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Bacterial etiologic data for acute otitis media (AOM) otopathogens in Poland are scarce. The aim of this study was to determine the bacterial etiology and antibiotic susceptibility patterns of otopathogens in children prior to the introduction of the pneumococcal conjugated vaccine (PCV) into the national immunization program (NIP) in Poland. Demographic and laboratory data of children < 5 years old who underwent tympanocentesis due to AOM in Nieklanska Hospital Warsaw between 2010 and 2016, were collected. All middle ear fluids (MEF) cultures were processed at the hospital according to conventional culture methods. Out of 940 MEF cultures, 407 (43.3%) were positive for 419 isolates. The most common etiologies of positive cultures were: S. pneumonaie , nontypeable H. infuenzae (NTHi), and S. pyogenes. Children aged 12–23 months had significantly more S. pneumoniae and NTHi positive cultures than children <12 months of age. S. pneumoniae isolates non-susceptible to penicillin, erythromycin, and clindamycin, declined over the study period (2010–2016). This is the largest dataset of MEF isolates from AOM patients in Poland, collected during the pre-PCV period. These data can help determine the appropriate treatment for AOM patients and can serve as a baseline for the period before the introduction of PCV to the NIP in Poland. [ABSTRACT FROM AUTHOR]

Utilizing multiplex real time polymerase chain reaction (RT-PCR) for rapid diagnosis of gastroenteritis, enables simultaneous detection of multiple pathogens. A comparative analysis of disease characteristics was conducted between cases with single and multiple viruses. Rotavirus vaccine was introduced in 2010, reaching a 70% coverage in 2 years. All rectal swabs collected from diarrheic children (<5 years) between December 2017 and March 2022 were included. Detection of the same viruses within 2 months was considered a single episode. Episodes with positive stool bacterial PCR were excluded. A total of 5879 samples were collected, revealing 86.9% (1509) with single virus detection and 13.1% (227) with multiple viruses. The most frequent combination was rotavirus and norovirus (27.8%), these infections followed a winter-spring seasonality akin to rotavirus. Children with multivirus infections exhibited higher immunodeficiency (OR 2.06) rates, but lower food allergy (OR 0.45) and prematurity rates (OR 0.55) compared to single infections. Greater disease severity, evaluated by the Vesikari score, was observed in multivirus episodes (p < 0.001, OR 1.12). Multivirus infections accounted for 13.1% of symptomatic cases in hospitalized young children. Despite vaccination efforts, rotavirus remained prominent, frequently in co-infections with norovirus. Overall, multivirus infections were linked to more severe diseases than single virus cases., (© 2023 Wiley Periodicals LLC.)

Objective: To compare dispensed oral antibiotic prescription rates (DAPRs) after implementation of pneumococcal conjugate vaccine (PCV) in high antibiotic-prescribing clinics (HPC) with low antibiotic-prescribing clinics (LPC) in 2 distinct ethnic groups of children (Jewish and Bedouin children) <5 years of age., Methods: Clinics with ≥50 insured children, active both pre-PCV (2005-2009) and post-PCV (2010-2018) implementation, were included. HPC and LPC were defined by DAPRs above or below the median in each age and ethnic group. Monthly dispensed antibiotic prescription rate (DAPR) trends (adjusted for age and ethnicity) were calculated using interrupted time series. Mean yearly incidence rate-ratios (late PCV13 vs pre-PCV) were calculated., Results: Bedouin HPC had the highest pre-PCV overall-DAPR per 1000 child-years ± SD (2520.4 ± 121.2), followed by Jewish HPC (1885.5 ± 47.6), Bedouin LPC (1314.8 ± 81.6), and Jewish LPC (996.0 ± 19.6). Shortly after PCV implementation, all DAPRs and amoxicillin/amoxicillin-clavulanate DAPRs declined in all groups except Jewish LPC, stabilizing within 4-5 years post-PCV. The rates and magnitudes of declines were directly proportional to the pre-PCV DAPR magnitudes, achieving near-complete closure of the pre-PCV DAPR gaps between the 4 groups (rates during late-PCV13 ranging from 1649.4 ± 23.5 [Bedouin HPC] to 1200.3 ± 72.4 [Jewish LPC])., Conclusions: PCVs are a powerful tool in reducing outpatient antibiotic consumption among young children, especially in HPC, resulting in partial closure of DAPR gap between HPC and LPC. The higher impact on HPC suggests that PCV-associated declines of respiratory disease may strongly contribute to a judicious antibiotic approach in clinics with high antibiotic consumption., Competing Interests: Declaration of Competing Interest R.D. reports grants from Pfizer, MSD, and MedImmune/AstraZeneca; scientific consultant to Pfizer and MSD; review board membership for Pfizer and MSD; speakers' bureau membership for of Pfizer, MSD, Sanofi Pasteur, and GSK. D.G. reports grants from MSD; scientific consultant to Pfizer, MSD, and GSK; speakers' bureau membership for Pfizer, MSD, and GSK. S.B.-S. reports grants from Pfizer; scientific consultant to Pfizer and MSD; review board membership for Pfizer and MSD; speakers' bureau membership for Pfizer, MSD, and GSK. D.D. reports grants from Pfizer. The other authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The proportion of remote clinic visits was expected to increase among children during the COVID-19 pandemic which might result in antibiotic overuse., Methods: In southern Israel, 2 ethnic groups, Jewish and Bedouin, live side-by-side. Computerized data on visits for children <18 years were examined from clinics with ≥50 insured children, active both pre-COVID-19 and during the COVID-19 pandemic. Visits were divided into in-person and remote. Monthly infectious diagnoses and dispensed antibiotic prescription rates were calculated by age (<5, 5-17 years) and ethnic groups. Mean monthly rates of 2 parallel seasons (pre-COVID-19 and COVID-19 periods) were compared., Results: Overall 2,120,253 outpatient clinic visits were recorded. Remote clinic visit rates (per 1000 children) increased from 97.04 and 33.86 in the pre-COVID-19 to 179.75 and 50.05 in the COVID-19 period in Jewish and Bedouin children, respectively ( P < 0.01) along with a reduction of in-person visit rates in both populations. Comparing pre-COVID-19 and COVID-19 periods, the rates of overall infectious diagnoses in remote visits increased. Nevertheless, dispensed antibiotic prescription rates in remote visits (per 1000 visits) remained unchanged (9.84 vs. 8.67, P = 0.70, in the Jewish population and 14.32 vs. 14.17, P = 1.00, in the Bedouin population in the pre-COVID-19 and COVID-19 periods, respectively) with a similar distribution of antibiotic categories., Conclusions: COVID-19 pandemic resulted in an expansion of remote visits of children <18 years with an increase in infectious diagnoses. However, remote dispensed antibiotic prescription rates remained unchanged. These dynamics were more accentuated in Jewish children, characterized by higher socio-economic conditions, compared to Bedouin children., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The COVID-19 pandemic led to improved hygiene and reduced social encounters. Near elimination of the activity of respiratory syncytial virus and influenza viruses were observed, worldwide. Therefore, we assessed the rates of pediatric outpatient clinic visits and medications prescribed at those visits during the coronavirus disease 2019 (COVID-19) pandemic and pre-COVID-19 period (2016-2019)., Methods: Monthly and annual incidence rates for respiratory and non-respiratory diagnoses and dispensed prescription rates were calculated. Acute gastroenteritis (AGE) visits were analyzed separately since the mode of transmission is influenced by hygiene and social distancing., Results: Overall, 5,588,702 visits were recorded. Respiratory and AGE visits declined by 49.9% and 47.3% comparing the COVID-19 and pre-COVID-19 periods. The respective rate reductions for urinary tract infections, trauma, and skin and soft tissue infections were 18.2%, 19.9%, and 21.8%. Epilepsy visits increased by 8.2%. Overall visits rates declined by 21.6%. Dispensed prescription rates of antibiotics and non-antibiotics respiratory medications declined by 49.3% and 44.4%, respectively. The respective declines for non-respiratory antibiotics and non-antibiotics were 15.1% and 0.2%. Clinic visits and prescription rates reductions were highest in April-May, following the first lockdown in Israel., Conclusions: COVID-19 pandemic resulted in a substantial reduction in respiratory outpatient clinic visits and dispensed respiratory drugs, with only a mild reduction seen for non-respiratory visits. These trends were probably driven by COVID-19 mitigation measures and by the profound disruption to non-SARS COV-2 respiratory virus activity., (© 2022. The Author(s).)

Importance: Individuals with schizophrenia are at higher risk for severe COVID-19 illness and mortality. Previous reports have demonstrated vaccination gaps among this high-risk population; however, it is unclear whether these gaps have continued to manifest with the booster dose., Objective: To assess gaps in first, second, and booster vaccinations among individuals with schizophrenia., Design, Setting, and Participants: This was a matched, controlled, retrospective cohort study conducted in November 2021, and included follow-up data from March 2020, to November 2021. The study used the databases of Clalit Health Services, the largest health care management organization in Israel. Individuals with a diagnosis of schizophrenia at the onset of the pandemic and matched controls were included in the analysis., Main Outcomes and Measures: Rates of first, second, and booster vaccinations and time to reach vaccination., Results: The study included 34 797 individuals (mean [SD] age, 50.8 [16.4] years; 20 851 men [59.9%]) with schizophrenia and 34 797 matched controls (mean [SD] age, 50.7 [16.4] years; 20 851 men [59.9]) for a total of 69 594 individuals. A total of 6845 of 33 045 individuals (20.7%) with schizophrenia were completely unvaccinated, compared with 4986 of 34 366 (14.5%) in the control group (odds ratio [OR], 0.65; 95% CI, 0.62-0.67, P < .001). Once vaccinated, no significant differences were observed in the uptake of the second vaccine. Gaps emerged again with the booster vaccine, with 18 469 individuals (74.7%) with schizophrenia completing the booster, compared with 21 563 (77.9%) in the control group (OR, 0.83; 95% CI, 0.80-0.87, P < .001). Kaplan-Meier analyses indicated significant differences in time to reach vaccination, although gaps were lower compared with those reported in the first vaccination (log-rank test, 601.99 days; P < .001 for the first vaccination, compared with log-rank test, 81.48 days, P < .001 for the booster). Multivariate Cox regression analyses indicated that gaps in the first and booster vaccine were sustained even after controlling for demographic and clinical variables (first vaccine: hazard ratio [HR], 0.80; 95% CI, 0.78-0.81; P < .001 and booster: HR, 0.88; 95% CI, 0.87-0.90; P < .001) but were not significant for the second vaccine., Conclusions and Relevance: Results of this cohort study of Israeli adults found lower rates of COVID-19 vaccination among individuals with schizophrenia compared with a control group without schizophrenia, especially during the vaccine initiation phase. Countries worldwide should adopt strategies to mitigate the persistence of vaccination gaps to improve health care for this vulnerable population.

Background: Invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae serotype 2 (Sp2) is infrequent. Large-scale outbreaks were not been reported following pneumococcal conjugate vaccine (PCV) implementation. We describe a Sp2 IPD outbreak in Israel, in the PCV13 era, with focus on Sp2 population structure and evolutionary dynamics., Methods: The data were derived from a population-based, nationwide active surveillance of IPD since 2009. PCV7/PCV13 vaccines were introduced in July 2009 and November 2010, respectively. Sp2 isolates were tested for antimicrobial susceptibility, multilocus sequence typing, and whole-genome sequencing (WGS) analysis., Results: Overall, 170 Sp2 IPD cases were identified during 2009-2019; Sp2 increased in 2015 and caused 6% of IPD during 2015-2019, a 7-fold increase compared with 2009-2014. The outbreak was caused by a previously unreported molecular type (ST-13578), initially observed in Israel in 2014. This clone caused 88% of Sp2 during 2015-2019. ST-13578 is a single-locus variant of ST-1504, previously reported globally including in Israel. WGS analysis confirmed clonality among the ST-13578 population. Single-nucleotide polymorphism-dense regions support a hypothesis that the ST-13578 outbreak clone evolved from ST-1504 by recombination. All tested strains were penicillin-susceptible (minimum inhibitory concentration <0.06 μg/mL). The ST-13578 clone was identified almost exclusively (99%) in the Jewish population and was mainly distributed in 3 of 7 Israeli districts. The outbreak is still ongoing, although it began declining in 2017., Conclusions: To the best of our knowledge, this is the first widespread Sp2 outbreak since PCV13 introduction worldwide, caused by the emerging ST-13578 clone., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: Streptococcus pneumoniae is a leading cause of pneumonia among children. However, owing to diagnostic limitations, the protection conferred by pneumococcal conjugate vaccines (PCVs) against pediatric pneumonia attributable to vaccine-serotype pneumococci remains unknown., Methods: We analyzed data on vaccination and nasopharyngeal pneumococcal detection among children <5 years old with community-acquired alveolar pneumonia (CAAP; "cases") and those without respiratory symptoms ("controls"), who were enrolled in population-based prospective surveillance studies in southern Israel between 2009 and 2018. We measured PCV-conferred protection against carriage of vaccine-serotype pneumococci via the relative risk of detecting these serotypes among vaccinated versus unvaccinated controls. We measured protection against progression of vaccine serotypes from carriage to CAAP via the relative association of vaccine-serotype detection in the nasopharynx with CAAP case status, among vaccinated and unvaccinated children. We measured PCV-conferred protection against CAAP attributable to vaccine-serotype pneumococci via the joint reduction in risks of carriage and disease progression., Results: Our analyses included 1032 CAAP cases and 7743 controls. At ages 12-35 months, a PCV13 schedule containing 2 primary doses and 1 booster dose provided 87.2% (95% confidence interval: 8.1-100.0%) protection against CAAP attributable to PCV13-serotype pneumococci, and 92.3% (-0.9%, 100.0%) protection against CAAP attributable to PCV7-serotype pneumococci. Protection against PCV13-serotype and PCV7-serotype CAAP was 67.0% (-424.3%, 100.0%) and 67.7% (-1962.9%, 100.0%), respectively, at ages 36-59 months. At ages 4-11 months, 2 PCV13 doses provided 98.9% (-309.8%, 100.0%) and 91.4% (-191.4%, 100.0%) against PCV13-serotype and PCV7-serotype CAAP., Conclusions: Among children, PCV-conferred protection against CAAP attributable to vaccine-targeted pneumococcal serotypes resembles protection against vaccine-serotype invasive pneumococcal disease., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

After worldwide implementation of 10-valent and 13-valent pneumococcal conjugate vaccines (PCV10/PCV13), a 20-valent PCV (PCV20) was developed. We assessed dynamics of non-PCV13 additional PCV20 serotypes (VT20-13), compared with all other non-VT20 serotypes, in children <2 years of age in late PCV13 (2015-2017) and early PCV (2009-2011) periods. Our prospective population-based multifaceted surveillance included isolates from carriage in healthy children, children requiring chest radiography for lower respiratory tract infections (LRTIs), and children with non-LRTI illness, as well as isolates from acute conjunctivitis, otitis media (OM), and invasive pneumococcal disease (IPD). After PCV13 implementation, VT20-13 increased disproportionally in OM, IPD, and carriage in LRTI. VT20-13/non-VT20 prevalence ratio range was 0.26-1.40. VT20-13 serotypes were more frequently antimicrobial-nonsusceptible than non-VT20 serotypes. The disproportionate increase of VT20-13 in respiratory infections and IPD points to their higher disease potential compared with all other non-VT20 as a group.

Background: Reduced-dose pneumococcal conjugate vaccine (PCV) schedules are under consideration in countries where children are recommended to receive 3 doses. Whereas PCV-derived protection against vaccine-serotype colonization is responsible for herd effects of vaccination, dose-specific PCV effectiveness against colonization endpoints is not known. We aimed to assess the performance of differing PCV schedules against vaccine-serotype colonization in children., Methods: From 2009-2016, we monitored pneumococcal carriage in southern Israel, where children should receive PCV at ages 2 months, 4 months, and 12 months (2 primary [p] +1 booster [b] schedule). We analyzed nasopharyngeal swabs and vaccination histories from 5928 children aged 0-59 months without symptoms of diseases potentially attributable to pneumococci. Matching individuals on age, sex, ethnicity, visit timing, and recent antibiotic receipt, we measured schedule-specific 7-valent PCV (PCV7) and 13-valent PCV (PCV13) effectiveness against vaccine-serotype colonization in a modified case-control framework. We sampled from the distribution of all possible case-control match assignments for statistical analyses., Results: Receiving 2 primary-series PCV13 doses conferred 53% (95% confidence interval [CI], 32-67%) protection against PCV13-serotype colonization at ages ≤12 months; 1 primary-series dose was not protective. A 2p+1b PCV13 series conferred 40% (95% CI, 4-67%) and 62% (95% CI, 33-83%) protection against PCV13-serotype colonization at ages 13-24 months and 25-59 months, respectively. Estimates suggested greater PCV13-conferred protection against PCV7-targeted serotypes than the 6 PCV13-only serotypes. As compared to children receiving 2p+1b PCV13 dosing, those receiving 1p+1b and 2p+0b schedules experienced 2.05-fold (95% CI, 1.12-5.00) and 3.33-fold (95% CI, 2.28-4.93) greater odds, respectively, of vaccine-serotype pneumococcal colonization at ages 13-24 months., Conclusions: Our results demonstrate real-world effectiveness of 2p+1b PCV dosing against vaccine-serotype colonization. Reduced-dose schedules may confer lower protection against vaccine-serotype carriage during and beyond the first year of life., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: In the pre-pneumococcal conjugated vaccines (PCVs) era, serotypes included in the 7/13-valent PCVs (PCV7/PCV13) caused most pneumococcal otitis media (OM) and antibiotic-non-susceptible pneumococcal OM (ANSP-OM) episodes. In southern Israel, sequential PCV7/PCV13 introduction resulted in >90% reduction of vaccine-serotype OM., Objectives: We assessed the dynamics of ANSP-OM necessitating middle ear fluid culture following PCV7/PCV13 sequential introduction in young children., Methods: This was a prospective, population-based, active surveillance. All episodes in children <3 years old, during 2004-16, were included. Two subperiods were defined: (i) pre-PCV: 2004-08; and (ii) PCV13: 2014-16. ANSP was defined for the following antibiotics: penicillin (MIC ≥0.1 mg/L and ≥1.0 mg/L), macrolide, tetracycline, clindamycin, ceftriaxone, trimethoprim/sulfamethoxazole and chloramphenicol. MDR was defined as ANSP for ≥3 classes., Results: Overall, 2270 pneumococcal OM episodes were identified. Annual overall pneumococcal, PCV13 and non-PCV13 serotype OM incidence declined by 86%, 97% and 33%, respectively, comparing pre-PCV with the PCV13 period. During 2004-08, 95% of ANSP was observed in vaccine serotypes. Incidence of penicillin (MIC ≥0.1 mg/L and ≥1.0 mg/L), macrolide, tetracycline, clindamycin, ceftriaxone and multidrug ANSP-OM declined by >90% in the PCV13 period. Rates of trimethoprim/sulfamethoxazole and chloramphenicol ANSP-OM declined by 85% and 79%, respectively. The proportions of ANSP of all pneumococcal isolates declined by ∼70% for penicillin, ceftriaxone and erythromycin; 53% for tetracycline; and 55% for MDR, versus no significant reductions observed for chloramphenicol, trimethoprim/sulfamethoxazole and clindamycin., Conclusions: PCV7/PCV13 sequential introduction resulted in rapid and substantial ANSP-OM reduction, in parallel with the near disappearance of PCV13-serotype OM and no increase in replacement disease., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The purpose of this study was to determine factors characterizing children admitted to the Pediatric Intensive Care Unit (PICU) with community-acquired alveolar pneumonia (CAAP) to help clinicians assess disease severity upon initial assessment in the emergency department., Methods: We prospectively collected demographic, clinical, and laboratory data of children <5 years with radiologically confirmed CAAP referred to the Soroka University Medical Center during 2001-2011. Three groups of children were compared: 1) those hospitalized in the PICU (PICU-CAAP); 2) those treated in the emergency department and discharged (ED-CAAP); and 3) those hospitalized in a pediatric ward (Hosp-CAAP)., Results: Of 9722 CAAP episodes, 367 (3.8%) were PICU-CAAP, 5552 (57.1%) Hosp-CAAP and 3803 (39.1%) ED-CAAP. In a univariate analysis, respiratory syncytial virus (RSV) was detected more commonly among PICU-CAAP than in Hosp-CAAP (P = 0.02) and ED-CAAP patients (P < 0.001). In a multivariate analysis, several factors were associated with PICU hospitalization versus ED-CAAP and Hosp-CAAP: Younger age (ORs: 1.04, [95%CI: 1.02-1.05] and 0.97 [0.96-0.98], respectively); prematurity (ORs: 2.16 [1.28-3.64] and 1.61 [1.15-2.26], respectively), lower O 2 saturation (ORs: 1.32 [1.25-1.41] and 0.94[0.92-0.96]), higher respiratory rate (ORs: 1.06 [1.04-1.07] and 1.00 [1-1.01], respectively)., Conclusion: Children admitted to PICU were younger, had more respiratory syncytial virus (RSV) detection, were premature, had lower O 2 saturation, and had a higher respiratory rate than those admitted to the general ward or those visiting the emergency department and subsequently discharged., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article., (Copyright © 2020. Published by Elsevier B.V.)

Background: The World Health Organization Pneumonia Expert Group (WHO-PEG) defined a standardized radiologic endpoint for childhood community-acquired alveolar pneumonia (RD-CAAP), as the most likely to be pneumococcal, not ruling out other bacteria or coinfecting viruses. We aimed to determine the characteristics associated with hospitalization among children <5 years old presenting to the pediatric emergency room (PER) with RD-CAAP., Methods: This study was a part of an ongoing prospective population-based surveillance on hospital visits for RD-CAAP. RD-CAAP was determined according to the WHO-PEG. The study was conducted in the prepneumococcal conjugate vaccine era (2004-2008)., Results: Of 24,432 episodes with chest radiographs, 3871)15.8%) were RD-CAAP: 2319 required hospitalization and 1552 were discharged (outpatients). Compared with outpatients, hospitalized children had lower temperature, peripheral white cell and absolute neutrophil counts and C reactive protein serum levels, but higher rates of hypoxemia, rhinorrhea, cough and respiratory virus detection. PER visits during the respiratory virus season presented a 1.83 times higher risk of hospitalization than visits during nonrespiratory season., Conclusions: Although RD-CAAP is most often a bacterial infection, the unique characteristics of those visiting the PER and subsequently hospitalized suggest a frequent involvement of respiratory viruses, potentially as viral-bacterial coinfections, compared with outpatients.

Background: The introduction of the pneumococcal conjugated vaccines (PCVs) resulted in a substantial reduction of invasive pneumococcal disease (IPD) rates. However, impact on nonsevere IPD (mostly occult bacteremia) has not yet been fully elucidated. We assessed severe and nonsevere IPD (SIPD and NSIPD, respectively) rate dynamics in children < 5 years in Israel before and after PCV7/PCV13 implementation., Methods: A prospective, population-based, nationwide surveillance. All IPD episodes recorded from 1999 through 2015 were included. NSIPD was defined as IPD episodes without meningitis, pneumonia or mastoiditis in a child with a favorable outcome (not hospitalized or hospitalized in a nonintensive care unit < 5 days, without mortality). Three subperiods were defined: pre-PCV (1999-2008), PCV7 (2010-2011) and PCV13 (2013-2015). Incidence rate ratios (IRRs) were calculated., Results: Overall, 4,457 IPD episodes were identified; 3,398 (76.2%) SIPD, 1,022 (22.9%) NSIPD and 37 (0.8%) unknown. In 90% of NSIPD episodes, no focus was identified. In the PCV7 period, NSIPD rates significantly declined by 52%, while SIPD rates declined less prominently by 24%. Following PCV13 introduction, compared with the PCV7 period, NSIPD rates declined nonsignificantly by 17% while SIPD rates declined significantly further by an additional 53%. These trends resulted in overall reductions (comparing PCV13 and pre-PCV periods) of NSIPD and SIPD of 60% (IRR = 0.4; 0.32-0.51) and 64% (IRR = 0.36; 0.32-0.42), respectively., Conclusions: Following PCV7/PCV13 introduction, SIPD and NSIPD rates substantially declined, with differences in rate-dynamics, alluding to differences in serotype distribution between the 2 groups. Future surveillance is warranted when considering modification in treatment protocols for suspected occult bacteremia/NSIPD cases.

All-cause otitis media (OM) incidence has declined in numerous settings following introduction of pneumococcal conjugate vaccines (PCVs) despite increases in carriage of nonvaccine pneumococcal serotypes escaping immune pressure. To understand the basis for the declining incidence, we assessed the intrinsic capacity of pneumococcal serotypes to cause OM independently and in polymicrobial infections involving nontypeable Haemophilus influenzae (NTHi) using samples obtained from middle ear fluid and nasopharyngeal cultures before PCV7/13 rollout. Data included samples from OM episodes (11,811) submitted for cultures during a 10-year prospective study in southern Israel and nasopharyngeal samples (1,588) from unvaccinated asymptomatic children in the same population. We compared data representing pneumococcal serotype diversity across carriage and disease isolates with and without NTHi coisolation. We also measured associations between the pneumococcal phenotype and the rate of progression from colonization to OM in the presence and absence of NTHi. Whereas pneumococcal serotype diversity was lower in single-species OM than in single-species colonization, levels of serotype diversity did not differ significantly between colonization and OM in mixed-species episodes. Serotypes differed roughly 100-fold in progression rates, and those differences were attenuated in polymicrobial episodes. Vaccine serotype pneumococci had higher rates of progression than nonvaccine serotypes. While serotype invasiveness was a weak predictor of the OM progression rate, efficient capsular metabolic properties-traditionally thought to serve as an advantage in colonization-predicted an enhanced rate of progression to complex OM. The lower capacity of nonvaccine serotypes to cause OM may partially account for reductions in all-cause OM incidence despite serotype replacement in carriage following rollout of PCVs., (Copyright © 2018 American Society for Microbiology.)

Background: Reductions in otitis media (OM) burden following rollout of pneumococcal conjugate vaccines (PCVs) have exceeded predictions of vaccine impact. In settings with active surveillance, reductions in OM caused by vaccine-targeted pneumococcal serotypes have co-occurred with reductions in OM caused by other pathogens carried in the upper-respiratory tract of children. To understand these changes, we investigated the progression of vaccine-targeted and non-vaccine pneumococcal serotypes from carriage to OM before and after vaccine rollout., Methods: Nasopharyngeal carriage prevalence of pneumococcus was monitored in prospective studies of Bedouin and Jewish children <3 years old in southern Israel between 2004 and 2016. Incidence of OM necessitating middle-ear fluid culture (predominantly complex OM including recurrent, spontaneously-draining, non-responsive, and chronic cases) was monitored via prospective, population-based active surveillance. We estimated rates of pneumococcal serotype-specific progression from carriage to disease before and after rollout of PCV7/13, measured as OM incidence per carrier. We pooled serotype-specific estimates using Bayesian random-effects models., Results: On average, rates of progression declined 92% (95% credible interval: 79-97%) and 80% (46-93%) for PCV7/13 serotypes among Bedouin and Jewish children <12 months old, respectively, and 32% (-58-71%) and 61% (-5-86%) among children aged 12-35m. For non-vaccine serotypes, rates of progression among Bedouin and Jewish children aged <12m declined 74% (55-85%) and 43% (4-68%), respectively., Conclusions: Vaccine-targeted and non-vaccine pneumococcal serotypes showed lower rates of progression to complex OM after rollout of PCV7/13. Early-life OM episodes historically associated with vaccine-serotype pneumococci may impact the susceptibility of children to OM progression., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Respiratory viruses and Streptococcus pneumoniae are known to be copathogens in childhood pneumonia. However, it is unclear whether all pneumococcal serotypes are equally prone to such interaction. We attempted to determine association between carried pneumococcal serotypes and respiratory viruses during childhood community-acquired alveolar pneumonia (CAAP)., Methods: The study was conducted during respiratory syncytial virus (RSV) seasons, before pneumococcal vaccine introduction. Children aged <5 years diagnosed with CAAP with positive pneumococcal nasopharyngeal cultures from whom viral diagnostic tests were obtained were enrolled. Viral detection was done by culture, direct immunofluorescence assay (DFA) or polymerase chain reaction. Adjusted odd ratios (ORs) for serotype-specific carriage rates by presence of specific viruses were calculated: single RSV-positive (RSV[+]); other respiratory viruses (ORspVs[+]); and no respiratory virus (RspVs[-]). We compared invasive and noninvasive pneumococcal serotypes according to previous publications., Results: Invasive serotype colonization was significantly lower in RSV(+) versus RspVs(-) CAAP (OR = 0.18; 95% confidence interval [CI] = .05-.60), whereas colonization with noninvasive serotypes tended to be higher in RSV(+) (OR = 2.39; 95% CI = .98-5.79)., Conclusions: We found an inverse relationship between pneumonia-associated invasive pneumococcal serotypes and RSV detection during CAAP. This finding may lead to better understanding of the interaction between respiratory viruses and S. pneumoniae in CAAP pathogenesis., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Pneumococcal conjugated vaccines (PCVs) impact on complex otitis media (OM; including recurrent, nonresponsive, and chronic OM with effusion) was greater than that on simple, acute OM in previous studies. Since complex OM is often a polymicrobial disease, we speculated that reduction of complex OM by PCVs would be associated with reduction of non-pneumococcal OM., Methods: In a prospective, population-based, active surveillance, all OM episodes submitted for middle ear fluid culture in children <3 years from 2004 through 2015 were included. Three sub-periods were established: pre-PCV, PCV7, and PCV13. Incidence rate ratios (IRRs) comparing the 3 periods were calculated for pneumococcal, nontypable Haemophilus influenzae (NTHi), Moraxella catarrhalis, Streptococcus pyogenes, and culture-negative OM., Results: Overall, 7475 episodes were included. Of all-NTHi cases in the pre-PCV period, 34% were mixed with Streptococcus pneumoniae IRRs (95% confidence interval) comparing the pre-PCV to the PCV13 period were 0.02 (0.01-0.04), 0.12 (0.08-0.20), and 0.18 (0.15-0.21) for PCV7+6A serotypes, 5 additional PCV13 serotypes, and all-pneumococcal OM, respectively; non-PCV13 serotype episodes were not significantly reduced. IRRs for single NTHi, mixed NTHi + S. pneumoniae, and all-NTHi OM were 0.30 (0.25-0.35), 0.18 (0.13-0.24), and 0.25 (0.22-0.29), respectively. Moraxella catarrhalis, S. pyogenes, and culture-negative episodes were also significantly reduced., Conclusions: Both pneumococcal and non-pneumococcal OM episodes, enriched with complex cases, declined substantially in children <3 years following sequential PCV7/PCV13 introduction. The reduction in non-pneumococcal episodes may be attributed to early OM episodes prevention, resulting in a lower rate of complex, often non-pneumococcal OM., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Cocolonization by Streptococcus pneumoniae and Haemophilus influenzae among children has been noted in numerous studies, as has an inverse relationship involving colonization with these species and Staphylococcus aureus. Interactions among these pathogens could mediate unanticipated outcomes of clinical interventions, including changes in H. influenzae and S. aureus disease incidence following pneumococcal vaccine introduction. However, it remains unclear whether cocolonization patterns represent true interspecies interactions or whether they result from confounding factors., Methods: We investigated polymicrobial carriage using longitudinal data from 369 Bedouin children and 400 Jewish children in Israel who were enrolled in a 7-valent pneumococcal conjugate vaccine (PCV7) trial. Children were swabbed 10 times between 2 and 30 months of age., Results: The pathogens followed distinct age and seasonal distributions, but polymicrobial carriage associations persisted after controlling for these and other confounding factors. Receipt of PCV7 resulted in pneumococcal serotype replacement but did not influence total carriage of S. pneumoniae, H. influenzae, or S. aureus., Conclusions: The fact that S. pneumoniae, H. influenzae, and S. aureus polymicrobial carriage patterns do not result from confounding by age and season supports the idea of active interspecies interactions. However, pneumococcal serotype replacement may prevent changes in H. influenzae and S. aureus carriage among PCV7 recipients., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Pentavalent rotavirus vaccine (RV5) was introduced into the Israeli National Immunization Program in January 2011. We determined RV5 vaccine effectiveness (VE) in southern Israel, a region characterized by 2 distinct populations: Bedouins living in a low- to middle-income, semirural setting, and Jews living in a high-income, urban setting., Methods: We enrolled vaccine-eligible children who visited the emergency department (ED) or were hospitalized due to acute gastroenteritis (AGE) during the first 3 rotavirus seasons after RV5 vaccine introduction (2011-2013). Fecal specimens were tested for rotavirus by enzyme immunoassay and genotyped. Vaccination among laboratory-confirmed rotavirus cases was compared with rotavirus-negative AGE controls. Regression models were used to calculate VE estimates by age, clinical setting, and ethnicity., Results: Of 515 enrolled patients, 359 (70%) were Bedouin. Overall, 185 (36%) patients were rotavirus positive; 79 of 119 (66%) were G1P[8] genotype. The adjusted VE for a full 3-dose course of RV5 against ED visit or hospitalization was 63% (95% confidence interval [CI], 38%-78%). RV5 provided G1P[8] genotype-specific effectiveness of 78% (95% CI, 58%-88%). By age, RV5 VE was 64% (95% CI, 21%-84%) and 71% (95% CI, 39%-86%) among children aged 6-11 months and 12-23 months, respectively. By clinical setting, RV5 VE was 59% (95% CI, 23%-78%) against hospitalization, and 67% (95% CI, 11%-88%) against ED visit. The adjusted VE of a full RV5 course among Bedouin children was 62% (95% CI, 29%-79%)., Conclusions: RV5 significantly protected against rotavirus-associated ED visits and hospitalizations in a diverse population of vaccine-eligible children living in southern Israel., (Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Alveolar community-acquired pneumonia (A-CAP) is mostly considered a bacterial disease, mainly pneumococcal. This study was conducted to document the impact of sequential 7-valent and the 13-valent pneumococcal conjugate vaccines (PCV7; PCV13) on emergency room and hospitalization for A-CAP among children <5 years of age., Methods: This is an ongoing prospective population-based study in southern Israel. The current analysis spans over the period July 2002 through June 2013. A-CAP was defined using the World Health Organization (WHO)'s criteria for radiologically-confirmed pneumonia. PCV7 was introduced in Israel in July 2009 and gradually replaced by PCV13 in November 2010. Pneumococcal conjugate vaccine (PCV) impact was calculated by comparing incidences during 3 pre-defined periods: pre-PCV (2002-2008), PCV7 (2010-2011) and PCV13 (2012-2013)., Results: Overall, 10,142 A-CAP episodes occurred. The annual incidences (per 1,000 inhabitants) in children <5 years old declined from a mean (±standard deviation) of 13.8 ± 0.9 in the pre-PCV period to 11.2 ± 2.7 in the PCV7 period and 7.4 in the PCV13 period, representing a reduction of 13% and 47%, respectively. The overall decrease was significantly faster among outpatients than among hospitalized children (42% and -8%, respectively in the PCV7 period; 68% vs. 32% in hospitalized children in the PCV13 period). While in children 12-23 months a significant decline was observed during the PCV7 and PCV13 periods, significant declines in A-CAP rates were observed only during the PCV13 period in the <12 months and 24-59 months age groups (44% and 46%, respectively)., Conclusions: A moderate decline in hospital A-CAP visits in children <5 years old was observed after PCV7 introduction. In contrast, after PCV13 introduction a substantial reduction in all visits was evident., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Rotavirus vaccines were licensed in Israel in 2007, and in 2011 the pentavalent-vaccine (RV5) was introduced into the Israeli National Immunization plan., Aim: To determine the effect of rotavirus-vaccines on the incidence of hospital visits due to rotavirus gastroenteritis (RVGE) and all-cause diarrhea in Jewish and Bedouin children <5 year residing in southern Israel., Methods: We conducted a population-based, prospective, observational study. Data from 2006 through 2013 were analyzed. Our hospital is the only medical center in the region, enabling age-specific incidences calculation., Results: In the pre-vaccine period, the overall RVGE hospital visits rates per 1000 in children <12, 12-23 and 24-59 m were 16.1, 18.6 and 1.4 in Jewish children, respectively. The respective rates in Bedouin children were 26.4, 12.5 and 0.7 (P<0.001 for <12 m). Hospitalization rates were higher among Bedouin than among Jewish children (60.0% vs. 39.7%, P<0.001). Vaccine uptake was faster in the Jewish vs. the Bedouin population. In the year following RV5 introduction, RVGE hospital visits rates declined by 82%, 70% (P<0.001 both) and 36% (P=0.092) in Jewish children <12, 12-23 and 24-59 m, respectively. In Bedouin children, the respective RVGE rates declined by 70% (P<0.001), 21% (P=ns) and 14% (P=ns). Throughout the study, RVGE rates declined significantly in children <12, and 12-23 m by 80% and 88% in Jewish children, respectively, and by 62 and 75% in Bedouin children, respectively (P<0.001 for all declines). In children 24-59 m, RVGE rates declined by 46% (P=0.025) in Jewish children, but no reduction was observed in Bedouin children. The dynamics of all-cause diarrhea rates were similar to that of RVGE., Conclusions: Significant reductions of RVGE rates were observed, following Rota-vaccine introduction in southern Israel in both Jewish and Bedouin children. However, the impact was faster and more profound in Jewish children, probably related to higher vaccine uptake and possibly to lifestyle differences., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Otitis media (OM) is common in early childhood. Streptococcus pneumoniae caused approximately 30%-60% of episodes before the pneumococcal conjugate vaccine (PCV) era. The 7-valent PCV (PCV7) was introduced to the Israeli National Immunization Plan in July 2009, and was gradually replaced by the 13-valent PCV (PCV13) starting in November 2010. We aimed at assessing the impact of PCV7/PCV13 sequential introduction on pneumococcal and overall OM necessitating middle ear fluid culture in children aged <2 years in southern Israel., Methods: This was a prospective, population-based, active surveillance. Our medical center is the only one in the region, enabling incidence calculation. All pneumococcal episodes submitted for culture between July 2004 and June 2013 were included. Three subperiods were defined: pre-PCV, PCV7, and PCV13., Results: Overall, 6122 OM episodes were recorded, and 1893 were pneumococcal. Compared with the pre-PCV period, OM caused by PCV7 plus serotype 6A and the 5 additional PCV13 serotypes (5VT : 1, 3, 5, 7F, 19A) decreased by 96% and 85%, respectively (incidence rate ratios [IRRs], 0.04 [95% confidence interval {CI}, .02-.08] and 0.15 [95% CI, .07-.30], respectively) in a 2-step pattern: In the PCV7 period, only OM caused by PCV7 + 6A serotypes was decreased; in the PCV13 period, 5VT OM rates decreased, along with an additional PCV7 + 6A OM reduction. A nonsignificant increase in non-PCV13 serotype OM was observed (IRR, 1.07 [95% CI, .72-1.58]). In total, 77% and 60% reductions of all-pneumococcal and all-cause OM incidences, respectively, were observed., Conclusions: A substantial 2-step reduction of pneumococcal OM rates, with near-elimination of PCV13 disease, was observed shortly after PCV7/PCV13 introduction., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Southern Israel is inhabited by Bedouins, living in conditions similar to developing countries and Jews, living in conditions similar to developed countries. We determined the epidemiology of Shigella spp. in these populations. We retrospectively reviewed Shigella spp. stool isolations between 2005-2009. Overall, 3295 isolates were analyzed. S. sonnei was isolated in 2057/3295 (62.4%) and S. flexneri in 1058 (32.1%). S. sonnei was isolated in 1567/1707 (91.8%) from Jewish patients and S. flexneri in 931/1542 (60.4%) from Bedouin patients. Ampicillin resistance increased linearly from 217/373 (58.2%) in 2005 to 186/256 (72.7%) in 2009, (P < 0.001). Trimethoprim-sulfamethoxazole resistance decreased linearly from 328/373 (87.9%) in 2005 to 133/256 (51.9%) in 2009 (P < 0.001). Higher resistance of Shigella spp. to ampicilin and trimethoprim-sulfamethoxazole were found in Jewish patients: 1527/1706 (89.5%) versus 977/1542 (63.4%) (P < 0.0001), 1635/1706 (95.8%) versus 1026/1542 (66.5%) (P < 0.0001). The epidemiology of Shigella spp. infections can differ in populations residing in the same geographical area., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Postlicensure surveillance of pneumonia incidence can be used to estimate whether pneumococcal conjugate vaccines (PCVs) affect incidence. We used Poisson regression models that control for baseline seasonality to determine the impact of PCVs and the possible effects of variations in virus activity in Israel on these surveillance estimates. PCV was associated with significant declines in radiologically confirmed alveolar pneumonia (RCAP) among patients <6 months, 6-17 months, and 18-35 months of age (-31% [95% CI -51% to -15%], -41% [95% CI -52 to -32%], and -34% [95% CI -42% to -25%], respectively). Respiratory syncytial virus (RSV) activity was associated with strong increases in RCAP incidence, with up to 44% of cases attributable to RSV among infants <6 months of age and lower but significant impacts in older children. Seasonal variations, particularly in RSV activity, masked the impact of 7-valent PCVs, especially for young children in the first 2 years after vaccine introduction.

Background: We aimed to determine whether serotype 1 (SP1) invasive pneumococcal disease (IPD) can be distinguished by demographic, clinical and laboratory characteristics from IPD caused by the other most common serotypes (MCS) in our region: 5, 14, 6A, 6B, 19A, 19F, 23F., Methods: Data for all IPD episodes in children <18 years old treated at the Soroka University Medical Center during 2000 to 2009 were retrospectively retrieved. Episodes caused by SP1-IPD were compared with those caused by MCS-IPD (both grouped and individual serotypes). Analyses were adjusted for age and ethnicity., Results: Ninety-four SP1-IPD and 250 MCS-IPD episodes were documented. SP1-IPD cases were older (68.3 ± 52.6 months versus 30.4 ± 39.2 months; P < 0.001) and more likely to be found in Bedouin children than MCS-IPD (87.5% versus 58.6%; P < 0.001). SP1 was less frequently isolated from patients with underlying disease than MCS (14.9% versus 31.6 %; P < 0.001; relative risk 0.15 [95% confidence interval: 0.07-0.32]). SP1 was more often associated with bacteremic pneumonia and primary peritonitis than MCS (66% versus 38.4% and 7.4% versus 0.8%, respectively; P < 0.001); the proportion of bacteremia without focus was higher in MCS-IPD (32.4% versus 12.5%; P < 0.001). There were no differences in hospitalization and mortality rates (70.2% versus 68.0% [P = 0.22] and 4.3% versus 5.6% [P = 0.26], respectively)., Conclusions: SP1 was found less frequently than MCS in children with underlying diseases, but it was more frequent in older and Bedouin children with IPD. SP1 was more frequently associated with bacteremic pneumonia and primary peritonitis than MCS grouped.

Background: The antibody response to pneumococcal conjugate vaccines (PCVs) in infants is variable. Factors responsible for this variability have not been fully elucidated. The objective of this study was to investigate whether pneumococcal carriage around the time of the first dose of 7-valent PCV (PCV7) affects serotype-specific immunologic response., Methods: Healthy 2-month old infants were randomized to receive 2 (at the ages of 4 and 6 months) or 3 (at the ages of 2, 4, and 6 months) PCV7 doses and a booster dose (at the age of 12 months). Nasopharyngeal or oropharyngeal specimens were obtained for culture shortly before the first PCV7 dose. Serotype-specific immunoglobulin (Ig) G levels were measured at ages 2, 7, and 13 months., Results: Of 545 children studied, 332 received a booster dose. The most common serotypes carried around the time of the first PCV7 dose were 6B (n = 37), 19F (n = 22), and 23F (n = 14). In carriers before the first dose, the IgG response to the carried serotype after 2 or 3 doses was significantly lower than in noncarriers. In contrast, response to the noncarried serotypes was not affected. Although all children responded to the booster dose, the response to the originally carried serotype was generally lower., Conclusions: Serotype-specific hyporesponsiveness to PCV7 after pneumococcal carriage in infants is demonstrated for the first time. This phenomenon was common, lasted for at least several months, and was only partially overcome by the 12-month booster., Trial Registration: isrctn.org identifier: ISRCTN28445844.

Background: Respiratory tract infections are a major cause of morbidity and mortality in children under the age of 5 years. The child population in southern Israel is divided into two main groups, Jewish and Bedouin, who differ in their socioeconomic status, with the Bedouin population living in lower socioeconomic conditions and overcrowding. Almost all children in southern Israel are treated at the Soroka University Medical Center., Study Objective: To compare the epidemiological and clinical data of Bedouin and Jewish children with community acquired pneumonia (CAP), who were treated at the Soroka University Medical Center., Methods: All chest X-rays of children under the age of 5 years, taken at the Pediatric Emergency room (PER) between the dates 4.11.2001 and 31.12.2007, were evaluated for pneumonia. Demographic and clinical data were collected to determine morbidity, hospitalization and mortality rates. Blood cultures and nasopharyngeal washes were taken to determine the pathogens of CAP., Results: A total of 38,045 chest radiographs were evaluated; CAP was diagnosed in 5,965 of them (15.6%). The risk of presenting to the PER with CAP in children under the age of 5 years was 8.3% in Bedouin children and 5.4% in Jewish children (p < 0.01). The cumulative risk for hospitalization due to CAP in children under the age of 5 years was 5.8% for the Bedouin children and 2.2% for the Jewish children (p < 0.01). The Bedouin children were younger than the Jewish children (43.5% under 1 year of age vs. 23.7% respectively, p < 0.01). Tachypnea, hypoxemia and mortality rates (71.9% vs. 61%, 31.7% vs. 18.6% and 3% vs. 0.3%, p < 0.01 respectively) were higher in Bedouin children than in Jewish children., Conclusions: PER visits due to CAP are common, especially in Bedouin children. Bedouin patients were younger, with a more severe clinical course and with higher rates of morbidity, hospitalization and mortality than Jewish children. Improving living conditions, parental perception of disease severity and immunization programs (e.g. pneumococcal and influenza vaccine) could lead to a reduction in the gap between the two populations.

Objectives: To determine the involvement of human metapneumovirus (HMPV) in childhood community-acquired alveolar pneumonia (CAAP) and compare the demographic, clinical, and laboratory features of HMPV-associated CAAP and CAAP associated with other respiratory viruses., Study Design: Nasopharyngeal wash specimens obtained prospectively over a 4-year period from children age < 5 years evaluated in the emergency department with radiologically diagnosed CAAP and from healthy controls were tested for HMPV by reverse-transcriptase polymerase chain reaction and for respiratory syncytial virus (RSV), adenovirus, influenza and parainfluenza viruses by direct immunofluorescence and culture., Results: HMPV was detected in 108 of 1296 patients (8.3%) versus RSV in 23.1%, adenovirus in 3.4%, influenza A virus in 2.9%, and parainfluenza viruse in 2.9%. During the period of peak activity (November to May), HMPV was detected in 95 of 1017 patients (9.3%) and in 3 of 136 controls (2.2%) (P = .005). The patients with HMPV were older than those with RSV (P < .001) with a more common history of acute otitis media requiring tympanocentesis (P = .032), wheezing (P = .001) and gastrointestinal symptoms (P < .001) and a lower hospitalization rate (P = .005)., Conclusions: The high detection rate suggests an important role for HMPV in childhood CAAP. Our findings identify demographic and clinical features of HMPV-positive CAAP and its age-related impact on hospital admissions.

Background: Introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the United States in 2000 was temporally associated with an increase in the incidence of disease caused by Streptococcus pneumoniae serotype 19A (Sp19A) and with increasing drug resistance within this serotype. A causative role of PCV7 was speculated. We prospectively studied the dynamics of acute otitis media (AOM) caused by Sp19A in southern Israel before the introduction of PCV7., Methods: AOM in children < 5 years old undergoing tympanocentesis during 1999-2006 was studied. Antibiotic prescriptions for approximately 20% of children < 5 years old were recorded. Sp19A isolates were studied for antibiotic-resistance and pulsed-field gel electrophoresis patterns; multilocus sequence typing of representative isolates was compared with that of international clones., Results: Sp19A caused 438 (9.8%) of 4449 pneumococcal AOM episodes, increasing by 63.1% from 1999-2001 (mean +/- SD, 8.4% +/- 0.8%) to 2004-2006 (mean +/- SD, 13.7% +/- 0.9%) among Bedouin children, who were characterized by overcrowding and high antibiotic use. Penicillin, erythromycin, and multidrug resistance increased from < 10% to 78.6%, 50.0%, and 50.0%, respectively (P < .001), and was associated with the introduction and proliferation of 2 multidrug-resistant clones that were not previously associated with multidrug resistance. This was temporally associated with the introduction of and rapid increase in azithromycin use and the frequent use of oral cephalosporins., Conclusions: The introduction and proliferation of multidrug-resistant Sp19A occurred before the introduction of PCV7. The increasing proportion of antibiotic-resistant Sp19A suggests that antibiotic use plays an important role in the community.

The role of IL-1 in susceptibility to Streptococcus pneumoniae infection was studied in mice deficient in genes of the IL-1 family [i.e. IL-1alpha-/-, IL-1beta-/-, IL-1alpha/beta-/- and IL-1R antagonist (IL-1Ra)-/- mice] following intra-nasal inoculation. Intra-nasal inoculation of S. pneumoniae of IL-1beta-/- and IL-1alpha/beta-/- mice displayed significantly lower survival rates and higher nasopharyngeal and lung bacterial load as compared with control, IL-1alpha-/- and IL-1Ra-/- mice. Treatment of IL-1beta-/- mice with rIL-1beta significantly improved their survival. A significant increase in blood neutrophils was found in control, IL-1alpha-/- and IL-1Ra-/- but not in IL-1beta-/- and IL-1alpha/beta-/- mice. Local infiltrates of neutrophils and relatively preserved organ architecture were observed in the lungs of IL-1alpha-/- and control mice. However, S. pneumoniae-infected IL-1beta-/-, IL-1alpha/beta-/- and IL-1Ra-/- mice demonstrated diffuse pneumonia and tissue damage. Altogether, all three isoforms contribute to protection against S. pneumoniae; our results point to differential role of IL-1alpha and IL-1beta in the pathogenesis and control of S. pneumoniae infection and suggest that IL-1beta has a major role in resistance to primary pneumococcal infection while the role of IL-1alpha is less important.

Background: Streptococcus pyogenes, or group A beta -hemolytic Streptococcus (GAS), is an important causative agent of bacterial pharyngotonsillititis and skin, soft-tissue, and invasive infections. Although it is also an important pathogen in acute otitis media (AOM), its exact role has not been determined., Methods: Patients aged 0-18 years with AOM, from whom a specimen of middle-ear fluid was obtained and cultured during 1999-2003, were enrolled. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and GAS were considered pathogens. Information collected included demographic characteristics, clinical history, and signs and symptoms., Results: GAS otitis was observed in 350 (3.1%) of 11,311 episodes (of which 117 were also culture-positive for other pathogens). The other 10,961 episodes involved H. influenzae only (n = 2507), S. pneumoniae only (n = 2131), dual infection with H. influenzae and S. pneumoniae (n = 1290), M. catarrhalis only (n = 129), and other combinations of pathogens (n = 271). Increased age and Jewish ethnicity were independent, significant, positive risk factors for GAS AOM, and fall season was a negative risk factor. Episodes of GAS infection were less frequently bilateral, febrile, and accompanied by other systemic findings than were other episodes of other types of infection. Most patients with GAS AOM presented with acute drainage from the ears. A lower proportion of cases of AOM were due to GAS in children with recurrent AOM and in patients recently treated with antibiotics, compared with patients with AOM who did not have these factors. The risk for mastoiditis was highest among patients with GAS AOM, compared with patients infected with other pathogens: 11.6 episodes per 1000 episodes of GAS AOM, compared with 2.2, 0.3, and 0 episodes of mastoiditis per 1000 episodes of AOM due to S. pneumoniae, H. influenzae, and M. catarrhalis, respectively., Conclusion: Compared with AOM caused by pathogens other than GAS, GAS AOM is characterized by older age and higher local aggressiveness manifested by lower rates of fever and respiratory symptoms and higher rates of tympanic perforation and mastoiditis.