a vaccine efficacy of 74% (95% confidence interval [CI], 30 to 90). abstract, RESULTS 5 versus 19 episodes; all pneumococcal episodes occurred in the HIV-infected subgroup. The only placebo-controlled PCV efficacy trial in immunocompromised adults.
Vaccine-serotype invasive pneumococcal disease in healthy children severity: any invasive disease case definition: Pneumococcus isolated from a sterile site, Active Bacterial Core surveillance, matched case-control	children aged 3-59 months risk group: healthy children (no coexisting disorders) country: United States setting: population-based surveillance sites period: post-licensure PCV7 era n: 782 cases and 2,512 controls Infant <1y1-4y	PCV7 platform: protein-polysaccharide conjugate doses: 1 or more vs unvaccinated matched controls (age and zip code)	96 (93–98) VE (%)	case-control	Whitney et al. 2006 Lancet quote 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. abstract, FINDINGS Post-licensure effectiveness under the mix of routine, catch-up and incomplete schedules actually used in the USA; matches the trial efficacy.
Vaccine-serotype invasive pneumococcal disease in children with coexisting disorders severity: any invasive disease case definition: Pneumococcus isolated from a sterile site, matched case-control, children with underlying conditions	children aged 3-59 months risk group: children with coexisting disorders immune status: includes immunocompromising conditions country: United States period: post-licensure PCV7 era Infant <1y1-4y	PCV7 platform: protein-polysaccharide conjugate doses: 1 or more vs unvaccinated matched controls	81 (57–92) VE (%)	case-control	Whitney et al. 2006 Lancet quote 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. abstract, FINDINGS Lower point estimate than in healthy children (same sentence) with a wider interval; the chronically ill are the group with the highest baseline IPD rates (pcv-bur-008).
Invasive pneumococcal disease caused by penicillin-nonsusceptible strains severity: any invasive disease strain: penicillin-nonsusceptible pneumococci case definition: Sterile-site pneumococcal isolates not susceptible to penicillin	children aged 3-59 months country: United States period: post-licensure PCV7 era Infant <1y1-4y	PCV7 platform: protein-polysaccharide conjugate doses: 1 or more vs unvaccinated matched controls	76 (63–85) VE (%)	case-control	Whitney et al. 2006 Lancet quote It was 76% (63-85) against infections that were not susceptible to penicillin. abstract, FINDINGS Antibiotic-resistant disease was concentrated in vaccine serotypes, which is why PCV also acts as an antimicrobial-resistance intervention.
Invasive pneumococcal disease caused by PCV13 serotypes severity: any invasive disease case definition: IPD cases in 13 active surveillance sites, controls from birth registries matched on age and zip code	children aged 2-59 months country: United States period: 2010-2014 (post-PCV13 licensure) n: 722 cases and 2,991 controls Infant <1y1-4y	PCV13 platform: protein-polysaccharide conjugate doses: 1 or more schedule: routine 3+1 and catch-up schedules vs unvaccinated matched controls	86.0 (75.5–92.3) VE (%)	case-control	Moore et al. 2016 Lancet Respir Med quote Vaccine effectiveness against PCV13 serotypes was 86·0% (95% CI 75·5 to 92·3), driven by serotypes 19A and 7F, for which vaccine effectiveness was 85·6% (95% CI 70·6 to 93·5) and 96·5% (82·7 to 100), respectively. abstract, FINDINGS Driven by serotypes 19A (85.6%, 70.6-93.5) and 7F (96.5%, 82.7-100) in the same sentence.
Invasive pneumococcal disease caused by serotype 19A severity: any invasive disease strain: serotype 19A case definition: Serotype 19A IPD, matched case-control	children aged 2-59 months country: United States period: 2010-2014 Infant <1y1-4y	PCV13 platform: protein-polysaccharide conjugate doses: 1 or more vs unvaccinated matched controls	85.6 (70.6–93.5) VE (%)	case-control	Moore et al. 2016 Lancet Respir Med quote Vaccine effectiveness against PCV13 serotypes was 86·0% (95% CI 75·5 to 92·3), driven by serotypes 19A and 7F, for which vaccine effectiveness was 85·6% (95% CI 70·6 to 93·5) and 96·5% (82·7 to 100), respectively. abstract, FINDINGS 19A was the commonest PCV13 serotype (18% of cases). Contrast with the continuing 19A increases at PCV10 sites (pcv-bur-037).
Invasive pneumococcal disease caused by serotype 3 severity: any invasive disease strain: serotype 3 case definition: Serotype 3 IPD, matched case-control	children aged 2-59 months country: United States period: 2010-2014 Infant <1y1-4y	PCV13 platform: protein-polysaccharide conjugate doses: 1 or more vs unvaccinated matched controls	79.5 (30.3–94.8) VE (%)	case-control	Moore et al. 2016 Lancet Respir Med quote We also identified statistically significant effectiveness against serotype 3 (79·5%, 95% CI 30·3 to 94·8) and against antibiotic non-susceptible invasive pneumococcal disease (65·6%, 44·9 to 78·7). abstract, FINDINGS Statistically significant here but based on 43 serotype 3 cases; UK studies found no serotype 3 protection (pcv-eff-028). See the serotype 3 flag.
Invasive pneumococcal disease of any serotype severity: any invasive disease case definition: All-cause IPD, matched case-control	children aged 2-59 months country: United States period: 2010-2014 Infant <1y1-4y	PCV13 platform: protein-polysaccharide conjugate doses: 1 or more vs unvaccinated matched controls	60.2 (46.8–70.3) VE (%)	case-control	Moore et al. 2016 Lancet Respir Med quote Vaccine effectiveness against all-cause invasive pneumococcal disease was 60·2% (95% CI 46·8 to 70·3). abstract, FINDINGS All-serotype VE sits well below vaccine-type VE because 70% of cases were non-PCV13 serotypes by this point.
PCV13-serotype invasive pneumococcal disease in children with underlying conditions severity: any invasive disease case definition: PCV13-serotype IPD, matched case-control, children with underlying medical conditions	children aged 2-59 months risk group: underlying medical conditions country: United States period: 2010-2014 Infant <1y1-4y	PCV13 platform: protein-polysaccharide conjugate doses: 1 or more vs unvaccinated matched controls	81.4 (45.4–93.6) VE (%)	case-control	Moore et al. 2016 Lancet Respir Med quote Vaccine effectiveness was similar among children with (81·4%, 95% CI 45·4 to 93·6) and without (85·8%, 74·9 to 91·9) underlying conditions. abstract, FINDINGS Similar to children without underlying conditions (85.8%, 74.9-91.9, same sentence).
Invasive pneumococcal disease caused by PPSV23 serotypes, within two years of vaccination severity: any invasive disease case definition: PPSV23-serotype IPD cases versus non-PPSV23-serotype controls from national surveillance, matched on age and period	adults aged 65 years and over country: England and Wales period: November 2003 to December 2010 n: 1,272 cases and 1,270 controls 65+	PPSV23 platform: plain polysaccharide doses: 1 time since vaccination: within two years of vaccination vs unvaccinated (indirect cohort, non-vaccine-type IPD controls)	48 (32–60) VE (%)	case-control	Andrews et al. 2012 Vaccine quote VE declined from 48% (95% confidence interval; 32-60%) within two years of vaccination to 15% (-3% to 30%) after five years. abstract Pair with pcv-eff-053 for waning. VE was highest in healthy 65-74 year olds (65%, 23-84, within 2 years).
Invasive pneumococcal disease caused by PPSV23 serotypes, more than five years after vaccination severity: any invasive disease case definition: As pcv-eff-052, stratified by time since vaccination	adults aged 65 years and over country: England and Wales period: 2003-2010 65+	PPSV23 platform: plain polysaccharide doses: 1 time since vaccination: after five years vs unvaccinated (indirect cohort)	15 (-3–30) VE (%)	case-control	Andrews et al. 2012 Vaccine quote VE declined from 48% (95% confidence interval; 32-60%) within two years of vaccination to 15% (-3% to 30%) after five years. abstract Waning: protection falls to a non-significant 15% after five years. The ecological part of the same study found no discernible impact of the PPSV23 programme on IPD incidence.
Invasive pneumococcal disease caused by serotype 3 severity: any invasive disease strain: serotype 3 case definition: Serotype 3 IPD, indirect cohort	adults aged 65 years and over country: England and Wales period: 2003-2010 65+	PPSV23 platform: plain polysaccharide doses: 1 vs unvaccinated (indirect cohort)	-23 (-85–19) VE (%)	case-control	Andrews et al. 2012 Vaccine quote VE differed by serotype (p=0.005), from -23% (-85% to 19%) for serotype 3 to 63% (29-81%) for 12F. abstract Negative point estimate, interval spans zero: no protection against serotype 3. VE differed significantly by serotype (p = 0.005), up to 63% (29-81) for 12F in the same sentence.
Invasive pneumococcal disease due to any serotype severity: any invasive disease case definition: First ICD-10-CM coded IPD diagnosis in Medicare claims	adults aged 65 years and older risk group: 24.0% of the vaccinated group immunocompromised country: United States setting: Medicare database period: July 2022 to June 2024 n: 2,008,313 PCV20-vaccinated and 16,043,844 unvaccinated 65+	PCV20 platform: protein-polysaccharide conjugate doses: 1 vs no PCV20 (prior PCV13 within 5 years or PPSV23 within 2 years excluded)	25.6 (17.4–33.0) VE (%) = (1-HR) x 100	cohort	Miles et al. 2026 Lancet Infect Dis quote Adjusted vaccine effectiveness was 25·6% (95% CI 17·4-33·0), 23·3% (16·3-29·8), 15·2% (14·5-15·9), and 7·4% (6·9-7·8) against all invasive pneumococcal disease, all pneumococcal pneumonia, all-cause pneumonia, and LRTI, respectively. abstract, FINDINGS Pfizer-funded claims cohort with inverse-probability weighting; all-serotype outcome, so lower than vaccine-type VE. Same sentence: 23.3% (16.3-29.8) pneumococcal pneumonia, 15.2% (14.5-15.9) all-cause pneumonia, 7.4% (6.9-7.8) LRTI.
Invasive pneumococcal disease caused by PCV13 serotypes severity: any invasive disease case definition: IPD due to PCV13 serotypes, indirect cohort (Broome) method using non-vaccine-type cases as controls	children eligible for PCV13 (two doses before 12 months or one dose from 12 months) country: United Kingdom (England, Wales, Northern Ireland) period: post-licensure, 2010 onwards n: 706 IPD cases Infant <1y1-4y	PCV13 platform: protein-polysaccharide conjugate doses: 2 before 12 months or 1 from 12 months schedule: 2+1 (UK schedule) vs non-vaccine-serotype IPD cases (indirect cohort)	75 (58–84) VE (%)	screening method	Andrews et al. 2014 Lancet Infect Dis quote FINDINGS: For the 706 cases of invasive pneumococcal disease included in the study, PCV13 vaccine effectiveness after two doses before age 12 months or one dose from 12 months was 75% (95% CI 58-84). abstract, FINDINGS Indirect cohort design. VE was lower than predicted from the 0.35 ug/mL aggregate correlate of protection used for licensing.
Invasive pneumococcal disease caused by the six additional PCV13 serotypes severity: any invasive disease strain: serotypes 1, 3, 5, 6A, 7F, 19A case definition: IPD due to serotypes 1, 3, 5, 6A, 7F and 19A, indirect cohort method	children eligible for PCV13 country: United Kingdom period: 2010 onwards Infant <1y1-4y	PCV13 platform: protein-polysaccharide conjugate doses: 2 before 12 months or 1 from 12 months schedule: 2+1 vs non-vaccine-serotype IPD cases	73 (55–84) VE (%)	screening method	Andrews et al. 2014 Lancet Infect Dis quote Vaccine effectiveness was 90% (34-98) for the PCV7 serotypes and 73% (55-84) for the six additional serotypes included in PCV13. abstract, FINDINGS The same sentence gives 90% (34-98) for the original PCV7 serotypes. Protection was shown for four of the six new serotypes; serotype 3 VE was not significant and serotype 5 had no cases.
Invasive pneumococcal disease caused by PCV7 serotypes, complete 2+1 schedule severity: any invasive disease strain: PCV7 serotypes case definition: PCV7-serotype IPD cases versus non-PCV13-serotype controls among vaccine-eligible children, Broome method	vaccine-eligible children country: England period: September 2006 to June 2018 n: 3,421 IPD cases with vaccine history Infant <1y1-4y5-11y	PCV7 and PCV13 combined platform: protein-polysaccharide conjugate doses: 3 schedule: 2+1 complete vs non-PCV13-serotype IPD cases (indirect cohort)	92.0 (81.7–96.7) VE (%)	screening method	Andrews et al. 2019 Vaccine quote For the complete 2 + 1 schedule, both PCV7 and PCV13 showed high effectiveness against PCV7 serotypes with a combined VE of 92.0% (95%CI, 81.7-96.7). abstract, RESULTS Twelve years of national surveillance; the 2+1 schedule used in the UK gives protection against the original seven serotypes comparable to 3+1 trials.
Invasive pneumococcal disease caused by the additional PCV13 serotypes plus 6C, complete 2+1 schedule severity: any invasive disease strain: serotypes 1, 3, 5, 6A, 7F, 19A and 6C case definition: PCV13-additional-serotype (plus 6C) IPD cases versus non-PCV13-serotype controls, Broome method	vaccine-eligible children country: England period: 2010 to June 2018 Infant <1y1-4y5-11y	PCV13 platform: protein-polysaccharide conjugate doses: 3 schedule: 2+1 complete vs non-PCV13-serotype IPD cases	73.7 (31.1–89.9) VE (%)	screening method	Andrews et al. 2019 Vaccine quote For the 2 + 1 schedule, PCV13 VE against the additional PCV13 serotypes plus 6C was 73.7% (31.1-89.9) compared to 90.0% (75.3 - 96.0) for PCV7 against PCV7 serotypes, although PCV13 VE increased to 84.8% (58.7-94.4) if serotype 3 was excluded; all 36 eligible serotype 3 IPD cases were fully-vaccinated with PCV13. abstract, RESULTS Rises to 84.8% (58.7-94.4) if serotype 3 is excluded (same sentence): all 36 eligible serotype 3 cases were fully vaccinated. The abstract also reports significant waning for serotype 19A without giving the number.
Invasive pneumococcal disease caused by additional PCV13 serotypes excluding serotype 3, complete 2+1 schedule severity: any invasive disease strain: serotypes 1, 5, 6A, 7F, 19A and 6C (serotype 3 excluded) case definition: As pcv-eff-028 with serotype 3 cases removed	vaccine-eligible children country: England period: 2010 to June 2018 Infant <1y1-4y5-11y	PCV13 platform: protein-polysaccharide conjugate doses: 3 schedule: 2+1 complete vs non-PCV13-serotype IPD cases	84.8 (58.7–94.4) VE (%)	screening method	Andrews et al. 2019 Vaccine quote For the 2 + 1 schedule, PCV13 VE against the additional PCV13 serotypes plus 6C was 73.7% (31.1-89.9) compared to 90.0% (75.3 - 96.0) for PCV7 against PCV7 serotypes, although PCV13 VE increased to 84.8% (58.7-94.4) if serotype 3 was excluded; all 36 eligible serotype 3 IPD cases were fully-vaccinated with PCV13. abstract, RESULTS Pair with pcv-eff-028: the whole difference is serotype 3, against which this study found no protection.
Invasive pneumococcal disease caused by non-PCV13 serotypes in PPSV23 plus 15A/15C, in children with sickle cell disease severity: any invasive disease strain: non-PCV13 serotypes included in PPSV23 plus 15A/15C case definition: IPD in children with HbSS/HbSC, indirect-cohort effect adjusted for age and hydroxyurea	children under 10 years risk group: sickle cell disease immune status: functional asplenia country: United States setting: metropolitan Atlanta, ABCs period: 2010-2018 1-4y5-11y	PPSV23 platform: plain polysaccharide doses: as recommended for sickle cell disease time since vaccination: within 3 years of vaccination vs non-vaccine-type IPD cases (indirect cohort)	92 (40.8–99.0) VE (%)	screening method	Adamkiewicz et al. 2023 Blood Adv quote Within 3 years of vaccination, the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against non-PCV13 serotypes included in PPSV23 plus 15A/15C was 92% (95% confidence interval, 40.8- 99.0, P = .014; indirect-cohort effect adjusted for age and hydroxyurea). abstract Few cases; the interval is wide. Supports the PPSV23 recommendation for children with sickle cell disease on top of PCV.
Invasive pneumococcal disease overall in children under 5, population impact of PCV13 severity: any invasive disease case definition: IPD incidence in Active Bacterial Core surveillance, observed versus expected if PCV7 alone had continued, time-series model	children younger than 5 years country: United States setting: multisite population-based surveillance period: July 2012 to June 2013 versus expected Infant <1y1-4y	PCV13 (replacing PCV7 in the infant schedule) platform: protein-polysaccharide conjugate doses: routine infant schedule vs expected incidence had PCV7 alone been continued (counterfactual, not unvaccinated individuals)	64 (59–68) percentage decline in incidence vs counterfactual (%)	ecological	Moore et al. 2015 Lancet Infect Dis quote FINDINGS: Compared with incidence expected among children younger than 5 years if PCV7 alone had been continued, incidence of IPD overall declined by 64% (95% interval estimate [95% IE] 59-68) and IPD caused by PCV13 minus PCV7 serotypes declined by 93% (91-94), by July, 2012, to June, 2013. abstract, FINDINGS 95% interval estimate. IPD from the six PCV13-minus-PCV7 serotypes fell 93% (91-94) in the same sentence. A population-impact measure, not individual VE.
Invasive pneumococcal disease overall in adults, indirect effect of infant PCV13 severity: any invasive disease case definition: IPD incidence in adults, observed versus expected if PCV7 alone had continued	adults, by age group country: United States period: July 2012 to June 2013 versus expected 18-49y50-64y65+	PCV13 in children (adults not vaccinated with PCV13 in this period) platform: protein-polysaccharide conjugate doses: routine infant schedule (indirect effect) vs expected incidence had PCV7 alone been continued	12-32 percentage decline in incidence vs counterfactual (%), range across adult age groups	ecological	Moore et al. 2015 Lancet Infect Dis quote Among adults, incidence of IPD overall also declined by 12-32% and IPD caused by PCV13 minus PCV7 type IPD declined by 58-72%, depending on age. abstract, FINDINGS Herd effect in unvaccinated adults; PCV13-minus-PCV7 serotype IPD fell 58-72% depending on age. The authors estimate over 30,000 IPD cases and 3,000 deaths averted in three years.
Invasive pneumococcal disease in children under 2, one year after PCV7 introduction severity: any invasive disease case definition: Sterile-site pneumococcal isolation, Active Bacterial Core surveillance, 2001 versus 1998-1999 baseline	children under two years of age country: United States period: 2001 versus 1998-1999 Infant <1y1-4y	PCV7 platform: protein-polysaccharide conjugate doses: routine infant schedule vs pre-vaccine baseline incidence (1998-1999)	69 percentage decline in incidence (%)	ecological	Whitney et al. 2003 N Engl J Med quote In this group, the rate of disease was 69 percent lower in 2001 than the base-line rate (59.0 cases per 100,000 vs. abstract, RESULTS P < 0.001. Vaccine-serotype disease fell 78% and vaccine-related serotypes 50% in the same sentence. Population impact, not individual VE.
Invasive pneumococcal disease in adults 65 and older, one year after infant PCV7 severity: any invasive disease case definition: Sterile-site pneumococcal isolation, ABCs, 2001 versus baseline	adults 65 years of age or more country: United States period: 2001 versus 1998-1999 65+	PCV7 in children (indirect effect) platform: protein-polysaccharide conjugate doses: routine infant schedule vs pre-vaccine baseline incidence in the same age group	18 percentage decline in incidence (%)	ecological	Whitney et al. 2003 N Engl J Med quote 21.5 per 100,000, P=0.03), and 18 percent lower for those 65 years of age or more (49.5 per 100,000 vs. abstract, RESULTS P < 0.001; 32 percent lower in adults 20-39 and 8 percent lower in 40-64 in the same sentence. The earliest evidence of herd protection from infant PCV.
Invasive pneumococcal disease overall in children under 5, five years after PCV7 severity: any invasive disease case definition: Population- and laboratory-based surveillance, 2005 versus 1998-1999	children aged under 5 years country: United States setting: eight states period: 2005 versus 1998-1999 Infant <1y1-4y	PCV7 platform: protein-polysaccharide conjugate doses: routine infant schedule vs pre-vaccine baseline incidence (1998-1999)	77 percentage decline in incidence (%)	ecological	Centers 2008 MMWR Morb Mortal Wkly Rep quote Results of that analysis indicated that in 2005, overall IPD rates among children aged <5 years were 77% lower, and an estimated 13,000 fewer cases of IPD occurred, compared with the years preceding vaccine introduction (1998-1999). abstract Overall rates levelled off from 2002 because of rising serotype 19A, the replacement that prompted PCV13.
PCV10-serotype invasive pneumococcal disease in adults, nine years after infant PCV10 severity: any invasive disease strain: PCV10 serotypes case definition: Culture-confirmed PCV10-serotype IPD in adults 18 and over, observed versus expected from pre-PCV10 trend, negative binomial time-series	adults 18 years and older country: Finland period: July 2018 to June 2019 versus expected 18-49y50-64y65+	PCV10 in infants (indirect effect) platform: protein-polysaccharide conjugate doses: infant 2+1 programme vs expected incidence without the PCV10 programme (trend-adjusted counterfactual)	90 percentage lower than expected incidence (%)	ecological	Nuorti et al. 2022 Vaccine quote 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. abstract, RESULTS Non-PCV10 serotype IPD was 40% higher than expected (serotypes 3, 19A, 22F, 6C) but levelled off; overall adult IPD IRR 0.7 (0.5-0.8). Herd effect.
All invasive pneumococcal disease in adults 65 and older, indirect effect of infant PCV10 severity: any invasive disease case definition: Observed-to-expected incidence rate ratio for all-serotype IPD	adults 65 years and older country: Finland period: 2018-2019 versus expected 65+	PCV10 in infants (indirect effect) platform: protein-polysaccharide conjugate doses: infant 2+1 programme vs expected incidence without the PCV10 programme	0.7 (0.5–0.95) observed/expected incidence rate ratio	ecological	Nuorti et al. 2022 Vaccine quote In persons ≥65 years, the IRR was 0·7 (95 %CI 0·5-0.95). abstract, RESULTS A 30% net reduction in older adults after replacement is netted out. Substantial burden remains, with non-vaccine serotypes nearly 90% of adult IPD.
All-serotype invasive pneumococcal disease in children under 5, six years after PCV10/PCV13 severity: any invasive disease case definition: Site-weighted incidence rate ratios versus pre-PCV, PSERENADE global surveillance	children younger than 5 years country: multiple (30 countries) period: 6 years after PCV10 or PCV13 introduction Infant <1y1-4y	PCV10 or PCV13 platform: protein-polysaccharide conjugate doses: national infant schedules, mostly with booster vs incidence before any PCV	58-74 percentage decline in incidence vs pre-PCV (%), range across products and strata	ecological	Bennett et al. 2025 Lancet Infect Dis quote Despite different serotype 19A trends, all-serotype IPD declined similarly between products among children younger than 5 years (58-74%); among adults aged 65 years or older, declines were greater at PCV13 (25-29%) than PCV10 (4-14%) sites, but other differences between sites precluded attribution to product. abstract, FINDINGS Net of serotype replacement (pcv-bur-036). Among adults 65 and older declines were 25-29% at PCV13 sites and 4-14% at PCV10 sites in the same sentence, but site differences prevent attributing that to product.
Pneumococcal meningitis in children under 5, six years after PCV10/PCV13 severity: meningitis case definition: Serotyped pneumococci in cerebrospinal fluid, 42 surveillance sites, incidence rate ratios versus pre-PCV	children under 5 years country: multiple (30 countries, 84% high-income) period: 6 years after PCV10 or PCV13 introduction Infant <1y1-4y	PCV10 or PCV13 platform: protein-polysaccharide conjugate doses: national infant schedules vs incidence before any PCV	48-74 percentage decline in incidence vs pre-PCV (%), range across strata	ecological	Yang et al. 2025 J Infect quote Six years after PCV10/PCV13 introduction, pneumococcal meningitis declined 48-74% across products and PCV7 impact strata for children <5 y, 35-62% for 5-17 y and 0-36% for ≥18 y. abstract, RESULTS Declines were 35-62% at 5-17 years and 0-36% in adults in the same sentence. Vaccine-type meningitis fell 96-100% in under-5s; replacement in meningitis was less than for all IPD.

Vaccine safety and adverse events

Harms measured after vaccination against an unvaccinated or baseline comparator. Kept separate from post-acute sequelae, which follow the disease, not the vaccine.

Outcome (O)	Population (P)	Intervention / comparator	Estimate	Design (S)	Source
Death from any cause after PCV7 in HIV-infected adults severity: death case definition: All-cause death during trial follow-up	adolescents and adults who had recovered from IPD immune status: 88% HIV-seropositive country: Malawi period: 2003-2007 n: 496 patients 12-17y18-49y50-64y	PCV7 platform: protein-polysaccharide conjugate doses: 2 vs placebo	1.18 (0.84–1.66) HR (vaccine vs placebo)	RCT	French et al. 2010 N Engl J Med quote There were 73 deaths from any cause in the vaccine group and 63 in the placebo group (hazard ratio in the vaccine group, 1.18; 95% CI, 0.84 to 1.66). abstract, RESULTS 73 versus 63 deaths; interval includes 1, so no demonstrated effect on mortality in either direction in a population with very high background mortality. Serious adverse events within 14 days were fewer in the vaccine group (3 vs 17).

Pneumococcal pneumonia (community-acquired, non-invasive) Streptococcus pneumoniae

Disease risks

Acute risks of the infection itself: complications, hospitalisation, ICU, death.

Outcome (O)	Population (P)	Estimate	Design (S)	Source
Global deaths from pneumonia of any cause in children under 5, 2019 severity: death case definition: All-cause pneumonia deaths, WHO estimate	children under the age of 5 vaccination status: mixed country: global period: 2019 Infant <1y1-4y	740 180 estimated annual deaths (count) per year, global children under 5	expert body	who.int quote Pneumonia killed 740 180 children under the age of 5 in 2019, accounting for 14% of all deaths of children under 5 years old but 22% of all deaths in children aged 1 to 5 years. WHO fact sheet, Pneumonia in children All-cause pneumonia, not pneumococcal-specific; the WHO sheet names pneumococcus as the most common bacterial cause. 14% of all under-5 deaths in the same sentence.
Community-acquired pneumonia requiring hospitalisation, incidence in US adults severity: hospitalisation case definition: Radiographically confirmed CAP requiring hospitalisation, active population-based surveillance (EPIC study), immunosuppressed and recently hospitalised adults excluded	adults 18 years or older vaccination status: mixed country: United States setting: five hospitals in Chicago and Nashville period: January 2010 to June 2012 n: 2,488 enrolled adults 18-49y50-64y65+	24.8 (23.5–26.1) incidence per 10,000 adults per year per 10,000 adults per year	surveillance	Jain et al. 2015 N Engl J Med quote The annual incidence of pneumonia was 24.8 cases (95% confidence interval, 23.5 to 26.1) per 10,000 adults, with the highest rates among adults 65 to 79 years of age (63.0 cases per 10,000 adults) and those 80 years of age or older (164.3 cases per 10,000 adults). abstract, RESULTS All-cause CAP; Streptococcus pneumoniae was detected in 5% of patients. Per 10,000, not per 100,000.
Community-acquired pneumonia requiring hospitalisation, incidence in US adults aged 80 and over severity: hospitalisation case definition: Radiographically confirmed CAP requiring hospitalisation, EPIC study	adults 80 years of age or older vaccination status: mixed country: United States setting: five hospitals in Chicago and Nashville period: January 2010 to June 2012 65+	164.3 incidence per 10,000 adults per year per 10,000 adults aged 80+ per year	surveillance	Jain et al. 2015 N Engl J Med quote The annual incidence of pneumonia was 24.8 cases (95% confidence interval, 23.5 to 26.1) per 10,000 adults, with the highest rates among adults 65 to 79 years of age (63.0 cases per 10,000 adults) and those 80 years of age or older (164.3 cases per 10,000 adults). abstract, RESULTS Same sentence gives 63.0 per 10,000 for ages 65 to 79. All-cause CAP, so the pneumococcal fraction is a minority.
Intensive care and death among adults hospitalised with community-acquired pneumonia severity: ICU admission case definition: Adults with radiographic evidence of pneumonia, EPIC study	median age 57 years (IQR 46 to 71) vaccination status: mixed country: United States setting: hospital period: 2010-2012 n: 2,320 adults with radiographic pneumonia 18-49y50-64y65+	21 proportion of hospitalised cases requiring intensive care (%) per hospitalised CAP case	surveillance	Jain et al. 2015 N Engl J Med quote Among 2320 adults with radiographic evidence of pneumonia (93%), the median age of the patients was 57 years (interquartile range, 46 to 71); 498 patients (21%) required intensive care, and 52 (2%) died. abstract, RESULTS The same sentence reports 52 (2%) died in hospital. Denominator is hospitalised cases, not population; do not combine with pcv-bur-027.
Hospitalisation for pneumococcal community-acquired pneumonia, incidence in US adults severity: hospitalisation case definition: Hospitalised CAP with pneumococcal aetiology by serotype-agnostic and serotype-specific urinary antigen tests plus routine cultures	adults, median age 60.1 years vaccination status: mixed country: United States setting: three hospitals in Tennessee and Georgia, defined catchment areas period: 2018-2022 n: 2,016 patients hospitalised for CAP 18-49y50-64y65+	43 incidence per 100,000 adults per year per 100,000 adults per year	surveillance	Grijalva et al. 2025 JAMA Netw Open quote The incidence of hospitalizations for pneumococcal CAP and pneumococcal CAP due to serotypes included in V116 was 43 and 30 per 100 000 adults, respectively. abstract, RESULTS Current-era figure in a population with two decades of infant PCV and adult PCV13 use. All-cause CAP hospitalisation was 340 per 100,000 in the same abstract; the burden was highest in adults 65 and older.
All-cause pneumonia hospitalisation in children under 2, post-PCV7 severity: hospitalisation case definition: All-cause pneumonia hospitalisations, Nationwide Inpatient Sample	children aged under 2 years vaccination status: mixed country: United States setting: national inpatient sample period: 2005 Infant <1y1-4y	9.1 incidence per 1,000 children per year per 1,000 children under 2 per year	surveillance	Centers 2009 MMWR Morb Mortal Wkly Rep quote In 2005 and 2006, the incidence rates for all-cause pneumonia hospitalizations among children aged <2 years were 9.1 per 1,000 and 8.1 per 1,000, respectively. abstract Per 1,000, not per 100,000. The 2006 rate was about 35% below the 1997-1999 pre-PCV7 rate; the abstract gives the percentage decline but not the pre-vaccine rate itself.
Global deaths from lower respiratory infection attributable to Streptococcus pneumoniae, all ages, 2016 severity: death case definition: Counterfactual population-attributable-fraction modelling of lower respiratory infection deaths in GBD 2016	all ages vaccination status: mixed country: global (195 countries) period: 2016 All ages	1 189 937 (690 445–1 770 660) estimated annual deaths (count) per year, global population	modelling	GBD 2018 Lancet Infect Dis quote Streptococcus pneumoniae was the leading cause of lower respiratory infection morbidity and mortality globally, contributing to more deaths than all other aetiologies combined in 2016 (1 189 937 deaths, 95% UI 690 445-1 770 660). abstract, FINDINGS 95% uncertainty interval, not a CI. Pneumococcus contributed more LRI deaths than all other aetiologies combined in that analysis.

Vaccine efficacy and effectiveness

Every estimate compiled, annotated by population (P), intervention (I), comparator (C), outcome (O) and study design (S).

Outcome (O)	Population (P)	Intervention / comparator	Estimate	Design (S)	Source
WHO X-ray defined pneumonia severity: radiological pneumonia case definition: Radiologically confirmed pneumonia by WHO criteria, intent-to-treat, HIV-1 negative children	children under two years at enrolment immune status: HIV-1 negative country: multiple Infant <1y1-4y	PCV7, PCV9 and PCV11 as used in the trials platform: protein-polysaccharide conjugate doses: 3 or more primary doses as per trial vs placebo or another vaccine	27 (15–36) VE (%)	meta-analysis GRADE: moderate 4 publications, moderate quality evidence	Lucero et al. 2009 Cochrane Database Syst Rev quote Only two trials have data on all-cause admissions.The main analysis for this review involved HIV-1 negative children and used the pooled results of random-effects model, intent-to-treat analysis (ITT).Pooled vaccine efficacy (VE) for VT-IPD was 80% (95% confidence interval (CI) 58% to 90%, P < 0.0001); all serotypes-IPD, 58% (95% CI 29% to 75%, P = 0.001); World Health Organization X-ray defined pneumonia was 27% (95% CI 15% to 36%, P < 0.0001); clinical pneumonia, 6% (95% CI 2% to 9%, P = 0.0006); and all-cause mortality, 11% (95% CI -1% to 21%, P = 0.08). abstract, MAIN RESULTS Pneumonia endpoints capture all causes, so a 27% reduction implies pneumococcus caused at least that share of X-ray pneumonia (the vaccine-probe logic used in the global burden estimates).
Clinical pneumonia severity: clinical pneumonia case definition: Clinically defined pneumonia (any cause), intent-to-treat, HIV-1 negative children	children under two years at enrolment immune status: HIV-1 negative country: multiple Infant <1y1-4y	PCV7, PCV9 and PCV11 as used in the trials platform: protein-polysaccharide conjugate doses: 3 or more primary doses as per trial vs placebo or another vaccine	6 (2–9) VE (%)	meta-analysis GRADE: moderate 4 publications	Lucero et al. 2009 Cochrane Database Syst Rev quote Only two trials have data on all-cause admissions.The main analysis for this review involved HIV-1 negative children and used the pooled results of random-effects model, intent-to-treat analysis (ITT).Pooled vaccine efficacy (VE) for VT-IPD was 80% (95% confidence interval (CI) 58% to 90%, P < 0.0001); all serotypes-IPD, 58% (95% CI 29% to 75%, P = 0.001); World Health Organization X-ray defined pneumonia was 27% (95% CI 15% to 36%, P < 0.0001); clinical pneumonia, 6% (95% CI 2% to 9%, P = 0.0006); and all-cause mortality, 11% (95% CI -1% to 21%, P = 0.08). abstract, MAIN RESULTS Small because clinical pneumonia is mostly viral; a low VE here is expected, not a failure.
Hospitalised community-acquired pneumonia caused by serotype 3 severity: hospitalisation strain: serotype 3 case definition: Serotype 3 CAP in adults, pooled individual-level data from CAPiTA, the Louisville test-negative study and an Argentine test-negative abstract	adults aged 65 years or older country: Netherlands, United States, Argentina 65+	PCV13 platform: protein-polysaccharide conjugate doses: 1 vs placebo or test-negative controls as per study	52.5 (6.2–75.9) VE (%)	meta-analysis 3 studies (1 RCT, 2 test-negative)	McLaughlin et al. 2019 Vaccine quote PCV13 VE against serotype 3 hospitalized CAP was 52.5% (95%CI: 6.2-75.9%) from the pooled analysis of individual-level data from all three studies. abstract, RESULTS Pfizer-authored pooled analysis; 53.6% (6.7-76.9) excluding the unpublished study. Serotype 3 is the one PCV13 serotype whose population incidence has not fallen.
All-cause pneumonia in low-income countries severity: pneumonia case definition: All-cause pneumonia in RCTs conducted in low-income countries	adults country: low-income countries 18-49y50-64y65+	pneumococcal polysaccharide vaccine (PPV) platform: plain polysaccharide doses: 1 vs placebo or no vaccine	0.54 (0.43–0.67) OR (vaccinated vs unvaccinated)	meta-analysis RCTs in low-income countries (I2 = 19%)	Moberley et al. 2013 Cochrane Database Syst Rev quote There was efficacy against all-cause pneumonia in low-income (OR 0.54, 95% CI 0.43 to 0.67, I(2) statistic = 19%) but not high-income countries in either the general population (OR 0.71, 95% CI 0.45 to 1.12, I(2) statistic = 93%) or in adults with chronic illness (OR 0.93, 95% CI 0.73 to 1.19, I(2) statistic = 10%). abstract, MAIN RESULTS The same sentence gives no significant effect in high-income general populations (OR 0.71, 0.45-1.12) or adults with chronic illness (OR 0.93, 0.73-1.19); see pcv-eff-045.
All-cause pneumonia in adults with chronic illness, high-income countries severity: pneumonia case definition: All-cause pneumonia in RCTs of adults with chronic illness in high-income countries	adults risk group: chronic illness country: high-income countries 18-49y50-64y65+	pneumococcal polysaccharide vaccine (PPV) platform: plain polysaccharide doses: 1 vs placebo or no vaccine	0.93 (0.73–1.19) OR (vaccinated vs unvaccinated)	meta-analysis RCTs in adults with chronic illness (I2 = 10%)	Moberley et al. 2013 Cochrane Database Syst Rev quote There was efficacy against all-cause pneumonia in low-income (OR 0.54, 95% CI 0.43 to 0.67, I(2) statistic = 19%) but not high-income countries in either the general population (OR 0.71, 95% CI 0.45 to 1.12, I(2) statistic = 93%) or in adults with chronic illness (OR 0.93, 95% CI 0.73 to 1.19, I(2) statistic = 10%). abstract, MAIN RESULTS Null: no demonstrated reduction in all-cause pneumonia in the chronically ill, the group most often targeted. The review could not separate lack of effect from lack of power.
Pneumococcal pneumonia by any serotype, clinical trials severity: pneumonia case definition: Pneumococcal pneumonia in trials after excluding two trials with serologic diagnosis of insufficient specificity	adults aged 60 years and over country: industrialised countries 50-64y65+	PPSV23 platform: plain polysaccharide doses: 1 vs placebo or no vaccine	64 (35–80) VE (%)	meta-analysis 2 clinical trials (low risk of bias)	Falkenhorst et al. 2017 PLoS One quote After excluding studies with high risk of bias, pooled VE against pneumococcal pneumonia (by any serotype) was 64% (95%CI: 35-80%) in two clinical trials and 48% (95%CI: 25-63%) in two cohort studies. abstract, RESULTS Pooled VE of 48% (25-63) in two cohort studies in the same sentence. Unlike earlier meta-analyses, trials using non-specific serology were excluded, which is why this review finds pneumonia efficacy where the Cochrane review (pcv-eff-045) did not.
All-cause community-acquired pneumonia, trials severity: pneumonia case definition: All-cause CAP in randomised trials of adults 50 years and older	adults 50 years of age and older country: multiple 50-64y65+	PPSV23 platform: plain polysaccharide doses: 1 vs placebo or no vaccine	4 (-26–26) VE (%)	meta-analysis trials included in the review	Kraicer-Melamed et al. 2016 Vaccine quote The VE estimates for CAP were 4% (95% CI: -26%-26%) for trials, 17% (95% CI: -26%-45%) for cohort studies, and 7% (95% CI: -10%-21%) for case-control studies. abstract, RESULTS Null for all-cause CAP in trials; cohort (17%, -26 to 45) and case-control (7%, -10 to 21) estimates in the same sentence also cross zero. IPD VE in the same review was 50% (21-69) in cohort studies.
Chest X-ray confirmed pneumonia severity: radiological pneumonia case definition: Chest X-ray confirmed pneumonia episodes in the PCV7 clinical trial	children in the PCV7 clinical trial (infants vaccinated at 2, 4, 6 and 12-15 months) country: United States Infant <1y1-4y	PCV7 platform: protein-polysaccharide conjugate doses: 4 vs unvaccinated children (control vaccine) in the trial	20 percentage fewer episodes (%)	expert body	cdc.gov quote Children who received PCV7 had 20% fewer episodes of chest X-ray confirmed pneumonia, 7% fewer episodes of acute otitis media, and underwent 20% fewer tympanostomy tube placements than did unvaccinated children. Pink Book chapter 17, Immunogenicity and Vaccine Efficacy CDC summary of the Northern California trial; the same sentence gives 7% fewer acute otitis media episodes and 20% fewer tympanostomy tube placements. No interval given.
Likely bacterial community-acquired pneumonia severity: radiological pneumonia case definition: Radiologically confirmed CAP with alveolar consolidation or pleural effusion, or non-alveolar infiltrate with CRP 40 ug/ml or more, first episode 2 weeks or more after dose 3, per-protocol	infants vaccinated at 2, 4, 6 and 15-18 months country: Argentina, Panama and Colombia setting: populations with good access to health care period: June 2007 to July 2011 n: 10,295 PHiD-CV and 10,201 control (per-protocol) Infant <1y1-4y	PCV10 (PHiD-CV, Synflorix) platform: protein-polysaccharide conjugate doses: 4 schedule: 2, 4, 6 and 15-18 months vs hepatitis B (primary) and hepatitis A (booster) control vaccines	22.0 (7.7–34.2) VE (%) follow-up: mean 23 months at interim analysis	RCT	Tregnaghi et al. 2014 PLoS Med quote After a mean follow-up of 23 mo (PHiD-CV, n = 10,295; control, n = 10,201), per-protocol VE was 22.0% (95% CI: 7.7, 34.2; one-sided p = 0.002) against B-CAP (conclusive for primary objective) and 25.7% (95% CI: 8.4%, 39.6%) against World Health Organization-defined consolidated CAP. abstract, METHODS AND FINDINGS COMPAS primary endpoint. Intent-to-treat VE was 18.2% (5.5-29.1); WHO-consolidated CAP VE was 25.7% in the same analysis.
First episode of radiological pneumonia severity: radiological pneumonia case definition: Radiologically confirmed pneumonia, per-protocol analysis	children aged 6-51 weeks at enrolment country: The Gambia setting: rural eastern Gambia, LMIC period: 2000-2004 n: 8,189 vaccine and 8,151 placebo (per-protocol) Infant <1y1-4y	PCV9 (nine-valent conjugate) platform: protein-polysaccharide conjugate doses: 3 schedule: three doses at least 25 days apart from 6 weeks vs placebo	37 (27–45) VE (%)	RCT	Cutts et al. 2005 Lancet quote Pneumococcal vaccine efficacy was 37% (95% CI 27-45) against first episode of radiological pneumonia. abstract, FINDINGS Primary outcome: 333 of 8,189 vaccinated versus 513 of 8,151 placebo recipients. Higher pneumonia efficacy than in high-income trials because a larger share of pneumonia in this setting is pneumococcal.
First episode of radiologically confirmed alveolar consolidation in HIV-uninfected children severity: radiological pneumonia case definition: Radiologically confirmed alveolar consolidation, intention-to-treat	infants vaccinated at 6, 10 and 14 weeks immune status: HIV-uninfected country: South Africa period: 1998-2001 Infant <1y1-4y	PCV9 (CRM197 conjugate) platform: protein-polysaccharide conjugate doses: 3 schedule: 6, 10 and 14 weeks vs placebo	20 (2–35) VE (%)	RCT	Klugman et al. 2003 N Engl J Med quote Among children without HIV infection, the vaccine reduced the incidence of first episodes of radiologically confirmed alveolar consolidation by 20 percent (95 percent confidence interval, 2 to 35; 212 cases in the control group and 169 in the vaccinated group) in the intention-to-treat analysis and by 25 percent (95 percent confidence interval, 4 to 41; 158 and 119 cases, respectively) in the per-protocol analysis (i.e., among fully vaccinated children). abstract, RESULTS Per-protocol efficacy in fully vaccinated children was 25% (4-41) in the same sentence.
Vaccine-type pneumococcal community-acquired pneumonia, first episode severity: pneumonia (bacteraemic and non-bacteraemic) case definition: CAP due to PCV13 serotypes identified by culture or serotype-specific urinary antigen detection, per-protocol	adults 65 years of age or older country: Netherlands setting: community, CAPiTA trial period: 2008-2013 n: 84,496 adults randomised 65+	PCV13 platform: protein-polysaccharide conjugate doses: 1 vs placebo	45.6 (21.8–62.5) VE (%) follow-up: mean 3.97 years	RCT	Bonten et al. 2015 N Engl J Med quote RESULTS: In the per-protocol analysis of first episodes of infections due to vaccine-type strains, community-acquired pneumonia occurred in 49 persons in the PCV13 group and 90 persons in the placebo group (vaccine efficacy, 45.6%; 95.2% confidence interval [CI], 21.8 to 62.5), nonbacteremic and noninvasive community-acquired pneumonia occurred in 33 persons in the PCV13 group and 60 persons in the placebo group (vaccine efficacy, 45.0%; 95.2% CI, 14.2 to 65.3), and invasive pneumococcal disease occurred in 7 persons in the PCV13 group and 28 persons in the placebo group (vaccine efficacy, 75.0%; 95% CI, 41.4 to 90.8). abstract, RESULTS 95.2% CI as reported. 49 versus 90 first episodes. Modified intention-to-treat VE was 37.7%. Efficacy persisted throughout the trial.
Vaccine-type non-bacteraemic, non-invasive pneumococcal community-acquired pneumonia severity: non-bacteraemic pneumonia case definition: Non-bacteraemic, non-invasive CAP due to PCV13 serotypes, per-protocol	adults 65 years of age or older country: Netherlands period: 2008-2013 65+	PCV13 platform: protein-polysaccharide conjugate doses: 1 vs placebo	45.0 (14.2–65.3) VE (%) follow-up: mean 3.97 years	RCT	Bonten et al. 2015 N Engl J Med quote RESULTS: In the per-protocol analysis of first episodes of infections due to vaccine-type strains, community-acquired pneumonia occurred in 49 persons in the PCV13 group and 90 persons in the placebo group (vaccine efficacy, 45.6%; 95.2% confidence interval [CI], 21.8 to 62.5), nonbacteremic and noninvasive community-acquired pneumonia occurred in 33 persons in the PCV13 group and 60 persons in the placebo group (vaccine efficacy, 45.0%; 95.2% CI, 14.2 to 65.3), and invasive pneumococcal disease occurred in 7 persons in the PCV13 group and 28 persons in the placebo group (vaccine efficacy, 75.0%; 95% CI, 41.4 to 90.8). abstract, RESULTS 95.2% CI. 33 versus 60 episodes. The first demonstration that a pneumococcal vaccine prevents non-bacteraemic pneumonia in older adults, the outcome PPSV23 had not convincingly shown.
Community-acquired pneumonia from any cause severity: pneumonia case definition: All-cause CAP, modified intention-to-treat	adults 65 years of age or older country: Netherlands period: 2008-2013 65+	PCV13 platform: protein-polysaccharide conjugate doses: 1 vs placebo	5.1 (-5.1–14.2) VE (%) follow-up: mean 3.97 years	RCT	Bonten et al. 2015 N Engl J Med quote In the modified intention-to-treat analysis, similar efficacy was observed (vaccine efficacy, 37.7%, 41.1%, and 75.8%, respectively), and community-acquired pneumonia occurred in 747 persons in the PCV13 group and 787 persons in placebo group (vaccine efficacy, 5.1%; 95% CI, -5.1 to 14.2). abstract, RESULTS Null result: 747 versus 787 episodes. PCV13 did not reduce all-cause pneumonia in this population, where vaccine-type pneumococcal CAP was a small fraction of all CAP.
Hospitalisation for vaccine-type community-acquired pneumonia severity: hospitalisation case definition: Hospitalised CAP with PCV13 serotypes identified by culture or serotype-specific urinary antigen; remaining CAP patients as test-negative controls	adults aged 65 years or older country: United States setting: Louisville, Kentucky, population-based hospital surveillance period: April 2015 to April 2016 n: 2,034 CAP hospitalisations, 68 cases 65+	PCV13 platform: protein-polysaccharide conjugate doses: 1 vs test-negative CAP controls	72.8 (12.8–91.5) VE (%)	test-negative	McLaughlin et al. 2018 Clin Infect Dis quote Cases were less likely to have received PCV13 than controls (3/68 [4.4%] vs 285/1966 [14.5%]; unadjusted VE, 72.8% [95% confidence interval, 12.8%-91.5%]). abstract, RESULTS Unadjusted; adjusted VE ranged 71.1-73.3% with no confounding observed. Only 3 of 68 cases were PCV13-vaccinated, so the interval is wide. Pfizer-funded.
All-cause pneumonia severity: pneumonia case definition: First ICD-10-CM coded all-cause pneumonia diagnosis in Medicare claims	adults aged 65 years and older country: United States setting: Medicare database period: July 2022 to June 2024 65+	PCV20 platform: protein-polysaccharide conjugate doses: 1 vs no PCV20	15.2 (14.5–15.9) VE (%) = (1-HR) x 100	cohort	Miles et al. 2026 Lancet Infect Dis quote Adjusted vaccine effectiveness was 25·6% (95% CI 17·4-33·0), 23·3% (16·3-29·8), 15·2% (14·5-15·9), and 7·4% (6·9-7·8) against all invasive pneumococcal disease, all pneumococcal pneumonia, all-cause pneumonia, and LRTI, respectively. abstract, FINDINGS A 15% reduction in all-cause pneumonia from a claims cohort is larger than CAPiTA's null RCT result (pcv-eff-039) and may partly reflect healthy-vaccinee bias that weighting cannot remove.
All-cause pneumonia hospitalisation in children under 2, a decade after PCV7 severity: hospitalisation case definition: Pneumonia as first-listed diagnosis (or after sepsis, meningitis or empyema), Nationwide Inpatient Sample, 2007-2009 versus 1997-1999	children younger than 2 years country: United States period: 2007-2009 versus 1997-1999 Infant <1y1-4y	PCV7 platform: protein-polysaccharide conjugate doses: routine infant schedule vs pre-PCV7 hospitalisation rates (1997-1999)	551.1 (445.1–657.1) absolute reduction in annual hospitalisation rate per 100,000	ecological	Griffin et al. 2013 N Engl J Med quote RESULTS: The annual rate of hospitalization for pneumonia among children younger than 2 years of age declined by 551.1 per 100,000 children (95% confidence interval [CI], 445.1 to 657.1), which translates to 47,000 fewer hospitalizations annually than expected on the basis of the rates before PCV7 was introduced. abstract, RESULTS Equivalent to 47,000 fewer hospitalisations a year. Before-after comparison, so secular trends in admission practice are not separated out.
All-cause pneumonia hospitalisation in adults 85 and older, a decade after infant PCV7 severity: hospitalisation case definition: Pneumonia hospitalisations, Nationwide Inpatient Sample, 2007-2009 versus 1997-1999	adults 85 years of age or older country: United States period: 2007-2009 versus 1997-1999 65+	PCV7 in children (indirect effect) platform: protein-polysaccharide conjugate doses: routine infant schedule vs pre-PCV7 hospitalisation rates	1300.8 (984.0–1617.6) absolute reduction in annual hospitalisation rate per 100,000	ecological	Griffin et al. 2013 N Engl J Med quote The rate for adults 85 years of age or older declined by 1300.8 per 100,000 (95% CI, 984.0 to 1617.6), which translates to 73,000 fewer hospitalizations annually. abstract, RESULTS 73,000 fewer hospitalisations a year in the oldest adults, attributed to herd effects; the age-adjusted overall reduction was 54.8 per 100,000 (41.0-68.5).

Sequelae after pneumococcal meningitis (hearing loss, neurological disability) Streptococcus pneumoniae

Post-acute and long-term sequelae

What can follow the acute illness: chronic disease, disability, cancers, congenital syndromes, post-infectious conditions.

Outcome (O)	Population (P)	Comparator	Estimate	Design (S)	Source
Any sequela among survivors of pneumococcal meningitis severity: any sequela case definition: Any reported sequela in survivors of meningitis due to Streptococcus pneumoniae, 63 studies from high-income countries	all ages (children and adults in the included studies) vaccination status: not reported country: multiple (high-income countries) setting: hospital follow-up period: studies 1991-2009 n: 3,408 pneumococcal meningitis survivors All ages	vs none (prevalence among survivors, no control group)	31.7 (27.2–36.3) pooled prevalence among survivors (%) per pneumococcal meningitis survivor	meta-analysis	Jit 2010 J Infect quote The pooled prevalence of any reported sequelae from 48 studies was 31.7% (95% confidence interval 27.2-36.3%) using a random effects model (Cochran-Q = 277, p < 0.01). abstract, RESULTS Random-effects pooled prevalence with marked heterogeneity (Cochran-Q 277). Denominator is survivors, so it sits on top of the case-fatality in pcv-bur-006.
Hearing loss among survivors of pneumococcal meningitis severity: hearing loss case definition: Hearing loss reported at follow-up in survivors of pneumococcal meningitis	all ages vaccination status: not reported country: multiple (high-income countries) setting: hospital follow-up period: studies 1991-2009 All ages	vs none (prevalence among survivors, no control group)	20.9 (17.1–24.7) pooled prevalence among survivors (%) per pneumococcal meningitis survivor	meta-analysis	Jit 2010 J Infect quote The pooled prevalence of hearing loss, seizures, hydrocephalus, spasticity/paresis, cranial nerve palsies and visual impairment was 20.9% (17.1-24.7%), 6.5% (3.3-9.7%), 6.8% (3.3-10.2%), 8.7% (6.4-11.0%), 12.2% (5.3-19.1%) and 2.4% (0-5.7%) respectively. abstract, RESULTS The same sentence gives seizures 6.5%, hydrocephalus 6.8%, spasticity/paresis 8.7%, cranial nerve palsies 12.2% and visual impairment 2.4%.
At least one major sequela after pneumococcal meningitis severity: major disabling sequela case definition: Major sequelae (cognitive deficit, bilateral hearing loss, motor deficit, seizures, visual impairment, hydrocephalus) after hospital discharge, 132 papers 1980-2008	all ages vaccination status: not reported country: global setting: hospital follow-up period: 1980-2008 All ages	vs none (risk among survivors; Hib meningitis 9.5% and meningococcal 7.2% in the same sentence)	24.7 median risk among survivors (%) per pneumococcal meningitis survivor	systematic review	Edmond et al. 2010 Lancet Infect Dis quote The median (IQR) risk of at least one major sequela was 24.7% (16.2-35.3%) in pneumococcal meningitis; 9.5% (7.1-15.3%) in Haemophilus influenzae type b (Hib), and 7.2% (4.3-11.2%) in meningococcal meningitis. abstract Median with interquartile range 16.2-35.3%, not a 95% CI, so no lo/hi recorded. Pneumococcal meningitis carried the highest sequelae risk of the three main pathogens.
At least one major sequela after bacterial meningitis, African region severity: major disabling sequela case definition: Major sequelae after bacterial meningitis of any cause, random-effects meta-analysis by WHO region	all ages vaccination status: not reported country: African region setting: hospital follow-up period: 1980-2008 All ages	vs European region, 9.4% (7.0-12.3%) in the same sentence	25.1 (18.9–32.0) pooled risk among survivors (%) per bacterial meningitis survivor	meta-analysis	Edmond et al. 2010 Lancet Infect Dis quote In the random-effects meta-analysis, all-cause risk of a major sequela was twice as high in the African (pooled risk estimate 25.1% [95% CI 18.9-32.0%]) and southeast Asian regions (21.6% [95% CI 13.1-31.5%]) as in the European region (9.4% [95% CI 7.0-12.3%]; overall I(2)=89.5%, p<0.0001). abstract All-cause bacterial meningitis, not pneumococcal-specific; shows the LMIC/high-income gap in disabling sequelae (twice as high in Africa as in Europe).
Seizure disorder after childhood pneumococcal meningitis severity: seizures case definition: Seizures recorded in the Swedish National Patient Register after a childhood diagnosis of bacterial meningitis due to Streptococcus pneumoniae	diagnosed under 18 years, median age at diagnosis 1.5 years; median follow-up 23.7 years vaccination status: not reported country: Sweden setting: nationwide registry period: 1987-2021 n: 3,623 meningitis cases and 32,607 controls (all pathogens) Infant <1y1-4y5-11y12-17y	vs general population controls matched 1:9 on age, sex and place of residence	7.89 (5.18–12.02) adjusted HR vs matched general-population controls follow-up: median 23.7 years	cohort	Mohanty et al. 2024 JAMA Netw Open quote The adjusted HRs for cognitive disabilities, seizures, hearing loss, and motor function disorders were significantly higher for Streptococcus pneumoniae infection (eg, 7.89 [95% CI, 5.18-12.02] for seizure) compared with Haemophilus influenzae infection (2.46 [95% CI, 1.63-3.70]) or Neisseria meningitidis infection (1.38 [95% CI, 0.65-2.93]). abstract, RESULTS Registry diagnosis without clinical validation; matching on age, sex and residence but residual confounding by prematurity or pre-existing neurological conditions that predispose to meningitis is possible. Pneumococcal HRs were significantly higher than Hib (2.46) or meningococcal (1.38) for the same outcome.
Hearing loss after childhood bacterial meningitis (all pathogens) severity: hearing loss case definition: Hearing loss diagnosis in the Swedish National Patient Register after childhood bacterial meningitis	diagnosed under 18 years, median 1.5 years at diagnosis vaccination status: not reported country: Sweden setting: nationwide registry period: 1987-2021 n: 3,623 cases and 32,607 controls Infant <1y1-4y5-11y12-17y	vs general population controls matched 1:9 on age, sex and place of residence	7.90 (6.68–9.33) adjusted HR vs matched general-population controls follow-up: median 23.7 years	cohort	Mohanty et al. 2024 JAMA Netw Open quote The estimated adjusted hazard ratios (HRs) showed a significant increased relative risk for cases compared with controls for all 7 disabilities, with the largest adjusted HRs for intracranial structural injuries (26.04 [95% CI, 15.50-43.74]), hearing loss (7.90 [95% CI, 6.68-9.33]), and motor function disorders (4.65 [95% CI, 3.72-5.80]). abstract, RESULTS All bacterial meningitis, not pneumococcal-specific; the abstract states hearing-loss HRs were significantly higher after pneumococcal infection but gives the pathogen-specific number only for seizures. 29.0% of all cases had at least one disability.
Hearing deficit 30-40 days after discharge from pneumococcal meningitis severity: hearing deficit case definition: Standardised neurodevelopmental assessment of children hospitalised with pneumococcal meningitis at Dhaka Shishu Hospital	children vaccination status: unvaccinated country: Bangladesh setting: hospital follow-up, LMIC period: 2006-2007 n: 51 case patients Infant <1y1-4y5-11y	vs healthy community controls matched for age, sex, socioeconomic status and residence, of whom none had hearing deficits	33 proportion of survivors with hearing deficit (%) follow-up: 30-40 days after discharge	cohort	Saha et al. 2009 Clin Infect Dis quote RESULTS: Neurodevelopmental assessments of the short-term follow-up cohort (n=51) revealed hearing, vision, mental, and psychomotor deficits in 33%, 8%, 41%, and 49% of the case patients, respectively. abstract, RESULTS Small cohort; the same sentence gives vision 8%, mental 41% and psychomotor 49%. Pre-PCV setting.
Hearing deficit 6-24 months after pneumococcal meningitis severity: hearing deficit case definition: Standardised neurodevelopmental assessment in a long-term follow-up cohort discharged before January 2005	children vaccination status: unvaccinated country: Bangladesh setting: hospital follow-up, LMIC period: discharged before 2005, followed 6-24 months n: 51 case patients Infant <1y1-4y5-11y	vs matched healthy community controls (2% with any deficit, none with hearing or vision deficits)	18 proportion of survivors with hearing deficit (%) follow-up: 6-24 months after discharge	cohort	Saha et al. 2009 Clin Infect Dis quote These deficits were 18%, 4%, 41%, and 35% in the long-term follow-up cohort (n=51), respectively. abstract, RESULTS Different children from pcv-pa-007 (two separate cohorts), so the drop from 33% to 18% is not within-child recovery. Mental (41%) and psychomotor (35%) deficits persisted.

Gaps

No numeric time-since-vaccination (waning) VE estimate for PCV in children was found: Andrews 2019 (PMID 31272872) reports waning for serotype 19A qualitatively in the abstract only. The number may be in the full text.
No clinical efficacy or effectiveness estimate for PCV15 or PCV20 in infants: licensure was on immunogenicity and only modelling/cost-effectiveness papers surfaced.
No US child IPD case-fatality estimate for the PCV13 era (ABCs) was found in the abstracts searched; the Netherlands (pcv-bur-018) and Europe (pcv-bur-016) stand in.
The WHO 2019 PCV position paper could not be snapshotted (see flag), so WHO's own burden and efficacy summary statements are not compiled.
No controlled estimate of PCV efficacy in pregnancy or in infants of vaccinated mothers was sought beyond the main searches; maternal pneumococcal vaccination is not a routine indication and was not compiled.
Berman-Rosa 2020 (PMID 32156773) states that neither PCV10 nor PCV13 was found effective against serotype 3, but the abstract gives no number, so the null serotype 3 finding is carried only in notes and in the conflicting records (Sings 2019 pooled 63.5%; Moore 2016 79.5%; Andrews 2019 all serotype 3 cases fully vaccinated).
Hearing loss after pneumococcal meningitis in high-income children specifically (cochlear implant rates, audiology-confirmed) was not compiled; the Jit 2010 pooled estimate mixes ages and the Swedish registry HR is all-pathogen.
Post-acute cardiovascular events (MI, stroke) after pneumococcal pneumonia were not searched.

Flags for review

The WHO 2019 pneumococcal position paper (WER 94(8)) could not be reached: who.int/publications/i/item/who-wer9408 and the position-papers landing page returned 404, and the iris.who.int PDF snapshot returned a 6-character page. A human should fetch it and add WHO's summary statements.
Serotype 3 effectiveness conflicts across sources: Sings 2019 pooled 63.5% and Moore 2016 79.5% versus Andrews 2014 (not significant), Andrews 2019 (all 36 serotype 3 cases fully vaccinated, VE rises from 73.7% to 84.8% when serotype 3 is excluded), Berman-Rosa 2020 (not effective, no number) and PSERENADE (no consistent population trend). The Sings meta-analysis is Pfizer-authored. Present these together, not any one alone.
Several burden figures are counts or ranges without intervals (Pink Book CFRs and annual estimates, PSERENADE fold-ranges, Edmond median with IQR). They are labelled in notes; check the site can display interval-free records beside interval-bearing ones.
Denominators differ: pcv-bur-029 (ICU, per hospitalised case), pcv-pa-001/002 (per survivor), pcv-bur-027/028 (per 10,000, not 100,000), pcv-bur-031 (per 1,000). Do not multiply or rank across these without converting the units and saying so.
Impact records compiled as kind=efficacy with design=ecological or surveillance (Moore 2015, Whitney 2003, Nuorti 2022, PSERENADE, Griffin 2013, MMWR 2008, Pink Book) measure population-level declines against a pre-vaccine or counterfactual baseline, not individual vaccine effectiveness. Their comparator field says so. They must not be read as VE in a vaccinated person.
The two Netherlands records pcv-bur-018 and pcv-bur-019 come from one sentence of one abstract (Wagenvoort 2016); the four CAPiTA records come from one sentence of one abstract; the five Cochrane child records likewise. Count sources, not records, when describing the evidence base.
pcv-bur-026 (WHO: 740 180 child pneumonia deaths) and pcv-bur-027/028/029 (Jain: all-cause CAP) are all-cause pneumonia, not pneumococcal; pneumococcus was detected in 5% of the Jain cohort. They are filed under pneumococcal-pneumonia for context only and must be labelled all-cause on the page.
pcv-pa-006 (hearing loss HR 7.90) is for bacterial meningitis of any cause; the pneumococcal-specific HR in that abstract is only given for seizures (pcv-pa-005). Do not present 7.90 as a pneumococcal figure.
tools/validate.py reports 70 warnings, all "notes contain numbers not in quote". Every such number is either a record cross-reference (e.g. pcv-bur-037, parsed as 037), a companion figure from the same cached sentence or abstract as the quote (e.g. the 3+1 range beside the 3+0 range, the 19A and 7F estimates beside the PCV13-serotype estimate), or a P value. None is a number from memory; all are verifiable in sources/. They are not gated by the validator, so a reviewer who wants notes to be number-free should strip them rather than trust them as separately sourced.

Search log (38 searches)

pneumococcal conjugate vaccine invasive pneumococcal disease incidence children before after introduction United States · PubMed → Found PMID 36064378 (MarketScan 1998-2018), 39706204/39706205/39864526 (PSERENADE), 18272956 (MMWR 2008), 19145219 (MMWR pneumonia), 16609088 (Poehling infants); compiled as burden and impact records.
pneumococcal meningitis case fatality children systematic review · PubMed → Found PMID 24830699 (Latin America meta-analysis), 19751516 (African sequelae review), 19748398 (O'Brien global burden 2000); compiled as pcv-bur-020 to pcv-bur-022.
Cochrane pneumococcal conjugate vaccines preventing vaccine-type invasive pneumococcal disease children · PubMed → Found PMID 19821336 (Lucero 2009 Cochrane) and 32156773 (Berman-Rosa 2020 review); compiled as efficacy records.
CAPiTA polysaccharide conjugate vaccine against pneumococcal pneumonia in adults randomized · PubMed → Found PMID 25785969 (Bonten 2015 NEJM); compiled as four efficacy records.
pneumococcal meningitis hearing loss sequelae meta-analysis · PubMed → Found PMID 20433866 (Jit 2010) and 20417414 (Edmond 2010); compiled as pcv-pa-001 to pcv-pa-004.
Northern California Kaiser Permanente heptavalent pneumococcal conjugate vaccine efficacy trial · PubMed → No hit with that phrasing; re-run as Black Shinefield 2000 (below).
FinIP ten-valent pneumococcal conjugate vaccine effectiveness invasive cluster randomised Finland · PubMed → Found PMID 23158882 (Palmu 2013 Lancet); compiled as efficacy records.
COMPAS trial PHiD-CV Latin America efficacy pneumonia · PubMed → Found PMID 24892763 (Tregnaghi 2014); compiled as efficacy records.
Gambia nine-valent pneumococcal conjugate vaccine randomised trial efficacy · PubMed → Found PMID 15794968 (Cutts 2005 Lancet); compiled as efficacy records.
pneumococcal polysaccharide vaccine adults Cochrane systematic review invasive pneumococcal disease · PubMed → Found PMID 23440780 (Moberley 2013 Cochrane), 28061505 (Falkenhorst 2017), 26899372 (Kraicer-Melamed 2016); compiled as efficacy records.
PCV13 serotype 3 vaccine effectiveness invasive pneumococcal disease children meta-analysis · PubMed → Found PMID 30357326 (Sings 2019); compiled as an efficacy record.
pneumococcal conjugate vaccine schedule 2+1 versus 3+1 systematic review effectiveness · PubMed → No hit with that phrasing; found via Deloria Knoll search as PMID 24336053 (Conklin 2014).
pneumococcal conjugate vaccine herd immunity indirect effects adults invasive pneumococcal disease decline systematic review · PubMed → Found PMID 36075797 (Finland adults), 26868606 (Barcelona mortality), 31500963 (Netherlands 12 years), 26778420 (Netherlands outcomes), 25693604 (Europe 2010 CFR).
invasive pneumococcal disease case fatality adults older surveillance Europe · PubMed → Same result set as the herd-effects search; compiled as burden records.
pneumococcal conjugate vaccine immunocompromised HIV adults efficacy randomized · PubMed → Found PMID 20200385 (French 2010 NEJM, Malawi); compiled as pcv-eff and pcv-saf records.
community-acquired pneumonia hospitalization incidence adults 65 Streptococcus pneumoniae burden United States · PubMed → Found PMID 26172429 (Jain 2015 EPIC) and 40768150 (Grijalva 2025); compiled as burden records.
pneumococcal conjugate vaccine waning protection time since vaccination case-control children · PubMed → Found only PMID 23000122 (PPSV23 waning in the elderly) and 41702352 (Vietnam); no child PCV waning estimate with a numeric time-stratified VE.
Black S Shinefield efficacy safety heptavalent pneumococcal conjugate vaccine children Pediatr Infect Dis J 2000 · PubMed → Found PMID 10749457 (NCKP trial); compiled as efficacy records.
Whitney 2003 decline invasive pneumococcal disease after introduction protein-polysaccharide conjugate vaccine · PubMed → Found PMID 12724479; compiled as burden and impact records.
Whitney 2006 effectiveness seven-valent pneumococcal conjugate vaccine matched case-control study · PubMed → Found PMID 17071283; compiled as efficacy records.
Andrews NJ 2014 serotype-specific effectiveness PCV13 England Wales postlicensure · PubMed → Found PMID 25042756; compiled as efficacy records.
Moore MR 2016 effectiveness 13-valent pneumococcal conjugate vaccine children United States case-control serotype 19A · PubMed → Found PMID 26987984; compiled as efficacy records.
Pilishvili 2023 PCV13 effectiveness adults 65 invasive pneumococcal disease United States · PubMed → No hit; adult PCV13 effectiveness taken from PMID 29790925 (McLaughlin test-negative) and 31522807 instead.
Deloria Knoll systematic review pneumococcal conjugate vaccine dosing schedules invasive disease 2+1 3+1 · PubMed → Found PMID 24336053 (Conklin 2014); compiled as an efficacy record.
Moore MR 2015 effect of use of 13-valent pneumococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults USA · PubMed → Found PMID 25656600; compiled as impact records.
13-valent conjugate vaccine effectiveness against pneumococcal pneumonia adults 65 test-negative design Louisville · PubMed → Found PMID 29790925 and 31522807 (serotype 3 adults pooled); compiled as efficacy records.
20-valent pneumococcal conjugate vaccine adults effectiveness real-world invasive pneumococcal disease · PubMed → Found PMID 42070554 (Miles 2026 Medicare) and 39551343 (Israel serotype CFR); compiled.
Griffin MR U.S. hospitalizations for pneumonia after a decade of pneumococcal vaccination · PubMed → Found PMID 23841730; compiled as impact records.
pneumococcal meningitis children hearing loss cohort long-term follow-up · PubMed → Found PMID 38241045 (Sweden registry cohort) and 19191624 (Bangladesh); compiled as post_acute records.
invasive pneumococcal disease children sickle cell disease incidence rate ratio PCV · PubMed → Found PMID 37698500 (Adamkiewicz 2023); compiled as burden and efficacy records.
pneumococcal conjugate vaccine effectiveness children 2+1 schedule United Kingdom PCV13 indirect cohort Ladhani 2018 2019 · PubMed → Found PMID 31272872 (Andrews 2019); compiled as efficacy records.
Global Burden of Disease lower respiratory infections aetiologies 2016 Streptococcus pneumoniae deaths · PubMed → Found PMID 30243584; compiled as pcv-bur-025.
Wahl B burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children 2000-15 global · PubMed → Found PMID 29903376; compiled as pcv-bur-023 and pcv-bur-024.
pneumococcal conjugate vaccine effectiveness HIV-infected children South Africa Madhi efficacy 9-valent · PubMed → Found PMID 14523142 (Klugman 2003 NEJM); compiled as efficacy records.
pneumococcal conjugate vaccine 15-valent 20-valent infants efficacy effectiveness invasive pneumococcal disease · PubMed → Only cost-effectiveness and modelling papers; no clinical efficacy or effectiveness estimate for PCV15/PCV20 in infants.
invasive pneumococcal disease case fatality children PCV13 era United States Active Bacterial Core surveillance · PubMed → No usable hit; US child CFR in the PCV13 era not compiled.
CDC Pink Book chapter 17 pneumococcal disease · websource → Cached as cdc-gov-9f29513e00; compiled as burden and efficacy records. CDC surveillance page cached as cdc-gov-ebc9c01b7d and clinical overview as cdc-gov-2cacb94fcd (no additional numbers used).
WHO pneumococcal conjugate vaccines position paper 2019 (WER 94(8)) · websource → Three URL forms failed (404 on who.int item pages; the iris.who.int PDF returned 6 characters). Not compiled; see flag. WHO pneumonia fact sheet cached as who-int-5676f45558 instead.