Effect of pneumococcal conjugate vaccines on viral respiratory infections: a systematic literature review.

BACKGROUND: In addition to preventing pneumococcal disease, emerging evidence indicates that pneumococcal conjugate vaccines (PCVs) might indirectly reduce viral respiratory tract infections (RTI) by affecting pneumococcal-viral interactions. METHODS: We performed a systematic review of interventional and observational studies published during 2000-2022 on vaccine efficacy/adjusted effectiveness (VE) and overall effect of PCV7, PCV9, PCV10, or PCV13 against viral RTI. RESULTS: Sixteen of 1671 records identified were included. Thirteen publications described effects of PCVs against viral RTIs in children. VE against influenza ranged between 41-86% (n=4), except for the 2010-2011 influenza season. In a randomized controlled trial, PCV9 displayed efficacy against any viral RTI, human seasonal coronavirus, parainfluenza, and human metapneumovirus. Data in adults were limited (n=3). PCV13 VE ranged between 4-25% against viral lower RTI, 32-35% against COVID-19 outcomes, 24-51% against human seasonal coronavirus, and 13-36% against influenza A lower RTI, with some 95%CI spanning zero. No protection was found against adenovirus or rhinovirus in children or adults. CONCLUSIONS: PCVs were associated with protection against some viral RTI, with the strongest evidence for influenza in children. Limited evidence for adults was generally consistent with pediatric data. Restricting public health evaluations to confirmed pneumococcal outcomes may underestimate the full impact of PCVs.

Effects of PCV10 and PCV13 on pneumococcal serotype 6C disease, carriage, and antimicrobial resistance.

BACKGROUND: The cross-protection of pneumococcal conjugate vaccines (PCV) against serotype 6C is not clearly documented, although 6C represents a substantial burden of pneumococcal disease in recent years. A systematic review by the World Health Organization that covered studies through 2016 concluded that available data were insufficient to determine if either PCV10 (which contains serotype 6B but not 6A) or PCV13 (containing serotype 6A and 6B) conferred protection against 6C. METHODS: We performed a systematic review of randomized controlled trials and observational studies published between January 2010 - August 2022 (Medline/Embase), covering the direct, indirect, and overall effect of PCV10 and PCV13 against 6C invasive pneumococcal disease (IPD), non-IPD, nasopharyngeal carriage (NPC), and antimicrobial resistance (AMR). RESULTS: Of 2548 publications identified, 112 were included. Direct vaccine effectiveness against 6C IPD in children ranged between 70 and 85 % for ≥ 1 dose PCV13 (n = 3 studies), was 94 % in fully PCV13 vaccinated children (n = 2), and -14 % for ≥ 1 dose of PCV10 (n = 1). Compared to PCV7, PCV13 efficacy against 6C NPC in children was 66 % (n = 1). Serotype 6C IPD rates or NPC prevalence declined post-PCV13 in most studies in children (n = 5/6) and almost half of studies in adults (n = 5/11), while it increased post-PCV10 for IPD and non-IPD in all studies (n = 6/6). Changes in AMR prevalence were inconsistent. CONCLUSIONS: In contrast to PCV10, PCV13 vaccination consistently protected against 6C IPD and NPC in children, and provided some level of indirect protection to adults, supporting that serotype 6A but not 6B provides cross-protection to 6C. Vaccine policy makers and regulators should consider the effects of serotype 6A-containing PCVs against serotype 6C disease in their decisions.

Surveillance of pneumococcal serotypes in adults hospitalised with acute lower respiratory tract infection in Bristol, UK.

INTRODUCTION: Pneumococcus remains a major cause of adult lower respiratory tract infections (LRTI). Few data exist on the relative contribution of serotypes included in pneumococcal vaccines to community-acquired pneumonia (CAP) and non-pneumonic (NP) LRTI. We measured the burden of all and vaccine-serotype pneumococcal respiratory infection following SARS-CoV-2 emergence to inform evidence-based vaccination policy. METHODS: A prospective cohort study at two Bristol hospitals (UK) including all adults age ≥ 18-years hospitalised with acute lower respiratory tract disease (aLRTD) from Nov2021-Nov2022. LRTI patients were classified as: a) radiographically-confirmed CAP (CAP+/RAD+), b) clinically-diagnosed CAP without radiological confirmation (CAP+/RAD-), or c) NP-LRTI. Pneumococcus was identified by blood culture, BinaxNOW™and serotype-specific urine antigen detection assays (UAD). RESULTS: Of 12,083 aLRTD admissions, 10,026 had LRTI and 2,445 provided urine: 1,097 CAP + RAD+; 207 CAP + RAD-; and 1,141 NP-LRTI. Median age was 71.1y (IQR57.9-80.2) and Charlson comorbidity index = 4 (IQR2-5); 2.7 % of patients required intensive care, and 4.4 % died within 30-days of hospitalisation. Pneumococcus was detected in 280/2445 (11.5 %) participants. Among adults aged ≥ 65y and 18-64y, 12.9 % (198/1534) and 9.0 % (82/911), respectively, tested pneumococcus positive. We identified pneumococcus in 165/1097 (15.0 %) CAP + RAD+, 23/207 (11.1 %) CAP + RAD-, and 92/1141 (8.1 %) NP-LRTI cases. Of the 280 pneumococcal cases, 102 (36.4 %) were due to serotypes included in PCV13 + 6C, 115 (41.7 %) in PCV15 + 6C, 210 (75.0 %) in PCV20 + 6C/15C and 228 (81.4 %) in PPV23 + 15C. The most frequently identified serotypes were 8 (n = 78; 27.9 % of all pneumococcus), 7F (n = 25; 8.9 %), and 3 (n = 24; 8.6 %). DISCUSSION: Among adults hospitalised with respiratory infection, pneumococcus is an important pathogen across all subgroups, including CAP+/RAD- and NP-LRTI. Despite 20-years of PPV23 use in adults ≥ 65-years and herd protection due to 17-years of PCV use in infants, vaccine-serotype pneumococcal disease still causes a significant proportion of LRTI adult hospitalizations. Direct adult vaccination with high-valency PCVs may reduce pneumococcal disease burden.

Multicountry Review of Streptococcus pneumoniae Serotype Distribution Among Adults With Community-Acquired Pneumonia.

BACKGROUND: Nonbacteremic community-acquired pneumonia (CAP) is a leading presentation of severe pneumococcal disease in adults. Serotype-specific urinary antigen detection (UAD) assay can detect serotypes causing pneumococcal CAP, including nonbacteremic cases, and guide recommendations for use of higher valency pneumococcal conjugate vaccines (PCVs). METHODS: Adult CAP serotype distribution studies that used both Pfizer UADs (UAD1, detects PCV13 serotypes; UAD2, detects PCV20 non-PCV13 serotypes plus 2, 9N, 17F, and 20) were identified by review of an internal study database and included if results were published. The percentages of all-cause radiologically confirmed CAP (RAD + CAP) due to individual or grouped (PCV13, PCV15, and PCV20) serotypes as detected from culture or UAD were reported. RESULTS: Six studies (n = 2, United States; n = 1 each, Germany, Sweden, Spain, and Greece) were included. The percentage of RAD + CAP among adults ≥18 years with PCV13 serotypes equaled 4.6% to 12.9%, with PCV15 serotypes 5.9% to 14.5%, and with PCV20 serotypes 7.8% to 23.8%. The percentage of RAD + CAP due to PCV15 and PCV20 serotypes was 1.1-1.3 and 1.3-1.8 times higher than PCV13 serotypes, respectively. CONCLUSIONS: PCV13 serotypes remain a cause of RAD + CAP among adults even in settings with pediatric PCV use. Higher valency PCVs among adults could address an important proportion of RAD + CAP in this population.

Estimated Effectiveness of Coadministration of the BNT162b2 BA.4/5 COVID-19 Vaccine With Influenza Vaccine.

Importance: No data comparing the estimated effectiveness of coadministering COVID-19 vaccines with seasonal influenza vaccine (SIV) in the community setting exist. Objective: To examine the comparative effectiveness associated with coadministering the BNT162b2 BA.4/5 bivalent mRNA COVID-19 vaccine (BNT162b2-biv [Pfizer BioNTech]) and SIV vs giving each vaccine alone. Design, Setting, and Participants: A retrospective comparative effectiveness study evaluated US adults aged 18 years or older enrolled in commercial health insurance or Medicare Advantage plans and vaccinated with BNT162b2-biv only, SIV only, or both on the same day between August 31, 2022, and January 30, 2023. Individuals with monovalent or another brand of mRNA bivalent COVID-19 vaccine were excluded. Exposure: Same-day coadministration of BNT162b2-biv and SIV; receipt of BNT162b2-biv only (for COVID-19-related outcomes) or SIV only (for influenza-related outcomes) were the comparator groups. For adults aged 65 years or older, only enhanced SIVs were included. Main Outcomes and Measures: COVID-19-related and influenza-related hospitalization, emergency department (ED) or urgent care (UC) encounters, and outpatient visits. Results: Overall, 3 442 996 individuals (57.0% female; mean [SD] age, 65 [16.7] years) were included. A total of 627 735 individuals had BNT162b2-biv and SIV vaccine coadministered, 369 423 had BNT162b2-biv alone, and 2 445 838 had SIV alone. Among those aged 65 years or older (n = 2 210 493; mean [SD] age, 75 [6.7] years; 57.9% female), the coadministration group had a similar incidence of COVID-19-related hospitalization (adjusted hazard ratio [AHR], 1.04; 95% CI, 0.87-1.24) and slightly higher incidence of emergency department or urgent care encounters (AHR, 1.12; 95% CI, 1.02-1.23) and outpatient visits (AHR, 1.06; 95% CI, 1.01-1.11) compared with the BNT162b2-biv-only group. Among individuals aged 18 to 64 years (n = 1 232 503; mean [SD] age, 47 [13.1] years; 55.4% female), the incidence of COVID-19-related outcomes was slightly higher among those who received both vaccines vs BNT162b2-biv alone (AHR point estimate range, 1.14-1.57); however, fewer events overall in this age group resulted in wider CIs. Overall, compared with those who received SIV alone, the coadministration group had a slightly lower incidence of most influenza-related end points (AHR point estimates 0.83-0.93 for those aged ≥65 years vs 0.76-1.08 for those aged 18-64 years). Negative control outcomes suggested residual bias and calibration of COVID-19-related and influenza-related outcomes with negative controls moved all estimates closer to the null, with most CIs crossing 1.00. Conclusions and Relevance: In this study, coadministration of BNT162b2-biv and SIV was associated with generally similar effectiveness in the community setting against COVID-19-related and SIV-related outcomes compared with giving each vaccine alone and may help improve uptake of both vaccines.

Effectiveness of BNT162b2 BA.4/5 bivalent mRNA vaccine against symptomatic COVID-19 among immunocompetent individuals testing at a large US retail pharmacy.

BACKGROUND: Data on the effectiveness of BA.4/5 bivalent vaccine stratified by age and prior infection are lacking. METHODS: This test-negative study used data from individuals ≥5 years of age testing for SARS-CoV-2 with symptoms (9/15/2022‒1/31/2023) at a large national retail pharmacy chain. The exposure was receipt of 2‒4 wild-type doses and a BNT162b2 BA.4/5 bivalent vaccine (>2 months since last wild-type dose). The outcome was a positive SARS-CoV-2 test. Absolute (vs. unvaccinated) and relative (vs. 2‒4 wild-type doses) vaccine effectiveness (VE) were calculated as (1‒adjusted odds ratio from logistic regression) x 100. VE was stratified by age and self-reported prior infection. RESULTS: Overall, 307,885 SARS-CoV-2 tests were included (7,916 5‒11-year-olds, 16,329 12‒17-year-olds, and 283,640 aged ≥18 years). SARS-CoV-2 positivity was 39%; 21% were unvaccinated, 70% received 2‒4 wild-type doses with no bivalent vaccine, and 9% received a BNT162b2 BA.4/5 bivalent dose. At a median of 1‒2 months after BNT162b2 BA.4/5 bivalent vaccination, depending on age group, absolute VE ranged 22-60% and was significantly higher among those reporting prior infection (range: 55‒79%) than not (range: no protection to 50%). Relative VE ranged 31-64%. CONCLUSIONS: BNT162b2 BA.4/5 bivalent showed early additional protection against Omicron-related symptomatic COVID-19, with hybrid immunity offering greater protection.

Safety and immunogenicity of a multivalent pneumococcal conjugate vaccine given with 13-valent pneumococcal conjugate vaccine in healthy infants: A phase 2 randomized trial.

Use of pneumococcal conjugate vaccines (PCVs) has led to substantial reductions in the global burden of pediatric pneumococcal disease. Expansion of serotype coverage has been achieved by increasing PCV valency, but this may carry the potential risk of antibody interference. A complementary 7-valent PCV (cPCV7) including polysaccharide conjugates from 7 non-13-valent (PCV13) serotypes was developed to potentially complement PCV13-mediated protection and expand serotype coverage. This study evaluated cPCV7 and PCV13 coadministered in separate limbs or separated in time in infants. This phase 2, multicenter, open-label study included 512 infants randomized 1:1:1 to receive cPCV7 coadministered with PCV13 at ages 2, 4, 6, and 12 months (cPCV7 Coadministered); cPCV7 given at ages 3, 5, 7, and 13 months, 3‒5 weeks after PCV13 (cPCV7 Separated); or PCV13 at ages 2, 4, 6, and 12 months followed by a single supplemental dose of cPCV7 at 13 months (PCV13 Control). Safety evaluations included local reactions, systemic events, and adverse events. Serotype-specific immunoglobulin G concentrations and opsonophagocytic activity titers were assessed. The safety profile of cPCV7 was similar to that of PCV13. cPCV7 was well-tolerated in infants when coadministered with or given separately from PCV13. Robust and functional immune responses for all cPCV7 serotypes were observed in both cPCV7 groups. No immunologic interference was observed for either the cPCV7 or PCV13 serotypes with coadministration. A single cPCV7 dose induced immune responses in toddlers. These findings support potential coadministration of a complementary PCV to supplement protection provided by existing PCVs.Trial registration: ClinicalTrials.gov, NCT03550313.

Estimated Incidence of Symptomatic Lyme Borreliosis Cases in Lublin, Poland in 2021.

Lyme borreliosis (LB), the most common tick-borne disease in Europe, is endemic to Poland. Despite public health surveillance with mandatory reporting of LB cases by physicians and laboratories, many symptomatic LB cases are not included in surveillance in Poland. We estimated the extent of the under-ascertainment of symptomatic LB cases via surveillance in the Polish province of Lublin to better understand Poland's LB burden. The number of incident symptomatic LB cases in Lublin in 2010 was estimated from two seroprevalence studies conducted among adults in Lublin, as well as estimates of the proportion of asymptomatic LB cases and the duration of LB antibody persistence. The estimated number of incident symptomatic LB cases was compared to the number of surveillance-reported cases in Lublin to derive an under-ascertainment multiplier. This multiplier was applied to the number of surveillance-reported cases in 2021 to estimate the number and population-based incidence of symptomatic LB cases in Lublin in 2021. We estimate that there are 5.9 symptomatic LB cases for every surveillance-reported LB case in Lublin. Adjusting for under-ascertainment, the estimated number of symptomatic LB cases in Lublin in 2021 was 6204 (population-based incidence: 467.6/100,000). After adjustment for under-ascertainment, the incidence of symptomatic LB in Lublin, Poland, is high.

A systematic literature review of the effectiveness of tick-borne encephalitis vaccines in Europe.

BACKGROUND: Tick-borne encephalitis (TBE) is an infectious disease caused by the tick-borne encephalitis virus (TBEV) in patients with symptoms of central nervous system (CNS) inflammation. More than 25 European countries have one or more TBE-endemic areas. Although two TBE vaccines, FSME-IMMUN® and Encepur®, are commonly used in Europe, there are no published reviews of the real-world effectiveness of TBE vaccines in Europe or elsewhere. METHODS: We searched PubMed for TBE vaccine effectiveness (VE) articles and extracted information on country, study design, study period, study population, number of TBEV-infected cases, number of participants, and VE against TBEV infection and outcomes. RESULTS: We identified 13 studies, conducted in Austria, the Czech Republic, Latvia, Germany, and Switzerland, published in 2003-2023. One study was a cohort investigation of a milk-borne outbreak. In the other studies, 11 (91.7%) used the screening method and two (16.7%) used a case-control design (one study used both). TBE vaccines were highly effective (VE estimates >92%) against TBEV infection in all age groups. Vaccines were also highly protective against mild infections (i.e., infections in patients without symptoms of CNS inflammation), and against infections resulting in TBE and hospitalization. Vaccines were also highly protective against the most serious outcomes such as hospitalization greater than 12 days. Product-specific VE estimates were also high, though limited data were available. Studies in Austria, the Czech Republic, Latvia, and Switzerland estimated that TBE vaccines prevented >1,000 TBE cases a year, avoiding many hospitalizations and deaths, in these countries combined. CONCLUSIONS: Published VE studies demonstrate a high real-world effectiveness of the commercially available TBE vaccines in Europe. Although cases averted have been estimated in only four countries, TBE vaccination prevents thousands of cases in Europe each year. To prevent life-threatening TBE, TBE vaccine uptake and compliance with the vaccination schedule should be increased in residents of, and travelers to, TBE-endemic countries in Europe.

Effectiveness of BNT162b2 BA.4/5 bivalent mRNA vaccine against a range of COVID-19 outcomes in a large health system in the USA: a test-negative case-control study.

BACKGROUND: XBB-related omicron sublineages have recently replaced BA.4/5 as the predominant omicron sublineages in the USA and other regions globally. Despite preliminary signs of immune evasion of XBB sublineages, few data exist describing the real-world effectiveness of bivalent COVID-19 vaccines, especially against XBB-related illness. We aimed to investigate the effectiveness of the Pfizer--BioNTech BNT162b2 BA.4/5 bivalent vaccine against both BA.4/5-related and XBB-related disease in adults aged 18 years or older. METHODS: In this test-negative case-control study, we estimated the effectiveness of the BNT162b2 BA.4/5 bivalent vaccine using data from electronic health records of Kaiser Permanente Southern California health system members aged 18 years or older who received at least two doses of the wild-type COVID-19 mRNA vaccines. Participants sought care for acute respiratory infection between Aug 31, 2022, and April 15, 2023, and were tested for SARS-CoV-2 via PCR tests. Relative vaccine effectiveness (≥2 doses of wild-type mRNA vaccine plus a BNT162b2 BA.4/5 bivalent booster vs ≥2 doses of a wild-type mRNA vaccine alone) and absolute vaccine effectiveness (vs unvaccinated individuals) was estimated against critical illness related to acute respiratory infection (intensive care unit [ICU] admission, mechanical ventilation, or inpatient death), hospital admission, emergency department or urgent care visits, and in-person outpatient encounters with odds ratios from logistic regression models adjusted for demographic and clinical factors. We stratified vaccine effectiveness estimates for hospital admission, emergency department or urgent care visits, and outpatient encounters by omicron sublineage (ie, likely BA.4/5-related vs likely XBB-related), time since bivalent booster receipt, age group, number of wild-type doses received, and immunocompromised status. This study is registered with ClinicalTrials.gov (NCT04848584). FINDINGS: Analyses were conducted for 123 419 encounters (24 246 COVID-19 cases and 99 173 test-negative controls), including 4131 episode of critical illness (a subset of hospital admissions), 14 529 hospital admissions, 63 566 emergency department or urgent care visits, and 45 324 outpatient visits. 20 555 infections were BA.4/5 related and 3691 were XBB related. In adjusted analyses, relative vaccine effectiveness for those who received the BNT162b2 BA.4/5 bivalent booster compared with those who received at least two doses of a wild-type mRNA vaccine alone was an additional 50% (95% CI 23-68) against critical illness, an additional 39% (28-49) against hospital admission, an additional 35% (30-40) against emergency department or urgent care visits, and an additional 28% (22-33) against outpatient encounters. Waning of the bivalent booster from 0-3 months to 4-7 months after vaccination was evident for outpatient outcomes but was not detected for critical illness, hospital admission, and emergency department or urgent care outcomes. The relative effectiveness of the BNT162b2 BA.4/5 bivalent booster for XBB-related infections compared with BA.4/5-related infections was 56% (95% CI 12-78) versus 40% (27-50) for hospital admission; 34% (21-45) versus 36% (30-41) against emergency department or urgent care visits; and 29% (19-38) versus 27% (20-33) for outpatient encounters. INTERPRETATION: By mid-April, 2023, individuals previously vaccinated only with wild-type vaccines had little protection against COVID-19-including hospital admission. A BNT162b2 BA.4/5 bivalent booster restored protection against a range of COVID-19 outcomes, including against XBB-related sublineages, with the most substantial protection observed against hospital admission and critical illness. FUNDING: Pfizer.

First evidence of tick-borne encephalitis (TBE) outside of Hokkaido Island in Japan.

Tick-borne encephalitis (TBE) is an infection of the central nervous system caused by the tick-borne encephalitis virus (TBEV). TBE is endemic in parts of Europe and Asia. TBEV is transmitted to humans primarily by Ixodes ticks. There have been 5 TBE cases identified in Japan, all on the northern island of Hokkaido. Rodents with TBEV antibodies and Ixodes ticks have been identified throughout Japan, indicating that TBEV infection might be undiagnosed in Japan. Residual serum and cerebrospinal fluid (CSF) collected in 2010-2021 from 520 patients ≥1 year-of-age previously hospitalized with encephalitis or meningitis of unknown etiology at 15 hospitals (including 13 hospitals outside of Hokkaido) were screened by ELISA for TBEV IgG and IgM antibodies; TBEV infection was confirmed by the gold standard neutralization test. Residual serum was available from 331 (63.6%) patients and CSF from 430 (82.6%) patients; both serum and CSF were available from 189 (36.3%). Two patients were TBE cases: a female aged 61 years hospitalized for 104 days in Oita (2000 km south of Hokkaido) and a male aged 24 years hospitalized for 11 days in Tokyo (1200 km south of Hokkaido). Retrospective testing also identified a previous TBEV infection in a female aged 45 years hospitalized for 12 days in Okayama (1700 km south of Hokkaido). TBEV infection should be considered as a potential cause of encephalitis or meningitis in Japan. TBE cases are likely undiagnosed in Japan, including outside of Hokkaido, due to limited clinical awareness and lack of availability of TBE diagnostic tests.

Risk of subsequent lower respiratory tract infection (LRTI) after hospitalization for COVID-19 LRTI and non-COVID-19 LRTI: a retrospective cohort study.

BACKGROUND: Respiratory pathogens, including SARS-CoV-2, can cause pulmonary structural damage and physiologic impairment, which may increase the risk of subsequent lower respiratory tract infections (LRTI). Prior hospitalization for any reason is a risk factor for LRTI, but data on the risk of subsequent new-onset LRTI following hospitalization for COVID-19 LRTI or non-COVID-19 LRTI are needed to inform strategies for immunizations targeting respiratory pathogens. METHODS: We conducted a retrospective cohort study at Kaiser Permanente Southern California (KPSC) among adults hospitalized from 3/1/2020 to 5/31/2022, excluding labor and delivery. We categorized individuals into 3 mutually exclusive baseline exposure groups: those hospitalized for COVID-19 LRTI, those hospitalized for non-COVID-19 LRTI, and those hospitalized for all other causes without LRTI or COVID-19 ("non-LRTI"). Following hospital discharge, patients were followed up for new-onset LRTI, beginning 30 antibiotic-free days after hospital discharge until 8/31/2022. We used multivariable cause-specific Cox regression with time-varying covariates to estimate hazard ratios (HR) of new-onset LRTI comparing those hospitalized for COVID-19 LRTI or non-COVID-19 LRTI to those hospitalized for non-LRTI, adjusting for demographic and clinical characteristics. RESULTS: The study included 22,417 individuals hospitalized for COVID-19 LRTI, 12,795 individuals hospitalized for non-COVID-19 LRTI, and 176,788 individuals hospitalized for non-LRTI. Individuals hospitalized for non-COVID-19 LRTI were older and had more comorbidities than those hospitalized for COVID-19 LRTI or non-LRTI. Incidence rates per 1,000 person-years (95% CI) of new-onset LRTI were 52.5 (51.4-53.6) among individuals hospitalized for COVID-19 LRTI, 253.5 (243.7-263.6) among those hospitalized for non-COVID-19 LRTI, and 52.5 (51.4-53.6) among those hospitalized for non-LRTI. The adjusted hazard of new-onset LRTI during follow-up was 20% higher among individuals hospitalized for COVID-19 LRTI (HR 1.20 [95% CI: 1.12-1.28]) and 301% higher among individuals hospitalized for non-COVID-19 LRTI (HR 3.01 [95% CI: 2.87-3.15]) compared to those hospitalized for non-LRTI. CONCLUSION: The risk of new-onset LRTI following hospital discharge was high, particularly among those hospitalized for non-COVID-19 LRTI, but also for COVID-19 LRTI. These data suggest that immunizations targeting respiratory pathogens, including COVID-19, should be considered for adults hospitalized for LRTI prior to hospital discharge.

Real-world impact and effectiveness of MenACWY-TT.

In response to escalating cases of serogroup W (MenW) invasive meningococcal disease (IMD), multiple countries introduced quadrivalent conjugate MenACWY vaccines into their national immunization programs (NIPs). Here, we summarize the real-world impact and vaccine effectiveness (VE) data of MenACWY-TT from Chile, England, the Netherlands, and Australia. Incidence rate reductions (IRRs) and VE from baseline to post-NIP period were extracted from publications or calculated. After the administration of a single dose of MenACWY-TT, substantial IRRs of MenCWY were observed across the countries in vaccine-eligible age groups (83%-85%) and via indirect protection in non-vaccine-eligible age groups (45%-53%). The impact of MenACWY-TT was primarily driven by MenW IRRs, as seen in vaccine-eligible age groups (65%-92%) and non-vaccine-eligible age groups (41%-57%). VE against MenW was reported in vaccine-eligible toddlers (92%) in the Netherlands and in vaccine-eligible adolescents/young adults (94%) in England. These real-world data support the implementation and continued use of MenACWY-TT in NIPs.

Receipt of BNT162b2 Vaccine and COVID-19 Ambulatory Visits in US Children Younger Than 5 Years.

This study examines the association of the receipt of wild-type BNT162b2 vaccine with medically attended COVID-19 outcomes among children younger than 5 years in the US.

Validation of Claims-Based Algorithm for Lyme Disease, Massachusetts, USA.

Compared with notifiable disease surveillance, claims-based algorithms estimate higher Lyme disease incidence, but their accuracy is unknown. We applied a previously developed Lyme disease algorithm (diagnosis code plus antimicrobial drug prescription dispensing within 30 days) to an administrative claims database in Massachusetts, USA, to identify a Lyme disease cohort during July 2000-June 2019. Clinicians reviewed and adjudicated medical charts from a cohort subset by using national surveillance case definitions. We calculated positive predictive values (PPVs). We identified 12,229 Lyme disease episodes in the claims database and reviewed and adjudicated 128 medical charts. The algorithm's PPV for confirmed, probable, or suspected cases was 93.8% (95% CI 88.1%-97.3%); the PPV was 66.4% (95% CI 57.5%-74.5%) for confirmed and probable cases only. In a high incidence setting, a claims-based algorithm identified cases with a high PPV, suggesting it can be used to assess Lyme disease burden and supplement traditional surveillance data.

Immunogenicity and safety of a pentavalent meningococcal ABCWY vaccine in adolescents and young adults: an observer-blind, active-controlled, randomised trial.

BACKGROUND: Meningococcal serogroups A, B, C, W, and Y cause nearly all meningococcal disease, and comprehensive protection requires vaccination against all five serogroups. We aimed to assess the immunogenicity and safety of a pentavalent MenABCWY vaccine comprising two licensed vaccines-meningococcal serogroup B-factor H binding protein vaccine (MenB-FHbp) and a quadrivalent meningococcal serogroup ACWY tetanus toxoid conjugate vaccine (MenACWY-TT)-compared with two doses of MenB-FHbp and a single dose of quadrivalent meningococcal serogroup ACWY CRM197-conjugate vaccine (MenACWY-CRM) as the active control. We previously reported the primary safety and immunogenicity data relating to the two-dose MenB-FHbp schedule. Here we report secondary outcomes and ad-hoc analyses relating to MenABCWY immunogenicity and safety. METHODS: We did an observer-blind, active-controlled trial at 68 sites in the USA, Czech Republic, Finland, and Poland. Healthy individuals (aged 10-25 years) who had or had not previously received a MenACWY vaccine were randomly assigned (1:2) using an interactive voice or web-based response system, stratified by previous receipt of a MenACWY vaccine, to receive 0·5 mL of MenABCWY (months 0 and 6) and placebo (month 0) or MenB-FHbp (months 0 and 6) and MenACWY-CRM (month 0) via intramuscular injection into the upper deltoid. All individuals were masked to group allocation, except staff involved in vaccine dispensation, preparation, and administration; and protocol adherence. Endpoints for serogroups A, C, W, and Y included the proportion of participants who achieved at least a four-fold increase in serum bactericidal antibody using human complement (hSBA) titres between baseline and 1 month after each vaccination. For serogroup B, secondary endpoints included the proportion of participants who achieved at least a four-fold increase in hSBA titres from baseline for each of four primary test strains and the proportion of participants who achieved titres of at least the lower limit of quantitation against all four test strains combined at 1 month after the second dose. Endpoints for serogroups A, C, W, and Y were assessed in the modified intent-to-treat (mITT) population, which included all randomly assigned participants who received at least one vaccine dose and had at least one valid and determinate MenB or serogroup A, C, W, or Y assay result before vaccination up to 1 month after the second dose, assessed in ACWY-experienced and ACWY-naive participants separately. Secondary endpoints for serogroup B were analysed in the evaluable immunogenicity population, which included all participants in the mITT population who were randomly assigned to the group of interest, received all investigational products as randomly assigned, had blood drawn for assay testing within the required time frames, had at least one valid and determinate MenB assay result after the second vaccination, and had no important protocol deviations; outcomes were assessed in both ACWY-experienced and ACWY-naive populations combined. Non-inferiority of MenABCWY to MenACWY-CRM and MenB-FHbp was determined using a -10% non-inferiority margin for these endpoints. Reactogenicity and adverse events were assessed among all participants who received at least one vaccine dose and who had available safety data. This trial is registered with Clinicaltrials.gov, NCT03135834, and is complete. FINDINGS: Between April 24 and November 10, 2017, 1610 participants (809 MenACWY-naive; 801 MenACWY-experienced) were randomly assigned: 544 to receive MenABCWY and placebo (n=272 MenACWY-naive; n=272 MenACWY-experienced) and 1066 to receive MenB-FHbp and MenACWY-CRM (n=537 MenACWY-naive; n=529 MenACWY-experienced). Among MenACWY-naive or MenACWY-experienced MenABCWY recipients, 75·5% (95% CI 69·8-80·6; 194 of 257; serogroup C) to 96·9% (94·1-98·7; 254 of 262; serogroup A) and 93·0% (88·4-96·2; 174 of 187; serogroup Y) to 97·4% (94·4-99·0; 224 of 230; serogroup W) achieved at least four-fold increases in hSBA titres against serogroups ACWY after dose 1 or 2, respectively, in ad-hoc analyses. Additionally, 75·8% (71·5-79·8; 320 of 422) to 94·7% (92·1-96·7; 396 of 418) of MenABCWY and 67·4% (64·1-70·6; 563 of 835) to 95·0% (93·3-96·4; 782 of 823) of MenB-FHbp recipients achieved at least four-fold increases in hSBA titres against MenB strains after dose 2 in secondary analyses; 79·9% (334 of 418; 75·7-83·6) and 74·3% (71·2-77·3; 605 of 814), respectively, achieved composite responses. MenABCWY was non-inferior to MenACWY-CRM (single dose) and to MenB-FHbp in ad-hoc analyses based on the proportion of participants with at least a four-fold increase in hSBA titres from baseline and (for MenB-FHbp only) composite responses. Reactogenicity events after vaccination were similarly frequent across groups, were mostly mild or moderate, and were unaffected by MenACWY experience. No adverse events causing withdrawals were related to the investigational product. Serious adverse events were reported in four (1·5%; 0·4-3·7) MenACWY-naive individuals in the MenABCWY group versus six (2·2%; 0·8-4·8) among MenACWY-experienced individuals in the MenABCWY group and 14 (1·3%; 0·7-2·2) in the active control group (MenACWY-experienced and MenACWY-naive individuals combined); none of these were considered related to the investigational product. INTERPRETATION: MenABCWY immune responses were robust and non-inferior to MenACWY-CRM and MenB-FHbp administered separately, and MenABCWY was well tolerated. The favourable benefit-risk profile supports further MenABCWY evaluation as a simplified schedule compared with current adolescent meningococcal vaccination programmes. FUNDING: Pfizer.

Distribution of serotypes causing invasive pneumococcal disease in older adults from high-income countries and impact of pediatric and adult vaccination policies.

BACKGROUND: Neither indirect protection through use of 13-valent and 10-valent pneumococcal conjugate vaccines (PCV13 and PCV10) in pediatric National Immunization Programs (NIPs) nor direct vaccination with the 23-valent polysaccharide vaccine have eliminated vaccine serotype invasive pneumococcal disease (IPD) in older adults. Vaccinating older adults with higher-valency PCV15 and PCV20 could address remaining IPD due to pediatric PCV serotypes plus additional IPD due to serotypes included in these vaccines. METHODS: We collected serotype-specific IPD data in older adults (≥65 years in most countries), from national or regional surveillance systems or hospital networks of 33 high-income countries. Data were from official government websites, online databases, surveillance system reports, published literature, and personal communication with in-country investigators. Average percentages of IPD serotypes were calculated. RESULTS: Among 52,905 cases of IPD with a serotype identified, PCV13 serotypes accounted for 33.7% of IPD (55.8% and 30.6% for countries with PCV10 and PCV13 in the pediatric NIP), most commonly serotypes 3 (14.9%) and 19A (7.0%). PCV15 and PCV20 would cover an additional 10.4% and 32.9% of older adult IPD beyond PCV13 serotypes (PCV10 countries: 7.7% and 23.3%; PCV13 countries: 10.6% and 34.6%). The most common of these additional serotypes were 8 (9.9%), 22F (7.9%), 12F (4.6%), and 11A (3.3%). PPSV23 policies for older adults were not correlated with lower IPD percentages due to PPSV23 serotypes. CONCLUSIONS: Vaccinating older adults with higher-valency PCVs, especially PCV20, could substantially reduce the remaining IPD burden in high-income countries, regardless of current PCV use in pediatric NIPs and adult PPSV23 policies.

Impact of SARS-CoV-2 infective exacerbation of chronic obstructive pulmonary disease on clinical outcomes in a prospective cohort study of hospitalised adults.

OBJECTIVES: To determine whether acute exacerbations of chronic obstructive pulmonary disease (AECOPD) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have worse outcomes than AECOPD caused by other infectious agents or non-infective AECOPD (NI-COPD). DESIGN: A two-hospital prospective cohort study of adults hospitalised with acute respiratory disease. We compared outcomes with AECOPD and a positive test for SARS-CoV-2 (n = 816), AECOPD triggered by other infections (n = 3038) and NI-COPD (n = 994). We used multivariable modelling to adjust for potential confounders and assessed variation by seasons associated with different SARS-CoV-2 variants. SETTING: Bristol UK, August 2020-May 2022. PARTICIPANTS: Adults (≥18 y) hospitalised with AECOPD. MAIN OUTCOME MEASURES: We determined the risk of positive pressure support, longer hospital admission and mortality following hospitalisation with AECOPD due to non-SARS-CoV-2 infection compared with SARS-CoV-2 AECOPD and NI-COPD. RESULTS: Patients with SARS-CoV-2 AECOPD, in comparison to non-SARS-CoV-2 infective AECOPD or NI-COPD, more frequently required positive pressure support (18.5% and 7.5% vs. 11.7%, respectively), longer hospital stays (median [interquartile range, IQR]: 7 [3-15] and 5 [2-10] vs. 4 [2-9] days, respectively) and had higher 30-day mortality (16.9% and 11.1% vs. 5.9%, respectively) (all p < 0.001). In adjusted analyses, SARS-CoV-2 AECOPD was associated with a 55% (95% confidence interval [95% CI]: 24-93), 26% (95% CI: 15-37) and 35% (95% CI: 10-65) increase in the risk of positive pressure support, hospitalisation length and 30-day mortality, respectively, relative to non-SARS-CoV-2 infective AECOPD. The difference in risk remained similar during periods of wild-type, Alpha and Delta SARS-CoV-2 strain dominance, but diminished during Omicron dominance. CONCLUSIONS: SARS-CoV-2-related AECOPD had worse patient outcomes compared with non-SARS-CoV-2 AECOPD or NI-AECOPD, although the difference in risks was less pronounced during Omicron dominance.

Effectiveness of tick-borne encephalitis vaccination in Latvia, 2018-2020: an observational study.

OBJECTIVES: Tick-borne encephalitis (TBE) is an infection by the tick-borne encephalitis virus (TBEV) that results in symptoms of central nervous system inflammation. TBE is endemic in Latvia and other European countries. TBE vaccines are commonly used in Latvia, but vaccine effectiveness estimates are limited. METHODS: Study staff at Riga Stradins University conducted nationwide active surveillance for TBEV infections. Serum and cerebrospinal fluid were ELISA-tested for TBEV-specific IgG and IgM antibodies. Vaccination history was collected by interview and medical record review. Utilizing data from surveillance and population surveys, vaccine effectiveness (with 95% CIs) and cases averted were estimated using the screening method. RESULTS: There were 587 laboratory-identified TBE cases from 2018 to 2020; 98.1% (576/587) were unvaccinated, 1.5% (9/587) were unknown or partially vaccinated, and 0.3% (2/587) were fully vaccinated (three-dose primary series and appropriately timed boosters). TBE resulted in the death of 1.7% (10/587) of TBE cases. TBE vaccine history was ascertained from 92.0% (13 247/14 399) people from the general population: 38.6% (5113/13 247) were unvaccinated, 26.3% (3484/13 247) were fully vaccinated, and 35.1% (4650/13 247) were partially vaccinated. TBE vaccine effectiveness was 99.5% (98.0-99.9) against TBE, 99.5% (97.9-99.9) against TBE hospitalization, 99.3% (94.8-99.9) against moderate/severe TBE, and 99.2% (94.4-99.9) against TBE hospitalization >12 days. From 2018 to 2020, vaccination averted 906 TBE cases, including 20 deaths. DISCUSSION: TBE vaccine was highly effective in preventing TBE, moderate and severe disease, and prolonged hospitalization. To prevent life-threatening TBE, TBE vaccine uptake and compliance should be increased in Latvia and other European regions where TBE is endemic.

Effectiveness of Tick-borne Encephalitis Vaccines in Children, Latvia, 2018-2020.

BACKGROUND: Tick-borne encephalitis (TBE) is an infection by the tick-borne encephalitis virus (TBEV) with symptoms of central nervous system inflammation. TBE is endemic in Latvia and other parts of Europe. TBE vaccination is recommended for children in Latvia. TBE vaccine effectiveness (VE) was estimated in Latvia, a country with high TBE incidence, providing the first VE estimates against a range of TBEV infection outcomes in children 1-15 years-of-age. METHODS: Riga Stradins University conducted nationwide surveillance for suspected TBE cases. Serum and cerebrospinal fluid were ELISA tested for TBEV-specific IgG and IgM antibodies. A fully vaccinated child was an individual who had received the 3-dose primary series and appropriately timed boosters. The proportion of laboratory-confirmed TBE cases fully vaccinated (PCV) was determined from interviews and medical records. The proportion of the general population fully vaccinated (PPV) was determined from national surveys conducted in 2019 and 2020. TBE VE in children 1-15 years-of-age was estimated using the screening method: VE = 1 - [PCV/(1 - PCV)/PPV/(1 - PPV)]. RESULTS: From 2018 to 2020, surveillance identified 36 TBE cases in children 1-15 years-of-age; all were hospitalized, 5 (13.9%) for >12 days. Of the TBE cases, 94.4% (34/36) were unvaccinated compared with 43.8% of children in the general population. VE against TBE hospitalization in children 1-15 years-of-age was 94.9% (95% confidence interval 63.1-99.3). In 2018-2020, vaccination in children 1-15 years-of-age averted 39 hospitalized TBE cases. CONCLUSION: Pediatric TBE vaccines were highly effective in preventing TBE in children. Increasing TBE vaccine uptake in children is essential to maximize the public health impact of TBE vaccination.