BACKGROUND: National case rates of chlamydia and gonorrhea (CT/GC) among American Indian and Alaska Native (AI/AN) persons are disproportionately high. The Indian Health Service (IHS), which provides healthcare to members of federally recognized tribes, does not currently have a dedicated CT/GC surveillance system. The purpose of this study was to validate the use of CT/GC diagnostic codes for estimating diagnosed CT/GC infections among AI/AN persons that use IHS services. METHODS: We conducted a retrospective study using IHS medical records from all persons aged 15 years and older from 2016 to 2021. We linked records with CT (A56, A74) and GC (A54, O98.2) ICD-10-CM diagnostic codes to laboratory results within 30 days for each person. We calculated the sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of CT/GC diagnostic codes using laboratory test results as the reference standard. RESULTS: We identified over 1.6 million CT/GC laboratory tests, and 52,815 CT and 19,971 GC diagnostic codes. Diagnostic code sensitivity was slightly higher for CT (54%) than GC (50%). Specificity, PPV, and NPV were high for CT and GC (range: 83.3-99.8%). About one-third of CT/GC diagnostic codes could not be linked to a test result. CONCLUSIONS: The validation indicates that diagnostic codes align well with linked laboratory test results. However, due to the relatively large number of diagnostic codes and positive tests that could not be linked, combining the two would inform more reliable estimates of diagnosed CT/GC infections among AI/AN persons who use IHS for healthcare.

Recommended vaccination at nine months of age with the measles-containing vaccine (MCV1) has been part of Ethiopia's routine immunization program since 1980. A second dose of MCV (MCV2) was introduced in 2019 for children 15 months of age. We examined MCV1 and MCV2 coverage and the factors associated with measles vaccination status. A cross-sectional household survey was conducted among caregivers of children aged 12-35 months in selected districts of Oromia Region. Measles vaccination status was determined using home-based records, when available, or caregivers' recall. We analyzed the association between MCV1 and MCV2 vaccination status and household, caregiver, and child factors using logistic regression. The caregivers of 1172 children aged 12-35 months were interviewed and included in the analysis. MCV1 and MCV2 coverage was 71% and 48%, respectively. The dropout rate (DOR) from the first dose of Pentavalent vaccine to MCV1 was 22% and from MCV1 to MCV2 was 46%. Caregivers were more likely to vaccinate their children with MCV if they gave birth at a health facility, believe that their child had received all recommended vaccines, and know the required number of vaccination visits and doses. MCV2 coverage was low, with a high measles dropout rate (DOR). Caregivers with high awareness of MCV and its schedule were more likely to vaccinate their children. Intensified demand generation, defaulter tracking, and vaccine-stock management should be strengthened to improve MCV uptake.

Invasive disease from Streptococcus pneumoniae (pneumococcus) is a major cause of illness and death in the United States, with an estimated 43,500 cases and 5,000 deaths among persons of all ages in 2009. This report provides updated recommendations from the Advisory Committee on Immunization Practices (ACIP) for prevention of invasive pneumococcal disease (IPD) (i.e., bacteremia, meningitis, or infection of other normally sterile sites) through use of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) among all adults aged >or=65 years and those adults aged 19-64 years with underlying medical conditions that put them at greater risk for serious pneumococcal infection. The new recommendations include the following changes from 1997 ACIP recommendations: 1) the indications for which PPSV23 vaccination is recommended now include smoking and asthma, and 2) routine use of PPSV23 is no longer recommended for Alaska Natives or American Indians aged <65 years unless they have medical or other indications for PPSV23. ACIP recommendations for revaccination with PPSV23 among the adult patient groups at greatest risk for IPD (i.e., persons with functional or anatomic asplenia and persons with immunocompromising conditions) remain unchanged. ACIP recommendations for prevention of pneumococcal disease among infants and youths aged <or=18 years using the 13-valent pneumococcal conjugate vaccine (PCV13) and PPSV23 are published separately.

On February 24, 2010, a 13-valent pneumococcal polysaccharide-protein conjugate vaccine (PCV13 [Prevnar 13, Wyeth Pharmaceuticals Inc., marketed by Pfizer Inc.]) was licensed by the Food and Drug Administration (FDA) for prevention of invasive pneumococcal disease (IPD) caused among infants and young children by the 13 pneumococcal serotypes covered by the vaccine and for prevention of otitis media caused by serotypes also covered by the 7-valent pneumococcal conjugate vaccine formulation (PCV7 [Prevnar, Wyeth]). PCV13 contains the seven serotypes included in PCV7 (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and six additional serotypes (serotypes 1, 3, 5, 6A, 7F, and 19A). PCV13 is approved for use among children aged 6 weeks-71 months and supersedes PCV7, which was licensed by FDA in 2000. This report summarizes recommendations approved by the Advisory Committee on Immunization Practices (ACIP) on February 24, 2010, for the use of PCV13 to prevent pneumococcal disease in infants and young children aged <6 years. Recommendations include 1) routine vaccination of all children aged 2-59 months, 2) vaccination of children aged 60-71 months with underlying medical conditions, and 3) vaccination of children who received ≥1 dose of PCV7 previously (CDC. Licensure of a 13-valent pneumococcal conjugate vaccine [PCV13] and recommendations for use among children-Advisory Committee on Immunization Practices [ACIP], 2010. MMWR 2010;59:258-61). Recommendations also are provided for targeted use of the 23-valent pneumococcal polysaccharide vaccine (PPSV23, formerly PPV23) in children aged 2-18 years with underlying medical conditions that increase their risk for contracting pneumococcal disease or experiencing complications of pneumococcal disease if infected. The ACIP recommendation for routine vaccination with PCV13 and the immunization schedules for children aged ≤59 months who have not received any previous PCV7 or PCV13 doses are the same as those published previously for PCV7 (CDC. Preventing pneumococcal disease among infants and young children: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2000;49[No. RR-9]; CDC. Updated recommendation from the Advisory Committee on Immunization Practices [ACIP] for use of 7-valent pneumococcal conjugate vaccine [PCV7] in children aged 24-59 months who are not completely vaccinated. MMWR 2008;57:343-4), with PCV13 replacing PCV7 for all doses. For routine immunization of infants, PCV13 is recommended as a 4-dose series at ages 2, 4, 6, and 12-15 months. Infants and children who have received ≥1 dose of PCV7 should complete the immunization series with PCV13. A single supplemental dose of PCV13 is recommended for all children aged 14-59 months who have received 4 doses of PCV7 or another age-appropriate, complete PCV7 schedule. For children who have underlying medical conditions, a supplemental PCV13 dose is recommended through age 71 months. Children aged 2-18 years with underlying medical conditions also should receive PPSV23 after completing all recommended doses of PCV13.

This corrects the article DOI: 10.3389/fpubh.2023.1245750. In the published article, there was an error in Table 1 as published. Row and column percentages were inverted for the age group variable. The corrected Table 1 and its caption appear below.

INTRODUCTION: Vaccination is a critical public health intervention, and vaccine hesitancy is a major threat. Globally, confidence in COVID-19 vaccines has been low, and rates of routine immunizations decreased during the COVID-19 pandemic. Because healthcare providers are a trusted source of information on vaccination in Kazakhstan, it was vital to understand their knowledge, attitudes and practices (KAP) related to both routine and COVID-19 vaccines. METHODS: From March to April 2021, we conducted a cross-sectional study among the healthcare providers responsible for vaccination in 54 primary care facilities in three cities in Kazakhstan. All consenting providers anonymously completed structured online questionnaires at their place of work. A provider was classified as having COVID-19 vaccine confidence if they planned to get a COVID-19 vaccine, believed that COVID-19 vaccines are important to protect their community and either believed the vaccine was important to protect themselves or believed that getting a vaccine was safer than getting COVID-19. Statistical analysis included chi-square, Spearman's rank correlation coefficient, and Poisson regression. RESULTS: Of 1,461 providers, 30% had COVID-19 vaccine confidence, 40% did not, and 30% would refuse vaccination. Participants were mostly female (92%) and ≤ 35 years old (57%). Additionally, 65% were nurses, 25% were family physicians, and 10% were pediatricians. Adequate KAP for routine vaccines was low (22, 17, and 32%, respectively). Adequate knowledge was highest among pediatricians (42%) and family physicians (28%) and lowest among nurses (17%). Misconceptions about vaccines were high; 54% believed that influenza vaccines cause flu, and 57% believed that there is a scientifically proven association between vaccination and autism and multiple sclerosis. About half (45%) of the practitioners felt confident answering patient vaccine-related concerns. In adjusted models, COVID-19 vaccine confidence was positively associated with adequate knowledge of vaccines (prevalence ratio: 1.2, 95% confidence interval: 1.0-1.4) and adequate attitudes related to routine vaccines (3.1, 2.7-3.6). CONCLUSION: Our study uncovers critical areas for interventions to improve KAP related to routine immunizations and COVID-19 vaccine confidence among providers in Kazakhstan. The complex relationship between KAP of routine vaccines and COVID-19 vaccine confidence underscores the importance of addressing vaccine hesitancy more broadly and not focusing solely on COVID-19.

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.

Streptococcus pneumoniae serotype 1 (ST1) was an important cause of invasive pneumococ-cal disease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) con-taining ST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERE‐ NADE) project gathered ST1 IPD surveillance data from sites globally and aimed to estimate PCV10/13 impact on ST1 IPD incidence. We estimated ST1 IPD incidence rate ratios (IRRs) compar-ing the pre‐PCV10/13 period to each post‐PCV10/13 year by site using a Bayesian multi‐level, mixed-effects Poisson regression and all‐site IRRs using a linear mixed‐effects regression (N = 45 sites). Following PCV10/13 introduction, the incidence rate (IR) of ST1 IPD declined among all ages. After six years of PCV10/13 use, the all‐site IRR was 0.05 (95% credibility interval 0.04–0.06) for all ages, 0.05 (0.04–0.05) for <5 years of age, 0.08 (0.06–0.09) for 5–17 years, 0.06 (0.05–0.08) for 18–49 years, 0.06 (0.05–0.07) for 50–64 years, and 0.05 (0.04–0.06) for ≥65 years. PCV10/13 use in infant immunization programs was followed by a 95% reduction in ST1 IPD in all ages after approximately 6 years. Limited data availability from the highest ST1 disease burden countries using a 3+0 schedule constrains generalizability and data from these settings are needed.

BACKGROUND: Influenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings. METHODS AND FINDINGS: We aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996-31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle-Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20-64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%-16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000-46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000-9,432,000) LRI hospitalizations occur each year among adults. While adults <65 years contribute most influenza-associated LRI hospitalizations and episodes (3,464,000 [95% CI 1,885,000-5,978,000] LRI hospitalizations and 31,087,000 [95% CI 19,987,000-44,444,000] LRI episodes), hospitalization rates were highest in those ≥65 years (437/100,000 person-years [95% CI 265-612/100,000 person-years]). For this analysis, published articles were limited in their inclusion of stratified testing data by year and age group. Lack of information regarding influenza vaccination of the study population was also a limitation across both types of data sources. CONCLUSIONS: In this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide.

BACKGROUND: Colonisation with Streptococcus pneumoniae can lead to invasive pneumococcal disease and pneumonia. Pneumococcal acquisition and prevalence of colonisation are high in children. In older adults, a population susceptible to pneumococcal disease, colonisation prevalence is reported to be lower, but studies are heterogeneous. METHODS: This is a systematic review and meta-analysis of prevalence of, and risk factors for, pneumococcal colonisation in adults ≥ 60 years of age (PROSPERO #42016036891). We identified peer-reviewed studies reporting the prevalence of S. pneumoniae colonisation using MEDLINE and EMBASE (until April 2016), excluding studies of acute disease. Participant-level data on risk factors were sought from each study. FINDINGS: Of 2202 studies screened, 29 were analysable: 18 provided participant-level data (representing 6290 participants). Prevalence of detected pneumococcal colonisation was 0-39% by conventional culture methods and 3-23% by molecular methods. In a multivariate analysis, colonisation was higher in persons from nursing facilities compared with the community (odds ratio (OR) 2•30, 95% CI 1•26-4•21 and OR 7•72, 95% CI 1•15-51•85, respectively), in those who were currently smoking (OR 1•69, 95% CI 1•12-2•53) or those who had regular contact with children (OR 1•93, 95%CI 1•27-2•93). Persons living in urban areas had significantly lower carriage prevalence (OR 0•43, 95%CI 0•27-0•70). INTERPRETATION: Overall prevalence of pneumococcal colonisation in older adults was higher than expected but varied by risk factors. Future studies should further explore risk factors for colonisation, to highlight targets for focussed intervention such as pneumococcal vaccination of high-risk groups. FUNDING: No funding was required.

BACKGROUND: Rotavirus vaccine was introduced in Kenya immunization program in July 2014. Pre-vaccine disease burden estimates are important for assessing vaccine impact. METHODS: Children with acute gastroenteritis (AGE) (>/=3 loose stools and/or >/= 1 episode of unexplained vomiting followed by loose stool within a 24-h period), hospitalized in Siaya County Referral Hospital (SCRH) from January 2010 through December 2013 were enrolled. Stool specimens were tested for rotavirus (RV) using an enzyme immunoassay (EIA). Hospitalization rates were calculated using person-years of observation (PYO) from the Health Demographic Surveillance System (HDSS) as a denominator, while adjusting for healthcare utilization at household level and proportion of stool specimen collected from patients who met the case definition at the surveillance hospital. Mortality rates were calculated using PYO as the denominator and number of deaths estimated using total deaths in the HDSS, proportion of deaths attributed to diarrhoea by verbal autopsy (VA) and percent positive for rotavirus AGE (RVAGE) hospitalizations. RESULTS: Of 7760 all-cause hospitalizations among children < 5 years of age, 3793 (49%) were included in the analysis. Of these, 21% (805) had AGE; RV was detected in 143 (26%) of 541 stools tested. Among children < 5 years, the estimated hospitalization rates per 100,000 PYO for AGE and RVAGE were 2413 and 429, respectively. Mortality rate associated with AGE and RVAGE were 176 and 45 per 100,000 PYO, respectively. CONCLUSION: AGE and RVAGE caused substantial health care burden (hospitalizations and deaths) before rotavirus vaccine introduction in Kenya.

SETTING: In 2009, the World Health Organization (WHO) conducted a survey of the quality of four anti-tuberculosis drugs in the former Soviet Union countries. Kazakhstan had the highest proportion of substandard drugs. OBJECTIVE: To assess the quality of anti-tuberculosis drugs used in Kazakhstan in 2014. DESIGN: Fourteen anti-tuberculosis drugs from the Almaty Interdistrict TB Dispensary were randomly selected and screened for quality using Global Pharma Health Fund Minilab testing. First, the product and packaging were physically inspected to determine whether tablets/capsules were intact (i.e., whether they contained the full amount of the drug, and whether the packaging was genuine). Second, the tablets/capsules were dissolved in water to test whether they could be adequately absorbed by the body. Finally, semi-quantitive analyses were undertaken using thin-layer chromatography to verify the presence and concentration of the active pharmaceutical ingredient and to detect impurities. RESULTS: We discovered no counterfeit medicines. However, 163 (19%) of the 854 anti-tuberculosis drugs sampled failed at least one of the three tests. These samples were found among 24/50 (48%) batches of 14 anti-tuberculosis drugs. CONCLUSION: Our study identified a high proportion of poor-quality first- and second-line anti-tuberculosis drugs. Use of these medicines may lead to treatment failure and the development of drug resistance. Confirmatory testing should be performed to determine if they should be removed from the market.

OBJECTIVE: To evaluate factors associated with rotavirus diarrhea and to describe severity of illness among children <5 years old with non-dysenteric, moderate-to-severe diarrhea (MSD) in rural western Kenya. METHODS: We analyzed data from children <5 years old with non-dysenteric MSD enrolled as cases in the Global Enteric Multicenter Study (GEMS) in Kenya. A non-dysenteric MSD case was defined as a child with ≥3 loose stools in 24 hrs. and one or more of the following: sunken eyes, skin tenting, intravenous rehydration, or hospitalization, who sought care at a sentinel health center within 7 days of illness onset. Rotavirus antigens in stool samples were detected by ELISA. Demographic and clinical information was collected at enrollment and during a single follow-up home visit at approximately 60 days. We analyzed diarrhea severity using a GEMS 17 point numerical scoring system adapted from the Vesikari score. We used logistic regression to evaluate factors associated with rotavirus infection. RESULTS: From January 31, 2008 to September 30, 2012, among 1,637 (92%) non-dysenteric MSD cases, rotavirus was detected in stools of 245 (15.0%). Rotavirus-positive compared with negative cases were: younger (median age, 8 vs. 13 months; p<0.0001), had more severe illness (median severity score, 9 vs 8; p<0.0001) and had to be hospitalized more frequently (37/245 [15.1%] vs. 134/1,392 [9.6%]), p <0.013). Independent factors associated with rotavirus infection included age 0-11 months old (aOR = 5.29, 95% CI 3.14-8.89) and presenting with vomiting ≥3 times/24hrs (aOR = 2.58, 95% CI [1.91-3.48]). Rotavirus was detected more commonly in warm and dry months than in the cool and rainy months (142/691 [20%] vs 70/673 [10%]) p<0.0001). CONCLUSIONS: Diarrhea caused by rotavirus is associated with severe symptoms leading to hospitalization. Consistent with other settings, infants had the greatest burden of disease.

To describe the epidemiology of intussusception before introduction of the rotavirus vaccine, we reviewed the records of 280 patients younger than 5 years who were hospitalized in Kenya between 2002 and 2013. The patients who died (18 [6.4%]) had sought care later after symptom onset than the patients who survived (median, 5 vs 3 days, respectively; P = .04). Seeking prompt care may improve therapeutic outcomes.

BACKGROUND: Nasopharyngeal (NP) carriage and invasive pneumococcal disease (IPD) due to serotypes in the 7-valent pneumococcal conjugate vaccine (PCV7) declined dramatically after vaccine introduction, whereas non-PCV7 serotypes increased modestly. Characteristics of pneumococcal carriage and IPD among children in Atlanta were compared during two time periods: pre-PCV7 introduction and pre-PCV13 introduction. METHODS: NP swabs from 231 and 451 children aged 6 to 59 months receiving outpatient medical care were obtained in 1995 and 2009, respectively. A total of 202 and 47 IPD cases were identified in children < 5 years of age in 1995 and 2008-2009, respectively, through active, population-based surveillance in Atlanta. Isolates were serotyped, sequence typed (ST), and tested for antimicrobial susceptibility RESULTS: Forty percent (93/231) of children in 1995 and 31% (139/451) in 2009 were colonized with Streptococcus pneumoniae; 60% and 0.7% were PCV7 serotypes, respectively. In 1995, PCV7 serotypes accounted for 83% and 19A 5% of IPD compared with no PCV7 serotypes and 49% 19A among IPD in 2009 [P<0.001]. In 2009, PCV13 serotypes accounted for 22% of carriage (mostly 19A) and 60% of invasive isolates [P<0.001]. ST320 accounted for 66% and 52% of 19A carriage and IPD isolates in 2009, respectively; all ST320 isolates were multi-drug resistant. No ST320 NP or IPD isolates were identified pre-PCV7. CONCLUSIONS: Serotype distribution among NP and IPD isolates in Atlanta has shifted to non-PCV7 serotypes; 19A was the leading serotype for both. The multi-drug resistant ST320 strain was responsible for two-thirds of 19A carriage isolates and nearly half of IPD isolates. The predominance of serotype 19A in carriage and IPD among children in Atlanta highlights the potential direct and indirect benefits anticipated by implementation of PCV13 in the community.

Since 1997, the Advisory Committee on Immunization Practices has recommended the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for nonelderly adults with certain medical conditions. In 2008, the Committee added asthma and cigarette smoking to the list of indications for PPSV23 vaccination. Using data from the 2009 National Health Interview Survey, the authors assessed PPSV23 uptake in people with established and new indications. To identify factors independently associated with receiving PPSV23, they used multivariable logistic regression and predictive marginal analyses. In 2009, a total of 35.2 million adults 18-64 years of age (18.6%) had established PPSV23 indications; adding asthma and smoking to the list of indications increased the high-risk population to 71.6 million people (37.9%). Overall, 26.1% of people with established indications for PPSV23 and 17.4% of people with any indication (those previously established, as well as asthma and smoking) had received the vaccine; overall coverage among persons 50-64 years of age was significantly higher than that among persons 18-49 years of age (34.6% vs. 16.7%; P < 0.001) and for all specific indications except cancer. For persons who had asthma or who smoked but had no other indications, rates of coverage were 12.3% and 8.5%, respectively. In persons who had established indications, being older, white, and unemployed and having more physician visits, a prior hospitalization, a regular physician, and health insurance were independently associated with PPSV23 receipt. PPSV23 uptake varies substantially by age and indication but remains low overall, with approximately 59 million unvaccinated high-risk working-age adults. Effective strategies to increase pneumococcal vaccination coverage among at-risk groups are needed.

CONTEXT: The cost-effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) compared with 23-valent pneumococcal polysaccharide vaccine (PPSV23) among US adults is unclear. OBJECTIVE: To estimate the cost-effectiveness of PCV13 vaccination strategies in adults. DESIGN, SETTING, AND PARTICIPANTS: A Markov state-transition model, lifetime time horizon, societal perspective. Simulations were performed in hypothetical cohorts of US 50-year-olds. Vaccination strategies and effectiveness estimates were developed by a Delphi expert panel; indirect (herd immunity) effects resulting from childhood PCV13 vaccination were extrapolated based on observed PCV7 effects. Data sources for model parameters included Centers for Disease Control and Prevention Active Bacterial Core surveillance, National Hospital Discharge Survey and Nationwide Inpatient Sample data, and the National Health Interview Survey. MAIN OUTCOME MEASURES: Pneumococcal disease cases prevented and incremental costs per quality-adjusted life-year (QALY) gained. RESULTS: In the base case scenario, administration of PCV13 as a substitute for PPSV23 in current recommendations (ie, vaccination at age 65 years and at younger ages if comorbidities are present) cost $28,900 per QALY gained compared with no vaccination and was more cost-effective than the currently recommended PPSV23 strategy. Routine PCV13 at ages 50 and 65 years cost $45,100 per QALY compared with PCV13 substituted in current recommendations. Adding PPSV23 at age 75 years to PCV13 at ages 50 and 65 years gained 0.00002 QALYs, costing $496,000 per QALY gained. Results were robust in sensitivity analyses and alternative scenarios, except when low PCV13 effectiveness against nonbacteremic pneumococcal pneumonia was assumed or when greater childhood vaccination indirect effects were modeled. In these cases, PPSV23 as currently recommended was favored. CONCLUSION: Overall, PCV13 vaccination was favored compared with PPSV23, but the analysis was sensitive to assumptions about PCV13 effectiveness against nonbacteremic pneumococcal pneumonia and the magnitude of potential indirect effects from childhood PCV13 on pneumococcal serotype distribution.

BACKGROUND: Although recent reports suggest that the incidence of parapneumonic empyema has increased in several regions of the USA, national trends in disease burden are unknown. National trends in the incidence of parapneumonic empyema hospitalisations and changes in empyema by associated pathogens were examined. METHODS: National hospitalisation data (1996-2008) were analysed and rates estimated using census estimates as denominators. Incidence rate ratios (IRR) compared 2008 with 1996 rates. Discharge diagnosis codes were used to characterise pathogens associated with empyema hospitalisations. RESULTS: Overall, national parapneumonic empyema-related hospitalisation rates increased from 3.04 per 100,000 in 1996 to 5.98 per 100,000 in 2008, a 2.0-fold increase (95% CI 1.8 to 2.1). The increases were observed among children (IRR 1.9 (95% CI 1.4 to 2.7)) and adults aged 18-39, 40-64 and ≥65 years (IRR 1.8 (95% CI 1.5 to 2.1), 2.0 (95% CI 1.6 to 3.1) and 1.7 (95% CI 1.5 to 2.0), respectively). Overall, pneumococcal empyema rates remained relatively stable in all age groups whereas streptococcal- (non-pneumococcal) and staphylococcal-related empyema rates increased 1.9-fold and 3.3-fold, respectively, with consistent increases across age groups. The overall in-hospital case fatality ratio for parapneumonic empyema-related hospitalisations was 8.0% (95% CI 6.4% to 9.5%) in 1996 and 7.2% (95% CI 6.3% to 8.1%) in 2008 (p=0.395). Of the empyemas where study pathogens were listed (37.6%), staphylococcal-related empyema had the largest absolute increases across age groups and was associated with longer hospital stay and higher in-hospital mortality than other empyemas. CONCLUSIONS: Although parapneumonic empyema-related hospitalisations remained relatively rare, they increased substantially during the study period. A number of pathogens, especially staphylococcus, contributed to this increase.

Alaska Native and some American Indian (AI/AN) populations suffer disproportionately high rates of invasive pneumococcal disease (IPD) in both the pediatric and adult populations compared to the general U.S. population. Two pneumococcal vaccines are currently available in the U.S.: a 23-valent pneumococcal polysaccharide vaccine (PPSV23), available since 1983 and recommended for the elderly and those over 2 years of age with underlying medical conditions, and a 13-valent pneumococcal conjugate vaccine (PCV13), used in the routine infant immunization schedule since 2010. The U.S. Advisory Committee on Immunization Practice (ACIP) previously recommended use of PPSV23 for persons living in special environments or social settings, including AN and certain AI persons 2-64 years of age, on the basis of higher disease rates. The recommendation for routine PPSV23 use among AI/AN persons <65 years of age, regardless of underlying conditions, was removed in 2008, although the option for use among those 50-64 years of age living in areas with high pneumococcal disease rates was maintained. The rationale for the revised recommendations lay in the recognition that much of the excess disease burden occurs among those with an existing medical indication for PPSV23. Other considerations for the change were the potential risks of giving multiple PPSV23 doses and the considerable heterogeneity in pneumococcal disease risk among American Indian populations requiring a more tailored approach to local recommendations based on local epidemiology.

BACKGROUND: Older adults are at highest risk of invasive pneumococcal disease (IPD) and are recommended to receive vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23). Antibody concentrations decline following vaccination. We evaluated the immunogenicity and reactogenicity of revaccination and repeat revaccination. METHODS: Adults aged 55-74 years were vaccinated with a 1st to 4th dose of PPV23. Participants were eligible for revaccination if a minimum of 6 years had passed since their last dose of PPV23. Blood collected on the day of vaccination and 30 days later was analyzed by ELISA for IgG to five serotypes. Functional antibody activity was measured using an opsonophagocytic killing (OPK) assay. Reactions to vaccination were documented. RESULTS: Subjects were vaccinated with a 1st dose (n=123), 2nd dose (n=121), or 3rd or 4th dose (n=71) of PPV23. The post-vaccination IgG geometric mean concentrations (GMCs) were similar among first-time vaccinees and re-vaccinees for all serotypes with the exception of a lower GMC for serotype 1 in re-vaccinees. The post-vaccination OPK geometric mean titers (GMTs) were similar among first-time vaccinees and re-vaccinees with the exception of a higher GMT for serotype 6B in re-vaccinees. Compared to first-time vaccinees, re-vaccinees reported more joint pain (p=0.003), fatigue (p=0.027), headache (p=0.011), swelling (p=0.009), and moderate limitation in arm movement (p=0.015). CONCLUSIONS: Repeat revaccination with PPV23, administered 6 or more years after the prior dose, was immunogenic and generally well tolerated.

BACKGROUND: The incidence of childhood pneumonia decreased following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in the United States. Recent regional reports suggest an increase in the incidence of childhood pneumonia complicated by empyema. We assessed whether early decreases in pneumonia hospitalization rates were sustained and trends in such hospitalizations complicated by empyema in United States children aged <5 years. METHODS: Nationwide Inpatient Sample and Census data were used to calculate annual all-cause and pneumococcal pneumonia hospitalization rates for pre-PCV7 (1996-1999) and post-PCV7 years (2001-2007) and to analyze national trends in total and pathogen-specific pneumonia-associated empyema. RESULTS: Among children aged <2 years, all-cause pneumonia hospitalizations decreased 33% (95% confidence interval, 28%-37%) from 1267 cases per 100,000 children in pre-PCV7 years to 852 cases per 100,000 children in post-PCV7 years. Pneumococcal pneumonia hospitalization rates decreased 61% (95% confidence interval, 55%-67%) post-PCV7, compared with pre-PCV7 years. Pneumonia hospitalizations complicated by empyema increased 2.01-fold from 3.5 cases per 100,000 children in 1996-1998 to 7.0 cases per 100,000 children in 2005-2007. Rates of pneumococcal and streptococcal empyema remained stable, whereas rates of staphylococcal and other or unspecified empyema increased 4.08- and 1.89-fold, respectively. Among children aged 2-4 years, all-cause pneumonia rates remained stable, whereas pneumococcal pneumonia decreased by 26% (95% confidence interval, 16-34). Pneumonia complicated by empyema increased 2.81-fold from 3.7 cases per 100,000 children in 1996-1998 to 10.3 cases per 100,000 children in 2005-2007. In this age group, there were 2.17-, 2.80-, 3.76-, and 3.09-fold increases in rates of pneumococcal, streptococcal, staphylococcal, and other or unspecified empyema, respectively. CONCLUSION: Decreases in childhood pneumonia hospitalization rates following PCV7 introduction were sustained. Although empyema complicated only a small fraction of pneumonia hospitalizations, its prevalence increased substantially. This increase was due to several pathogens and warrants continuing monitoring.

CONTEXT: During the 1990s, antibiotic prescriptions for acute respiratory tract infection (ARTI) decreased in the United States. The sustainability of those changes is unknown. OBJECTIVE: To assess trends in antibiotic prescriptions for ARTI. DESIGN, SETTING, AND PARTICIPANTS: The National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey data (1995-2006) were used to examine trends in antibiotic prescription rates by antibiotic indication and class. Annual survey data and census denominators were combined in 2-year intervals for rate calculations. MAIN OUTCOME MEASURES: National annual visit rates and antibiotic prescription rates for ARTI, including otitis media (OM) and non-ARTI. RESULTS: Among children younger than 5 years, annual ARTI visit rates decreased by 17% (95% confidence interval [CI], 9%-24%), from 1883 per 1000 population in 1995-1996 to 1560 per 1000 population in 2005-2006, primarily due to a 33% (95% CI, 22%-43%) decrease in OM visit rates (950 to 634 per 1000 population, respectively). This decrease was accompanied by a 36% (95% CI, 26%-45%) decrease in ARTI-associated antibiotic prescriptions (1216 to 779 per 1000 population). Among persons aged 5 years or older, ARTI visit rates remained stable but associated antibiotic prescription rates decreased by 18% (95% CI, 6%-29%), from 178 to 146 per 1000 population. Antibiotic prescription rates for non-OM ARTI for which antibiotics are rarely indicated decreased by 41% (95% CI, 22%-55%) and 24% (95% CI, 10%-37%) among persons younger than 5 years and 5 years or older, respectively. Overall, ARTI-associated prescription rates for penicillin, cephalosporin, and sulfonamide/tetracycline decreased. Prescription rates for azithromycin increased and it became the most commonly prescribed macrolide for ARTI and OM (10% of OM visits). Among adults, quinolone prescriptions increased. CONCLUSIONS: Overall antibiotic prescription rates for ARTI decreased, associated with fewer OM visits in children younger than 5 years and with fewer prescriptions for ARTI for which antibiotics are rarely indicated. However, prescription rates for broad-spectrum antibiotics increased significantly.