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INTRODUCTION: Immunosenescence is a normal biologic process involving deterioration of protective immune responses. Consequently, older adults experience increased risk of infectious diseases, particularly pneumonia, and its leading bacterial cause, Streptococcus pneumoniae. Pneumococcal vaccine recommendations are often limited to adults with specific medical conditions despite similar disease risks among older adults due to immunosenescence. AREAS COVERED: This article reviews epidemiologic, biologic, and clinical evidence supporting the consideration of older age due to immunosenescence as an immunocompromising condition for the purpose of pneumococcal vaccine policy and the role vaccination can play in healthy aging. EXPERT OPINION: Epidemiologic and biologic evidence suggest that pneumococcal disease risk increases with age and is comparable for healthy older adults and younger adults with immunocompromising conditions. Because immunocompromising conditions are already indicated for pneumococcal conjugate vaccines (PCVs), a comprehensive public health strategy would also recognize immunosenescence. Moreover, older persons should be vaccinated before reaching the highest risk ages, consistent with the approach for other immunocompromising conditions. To facilitate PCV use among older adults, vaccine technical committees (VTCs) could classify older age as an immunocompromising condition based on the process of immunosenescence. With global aging, VTCs will need to consider immunosenescence and vaccine use during healthy aging.

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., A novel urinary antigen detection assay substantially increased detection of non-pneumococcal conjugate vaccine 13 (PCV13) serotypes included in an investigational PCV20 among US adults with community-acquired pneumonia (CAP). PCV20 may address the burden of CAP due to the additional serotypes.

Background Pneumonia is a common, serious illness in the elderly, with a poorly characterized long-term impact on health-related quality of life (HRQoL). The Japanese Goto Epidemiology Study is a prospective, active, population-based surveillance study of adults with X-ray/CT scan–confirmed community-onset pneumonia, assessing the HRQoL outcome quality-adjusted life-years (QALYs). We report QALY scores and losses among a subset of participants in this study. Methods QALYs were derived from responses to the Japanese version of the EuroQol-5D-5L health-state classification instrument at days 0, 7, 15, 30, 90, 180, and 365 after pneumonia diagnosis from participants enrolled from June 2017 to May 2018. We used patients as their own controls, calculating comparison QALYs by extrapolating EuroQol-5D-5L scores for day −30, accounting for mortality and changes in scores with age. Results Of 405 participants, 85% were aged ≥65 years, 58% were male, and 69% were hospitalized for clinically and radiologically confirmed pneumonia. Compliance with interviews by patients or proxies was 100%. Adjusted EuroQol-5D-5L scores were 0.759, 0.561, 0.702, and 0.689 at days −30, 0 (diagnosis), 180, and 365, respectively. Average scores at all time points remained below the average day −30 scores (P ≤ .001). Pneumonia resulted in a 1-year adjusted loss of 0.13 QALYs (~47.5 quality-adjusted days) (P < .001). Conclusions Substantial QALY losses were observed among Japanese adults following pneumonia diagnosis, and scores had not returned to prediagnosis levels at 1 year postdiagnosis. QALY scores and cumulative losses were comparable to those in US adults with chronic heart failure, stroke, or renal failure., This prospective study evaluated quality-adjusted life-year (QALY) scores and losses due to pneumonia among adults in Japan. The average 1-year QALY loss was 0.13 (P < .001), which is larger than many evaluations of pneumonia-prevention programs assume.

BACKGROUND Community-acquired pneumonia (CAP) is associated with significant disease burden in adults but has not been measured uniformly. Reconciling differences across studies is critical for understanding the true burden of CAP. METHODS We performed a systematic literature review of the incidence of hospitalized CAP among US adults and described the impact of key study characteristics on these estimates. RESULTS After review of 8361 articles as of January 31, 2019, we identified 28 studies with 41 unique estimates of hospitalized CAP incidence. Among adults ≥65 years of age, annual rates of hospitalized CAP ranged from 847 to 3500 per 100,000 persons with median = 1830. Rates were lower in studies that excluded patients with healthcare-associated (but community-onset) pneumonia (HCAP; median = 2003 vs 1286; P = 0.02) or immunocompromising conditions (median = 1895 vs 1409; P = 0.27) compared to those that did not. Rates of CAP were also lower in studies that used more restrictive criteria for diagnosing pneumonia (eg, pneumonia coded in any diagnosis position [median = 2270] vs pneumonia coded in the first position only [median = 1375] in studies of administrative claims; P = 0.02). For adults

Background Serotype 3 pneumococcal disease has not substantially declined at the population level after the routine introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into pediatric immunization programs across the globe. This epidemiological finding has generated debate regarding the effectiveness of PCV13 against serotype 3 disease. Evaluating PCV13 effectiveness against serotype 3 is especially critical in adults, where serotype 3 makes up an important amount of remaining pneumococcal disease. Methods We performed a systematic review of the published literature to assess the direct effectiveness of PCV13 against serotype 3 community-acquired pneumonia (CAP) among adults. We then estimated overall vaccine effectiveness (VE) using a pooled analysis of the individual-level, raw data. Results Two published studies met inclusion criteria. One was a randomized controlled trial conducted in the Netherlands and published in 2014. The other was a recently-published case-control study conducted in Louisville, Kentucky that used a test-negative design (TND). We also identified a third TND study conducted in Argentina that was recently presented as a conference abstract but is not yet published. All three studies were conducted in adults aged ≥65 years. 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. Results were similar if the unpublished estimate was excluded (serotype 3 VE = 53.6% [95%CI: 6.7–76.9%]). No heterogeneity was observed. Conclusions Currently-available evidence, although limited to three studies, suggests that PCV13 provides direct protection against serotype 3 hospitalized CAP in adults aged ≥65 years.

Publicly available surveillance data, Centers for Disease Control and Prevention reports, and other sources suggest that college students in the United States are at increased risk for meningococcus serogroup B (MenB) disease. US surveillance data from 2015 to 2017 show that the incidence of invasive meningococcal disease (IMD) was greater among college students than among those not attending college; the average annual incidence of MenB disease was >5-fold higher among college students, and all college IMD outbreaks between 2011 and March 2019 were caused by MenB.

Background Few studies have measured the burden of adult pneumococcal disease after the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the US infant vaccination schedule. Further, most data regarding pneumococcal serotypes are derived from invasive pneumococcal disease (IPD), which represents only a fraction of all adult pneumococcal disease burden. Understanding which pneumococcal serotypes cause pneumonia in adults is critical for informing current immunization policy. The objective of this study was to measure the proportion of radiographically-confirmed (CXR+) community-acquired pneumonia (CAP) caused by PCV13 serotypes in hospitalized US adults. Methods This observational, prospective surveillance study recruited hospitalized adults aged ≥18 years from 21 acute care hospitals across 10 geographically-dispersed cities in the United States between October 2013 and September 2016. Clinical and demographic data were collected during hospitalization. Vital status was ascertained 30 days after enrollment. Pneumococcal serotypes were detected via culture from the respiratory tract and normally-sterile sites (including blood and pleural fluid). Additionally, a novel, Luminex-based serotype-specific urinary antigen detection (UAD) assay was used to detect serotypes included in PCV13. Results Of 15,572 enrolled participants, 12,055 eligible patients with CXR+CAP were included in the final analysis population. Mean age was 64.1 years and 52.7% were aged ≥65 years. Common comorbidities included chronic obstructive pulmonary disease (43.0%) and diabetes mellitus (28.6%). PCV13 serotypes were detected in 552/12,055 (4.6%) of all patients and 265/6347 (4.2%) of those aged ≥65 years. Among patients aged 18–64 years PCV13 serotypes were detected in 3.8–5.3% of patients depending on their risk status. Conclusions After implementation of a pneumococcal conjugate vaccination program in US children, and despite the herd protection observed in US adults, a persistent burden of PCV13-type CAP remains in this population.

Objectives Pneumonia hospitalization studies using administrative claims rely on pneumonia coded in the first discharge diagnosis field over pneumonia in any coded field, and few have evaluated disposition following discharge. This study reports the total disease burden and discharge disposition among patients with pneumonia coded in any diagnosis field. Study design Retrospective database review. Methods Data from the 2014 National Inpatient Sample of the Healthcare Cost and Utilization Project, a population-weighted, 20% sample of all US community hospitalizations, were analyzed for all pneumonia hospitalizations in adults aged 18 to 64 years and 65 years or older. Number of hospitalizations, hospital stay length, direct medical costs, in-hospital mortality, patient discharge disposition, illness severity, and likelihood of dying were evaluated based on the diagnosis field of pneumonia as a discharge diagnosis (eg, first, second, third, or further). Results In 2014, an estimated 2.4 million US adult hospitalizations were associated with pneumonia in any of the discharge diagnosis positions (33%-35% in first, 33%-36% in second, and 29%-34% in further positions). When estimates were based only on hospitalizations with pneumonia in the first diagnosis field, approximately 66% of hospitalizations, 78% of hospital days, 87% of in-hospital deaths, 76% and 73% of transfers to short-term hospitals and skilled nursing facilities, 68% of discharges with home health care services, and 82% of direct medical costs were excluded. Conclusions Pneumonia hospitalizations were associated with substantial health care resource utilization and in-hospital mortality. Relying only on pneumonia in the first hospital diagnosis field may potentially underestimate the burden associated with pneumonia hospitalizations.

Introduction: When evaluating the public health value of adult pneumococcal conjugate vaccine (PCV) for pneumonia, regulatory agencies and vaccine technical committees (VTCs) emphasize vaccine serotype (VT), radiologically confirmed community-acquired pneumonia (CAP) to the exclusion of clinically defined pneumonia and thus may underestimate PCV's public health value.Areas covered: We review the critiques that have been raised to using clinically defined pneumonia as a complement to VT-CAP in evaluating the public health value of adult PCVs.Expert opinion: PCV13 efficacies for preventing hospitalized CAP ranged from 6% to 11% and for a combination of primary and secondary care from 4% to 12%, with relatively high associated rate reductions. These efficacy values are larger than estimated from multiplying PCV13 efficacy against vaccine-type CAP by the proportion of CAP identified as vaccine-type through tests, such as a serotype-specific urinary antigen detection assay. Current understanding of pneumococcal epidemiology and limitations of diagnostic tests suggest the efficacy values for clinically defined outcomes are plausible and potentially generalizable. Regulatory agencies and VTCs have accepted clinically defined outcomes for assessing pediatric vaccines and - while additional studies assessing adult clinical CAP VE are needed - they might consider existing data when evaluating adult PCV use.

College students in the United States are at an increased risk for meningococcal serogroup B disease or MenB, which causes the majority of invasive meningococcal disease in the country among adolescents and young adults (62%) and also across all age groups (36%) as of 2018. Approximately one-third of MenB cases among college students occur during campus outbreaks, which trigger substantial public health concern and costs associated with conducting rapid mass vaccination campaigns in an emergency setting. Eleven US college outbreaks of MenB disease have occurred since the initial licensure and recommendation of two MenB vaccines in 2014/2015; both vaccines have been used as part of outbreak responses on campuses, but vaccine coverage and multidose series completion among the general adolescent population are very low (approximately 17% of 17-year-olds in the United States received ≥1 dose in 2018). This review recounts shifts in US meningococcal outbreak epidemiology, lessons from immunogenicity evaluations of MenB vaccines with outbreak strains, and recent college outbreak experiences and mass vaccination responses. The challenges of reactive MenB outbreak containment and potential benefits of preventive immunization of US adolescents are also considered.

Background Background incidence rates (IRs) of potential safety outcomes among vaccine eligible individuals can inform assessment of vaccine safety. Vaccine safety surveillance often uses claims databases, but the impact of outcome definitions on background IR estimates is largely unexplored. Using two definitions for each outcome, we estimated background IRs of 32 cardiac, metabolic, allergic, autoimmune, neurologic, hematologic and nephrologic outcomes among individuals eligible to receive pneumococcal vaccination. Methods We defined a cohort of individuals aged 6–100 years in US commercial health plans who had ≥12 months of health plan enrollment between January 2007 and August 2014 and no previous record of conjugate or simple polysaccharide pneumococcal vaccination. We developed a sensitive and a specific definition for each outcome, with the specific definition requiring evidence of additional care consistent with the outcome. IRs per 100,000 person-years for each outcome were presented overall and stratified by age, gender, and invasive pneumococcal disease (IPD) risk category. Results We followed 19.9 million individuals for a median of 2.5 years. Wide variation was seen in IRs across different definitions of the 32 outcomes, with 19 (59%) outcomes having a specific definition IR less than half of the sensitive definition IR. IRs were particularly variable by definition for outcomes categorized as either hematologic/nephrologic or neurologic (mean ratio of specific IR to sensitive IR = 0.26 and 0.30, respectively). Across definitions, the IRs of the 32 outcomes were often highest in females, adults ≥65, and those at higher IPD risk. Conclusions Background IRs of safety outcomes relevant to populations indicated for pneumococcal vaccine varied by outcome definitions and population subgroups in this large US commercially-insured population. Given large differences in estimated IRs using sensitive versus specific case definitions, neurologic, and hematologic/nephrologic safety outcomes as compared to allergic and autoimmune outcomes may warrant more refined definitions and medical record validation.

Thirteen-valent pneumococcal conjugate vaccine (PCV13) was licensed in adults to address the unmet medical need of vaccine-type community acquired pneumonia (CAP) and the limitations of previous plain-polysaccharide vaccines. Since then, some have questioned the utility of adult PCV13 use, arguing that: i) high PCV13 uptake in young children would provide indirect effects that, by themselves, would sufficiently protect unvaccinated adults and ii) no data describing the real-world effectiveness of PCV13 use in adults, especially with immunocompromising conditions, exist. Even in countries like the United States where PCV13 has been routinely recommended for all adults aged ≥ 65 years, the recommendation is contingent on a re-evaluation to determine if continued use is needed in the context of a mature PCV13 pediatric immunization program. Emerging evidence, however, suggests that i) a meaningful burden of PCV13-type pneumococcal pneumonia still persists in adults at increased risk for pneumococcal disease, despite indirect effects from long-standing pediatric PCV13 use, ii) adult PCV13 use is effective and has reduced pneumococcal CAP, even in the elderly and those with chronic medical or immunocompromising conditions – and disease could come back if PCV13 were removed, and iii) ethical and pragmatic vaccine policy considerations support continued adult PCV13 use in countries that have already introduced the vaccine (eg, disparities in adult PCV13 uptake, confusion stemming from removing a previously-recommended vaccine for a non-safety-related concern, and the reality that next-generation PCVs are only a few years away). Together, these findings suggest that continued PCV13 vaccination in adults is needed to control vaccine-type CAP.

The 13-valent pneumococcal conjugate vaccine (PCV13) is the only licensed PCV with serotype 3 polysaccharide in its formulation. Postlicensure PCV13 effectiveness studies against serotype 3 invasive pneumococcal disease (IPD) in children have shown inconsistent results. We performed a systematic review and meta-analysis of observational studies to assess PCV13 vaccine effectiveness (VE) for serotype 3 IPD in children. We systematically searched PubMed, Embase, and the Cochrane library for studies published before 14 August 2017. We identified 4 published studies and 2 conference posters that provided PCV13 VE estimates stratified by serotype. 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%). A sensitivity analysis including conference posters gave a pooled VE estimate of 72.4% (95% CI, 56.7%–88.0%). The pooled data from case-control studies with similar methodologies and high quality support direct PCV13 protection against serotype 3 IPD in children., Meta-analysis of published case-control studies of 13-valent pneumococcal conjugate vaccine gave a pooled vaccine effectiveness of 63.5% against serotype 3 invasive pneumococcal disease (IPD). The pooled data from case-control studies with similar methodologies and high quality support direct protection against serotype 3 IPD in children.

Our study demonstrated real-world, direct effectiveness of 13-valent pneumococcal conjugate vaccine against vaccine-type community-acquired pneumonia following introduction into a routine immunization program among adults aged ≥65 years, many of whom had immunocompromising and chronic medical conditions., Background Following universal recommendation for use of 13-valent pneumococcal conjugate vaccine (PCV13) in US adults aged ≥65 years in September 2014, we conducted the first real-world evaluation of PCV13 vaccine effectiveness (VE) against hospitalized vaccine-type community-acquired pneumonia (CAP) in this population. Methods Using a test-negative design, we identified cases and controls from a population-based surveillance study of adults in Louisville, Kentucky, who were hospitalized with CAP. We analyzed a subset of CAP patients enrolled 1 April 2015 through 30 April 2016 who were aged ≥65 years and consented to have their pneumococcal vaccination history confirmed by health insurance records. Cases were defined as hospitalized CAP patients with PCV13 serotypes identified via culture or serotype-specific urinary antigen detection assay. Remaining CAP patients served as test-negative controls. Results Of 2034 CAP hospitalizations, we identified PCV13 serotypes in 68 (3.3%) participants (ie, cases), of whom 6 of 68 (8.8%) had a positive blood culture. Cases were less likely to be immunocompromised (29.4% vs 46.4%, P = .02) and overweight or obese (41.2% vs 58.6%, P = .01) compared to controls, but were otherwise similar. 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%]). No confounding was observed during adjustment for patient characteristics, including immunocompromised status, body mass index, and history of influenza and pneumococcal polysaccharide vaccination (adjusted VE range, 71.1%−73.3%). Conclusions Our study is the first to demonstrate real-world effectiveness of PCV13 against vaccine-type CAP in adults aged ≥65 years following introduction into a national immunization program.

Background Individuals with certain chronic medical conditions are at higher risk of developing pneumonia and pneumococcal disease than those without. Using data from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA), this post hoc analysis assessed the efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ≥65 years with at-risk conditions. Methods The Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) was a double-blind, parallel-group, randomized, placebo-controlled study in the Netherlands in which adults aged ≥65 years received either PCV13 or placebo. Outcomes of interest were identified using prespecified clinical criteria, radiographic confirmation, routine microbiologic testing, and a serotype-specific urinary antigen detection assay. In this post hoc analysis, participants were classified by at-risk status based on self-reporting of any of the following chronic medical conditions: heart disease, lung disease, asthma, diabetes, liver disease, and smoking. The objective of this analysis was to assess PCV13 vaccine efficacy (VE) against a first episode of vaccine-serotype community-acquired pneumonia (VT-CAP) in at-risk participants. Results Of the 84,496 adults enrolled in the study, 41,385 (49.2%) were considered at risk owing to chronic medical conditions. Of the 139 VT-CAP cases, 115 (82.7%) occurred in these participants. VE of PCV13 against a first episode of VT-CAP among participants with at-risk conditions was 40.3% (95.2% CI: 11.4%, 60.2%). Average duration of follow-up since vaccination was 3.95 years for at-risk participants; protection did not wane over the study period. Conclusions This post hoc analysis of the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) showed significant and persistent efficacy of PCV13 against VT-CAP in at-risk older adults. ClinicalTrials.gov identifier: NCT00744263 .

Number-needed-to-vaccinate (NNV) is increasingly used to inform decisions about vaccine use, but it is not calculated uniformly across studies. This study compared two methodologies for calculating NNV with 13-valent pneumococcal conjugate vaccine (PCV13) to prevent one case of community-acquired pneumonia (CAP) among US adults aged ≥65years: (i) using one-year absolute rate differences as was originally performed by the Centers for Disease Control and Prevention (CDC) and (ii) using absolute risk reduction over 5years.We constructed a hypothetical fixed cohort of 200,000 adults aged ≥65years equally separated into PCV13-vaccinated and PCV13-unvaccinated groups. We incorporated the same conservative assumptions used by CDC in 2014 regarding annual incidence of hospitalized (1375 per 100,000) and outpatient (2010 per 100,000) CAP, the initial (2014) proportion of adult PCV13-type CAP (10%), and PCV13 efficacy against vaccine-type CAP (45%). To model PCV13 impact over time, we assumed annual mortality was 5% for both groups, the percentage of adult PCV13-type CAP declined annually due to pediatric herd effects, and PCV13 efficacy did not wane over 5years.Among adults aged ≥65years, NNV with PCV13 to prevent one hospitalized and one outpatient case of CAP as originally calculated by CDC in 2014 were 1620 and 1110, respectively. Accounting for 5-year cumulative effects, NNV with PCV13 to prevent one hospitalized and one outpatient case of CAP over 5years were 576 and 394, respectively. These revised NNV estimates are roughly one third of initial estimates in which cumulative effects were ignored. NNV to prevent any CAP (inpatient or outpatient) over 5years with one PCV13 dose was 234.Accounting for cumulative preventive effects of PCV13 vaccination over time is critical. Failing to do so, even when using conservative disease burden parameters, can grossly underestimate the public health impact of adult PCV13 use.

Introduction: Streptococcus pneumoniae causes mucosal and invasive diseases with high morbidity and mortality. Introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) into routine infant immunization programs worldwide resulted in serotype 19A becoming a leading cause of the remaining pneumococcal disease burden in vaccinated and nonvaccinated individuals. This article reviews the impact of the latest generation PCVs (10-valent PCV, PCV10, and 13-valent PCV, PCV13) on serotype 19A.Areas covered: This article covers immune responses elicited by PCV7, PCV10 and PCV13 against serotype 19A and their impact on nasopharyngeal (NP) carriage and disease in vaccinated and unvaccinated populations using data from surveillance systems, randomized controlled trials, and observational studies.Expert commentary: As expected from a PCV containing serotype 19A, PCV13 elicits significantly higher functional immune responses against serotype 19A than PCV7 and PCV10. Higher responses are likely to be link...

Introduction: Adolescents and young adults are the primary reservoirs and transmitters of meningococci. In the US, meningococcal serogroup B (MenB) disease predominates over A, C, W, and Y; ACIP-re...

Invasive meningococcal disease (IMD), a rapidly progressing and potentially fatal illness, disproportionately affects adolescents and young adults. While IMD is best prevented by vaccination, vaccine uptake in these groups is low. An evidence-based understanding of the safety and effectiveness of concomitant vaccination of meningococcal vaccines, including the newer MenB protein vaccines and the more established MenACWY conjugate vaccines, with other vaccines recommended for adolescents and young adults may help maximize vaccination opportunities. We identified 21 studies assessing concomitant administration of meningococcal vaccines with other vaccines in adolescents and adults. Although studies varied in methodology, concomitant administration generally did not affect immunogenicity of the meningococcal or coadministered vaccines. In some cases, reactogenicity increased following concomitant administration, but no definitive safety concerns were raised. In general, data suggest that meningococcal vaccines can be safely and effectively coadministered with other vaccines.

Background: In September 2014, 13-valent pneumococcal conjugate vaccine (PCV13) was universally recommended for all US adults aged ≥65 years. Adult PCV13 coverage, including whether disparities in uptake exist, however, is not well-described. Methods: We used a monthly series of cross-sectional analyses of administrative medical and prescription claims data collected by IQVIA and linked to sociodemographic data collected by Experian to estimate overall and subpopulation-level uptake of PCV13 among US adults aged ≥65 years. Results: Among adults aged ≥65 years, 43.3% received PCV13 by the end of November 2017. Race/ethnicity, annual household income, education status, and neighborhood urbanicity were strongly related to PCV13 uptake among adults aged ≥65 years. Lower uptake of PCV13 was observed for non-Hispanic black (36.3%) and Hispanic (30.0%) adults (vs 45.6% for non-Hispanic whites, P

We thank Mungall and colleagues for their interest in our manuscript that focused on serotype 19A. The letter addresses a diversity of issues beyond the original topic of our article. It also conta...

Background Community-acquired pneumonia (CAP) develops in persons outside of a healthcare facility and is associated with significant morbidity and mortality. Estimating the incidence of CAP is challenging because it lacks a standardized case definition and because study designs and selection criteria vary. Reconciling these differences across studies is critical for understanding the true burden of CAP which, in turn, informs prevention strategies, including vaccination. Methods We performed a systemic literature review of studies describing the incidence of hospitalized CAP among adults in the United States. Specifically, we examined the impact of the following study characteristics on estimates of incidence: (i) study population, (ii) study type and data source, and (iii) diagnostic criteria for pneumonia. Results After review of 8361 articles as of January 31, 2019, we identified 26 studies which contained 39 unique CAP estimates. Among adults ≥65 years of age, annual rates of hospitalized CAP ranged from 847 to 3,500 per 100,000 persons with median = 1,830. Rates were lower in studies that excluded patients with healthcare-associated (but community-onset) pneumonia (HCAP; median = 2,003 vs. 1,286; P = .02) or immunocompromising conditions (median = 1,895 vs. 1,409; P = .29). Rates of CAP were also lower in studies that used more restrictive criteria for diagnosing pneumonia (e.g., pneumonia coded in any diagnosis position [median = 2,246] vs. pneumonia coded in the first position only [median = 1,375] in studies of administrative claims; P = 0.03). For adults Conclusion CAP causes a significant disease burden among adults, particularly among those ≥65 years of age where the incidence of hospitalization is approximately 2,000 per 100,000 annually. Commonly-applied exclusion criteria (e.g., persons with HCAP or immunocompromising conditions) or restrictive case definitions (e.g., only including pneumonias coded in the primary diagnosis position) have led to systematic underestimation of CAP incidence in many previous studies. Understanding the true burden of adult CAP is critical for highlighting the ongoing need for expanded prevention programs, including vaccination. Disclosures All authors: No reported disclosures.

Background Native Americans experience a high burden of community-acquired pneumonia (CAP). Thirteen-valent pneumococcal conjugate vaccine (PCV13) was introduced for adults ≥65yrs in 2014. Data on CAP etiology can guide prevention and treatment. Methods We enrolled adults hospitalized with CAP and age-group-matched non-hospitalized controls on Navajo and White Mountain Apache tribal lands. Nasopharyngeal/oropharyngeal (NP/OP) swabs from cases and controls were tested by multiplex PCR for respiratory pathogens. Urine from cases and controls was tested for pneumococcus (Sp) by conventional (BinaxNOW) and serotype-specific urine antigen detection (UAD) for 24 serotypes (PCV13 types plus 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, 33F). Blood culture and chest radiographs (CXRs) were obtained from cases at the provider’s discretion. Radiographic pneumonia was determined by clinical interpretation of CXRs. Results From March 2016 to March 2018, we enrolled 580 CAP cases with CXR confirmation and 411 controls. Positive blood culture was identified in 42/483 (9%), of which 29 (69%) were Sp. Sp was detected in 164/572 (29%) cases (table). Of 125 cases with serotype information available, serotypes 3 (n = 35; 28%) 8 (n = 19; 15%) and 20 (n = 15; 12%) were the most common. Among 53 Sp cases aged ≥65 years, 26 (49%) were PCV13-type. Compared with blood culture, UAD was 100% sensitive and 100% concordant (n = 24). Viruses were detected by NP/OP PCR in 43% of CAP cases and 18% of controls. Influenza A, parainfluenza type 3, rhinovirus, and RSV were statistically significantly associated with case status. Among 263 cases in whom all diagnostic tests were collected, 63% had a pathogen detected: bacteria alone in 19%, viruses alone in 23%, and both bacterial and viral infection in 22%. Bacterial causes outnumbered viral causes when adjusting for virus detection in the control population. Conclusion Pneumococci were the most common etiology identified among Native American adults with CAP. UAD improved detection of pneumococcal CAP. Respiratory viruses also contributed substantially to CAP burden. Broader prevention strategies, including new vaccines, are required to prevent viral pneumonia and pneumococcal pneumonia caused by serotypes not contained in currently-available vaccines. Disclosures All authors: No reported disclosures.

Summary Objective To analyze the available published data (2005–2014) describing the prevalence of multimorbidity in adult patients with pneumococcal disease, with a focus on the comorbidities considered by the Advisory Committee on Immunization Practices (ACIP) of the US Centers for Disease Control and Prevention to increase the risk of pneumococcal disease in adults (immunocompetent persons with chronic medical conditions (at risk) and immunocompromised or immunosuppressed persons (high risk)). An analysis of case–control and population-based surveillance studies that have evaluated risk factors for community-acquired pneumonia (CAP) and invasive pneumococcal disease (IPD) was also performed in order to estimate the importance of risk stacking. Methods Studies that established the enrolment procedure for patients and reported the incidence of multimorbidity and risk factors for CAP and/or IPD were included. In order to obtain a risk stacking value based on the at-risk comorbidity odds ratios (OR), the multiplicative method described by Campbell was used. Results Thirty-eight articles were selected, 19 for multimorbidity and 19 for risk factors for CAP/IPD. With regard to multimorbidity, the prevalence among adults aged ≥65 years ranged from 23% to 98.7% for two or more comorbidities and from 18% to 89.7% for three or more comorbidities. Diabetes (DBT), chronic heart disease (CHD), and chronic obstructive pulmonary disease (COPD) were the three most frequent comorbidities described (7.6–28.5%, 6.9–25.8%, and 3.8–15.4%, respectively). With regard to risk factors, based on the multiplicative method, the hypothetical scenario of concurrence of the three most frequent at-risk conditions (DBT+CHD+COPD) showed an OR of ≥7.5. In this group of patients, the addition of smoking, another common at-risk factor for CAP (stacking four concurrent conditions) increased the OR from 8.5 to >40. These ORs were generally similar to rates described by other authors in persons with a high risk. Conclusions The ORs for CAP and IPD of patients with two or more comorbidities, with or without smoking, were found to be similar to the ORs for CAP and IPD described in the literature for patients currently classified as high risk. The potential impact of multiple, stacking comorbidities is underestimated and there is a need for the risk categories for pneumococcal disease to be redefined.

Adults, particularly those with underlying chronic conditions, eg, cardiovascular, liver, and pulmonary diseases and diabetes mellitus, have a persistent pneumococcal disease burden. Thirteen-valent pneumococcal conjugate vaccine (PCV13) is recommended in the United States for all adults aged ≥65 years and immunocompromised adults aged65 years to protect against vaccine-serotype (VT) invasive pneumococcal disease (IPD) and pneumonia. PCV13 is not recommended for immunocompetent adults aged ≥18 years with comorbidities associated with increased pneumococcal disease risk.This US-focused review summarizes PCV13-type IPD and community-acquired pneumonia burden in adults aged50 years, PCV13 immunogenicity and safety in this population, and adult pneumococcal vaccination recommendations.Considering (i) PCV13 has demonstrated efficacy against VT-IPD and pneumonia in adults aged ≥65 years (with or without underlying chronic conditions), and (ii) immune responses to PCV13 in younger adults are comparable or better than in older adults, PCV13 would likely have similar efficacy in adults aged50 years. Recommending PCV13 for at-risk adults aged50 years would provide direct immunologic benefit of a conjugate vaccine and could address an important unmet medical need for pneumococcal pneumonia prevention. Although not directly addressed here, this benefit would likely extend to at-risk adults aged 50-64 years.

Background At the meeting of the Advisory Committee on Immunization Practices (ACIP) on February 28, 2019, the US Centers for Disease Control and Prevention (CDC) and the Pneumococcal Work Group (PWG) presented data to inform the public health question of whether the 13-valent pneumococcal conjugate vaccine (PCV13) should continue to be recommended for routine immunization of all adults age 65 years and older in the United States. Methods We reviewed all three available studies reporting adult PCV13 vaccine effectiveness against all-cause pneumonia, calculated numbers needed to vaccinate (NNV), and compared these results to NNV data presented to the ACIP based on etiologically and radiologically confirmed vaccine-type (VT) disease. Studies included a randomized controlled trial of inpatient pneumonia among Dutch persons age 65+ years, a US CDC-led observational study among the US Medicare population of inpatient pneumonia, and an observational study of inpatient and outpatient pneumonia in Germany. Results Based on a background incidence of etiologically and radiologically confirmed VT community-acquired pneumonia of 17–76 per 100,000 per year and PCV13 VE of 43%, the CDC presented to ACIP an annual NNV estimate for preventing one pneumonia case of 3,000 to 14,000. For the three studies we reviewed, VEs were 6% to 12% against all-cause pneumonia and background all-cause pneumonia incidences were 891 to 1776 per 100,000 per year. Assuming a 5-year PCV13 duration of protection, for these three studies NNVs to prevent a case of pneumonia were 95 to 277, or 11- to 147-fold lower than what was presented at ACIP. Conclusion To avoid inaccurate conclusions for potentially efficient interventions, calculations of NNVs, rate reductions, and economic benefits should include sensitive outcomes, such as all-cause pneumonia, in addition to more specific but lower sensitivity outcomes such as VT, radiologically confirmed pneumonia. Disclosures All authors: No reported disclosures.

The aging of the world population is expected to be accompanied by increased pneumococcal pneumonia in older adults. To address this, the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA), a large, randomized, placebo-controlled trial conducted to assess the 13-valent pneumococcal conjugate vaccine (PCV13) in adults ≥ 65 years, found statistically significant vaccine efficacy for first episodes of vaccine-type community-acquired pneumonia (VT-CAP; 46%), nonbacteremic/noninvasive VT-CAP (45%), and VT invasive pneumococcal disease (75%), along with an acceptable safety profile. Study results were presented to the US Advisory Committee on Immunization Practices in June 2014, which subsequently recommended sequential PCV13 and 23-valent pneumococcal polysaccharide vaccination for adults ≥ 65 years. Thus, appropriate protection of adults at risk for pneumococcal CAP will include vaccination with PCV13.

Background In Canada, 13-valent pneumococcal conjugate vaccine (PCV13) was licensed for the prevention of vaccine-type (VT) pneumonia in adults in July 2015. Herd effects stemming from the routine pediatric PCV13 program have historically led to reductions in VT disease in older adults, and there is currently no recommendation for a routine age-based PCV13 program for this age group. However, recent data suggest these indirect effects may have plateaued, leaving a persistent and substantial burden of potentially preventable pneumococcal disease in older adults. We evaluated the potential impact of PCV13 immunization program for Canadian adults aged ≥65 years on hospitalizations for community-acquired pneumonia (CAP). Methods We constructed a mathematical model based on Canada-specific burden of disease estimates and published estimates of PCV13 effectiveness and durability. We estimated the number of hospitalizations averted as the product of (i) the size of the Canadian population aged ≥65 years, (ii) the incidence of all-cause CAP, (iii) the proportion of CAP that is VT, (iv) PCV13 effectiveness, and (v) the duration of protection for PCV13 over a 5-year time horizon. We assumed that rates of all-cause CAP, the proportion of VT CAP, and PCV13 effectiveness remained constant over the 5-year assessment period. We assumed a 5% annual all-cause mortality rate in the overall population. We estimated hospital days averted as the product of hospitalizations averted and median length of stay. Model assumptions are summarized in Table 1. Results Based on model assumptions, PCV13 use in Canadian adults aged ≥65 years would lead to an annual rate reduction of 62 (11–77) hospitalizations per 100,000 persons, per year. This reduction, applied to the entire Canadian population of older adults, would avert an estimated 17,274 (3,037–21,711) hospitalizations and 138,192 (24,298–173,690) hospital days over a 5-year period. Conclusion Despite herd effects from the routine pediatric program, direct PCV13 immunization of older adults in Canada could result in considerable additional reduction in hospitalizations for pneumonia. Disclosures J. Vojicic, S. Dion, R. E. Isturiz, C. Laferriere, M. Major, R. M. Nepal, and J. A. Suaya: Pfizer: Employee and Shareholder, Benefits and stock and Salary; J. M. McLaughlin, Pfizer: Employee, Salary.

Background In October 2015, ACIP recommended that serogroup B meningococcal (MenB) vaccine may be administered to persons aged 16–23 years (age 16–18 preferentially) as Category B (individual clinical decision-making), in addition to the Category A recommendation made in June 2015 for at-risk individuals aged ≥10 years. Currently, MenB vaccine coverage among adolescents and young adults (AYAs), including whether disparities exist, is not well-described. Methods We performed a cross-sectional analysis of claims data collected by IQVIA and linked to sociodemographic data collected by Experian to estimate overall and subpopulation-level uptake of MenB vaccine (≥1 dose) among AYAs aged 10–25 years as of May 31, 2017. Results Among 2,501,188 AYAs aged 10–25 years, MenB vaccine uptake was only 1.4% at the end of May 2017. MenB vaccination varied by age, with uptake of 0.2%, 2.5%, 1.6%, and 0.2% among individuals aged 10‒15, 16‒18, 19‒23, and 24‒25 years (P < 0.01), respectively. Lower uptake was observed for non-Hispanic blacks (1.0% vs. 1.4% among non-Hispanic whites, P < 0.01), AYAs in lower income households (1.0% vs. 2.2% among lowest vs. highest income deciles, P < 0.01), and those living in rural (0.6%) or urban/inner-city (0.9%) areas (vs. 1.5% in suburban areas, P < 0.01). The strongest predictors of MenB vaccination were previously receiving quadravalent meningococcal (MenACWY) or human papillomavirus (HPV) vaccines. These AYAs were 36.1 and 5.1 times more likely to have received MenB vaccine and had MenB uptake of 9.8% and 5.1%, respectively. Conclusion As of May 2017, MenB vaccine uptake among AYAs aged 10‒25 years was low (

Background Pneumonia is a serious illness with potentially long-lasting but poorly-characterized impact on quality of life. The Japanese Goto Epidemiology Study is a prospective, active, population-based surveillance study of adults with community-onset pneumonia (COP), that includes assessment of Quality Adjusted Life Years (QALYs). Methods Patients with X-ray/CT scan confirmed COP enrolled in the Goto study and consented to participate in QALY assessment responded to Japanese versions of EuroQol-5D-5L (EQ-5D-5L) health state classification (primary), EQ-5D visual analog scale, and SF-6D (secondary) instruments. This interim analysis reports 91-day QALYs based on Day 1 (diagnosis), 8, 16, 31, and 91 EQ-5D-5L responses of patients enrolled between June 1, 2017 and February 7, 2008. For comparison, we developed hypothetical QALYs had the patients not developed pneumonia (control) using the EQ-5D-5L scores from Day -30 (via recall) carried forward and adjusted by the natural decline in scores and death with age. QALYs were calculated as the area (trapezoidal method) under the survival weighted pneumonia and control EQ-5D-5L QALY score curves. Results The 234 patients were 55% male, 88% aged ≥64 years, 45% nursing home residents, and 65% initially hospitalized (35% initially outpatient) for COP. Compliance for interviews among survivors was 100%. EQ-5D-5L scores were 0.732 at Day −30, decreased to 0.590 at diagnosis, and rose to 0.675 by Day 91. The average scores at all time points remained below Day −30 (all P values

Background Diabetes, a prevalent chronic condition in younger adults, increases the risk of pneumonia. The incidence of pneumonia hospitalization among adults aged

Antibiotics are universally prescribed drugs. Because they exert selective pressure and because of the innate bacterial ability for adaptation, even the appropriate clinical use of these potentially life-preserving agents inevitably fosters the development and spread of resistance by a variety of microorganisms. Inappropriate use has accelerated and increased the magnitude of a problem that is now considered a public health crisis. For Gram-positive pathogens some compounds offer limited hope, but for Gram-negative organisms no new drugs with radically increased spectra are available for clinical trials. Patients with serious infections due to multiresistant organisms are experiencing adverse, sometimes fatal, clinical outcomes. Use of multiple drugs increases side effects and exposes additional susceptible bacteria to selective pressure. There is evidence that the appropriate use of currently available antibiotics can be associated with a reduction of the spread of resistance. Antibiotic stewardship programmes and the antibiotic 'care bundle' approach can be effective measures to lengthen the useful life of antibiotics and can be implemented in most clinical situations.

SummaryThe clinical and economic burden of adult community-acquired pneumonia (CAP) in Latin America is not well known. We conducted a literature review to describe the etiology, incidence, hospitalization, morbidity and mortality, antibiotic resistance, costs associated with care, and the potential benefits of pneumococcal vaccination in the reduction of adult CAP in Latin America. Data that were published during the period from January 1970 through August 2008 were identified via the Web sites and databases of the Pan American Health Organization, Latin American health agencies, and the US National Institutes of Health, National Library of Medicine (MEDLINE). Streptococcus pneumoniae was identified as the most common pathogen, accounting for up to 35% of CAP cases. The mean rate of CAP due to penicillin-resistant S. pneumoniae was 39%. The mortality in Latin America due to lower respiratory tract infections has been reported to be 6%, compared with 4% in developed regions, and CAP was the third most frequent cause of death in adults in 31 Latin American countries in 2001–2003. Although S. pneumoniae caused the majority of CAP, similar to other regions of the world, mortality due to CAP in Latin America was substantially greater than that in developed countries. This review demonstrates the need to facilitate standardized surveillance and reporting systems to monitor the burden of CAP and to implement prevention strategies to decrease the clinical and economic burden of CAP in Latin American adults.

Methicillin-resistant Staphylococcus aureus (MRSA) has become a serious threat to public health worldwide. Ongoing surveillance is essential to support infection control committees and clinicians in the prevention and treatment of infection. However, in Latin America, resources for monitoring the changing epidemiology of MRSA remain limited. In this article, we review the current situation of MRSA in Latin America in order to highlight the need for a more harmonised effort to improve its management. Literature in the PubMed and SciELO databases as well as the website of the Pan American Health Organization were searched for articles and information about the epidemiology of MRSA in Latin America. MRSA is already the leading cause of nosocomial infection in the Latin American region, and the number of reports of community-acquired MRSA infections is also rising. However, the extent of the problem is not fully understood, especially since data tend to come from large hospitals whereas much of the population is served by small community healthcare centres that do not have extensive facilities for performing microbiological surveillance. In conclusion, wider-reaching and co-ordinated programmes to provide regular MRSA surveillance reports are required across the Latin American region.

Globally, antibiotic resistance continues to be an increasing problem. The emergence of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and extended spectrum β-lactamase-producing Enterobacteriaceae has seriously reduced the number of empirical agents suitable for selected indications. Increasing Gram-negative resistance has also negatively impacted the physician's alternatives when choosing adequate initial therapy; increased reliance on the carbapenem class as empirical agents has led to the emergence of multidrug resistance in non-enteric Gram-negative bacilli. There is a critical need for new, broad-spectrum alternatives to the currently available broad-spectrum agents.

Because all important assumptions used in the model are simultaneously biased toward PCV10, the model results are erroneous and misleading. Routine infant pneumococcal vaccination in Japan would undoubtedly bring substantial reductions in morbidity and mortality. However, given the current epidemiologic landscape in Japan and the current evidence, the clinical and economic gains from the use of PCV13 would, undoubtedly, far exceed those potentially observed from the use of PCV10. We urge those who conduct, critique, and consider cost-effectiveness studies to evaluate the strength of the evidence of clinical claims for the products and the influence these assumptions have on the overall findings. In addition, when performing economic predictive modeling, it is critical to provide a balanced perspective by weighing the strengths and weaknesses of all available data to construct the base case analysis.

Sirs:We appreciate the opportunity to respond to Dr Fedson’s reply1 to our letter2 in which we stated that effectiveness of polysaccharide pneumococcal vaccines for the prevention of non-invasive p...

Background In the fall of 2014, the Advisory Committee on Immunization Practices (ACIP) recommended 13-valent pneumococcal conjugate vaccine (PCV13) for all US adults age ≥65 years. Coverage rates are currently unknown. This study estimated overall PCV13 coverage rates in older adults and determined if disparities in uptake existed for some sociodemographic groups. Methods A monthly series (August 1, 2014 – Feb 28, 2017) of cross-sectional analyses of administrative diagnosis and prescription claims data collected by QuintilesIMS and linked to sociodemographic data collected by Experian were used to estimate overall and subpopulation-level uptake of PCV13 among US adults age ≥65. Uptake estimates were adjusted to PCV13 manufacturer sales data to account for missingness patterns in QuintilesIMS claims data. Univariate and multivariable analyses of PCV13 uptake were performed across sociodemographic factors (e.g., race/ethnicity, household income, neighborhood urbanicity, education status). Results Among adults age ≥65, 50% received PCV13 by the end of February 2017. Disparities in PCV13 uptake were apparent. Black adults (39%) and Hispanics (32%) (vs. 53% for whites), the poor (36% vs. 64% for lowest vs. highest income deciles), adults with low educational status (37% vs. 58% for those without high school education vs. college educated), and those living in rural (33%) or urban/inner city (41%) areas (vs. 52% in suburban areas) had significantly lower PCV13 uptake (all P < .001) (Figure). These differences persisted in multivariable analyses. Conclusion PCV13 uptake among adults age ≥65 occurred rapidly after ACIP recommendation in late 2014. Yet, poor and minority communities, rural and urban/inner city areas, and communities with low educational attainment may need more time to adequately implement adult vaccine guidelines following ACIP recommendation. In 2018, current adult pneumococcal recommendations will be revisited by ACIP. Changes to existing recommendations for older adults, however, could cement these disparities in adult PCV13 uptake in the very communities at increased risk for pneumococcal disease. These vulnerable communities may instead benefit from targeted and tailored interventions to increase pneumococcal vaccination. Disclosures J. McLaughlin, Pfizer Inc: Employee and Shareholder, Salary; F. Khan, Pfizer Inc: Employee and Shareholder, Salary; A. Curry, Pfizer Inc: Employee and Shareholder, Salary; V. Snow, Pfizer Inc: Employee and Shareholder, Salary; R. Isturiz, Pfizer Inc: Employee and Shareholder, Salary; D. Swerdlow, Pfizer Inc: Employee and Shareholder, Salary

This study was conducted to determine the serotype distribution and trends over time of Streptococcus pneumoniae strains associated with noninvasive infections among adult patients ≥18 years of age in the United States (2009 to 2012). A total of 2,927 S. pneumoniae isolates recovered from patients presenting with respiratory infections and obtained mainly (87.0%) from lower respiratory tract specimens (sputum) were included. The levels of the 7-valent pneumococcal conjugate vaccine (PCV7) serotypes remained stable over the 4-year study period (4.6% to 5.5%; P = 0.953). Overall, 13-valent pneumococcal conjugate vaccine (PCV13) serotypes were identified in 32.7% of samples, declining from 33.7% to 35.5% in 2009 to 2011 to 28.2% in 2012 ( P = 0.007), with a significant decrease in the levels of serotypes 7F ( P = 0.013) and 6A ( P = 0.010). The levels of 19A remained constant (15.8% to 17.1%) during 2009 to 2011, dropping to 12.2% in 2012 ( P = 0.089). The prevalence of serotypes associated with the 23-valent pneumococcal polysaccharide vaccine (PPSV23), but not PCV13, remained generally stable; however, the prevalence of serotypes 15B and 15C (15B/15C) increased from 2.7% to 6.3% ( P = 0.010). The proportion of nonvaccine serotypes increased gradually during the study period ( P = 0.044), particularly for serotype 35B (from 3.6% in 2009 to 8.2% in 2012; P = 0.001). Nonsusceptibility rates for penicillin (susceptible breakpoint, ≤2 μg/ml) and clindamycin against PCV7 serotypes decreased over the period. These results suggest the emergence of indirect effects following introduction of PCV13 for infants and young children; continued surveillance is needed to assess the burden of PCV13 serotypes in the adult population after the implementation of age-based recommendations in the United States.

Four serotypes of dengue viruses produce dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. They are the most important arbovirus infections of humans, in terms of both morbidity and mortality, constituting one of the most rapidly expanding and re-emerging infectious disease problems in Latin America. In less than 20 years, the region has transformed itself from hypoendemic to hyperendemic, while serotype circulation in most countries has gone from none or single to multiple. Changes in endemicity have coincided with the emergence and increasing incidence of the severer forms of dengue infection. This article reviews the clinical presentations of these diseases. Health care providers who see patients in or returning from areas of Latin America, the Caribbean, and other tropical areas must consider dengue in the differential diagnosis of patients presenting with compatible symptoms, and must be knowledgeable in the current management of this important disease.

Background A pneumococcal polysaccharide vaccine (PPSV23) has been available for use in adults ≥65 years old since 1983 with vaccination rates of ~65% in the past decade. A conjugate vaccine (PCV13) has been recommended for adults since 2014, and for children since 2010 (replaced PCV7 which was used since 2000). The serotype distribution of pneumococci causing infections in adult patients in the US was evaluated. Methods 6,491 S. pneumoniae isolates were collected from patients (≥18 years old) seen/hospitalized in 105 US centers and recovered primarily (77.8%; 5,052/6,491) from lower respiratory tract specimens. Identification was performed by biochemical algorithms and/or PCR. The cpsB sequence was obtained by PCR or next genome sequencing for serotype determination. Multiplex PCR and/or Quellung reaction were performed, as needed. Results 19F was the most prevalent PCV7 serotypes with annual rates of 1.6–3.1%, but no trends were observed for this serotype during the period. Overall, PCV13 serotype prevalence declined considerably from 38.6% in 2009 to 23.1% in 2016, but rates remained stable during 2013–2016 (21.5–24.6%). Serotype 19A (12.4%) and 3 (9.1%) were the most common PCV13 serotypes (2009–2016), followed by 7F (2.4%). Prevalence of 19A and 7F declined from 17.5% to 7.1% and from 4.6% to 0.7%, respectively, while the prevalence of serotype 3 remained stable. The proportion of non-vaccine serotypes increased, as did PPSV23 (non-PCV13). Among non-vaccine serotypes, 35B (8.1%), 23A (6.2%), and 6C/6D (5.8%) were the most common, followed by 23B (4.8%) and 15A/15F (4.8%). Prevalence of serotype 35B (from 3.9% to 12.6%) and 23B (from 3.7% to 7.8%) increased considerably during the study period. Serotypes 23A and 15A/15F remained stable throughout; however, serotype 6C/6D decreased from 7.6% to 3.4%. Conclusion Prevalence of serotype 19F remained low and stable during the study period. PCV13 serotypes declined considerably, but serotypes 19A and 3 remained elevated. The consistent increase of non-vaccine serotypes, especially 35B, may be a reason for concern since it exhibits decreased susceptibility to β-lactams. Continued surveillance is needed to constantly assess the dynamic changes of serotypes affecting the adult US population. Disclosures R. E. Mendes, Pfizer, Inc.: Research Contractor, Research grant; H. L. Sings, Pfizer, Inc.: Employee, Salary; B. Hilton, Pfizer, Inc.: Employee, Salary; T. P. Doyle, Pfizer, Inc.: Research Contractor, Research grant; L. N. Woosley, Pfizer, Inc.: Research Contractor, Research grant; R. K. Flamm, Pfizer, Inc.: Research Contractor, Research grant; R. E. Isturiz, Pfizer, Inc.: Employee, Salary

Practical and precise information about the potential infectious health hazards that travelers to Latin America may encounter is reviewed in this article. Some diseases are briefly described, others are only mentioned. The countries have been grouped into four geographical areas following the classification of the World Health Organization. The discussion on each area includes information on travelers' diarrhea, malaria, cholera, typhoid fever, yellow fever, and other diseases or special problems.