Community-acquired Alveolar Pneumonia Research Articles

2618. Four Respiratory Viruses are Involved in the Majority of Community-Acquired Alveolar Pneumonia (CAAP) Episodes in Children < 5 Years

Abstract Background Community-acquired alveolar pneumonia (CAAP) is considered a bacterial disease in most cases. However, multiple studies in young children have shown a high correlation of its incidence with the epidemiological activity of four respiratory viruses (RSV, hMPV, influenza, and parainfluenza [pneumonia-associated viruses; PAV]). This strongly suggests an important role for bacterial-viral coinfections. The current study examines the detection rate of PAV in radiologically-confirmed CAAP in young children. Methods Hospitalization for CAAP episodes and viral detection were prospectively studied among all children under 5 years living in southern Israel (the Negev district); over 95% of these children are born and treated at the only medical center in the region. This prospective active surveillance was previously described (Dagan, EBioMedicine, 90:104493, 2023). Viral activity was defined by all PAV-positive tests in children under 5 years in the community. Nasal samples of children with CAAP were obtained for virus detection by PCR within 48 hours from admission. Only episodes tested for all four PAVs were included. The monthly incidence of PAV-positive CAAP was calculated by extrapolating to all-CAAP episodes, in each month. Results During the study period, 2,592 CAAP hospitalizations occurred. Specimens for all four PAVs were obtained in 1,851 (71.4%) CAAP episodes (< 12 months, 1,009; 12-23 months, 443; 24-59 months, 399) (Table). Overall, 59% of all episodes were positive for one or more PAVs, 64% of which were RSV (either as single or mixed detection). The surveillance of PAV activity in the community yielded 9,021 positive specimens for one or more PAVs. The dynamic patterns of both all-cause and PAV-positive CAAP hospitalizations from July 2016 through December 2022 closely resembled that of the PAV activity in the community, including the unusual pattern during the COVID-19 years 2020 through 2022 (Figure 1). The PAV-CAAP episodes were the main contributors of the CAAP seasonality (Figure 2). Conclusion RSV, followed by hMPV, and to a lesser degree influenza and parainfluenza viruses, were the main viruses detected in children under 5 years hospitalized for CAAP. These four viruses were responsible for the seasonal pattern of CAAP hospitalizations. Disclosures Ron Dagan, Professor MD, GSK: Honoraria|MedIMmune/AstraZeneca: Grant/Research Support|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Expert Testimony|Pfizer: Grant/Research Support|Pfizer: Honoraria|Sanofi Pasteur: Honoraria David Greenberg, Professor MD, GSK: Advisor/Consultant|GSK: Honoraria|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria Shalom Ben-Shimol, Dr. MD, GSK: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria Daniel M. Weinberger, PhD, GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support Dana Danino, Dr. MD, Pfizer: Grant/Research Support

1940. Real-Life Impact of Pneumococcal Conjugate Vaccines (PCVs) on Hospitalization of Young Children with RSV-Associated Community-acquired Alveolar Pneumonia (CAAP)

Abstract Background The important role of streptococcus pneumoniae in pediatric community-acquired alveolar pneumonia (CAAP) has been demonstrated, mainly through PCV impact on CAAP rates in young children, in whom RSV is also frequently detected. The causative role of RSV on CAAP has been strongly suggested from multiple epidemiological studies. Although pneumococcal-RSV coinfections in pneumonia were suggested by a pre-licensee PCV9 study, no solid real-life data were generated to substantiate the potential effect of PCVs on RSV-associated CAAP (RSV-CAAP). The current prospective study evaluates the impact of PCV7/PCV13 implementation in Israel on all-cause CAAP and RSV-CAAP incidence dynamics in young children during RSV seasons. Methods PCV7/PCV13 were implemented in Israel in July 2009/November 2010. A prospective population-based surveillance on CAAP rates in children < 5 years in southern Israel has been ongoing since 2002 (Ben-Shimol, CID 71:177, 2020). Nasal samples of RSV (by PCR) were tested in most episodes and were extrapolated for total CAAP episodes. RSV season was defined as all months with >5 positive RSV tests in southern Israel. The impact was determined by incidence rate ratio (IRR) comparing each RSV season (and the four years 2015-19 combined) to the five pre-PCV implementation years, 2004-09, combined). Results From Jul-2004 to Jun-2019, 7,654 CAAP episodes were recorded; 3,661 (47.8%) were tested for RSV, of which 1,662 (45.4%) were positive. The seasonal proportions of RSV-CAAP of all episodes ranged from 37.4% to 67.2%. Compared to 2004-09 (combined), IRR (95% CI) for 2015-19 were 0.68 (0.56-0.84) for RSV CAAP and 0.70 (0.61 – 0.80) for all-cause CAAP (Table, Figure). Generally, yearly seasonal IRRs for all-cause CAAP and RSV-CAAP were similar. Conclusion The abrupt, steep , and seasonal reduction of hospitalization of young children for both all-cause CAAP and RSV-CAAP strongly support the important role of RSV-S. pneumoniae coinfections in CAAP. The dynamics observed in CAAP and other pneumococcus-associated diseases in association with RSV activities during COVID-19 (Dagan, EBioMedicne, 90:104993, 2023) together with the real-life impact of PCVs on RSV-CAAP confirm the mutual role of RSV and S. pneumoniae in CAAP. Disclosures Ron Dagan, Professor MD, GSK: Honoraria|MedIMmune/AstraZeneca: Grant/Research Support|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Expert Testimony|Pfizer: Grant/Research Support|Pfizer: Honoraria|Sanofi Pasteur: Honoraria David Greenberg, Professor MD, GSK: Advisor/Consultant|GSK: Honoraria|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria Shalom Ben-Shimol, Dr. MD, GSK: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria

The COVID-19 pandemic as an opportunity for unravelling the causative association between respiratory viruses and pneumococcus-associated disease in young children: a prospective study.

In young children, rates of lower respiratory infections (LRI) and invasive pneumococcal disease (IPD) have been associated with respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (flu), and parainfluenza (PIV) (collectively termed here as pneumonia and pneumococcal disease-associated viruses [PDA-viruses]). However, their contribution to the pathogenesis of these disease endpoints has not yet been elucidated. The COVID-19 pandemic provided a unique opportunity to examine the question. This prospective study comprised all children <5 years, living in southern Israel, during 2016 through 2021. The data were previously collected in multiple ongoing prospective surveillance programs and include: hospital visits for community-acquired alveolar pneumonia (CAAP), non-CAAP LRI; nasopharyngeal pneumococcal carriage (<3 years of age); respiratory virus activity; and nationwide, all-ages COVID-19 episodes and IPD in children <5 years. A hierarchical statistical model was developed to estimate the proportion of the different clinical endpoints attributable to each virus from monthly time series data, stratified by age and ethnicity. A separate model was fit for each endpoint, with covariates that included a linear time trend, 12-month harmonic variables to capture unexplained seasonal variations, and the proportion of tests positive for each virus in that month. During 2016 through 2021, 3,204, 26,695, 257, and 619 episodes of CAAP, non-CAAP LRI, pneumococcal bacteremic pneumonia and non-pneumonia IPD, respectively, were reported. Compared to 2016-2019, broad declines in the disease endpoints were observed shortly after the pandemic surge, coincident with a complete disappearance of all PDA-viruses and continued circulation of rhinovirus (RhV) and adenovirus (AdV). From April 2021, off-season and abrupt surges of all disease endpoints occurred, associated with similar dynamics among the PDA-viruses, which re-emerged sequentially. Using our model fit to the entire 2016-2021 period, 82% (95% CI, 75-88%) of CAAP episodes in 2021 were attributable to the common respiratory viruses, as were 22%-31% of the other disease endpoints. Virus-specific contributions to CAAP were: RSV, 49% (95% CI, 43-55%); hMPV, 13% (10-17%); PIV, 11% (7-15%); flu, 7% (1-13%). RhV and AdV did not contribute. RSV was the main contributor in all endpoints, especially in infants. Pneumococcal carriage prevalence remained largely stable throughout the study. RSV and hMPV play a critical role in the burden of CAAP and pneumococcal disease in children. Interventions targeting these viruses could have a secondary effect on the burden of disease typically attributed to bacteria. There was no funding for this study.

A Hypothesis-Generating Prospective Longitudinal Study to Assess the Relative Contribution of Common Respiratory Viruses to Severe Lower Respiratory Infections in Young Children.

Respiratory viruses such as respiratory syncytial virus (RSV), influenza, parainfluenza and human metapneumovirus are well-established etiologies of acute lower respiratory tract infections (ALRIs; LRI-viruses). In contrast, adenovirus (AdV), rhinovirus/enterovirus (RV/EV) and seasonal human coronaviruses (CoV), collectively termed AdV/RV/CoV, are detected both in healthy children and children with ALRI. The methods include a prospective longitudinal case-control study, assessing the prevalence of LRI-viruses versus AdV/RV/CoV in ALRI [community-acquired alveolar pneumonia (CAAP) and bronchiolitis] during hospitalization (visit 1), 7-14 days (visit 2) and 28-35 days (visit 3) in 2-17-month-old children. Controls were 2-27-month-old children hospitalized for elective surgery during the same respiratory seasons. We enrolled 99 infants (37 CAAP, 38 bronchiolitis and 24 controls) and obtained 211 nasopharyngeal swabs. Overall, 163 (77%) had greater than or equal to 1 viruses detected; RV/EV (n = 94; 45%) and RSV (n = 71; 34%) were the most frequently detected viruses. In CAAP, the overall LRI-virus prevalence was 78.4%, 32.4% and 5.4% in visits 1, 2 and 3, respectively; the respective rates in bronchiolitis were 73.7%, 34.5% and 8.0%. In controls, no LRI-viruses were detected. In contrast, the overall AdV/RV/CoV prevalence was high among controls (70.8%) and similar among CAAP (48.6%, 40.5% and 40.5%) and bronchiolitis (47.4, 58.6% and 64.0%) across visits. Among ALRI cases, LRI-viruses dominated during the acute disease, with prevalence declining within 28-35 days, suggesting their causative role. In contrast, AdV/RV/CoV prevalence was similar during all 3 visits and in controls, suggesting that carriage of these viruses is common during the viral respiratory season. The current study is relatively small and of short duration; however, the findings are supported by other recent studies.

2203. Involvement of Respiratory Viruses in Community-Acquired Alveolar Pneumonia (CAAP) in Children &amp;lt; 5 Years in Southern Israel, Before and During the COVID-19 Pandemic

Abstract Background Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) and to a lesser extent, parainfluenza and influenza viruses have been associated with pneumonia in young children. In contrast, adenovirus (AdV) and rhinovirus (RhV) are usually not associated with pneumonia. We aimed to evaluate the involvement of the four pneumonia associated viruses (grouped as PAV) in pediatric CAAP, before and during the COVID-19 pandemic. Methods CAAP incidence and viral activity surveillance in southern Israel in children &amp;lt; 5y and virological detection methods were described previously (Danino. CID 2022, https://doi.org/10.1093/cid/ciab1014). We reviewed the period of Jan 2016 - Mar 2022. Most cases of COVID-19 in children &amp;lt; 5y occurred during Dec 2021 - Mar 2022 (Figure 1); Over 95% of children admitted for respiratory disease were tested for COVID-19 (PCR). Since AdV and RhV activity was previously not associated with CAAP and tended to be equally involved in mixed and single infections, the current analysis was done for the four PAV only. Results CAAP incidence dynamics closely resembled the four PAV (grouped) activity dynamics (Figure 2A, 2B) with very low activity during the expected peak in winter 2020-2021, but with an off-season resurgence from spring 2021. Even though most CAAP episodes during the pandemic coincided with peak COVID-19 rates, only 9 CAAP episodes were COVID-19 positive (7 in 2022, of which 5 were RSV positive). Out of 3,430 CAAP episodes 55% were tested for PAV, of which 61% were positive, with similar rates before and during the pandemic. RSV was the most common involved virus, followed by hMPV. The virus distribution in CAAP during the entire period reflected their activity in the community (Figure 2C). Unlike pre-pandemic years where all four PAV appeared almost simultaneously, in 2021 PAV resurged sequentially, resulting in successive involvement in CAAP episodes, suggesting a causative association. Conclusion 1. SARS-CoV-2 was only rarely involved in CAAP in young children. 2. PAV were involved in 61% of CAAP episodes in children &amp;lt; 5y with predominance of RSV and hMPV. 3. The atypical dynamics imposed by the COVID-19 pandemic suggests a causative association between PAV and CAAP. Disclosures All Authors: No reported disclosures.

2205. Potential Causative Association between Respiratory Viruses and Pneumococcus-Associated Disease in Young Children in Israel: Lessons from the COVID-19 Pandemic

Abstract Background During the early Covid-19 pandemic, we observed a close-to-full disappearance of the activity of 4 respiratory viruses (RSV, hMPV, influenza, and parainfluenza), followed by an off-season sequential re-emergence in 2021. Surprisingly, a striking similarity between the dynamics of pneumococcus-associated disease (PAD; namely community-acquired alveolar pneumonia [CAAP; often considered pneumococcal] and bacteremic-pneumococcal pneumonia [IPD-Pneumonia]), was also observed. In contrast, adenovirus and rhinovirus activities did not change during COVID-19. We examined the association between PAD and RSV, hMPV, influenza, and parainfluenza (PAD-viruses). Methods Surveillance of CAAP and IPD-Pneumonia incidences and viral activity in children &amp;lt; 5 years was described in detail previously [Danino D. et al. Clin Infect Dis. 2022, https://doi.org/10.1093/cid/ciab1014]. We extended the observations until December 2021, to capture the sequential re-emergence of the 4 PAD-viruses. A hierarchical linear regression model was used to quantify the association between PAD-viruses (each virus individually and combined), adenovirus and PAD. After fitting the models, the contribution of each virus was estimated. Results The Figure shows striking similarities in the dynamics of CAAP, IPD-Pneumonia, and PAD-viruses both before and during the COVID-19 pandemic. During the expected peak season (Oct 2020 – Apr 2021) PAD episodes were extremely low. However, off-season peaks were seen during May – Dec 2021. Overall, 78% and 25% of all CAAP and IPD-Pneumonia episodes, respectively, were attributable to these viruses in children &amp;lt; 5 (Table). In CAAP, cases were attributable to each of the 4 PAD-viruses individually throughout the first 5 years of life: RSV and hMPV combined contributed 80%, 63%, and 42% of all CAAP episodes in children aged &amp;lt; 1, 1, and 2-4 years, respectively. The respective figures for influenza and parainfluenza combined were 13%, 21%, and 22%. Only RSV significantly contributed to IPD-Pneumonia (19%). Adenovirus did not contribute to PAD episodes. Conclusion Our model suggests an important causative association between RSV, hMPV, influenza, and parainfluenza viruses and CAAP, and between RSV and IPD-Pneumonia. Disclosures All Authors: No reported disclosures.

The impact of the pneumococcal conjugate vaccines on the incidence of community-acquired alveolar pneumonia in premature compared with in term-born infants

BackgroundPreterm-born children are prone to respiratory infections and complications during infancy and early childhood. In Israel, pneumococcal conjugated vaccines (PCVs) were introduced in 2009–2010, with high vaccination coverage. We assessed the impact of PCV implementation on community-acquired alveolar pneumonia (CAAP) in children < 2 years old born prematurely, in comparison with term born infants. MethodsWe conducted a prospective, active, population-based surveillance of children < 2 years old with radiologically-proven CAAP, visiting the only regional medical center. CAAP incidence in the pre-PCV and post-PCV eras were compared in early premature (29–32 weeks gestational age [WGA]), late premature (33–36 WGA) and term-born infants (>36 WGA). ResultsOf 214,947 births during the study period, 6'791 CAAP episodes were diagnosed; 211, 653 and 5,806 were in early premature, late premature and term infants, respectively. After PCV implementation, overall CAAP visits were reduced by 44% (95% CI 36–51): 60%, 21% and 45% among those born early preterm, late preterm and at term, respectively (statistically significant for children born early preterm and at term). For outpatients, the respective rate reductions were 79%, 40% and 65% (statistically significant for the children born at term). Importantly, the mean annual rates in the post-PCV period became similar in all 3 groups.The rate reductions among the hospitalized children were lower those that among the non-hospitalized children, with reductions of 56%, 16% and 33% for the three groups, respectively (statistically significant for early preterm and at term children). ConclusionsCAAP reduction trends after PCV implementation for preterm-born infants were similar to those for term-born infants. Whether this was because of similar direct PCV- protection, because of indirect (herd) protection or both, is unclear. Post-PCV implementation, the gaps in CAAP rates between infants born prematurely and at term were reduced.

Decline in Pneumococcal Disease in Young Children During the Coronavirus Disease 2019 (COVID-19) Pandemic in Israel Associated With Suppression of Seasonal Respiratory Viruses, Despite Persistent Pneumococcal Carriage: A Prospective Cohort Study.

BackgroundThe incidence of invasive pneumococcal disease (IPD) declined during the COVID-19 pandemic. Previous studies hypothesized that this was due to reduced pneumococcal transmission resulting from non-pharmaceutical interventions. We used multiple ongoing cohort surveillance projects in children <5 years to test this hypothesis.MethodsThe first SARS-CoV-2 cases were detected in February-2020, resulting in a full lockdown, followed by several partial restrictions. Data from ongoing surveillance projects captured the incidence dynamics of community-acquired alveolar pneumonia (CAAP), non-alveolar lower respiratory infections necessitating chest X-rays (NA-LRI), nasopharyngeal pneumococcal carriage in non-respiratory visits, nasopharyngeal respiratory virus detection (by PCR), and nationwide invasive pneumococcal disease (IPD). Monthly rates (January-2020 through February-2021 vs. mean monthly rates 2016-2019 [expected rates]) adjusted for age and ethnicity, were compared.ResultsCAAP and bacteremic pneumococcal pneumonia were strongly reduced (incidence rate ratios, [IRRs] .07 and .19, respectively); NA-LRI and non-pneumonia IPD were also reduced, with a lesser magnitude (IRRs, .46 and .42, respectively). In contrast, pneumococcal carriage prevalence was only slightly reduced, and density of colonization and pneumococcal serotype distributions were similar to previous years. The decline in pneumococcus-associated disease was temporally associated with a full suppression of RSV, influenza viruses, and hMPV, often implicated as co-pathogens with pneumococcus. In contrast, adenovirus, rhinovirus, and parainfluenza activities were within or above expected levels.ConclusionsReductions in pneumococcal and pneumococcus-associated diseases occurring during the COVID-19 pandemic in Israel were not predominantly related to reduced pneumococcal carriage and density, but were strongly associated with the disappearance of specific respiratory viruses.

Decline in pneumococcal nasopharyngeal carriage in children 6–23 months with respiratory illnesses following pneumococcal conjugate vaccine implementation

BackgroundFollowing pneumococcal conjugate vaccines (PCVs) implementation, worldwide, pneumococcal carriage rates remained stable, indicating full replacement of vaccine-serotypes (VT) with non-VT. However, data are scarce regarding PCV impact on pneumococcal carriage rates in healthy vs. sick children. We assessed pneumococcal carriage rates dynamics in healthy and sick children 6–23 months, following PCV introduction. MethodsThis is a prospective, population-based surveillance conducted during the years 2009–2017, in southern Israel. Three groups were defined as follows: Children without respiratory infection signs (the healthy/non-respiratory group); Children who had a chest radiography at the hospital (the Hosp-CXR group); and children with community-acquired alveolar pneumonia (CAAP).Rate ratios (RRs; 95% CI) were calculated, comparing between late-13-valent PCV (PCV13) period (2016–2017) and early-PCV period (2009–2010). Rate ratios were adjusted for antibiotic administration, seasonality and ethnicity, and separate calculations were performed for 6–11 and 12–23 month old children. ResultsOverall, 51% of 8627 nasopharyngeal cultures were positive.In 2009–2010 (early-PCV period), the overall carriage rate was 55%; serotypes included in the PCV13 carriage rates were 28%, 31% and 38% in the healthy/non-respiratory, Hosp-CXR, and CAAP groups, respectively.Overall carriage rates in healthy/non-respiratory episodes were stable (~54%) when comparing between 2016 and 17 and 2009–10 (RR = 0.98; 0.84–1.15). In contrast, rates significantly declined for Hosp-CXR (RR = 0.78; 0.63–0.98) and CAAP (RR = 0.65; 0.47–0.89). These trends were driven by ~ 80% VT reductions, coupled with non-VT increase. ConclusionsFollowing 7-valent PCV/ PCV13 introduction, pneumococcal carriage rates declined in respiratory diseases, but not in healthy children and children without respiratory infections. These trends suggest that a reduction in pneumococcal carriage rates during respiratory infections indicates a decline in respiratory infections caused by VT, while carriage rates in non-respiratory cases reflect non-VT predominance, that have low disease potential for respiratory disease.

Effectiveness of Pneumococcal Conjugate Vaccines Against Community-acquired Alveolar Pneumonia Attributable to Vaccine-serotype Streptococcus pneumoniae Among Children

Abstract 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 &amp;lt;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.

Unique Features of Hospitalized Children with Alveolar Pneumonia Suggest Frequent Viral-Bacterial Coinfections.

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. 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). 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. 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.

Characterization of children younger than 5 Years of age with severe community-acquired alveolar pneumonia (CAAP) requiring Pediatric Intensive Care Unit (PICU) admission

BackgroundThe 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.MethodsWe 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).ResultsOf 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 O2 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).ConclusionChildren admitted to PICU were younger, had more respiratory syncytial virus (RSV) detection, were premature, had lower O2 saturation, and had a higher respiratory rate than those admitted to the general ward or those visiting the emergency department and subsequently discharged.

Pneumococcal conjugate vaccines decrease community-acquired alveolar pneumonia with and without pleural effusion in children

Background: Radiographically-proven community-acquired alveolar pneumonia with pleural effusion (PE-CAP) has a less favourable outcome than pneumonia without pleural effusion (NPE-CAP). We assessed PE-CAP and NPE-CAP rate dynamics in children <60 months in southern Israel before and after 7- and 13-valent pneumococcal conjugate vaccine (PCV7/PCV13) implementation (2002–2016).Methods: An ongoing, prospective observational study. Our hospital serves a captive population of ∼75,000 children <60 months, enabling incidence calculation. PCV7/PCV13 were implemented in Israel in July 2009/November 2010, respectively. All chest radiographs (CXRs) were digitalized and analysed according to the WHO Standardization of Interpretation. Annual incidences of PE-CAP and NPE-CAP were calculated, 2002–2016. Incidence-rate ratios (IRRs) comparing PCV13 (2013–2016), PCV7 (2010–2011) and pre-PCV (2002–2008) periods were calculated.Results: Overall, 12,271 CAP episodes were identified; 159 (1.3%) PE-CAP and 12,112 (98.7%) NPE-CAP. In total, 65.8% and 34.2% were children <24 and 24–59 months, respectively; 61.0% and 39.0% were Bedouin and Jewish children, respectively. Following PCV7 introduction, PE-CAP rates declined by 48% (Incidence rate ratios [IRR] = 0.52; 0.26–1.03), while NPE-CAP rates declined by 20% (IRR = 0.80; 0.75–0.86). In the PCV13 period, PE-CAP and NPE-CAP rates further declined, resulting in overall 70% (IRR = 0.30; 0.18–0.50) and 55% (IRR = 0.45; 0.43–0.48) reductions, respectively, comparing the PCV13 and the pre-PCV periods. Similar trends were observed in all subgroups (Bedouin vs. Jewish and age < 24 months vs. 24–59 months).Conclusions: Following PCV7/PCV13 introduction, PE-CAP and NPE-CAP rates substantially declined. However, the rate dynamics were different, with steeper declines observed in PE-CAP rates, possibly deriving from differences in disease aetiology.

Nasopharyngeal Carriage of Invasive Pneumococcal Serotypes During Childhood Community-Acquired Alveolar Pneumonia Is Associated With Specific Clinical Presentation.

Streptococcus pneumoniae (Pnc) serotypes differ in invasive potential. We examined whether community-acquired alveolar pneumonia (CAAP) in children carrying commonly recognized pneumonia invasive pneumococcal serotypes ([PnIST] 1, 5, 7F, 14, and 19A) differs from CAAP in children carrying less invasive serotypes (non-PnIST) or no Pnc (Pnc-neg). Children <5 years, visiting the only regional Pediatric Emergency Room, with radiologically proven CAAP were enrolled. Nasopharyngeal cultures were processed for pneumococcal isolation and serotyping. Clinical and demographic characteristics were recorded. The study was conducted before pneumococcal conjugate vaccine implementation in Israel. A total of 1423 CAAP episodes were recorded: PnIST, 300 (21.1%); non-PnIST, 591 (41.5%); and Pnc-neg, 532 (37.4%). After adjustment for age, ethnicity, seasonality, and previous antibiotics, the following variables were positively associated with PnIST carriage compared with both groups: temperature ≥39°C, peripheral white blood cell count ≥20 000/mm3, C-reactive protein ≥70.0 mg/L, and serum sodium <135 mEq/L. Lower oxygen saturation, viral detection, and comorbidities were negatively associated with Pn-IST carriage (odds ratios, <1.0). Differences between non-PnIST carriers and Pnc-neg groups were smaller or nonsignificant. Young children with CAAP carrying common PnIST had a lower proportion of comorbidities, hypoxemia, and viral detection and had more intense systemic inflammatory response than those carrying non-PnIST or not carrying Pnc.

Use of Chest Radiography Examination as a Probe for Pneumococcal Conjugate Vaccine Impact on Lower Respiratory Tract Infections in Young Children.

Community-acquired alveolar pneumonia (CAAP) is considered a bacterial disease, mainly pneumococcal. CAAP rates markedly declined following 7- and 13-valent pneumococcal conjugate vaccine (PCV) introductions worldwide. In contrast, non-CAAP lower respiratory tract infections (NA-LRIs) are generally not considered pneumococcal diseases. We assessed CAAP, NA-LRIs, and overall visits with chest radiograph (CXR) examination rates in the pediatric emergency room in southern Israel before and after PCV implementation. This was an ongoing, prospective observational study. Our hospital serves a captive population of approximately 75 000 children aged <5 years, enabling incidence calculation. PCV7 and PCV13 were implemented in Israel in July 2009 and November 2010, respectively. All CXRs were analyzed according to the World Health Organization Standardization of Interpretation. We calculated CAAP, NA-LRI, and CXR examinations annual incidences from 2004 to 2017 and incidence rate ratios comparing the PCV13 (2014-2017) with the pre-PCV (2004-2008) periods. Overall, 72 746 CXR examinations were recorded: 14% CAAP and 86% NA-LRI. CAAP, NA-LRI, and CXR examination visit rates declined by 49%, 34%, and 37%, respectively. This pattern was seen in Jewish and Bedouin children (the 2 ethnically distinct populations), with steeper declines observed among Jewish children and children aged >12 months. PCV7/PCV13 implementation resulted in a marked decline in CAAP and overall visits with CXR examination rates in young children. Overall, approximately 14 750 hospital visits with CXR were prevented annually per 100 000 population aged <5 years. These findings suggest that although NA-LRIs are usually not considered pneumococcal, many can be prevented by PCVs.Pneumococcal conjugate vaccine (PCV7/PCV13) implementation resulted in significant declines in community-acquired alveolar pneumonia (CAAP) and overall chest radiography examination rates in young children. Although non-CAAP lower respiratory tract infections are usually not considered pneumococcal, many can be prevented by PCVs.

Streptococcus pneumoniae Serotypes and Antibiotic Susceptibility Patterns in Middle Ear Fluid Isolates During Acute Otitis Media and Nasopharyngeal Isolates During Community-acquired Alveolar Pneumonia in Central Romania.

Streptococcus pneumoniae is a common cause of community-acquired alveolar pneumonia (CAAP) and acute otitis media (AOM) in children. Romania has high rates of S. pneumoniae antibiotic resistance. The pneumococcal conjugated vaccines (PCVs) are not being used routinely in this country. The aims of the study were as follows: 1) to compare pneumococcal antibiotic resistance patterns in AOM and CAAP in children from central Romania and 2) to compare differences in the distribution of pneumococcal serotypes isolated from the middle ear fluid (MEF) of children with AOM and from the nasopharynx (NP) of children with CAAP. Children younger than 5 years old with AOM or with radiologically confirmed CAAP were prospectively enrolled. Samples from MEF and NP were evaluated for antibiotic susceptibility and serotyping. Eighty-eight children with CAAP and 68 with AOM were enrolled. Of the MEF and CAAP isolates, 64 (94.1%) and 79 (89.7%) were penicillin nonsusceptible, respectively. The pneumococcal serotypes distribution in AOM was similar to those in CAAP except for serotype 19F, which was more common in AOM. Overall, 89.7% and 85.8% of all serotypes in AOM and CAAP patients, respectively, were covered by 13-valent PCV. MEF and NP-CAAP S. pneumoniae isolates were similar in regard to serotype distribution and antibiotic resistance. S. pneumoniae antibiotic resistance rates were extremely high. Thirteen-valent PCV has the potential to reduce both the burden of disease as well as the rates of antibiotic-resistant S. pneumoniae in both diseases.

Nasopharyngeal Pneumococcal Carriage During Childhood Community-Acquired Alveolar Pneumonia: Relationship Between Specific Serotypes and Coinfecting Viruses.

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). 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. 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). 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.

Cocontribution of Rotavirus and Pneumococcal Conjugate Vaccines to the Reduction of Pediatric Hospital Visits in Young Children

To assess rotavirus vaccine and pneumococcal conjugate vaccines (PCVs) cumulative impact on the pediatric emergency department visits and hospitalization rates in children <2 years of age in southern Israel between April 2006 and March 2014. This prospective, population-based observational study calculated the rates of rotavirus gastroenteritis (RVGE), non-RVGE, community-acquired alveolar pneumonia (CAAP), nonalveolar lower respiratory tract infection, and all-cause hospital visits. PCV7, PCV13, and rotavirus vaccination programs were implemented in Israel in July 2009, November 2010, and January 2011, respectively. From 2006-2009 to 2013-2014, the rates of hospitilizations for RVGE, non-RVGE, CAAP, and nonalveolar lower respiratory tract infection decreased by 78%, 21%, 46%, and 7%, respectively. In outpatients, the respective decreases were 80%, 16%, 67%, and 14%. All-cause outpatient pediatric emergency department visits and hospitalization rates were reduced by 12% and 11%, respectively. During the peak season (October through March), RVGE, non-RVGE, CAAP, and nonalveolar lower respiratory tract infection hospitalization rates decreased significantly by 86%, 44.6%, 23.3%, and 10.5%, respectively. In outpatients, the respective decreases were 81.7%, 73.5%, 13.8%, and 10.7%. The proportion of RVGE and CAAP (grouped) of all-cause hospitalizations and outpatient pediatric ED visits decreased from 19.9% to 12.3% and from 6.9% to 1.8%, respectively. Rotavirus vaccine and PCV introduction cocontributed to a rapid, considerable reduction in hospital burden in children <2 years of age. Because seasonalities of both diseases overlap, this reduction is particularly helpful in relieving burdens of disease and care during the most cumbersome morbidity season.

Impact of PCV7/PCV13 introduction on community-acquired alveolar pneumonia in children

BackgroundAlveolar 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. MethodsThis 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). ResultsOverall, 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). ConclusionsA 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.

Increased Risk for Respiratory Syncytial Virus-associated, Community-acquired Alveolar Pneumonia in Infants Born at 31–36 Weeks of Gestation

We compared hospitalization and pediatric intensive care unit (PICU) admission rates for community-acquired alveolar pneumonia (CAAP) and respiratory syncytial virus (RSV)-associated CAAP (RSV-CAAP) in non-RSV-immunized children <24-month-old born at 31-36 weeks gestational age (GA) versus those born at term (>36 weeks GA). Nasopharyngeal samples for RSV were obtained prospectively (2004-2011) during RSV season, from hospitalized children with radiographic-diagnosed CAAP. Soroka University Medical Center is the only hospital in the region, enabling population-based rate calculation. Relative risks (RR) and 95% confidence intervals (95% CI) were calculated comparing RSV-CAAP incidence in 31-36 weeks GA with >36 weeks GA children. CAAP hospitalization incidences (per 1000 population) were 23.6 and 9.4 (RR: 2.52; 95% CI: 2.13-2.68), respectively; the respective incidences of PICU admission for overall CAAP were 1.8 and 0.2 (RR: 7.88; 95% CI: 4.59-11.83). The RRs (and 95% CI) for RSV-CAAP hospitalizations and PICU admission rates were (after extrapolation) 15.2 and 5.8 (RR: 2.79; 95% CI: 2.31-3.06) and 1.1 and 0.1 (RR: 9.14; 95% CI: 4.93-16.96), respectively. In a multiregression analysis in patients with RSV-CAAP versus CAAP, 31-36 weeks GA was an independent risk factor for hospitalization (RR: 1.485; 95% CI: 1.03-2.14). Children <24-month-old born at 31-36 weeks GA are at increased risk for hospitalization and PICU admission for both overall CAAP and RSV-associated CAAP compared with those born at >36 weeks GA. Moreover, in late premature children, RSV represented a 50% increased risk for CAAP compared with infants born at term.