A low-dose multicomponent medication as a new approach in prevention and early add-on treatment of recurrent respiratory infections in children: a Delphi Consensus.

OBJECTIVE: Recurrent respiratory infections (RRIs) represent a demanding challenge in pediatricians' clinical practice. A previous Inter-Society Consensus defined criteria for identifying children with RRIs and assessed the available treatments, considering the evidence grade. MATERIALS AND METHODS: The present Delphi consensus proposed a series of statements concerning the practical use of Citomix, a multicomponent low-dose medication. The participants should be primary care, private practice, and hospital/university pediatricians with extensive experience using this product to manage children with RRIs. One hundred twelve Italian pediatricians voted for the statements. RESULTS: The agreement grade was high for all statements (ranging from 69.6% to 99.1%). The participants expressed their satisfaction with using this medication, which may represent a valuable and safe option for preventing and adding on treating children with RRIs. These statements reflected their personal opinions based on daily clinical practice. CONCLUSIONS: The results of this Delphi consensus represented an input for further evidence-based studies highlighting the effectiveness of low-dose medications for both the prevention and treatment of RRIs.

Respiratory viruses: Preventive and therapeutic approaches to diverse pathogens.

Viral respiratory diseases affect millions of individuals worldwide each year. Annual vaccinations are recommended by the World Health Organization for some of them, such as influenza and more recently for the coronavirus disease of 2019 (COVID-19) and respiratory syncytial virus, with the goal of reducing disease severity and limiting transmission. In the context of infection and vaccination, it is of primary importance to evaluate the immune response to pathogens to shed light on the mechanisms of protection.

Assessing the impact of COVID-19 non-pharmaceutical interventions and relaxation policies on Class B respiratory infectious diseases transmission in China.

This study investigates the incidence of Class B respiratory infectious diseases (RIDs) in China under the Coronavirus disease 2019 (COVID-19) epidemic and examines variations post-epidemic, following the relaxation of non-pharmaceutical interventions (NPIs). Two-stage evaluation was used in our study. In the first stage evaluation, we established counterfactual models for the pre-COVID-19 period to estimate expected incidences of Class B RIDs without the onset of the epidemic. In the second stage evaluation, we constructed seasonal autoregressive integrated moving average intervention (SARIMA-Intervention) models to evaluate the impact on the Class B RIDs after NPIs aimed at COVID-19 pandemic were relaxed. The counterfactual model in the first stage evaluation suggested average annual increases of 10.015%, 78.019%, 70.439%, and 67.799% for tuberculosis, scarlet fever, measles, and pertussis respectively, had the epidemic not occurred. In the second stage evaluation, the total relative reduction in 2023 of tuberculosis, scarlet fever, measles and pertussis were - 35.209%, - 59.184%, - 4.481%, and - 9.943% respectively. The actual incidence declined significantly in the first stage evaluation. However, the results of the second stage evaluation indicated that a rebound occurred in four Class B RIDs after the relaxation of NPIs; all of these showed a negative total relative reduction rate.

Consistent FFP2-masking as part of reducing viral respiratory infections on medical wards for allogeneic hematopoietic stem cell transplantation.

Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are highly susceptible to infections. The consequent use of masks on wards for allo-HSCT has been controversial in the past decades and was not common before the COVID-19 pandemic. We retrospectively compared incidence and outcomes of viral respiratory infections during allo-HSCT on our specialized ward between 01/2018 and 09/2020 to the era of FFP2 masking between 10/2020 and 10/2022 covering similar seasons of the year. Each group consisted of 150 matched patients. The usage of FFP2 masks reduced the incidence of viral respiratory infections from 22.1 to 2.1% (p < 0.005). This reduced the time on ward from a median of 26 days to 23.5 days (p = 0.002). It also resulted in less use of CT-scans (p = 0.003) and bronchoalveolar lavage procedures (p = 0.057). Median time to proof of infection was 21 days after admission in both groups. No difference was detected in progression free survival, hospital survival or non-relapse mortality (p = 0.78). Our retrospective results indicate that FFP2 masks worn by patients and hospital staff may help to significantly reduce the incidence of viral respiratory infections, including COVID-19, shorten the in-hospital time, and reduce costs without affecting survival.

[Effect of non-pharmacological preventive measures on the incidence of respiratory and gastrointestinal pathologies]. / Efecto de las medidas preventivas no farmacológicas en la incidencia de patología respiratoria y gastrointestinal.

OBJECTIVE: The use of non-pharmacological preventive measures during the COVID-19 pandemic has helped to reduce the incidence of multiple airborne or contact diseases. The objective of this paper was to evaluate the impact that all preventive measures have had on the transmission of different microorganisms, both by respiratory and contact transmission. METHODS: We compared the incidence of different infectious episodes coded with the CIAP-2 code (International Classification of Primary Care second edition of the WONCA International Classification Committee) collected from the computerized history of primary care, both with respiratory tract and digestive tract involvement, in the period from March 2018 to February 2020 (pre-pandemic period) and from March 2020 to February 2022 (pandemic period). The data corresponded to the entire region, with an estimated average population for the four years of 650,000 people. The statistical treatment of the data consisted of a descriptive analysis with the calculation of absolute values and percentages. Rates were calculated and compared using data provided by the National Institute of Statistics as a denominator. The P was obtained by statistical comparison by the exact method. A comparison of rates was made. RESULTS: The incidence in the number of CIAP-2 episodes studied, both corresponding to respiratory and gastrointestinal pathologies, comparing the period March 2018-February 2020 with the period March 2020-February 2022 decreased by 65.81%, from 534,439 cases to 182,707. CONCLUSIONS: The preventive measures applied during the pandemic produce a significant decrease in pathology involving the respiratory or the digestive tract.

OBJETIVO: El uso de medidas preventivas no farmacológicas durante la pandemia de la COVID-19 ayudó a reducir la incidencia de múltiples enfermedades de transmisión aérea o por contacto. El objetivo de este trabajo fue evaluar el impacto que habían tenido todas las medidas preventivas en la transmisión de diferentes microorganismos, tanto por transmisión respiratoria como por contacto. METODOS: Comparamos la incidencia de diferentes episodios infecciosos codificados con el código CIAP-2 (Clasificación Internacional de Atención Primaria, segunda edición, del Comité de Clasificación Internacional WONCA-World Organization of Family Doctors) recogidos de la historia informatizada de Atención Primaria, tanto con afectación del tracto respiratorio como del tracto digestivo, en el período de marzo de 2018 a febrero de 2020 (período prepandemia) y de marzo de 2020 a febrero de 2022 (período de pandemia). Los datos correspondieron a toda la región, con una población media estimada para los cuatro años de 650.000 personas. El tratamiento estadístico de los datos consistió en un análisis descriptivo con el cálculo de valores absolutos y porcentajes. Se calcularon y compararon tasas tomando como denominador los datos proporcionados por el Instituto Nacional de Estadística. La P fue obtenida mediante comparación estadística por el método exacto. Se realizó una comparación de tasas. RESULTADOS: La incidencia en el número de episodios CIAP-2 estudiados, tanto correspondientes a patología respiratoria como gastrointestinal, comparando el periodo de marzo de 2018-febrero de 2020 con el periodo marzo de 2020-febrero de 2022, disminuyó en un 65,81%, pasando de 534.439 casos a 182.707. CONCLUSIONES: Las medidas preventivas aplicadas durante la pandemia producen una disminución significativa de la patología del tracto respiratorio o digestivo.

Severe respiratory syncytial virus infection in children: burden, management, and emerging therapies.

The global burden of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in young children is high. The RSV prevention strategies approved in 2023 will be essential to lowering the global disease burden. In this Series paper, we describe clinical presentation, burden of disease, hospital management, emerging therapies, and targeted prevention focusing on developments and groundbreaking publications for RSV. We conducted a systematic search for literature published in the past 15 years and used a non-systematic approach to analyse the results, prioritising important papers and the most recent reviews per subtopic. Annually, 33 million episodes of RSV LRTI occur in children younger than 5 years, resulting in 3·6 million hospitalisations and 118 200 deaths. RSV LRTI is a clinical diagnosis but a clinical case definition and universal clinical tool to predict severe disease are non-existent. The advent of molecular point-of-care testing allows rapid and accurate confirmation of RSV infection and could reduce antibiotic use. There is no evidence-based treatment of RSV, only supportive care. Despite widespread use, evidence for high-flow nasal cannula (HFNC) therapy is insufficient and increased paediatric intensive care admissions and intubation indicate the need to remove HFNC therapy from standard care. RSV is now a vaccine-preventable disease in young children with a market-approved long-acting monoclonal antibody and a maternal vaccine targeting the RSV prefusion protein. To have a high impact on life-threatening RSV infection, infants at high risk, especially in low-income and middle-income countries, should be prioritised as an interim strategy towards universal immunisation. The implementation of RSV preventive strategies will clarify the full burden of RSV infection. Vaccine probe studies can address existing knowledge gaps including the effect of RSV prevention on transmission dynamics, antibiotic misuse, the respiratory microbiome composition, and long-term sequalae.

Integrated environmental and clinical surveillance for the prevention of acute respiratory infections (ARIs) in indoor environments and vulnerable communities (Stell-ARI): Protocol.

The epidemiological relevance of viral acute respiratory infections (ARIs) has been dramatically highlighted by COVID-19. However, other viruses cannot be neglected, such as influenza virus, respiratory syncytial virus, human adenovirus. These viruses thrive in closed spaces, influenced by human and environmental factors. High-risk closed communities are the most vulnerable settings, where the real extent of viral ARIs is often difficult to evaluate, due to the natural disease progression and case identification complexities. During the COVID-19 pandemic, wastewater-based epidemiology has demonstrated its great potential for monitoring the circulation and evolution of the virus in the environment. The "Prevention of ARIs in indoor environments and vulnerable communities" study (Stell-ARI) addresses the urgent need for integrated surveillance and early detection of ARIs within enclosed and vulnerable communities such as long-term care facilities, prisons and primary schools. The rapid transmission of ARIs in such environments underscores the importance of comprehensive surveillance strategies to minimise the risk of outbreaks and safeguard community health, enabling proactive prevention and control strategies to protect the health of vulnerable populations. This study consists of designing and validating tools for integrated clinical and environmental-based surveillance for each setting, coupled with analytical methods for environmental matrices. The clinical surveillance involves specialized questionnaires and nasopharyngeal swabs for virus identification, while the environmental surveillance includes air and surface microbiological and chemical monitoring, and virological analysis of wastewater. Integrating this information and the collection of behavioural and environmental risk factors into predictive and risk assessment models will provide a useful tool for early warning, risk assessment and informed decision-making. The study aims to integrate clinical, behavioural, and environmental data to establish and validate a predictive model and risk assessment tool for the early warning and risk management of viral ARIs in closed and vulnerable communities prior to the onset of an outbreak.

Nourishing the Infant Gut Microbiome to Support Immune Health: Protocol of SUN (Seeding Through Feeding) Randomized Controlled Trial.

BACKGROUND: The introduction of complementary foods during the first year of life influences the diversity of the gut microbiome. How this diversity affects immune development and health is unclear. OBJECTIVE: This study evaluates the effect of consuming kumara or kumara with added banana powder (resistant starch) compared to a reference control at 4 months post randomization on the prevalence of respiratory tract infections and the development of the gut microbiome. METHODS: This study is a double-blind, randomized controlled trial of mothers and their 6-month-old infants (up to n=300) who have not yet started solids. Infants are randomized into one of 3 groups: control arm (C), standard kumara intervention (K), and a kumara intervention with added banana powder product (K+) to be consumed daily for 4 months until the infant is approximately 10 months old. Infants are matched for sex using stratified randomization. Data are collected at baseline (prior to commencing solid food) and at 2 and 4 months after commencing solid food (at around 8 and 10 months of age). Data and samples collected at each timepoint include weight and length, intervention adherence (months 2 and 4), illness and medication history, dietary intake (months 2 and 4), sleep (diary and actigraphy), maternal dietary intake, breast milk, feces (baseline and 4 months), and blood samples (baseline and 4 months). RESULTS: The trial was approved by the Health and Disability Ethics Committee of the Ministry of Health, New Zealand (reference 20/NTA/9). Recruitment and data collection did not commence until January 2022 due to the COVID-19 pandemic. Data collection and analyses are expected to conclude in January 2024 and early 2025, respectively. Results are to be published in 2024 and 2025. CONCLUSIONS: The results of this study will help us understand how the introduction of a specific prebiotic complementary food affects the microbiota and relative abundances of the microbial species, the modulation of immune development, and infant health. It will contribute to the expanding body of research that aims to deepen our understanding of the connections between nutrition, gut microbiota, and early-life postnatal health. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12620000026921; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378654. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56772.

Trends in Hospitalisations for Vaccine Preventable Respiratory Infections Following Emergency Department Presentations in New South Wales, Australia, 2012-2022.

BACKGROUND: Vaccine-preventable respiratory infections impact on healthcare systems globally. Despite availability of vaccines, fluctuations in vaccination rates, pathogen virulence and community transmission dynamics mean that these respiratory infections continue to pose substantial public health risks. To understand trends in vaccine-preventable respiratory infections, we analysed linked data from emergency department (ED), hospitalisations and deaths in New South Wales, Australia, from 2012 to 2022. METHODS: ED presentations with respiratory infection like illness were linked to hospitalisation and death records. Age-standardised rates of ED presentations, proportions subsequently hospitalised for acute respiratory infection (ARI) and specific vaccine-preventable disease diagnoses and 28-day mortality rates were estimated by year and age. RESULTS: From 2012 to 2022, there were 3,127,090 ARI-like ED presentations. Age-standardised rates increased until 2020, declined in 2021 and rebounded in 2022. Across all years, of these ARI-like ED presentations, 16.6% were hospitalised for acute respiratory infections, including pneumonia (7.9%), influenza (1.1%), RSV disease (1.3%), COVID-19 (0.8%) and pneumococcal disease (0.3%). Proportions hospitalised were highest in those aged 65+ years, except for RSV, which was highest in children aged 0-4 years. The highest 28-day mortality post-ARI-like ED presentation was observed with COVID-19 in adults aged 65+ years at 13.1%. CONCLUSIONS: This study highlights the continuing burden of vaccine-preventable respiratory infections on an Australian healthcare system. These data can be used to monitor the effectiveness of vaccination programmes and other public health interventions. Future efforts should focus on enhancing surveillance and data linkage to improve precision and guide targeted public health strategies.

Nirsevimab and Acute Bronchiolitis Episodes in Pediatric Emergency Departments.

BACKGROUND AND OBJECTIVES: In the 2023-2024 respiratory syncytial virus (RSV) season, Spain became one of the first countries to introduce universal RSV prophylaxis, during which all infants born at this time were eligible to receive nirsevimab. Locally, most Spanish regions also immunized infants younger than age 6 months at the start of the season (extended catch-up). The aim of this study was to assess how RSV prophylaxis affected the number of infants presenting to pediatric emergency departments with acute respiratory infections. METHODS: A retrospective study was conducted in 15 Spanish pediatric emergency departments from 9 different regions between the 2018 and 2024 epidemic seasons (November-January). We compared the seasons occurring in 2018-2023 and the 2023-2024 season regarding the number of episodes of lower respiratory tract infection and acute bronchiolitis, acute bronchiolitis-related hospital admissions, and PICU admissions. RESULTS: A comparison with the average rates for the previous epidemic seasons revealed a 57.7% decrease in episodes of lower respiratory tract infection in 2023-2024 (95% CI, 56.5-58.8; P < .001; range among hospitals, 4.8-82.8), a 59.2% decrease in episodes of acute bronchiolitis (95% CI, 57.9-60.4; P < .001; range, 6.9-84.1), a 63.1% reduction in acute bronchiolitis-related hospital admissions (95% CI, 60.9-65.2; P < .001; range, 31.4-86.8), and a 63.1% reduction in PICU admissions (95% CI, 58.1-67.9; P < .001; range, 18.2-81.8). Hospitals in regions applying extended catch-up showed better results. CONCLUSIONS: Nirsevimab can protect a broad infant population against RSV infection with high effectiveness. Approaches including extended catch-up are the most effective, although cost- effectiveness must be considered.

Early-life respiratory syncytial virus disease and long-term respiratory health.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI), hospital admission, and mortality in children worldwide. Early-life RSV LRTI has also been associated with subsequent long-term respiratory sequelae, including recurrent LRTI, recurrent wheezing, asthma, and lung function impairment, and these effects can persist into adulthood as chronic respiratory disease. New preventive measures (maternal vaccine or long-acting monoclonal antibodies) have been licensed to reduce the burden of acute RSV LRTI in infants and children at high risk through passive immunisation. Studies of these RSV prevention products show high efficacy and effectiveness, particularly for preventing severe RSV LRTI, with implementation in many high-income countries, but limited access in low-income and middle-income countries (LMICs). These interventions might also reduce the risk of additional health outcomes and long-term morbidity. This Series paper provides the evidence for the long-term effects of early-life RSV disease, discusses mechanisms of disease development, and addresses the potential full public health value of prevention of RSV illness. Further research is needed to determine whether prevention of RSV LRTI or delay of RSV illness in early life might prevent or ameliorate the development of associated long-term respiratory disease. This potential further underscores the urgency for access and availability of new interventions to prevent early-life RSV LRTI in LMICs.

The effect of the implementation of the international code of marketing of breast-milk substitutes on child mortality in Ghana and Tanzania.

OBJECTIVE: The International Code of Marketing of Breast-Milk Substitutes is an important instrument to protect and promote appropriate infant and young child feeding and the safe use of commercial milk formulas. Ghana and Tanzania implemented the Code into national legislation in 2000 and 1994, respectively. We aimed to estimate the effects of the Code implementation on child mortality (CM) in both countries. SETTING: The countries analysed were Ghana and Tanzania. PARTICIPANTS: For CM and HIV rates, data from the Institute for Health Metrics and Evaluation from up to 2019 were used. Data for income and skilled birth rates were retrieved from the World Bank, for fertility from the World Population Prospects, for vaccination from the Global Health Observatory and for employment from the International Labour Organization. DESIGN: We used the synthetic control group method and performed placebo tests to assess statistical inference. The primary outcomes were CM by lower respiratory infections, mainly pneumonia, and diarrhoea and the secondary outcome was overall CM. RESULTS: One-sided inference tests showed statistically significant treatment effects for child deaths by lower respiratory infections in Ghana (P = 0·0476) and Tanzania (P = 0·0476) and for diarrhoea in Tanzania (P = 0·0476). More restrictive two-sided inference tests showed a statistically significant treatment effect for child deaths by lower respiratory infections in Ghana (P = 0·0476). No statistically significant results were found for overall CM. CONCLUSION: The results suggest that the implementation of the Code in both countries had a potentially beneficial effect on CM due to infectious diseases; however, further research is needed to corroborate these findings.

Federated systems for automated infection surveillance: a perspective.

Automation of surveillance of infectious diseases-where algorithms are applied to routine care data to replace manual decisions-likely reduces workload and improves quality of surveillance. However, various barriers limit large-scale implementation of automated surveillance (AS). Current implementation strategies for AS in surveillance networks include central implementation (i.e. collecting all data centrally, and central algorithm application for case ascertainment) or local implementation (i.e. local algorithm application and sharing surveillance results with the network coordinating center). In this perspective, we explore whether current challenges can be solved by federated AS. In federated AS, scripts for analyses are developed centrally and applied locally. We focus on the potential of federated AS in the context of healthcare associated infections (AS-HAI) and of severe acute respiratory illness (AS-SARI). AS-HAI and AS-SARI have common and specific requirements, but both would benefit from decreased local surveillance burden, alignment of AS and increased central and local oversight, and improved access to data while preserving privacy. Federated AS combines some benefits of a centrally implemented system, such as standardization and alignment of an easily scalable methodology, with some of the benefits of a locally implemented system including (near) real-time access to data and flexibility in algorithms, meeting different information needs and improving sustainability, and allowance of a broader range of clinically relevant case-definitions. From a global perspective, it can promote the development of automated surveillance where it is not currently possible and foster international collaboration.The necessary transformation of source data likely will place a significant burden on healthcare facilities. However, this may be outweighed by the potential benefits: improved comparability of surveillance results, flexibility and reuse of data for multiple purposes. Governance and stakeholder agreement to address accuracy, accountability, transparency, digital literacy, and data protection, warrants clear attention to create acceptance of the methodology. In conclusion, federated automated surveillance seems a potential solution for current barriers of large-scale implementation of AS-HAI and AS-SARI. Prerequisites for successful implementation include validation of results and evaluation requirements of network participants to govern understanding and acceptance of the methodology.

The real-world effectiveness of preschoolers wearing masks on campus to prevent respiratory infectious diseases: a cohort study.

Background: Respiratory infections are common in the pediatric population. Preschoolers, especially those in kindergarten and 3-6 years old, are highly vulnerable to various respiratory infections. Objective: To investigate the efficacy of indoor mask-wearing in mitigating respiratory infections in preschoolers in a real-world campus setting. Methods: The study was conducted over a 115-day period in a kindergarten. Eligible children were assigned into study and control groups. The study group wore masks indoors but not outdoors, and the control group did not wear masks in either setting. We used a questionnaire to collect participant information, including age, height, weight, monthly dietary living expenses, family annual income, parent education level, primary caregiver, number of family members, and number of children under 6 years of age in the household. Incidences of clinical respiratory infections were recorded. We calculated the relative risk and analyzed the relationship between mask-wearing and respiratory infections by inter-group comparison, logistic regression, and Cox regression analyses. Results: A total of 135 preschoolers were included, with 35 and 100 preschoolers in the study and control groups, respectively. Baseline comparisons showed a significant difference in the number of children under 6 years old in the household between the two groups. Mask-wearing did not significantly reduce the risk of respiratory infections (RR = 1.086, 95% CI: 0.713, 1.435). Logistic and Cox regression analyses also showed no significant relationship between mask-wearing and occurrence of respiratory infections after controlling for potential confounders (OR = 0.816, 95% CI: 0.364, 1.826, and HR = 0.845, 95% CI: 0.495, 1.444). Conclusion: Indoor mask-wearing did not reduce the incidence of respiratory infections in preschoolers in a real-world campus setting. However, this study included a small number of preschoolers and observed them for a short period of time. Preschoolers were instructed to wear masks only when indoors. These factors could lead to bias and limit the generalizability of the study results.

Recomendaciones ALAT para el uso de vacunas respiratorias. Guía de práctica clínica basada en evidencias / ALAT Recommendations for the Use of Respiratory VaccinesEvidence-Based Clinical Practice Guideline

Introducción: Las infecciones respiratorias son las enfermedades respiratorias con mayor mortalidad en el mundo. Las causadas por Streptococcus pneumoniae, virus de influenza, Bordetella pertussis, SARS-CoV-2 y el Virus Sincitial Respiratorio, cuentan hoy día con vacunas seguras y efectivas. Este documento representa una guía de práctica clínica (GPC) de la Asociación Latinoamericana de Tórax (ALAT), elaborada por iniciativa de los departamentos de enfermedades infecciosas y pediatría, con el objetivo de establecer recomendaciones sobre vacunas respiratorias, utilizando la evidencia disponible. Método: Se estableció un grupo de desarrollo de las guías conformado por cinco médicos responsables globales del proyecto, se crearon cinco subgrupos de trabajo, uno por cada vacuna, con expertos neumólogos de adulto, pediatras e infectólogos invitados, que generaron preguntas clínicas. Se trabajó con un grupo de expertos metodólogos que transformaron preguntas clínicas en preguntas PICO, seleccionándose nueve preguntas por método DELPHI. Luego, se utilizó el sistema GRADE (Grading of Recommendations Assessment, Development and Evaluation) para evaluar la evidencia disponible. Resultados: Se obtuvieron recomendaciones para población adulta y pediátrica de las vacunas de neumococo, influenza, tos ferina, COVID-19 y Virus Respiratorio Sincitial basadas en preguntas PICO. También se agregaron recomendaciones basadas en preguntas narrativas relacionadas al uso de vacunas respiratorias en población con enfermedades respiratorias crónicas como asma, EPOC y fibrosis pulmonar.

Introduction: Respiratory infections are the leading cause of respiratory disease-related mortality worldwide. Infections caused by Streptococcus pneumoniae, influenza virus, Bordetella pertussis, SARS-CoV-2 and Respiratory Syncytial Virus (RSV) now have safe and effective vaccines available.This document represents a Clinical Practice Guideline (CPG) by the Latin American Thoracic Association (ALAT), developed through the initiative of the departments of in-fectious diseases and pediatrics, with the goal of establishing recommendations on respiratory vaccines using the available evidence. Method: A guideline development group was established, composed of five lead physicians responsible for the overall project. Five working subgroups were created, one for each vaccine, involving invited experts in adult pulmonology, pediatrics, and infectious diseases, who formulated clinical questions. A group of expert methodologists then transformed these clinical questions into PICO questions, with nine questions selected using the DELPHI method. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was then used to assess the available evidence. Results: Recommendations were obtained for the adult and pediatric populations for pneumococcal, influenza, pertussis, COVID-19 and Respiratory Syncytial Virus vaccines based on PICO questions. Additionally, recommendations based on narrative questions related to the use of respiratory vaccines in populations with chronic respiratory diseases such as asthma, COPD, and pulmonary fibrosis were included.

Supporting vaccine (co)-administration decisions: Development and validation of a tool for assessing the risk of severe outcomes due to lower respiratory tract infections.

OBJECTIVE: To develop and validate a score to predict the 90-day risk of hospitalization/death in patients with low respiratory tract infections (LRTIs) with the aim to support clinical decision making on vaccine (co)-administration. METHODS: We formed a cohort of patients aged 18 years or older being diagnosed with LRTIs in the period between January 1, 2012 and December 31, 2022. Each patient was followed until occurrence of respiratory-related hospitalization/death up to the end of the study period (December 31, 2022). Along with age and sex, forty determinants were adopted to assemble the respiratory tract infection (RTI)-Health Search (HS) core using the development sub-cohort. The prediction accuracy of the score was therefore assessed in the validation sub-cohort. RESULTS: We identified 252,319 patients being diagnosed with LRTIs (females: 54.7 %; mean age: 60 (SD:18.1)). When the risk of LRTIs-related hospitalizations/deaths was estimated via RTI-HScore, its predicted value was equal to 1.4 % over a 90-day event horizon. The score showed explained variation and discrimination accuracy were equal to 45 % (95 % CI: 44-47 %) and 81 % (95 % CI: 79-84 %), respectively. The calibration slope did not significantly differ from the unit (p = 0.8314). CONCLUSIONS: The RTI-HScore was featured by good accuracy for prediction of LRTIs-related complications over a 90-day follow-up. Such a tool might therefore support general practitioners to enhance patients' care by facilitating approaches for (co)-administration of vaccines for respiratory infections through a score-based decision support system.

Preparing for the next respiratory pathogen pandemic: using tabletop simulation exercises to strengthen national planning in Cook Islands, Costa Rica, Lebanon and Mongolia.

The Preparedness and Resilience for Emerging Threats (PRET) initiative takes an innovative mode-of-transmission approach to pandemic planning by advocating for integrated preparedness and response systems and capacities for groups of pathogens with common transmission pathways. The World Health Organization (WHO) launched this initiative in 2023 with the publication of PRET Module 1 addressing respiratory pathogens. Exercise PanPRET-1 is a customizable tabletop simulation exercise (TTX) package developed to complement PRET Module 1. The exercise scenario focuses on strengthening capacities for multisectoral coordination, risk communication and community engagement, and the triggers for operational decision-making. This article reports on the experiences of the first four countries to implement Exercise PanPRET-1: Cook Islands, Costa Rica, Lebanon and Mongolia. Exercise outcomes demonstrated that PanPRET-1 can be an effective tool for testing pandemic plans in a multisectoral forum and identifying opportunities to improve preparedness and response in key domains. In quantitative evaluations in Cook Islands, Costa Rica and Mongolia, high proportions of exercise participants indicated that multiple aspects of the exercise were well-designed and were beneficial for improving health emergency preparedness. Exercise participants in Lebanon provided qualitative feedback indicating that they found the exercise to be beneficial. Conducting a TTX and monitoring the implementation of action plans based on exercise findings facilitates a country-owned whole-of-society vision for pandemic planning. Countries are encouraged to incorporate TTX such as Exercise PanPRET-1 into a continuous cycle of activity to improve pandemic preparedness.

Advancement in the development of mRNA-based vaccines for respiratory viruses.

Acute respiratory infections are the leading cause of death and illness in children under 5 years old and represent a significant burden in older adults. Primarily caused by viruses infecting the lower respiratory tract, symptoms include cough, congestion, and low-grade fever, potentially leading to bronchiolitis and pneumonia. Messenger ribonucleic acid (mRNA)-based vaccines are biopharmaceutical formulations that employ mRNA molecules to induce specific immune responses, facilitating the expression of viral or bacterial antigens and promoting immunization against infectious diseases. Notably, this technology had significant relevance during the COVID-19 pandemic, as these formulations helped to limit SARS-CoV-2 virus infections, hospitalizations, and deaths. Importantly, mRNA vaccines promise to be implemented as new alternatives for fighting other respiratory viruses, such as influenza, human respiratory syncytial virus, and human metapneumovirus. This review article analyzes mRNA-based vaccines' main contributions, perspectives, challenges, and implications against respiratory viruses.

Paid Family Leave and Prevention of Acute Respiratory Infections in Young Infants.

Importance: Acute respiratory tract infections are the leading cause of emergency department visits and hospitalizations in US children, with highest risks in the first 2 months after birth. Out-of-home childcare settings increase the spread of respiratory tract infections. The study team hypothesized that access to state-paid family leave could reduce acute care encounters (hospital admissions or emergency department visits) for respiratory tract infections in young infants by reducing out-of-home childcare transmissions. Objective: To determine if the 2018 introduction of paid family leave in New York state reduced acute care encounters for respiratory tract infections in infants 8 weeks or younger. Design, Setting, and Participants: This population-based study of acute care encounters took place in New York state and New England control states (Maine, Massachusetts, New Hampshire, Vermont) from October 2015 through February 2020. Participants included infants aged 8 weeks or younger. Controlled time series analysis using Poisson regression was used to estimate the impact of paid family leave on acute care encounters for respiratory tract infections, comparing observed counts during respiratory virus season (October through March) with those predicted in the absence of the policy. Acute care encounters for respiratory tract infections in 1-year-olds (who would not be expected to benefit as directly from the policy) were modeled as a placebo test. Intervention: New York State Paid Family Leave policy, introduced on January 1, 2018, providing 8 weeks of paid leave for eligible parents. Main Outcomes and Measures: Emergency department visits or hospitalizations with International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD) codes for upper or lower respiratory tract infections or associated symptoms (ie, fever, cough), excluding newborn hospitalizations. The secondary outcome was acute care encounters for respiratory syncytial virus (RSV) bronchiolitis. Results: There were 52 943 acute care encounters for respiratory infection among infants 8 weeks or younger. There were 15 932 encounters that were hospitalizations (30%) and 33 304 of the encounters were paid for by Medicaid (63%). Encounters were 18% lower than predicted (relative percentage change = -17.9; 95% CI, -20.3 to -15.7) after the introduction of paid family leave. RSV encounters were 27.0% lower (95% CI, -30.9 to -23.5) than predicted. Similar reductions were not observed in 1-year-olds (relative percentage change = -1.5; 95% CI, -2.5 to -0.6). Conclusions: New York state's paid family leave policy was associated with reduced acute care encounters for respiratory tract infections in young infants. These findings may be useful for informing implementation of paid family leave federally and in the states that have not enacted paid family leave policies.