Reducing Transmission of Airborne Respiratory Pathogens: A New Beginning as the COVID-19 Emergency Ends.

BACKGROUND: In response to the COVID-19 pandemic, new evidence-based strategies have emerged for reducing transmission of respiratory infections through management of indoor air. OBJECTIVES: This paper reviews critical advances that could reduce the burden of disease from inhaled pathogens and describes challenges in their implementation. DISCUSSION: Proven strategies include assuring sufficient ventilation, air cleaning by filtration, and air disinfection by germicidal ultraviolet (UV) light. Layered intervention strategies are needed to maximize risk reduction. Case studies demonstrate how to implement these tools while also revealing barriers to implementation. Future needs include standards designed with infection resilience and equity in mind, buildings optimized for infection resilience among other drivers, new approaches and technologies to improve ventilation, scientific consensus on the amount of ventilation needed to achieve a desired level of risk, methods for evaluating new air-cleaning technologies, studies of their long-term health effects, workforce training on ventilation systems, easier access to federal funds, demonstration projects in schools, and communication with the public about the importance of indoor air quality and actions people can take to improve it. https://doi.org/10.1289/EHP13878.

Adult vaccination against respiratory infections in Egypt: a review of expert opinions.

INTRODUCTION: Lower respiratory tract infection is one of the leading causes of morbidity and mortality all over the world, with a substantial impact on healthcare costs. In Egypt, local consensus on its burden, diagnosis, and vaccination is scarce. This expert opinion is the first to address the local recommendations for vaccinating adults against respiratory infection. It sheds light on the growing need to understand the barriers and underpublicized concept of adult vaccination in Egypt. AREAS COVERED: A collaborative multidisciplinary panel from Egypt developed an expert opinion-based suggestions/points, including epidemiology, microbiology, and highlights on vaccination in Egypt, as well as challenges and recommendations regarding adult vaccination. EXPERT OPINION: Adult vaccinations against respiratory infections are now recommended for high-risk people by all healthcare regulatory bodies. However, it was acknowledged that there may be hesitancy and concerns among patients; in addition, healthcare professionals' awareness about vaccination guidelines and benefits needs improvement. There are several strategies that could be implemented to enhance vaccine adherence in Egypt. These approaches encompass conducting community education programs, addressing the concerns of patients, and enhancing awareness among healthcare professionals through education, policy changes, and periodical reminders in each healthcare setting.

Zinc for prevention and treatment of the common cold.

BACKGROUND: The common cold is an acute, self-limiting viral respiratory illness. Symptoms include nasal congestion and mucus discharge, sneezing, sore throat, cough, and general malaise. Given the frequency of colds, they are a public health burden and a significant cause of lost work productivity and school absenteeism. There are no established interventions to prevent colds or shorten their duration. However, zinc supplements are commonly recommended and taken for this purpose. OBJECTIVES: To assess the effectiveness and safety of zinc for the prevention and treatment of the common cold. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and LILACS to 22 May 2023, and searched Web of Science Core Collection and two trials registries to 14 June 2023. We also used reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children or adults that tested any form of zinc against placebo to prevent or treat the common cold or upper respiratory infection (URTI). We excluded zinc interventions in which zinc was combined with other minerals, vitamins, or herbs (e.g. a multivitamin, or mineral supplement containing zinc). DATA COLLECTION AND ANALYSIS: We used the Cochrane risk of bias tool to assess risks of bias, and GRADE to assess the certainty of the evidence. We independently extracted data. When necessary, we contacted study authors for additional information. We assessed zinc (type and route) with placebo in the prevention and treatment of the common cold. Primary outcomes included the proportion of participants developing colds (for analyses of prevention trials only), duration of cold (measured in days from start to resolution of the cold), adverse events potentially due to zinc supplements (e.g. unpleasant taste, loss of smell, vomiting, stomach cramps, and diarrhoea), and adverse events considered to be potential complications of the common cold (e.g. respiratory bacterial infections). MAIN RESULTS: We included 34 studies (15 prevention, 19 treatment) involving 8526 participants. Twenty-two studies were conducted on adults and 12 studies were conducted on children. Most trials were conducted in the USA (n = 18), followed by India, Indonesia, Iran, and Turkey (two studies each), and Australia, Burkina Faso, Colombia, Denmark, Finland, Tanzania, Thailand, and the UK (one study each). The 15 prevention studies identified the condition as either common cold (n = 8) or URTI (n = 7). However, almost all therapeutic studies (17/19) focused on the common cold. Most studies (17/34) evaluated the effectiveness of zinc administered as lozenges (3 prevention; 14 treatment) in acetate, gluconate, and orotate forms; gluconate lozenges were the most common (9/17). Zinc gluconate was given at doses between 45 and 276 mg/day for between 4.5 and 21 days. Five (5/17) lozenge studies gave acetate lozenges and two (2/17) gave both acetate and gluconate lozenges. One (1/17) lozenge study administered intranasal (gluconate) and lozenge (orotate) zinc in tandem for cold treatment. Of the 17/34 studies that did not use lozenges, 1/17 gave capsules, 3/17 administered dissolved powders, 5/17 gave tablets, 4/17 used syrups, and 4/17 used intranasal administration. Most studies were at unclear or high risk of bias in at least one domain. There may be little or no reduction in the risk of developing a cold with zinc compared to placebo (risk ratio (RR) 0.93, 95% CI 0.85 to 1.01; I2 = 20%; 9 studies, 1449 participants; low-certainty evidence). There may be little or no reduction in the mean number of colds that occur over five to 18 months of follow-up (mean difference (MD) -0.90, 95% CI -1.93 to 0.12; I2 = 96%; 2 studies, 1284 participants; low-certainty evidence). When colds occur, there is probably little or no difference in the duration of colds in days (MD -0.63, 95% CI -1.29 to 0.04; I² = 77%; 3 studies, 740 participants; moderate-certainty evidence), and there may be little or no difference in global symptom severity (standardised mean difference (SMD) 0.04, 95% CI -0.35 to 0.43; I² = 0%; 2 studies, 101 participants; low-certainty evidence). When zinc is used for cold treatment, there may be a reduction in the mean duration of the cold in days (MD -2.37, 95% CI -4.21 to -0.53; I² = 97%; 8 studies, 972 participants; low-certainty evidence), although it is uncertain whether there is a reduction in the risk of having an ongoing cold at the end of follow-up (RR 0.52, 95% CI 0.21 to 1.27; I² = 65%; 5 studies, 357 participants; very low-certainty evidence), or global symptom severity (SMD -0.03, 95% CI -0.56 to 0.50; I² = 78%; 2 studies, 261 participants; very low-certainty evidence), and there may be little or no difference in the risk of a change in global symptom severity (RR 1.02, 95% CI 0.85 to 1.23; 1 study, 114 participants; low-certainty evidence). Thirty-one studies reported non-serious adverse events (2422 participants). It is uncertain whether there is a difference in the risk of adverse events with zinc used for cold prevention (RR 1.11, 95% CI 0.84 to 1.47; I2 = 0%; 7 studies, 1517 participants; very low-certainty evidence) or an increase in the risk of serious adverse events (RR 1.67, 95% CI 0.78 to 3.57; I2 = 0%; 3 studies, 1563 participants; low-certainty evidence). There is probably an increase in the risk of non-serious adverse events when zinc is used for cold treatment (RR 1.34, 95% CI 1.15 to 1.55; I2 = 44%; 2084 participants, 16 studies; moderate-certainty evidence); no treatment study provided information on serious adverse events. No study provided clear information about adverse events considered to be potential complications of the common cold. AUTHORS' CONCLUSIONS: The findings suggest that zinc supplementation may have little or no effect on the prevention of colds but may reduce the duration of ongoing colds, with an increase in non-serious adverse events. Overall, there was wide variation in interventions (including concomitant therapy) and outcomes across the studies, as well as incomplete reporting of several domains, which should be considered when making conclusions about the efficacy of zinc for the common cold.

Oral vitamin A supplements to prevent acute upper respiratory tract infections in children up to seven years of age.

BACKGROUND: According to global prevalence analysis studies, acute upper respiratory tract infections (URTIs) are the most common acute infectious disease in children, especially in preschool children. Acute URTIs lead to an economic burden on families and society. Vitamin A refers to the fat-soluble compound all-trans-retinol and also represents retinol and its active metabolites. Vitamin A interacts with both the innate immune system and the adaptive immune system and improves the host's defences against infections. Correlation studies show that serum retinol deficiency was associated with a higher risk of respiratory tract infections. Therefore, vitamin A supplementation may be important in preventing acute URTIs. OBJECTIVES: To assess the effectiveness and safety of vitamin A supplements for preventing acute upper respiratory tract infections in children up to seven years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the Chinese Biomedical Literature Database, and two trial registration platforms to 8 June 2023. We also checked the reference lists of all primary studies and reviewed relevant systematic reviews and trials for additional references. We imposed no language or publication restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs), which evaluated the role of vitamin A supplementation in the prevention of acute URTIs in children up to seven years of age. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included six studies (27,351 participants). Four studies were RCTs and two were cluster-RCTs. The included studies were all conducted in lower-middle-income countries (two in India, two in South Africa, one in Ecuador, and one in Haiti). Three studies included healthy children who had no vitamin A deficiency, one study included children born to HIV-infected women, one study included low-birthweight neonates, and one study included children in areas with a high local prevalence of malnutrition and xerophthalmia. In two studies, vitamin E was a co-treatment administered in addition to vitamin A. We judged the included studies to be at either a high or unclear risk of bias for random sequence generation, incomplete outcome data, and blinding. Primary outcomes Six studies reported the incidence of acute URTIs during the study period. Five studies reported the number of acute URTIs over a period of time, but there was population heterogeneity and the results were presented in different forms, therefore only three studies were meta-analysed. We are uncertain of the effect of vitamin A supplementation on the number of acute URTIs over two weeks (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.92 to 1.09; I2 = 44%; 3 studies, 22,668 participants; low-certainty evidence). Two studies reported the proportion of participants with an acute URTI. We are uncertain of the effect of vitamin A supplementation on the proportion of participants with an acute URTI (2 studies, 15,535 participants; low-certainty evidence). Only one study (116 participants) reported adverse events. No infant in either the placebo or vitamin A group was found to have feeding difficulties (failure to feed or vomiting), a bulging fontanelle, or neurological signs before or after vitamin A administration (very low-certainty evidence). Secondary outcomes Two studies (296 participants) reported the severity of subjective symptoms, presented by the mean duration of acute URTI. Vitamin A may have little to no effect on the mean duration of acute URTI (very low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence for the use of vitamin A supplementation to prevent acute URTI is uncertain, because population, dose and duration of interventions, and outcomes vary between studies. From generally very low- to low-certainty evidence, we found that there may be no benefit in the use of vitamin A supplementation to prevent acute URTI in children up to seven years of age. More RCTs are needed to strengthen the current evidence. Future research should report over longer time frames using validated tools and consistent reporting, and ensure adequate power calculations, to allow for easier synthesis of data. Finally, it is important to assess vitamin A supplementation for preschool children with vitamin A deficiency.

Assessment of effectiveness and impact of universal prophylaxis with nirsevimab for prevention of hospitalizations due to respiratory syncytial virus in infants. The NIRSE-GAL study protocol.

Nirsevimab has been recently licensed for universal RSV prophylaxis in infants. NIRSE-GAL is a three-year population-based study initiated in Galicia in September 2023. It aims to evaluate nirsevimab effectiveness against RSV-related hospitalizations lower respiratory tract infections (LRTI), severe RSV, all-cause LRTI, and all-cause hospitalization. NIRSE-GAL also aims to estimate nirsevimab impact on primary healthcare use in the short and mid-term, children's wheezing and asthma, and medical prescriptions for RSV. The immunization campaigns will be scheduled based on the expected start week for the RSV season and will last the whole season. Immunization will be offered to: i) infants born during the campaign (seasonal), ii) infants < 6 months at the start of the campaign (catch-up), and iii) infants with high-risk factors, aged 6-24 months at the start of the campaign (high-risk). The follow-up period will start: i) the immunization date for all immunized infants, ii) the start of the campaign, for the non-immunized catch-up or high-risk groups, or iii) the birthdate for the non-immunized seasonal group. Infants will be followed up until outcome occurrence, death, or end of study. Nirsevimab effectiveness will be estimated using Poisson and Cox regression models. Sensitivity and stratified analyses will be undertaken. The number of averted cases and the number needed to immunize will be estimated. Immunization failure and nirsevimab safety will be monitored. NIRSE-GAL was approved by the ethics committee of Galicia (CEIC 2023-377) and registered in ClinicalTrials.gov (ID: NCT06180993). Findings will be mainly shared via peer-reviewed publications and scientific conferences.

Effectiveness of cocoon strategy vaccination on prevention of influenza-like illness in young infants.

During the initial half-year of their existence, infants cannot receive the influenza vaccine, yet they face the greatest susceptibility to severe influenza complications. In this study, we seek to determine whether influenza vaccination of maternal and household contacts is associated with a reduced risk of influenza-like illness (ILI) and severe acute respiratory infection (SARI) in infants. This work was prospectively conducted during the influenza season. A total of 206 infants were included in this study. The percentage of infants with only the mother vaccinated is 12.6% (n:26), and the percent of infants with all household contacts vaccinated is 16% (n:33). Among the infants with only the mother vaccinated, the effectiveness of influenza vaccine is estimated as 35.3% for ILI and 41.3% for SARI. Among infants with all household contacts vaccinated, the effectiveness is estimated as 48.9% for ILI and 76.9% for SARI. Based on the results of multivariate logistic regression analysis, all-household vaccination is a protective factor against SARI (OR: 0.07 95% CI [0.01-0.56]), household size (OR: 1.75, 95% CI [1.24-2.48]) and presence of secondhand smoke (OR: 2.2, 95% CI [1.12-4.45]) significant risk factors for SARI in infants. The mother alone being vaccinated is not a statistically significant protective factor against ILI (OR: 0.46, 95% CI [0.19-1.18]) or SARI (OR: 0.3, 95% CI [0.11-1.21]). Along with the obtained results and analysis, this study provides clear evidence that influenza vaccination of all household contacts of infants aged 0-6 months is significantly associated with protecting infants from both ILI and SARI.

Curcumin and quercetin co-encapsulated in nanoemulsions for nasal administration: A promising therapeutic and prophylactic treatment for viral respiratory infections.

One of the most frequent causes of respiratory infections are viruses. Viruses reaching the airways can be absorbed by the human body through the respiratory mucosa and mainly infect lung cells. Several viral infections are not yet curable, such as coronavirus-2 (SARS-CoV-2). Furthermore, the side effect of synthetic antiviral drugs and reduced efficacy against resistant variants have reinforced the search for alternative and effective treatment options, such as plant-derived antiviral molecules. Curcumin (CUR) and quercetin (QUE) are two natural compounds that have been widely studied for their health benefits, such as antiviral and anti-inflammatory activity. However, poor oral bioavailability limits the clinical applications of these natural compounds. In this work, nanoemulsions (NE) co-encapsulating CUR and QUE designed for nasal administration were developed as promising prophylactic and therapeutic treatments for viral respiratory infections. The NEs were prepared by high-pressure homogenization combined with the phase inversion temperature technique and evaluated for their physical and chemical characteristics. In vitro assays were performed to evaluate the nanoemulsion retention into the porcine nasal mucosa. In addition, the CUR and QUE-loaded NE antiviral activity was tested against a murine ß-COV, namely MHV-3. The results evidenced that CUR and QUE loaded NE had a particle size of 400 nm and retention in the porcine nasal mucosa. The antiviral activity of the NEs showed a percentage of inhibition of around 99 %, indicating that the developed NEs has interesting properties as a therapeutic and prophylactic treatment against viral respiratory infections.

Pneumococcal vaccination and primary care presentations for acute respiratory tract infection and antibiotic prescribing in older adults.

BACKGROUND: While the 23-valent pneumococcal polysaccharide vaccine (PPV23) has demonstrated its role in preventing severe pneumococcal disease, its impact on more non-specific conditions like acute respiratory tract infection (ARI) and lower respiratory tract infections (LRTI) remains unclear. We aimed to investigate the role of PPV23 in prevention of presentations for ARI and LRTI and related antibiotic prescriptions among older adults in primary care. METHODS: Using a nationwide general practice dataset, we followed a cohort of regularly attending patients aged ≥65 years from 1 January 2014 until 31 December 2018 for presentations for ARI, LRTI, and related antibiotic prescriptions. Associations between PPV23 receipt and each outcome were assessed using a multiple failures survival model to estimate hazard ratios (HR) adjusted for age, sex, socioeconomic status, and various health measures. RESULTS: A cohort of 75,264 patients aged ≥65 years (mean 75.4, 56% female) in 2014 was followed. The incidence of presentations for ARI, ARI-related antibiotic prescription, LRTI, and LRTI-related antibiotic prescription was 157.6, 76.0, 49.6, and 24.3 per 1000 person-years, respectively. Recent PPV23 vaccine receipt was associated with a small reduction in ARI presentations (adjusted HR vaccinated vs. unvaccinated 0.96; 95%CI 0.94-0.98; p = 0.002); however, there was no reduction in ARI-related antibiotic prescription, LRTI presentation, nor LRTI-related antibiotic prescription (adjusted HR were 0.99[95%CI 0.96-1.03], 1.04[95%CI 0.99-1.09], 1.07[95%CI 1.00-1.14]). CONCLUSION: PPV23 vaccination in older adults may result in a small reduction in the incidence of total ARI presentations in primary care. However, the effect is small and residual confounding cannot be excluded.

The impact of non-pharmaceutical interventions on community non-SARS-CoV-2 respiratory infections in preschool children.

BACKGROUND: Effects of non-pharmaceutical interventions during the pandemic were mainly studied for severe outcomes. Among children, most of the burden of respiratory infections is related to infections which are not medically attended. The perspective on infections in the community setting is necessary to understand the effects of the pandemic on non-pharmaceutical interventions. METHODS: In the unique prospective LoewenKIDS cohort study, we compared the true monthly incidence of self-reported acute respiratory infections (ARI) in about 350 participants (aged 3-4 years old) between October 2019 to March 2020 (pre-pandemic period) and October 2020 to March 2021 (pandemic period). Parents reported children's symptoms using a diary. Parents were asked to take a nasal swab of their child during all respiratory symptoms. We analysed 718 swabs using Multiplex PCR for 25 common respiratory viruses and bacteria. RESULTS: During the pre-pandemic period, on average 44.6% (95% CI: 39.5-49.8%) of children acquired at least one ARI per month compared to 19.9% (95% CI: 11.1-28.7%) during the pandemic period (Incidence Rate Ratio = 0.47; 95% CI: 0.41-0.54). The detection of influenza virus decreased absolute by 96%, respiratory syncytial virus by 65%, metapneumovirus by 95%, parainfluenza virus by 100%, human enterovirus by 96% and human bocavirus by 70% when comparing the pre-pandemic to the pandemic period. However, rhinoviruses were nearly unaffected by NPI. Co-detection (detection of more than one virus in a single symptomatic swab) was common in the pre-pandemic period (222 of 390 samples with viral detection; 56.9%) and substantially less common during the pandemic period (46 of 216 samples; 21.3%). CONCLUSION: Non-pharmaceutical interventions strongly reduced the incidence of all respiratory infections in preschool children but did not affect rhinovirus.

Gut microbial features may influence antiviral IgG levels after vaccination against viral respiratory infectious diseases: the evidence from two-sample bidirectional mendelian randomization.

BACKGROUND: Vaccination is effective in preventing viral respiratory infectious diseases through protective antibodies and the gut microbiome has been proven to regulate human immunity. This study explores the causal correlations between gut microbial features and serum-specific antiviral immunoglobulin G (IgG) levels. METHODS: We conduct a two-sample bidirectional Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary data to explore the causal relationships between 412 gut microbial features and four antiviral IgG (for influenza A, measles, rubella, and mumps) levels. To make the results more reliable, we used four robust methods and performed comprehensive sensitivity analyses. RESULTS: The MR analyses revealed 26, 13, 20, and 18 causal associations of the gut microbial features influencing four IgG levels separately. ​Interestingly, ten microbial features, like genus Collinsella, species Bifidobacterium longum, and the biosynthesis of L-alanine have shown the capacity to regulate multiple IgG levels with consistent direction (rise or fall). The ​reverse MR analysis suggested several potential causal associations of IgG levels affecting microbial features. CONCLUSIONS: The human immune response against viral respiratory infectious diseases could be modulated by changing the abundance of gut microbes, which provided new approaches for the intervention of viral respiratory infections.

Effect of housing construction material on childhood acute respiratory infection: a hospital based case control study in Bangladesh.

Despite several studies conducted to investigate housing factors, the effects of housing construction materials on childhood ARI symptoms in Bangladesh remain unclear. Hence, the study aimed to measure such a correlation among children under the age of five. A hospital-based case-control study was conducted, involving 221 cases and 221 controls from January to April 2023. Bivariate and multivariate binary logistic regression was performed to measure the degree of correlation between housing construction materials and childhood ARI symptoms. Households composed of natural floor materials had 2.7 times (95% confidence interval 1.27-5.57) and households composed of natural roof materials had 1.8 times (95% confidence interval 1.01-3.11) higher adjusted odds of having under-five children with ARI symptoms than household composed of the finished floor and finished roof materials respectively. Households with natural wall type were found protective against ARI symptoms with adjusted indoor air pollution determinants. The study indicates that poor housing construction materials are associated with an increased risk of developing ARI symptoms among under-five children in Bangladesh. National policy regarding replacing poor housing materials with concrete, increasing livelihood opportunities, and behavioral strategies programs encouraging to choice of quality housing construction materials could eliminate a fraction of the ARI burden.

Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract.

Respiratory virus infections in humans cause a broad-spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that are accessible and effective are urgently needed, especially in countries that are disproportionately affected. Repurposing generic medicine has the potential to bring new treatments for infectious diseases to patients efficiently and equitably. In this study, we found that intranasal delivery of neomycin, a generic aminoglycoside antibiotic, induces the expression of interferon-stimulated genes (ISGs) in the nasal mucosa that is independent of the commensal microbiota. Prophylactic or therapeutic administration of neomycin provided significant protection against upper respiratory infection and lethal disease in a mouse model of COVID-19. Furthermore, neomycin treatment protected Mx1 congenic mice from upper and lower respiratory infections with a highly virulent strain of influenza A virus. In Syrian hamsters, neomycin treatment potently mitigated contact transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In healthy humans, intranasal application of neomycin-containing Neosporin ointment was well tolerated and effective at inducing ISG expression in the nose in a subset of participants. These findings suggest that neomycin has the potential to be harnessed as a host-directed antiviral strategy for the prevention and treatment of respiratory viral infections.

Efficacy and safety of a synbiotic infant formula for the prevention of respiratory and gastrointestinal infections: a randomized controlled trial.

BACKGROUND: Early life nutrition is crucial for the development of the gut microbiota that, in turn, plays an essential role in the maturation of the immune system and the prevention of infections. OBJECTIVES: The aim of this study was to investigate whether feeding synbiotic infants and follow-on formulas during the first year of life reduces the incidence rate (IR) of infectious diarrhea compared with standard formulas. Secondary endpoints included the IR of other infectious diseases as well as fecal milieu parameters. METHODS: In this double-blind, controlled trial, 460 healthy, 1-mo-old infants were randomly assigned to receive a synbiotic [galacto-oligosaccharides (GOS)/Limosilactobacillus fermentum CECT 5716] (IF, n = 230) or a control formula (CF, n = 230) until 12 mo of age. A reference group of breastfed infants (HM, n = 80) was included. Data on infections were recorded throughout the study period and stool samples were collected at 4 and 12 mo of age. RESULTS: IR of infectious diarrhea during the first year of life was 0.60 (CF), 0.56 (IF), and 0.29 (HM), with no statistically significant difference between groups. The IR of lower respiratory tract infections, 1 of the secondary endpoints, however, was lower in IF than in CF [0.79 compared with 1.01, IR ratio = 0.77 (0.60-1.00)]. Additionally, fecal pH was significantly lower at 4 mo (P < 0.0001), whereas secretory IgA was significantly higher at 12 mo of age (P = 0.015) in IF compared with CF. CONCLUSIONS: Although no difference is observed in the incidence of diarrhea, consumption of a synbiotic formula containing L. fermentum CECT5716 and GOS in infancy may reduce the incidence of lower respiratory tract infections and affect the immune system and fecal milieu. Additional research is warranted to further investigate the potential interaction of the gut-lung axis. This trial was registered at clinicaltrials.gov as NCT02221687.

Changes in Viral Dynamics Following the Legal Relaxation of COVID-19 Mitigation Measures in Japan From Children to Adults: A Single Center Study, 2020-2023.

INTRODUCTION: Respiratory infections are an ongoing global health challenge. The COVID-19 pandemic triggered global nonpharmacological measures that reshaped public health. In Japan, the shift from legal to individual discretion in pandemic management started on May 8, 2023. However, it still unknown how the relaxation of measures affects respiratory pathogens across age groups. METHODS: We collected 16,946 samples from 13,526 patients between February 2020 and September 2023, analyzing the circulating respiratory pathogen dynamics using FilmArray respiratory panel. RESULTS: Our analysis revealed significant increases in the positivity rates of respiratory pathogens across multiple age groups after relaxation. The pathogens including adenovirus, Bordetella pertussis, parainfluenza 2 and parainfluenza 4 showed increased positivity predominantly in children aged under 10 years. Conversely, some pathogens including human metapneumovirus, rhinovirus/enterovirus, and respiratory virus (RSV) increased in broad range of age groups. SARS-CoV-2 positivity rates decreased in children under 10 years but increased in those aged over 60 years. DISCUSSION: Age-stratified analysis reveals a dynamic pattern of circulating pathogen in each age group after relaxation measures. This study provides essential epidemiologic data that can guide strategies to protect different age groups and effectively respond to respiratory infections in post-COVID-19 era.

Investigating Nonspecific Effects of the Live-Attenuated Japanese Encephalitis Vaccine on Lower Respiratory Tract Infections in Children Aged 25-35 Months: Retrospective Cohort Study.

BACKGROUND: Live attenuated vaccines may be used to prevent nontargeted diseases such as lower respiratory tract infections (LRTIs) due to their nonspecific effects (NSEs). OBJECTIVE: We aimed to analyze the NSEs of the Japanese encephalitis vaccine on pediatric LRTIs in children aged 25 months to 35 months. METHODS: A retrospective cohort study was conducted by using a population-based electronic health record database in Zhejiang, China. Enrolled participants were children born from January 1, 2017, to December 31, 2017, and who were inoculated with the live-attenuated Japanese encephalitis vaccine (JE-L) or inactivated Japanese encephalitis vaccine (JE-I) as the most recent vaccine at 24 months of age. The study was carried out between January 1, 2019, and December 31, 2019. All inpatient and outpatient hospital visits for LRTIs among children aged 25 months to 35 months were recorded. The Andersen-Gill model was used to assess the NSEs of JE-L against LRTIs in children and compared with those of JE-I as the most recent vaccine. RESULTS: A total of 810 children born in 2017 were enrolled, of whom 585 received JE-L (JE-L cohort) and 225 received JE-I (JE-I cohort) as their last vaccine. The JE-L cohort showed a reduced risk of LRTIs (adjusted hazard ratio [aHR] 0.537, 95% CI 0.416-0.693), including pneumonia (aHR 0.501, 95% CI 0.393-0.638) and acute bronchitis (aHR 0.525, 95% CI 0.396-0.698) at 25 months to 35 months of age. The NSEs provided by JE-L were especially pronounced in female children (aHR 0.305, 95% CI 0.198-0.469) and children without chronic diseases (aHR 0.553, 95% CI 0.420-0.729), without siblings (aHR 0.361, 95% CI 0.255-0.511), with more than 30 inpatient and outpatient hospital visits prior to 24 months of age (aHR 0.163, 95% CI 0.091-0.290), or with 5 to 10 inpatient and outpatient hospital visits due to infectious diseases prior to 24 months old (aHR 0.058, 95% CI 0.017-0.202). CONCLUSIONS: Compared with JE-I, receiving JE-L as the most recent vaccine was associated with lower risk of inpatient and outpatient hospital visits for LRTIs among children aged 25 months to 35 months. The nature of NSEs induced by JE-L should be considered for policymakers and physicians when recommending JE vaccines to those at high risk of infection from the Japanese encephalitis virus.

Impact of Nonpharmaceutical Interventions during the COVID-19 Pandemic on the Prevalence of Respiratory Syncytial Virus in Hospitalized Children with Lower Respiratory Tract Infections: A Systematic Review and Meta-Analysis.

During the COVID-19 pandemic, nonpharmaceutical interventions (NPIs) were implemented in order to control the transmission of SARS-CoV-2, potentially affecting the prevalence of respiratory syncytial virus (RSV). This review evaluated the impact of NPIs on RSV-related hospitalizations in children during the lockdown (2020-2021) compared to the pre-pandemic (2015-2020) and post-lockdown (2021-2022) periods. In this systematic review and meta-analysis, we searched through PubMed, Scopus, and Web of Science for studies published in English between 1 January 2015 and 31 December 2022. Additionally, we conducted hand searches of other records published between 1 January 2023 and 22 January 2024. Our target population was hospitalized children aged 0-18 years with RSV-related lower respiratory tract infections confirmed through immunofluorescence, antigen testing, or molecular assays. We focused on peer-reviewed observational studies, analyzing the primary outcome of pooled RSV prevalence. A generalized linear mixed model with a random-effects model was utilized to pool each RSV prevalence. Heterogeneity was assessed using Cochran's Q and I2 statistics, while publication bias was evaluated through funnel plots and Egger's tests. We identified and analyzed 5815 publications and included 112 studies with 308,985 participants. Notably, RSV prevalence was significantly lower during the lockdown period (5.03% [95% CI: 2.67; 9.28]) than during the pre-pandemic period (25.60% [95% CI: 22.57; 28.88], p < 0.0001). However, RSV prevalence increased notably in the post-lockdown period after the relaxation of COVID-19 prevention measures (42.02% [95% CI: 31.49; 53.33] vs. 5.03% [95% CI: 2.67; 9.28], p < 0.0001). Most pooled effect estimates exhibited significant heterogeneity (I2: 91.2% to 99.3%). Our findings emphasize the effectiveness of NPIs in reducing RSV transmission. NPIs should be considered significant public health measures to address RSV outbreaks.

Human papilloma virus (HPV) vaccination is associated with reduced number of surgical treatments, an observational study on recurrent respiratory papillomatosis in Northern Sweden.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a wart-like lesion mainly affecting the larynx, caused by human papillomavirus (HPV) genotypes 6 and 11. The disease affects both children and adults, and there is no cure. Surgery is the current symptom-relieving treatment; however, HPV vaccination is used as an adjuvant treatment. AIMS AND OBJECTIVES: The aims were to study effects of HPV vaccination in RRP cases and to compare juvenile-onset to adult-onset disease and high treatment frequency (TF) to low TF cases. MATERIAL AND METHODS: Medical records of RRP patients were studied from May 2006 to January 2023. Eighty-five RRP cases, tested for HPV genotypes with PapilloCheck®, were included. Vaccination- onset- and treatment analysis were performed. RESULTS: Twelve percent of the cases were vaccinated. The number of surgeries decreased from 2.0 to 0.8/year after HPV vaccination. Most cases had an adult-onset and less than one treatment per year. Juvenile-onset cases had a higher vaccination treatment ratio compared to adult-onset. CONCLUSIONS: HPV vaccination was associated with a lower number of treatments per year, supporting the use of vaccination as an adjuvant treatment. SIGNIFICANCE: Vaccination as adjuvant treatment to surgery may lead to increased quality of life for RRP patients and saved healthcare resources.

Frequency of Asthma Exacerbations and Upper Respiratory Tract Infections Among Adults With Asthma According to Vaccination Status: Does the annual influenza vaccine have a protective effect?

Objectives: Annual influenza vaccinations are recommended for asthma patients to prevent seasonal influenza and influenza-triggered asthma exacerbations. However, data on the beneficial effect of this vaccine on the frequency of asthma exacerbations are conflicting. Therefore, this study aimed to assess the effectiveness of the influenza vaccine in terms of reducing the frequency of asthma-related exacerbations and upper respiratory tract infections among adult patients with asthma. Methods: This retrospective cohort study was performed from January to December 2018 in Muscat Governorate, Oman. A total of 466 patients attending 9 randomly selected primary health centres in Muscat Governorate were enrolled in the study and followed up for one year post vaccination. Results: Most of the patients were female (70.6%) and had moderate persistent asthma (42.9%). There were 203 patients (43.6%) in the vaccinated group and 263 patients (56.4%) in the non-vaccinated group. A proportion of patients in each group had allergic rhinitis (28.6% and 25.5%, respectively). The frequency of upper respiratory tract infections over the one-year follow-up period was significantly lower in the vaccinated group than in the non-vaccinated group (37.9% versus 73%; relative risk [RR]: 2.299; 95% confidence interval [CI]: 1.834-2.882; P <0.001); however, there was no significant difference in terms of the frequency of asthma exacerbations (41.9% versus 45.2%; RR: 0.925; 95% CI: 0.750-1.141; P >0.050). Conclusion: The influenza vaccine significantly reduces the frequency of upper respiratory tract infections over the following year. However, it does not significantly reduce the frequency of asthma exacerbations among Omani adults with asthma. Further studies are recommended to support the protective effect of the vaccine in this regard.

Changes in Spectrum of Respiratory Pathogen Infections and Disease Severity Among Children in Hohhot, China: Impact of COVID-19 Prevention Measures.

BACKGROUND This retrospective study evaluated the effects of specific COVID-19 preventive measures, including the use of medical masks, nucleic acid testing, and patient isolation, on respiratory infections, disease severity, and seasonal patterns among children in Hohhot, located in northern China. Understanding these alterations is pivotal in developing effective strategies to handle pediatric respiratory infections within the context of continuous public health initiatives. MATERIAL AND METHODS At the First Hospital of Hohhot, throat swabs were collected from 605 children with community-acquired respiratory between January 2022 and March 2023 for pathogen infection spectrum detection using microarray testing. RESULTS Among the patients, 56.03% were male, and their average age was 3.45 years. SARS-CoV-2 infections were highest between October 2022 and January 2023. Influenza A peaked in March 2023, and other pathogens such as respiratory syncytial virus and influenza B virus disappeared after December 2022. The proportion of mixed infections was 41.94% among SARS-CoV-2 patients, while other pathogens had mixed infection rates exceeding 57.14%. Before December 2022, the mean WBC count for Streptococcus pneumoniae and Haemophilus influenzae was 8.83×109/L, CRP was 18.36 mg/L, and PCT was 1.11 ng/ml. After December 2022, these values decreased significantly. Coughing, difficulty breathing, running nose, and lower respiratory tract infection diagnoses decreased in December 2022, except for SARS-CoV-2 infections. CONCLUSIONS SARS-CoV-2 peaked around November 2022, influenza A peaked in March 2023, and other pathogens like respiratory syncytial virus and influenza B virus were greatly reduced after December 2022. Inflammatory markers and respiratory symptoms decreased after December 2022, except for SARS-CoV-2.