As authorities braced for the arrival of the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infrastructure investments and government directives prompted action in central Viet Nam to establish capacity for genomic surveillance sequencing. From 17 November 2021 to 7 January 2022, the Pasteur Institute in Nha Trang sequenced 162 specimens from 98 150 confirmed SARS-CoV-2 cases in the region collected from 8 November to 31 December 2021. Of these, all 127 domestic cases were identified as the B.1.617.2 (Delta) variant, whereas 92% (32/35) of imported cases were identified as the B.1.1.529 (Omicron) variant, all among international flight passengers. Patients were successfully isolated, enabling health-care workers to prepare for additional cases. Most (78%) of the 32 Omicron cases were fully vaccinated, suggesting continued importance of public health and social measures to control the spread of new variants.

BACKGROUND: Before the SARS-CoV-2 Delta variant arrived in Vietnam, case rates suggested seroprevalence of SARS-CoV-2 was low. Beginning in March 2021, we assessed different dosing schedules and adverse events following immunization (AEFIs) for ChAdOx1 nCoV-19 vaccine among healthcare workers (HCWs). METHODS: We performed a prospective cohort study to estimate the prevalence of IgG antibodies to SARS-CoV-2 before and after ChAdOx1 nCoV-19 vaccination. We conducted antibody testing among HCWs in February 2021 (baseline), before the second dose (June-July 2021), and 1 and 3 months after the second dose. We detected antibodies to SARS-CoV-2 using Tetracore® FlexImmArray™, and surrogate neutralizing antibodies using GenScript cPass™. Neither assay can distinguish natural from vaccine-induced antibodies. We assessed AEFIs through interview post-dose 1 and 1 month post-dose 2. RESULTS: Before vaccination, 1/617 participants (0.16%) had antibodies to SARS-CoV-2. Of these 617, 405 were vaccinated with ChAdOx1 nCoV-19 with 4-8- (60%), 9-12- (27%), or ≥13-week (13%) intervals between the 2 doses. Three months following series completion, 99% and 97% of vaccinated participants had ≥1 sample with detectable antibodies and surrogate neutralizing antibodies against SARS-CoV-2, respectively. We observed no significant differences among those with different dosing intervals at last follow-up. All participants reported PCR testing for SARS-CoV-2 during the study; 2 (0.5%) were laboratory-confirmed. AEFIs were more frequent post-dose 1 (81%) vs post-dose 2 (21%). CONCLUSIONS: In this population, regardless of dosing interval, ChAdOx1 nCoV-19 induced antibodies within 3 months of the second dose. These findings may offer flexibility to policymakers when balancing programmatic considerations with vaccine effectiveness.

Background: Streptococcus pneumoniae is considered the leading bacterial cause of pneumonia in adults. Yet, it was not commonly detected by traditional culture-based and conventional urinary testing in a recent multicenter etiology study of adults hospitalized with community-acquired pneumonia (CAP). We used novel serotype-specific urinary antigen detection (SSUAD) assays to determine whether pneumococcal cases were missed by traditional testing. Methods: We studied adult patients hospitalized with CAP at 5 hospitals in Chicago and Nashville (2010-2012) and enrolled in the Etiology of Pneumonia in the Community (EPIC) study. Traditional diagnostic testing included blood and sputum cultures and conventional urine antigen detection (ie, BinaxNOW). We applied SSUAD assays that target serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13) to stored residual urine specimens. Results: Among 1736 patients with SSUAD and >/=1 traditional pneumococcal test performed, we identified 169 (9.7%) cases of pneumococcal CAP. Traditional tests identified 93 (5.4%) and SSUAD identified 76 (4.4%) additional cases. Among 14 PCV13-serotype cases identified by culture, SSUAD correctly identified the same serotype in all of them. Cases identified by SSUAD vs traditional tests were similar in most demographic and clinical characteristics, although disease severity and procalcitonin concentration were highest among those with positive blood cultures. The proportion of PCV13 serotype cases identified was not significantly different between the first and second July-June study periods (6.4% vs 4.0%). Conclusions: Although restricted to the detection of only 13 serotypes, SSUAD testing substantially increased the detection of pneumococcal pneumonia among adults hospitalized with CAP.

OBJECTIVE: This study presents child helmet use before, during and after implementing the Vietnamese National Child Helmet Action Plan (NCHAP) and evaluates its effect on child helmet use. The NCHAP, an integrated multisector campaign, incorporated a wide-scale public awareness campaign, school-based interventions, increased police patrolling and enforcement, and capacity building and support to relevant government departments in target provinces. METHODS: In Vietnam's three largest cities, 100 schools in 20 districts were selected to monitor motorcycle helmet use behaviour. The effectiveness of the NCHAP was measured by unannounced, filmed observations of student motorcycle passengers and their adult drivers as they arrived or left their schools at four points. Baseline observations at each school were conducted in March 2014, with subsequent observations in April 2015, December 2015 and May 2016. RESULTS: Across the 84 218 observed students, student helmet prevalence increased from 36.1% in March 2014 to 69.3% immediately after the initiation in April 2015. Subsequent observations in December 2015 and May 2016 showed a reduction and stabilisation of helmet use, with 49.8% and 56.9% of students wearing helmets, respectively. Helmet use in students was higher when adult drivers were also wearing helmets. CONCLUSIONS: Integrated multisectoral interventions between governments, civil society and the corporate sector that incorporate communications, school-based education, incentives for change and police enforcement have the potential to increase helmet use among children. Future integrated campaigns may be more effective with an increased focus on parents and other adult drivers given their potential influence on child helmet use.

OBJECTIVES: External validity, or generalisability, is the measure of how well results from a study pertain to individuals in the target population. We assessed generalisability, with respect to socioeconomic status, of estimates from a matched case-control study of 13-valent pneumococcal conjugate vaccine effectiveness for the prevention of invasive pneumococcal disease in children in the USA. DESIGN: Matched case-control study. SETTING: Thirteen active surveillance sites for invasive pneumococcal disease in the USA. PARTICIPANTS: Cases were identified from active surveillance and controls were age and zip code matched. OUTCOME MEASURES: Socioeconomic status was assessed at the individual level via parent interview (for enrolled individuals only) and birth certificate data (for both enrolled and unenrolled individuals) and at the neighbourhood level by geocoding to the census tract (for both enrolled and unenrolled individuals). Prediction models were used to determine if socioeconomic status was associated with enrolment. RESULTS: We enrolled 54.6% of 1211 eligible cases and found a trend toward enrolled cases being more affluent than unenrolled cases. Enrolled cases were slightly more likely to have private insurance at birth (p=0.08) and have mothers with at least some college education (p<0.01). Enrolled cases also tended to come from more affluent census tracts. Despite these differences, our best predictive model for enrolment yielded a concordance statistic of only 0.703, indicating mediocre predictive value. Variables retained in the final model were assessed for effect measure modification, and none were found to be significant modifiers of vaccine effectiveness. CONCLUSIONS: We conclude that although enrolled cases are somewhat more affluent than unenrolled cases, our estimates are externally valid with respect to socioeconomic status. Our analysis provides evidence that this study design can yield valid estimates and the assessing generalisability of observational data is feasible, even when unenrolled individuals cannot be contacted.

In 2014, an acute respiratory illness outbreak affected unaccompanied children from Central America entering the US; 9% of 774 surveyed children were colonized with Streptococcus pneumoniae serotype 5. In our 2015 follow-up survey of 475 children, serotype 5 was not detected, and an interim recommendation to administer 13-valent pneumococcal conjugate vaccine to all unaccompanied children was discontinued.

In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the US for prevention of invasive pneumococcal disease in children. Individual-level socioeconomic status (SES) is a potential confounder of the estimated effectiveness of PCV13 and is often controlled for in observational studies using zip code as a proxy. We assessed the utility of zip code matching for control of SES in a post-licensure evaluation of the effectiveness of PCV13 (calculated as [1-matched odds ratio]*100). We used a directed acyclic graph to identify subsets of confounders and collected SES variables from birth certificates, geocoding, a parent interview, and follow-up with medical providers. Cases tended to be more affluent than eligible controls (for example, 48.3% of cases had private insurance vs. 44.6% of eligible controls), but less affluent than enrolled controls (52.9% of whom had private insurance). Control of confounding subsets, however, did not result in a meaningful change in estimated vaccine effectiveness (original estimate: 85.1%, 95% CI 74.8–91.9%; adjusted estimate: 82.5%, 95% CI 65.6–91.1%). In the context of a post-licensure vaccine effectiveness study, zip code appears to be an adequate, though not perfect, proxy for individual SES.

BACKGROUND: The number of reported cases of Legionnaires' disease, a severe pneumonia caused by the bacterium Legionella, is increasing in the United States. During 2000-2014, the rate of reported legionellosis cases increased from 0.42 to 1.62 per 100,000 persons; 4% of reported cases were outbreak-associated. Legionella is transmitted through aerosolization of contaminated water. A new industry standard for prevention of Legionella growth and transmission in water systems in buildings was published in 2015. CDC investigated outbreaks of Legionnaires' disease to identify gaps in building water system maintenance and guide prevention efforts. METHODS: Information from summaries of CDC Legionnaires' disease outbreak investigations during 2000-2014 was systematically abstracted, and water system maintenance deficiencies from land-based investigations were categorized as process failures, human errors, equipment failures, or unmanaged external changes. RESULTS: During 2000-2014, CDC participated in 38 field investigations of Legionnaires' disease. Among 27 land-based outbreaks, the median number of cases was 10 (range = 3-82) and median outbreak case fatality rate was 7% (range = 0%-80%). Sufficient information to evaluate maintenance deficiencies was available for 23 (85%) investigations. Of these, all had at least one deficiency; 11 (48%) had deficiencies in ≥2 categories. Fifteen cases (65%) were linked to process failures, 12 (52%) to human errors, eight (35%) to equipment failures, and eight (35%) to unmanaged external changes. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Multiple common preventable maintenance deficiencies were identified in association with disease outbreaks, highlighting the importance of comprehensive water management programs for water systems in buildings. Properly implemented programs, as described in the new industry standard, could reduce Legionella growth and transmission, preventing Legionnaires' disease outbreaks and reducing disease.

BACKGROUND: In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was licensed and recommended in the USA for prevention of invasive pneumococcal disease in children. Licensure was based on immunogenicity data comparing PCV13 with the earlier seven-valent formulation. Because clinical endpoints were not assessed for the new antigens, we did a postlicensure matched case-control study to assess vaccine effectiveness. METHODS: Cases in children aged 2-59 months were identified through active surveillance in 13 sites. Controls were identified via birth registries and matched to cases by age and postal (zip) code. The primary objective was the vaccine effectiveness of at least one dose against the 13 serotypes included in PCV13. Secondary objectives included vaccine effectiveness against all-cause invasive pneumococcal disease, against antibiotic non-susceptible invasive pneumococcal disease, and among children with and without underlying conditions. Vaccine effectiveness was calculated as (1 - matched odds ratio) x 100%. FINDINGS: We enrolled 722 children with invasive pneumococcal disease and 2991 controls; PCV13 serotype cases (217 [30%]) included most commonly serotypes 19A (128 [18%]), 7F (32 [4%]), and 3 (43 [6%]). Vaccine effectiveness against PCV13 serotypes was 86.0% (95% CI 75.5 to 92.3), driven by serotypes 19A and 7F, for which vaccine effectiveness was 85.6% (95% CI 70.6 to 93.5) and 96.5% (82.7 to 100), respectively. We also identified statistically significant effectiveness against serotype 3 (79.5%, 95% CI 30.3 to 94.8) and against antibiotic non-susceptible invasive pneumococcal disease (65.6%, 44.9 to 78.7). Vaccine effectiveness against all-cause invasive pneumococcal disease was 60.2% (95% CI 46.8 to 70.3). Vaccine effectiveness was similar among children with (81.4%, 95% CI 45.4 to 93.6) and without (85.8%, 74.9 to 91.9) underlying conditions. INTERPRETATION: PCV13 appears highly effective against invasive pneumococcal disease among children in the USA in the context of routine and catch-up schedules, although some new vaccine antigens could not be assessed. PCV13 immunisation provides a robust strategy for combating pneumococcal antimicrobial resistance. FUNDING: Centers for Disease Control and Prevention.

BACKGROUND: From January-July 2014, >46,000 unaccompanied children (UC) from Central America crossed the U.S.-Mexico border. In June-July, UC aged 9-17 years in four shelters and a processing center in four U.S. states were hospitalized with acute respiratory illness. We conducted a multistate investigation to interrupt disease transmission. METHODS: Medical charts were abstracted for hospitalized UC. Non-hospitalized UC with influenza-like illness were interviewed, and nasopharyngeal and oropharyngeal swabs for PCR-based detection of respiratory pathogens were collected. Nasopharyngeal swabs were used to assess pneumococcal colonization in symptomatic and asymptomatic UC. Pneumococcal blood isolates from hospitalized UC and nasopharyngeal isolates were characterized by serotyping (Quellung) and whole-genome sequencing. RESULTS: Among the 15 hospitalized UC, 4 (44%) of 9 tested positive for influenza viruses, and 6 (43%) of 14 with blood cultures grew pneumococcus, all serotype 5. Among 48 non-hospitalized children with influenza-like illness, >1 respiratory pathogen was identified in 46 (96%). Among 774 non-hospitalized UC, 185 (24%) yielded pneumococcus, and 70 (38%) were serotype 5. UC who transferred through the processing center were more likely than others to be colonized with serotype 5 (OR 3.8; 95% CI, 2.1-6.9). Analysis of the core pneumococcal genomes detected two related, yet independent, clusters. No pneumococcus cases were reported after pneumococcal and influenza immunization campaigns were implemented. CONCLUSIONS: This outbreak of respiratory disease was due to multiple pathogens, including Streptococcus pneumoniae serotype 5 and influenza viruses. Pneumococcal and influenza vaccinations prevented further transmission. Future efforts to prevent similar outbreaks will benefit from use of both vaccines.

During an etiology study of adults hospitalized for pneumonia, in which urine specimens were examined for serotype-specific pneumococcal antigen detection, we observed that some patients received 23-valent pneumococcal polysaccharide vaccine before urine collection. Some urine samples became positive for specific vaccine pneumococcal serotypes shortly after vaccination, suggesting false-positive test results.

The incidence of pneumococcal pneumonia among adults is a key driver for the cost-effectiveness of pneumococcal conjugate vaccine used among children. We sought to obtain more accurate incidence estimates among adults by including results of pneumococcal urine antigen testing (UAT) from population-based pneumonia surveillance in two Thai provinces. Active surveillance from 2006 to 2011 identified acute lower respiratory infection (ALRI)-related hospital admissions. Adult cases of pneumococcal pneumonia were defined as hospitalized ALRI patients aged ≥ 18 years with isolation of Streptococcus pneumoniae from blood or with positive UAT. Among 39,525 adult ALRI patients, we identified 481 pneumococcal pneumonia cases (105 by blood culture, 376 by UAT only). Estimated incidence of pneumococcal pneumonia hospitalizations was 30.5 cases per 100,000 person-years (2.2 and 28.3 cases per 100,000 person-years by blood culture and UAT, respectively). Incidence varied between 22.7 in 2007 and 43.5 in 2010, and increased with age to over 150 per 100,000 person-years among persons aged ≥ 70 years. Viral coinfections including influenza A/B, respiratory syncytial virus (RSV), and adenovirus occurred in 11% (44/405) of pneumococcal pneumonia cases tested. Use of UAT to identify cases of pneumococcal pneumonia among adults in rural Thailand substantially increases estimates of pneumococcal pneumonia burden, thereby informing cost-effectiveness analyses and vaccine policy decisions.

Two pneumococcal vaccines are currently licensed for use in the United States: the 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Wyeth Pharmaceuticals, Inc., a subsidiary of Pfizer Inc.]) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Pneumovax 23, Merck and Co., Inc.]). The Advisory Committee on Immunization Practices (ACIP) currently recommends that a dose of PCV13 be followed by a dose of PPSV23 in all adults aged >/=65 years who have not previously received pneumococcal vaccine and in persons aged >/=2 years who are at high risk for pneumococcal disease because of underlying medical conditions (Table) (1-4). The recommended intervals between PCV13 and PPSV23 given in series differ by age and risk group and the order in which the two vaccines are given (1-4).

Active Bacterial Core surveillance (ABCs) was established in 1995 as part of the Centers for Disease Control and Prevention Emerging Infections Program (EIP) network to assess the extent of invasive bacterial infections of public health importance. ABCs is distinctive among surveillance systems because of its large, population-based, geographically diverse catchment area; active laboratory-based identification of cases to ensure complete case capture; detailed collection of epidemiologic information paired with laboratory isolates; infrastructure that allows for more in-depth investigations; and sustained commitment of public health, academic, and clinical partners to maintain the system. ABCs has directly affected public health policies and practices through the development and evaluation of vaccines and other prevention strategies, the monitoring of antimicrobial drug resistance, and the response to public health emergencies and other emerging infections.

Two decades ago, the Emerging Infections Program of the US Centers for Disease Control and Prevention implemented what seemed like a simple yet novel idea: a population- and laboratory-based surveillance system designed to identify and characterize invasive bacterial infections, including those caused by Streptococcus pneumoniae. This system, known as Active Bacterial Core surveillance, has since served as a flexible platform for following trends in invasive pneumococcal disease and studying vaccination as the most effective method for prevention. We report the contributions of Active Bacterial Core surveillance to every pneumococcal vaccine policy decision in the United States during the past 20 years.

The Emerging Infections Program (EIP), a collaboration between (currently) 10 state health departments, their academic center partners, and the Centers for Disease Control and Prevention, was established in 1995. The EIP performs active, population-based surveillance for important infectious diseases, addresses new problems as they arise, emphasizes projects that lead to prevention, and develops and evaluates public health practices. The EIP has increasingly addressed the health equity challenges posed by Healthy People 2020. These challenges include objectives to increase the proportion of Healthy People-specified conditions for which national data are available by race/ethnicity and socioeconomic status as a step toward first recognizing and subsequently eliminating health inequities. EIP has made substantial progress in moving from an initial focus on monitoring social determinants exclusively through collecting and analyzing data by race/ethnicity to identifying and piloting ways to conduct population-based surveillance by using area-based socioeconomic status measures.

BACKGROUND: Streptococcus pneumoniae (SP) serotype distribution among nasopharyngeal (NP) carriage isolates changed significantly after the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7). We evaluated the impact on NP carriage and invasive disease of SP after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in March 2010. METHODS: NP swabs were collected from children 6-59 months of age in an emergency department from July 2010-June 2013. After broth enrichment, samples were cultured for SP and isolates were serotyped. Clinical and immunization records were reviewed. Findings during six sequential 6-month study periods were compared. Surveillance isolates of invasive disease isolates were reviewed. RESULTS: A total of 2,048 children were enrolled and 656 (32%) were SP carriers. Mean age of carriers was 27 months, 54% were males. Carriage was higher among daycare attendees (p<0.01) and children with respiratory tract illnesses (p<0.5) and otitis media (p<0.01). Commonly carried serotypes included 35B (15.2%), 15B/C (14.2%), 19A (9.6%), 11A (8%), 23B (5.6%), 6C (5.3%), 21 (5%), and 15A (5%); 13.9% were PCV13 serotypes. The proportion of children with SP carriage remained stable but the serotype distribution changed over the study period. Among carriers, PCV13 serotypes declined from 29% (36/124) to 3% (3/99) (p<0.0001), predominantly due to decline of serotype 19A from 25.8% (32/124) to 3% (3/99) (p<0.0001); non-PCV13 serotypes (excluding 6C) increased from 68.4% (78/114) to 97% (95/98) (p<0.0001); serotype 35B significantly increased from 8.9% (11/124) to 25.3% (25/99) (p<0.05). Nonsusceptibility to ceftriaxone declined from 22.6% (28/124) to 0% (0/99) (p<0.0001), with a similar decline in penicillin nonsusceptibility. CONCLUSIONS: Introduction of PCV13 for universal infant use was associated with significant reductions in nasopharyngeal carriage of PCV13 serotypes and resistant strains. Carriage of non-PCV13 serotypes increased modestly, particularly serotype 35B. Further investigation is warranted to determine whether non-vaccine pneumococcal serotypes carried in the nasopharynx are associated with significant replacement disease.

BACKGROUND: In 2000, seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the USA and resulted in dramatic reductions in invasive pneumococcal disease (IPD) and moderate increases in non-PCV7 type IPD. In 2010, PCV13 replaced PCV7 in the US immunisation schedule. We aimed to assess the effect of use of PCV13 in children on IPD in children and adults in the USA. METHODS: We used laboratory-based and population-based data on incidence of IPD from the Active Bacterial Core surveillance (part of the Centers for Disease Control and Prevention's Emerging Infections Program) in a time-series model to compare rates of IPD before and after the introduction of PCV13. Cases of IPD between July 1, 2004, and June 30, 2013, were classified as being caused by the PCV13 serotypes against which PCV7 has no effect (PCV13 minus PCV7). In a time-series model, we used an expected outcomes approach to compare the reported incidence of IPD to that which would have been expected if PCV13 had not replaced PCV7. FINDINGS: Compared with incidence expected among children younger than 5 years if PCV7 alone had been continued, incidence of IPD overall declined by 64% (95% interval estimate [95% IE] 59-68) and IPD caused by PCV13 minus PCV7 serotypes declined by 93% (91-94), by July, 2012, to June, 2013. Among adults, incidence of IPD overall also declined by 12-32% and IPD caused by PCV13 minus PCV7 type IPD declined by 58-72%, depending on age. We estimated that over 30 000 cases of IPD and 3000 deaths were averted in the first 3 years after the introduction of PCV13. INTERPRETATION: PCV13 reduced IPD across all age groups when used routinely in children in the USA. These findings provide reassurance that, similar to PCV7, PCVs with additional serotypes can also prevent transmission to unvaccinated populations. FUNDING: Centers for Disease Control and Prevention.

The 7-valent pneumococcal conjugate vaccine (PCV7) was added to the U.S. infant immunization schedule in the year 2000. By 2009, PCV7 introduction was associated with a 43% decline in all-cause pneumonia among U.S. children aged <2 years. In 2010, a new 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the infant immunization schedule, expanding protection from seven to 13 pneumococcal serotypes. To examine changes in all-cause pneumonia hospitalizations among children aged <2 years after the switch to PCV13, Tennessee hospital discharge data for 1998-2012 were analyzed. By 2012, all-cause pneumonia hospitalizations in children aged <2 years had declined an additional 27%, relative to the PCV7 years. Pneumonia hospitalizations were estimated to be 4.1 per 1,000 population in 2012, a historically low rate that represents a 72% decline from the rate before PCV7 introduction. Tennessee children aged <2 years experienced about 1,300 fewer pneumonia hospitalizations annually in 2011 and 2012 than in the years before pneumococcal conjugate vaccine (PCV) use. These data attest to the powerful impact of the PCV program on pneumonia in Tennessee children. The observed trend likely represents a major decline in pneumococcal pneumonia, which should stimulate a reassessment of current causes and appropriate management of pneumonia in children.

On August 13, 2014, the Advisory Committee on Immunization Practices (ACIP) recommended routine use of 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Wyeth Pharmaceuticals, Inc., a subsidiary of Pfizer Inc.]) among adults aged ≥65 years. PCV13 should be administered in series with the 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Pneumovax23, Merck & Co., Inc.]), the vaccine currently recommended for adults aged ≥65 years. PCV13 was approved by the Food and Drug Administration (FDA) in late 2011 for use among adults aged ≥50 years. In June 2014, the results of a randomized placebo-controlled trial evaluating efficacy of PCV13 for preventing community-acquired pneumonia among approximately 85,000 adults aged ≥65 years with no prior pneumococcal vaccination history (CAPiTA trial) became available and were presented to ACIP. The evidence supporting PCV13 vaccination of adults was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework and determined to be type 2 (moderate level of evidence); the recommendation was categorized as a Category A recommendation. This report outlines the new recommendations for PCV13 use, provides guidance for use of PCV13 and PPSV23 among adults aged ≥65 years, and summarizes the evidence considered by ACIP to make this recommendation.

Streptococcus pneumoniae (pneumococcus) is the most common bacterial etiology of community-acquired pneumonia (CAP) in adults, a leading cause of death. The majority of pneumococcal CAP is diagnosed by blood culture, which likely underestimates the burden of disease. The 2007 CAP guidelines recommend routine use of the rapid pneumococcal urinary antigen (UAg) test. To assess the how pneumococcal UAg testing is being used among hospitalized adult CAP patients and what barriers restrict its use, a Web-based survey was distributed in 2013 to 1287 infectious disease physician members of the Emerging Infectious disease Network of the Infectious Disease Society of America. Of 493 eligible responses, 65% use the pneumococcal UAg test. The primary barrier to UAg use was availability (46%). UAg users reported ordering fewer other diagnostic tests and tailoring antibiotic therapy. Increased access to UAg tests could improve pneumonia management and pneumococcal CAP surveillance.

BACKGROUND: The burden of disease due to S. pneumoniae (pneumococcus), particularly pneumonia, remains high despite the widespread use of vaccines. Drug resistant strains complicate clinical treatment and may increase costs. We estimated the annual burden and incremental costs attributable to antibiotic resistance in pneumococcal pneumonia. METHODS: We derived estimates of healthcare utilization and cost (in 2012 dollars) attributable to penicillin, erythromycin and fluoroquinolone resistance by taking the estimate of disease burden from a previously described decision tree model of pneumococcal pneumonia in the U.S. We analyzed model outputs assuming only the existence of susceptible strains and calculating the resulting differences in cost and utilization. We modeled the cost of resistance from delayed resolution of illness and the resulting additional health services. RESULTS: Our model estimated that non-susceptibility to penicillin, erythromycin and fluoroquinolones directly caused 32,398 additional outpatient visits and 19,336 hospitalizations for pneumococcal pneumonia. The incremental cost of antibiotic resistance was estimated to account for 4% ($91 million) of direct medical costs and 5% ($233 million) of total costs including work and productivity loss. Most of the incremental medical cost ($82 million) was related to hospitalizations resulting from erythromycin non-susceptibility. Among patients under age 18 years, erythromycin non-susceptibility was estimated to cause 17% of hospitalizations for pneumonia and $38 million in costs, or 39% of pneumococcal pneumonia costs attributable to resistance. CONCLUSIONS: We estimate that antibiotic resistance in pneumococcal pneumonia leads to substantial healthcare utilization and cost, with more than one-third driven by macrolide resistance in children. With 5% of total pneumococcal costs directly attributable to resistance, strategies to reduce antibiotic resistance or improve antibiotic selection could lead to substantial savings.

BACKGROUND: In June, 2012 a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) was added to the recommendation for immunocompromised adults who were previously recommended to receive only 23-valent pneumococcal polysaccharide vaccine (PPSV23). PCV13 may be more effective, though it covers fewer disease-causing strains. OBJECTIVE: We examined the incremental cost-effectiveness of adding one dose of PCV13 to the pre-2012 recommendation of PPSV23 for adults with 4 immunocompromising conditions who are at increased risk of pneumococcal disease: HIV/AIDS, hematologic cancer, solid organ transplants, and end stage renal disease. METHODS: We used a probabilistic model following a single cohort of 302,397 immunocompromised adults. We used vaccination coverage and disease incidence data specific to each immunocompromising condition. Assumptions about PPSV23 and PCV13 vaccine effectiveness were based on two randomized controlled trials and several observational studies conducted among HIV-infected adults. Because no such studies have been conducted among other immunocompromised populations, we made further assumptions about the relative vaccine effectiveness in those groups. Cost-effectiveness ratios were determined for each condition and for all 4 groups in total. RESULTS: Our model indicated that adding one dose of PCV13 to adults in the United States with 4 immunocompromising conditions would cost $16 million (in 2009$) but provide off-setting savings of $21 million per cohort from the societal perspective. These savings come largely from decreased medical costs among adults with end stage renal disease. This dose of PCV13 would prevent 57 cases of invasive pneumococcal disease, 619 cases of hospitalized all-cause pneumonia, avert 93 deaths, and save 1360 quality adjusted life years per cohort. CONCLUSION: The addition of one dose of PCV13 to the previously recommended PPSV23 doses for adults with selected immunocompromised conditions potentially reduces both disease and costs.

BACKGROUND: The introduction of 7-valent pneumococcal conjugate vaccine (PCV7) into the U.S. childhood immunization schedule in 2000 has substantially reduced the incidence of vaccine-serotype invasive pneumococcal disease in young children and in unvaccinated older children and adults. By 2004, hospitalizations associated with pneumonia from any cause had also declined markedly among young children. Because of concerns about increases in disease caused by nonvaccine serotypes, we wanted to determine whether the reduction in pneumonia-related hospitalizations among young children had been sustained through 2009 and whether such hospitalizations in older age groups had also declined. METHODS: We estimated annual rates of hospitalization for pneumonia from any cause using the Nationwide Inpatient Sample database. The reason for hospitalization was classified as pneumonia if pneumonia was the first listed diagnosis or if it was listed after a first diagnosis of sepsis, meningitis, or empyema. Average annual rates of pneumonia-related hospitalizations from 1997 through 1999 (before the introduction of PCV7) and from 2007 through 2009 (well after its introduction) were used to estimate annual declines in hospitalizations due to pneumonia. RESULTS: The annual rate of hospitalization for pneumonia among children younger than 2 years of age declined by 551.1 per 100,000 children (95% confidence interval [CI], 445.1 to 657.1), which translates to 47,000 fewer hospitalizations annually than expected on the basis of the rates before PCV7 was introduced. The rate for adults 85 years of age or older declined by 1300.8 per 100,000 (95% CI, 984.0 to 1617.6), which translates to 73,000 fewer hospitalizations annually. For the three age groups of 18 to 39 years, 65 to 74 years, and 75 to 84 years, the annual rate of hospitalization for pneumonia declined by 8.4 per 100,000 (95% CI, 0.6 to 16.2), 85.3 per 100,000 (95% CI, 7.0 to 163.6), and 359.8 per 100,000 (95% CI, 199.6 to 520.0), respectively. Overall, we estimated an age-adjusted annual reduction of 54.8 per 100,000 (95% CI, 41.0 to 68.5), or 168,000 fewer hospitalizations for pneumonia annually. CONCLUSIONS: Declines in hospitalizations for childhood pneumonia were sustained during the decade after the introduction of PCV7. Substantial reductions in hospitalizations for pneumonia among adults were also observed.

INTRODUCTION: Pneumococcal vaccines are highly effective at preventing invasive pneumococcal disease (IPD), a leading cause of global morbidity. Because pneumococcal vaccines can be expensive, it is useful to estimate what impact might be expected from their introduction. Our objective was to develop a statistical model that could predict rates of IPD following introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in the U.S. METHODS: We used active surveillance data to design and validate a Poisson model forecasting the reductions in IPD observed after U.S. introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in 2000. We used this model to forecast rates of IPD from 2010 to 2020 in the presence of PCV13. Because increases in non-PCV7-type IPD were evident following PCV7 introduction, we evaluated varying levels of increase in non-PCV13-type IPD ("serotype replacement") by sensitivity analyses. RESULTS: A total of 43,507 cases of IPD were identified during 1998-2009; cases from this period were used to develop the model, which accurately predicted indirect effects of PCV7 in adults, as well as serotype replacement. Assuming that PCV13 provides similar protection against PCV13 serotypes as PCV7 did against PCV7 serotypes, the base-case model predicted approximately 168,000 cases of IPD prevented from 2011 to 2020. When serotype replacement was varied in sensitivity analyses from 0 to levels comparable to that seen with serotype 19A (the most common replacement serotype since PCV7 was introduced), the model predicted 167,000-170,000 cases prevented. The base-case model predicted rates of IPD in children under five years of age decreasing from 21.9 to 9.3 cases per 100,000 population. CONCLUSIONS: This model provides a "benchmark" for assessing progress in the prevention of IPD in the years after PCV13 introduction. The amount of serotype replacement is unlikely to greatly affect the overall number of cases prevented by PCV13.

BACKGROUND: Because pneumococcal pneumonia was prevalent during previous influenza pandemics, we evaluated invasive pneumococcal pneumonia (IPP) rates during the 2009 influenza A(H1N1) pandemic. METHODS: We identified laboratory-confirmed, influenza-associated hospitalizations and IPP cases (pneumococcus isolated from normally sterile sites with discharge diagnoses of pneumonia) using active, population-based surveillance in the U.S. We compared IPP rates during peak pandemic months (April 2009-March 2010) to mean IPP rates in non-pandemic years (April 2004-March 2009) and, using Poisson models, to 2006-8 influenza seasons. RESULTS: Higher IPP rates occurred during the peak pandemic month compared to non-pandemic periods in 5-24 (IPP rate per 10 million: 48 v. 9 (95% confidence interval (CI) 5-13), 25-49 (74 v. 53 (CI 41-65)), 50-64 (188 v. 114 (CI 85-143)), and ≥65 year-olds (229 v. 187 (CI 159-216)). In the models with seasonal influenza rates included, observed IPP rates during the pandemic peak were within the predicted 95% CIs, suggesting this increase was not greater than observed with seasonal influenza. CONCLUSIONS: The recent influenza pandemic likely resulted in an out-of-season IPP peak among persons ≥5 years. The IPP peak's magnitude was similar to that seen during seasonal influenza epidemics.

BACKGROUND: Certain chronic diseases increase risk for invasive pneumococcal disease (IPD) and are indications for receipt of 23-valent pneumococcal polysaccharide vaccine (PPV23). Since the pediatric introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in 2000, incidence of IPD among adults has declined. The relative magnitude of these indirect effects among persons with and without PPV23 indications is unknown. METHODS: We evaluated IPD incidence among adults with and without PPV23 indications using population- and laboratory-based data collected during 1998-2009 and estimates of the denominator populations with PPV23 indications from the National Health Interview Survey. We compared rates before and after PCV7 use by age, race, PPV23 indication and serotype. RESULTS: The proportion of adult IPD cases with PPV23 indications increased from 51% before to 61% after PCV7 introduction (p<0.0001). PCV7-serotype IPD declined among all race, age and PPV23 indication strata, ranging from 82-97%. Overall IPD rates declined in most strata, by up to 65%. However, incidence remained highest among adults with PPV23 indications compared to those without (34.9 vs. 8.8 cases per 100,000 population, respectively). Apart from age ≥65 years, diabetes is now the most common indication for PPV23 (20% of all cases vs. 10% of cases in 1998-99). CONCLUSIONS: Although IPD rates have declined among adults, adults with underlying conditions remain at increased risk of IPD and comprise a larger proportion of adult IPD cases in 2009 compared to 2000. A continued increase in the prevalence of diabetes among U.S. adults could lead to increased burden of pneumococcal disease.

During a pneumococcal disease outbreak in a pediatric psychiatric unit in a hospital in Rhode Island, USA, 6 (30%) of 20 patients and staff were colonized with Streptococcus pneumoniae serotype 15A, which is not included in pneumococcal vaccines. The outbreak subsided after implementation of antimicrobial drug prophylaxis and enhanced infection control measures.

BACKGROUND: Seven-valent pneumococcal conjugate vaccination (PCV7) has been shown to reduce rates of otitis media (OM) when given as a 2- or 3-dose primary series followed by a booster dose. However, data on the 2- or 3-dose primary series' relative effectiveness against OM is very limited. Using data from the United States after the 2000 introduction of PCV7, we compared the effectiveness of a 2- versus a 3-dose primary series against acute otitis media (AOM). METHODS: We examined the 2002 birth cohort from the Medstat MarketScan insurance claims database and compared the incidence of AOM in children that received two or three doses in the primary PCV7 series using propensity score matching. We assessed AOM rates after completion of the primary series and before the booster dose, and after the booster dose until four years of age. RESULTS: Among the 2002 birth cohort captured by MarketScan, we identified 38,786 children we could match with immunization data; of these 8515 (22%) received a 2-dose primary series and 10,152 (26%) received a 3-dose primary series. After matching, cumulative AOM incidence between 6 and 12 months among children who did not receive a PCV7 dose between the primary series and the booster dose was 37.6% for the 2-dose series and 35.0% for the 3-dose series. This difference was not statistically significant (p=0.22). Cumulative AOM incidence between one and four years, i.e., after the booster dose, was 104.4% for the 2-dose primary series and 102.5% for the 3-dose primary series and was also statistically insignificant (p=0.87). CONCLUSION: In a population of highly-insured children, a 2-dose primary series of PCV7 appears to provide similar protection against AOM as a 3-dose primary series. These data have important implications for national immunization programs where AOM is an important driver of cost-effectiveness.

Pneumococcal pneumonia is concentrated among the elderly. Using a decision analytic model, we projected the future incidence of pneumococcal pneumonia and associated healthcare utilization and costs accounting for an aging US population. Between 2004 and 2040, as the population increases by 38%, pneumococcal pneumonia hospitalizations will increase by 96% (from 401,000 to 790,000), because population growth is fastest in older age groups experiencing the highest rates of pneumococcal disease. Absent intervention, the total cost of pneumococcal pneumonia will increase by $2.5 billion annually, and the demand for healthcare services for pneumococcal pneumonia, especially inpatient capacity, will double in coming decades.