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.

Effectiveness of Pneumococcal Conjugate Vaccination Against Virus-Associated Lower Respiratory Tract Infection Among Adults: A Case-Control Study.

BACKGROUND: Interactions of Streptococcus pneumoniae with viruses feature in the pathogenesis of numerous respiratory illnesses. METHODS: We undertook a case-control study among adults at Kaiser Permanente Southern California between 2015 and 2019. Case patients had diagnoses of lower respiratory tract infection (LRTI; including pneumonia or nonpneumonia LRTI diagnoses), with viral infections detected by multiplex polymerase chain reaction testing. Controls without LRTI diagnoses were matched to case patients by demographic and clinical attributes. We measured vaccine effectiveness (VE) for 13-valent (PCV13) against virus-associated LRTI by determining the adjusted odds ratio for PCV13 receipt, comparing case patients and controls. RESULTS: Primary analyses included 13 856 case patients with virus-associated LRTI and 227 887 matched controls. Receipt of PCV13 was associated with a VE of 24.9% (95% confidence interval, 18.4%-30.9%) against virus-associated pneumonia and 21.5% (10.9%-30.9%) against other (nonpneumonia) virus-associated LRTIs. We estimated VEs of 26.8% (95% confidence interval, 19.9%-33.1%) and 18.6% (9.3%-27.0%) against all virus-associated LRTI episodes diagnosed in inpatient and outpatient settings, respectively. We identified statistically significant protection against LRTI episodes associated with influenza A and B viruses, endemic human coronaviruses, parainfluenza viruses, human metapneumovirus, and enteroviruses but not respiratory syncytial virus or adenoviruses. CONCLUSIONS: Among adults, PCV13 conferred moderate protection against virus-associated LRTI. The impacts of pneumococcal conjugate vaccines may be mediated, in part, by effects on polymicrobial interactions between pneumococci and respiratory viruses.

Distribution of Serotypes Causing Invasive Pneumococcal Disease in Children From High-Income Countries and the Impact of Pediatric Pneumococcal Vaccination.

BACKGROUND: The introduction and adoption of pneumococcal conjugate vaccines (PCVs) into pediatric national immunization programs (NIPs) has led to large decreases in invasive pneumococcal disease (IPD) incidence caused by vaccine serotypes. Despite these reductions, the global IPD burden in children remains significant. METHODS: We collected serotype-specific IPD data from surveillance systems or hospital networks of all 30 high-income countries that met inclusion criteria. Data sources included online databases, surveillance system reports, and peer-reviewed literature. Percentage of serotyped cases covered were calculated for all countries combined and by PCV type in the pediatric NIP. RESULTS: We identified 8012 serotyped IPD cases in children <5 or ≤5 years old. PCV13 serotype IPD caused 37.4% of total IPD cases, including 57.1% and 25.2% for countries with PCV10 or PCV13 in the pediatric NIP, respectively, most commonly due to serotypes 3 and 19A (11.4% and 13.3%, respectively, across all countries). In PCV10 countries, PCV15 and PCV20 would cover an additional 45.1% and 55.6% of IPD beyond serotypes contained in PCV10, largely due to coverage of serotype 19A. In PCV13 countries, PCV15 and PCV20 would cover an additional 10.6% and 38.2% of IPD beyond serotypes contained in PCV13. The most common IPD serotypes covered by higher valency PCVs were 10A (5.2%), 12F (5.1%), and 22F and 33F (3.5% each). CONCLUSIONS: Much of the remaining IPD burden is due to serotypes included in PCV15 and PCV20. The inclusion of these next generation PCVs into existing pediatric NIPs may further reduce the incidence of childhood IPD.

Burden of Lower Respiratory Tract Infections Preventable by Adult Immunization With 15- and 20-Valent Pneumococcal Conjugate Vaccines in the United States.

BACKGROUND: Updated recommendations of the US Advisory Committee on Immunization Practices indicate that all adults aged ≥65 years and adults aged <65 years with comorbid conditions should receive 15- and 20-valent pneumococcal conjugate vaccines (PCV15/20). We aimed to assess the potential impact of these recommendations on the burden of lower respiratory tract infections (LRTIs) among adults. METHODS: We estimated the incidence of LRTI cases and associated hospital admissions among enrollees of Kaiser Permanente Southern California from 2016 through 2019. We used a counterfactual inference framework to estimate excess LRTI-associated risk of death up to 180 days after diagnosis. We used prior estimates of PCV13 effectiveness against LRTI to model potential direct effects of PCV15/20 by age group and risk status. RESULTS: Use of PCV15 and PCV20, respectively, could prevent 89.3 (95% confidence interval, 41.3-131.8) and 108.6 (50.4-159.1) medically attended LRTI cases; 21.9 (10.1-32.0) and 26.6 (12.4-38.7) hospitalized LRTI cases; and 7.1 (3.3-10.5) and 8.7 (4.0-12.7) excess LRTI-associated deaths, each per 10 000 person-years. Among at-risk adults aged <65 years, use of PCV15 and PCV20 could prevent 85.7 (39.6-131.5) and 102.7 (47.8-156.7) medically attended LRTI cases per 10 000 person-years; 5.1 (2.4-8.6) and 6.2 (2.8-10.2) LRTI hospitalizations per 10 000 person-years, and 0.9 (0.4-1.4) and 1.1 (0.5-1.7) excess LRTI-associated deaths per 10 000 person-years. CONCLUSIONS: Our findings suggest recent recommendations, including PCV15/20 within adult pneumococcal vaccine series, may substantially reduce LRTI burden.

Frequency-dependent selection can forecast evolution in Streptococcus pneumoniae.

Predicting how pathogen populations will change over time is challenging. Such has been the case with Streptococcus pneumoniae, an important human pathogen, and the pneumococcal conjugate vaccines (PCVs), which target only a fraction of the strains in the population. Here, we use the frequencies of accessory genes to predict changes in the pneumococcal population after vaccination, hypothesizing that these frequencies reflect negative frequency-dependent selection (NFDS) on the gene products. We find that the standardized predicted fitness of a strain, estimated by an NFDS-based model at the time the vaccine is introduced, enables us to predict whether the strain increases or decreases in prevalence following vaccination. Further, we are able to forecast the equilibrium post-vaccine population composition and assess the invasion capacity of emerging lineages. Overall, we provide a method for predicting the impact of an intervention on pneumococcal populations with potential application to other bacterial pathogens in which NFDS is a driving force.

Prevention of Coronavirus Disease 2019 Among Older Adults Receiving Pneumococcal Conjugate Vaccine Suggests Interactions Between Streptococcus pneumoniae and Severe Acute Respiratory Syndrome Coronavirus 2 in the Respiratory Tract.

BACKGROUND: While secondary pneumococcal pneumonia occurs less commonly after coronavirus disease 2019 (COVID-19) than after other viral infections, it remains unclear whether other interactions occur between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Streptococcus pneumoniae. METHODS: We probed potential interactions between these pathogens among adults aged ≥65 years by measuring associations of COVID-19 outcomes with pneumococcal vaccination (13-valent conjugate vaccine [PCV13] and 23-valent pneumococcal polysaccharide vaccine [PPSV23]). We estimated adjusted hazard ratios (aHRs) using Cox proportional hazards models with doubly robust inverse-propensity weighting. We assessed effect modification by antibiotic exposure to further test the biologic plausibility of a causal role for pneumococci. RESULTS: Among 531 033 adults, there were 3677 COVID-19 diagnoses, leading to 1075 hospitalizations and 334 fatalities, between 1 March and 22 July 2020. Estimated aHRs for COVID-19 diagnosis, hospitalization, and mortality associated with prior PCV13 receipt were 0.65 (95% confidence interval [CI], .59-.72), 0.68 (95% CI, .57-.83), and 0.68 (95% CI, .49-.95), respectively. Prior PPSV23 receipt was not associated with protection against the 3 outcomes. COVID-19 diagnosis was not associated with prior PCV13 within 90 days following antibiotic receipt, whereas aHR estimates were 0.65 (95% CI, .50-.84) and 0.62 (95% CI, .56-.70) during the risk periods 91-365 days and >365 days, respectively, following antibiotic receipt. CONCLUSIONS: Reduced risk of COVID-19 among PCV13 recipients, transiently attenuated by antibiotic exposure, suggests that pneumococci may interact with SARS-CoV-2.

Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Medically Attended Lower Respiratory Tract Infection and Pneumonia Among Older Adults.

BACKGROUND: Among older adults, 13-valent pneumococcal conjugate vaccine (PCV13) has been found efficacious against nonbacteremic pneumonia associated with vaccine-serotype pneumococci. However, the burden of lower respiratory tract infection (LRTI) and pneumonia preventable by direct immunization of older adults continues to be debated. METHODS: We analyzed data from an open cohort of adults aged ≥65 years enrolled in Kaiser Permanente Southern California health plans from 2016 to 2019 who received PCV13 concordant with US Advisory Committee on Immunization Practices guidelines. We estimated PCV13 vaccine effectiveness (VE) via the adjusted hazard ratio for first LRTI and pneumonia episodes during each respiratory season, comparing PCV13-exposed and PCV13-unexposed time at risk for each participant using a self-matched inference framework. Analyses used Cox proportional hazards models, stratified by individual. RESULTS: Among 42 700 adults who met inclusion criteria, VE was 9.5% (95% confidence interval [CI], 2.2% to 16.3%) against all-cause medically attended LRTI and 8.8% (95% CI, -.2% to 17.0%) against all-cause medically attended pneumonia. In contrast, we did not identify evidence of protection against LRTI and pneumonia following receipt of the 23-valent pneumococcal polysaccharide vaccine. PCV13 prevented 0.7 (95% CI, .2 to 1.4) and 0.5 (95% CI, .0 to 1.0) cases of LRTI and pneumonia, respectively, per 100 vaccinated persons annually; over 5 years, 1 case of LRTI and 1 case of pneumonia were prevented for every 27 and 42 individuals vaccinated, respectively. CONCLUSIONS: PCV13 vaccination among older adults substantially reduced incidence of medically attended respiratory illness. Direct immunization of older adults is an effective strategy to combat residual disease burden associated with PCV13-type pneumococci.

Expanded Analysis of 20 Pneumococcal Serotypes Associated With Radiographically Confirmed Community-acquired Pneumonia in Hospitalized US Adults.

BACKGROUND: Streptococcus pneumoniae is a causative agent of community-acquired pneumonia (CAP). The 13-valent pneumococcal conjugate vaccine (PCV13) has significantly decreased the burden of PCV13-serotype pneumococcal disease; however, disease from nonvaccine serotypes remains substantial. A recent study documented the persistence of PCV13 serotypes among US adults hospitalized with radiographically confirmed CAP. The current analysis used a recently developed urinary antigen detection (UAD) assay (UAD2) to extend these results to additional serotypes included in an investigational PCV20 vaccine. METHODS: This prospective study enrolled adults aged ≥18 years hospitalized with radiographically confirmed CAP between October 2013 and September 2016. Presence of S pneumoniae was determined by blood and respiratory sample culture, BinaxNOW urine testing, and UAD. In addition to Quellung on cultured isolates when available, serotypes were identified from urine specimens using UAD1 for PCV13 serotypes and UAD2 for 7 PCV20-unique serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) and 4 additional serotypes (2, 9N, 17F, and 20). RESULTS: Among 12 055 subjects with radiographically confirmed CAP, 1482 were positive for S pneumoniae. PCV13- and PCV20-unique serotypes were associated with 37.7% (n = 559) and 27.0% (n = 400) of cases, respectively; 288 subjects were exclusively diagnosed as positive for S pneumoniae by UAD2. Demographic and clinical disease characteristics were similar between subjects with CAP caused by PCV13 and PCV20-unique serotypes. CONCLUSIONS: The current analysis using UAD2 identified a sizeable proportion of hospitalized adult CAP associated with PCV20-unique serotypes. PCV20 may therefore address the burden of CAP caused by the additional serotypes present in the vaccine.

The impact of serotype-specific vaccination on phylodynamic parameters of Streptococcus pneumoniae and the pneumococcal pan-genome.

In the United States, the introduction of the heptavalent pneumococcal conjugate vaccine (PCV) largely eliminated vaccine serotypes (VT); non-vaccine serotypes (NVT) subsequently increased in carriage and disease. Vaccination also disrupts the composition of the pneumococcal pangenome, which includes mobile genetic elements and polymorphic non-capsular antigens important for virulence, transmission, and pneumococcal ecology. Antigenic proteins are of interest for future vaccines; yet, little is known about how the they are affected by PCV use. To investigate the evolutionary impact of vaccination, we assessed recombination, evolution, and pathogen demographic history of 937 pneumococci collected from 1998-2012 among Navajo and White Mountain Apache Native American communities. We analyzed changes in the pneumococcal pangenome, focusing on metabolic loci and 19 polymorphic protein antigens. We found the impact of PCV on the pneumococcal population could be observed in reduced diversity, a smaller pangenome, and changing frequencies of accessory clusters of orthologous groups (COGs). Post-PCV7, diversity rebounded through clonal expansion of NVT lineages and inferred in-migration of two previously unobserved lineages. Accessory COGs frequencies trended toward pre-PCV7 values with increasing time since vaccine introduction. Contemporary frequencies of protein antigen variants are better predicted by pre-PCV7 values (1998-2000) than the preceding period (2006-2008), suggesting balancing selection may have acted in maintaining variant frequencies in this population. Overall, we present the largest genomic analysis of pneumococcal carriage in the United States to date, which includes a snapshot of a true vaccine-naïve community prior to the introduction of PCV7. These data improve our understanding of pneumococcal evolution and emphasize the need to consider pangenome composition when inferring the impact of vaccination and developing future protein-based pneumococcal vaccines.

Association of Laboratory Methods, Colonization Density, and Age With Detection of Streptococcus pneumoniae in the Nasopharynx.

Culture-based methods for detecting Streptococcus pneumoniae in the nasopharynx lack sensitivity. In this study, we aimed to compare the performance of culture and molecular methods in detecting pneumococcus in the nasopharynx of healthy individuals and to evaluate the associations of age and colonization density with detection. Between 2010 and 2012, nasopharyngeal specimens were collected from healthy individuals living on Navajo Nation and White Mountain Apache Tribal lands in the United States. Pneumococci were detected by means of broth-enrichment culture and autolysin-encoding gene (lytA) quantitative polymerase chain reaction (qPCR). Among 982 persons evaluated (median age, 18.7 years; 47% male), 35% were culture-positive and an additional 27% were qPCR-positive. Agreement between culture and qPCR was 70.9% but was higher among children (age <18 years) (75.9%-84.4%) than among adults (age ≥18 years) (61.0%-74.6%). The mean density of colonization was lower for culture-negative samples (3.14 log10 copies/mL) than for culture-positive samples (5.02 log10 copies/mL), overall and for all age groups. The percent culture-positive increased with increasing density, exceeding 80% at densities of ≥10,000 copies/mL. Mean colonization density decreased with age. Use of qPCR improved detection of pneumococcus in the nasopharynx of healthy individuals. This finding was most notable among adults, probably because of improved detection of low-density colonization.

Second Generation Small Pixel Technology Using Hybrid Bond Stacking.

In this work, OmniVision's second generation (Gen2) of small-pixel BSI stacking technologies is reviewed. The key features of this technology are hybrid-bond stacking, deeper back-side, deep-trench isolation, new back-side composite metal-oxide grid, and improved gate oxide quality. This Gen2 technology achieves state-of-the-art low-light image-sensor performance for 1.1, 1.0, and 0.9 µm pixel products. Additional improvements on this technology include less than 100 ppm white-pixel process and a high near-infrared (NIR) QE technology.

Association of Pneumococcal Protein Antigen Serology With Age and Antigenic Profile of Colonizing Isolates.

Background: Several Streptococcus pneumoniae proteins play a role in pathogenesis and are being investigated as vaccine targets. It is largely unknown whether naturally acquired antibodies reduce the risk of colonization with strains expressing a particular antigenic variant. Methods: Serum immunoglobulin G (IgG) titers to 28 pneumococcal protein antigens were measured among 242 individuals aged <6 months-78 years in Native American communities between 2007 and 2009. Nasopharyngeal swabs were collected >- 30 days after serum collection, and the antigen variant in each pneumococcal isolate was determined using genomic data. We assessed the association between preexisting variant-specific antibody titers and subsequent carriage of pneumococcus expressing a particular antigen variant. Results: Antibody titers often increased across pediatric groups before decreasing among adults. Individuals with low titers against group 3 pneumococcal surface protein C (PspC) variants were more likely to be colonized with pneumococci expressing those variants. For other antigens, variant-specific IgG titers do not predict colonization. Conclusion: We observed an inverse association between variant-specific antibody concentration and homologous pneumococcal colonization for only 1 protein. Further assessment of antibody repertoires may elucidate the nature of antipneumococcal antibody-mediated mucosal immunity while informing vaccine development.

Relating Pneumococcal Carriage Among Children to Disease Rates Among Adults Before and After the Introduction of Conjugate Vaccines.

The use of pneumococcal conjugate vaccines (PCVs) in children has a strong indirect effect on disease rates in adults. When children are vaccinated with PCVs, other serotypes that are not targeted by the vaccine can increase in frequency (serotype replacement) and reduce the direct and indirect benefits of the vaccine. To understand and predict the likely impacts of serotype replacement, it is important to know how patterns in the transmission of serotypes among children relate to disease rates in adults. We used data on pneumococcal carriage and disease from Navajo Nation children and adults collected before and after the routine use of PCVs (1998-2012). Using regression models within a Bayesian framework, we found that serotype-specific carriage and invasiveness (disease incidence divided by carriage prevalence) had similar patterns in children and adults. Moreover, carriage in children, invasiveness in children, and a serotype-specific random intercept (which captured additional variation associated with the serotypes) could predict the incidence serotype-specific pneumococcal disease in adults 18-39 years of age and those 40 years of age or older in the era of routine use of PCVs. These models could help us predict the effects of future pneumococcal vaccine use in children on disease rates in adults, and the modeling approach developed here could be used to test these findings in other settings.

Electromagnetic interference from lasers and intense light sources in the treatment of patients with artificial pacemakers and other implantable cardiac devices.

Measurements of the electric and magnetic field strengths surrounding six laser systems and one intense pulsed light system were carried out. The results were compared to exposure limits published by cardiac device manufacturers to assess the risk of electromagnetic interference to implantable cardiac devices such as pacemakers or implantable cardioverter defibrillators. The majority of lasers assessed in this study were found to produce electric and magnetic field strengths below the published exposure limits for cardiac devices. However, the low-frequency electric field and static magnetic field of both the CO2 laser and the ruby laser were found to exceed these limits. Ensuring that a small separation is maintained at all times between the laser unit and any patient with a pacemaker or implantable cardioverter defibrillator appears to be a sensible expedient in avoiding overexposure of an implantable cardiac device to electromagnetic interference. Due to the single-shot fast discharge nature of the intense pulsed light system, changes in electromagnetic field strength were too fast for some of the measuring equipment used in this study to register accurate readings during operation.

Seasonal drivers of pneumococcal disease incidence: impact of bacterial carriage and viral activity.

BACKGROUND: Winter-seasonal epidemics of pneumococcal disease provide an opportunity to understand the drivers of incidence. We sought to determine whether seasonality of invasive pneumococcal disease is caused by increased nasopharyngeal transmission of the bacteria or increased susceptibility to invasive infections driven by cocirculating winter respiratory viruses. METHODS: We analyzed pneumococcal carriage and invasive disease data collected from children <7 years old in the Navajo/White Mountain Apache populations between 1996 and 2012. Regression models were used to quantify seasonal variations in carriage prevalence, carriage density, and disease incidence. We also fit a multivariate model to determine the contribution of carriage prevalence and RSV activity to pneumococcal disease incidence while controlling for shared seasonal factors. RESULTS: The seasonal patterns of invasive pneumococcal disease epidemics varied significantly by clinical presentation: bacteremic pneumococcal pneumonia incidence peaked in late winter, whereas invasive nonpneumonia pneumococcal incidence peaked in autumn. Pneumococcal carriage prevalence and density also varied seasonally, with peak prevalence occurring in late autumn. In a multivariate model, RSV activity was associated with significant increases in bacteremic pneumonia cases (attributable percentage, 15.5%; 95% confidence interval [CI], 1.8%-26.1%) but was not associated with invasive nonpneumonia infections (8.0%; 95% CI, -4.8% to 19.3%). In contrast, seasonal variations in carriage prevalence were associated with significant increases in invasive nonpneumonia infections (31.4%; 95% CI, 8.8%-51.4%) but not with bacteremic pneumonia. CONCLUSIONS: The seasonality of invasive pneumococcal pneumonia could be due to increased susceptibility to invasive infection triggered by viral pathogens, whereas seasonality of other invasive pneumococcal infections might be primarily driven by increased nasopharyngeal transmission of the bacteria.

Systematic review and meta-analysis of HIV prevalence among men in militaries in low income and middle income countries.

OBJECTIVES: To determine whether the current HIV prevalence in militaries of low-income and middle-income countries is higher, the same, or lower than the HIV prevalence in the adult male population of those countries. METHODS: HIV prevalence data from low-income and middle-income countries' military men were systematically reviewed during 2000-2012 from peer reviewed journals, clearing-house databases and the internet. Standardised data abstraction forms were used to collect information on HIV prevalence, military branch and sample size. Random effects meta-analyses were completed with the Mantel-Haenszel method comparing HIV prevalence among military populations with other men in each country. RESULTS: 2214 studies were retrieved, of which 18 studies representing nearly 150000 military men across 11 countries and 4 regions were included. Military male HIV prevalence across the studies ranged from 0.06% (n=22666) in India to 13.8% (n=2733) in Tanzania with a pooled prevalence of 1.1% (n=147591). HIV prevalence in male military populations in sub-Saharan Africa was significantly higher when compared with reproductive age (15-49 years) adult men (OR: 2.8, 95% CI 1.01 to 7.81). HIV prevalence in longer-serving male military populations compared with reproductive age adult men was significantly higher (OR: 2.68, 95% CI 1.65 to 4.35). CONCLUSIONS: Our data reveals that across the different settings, the burden of HIV among militaries may be higher or lower than the civilian male populations. In this study, male military populations in sub-Saharan Africa, low-income countries and longer-serving men have significantly higher HIV prevalence. Given the national security implications of the increased burden of HIV, interventions targeting military personnel in these populations should be scaled up where appropriate.

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.

Invasive Pneumococcal Disease After 2 Decades of Pneumococcal Conjugate Vaccine Use.

OBJECTIVES: We sought to describe the evolving epidemiology of invasive pneumococcal disease (IPD) among children in Massachusetts, United States, over the last 2 decades during which sequential 7-valent pneumococcal conjugate vaccines (PCV7) and 13-valent PCVs (PCV13) were implemented. METHODS: Cases of IPD in children aged <18 years were detected between 2002 and 2021 through an enhanced population-based, statewide surveillance system. Streptococcus pneumoniae isolates from normally sterile sites were serotyped and evaluated for antimicrobial susceptibility. IPD incidence rates and rate ratios with 95% confidence intervals (CIs) were calculated. RESULTS: We identified 1347 IPD cases. Incidence of IPD in children aged <18 years declined 72% over 2 decades between 2002 and 2021 (incidence rate ratios 0.28, 95% CI 0.18-0.45). IPD rates continued to decline after replacement of PCV7 with PCV13 (incidence rate ratios 0.25, 95% CI 0.16-0.39, late PCV7 era [2010] versus late PCV13 era [2021]). During the coronavirus disease 2019 pandemic years, 2020 to 2021, the rate of IPD among children aged <18 years reached 1.6 per 100 000, the lowest incidence observed over the 20 years. In PCV13 era, approximately one-third of the IPD cases in children aged >5 years had at least 1 underlying condition (98, 30.3%). Serotypes 19A and 7F contributed 342 (48.9%) of all cases before implementation of PCV13 (2002-2010). Serotype 3 (31, 8.6%), and non-PCV13 serotypes 15B/C (39, 10.8%), 33F (29, 8.0%), 23B (21, 0.8%), and 35B (17, 4.7%) were responsible for 37.8% of cases in PCV13 era (2011-2021). Penicillin nonsusceptibility continued to decline (9.8% vs 5.3% in pre-/late PCV13 era, P = .003), however has become more common among non-PCV13 serotypes compared with vaccine serotypes (14.8% vs 1.4%, P < .001). CONCLUSIONS: Robust ongoing surveillance networks are critical for identifying emerging serotypes and development of next-generation vaccine formulations.

Streptococcus pneumoniae serotype 3 population structure in the era of conjugate vaccines, 2001-2018.

Background. Despite use of highly effective conjugate vaccines, invasive pneumococcal disease (IPD) remains a leading cause of morbidity and mortality and disproportionately affects Indigenous populations. Although included in the 13-valent pneumococcal conjugate vaccine (PCV13), which was introduced in 2010, serotype 3 continues to cause disease among Indigenous communities in the Southwest USA. In the Navajo Nation, serotype 3 IPD incidence increased among adults (3.8/100 000 in 2001-2009 and 6.2/100 000 in 2011-2019); in children the disease persisted although the rates dropped from 5.8/100 000 to 2.3/100 000.Methods. We analysed the genomic epidemiology of serotype 3 isolates collected from 129 adults and 63 children with pneumococcal carriage (n=61) or IPD (n=131) from 2001 to 2018 of the Navajo Nation. Using whole-genome sequencing data, we determined clade membership and assessed changes in serotype 3 population structure over time.Results. The serotype 3 population structure was characterized by three dominant subpopulations: clade II (n=90, 46.9 %) and clade Iα (n=59, 30.7 %), which fall into Clonal Complex (CC) 180, and a non-CC180 clade (n=43, 22.4 %). The proportion of clade II-associated IPD cases increased significantly from 2001 to 2010 to 2011-2018 among adults (23.1-71.8 %; P<0.001) but not in children (27.3-33.3 %; P=0.84). Over the same period, the proportion of clade II-associated carriage increased; this was statistically significant among children (23.3-52.6 %; P=0.04) but not adults (0-50.0 %, P=0.08).Conclusions. In this setting with persistent serotype 3 IPD and carriage, clade II has increased since 2010. Genomic changes may be contributing to the observed trends in serotype 3 carriage and disease over time.

Using pneumococcal carriage data to monitor postvaccination changes in invasive disease.

Pneumococcal conjugate vaccines (PCVs) have been introduced worldwide. However, few developing countries have high-quality surveillance systems available for monitoring vaccine impact. We evaluated whether data from nasopharyngeal carriage studies can be used to accurately monitor post-PCV changes in the incidence of invasive pneumococcal disease (IPD) among children under 5 years of age. For various dates during 1991-2010, data on nasopharyngeal pneumococcal carriage and on IPD before and after administration of 7-valent PCV (PCV7) were available from England and Wales, the Netherlands, the Navajo and White Mountain Apache American Indian populations, and the US states of Massachusetts and Alaska. We estimated the change in carriage prevalence for each serotype in each study and then either calculated the average change (inverse variance-weighted) among vaccine and nonvaccine serotypes (model 1) or used mixed-effects models to estimate the change for each serotype individually, pooling serotype data within or between studies (models 2 and 3). We then multiplied these values by the proportion of IPD caused by each serotype during the pre-PCV7 period to obtain an estimate of post-PCV7 disease incidence. Model 1 accurately captured overall changes in IPD incidence following PCV7 introduction for most studies, while the more detailed models, models 2 and 3, were less accurate. Carriage data can be used in this simple model to estimate post-PCV changes in IPD incidence.