Modelling the potential clinical and economic impact of universal immunisation with nirsevimab versus standard of practice for protecting all neonates and infants in their first respiratory syncytial virus season in Spain.

BACKGROUND: Respiratory syncytial virus (RSV) is associated with substantial morbidity among infants. This study modelled the potential public health and economic impact of nirsevimab, a long-acting monoclonal antibody, as an immunoprophylactic strategy for all infants in Spain in their first RSV season. METHODS: A static decision-analytic model of the Spanish birth cohort during its first RSV season was developed to estimate the impact of nirsevimab on RSV-related health events and costs versus the standard of practice (SoP). Spain-specific costs and epidemiological data were used as model inputs. Modelled outcomes included RSV-related outpatient visits, emerging room (ER) visits, hospitalisations - including pediatric intensive care unit (PICU) admission, mechanical ventilation, and inpatient mortality. RESULTS: Under the current SoP, RSV caused 151,741 primary care visits, 38,798 ER visits, 12,889 hospitalisations, 1,412 PICU admissions, and 16 deaths over a single season, representing a cost of €71.8 million from a healthcare payer perspective. Universal immunisation of all infants with nirsevimab was expected to prevent 97,157 primary care visits (64.0% reduction), 24,789 ER visits (63.9%), 8,185 hospitalisations (63.5%), 869 PICU admissions (61.5%), and 9 inpatient deaths (52.6%), saving €47.8 million (62.4%) in healthcare costs. CONCLUSIONS: These results suggest that immunisation with nirsevimab of all infants experiencing their first RSV season in Spain is likely to prevent thousands of RSV-related health events and save considerable costs versus the current SoP.

Estimating the burden of vaccine preventable lower respiratory tract disease in primary care, UK: protocol for a prospective surveillance study (AvonCAP GP2).

BACKGROUND: The true burden of acute lower respiratory tract diseases (aLRTD; includes acute lower respiratory tract infection, acute exacerbation of pre-existing heart failure and chronic lung disease) among adults presenting to primary care, and the proportion that are potentially vaccine preventable, is unknown. AIMS: To describe aLRTD incidence in adults presenting to primary care; estimate proportions caused by RSV, SARS-CoV-2 and pneumococcus; and investigate disease burden from patient and NHS perspectives. DESIGN & SETTING: Primary care prospective cohort study conducted in six representative General Practices (total Ì´83 000 registered adults) in Bristol, UK. METHOD: Adults (aged≥18 years) registered at participating General Practices and presenting to primary care (in-hours or out-of-hours) or emergency department (if not admitted) with aLRTD will be eligible and identified by real-time primary care record searches. Researchers will screen electronic GP records, including free text, contact patients to assess eligibility, and offer enrolment in a surveillance study and an enhanced diagnostic study (urine, saliva and respiratory samples; physical examination; and symptom diaries). Data will be collected for all aLRTD episodes, with patients assigned to one of three arms: surveillance, embedded diagnostic, and descriptive dataset. Outcome measures will include clinical and pathogen defined aLRTD incidence rates, symptom severity and duration, NHS contacts and costs, health-related quality of life changes, and mortality (≤30 days post identification). CONCLUSION: This comprehensive surveillance study of adults presenting to primary care with aLRTD, with embedded detailed data and sample collection, will provide an accurate assessment of aLRTD burden due to vaccine preventable infections.

Adult Respiratory Syncytial Virus Infection: Defining Incidence, Risk Factors for Hospitalization, and Poor Outcomes, a Regional Cohort Study, 2016-2022.

BACKGROUND: Respiratory syncytial virus (RSV) is a significant cause of illness in adults, especially older adults and those with underlying conditions. This study aimed to assess the incidence of RSV hospitalizations in adults and identify risk factors for hospitalization and poor outcomes. METHODS: A retrospective cohort study was conducted using data from two hospitals in southern Israel from 2016-2022. We calculated incidence rates of RSV and influenza hospitalizations. Risk factors for hospitalization were analyzed using Poisson regression. We evaluated poor outcomes (death, ICU admission, or mechanical ventilation) among RSV-hospitalized patients. RESULTS: The median annual incidence of RSV hospitalization was 28.2/100,000 population, increasing with age to 199/100,000 in those ≥75 years. Significant risk factors for RSV hospitalization included pulmonary diseases (RR 4.2, 95% CI 3.4-5.2), cardiovascular diseases (RR 3.3, 95% CI 2.6-4.2), and chronic renal failure (RR 2.9, 95% CI 2.3-3.7). Among hospitalized RSV patients, 13.9% had poor outcomes. Renal failure (RR 1.81, 95% CI 1.23-2.66), neutropenia (RR 2.53, 95% CI 1.19-5.35), neutrophilia (RR 1.66, 95% CI 1.81-2.34), and lymphopenia (RR 2.03, 95% CI 1.37-3.0) were associated with poor outcomes. CONCLUSIONS: RSV causes a substantial burden of hospitalizations in adults, particularly among older adults and those with comorbidities. Identifying high-risk groups can help target prevention and treatment strategies, including vaccination.

Healthcare costs related to respiratory syncytial virus in paediatric intensive care units in the Netherlands: a nationwide prospective observational study (the BRICK study).

Background: The implementation of the approved respiratory syncytial virus (RSV) preventive interventions in immunisation programmes is advancing rapidly. Insight into healthcare costs of RSV-related paediatric intensive care unit (PICU) admissions is lacking, but of great importance to evaluate the impact of implementation. Therefore, this study aimed to determine the total annual RSV-related paediatric intensive care healthcare costs in the Netherlands. Methods: A nationwide prospective, observational, multicenter study was performed from September 2021 until June 2023. The total annual RSV-related healthcare costs on PICUs in the Netherlands were calculated using RSV-related costs (subgroup I) and consequential costs (subgroup II and III). Subgroup I comprised all PICU admitted infants ≤12 months of age with laboratory-confirmed RSV infection. Subgroup II and III consisted of postponed elective PICU admissions and refused acute PICU admissions due to RSV-related lack of PICU capacity. Findings: A total of 424 infants with RSV-related PICU admission were included. Median age at PICU admission was 46 days (IQR 25-89). The median length of PICU admission was 5 days (IQR 3-8). The total RSV-related PICU costs are € 3,826,386 in 2021-2022, and € 3,183,888 in 2022-2023. Potential costs averted by RSV preventive interventions is € 1.9 to € 2.6 million depending on season, and the duration of protection. Interpretation: RSV-related PICU admissions cost €3.1 to €3.8 million in the Netherlands during one season. The introduction of new RSV preventive interventions into the Dutch immunisation programme will generate significant cost-savings on PICUs and decreases the admission burden of PICUs. Funding: None.

Infection of respiratory syncytial viruses (RSV) in the Czech Republic - analysis of hospitalizations and deaths in 2017-2022. / Infekce respiracními syncytiálními viry (RSV) v Ceské republice ­ analýza hospitalizací a úmrtí v letech 2017­2022.

OBJECTIVES: Given the lack of data on the seriousness of respiratory syncytial virus (RSV) infections in the Czech Republic, an analysis was made of available data on hospitalizations and the hospitalization risk was estimated by age group. METHODS: Data from the National Registry of Reimbursed Health Services and the National Registry of Hospitalizations were used for the analyses. Hospitalizations and deaths due to RSV infection (diagnoses J12.1, J20.5, J21.0) from 2017-2022 were analyzed by age group. RESULTS: Over the six-year period, there were 6,138 hospitalizations with the above diagnoses, ranging between years from 307 to 2,162. The estimated overall hospitalization risk per 100,000 population and year for diagnoses J12.1, J20.5, and J21.0 was 9.64, varying between 2.87 (2020) and 20.56 (2021). Age-group analysis showed the highest risk for children under 6 months of age (891.6/100,000 population and year) and the lowest for 20-34-year-olds (0.1/100,000 population and year). Children under 1 year of age accounted for 63.1% of hospitalizations with the above diagnoses. For patients 65 years and older, the annual hospitalization rates varied between 3.3-15.3%. The most frequent cause of RSV-associated hospitalizations was bronchitis, diagnosed in 55.4% of patients. Among those hospitalized with diagnoses J12.1, J20.5, and J21.0, 38 deaths were reported, representing a case fatality rate of 0.62%. The highest case fatality rate (6.5%) was observed in the age group 35-49 years. CONCLUSIONS: RSV-associated hospitalizations have been reported in all age groups in the Czech Republic. The highest RSV-associated hospitalization risk in 2017-2022 was estimated among children under 6 months of age. Passive surveillance using the available registries could currently provide the basis for measures specifically tailored to the youngest age categories. Data on the hospitalization of adults, particularly senior citizens, must be improved and complemented with active surveillance.

Cost-utility analysis of palivizumab for preventing respiratory syncytial virus in preterm neonates and infants in Colombia.

AIM: Palivizumab has proven effective in reducing hospitalizations, preventing severe illness, improving health outcomes, and reducing healthcare costs for infants at risk of respiratory syncytial virus (RSV) infection. We aim to assess the value of palivizumab in preventing RSV infection in high-risk infants in Colombia, where RSV poses a significant threat, causing severe respiratory illness and hospitalizations. METHODS: We conducted a decision tree analysis to compare five doses of palivizumab with no palivizumab. The study considered three population groups: preterm neonates (≤ 35 weeks gestational age), infants with bronchopulmonary dysplasia (BPD), and infants with hemodynamically significant congenital heart disease (CHD). We obtained clinical efficacy data from IMpact-RSV and Cardiac Synagis trials, while we derived neonatal hospitalization risks from the SENTINEL-1 study. We based hospitalization and recurrent wheezing management costs on Colombian analyses and validated them by experts. We estimated incremental cost-effectiveness ratios and performed 1,000 Monte Carlo simulations for probabilistic sensitivity analyses. RESULTS: Palivizumab is a dominant strategy for preventing RSV infection in preterm neonates and infants with BPD and CHD. Its high efficacy (78% in preventing RSV in preterm infants), the substantial risk of illness and hospitalization, and the high costs associated with hospitalization, particularly in neonatal intensive care settings, support this finding. The scatter plots and willingness-to-pay curves align with these results. CONCLUSION: Palivizumab is a cost-saving strategy in Colombia, effectively preventing RSV infection in preterm neonates and infants with BPD and CHD by reducing hospitalizations and lowering healthcare costs.

COVID-19, Influenza, and RSV in Children and Adults: A Clinical Comparative Study of 12,000 Cases.

(1) Background: Respiratory virus infections, including Coronavirus disease 2019 (COVID-19), seasonal influenza (FLU), and respiratory syncytial virus (RSV) as prominent examples, can severely affect both children and adults. This study aimed to investigate the clinical characteristics of respiratory viral infections in pediatric and adult populations and to identify determinants influencing patient hospitalization. (2) Methods: This retrospective study analyzed the electronic medical records of patients admitted to a regional hospital's emergency department from 1 January 2015 to 31 December 2022, to investigate the clinical characteristics and hospitalization risk factors associated with these three viruses. (3) Results: Infants aged 1 to 11 months were most affected by COVID-19 and RSV, whereas FLU more commonly infected children aged 3 to 5 years. Key factors influencing hospitalization included age and abnormal chest X-ray findings, with higher risks observed in younger children and adults over 65. Notably, the presence of abnormal chest x-ray findings significantly increased the hospitalization risk by 1.9 times [1.5-2.4] in children and 21.4 times [2.4-189.0] in adults. (4) Conclusions: This analysis underscores the impact of COVID-19, FLU, and RSV on hospitalization risk, offering insights for managing these respiratory viral infections (RVIs). Age-related risk differences highlight the necessity for tailored strategies, improving understanding of and treatment development for RVIs.

Reduction of acute respiratory infections in day-care by non-pharmaceutical interventions: a narrative review.

Objective: Children who start in day-care have 2-4 times as many respiratory infections compared to children who are cared for at home, and day-care staff are among the employees with the highest absenteeism. The extensive new knowledge that has been generated in the COVID-19 era should be used in the prevention measures we prioritize. The purpose of this narrative review is to answer the questions: Which respiratory viruses are the most significant in day-care centers and similar indoor environments? What do we know about the transmission route of these viruses? What evidence is there for the effectiveness of different non-pharmaceutical prevention measures? Design: Literature searches with different terms related to respiratory infections in humans, mitigation strategies, viral transmission mechanisms, and with special focus on day-care, kindergarten or child nurseries, were conducted in PubMed database and Web of Science. Searches with each of the main viruses in combination with transmission, infectivity, and infectious spread were conducted separately supplemented through the references of articles that were retrieved. Results: Five viruses were found to be responsible for ≈95% of respiratory infections: rhinovirus, (RV), influenza virus (IV), respiratory syncytial virus (RSV), coronavirus (CoV), and adenovirus (AdV). Novel research, emerged during the COVID-19 pandemic, suggests that most respiratory viruses are primarily transmitted in an airborne manner carried by aerosols (microdroplets). Conclusion: Since airborne transmission is dominant for the most common respiratory viruses, the most important preventive measures consist of better indoor air quality that reduces viral concentrations and viability by appropriate ventilation strategies. Furthermore, control of the relative humidity and temperature, which ensures optimal respiratory functionality and, together with low resident density (or mask use) and increased time outdoors, can reduce the occurrence of respiratory infections.

Respiratory Syncytial Virus (RSV) Burden in Infants in the Kingdom of Saudi Arabia and the Impact of All-Infant RSV Protection: A Modeling Study.

INTRODUCTION: Respiratory syncytial virus (RSV) represents a considerable burden on the healthcare system and hospital resources. This study explored the impact of universal immunoprophylaxis with long-acting monoclonal antibody (nirsevimab) during infants' first RSV season on RSV-induced health events and related costs in the Kingdom of Saudi Arabia (KSA). METHODS: The burden of RSV-induced health events and related costs under the current standard of practice (SoP) and the impact of universal immunoprophylaxis with nirsevimab was estimated using a static decision-analytic model in a cohort of infants experiencing their first RSV season in the KSA. The model estimated hospital admissions (including pediatric intensive care unit [PICU] admissions and mechanical ventilation [MV]), emergency room (ER) visits, primary care (PC) visits, long-term sequelae, and RSV mortality. RESULTS: The model estimated that under the current SoP, RSV results in 17,179-19,607 hospitalizations (including 2932-3625 PICU and 172-525 MV admissions), 57,654-191,115 ER visits, 219,053-219,970 PC visits, 14 deaths, 12,884-14,705 cases of recurrent wheezing, and a total cost of SAR 480-619 million. Universal nirsevimab immunoprophylaxis was estimated to avert 58% of hospitalizations (58% PICU admissions, 58% MV episodes), 53% of ER visits, 53% of PC visits, 58% of episodes of recurrent wheezing, 8 deaths, and result in savings of SAR 274-343 million in total healthcare cost. CONCLUSION: Compared with current SoP, an nirsevimab immunoprophylaxis strategy in the KSA for all infants during their first RSV season was estimated to dramatically decrease healthcare resource use, and economic burden associated with RSV.

Cost-effectiveness of nirsevimab and palivizumab for respiratory syncytial virus prophylaxis in preterm infants 29-34 6/7 weeks' gestation in the United States.

BACKGROUND: Respiratory syncytial virus (RSV) hospitalizations have increased since the 2014 guideline update recommended against the use of palivizumab for preterm infants born ≥29 0/7 weeks' gestational age (GA) without additional risk factors. A novel drug candidate, nirsevimab, has been developed for this population. We analyzed the cost-effectiveness of palivizumab/nirsevimab vs. no prophylaxis in this population. METHODS: A hybrid-Markov model predicted the RSV clinical course in the first year of life and sequelae in the subsequent four years for preterm infants from the healthcare and societal perspectives. Model parameters were derived from the literature. We calculated costs and quality-adjusted life-years (QALYs) to produce an incremental cost-effectiveness ratio (ICER) evaluated at a willingness-to-pay threshold of $150,000/QALY. Sensitivity analyses assessed model robustness. A threshold analysis examined nirsevimab pricing uncertainty. RESULTS: Compared to no prophylaxis, palivizumab costs $9572 and $9584 more from the healthcare and societal perspectives, respectively, with 0.0019 QALYs gained per patient over five years, resulting in ICERs >$5 million per QALY from each perspective. Results were robust to parameter uncertainties; probabilistic sensitivity analysis revealed that no prophylaxis had a 100% probability of being cost-effective. The threshold analysis suggested that nirsevimab is not cost-effective when compared to no prophylaxis if the price exceeds $1962 from a societal perspective. CONCLUSION: Palivizumab is dominated by no prophylaxis for preterm infants 29 0/7-34 6/7 weeks' GA with no additional risk factors. Relevant stakeholders should consider alternatives to palivizumab for this population that are both effective and economical.

Episodic Cost of Lower Respiratory Tract Illness due to Respiratory Syncytial Virus Among US Infants During the First Year of Life.

A study of 2 health care claims databases (commercial, Medicaid) was undertaken to estimate the episodic cost of lower respiratory tract illness due to respiratory syncytial virus among infants aged <12 months overall, by age, and by birth gestational age. Among commercial-insured infants, mean costs were $28 812 for hospitalized episodes, $2575 for emergency department episodes, and $336 for outpatient clinic episodes. Costs were highest among infants aged <1 month and infants with a gestational age ≤32 weeks and were comparable among Medicaid-insured infants, albeit somewhat lower. The cost of lower respiratory tract illness due to respiratory syncytial virus during the acute phase of illness is high, especially among the youngest infants and those born premature.

Frequency and burden of disease for SARS-CoV-2 and other viral respiratory tract infections in children under the age of 2 months.

OBJECTIVE: To evaluate the frequency and burden of disease of SARS-CoV-2 and other respiratory viruses in children under the age of 2 months. METHODS: A retrospective, cross-sectional, single-center study was conducted between March 2021 and February 2022. All children under the age of 2 months and tested for SARS-CoV-2 were included. The frequency of SARS-CoV-2, of other respiratory viruses and the burden of disease caused by SARS-CoV-2 and other respiratory viruses were evaluated. RESULTS: Seven hundred and twenty-seven children with an RT-PCR test for SARS-CoV-2 were included (mean age: 0.9 months (±0.6); boys: 57%); 514 (71%) in the emergency room and 213 (29%) in hospital. Among them, 62 (8.5%) had a positive RT-PCR test for SARS-CoV-2, more often in the Omicron period (23%) than in the Alpha period (4%). Of the 565 (78%) with a multiplex RT-PCR test for other viruses, 325 (58%) were positive. Children with a positive SARS-CoV-2 were less likely to have required respiratory support (p = 0.001), enteral nutrition (p = 0.03), or intensive care admission (p = 0.01) and had a shorter hospital stay than children with other respiratory viruses (5 days vs. 7 days, p = 0.007). CONCLUSION: In this young population of children, SARS-CoV-2 infection was less frequent and less severe than other viral respiratory infections.

Vigilancia de Infecciones Respiratorias Agudas en niños y adolescentes en un Servicio de Pediatría

Introducción: Las infecciones agudas de vías respiratorias inferiores, de etiología viral, constituyen la principal causa de hospitalización y mortalidad infantil. El objetivo del presente estudio es conocer la frecuencia de las infecciones respiratorias agudas grave (IRAG) y los virus prevalentes en pacientes ≤15 años. Materiales y Métodos: Estudio observacional, descriptivo, producto de la vigilancia de IRAG, periodo enero/2019-mayo/2023. Se incluyeron todos los pacientes ≤15 años hospitalizados con diagnóstico de IRAG. Se analizaron datos demográficos, características clínicas y evolutivas. Resultados: Fueron hospitalizados 256 pacientes ≤15 años con diagnóstico de IRAG, 54,3%(139/256) de sexo masculino. El 69,1% correspondían a <2años, 15,6% de 2 a 4 años y 15,2% de 5 a 19 años. El 17,5% presentaban factores de riesgo. El 3,5% (9/256) tenía vacuna anti-influenza. El mayor número de casos se objetivó en 2019. En 2020 y 2021 se registró el menor número de casos, relacionado a la política de encierro durante la pandemia de COVID-19. El virus prevalente fue el Virus Sincitial Respiratorio (VSR). En el 2019, el VSR fue el virus más frecuente (p<0.0001.RR=1,56.IC95%= 1,18 - 2,06); el SARS - CoV2 fue el más frecuente en 2020. Según grupo etario el VSR fue más frecuente en <2 años (p<0.0001.RR=1,70.IC95%=1,18-2,06) y el SARS - CoV2 en los ≥2 años (p<0.0001.RR=2,50.IC95%=2,53-3,53). El VSR no fue asociado a factores de riesgo. El 39,4%(101/256) requirió ingreso a la UCIP, situación más frecuente en pacientes con factores de riesgo (21,7%vs14,8%,NS). El ingreso a UCI fue más frecuente en los <2 años (44,1% vs 29,1%;p<0,02.RR=1,51.IC95%=1,03-2,22). No hubo diferencias significativas del requerimiento de UCI y los virus aislados. La letalidad fue del 7,8%(20/256), más frecuente en el sexo femenino (p<0.02.RR=0,36.IC95%=0,1-0,9), no asociado a la edad ni etiología. Conclusion: La IRAG por VSR constituye una causa importante de hospitalización en <2 años, más frecuente en el sexo masculino. El ingreso a UCIP fue más frecuente en los <2años. La letalidad fue más frecuente en el sexo femenino.

Introduction: Acute lower respiratory tract infections, of viral etiology, are the main cause of hospitalization and infant mortality. The objective of the present study is to know the frequency of severe acute respiratory infections (SARI) and prevalent viruses in patients ≤15 years of age. Materials and Methods: Observational, descriptive study, product of SARI surveillance, period January/2019-May/2023. All patients ≤15 years of age hospitalized with a diagnosis of SARI were included. Demographic data, clinical and evolutionary characteristics were analyzed. Results: 256 patients ≤15 years old with a diagnosis of SARI were hospitalized, 54.3% (139/256) male. 69.1% corresponded to <2 years, 15.6% from 2 to 4 years and 15.2% from 5 to 19 years. 17.5% had risk factors. 3.5% (9/256) had an anti-influenza vaccine. The highest number of cases was observed in 2019. In 2020 and 2021, the lowest number of cases was recorded, related to the confinement policy during the COVID-19 pandemic. The prevalent virus was Respiratory Syncytial Virus (RSV). In 2019, RSV was the most common virus (p<0.0001.RR=1.56.95%CI= 1.18 - 2.06); SARS - CoV2 was the most frequent in 2020. According to age group, RSV was more frequent in <2 years (p<0.0001.RR=1.70.CI95%=1.18-2.06) and SARS - CoV2 in those ≥2 years (p<0.0001.RR=2.50.95%CI=2.53-3.53). RSV was not associated with risk factors. 39.4% (101/256) required admission to the PICU, a more frequent situation in patients with risk factors (21.7% vs 14.8%,NS). Admission to the ICU was more frequent in those <2 years (44.1% vs 29.1%; p<0.02.RR=1.51.95%CI=1.03-2.22). There were no significant differences in the ICU requirement and the isolated viruses. The fatality rate was 7.8% (20/256), more frequent in females (p<0.02.RR=0.36.95%CI=0.1-0.9), not associated with age or etiology. Conclusion: SARI due to RSV is an important cause of hospitalization in <2 years, more frequent in males. Admission to the PICU was more frequent in those <2 years old. Fatality was more frequent in females.

Respiratory syncytial virus and other respiratory virus infections in residents of homeless shelters - King County, Washington, 2019-2021.

Respiratory syncytial virus (RSV) causes disproportionate morbidity and mortality in vulnerable populations. We tested residents of homeless shelters in Seattle, Washington for RSV in a repeated cross-sectional study as part of community surveillance for respiratory viruses. Of 15 364 specimens tested, 35 had RSV detected, compared to 77 with influenza. The most common symptoms for both RSV and influenza were cough and rhinorrhea. Many individuals with RSV (39%) and influenza (58%) reported that their illness significantly impacted their ability to perform their regular activities. RSV and influenza demonstrated similar clinical presentations and burden of illness in vulnerable populations living in congregate settings.

Modelado matemático del efecto de las medidas de cuidado por COVID-19 sobre otras enfermedades respiratorias / Mathematical modelling of the impact of COVID-19 care measures on other respiratory diseases

RESUMEN INTRODUCCIÓN Los modelos matemáticos de la transmisión de enfermedades infecciosas permiten estudiar distintos mecanismos que afectan su comportamiento temporal. Este trabajo analizó el efecto sobre la dinámica de la influenza y el virus sincitial respiratorio (VSR) de la disminución de la transmisibilidad debida a las medidas de cuidado adoptadas para reducir la circulación de COVID-19. MÉTODOS Se empleó un modelo determinista tipo SIRS (susceptible-infectado-recuperado-susceptible) con modulación estacional para representar la influenza y el VSR, en ambos casos con inmunidad de corta duración y ciclo anual. Los cambios en la transmisibilidad de la enfermedad se modelaron reduciéndola durante dos años y planteando distintos escenarios. RESULTADOS En el modelo planteado, la reducción en la transmisibilidad genera cambios que se sostienen en los años siguientes: eventos epidémicos muy pronunciados con alargamiento del intervalo interbrote. Este efecto resulta dominante respecto del comportamiento estacional. El escenario de una reducción inicial de la transmisibilidad del 40% resulta compatible con el comportamiento de influenza y VSR reportados actualmente para Argentina. DISCUSIÓN El modelo general propuesto, en condiciones de disminución transitoria en la transmisibilidad, exhibe una epidemiología compatible con la observada recientemente en Argentina para ambas enfermedades e ilustra el modelado como herramienta útil en la comprensión de efectos no intuitivos.

ABSTRACT INTRODUCTION Mathematical models of infectious diseases transmission allow to study different mechanisms which affect their temporal behavior. This work analyzed the impact of the decrease in transmissibility, as a result of measures of personal care adopted to reduce circulation of COVID-19, on the dynamics of influenza and respiratory syncytial virus (RSV). METHODS A deterministic SIRS (susceptible-infected-recovered-susceptible) model with seasonal modulation was used to represent two diseases with short-term immunity and annual cycle: influenza and RSV. Changes in disease transmissibility were modeled by reducing it for two years and analyzing different scenarios. RESULTS In the proposed model, transmissibility reduction brings changes which sustain in the following years: very pronounced epidemic events with lengthening of the inter-outbreak interval. This effect prevails over the seasonal behavior. The scenario of 40% initial reduction in transmissibility is compatible with the behavior of influenza and RSV currently reported in Argentina. DISCUSSION The general model proposed here, under conditions of temporary reduced transmissibility, shows an epidemiology compatible with recently reported data of influenza and RSV in Argentina. This result illustrates modeling as a useful tool to understand non-intuitive effects.

Economic burden of respiratory syncytial and parainfluenza viruses in children of upper-middle-income countries: a systematic review.

OBJECTIVE: To identify and assess the current evidence available about the costs of managing hospitalized pediatric patients diagnosed with Respiratory Syncytial Virus (RSV) and Parainfluenza Virus Type 3 (PIV3) in upper-middle-income countries. METHODS: The authors conducted a systematic review across seven key databases from database inception to July 2022. Costs extracted were converted into 2022 International Dollars using the Purchasing Power Parity-adjusted. PROSPERO identifier: CRD42020225757. RESULTS: No eligible study for PIV3 was recovered. For RSV, cost analysis and COI studies were performed for populations in Colombia, China, Malaysia, and Mexico. Comparing the total economic impact, the lowest cost per patient at the pediatric ward was observed in Malaysia ($ 347.60), while the highest was in Colombia ($ 709.66). On the other hand, at pediatric ICU, the lowest cost was observed in China ($ 1068.26), while the highest was in Mexico ($ 3815.56). Although there is no consensus on the major cost driver, all included studies described that the medications (treatment) consumed over 30% of the total cost. A high rate of inappropriate prescription drugs was observed. CONCLUSION: The present study highlighted how RSV infection represents a substantial economic burden to health care systems and to society. The findings of the included studies suggest a possible association between baseline risk status and expenditures. Moreover, it was observed that an important amount of the cost is destinated to treatments that have no evidence or support in most clinical practice guidelines.

Case-control study of exclusive breast feeding and severe bronchiolitis in the United States.

BACKGROUND: Bronchiolitis is a major cause of infant illness, with few known modifiable risk factors. Breast feeding may reduce risk of severe bronchiolitis, but the association of exclusive vs. partial breast feeding with severe bronchiolitis is unclear. OBJECTIVE: To estimate the association of exclusive vs. partial breast feeding during ages 0-2.9 months with bronchiolitis hospitalisation during infancy. METHODS: We conducted a case-control study as a secondary analysis of two prospective US cohorts in the Multicenter Airway Research Collaboration. Cases were enrolled in a 17-centre study of infants hospitalised for bronchiolitis during 2011-2014 (n = 921). Controls were enrolled in a five-centre study of healthy infants during 2013-2014 and 2017 (n = 719). Breast feeding history during ages 0-2.9 months was collected by parent interview. Among breastfed infants, the association of exclusive vs. partial breast feeding with odds of bronchiolitis hospitalisation was estimated using a multivariable logistic regression model adjusted for demographic variables, parental asthma history, and early-life exposures. As a secondary analysis, we estimated the associations of exclusive, predominant, and occasional breast feeding vs. no breast feeding with the odds of bronchiolitis hospitalisation. RESULTS: Among 1640 infants, the prevalence of exclusive breast feeding was 187/921 (20.3%) among cases and 275/719 (38.3%) among controls. Exclusive vs. partial breast feeding was associated with 48% reduced odds of bronchiolitis hospitalisation (adjusted odds ratio [OR] 0.52, 95% confidence interval [CI] 0.39, 0.69). In the secondary analysis, exclusive vs. no breast feeding was associated with 58% reduced odds of bronchiolitis hospitalisation (OR 0.42, 95% CI 0.23, 0.77), whereas predominant breast feeding (OR 0.77, 95% CI 0.37, 1.57) and occasional breast feeding (OR 0.98, 95% CI 0.57, 1.69) were not associated with meaningfully reduced odds of bronchiolitis hospitalisation. CONCLUSION: Exclusive breast feeding had a strong protective association against bronchiolitis hospitalisation.

Economic burden of respiratory syncytial and parainfluenza viruses in children of upper-middle-income countries: a systematic review

Abstract Objective: To identify and assess the current evidence available about the costs of managing hospitalized pediatric patients diagnosed with Respiratory Syncytial Virus (RSV) and Parainfluenza Virus Type 3 (PIV3) in upper-middle-income countries. Methods: The authors conducted a systematic review across seven key databases from database inception to July 2022. Costs extracted were converted into 2022 International Dollars using the Purchasing Power Parity-adjusted. PROSPERO identifier: CRD42020225757. Results: No eligible study for PIV3 was recovered. For RSV, cost analysis and COI studies were performed for populations in Colombia, China, Malaysia, and Mexico. Comparing the total economic impact, the lowest cost per patient at the pediatric ward was observed in Malaysia ($ 347.60), while the highest was in Colombia ($ 709.66). On the other hand, at pediatric ICU, the lowest cost was observed in China ($ 1068.26), while the highest was in Mexico ($ 3815.56). Although there is no consensus on the major cost driver, all included studies described that the medications (treatment) consumed over 30% of the total cost. A high rate of inappropriate prescription drugs was observed. Conclusion: The present study highlighted how RSV infection represents a substantial economic burden to health care systems and to society. The findings of the included studies suggest a possible association between baseline risk status and expenditures. Moreover, it was observed that an important amount of the cost is destinated to treatments that have no evidence or support in most clinical practice guidelines.

Long-Term Pulmonary Dysfunction by Hyperoxia Exposure during Severe Viral Lower Respiratory Tract Infection in Mice.

Viral-induced lower respiratory tract infection (LRTI), mainly by respiratory syncytial virus (RSV), causes a major health burden among young children and has been associated with long-term respiratory dysfunction. Children with severe viral LRTI are frequently treated with oxygen therapy, hypothetically posing an additional risk factor for pulmonary sequelae. The main goal of this study was to determine the effect of concurrent hyperoxia exposure during the acute phase of viral LRTI on long-term pulmonary outcome. As an experimental model for severe RSV LRTI in infants, C57Bl/6J mice received an intranasal inoculation with the pneumonia virus of mice J3666 strain at post-natal day 7, and were subsequently exposed to hyperoxia (85% O2) or normoxia (21% O2) from post-natal day 10 to 17 during the acute phase of disease. Long-term outcomes, including lung function and structural development, were assessed 3 weeks post-inoculation at post-natal day 28. Compared to normoxic conditions, hyperoxia exposure in PVM-inoculated mice induced a transient growth arrest without subsequent catchup growth, as well as a long-term increase in airway resistance. This hyperoxia-induced pulmonary dysfunction was not associated with developmental changes to the airway or lung structure. These findings suggest that hyperoxia exposure during viral LRTI at young age may aggravate subsequent long-term pulmonary sequelae. Further research is needed to investigate the specific mechanisms underlying this alteration to pulmonary function.