BACKGROUND: Next-generation pneumococcal conjugate vaccines (PCVs) target an expanding array of serotype antigens. We assessed the proportions of invasive pneumococcal disease (IPD) and pneumococcal acute respiratory infections (ARIs) caused by serotypes targeted by existing and pipeline PCVs, and annual U.S. pneumococcal disease burdens potentially preventable by these products. METHODS: We estimated serotype distribution and proportions of pneumococcal ARIs (acute otitis media [AOM; children only], sinusitis, non-bacteremic pneumonia) and IPD attributable to serotypes targeted by each PCV using Markov chain Monte Carlo approaches incorporating data from epidemiological studies and Active Bacterial Core Surveillance. We then estimated annual numbers of outpatient-managed ARIs, non-bacteremic pneumonia hospitalizations, and IPD cases potentially preventable by PCVs by multiplying disease incidence rates by PCV-targeted disease proportions and vaccine effectiveness estimates. RESULTS: In children, PCV15, PCV20, PCV24, PCV25, and PCV31 serotypes account for 16% (95% confidence interval: 15-17%), 31% (30-32%), 34% (32-35%), 43% (42-44%), and 68% (67-69%) of pneumococcal AOM, respectively. In adults, PCV15, PCV20, PCV21, PCV24, PCV25, and PCV31 serotypes account for 43% (38-47%), 52% (47-57%), 69% (64-73%), 65% (61-70%), 62% (57-67%), and 87% (83-90%) of pneumococcal non-bacteremic pneumonia. For IPD, 42-85% of pediatric and 42-94% of adult cases were due to PCV-targeted serotypes. PCV-preventable burdens encompassed 270,000-3,300,000 outpatient-managed ARIs, 2,000-17,000 pneumonia hospitalizations, and 3,000-14,000 IPD cases annually. CONCLUSIONS: Across pneumococcal conditions, coverage and preventable burdens were lowest for PCV15 and highest for PCV31, with PCV21 also targeting sizeable burdens of adult disease. Comparative estimates of preventable disease burden may inform future policy.

BACKGROUND: In 2022-2023, 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recommended for infants. We aimed to estimate the incidence of outpatient visits and antibiotic prescriptions in US children (≤17 years) from 2016-2019 for acute otitis media, pneumonia, and sinusitis associated with PCV15- and PCV20-additional (non-PCV13) serotypes to quantify PCV15/20 potential impacts. METHODS: We estimated the incidence of PCV15/20-additional serotype-attributable visits and antibiotic prescriptions as the product of all-cause incidence rates, derived from national health care surveys and MarketScan databases, and PCV15/20-additional serotype-attributable fractions. We estimated serotype-specific attributable fractions using modified vaccine-probe approaches incorporating incidence changes post-PCV13 and ratios of PCV13 versus PCV15/20 serotype frequencies, estimated through meta-analyses. RESULTS: Per 1000 children annually, PCV15-additional serotypes accounted for an estimated 2.7 (95% confidence interval, 1.8-3.9) visits and 2.4 (95% CI, 1.6-3.4) antibiotic prescriptions. PCV20-additional serotypes resulted in 15.0 (95% CI, 11.2-20.4) visits and 13.2 (95% CI, 9.9-18.0) antibiotic prescriptions annually per 1000 children. PCV15/20-additional serotypes account for 0.4% (95% CI, 0.2%-0.6%) and 2.1% (95% CI, 1.5%-3.0%) of pediatric outpatient antibiotic use. CONCLUSIONS: Compared with PCV15-additional serotypes, PCV20-additional serotypes account for > 5 times the burden of visits and antibiotic prescriptions. Higher-valency PCVs, especially PCV20, may contribute to preventing pediatric pneumococcal respiratory infections and antibiotic use.

BACKGROUND: A U.S. case-control study (2010-2014) demonstrated vaccine effectiveness (VE) for ≥ 1 dose of the thirteen-valent pneumococcal conjugate vaccine (PCV13) against vaccine-type (VT) invasive pneumococcal disease (IPD) at 86 %; however, it lacked statistical power to examine VE by number of doses and against individual serotypes. METHODS: We used the indirect cohort method to estimate PCV13 VE against VT-IPD among children aged < 5 years in the United States from May 1, 2010 through December 31, 2019 using cases from CDC's Active Bacterial Core surveillance, including cases enrolled in a matched case-control study (2010-2014). Cases and controls were defined as individuals with VT-IPD and non-PCV13-type-IPD (NVT-IPD), respectively. We estimated absolute VE using the adjusted odds ratio of prior PCV13 receipt (1-aOR x 100 %). RESULTS: Among 1,161 IPD cases, 223 (19.2 %) were VT cases and 938 (80.8 %) were NVT controls. Of those, 108 cases (48.4 %; 108/223) and 600 controls (64.0 %; 600/938) had received > 3 PCV13 doses; 23 cases (17.6 %) and 15 controls (2.4 %) had received no PCV doses. VE ≥ 3 PCV13 doses against VT-IPD was 90.2 % (95 % Confidence Interval75.4-96.1 %), respectively. Among the most commonly circulating VT-IPD serotypes, VE of ≥ 3 PCV13 doses was 86.8 % (73.7-93.3 %), 50.2 % (28.4-80.5 %), and 93.8 % (69.8-98.8 %) against serotypes 19A, 3, and 19F, respectively. CONCLUSIONS: At least three doses of PCV13 continue to be effective in preventing VT-IPD among children aged < 5 years in the US. PCV13 was protective against serotypes 19A and 19F IPD; protection against serotype 3 IPD did not reach statistical significance.

BACKGROUND: Malaria infection poses a significant risk in pregnancy, yet chemoprophylaxis for pregnant women is limited. A systematic review was conducted to evaluate the incidence of adverse outcomes after atovaquone-proguanil (AP) exposure during pregnancy. METHODS: Following PRISMA guidelines, the authors searched PubMed, MEDLINE, and the Malaria in Pregnancy Consortium Library to identify relevant literature including infant outcomes after exposure to atovaquone, proguanil, or AP in pregnancy. Two authors independently screened the titles, abstracts, and full texts, and extracted data into an EpiInfo database. Overall proportions and 95% confidence intervals of adverse outcomes were determined by pooling data across studies. RESULTS: Of 455 records identified, 16 studies were included: ten AP studies and six proguanil studies. The overall proportions and 95% confidence intervals (CI) of adverse outcomes reported for the 446 women exposed to AP include miscarriage (8.08% CI: 5.07, 12.08%), stillbirth (1.05% CI: 0.03, 5.73%), early neonatal death (0% CI: 0, 7.4%), and congenital anomalies (2.56% CI: 1.28, 4.53%). CONCLUSIONS: The limited available data suggest that outcomes following AP exposure during pregnancy are similar to expected rates in similar populations. AP may be a promising option for pregnant women, but further data are needed on its safety in pregnancy.