Cause Of Respiratory Infections Research Articles

Demographics, Clinical Presentation and Outcome of Metapneumovirus Infection in Adults: A Case Series Analysis at Scarborough General Hospital, United Kingdom.

Human metapneumovirus (hMPV) was first discovered in 2001 in Netherlands as a leading cause of respiratory infections. hMPV infection is more common in kids, elderly (age ≥ 65) and immuno-compromised adults. Treatment is mainly symptomatic. We collected retrospective data from 31-8-2022 to 01-09-2023 from Microbiology for patients who tested positive for hMPV by polymerase chain reaction (PCR). Only patients aged 18 years and above and admitted to Scarborough General Hospital (SGH) were included in the study. Total patients who tested positive were 38, out of which 73% (n=24) of patients were ≥ 65 years of age. 76.3% (n=29) of these adults were living in their own residence and 53% (n=20) patients never smoked. The most common presentation of these patients was shortness of breath and cough. Fifty-eight percent (n=22) patients had no radiological findings and 74% (n=28) had raised C-reactive protein (CRP). hMPV management was analyzed based on six modalities, we found out that 76% (n=29) patients received antibiotics, 47% (n=18) received nebulizers, 45% (n=17) required oxygen, 37% (n=14) were treated with steroids, 21% (n=8) patients were given inhalers and only one received antivirals. Majority of the patients were discharged and 13% (n=5) of patients died during their inpatient stay. All the deceased patients were aged 65 and above and 80% (n=4) of deceased (n=5) had pre-existing co-morbidities or other acute diagnoses at admission. The patients who tested positive for hMPV were mostly aged ≥ 65 years, 76.3% (n=28) were from personal residence and there was no association of smoking history with hMPV infection. Patients who tested positive for hMPV would mostly present with flu-like symptoms with raised CRP and no radiological manifestation. All these patients were managed conservatively with antibiotics, nebulizers, oxygen, inhalers and antivirals (only one patient). Most of the patients were discharged home and five died during the inpatient stay, all of them were >65 of age and 80% had pre-existing co-morbidities and other acute diagnoses at the time of admission. We could not conclude or hypothesize anything due to small sample size. This data was collected over a one-year period only, and the sample size was very small. Another limitation was that we did not follow up patients after discharge.

Vaccination against respiratory syncytial virus (RSV)-For the protection of infants and older adults

Respiratory syncytial virus (RSV) is afrequent cause of respiratory infections in all age groups. Infections in infants and older adults frequently result in severe disease and complications. There is no specific antiviral treatment against RSV. The characterization of the structure of the fusion (F) protein in its immunogenic prefusion conformation has enabled the development of novel vaccines directed against the prefusion protein as the antigen. These include an adjuvanted monovalent vaccine (Arexvy) and anonadjuvanted bivalent vaccine (Abrysvo). Both are approved and indicated for use in older adults, in whom they have been shown to be over 80% effective in the protection against symptomatic RSV infections and associated lower respiratory tract diseases. Abrysvo is approved for use in pregnancy to protect the newborn through the transplacental transfer of high-titer maternal antibodies. The vaccine has been shown to have an efficacy of over 80% in the first 3 months of life to protect the infant from severe RSV-associated lower respiratory disease but slightly deceases after an age of 6 months. The clinical studies demonstrated the safety of the vaccines in both adults and pregnant women. The rate of undesired side effects was low in all studies and severe side effects were very rare. The new vaccines are efficacious new tools to prevent RSV-associated disease and complications in high-risk groups. For infants, an alternative strategy can be passive immunization with monoclonal antibodies, including the recently developed nirsevimab, which has also shown high efficacy.

Vaccinations in pulmonary diseases - part 2: herpes zoste, RSV, pneumococcal infection and pertussis

RSV is a common cause of respiratory tract infections, posing a risk of severe disease, particularly for newborns and infants, as well as in older individuals with pre-existing conditions. Two safe and effective RSV vaccines were approved in 2023. These vaccines elicit protective antibodies and offer robust protection with no additional benefit from annual boosters. Both vaccines have been approved for individuals aged 60 years and older, while one of the vaccines has also been approved in pregnant women to elicit maternal immunity for passive protection of the unborn child. In Germany, RSV vaccination is currently recommended for all individuals aged 75 years and older, as well as people aged 60-74 years of age with severe underlying conditions. PNEUMOCOCCAL INFECTION: Streptococcus pneumoniae is a primary cause of community-acquired pneumonia (CAP). Since early 2022, a 20-valent conjugate vaccine (PCV20) is approved and recommended for people over 60 years of age and individuals over 18 years of age with risk factors. PCV20 replaces the 23-valent polysaccharide vaccine (PPV23) previously recommended for those over 60 years of age. Although viewed primarily as a childhood disease, the majority of infections affect adults. Patients with chronic respiratory diseases are at a higher risk for severe clinical course of pertussis infection. It has therefore been recommended that all adults should get a pertussis booster with their next scheduled tetanus vaccination, given as a combination vaccine (Tdap). For risk groups (healthcare personnel, community facilities) a booster vaccination every 10 years is recommended. Herpes Zoster (shingles) is caused by the varicella-zoster virus, and reactivations can lead to painful skin lesions and potential complications such as herpes zoster oticus, meningitis, or postherpetic neuralgia. People with chronic lung diseases such as COPD or asthma are at increased risk of herpes zoster-related complications. A recombinant adjuvanted inactivated vaccine was approved in 2018 and offers robust protection against herpes zoster and its complications. The vaccine is recommended for all people over 60 years of age and for certain risk groups over 50 years of age.

Human metapneumovirus SH protein promotes JAK1 degradation to impair host IL-6 signaling.

Human metapneumovirus (HMPV) is a leading cause of respiratory infections in children, older adults, and those with underlying conditions (K. M. Edwards et al., N Engl J Med 368:633-643, 2013, https://doi.org/10.1056/NEJMoa1204630; A. R. Falsey et al., J Infect Dis 187:785-790, 2003, https://doi.org/10.1086/367901; J. S. Kahn, Clin Microbiol Rev 19:546-557, 2006, https://doi.org/10.1128/CMR.00014-06; N. Shafagati and J. Williams, F1000Res 7:135, 2018, https://doi.org/10.12688/f1000research.12625.1). HMPV must evade immune defenses to replicate successfully; however, the viral proteins used to accomplish this are poorly characterized. The HMPV small hydrophobic (SH) protein has been reported to inhibit signaling through type I and type II interferon (IFN) receptors in vitro in part by preventing STAT1 phosphorylation (A. K. Hastings et al., Virology (Auckl) 494:248-256, 2016, https://doi.org/10.1016/j.virol.2016.04.022). HMPV infection also inhibits IL-6 signaling. However, the mechanisms by which SH inhibits signaling and its involvement in IL-6 signaling inhibition are unknown. Here, we used transfection of SH expression plasmids and SH-deleted virus (ΔSH) to show that SH is the viral factor responsible for the inhibition of IL-6 signaling during HMPV infection. Transfection of SH-expression vectors or infection with wild-type, but not ΔSH virus, blocked IL-6-mediated STAT3 activation. Furthermore, JAK1 protein (but not RNA) was significantly reduced in cells infected with wild-type, but not ΔSH virus. The SH-mediated reduction of JAK1 was partially restored by the addition of proteasome inhibitors, suggesting proteasomal degradation of JAK1. Confocal microscopy indicated that infection relocalized JAK1 to viral replication factories. Co-immunoprecipitation showed that SH interacts with JAK1 and ubiquitin, further linking SH to proteasomal degradation machinery. These data indicate that SH inhibits IL-6 and IFN signaling in infected cells in part by promoting proteasomal degradation of JAK1 and that SH is necessary for IL-6 and IFN signaling inhibition in infection. These findings enhance our understanding of the immune evasion mechanisms of an important respiratory pathogen.IMPORTANCEHuman metapneumovirus (HMPV) is a common cause of severe respiratory illness, especially in children and older adults, in whom it is a leading cause of hospitalization. Prior research suggests that severe HMPV infection is driven by a strong immune response to the virus, especially by inflammatory immune signals like interferons (IFN). HMPV produces a small hydrophobic (SH) protein that is known to block IFN signaling, but the mechanism by which it functions and its ability to inhibit other important immune signals remains unexplored. This paper demonstrates that SH can inhibit another related immune signal, IL-6, and that SH depletes JAKs, which are critical proteins involved in both IL-6 and IFN signaling. A robust understanding of how HMPV and related viruses interfere with immune signals important for disease could pave the way for future treatments aimed at mitigating severe infections.

Prospective cohort study on the clinical significance of interferon-γ, D-dimer, LDH, and CRP tests in children with severe mycoplasma pneumonia.

Mycoplasma pneumoniae is a significant cause of respiratory infections in children, often leading to severe pneumonia. This study aimed to assess the clinical relevance of interferon-gamma (interferon-γ), D-dimer, lactate dehydrogenase (LDH), and C-reactive protein (CRP) as biomarkers in the severity of mycoplasma pneumonia in pediatric patients. In this prospective study, 203 pediatric patients with mycoplasma pneumonia were classified into mild (123 patients) and severe (80 patients) groups. Biomarkers including interferon-γ, D-dimer, LDH, and CRP were measured and analyzed. Statistical methods employed included Pearson and Spearman correlation analyses, logistic regression, and receiver operating characteristic curve analysis. The severe group exhibited significantly higher median and interquartile ranges for interferon-γ, D-dimer, LDH, and CRP compared to the mild group. Logistic regression identified IL-10, IL-6, interferon-γ, tumor necrosis factor-alpha, D-dimer, and LDH as independent predictors of severity, with the model achieving 92% accuracy. Receiver operating characteristic curve analysis showed optimal diagnostic efficacy for interferon-γ, D-dimer, and LDH, with the best threshold values being 8.11, 0.64, and 379, respectively. A significant positive correlation was observed between IL-6 and LDH, as well as between interferon-γ and D-dimer. This study showed that interferon-γ >8.11, D-dimer >0.64, and LDH >379 have an important role in the assessment of severe mycoplasma pneumonia.

The deadly dance of alveolar macrophages and influenza virus.

Influenza A virus (IAV) is one of the leading causes of respiratory infections. The lack of efficient anti-influenza therapeutics requires a better understanding of how IAV interacts with host cells. Alveolar macrophages are tissue-specific macrophages that play a critical role in lung innate immunity and homeostasis, yet their role during influenza infection remains unclear. First, our review highlights an active IAV replication within alveolar macrophages, despite an abortive viral cycle. Such infection leads to persistent alveolar macrophage inflammation and diminished phagocytic function, alongside direct mitochondrial damage and indirect metabolic shifts in the alveolar micro-environment. We also discuss the "macrophage disappearance reaction", which is a drastic reduction of the alveolar macrophage population observed after influenza infection in mice but debated in humans, with unclear underlying mechanisms. Furthermore, we explore the dual nature of alveolar macrophage responses to IAV infection, questioning whether they are deleterious or protective for the host. While IAV may exploit immuno-evasion strategies and induce alveolar macrophage alteration or depletion, this could potentially reduce excessive inflammation and allow for the replacement of more effective cells. Despite these insights, the pathophysiological role of alveolar macrophages during IAV infection in humans remains understudied, urging further exploration to unravel their precise contributions to disease progression and resolution.

Ethanolic Extract from Echinacea purpurea (L.) Moench Inhibits Influenza A/B and Respiratory Syncytial Virus Infection in vitro: Preventive Agent for Viral Respiratory Infections.

Among the most frequent causes of respiratory infections in humans are influenza A virus H1N1 (H1N1), influenza B virus (IVB), and respiratory syncytial virus (RSV). Echinacea is a perennial wildflower belonging to the Asteraceae family. Echinacea purpurea (L.) Moench is a species belonging to the Echinacea genus. Its characteristic compound, chicoric acid (CA), is known for its physiological activities, including antiviral effects and immune enhancement. Activities of E. purpurea 60% ethanol extract (EPE) and CA in inhibiting infections caused by H1N1, IVB, and RSV subtype A (RSV-A) were evaluated through plaque inhibition tests, quantification of viral gene expression, and analysis of transmission electron microscopy (TEM) images. Additionally, inhibitory activities of EPE and CA for hemagglutination and neuraminidase (NA) of H1N1 and IVB were determined. In the plaque reduction assays, both EPE and CA reduced infectivity against H1N1, IVB, and RSV-A. Furthermore, quantitative real-time polymerase chain reaction analysis revealed that EPE and CA reduced gene expression levels for H1N1, IVB, and RSV-A, whereas TEM image analysis confirmed their inhibitory effects on host cell infection by these viruses. Hemagglutination assays exhibited the ability of EPE and CA to hinder H1N1 and IVB attachment to host cell receptors. Furthermore, EPE and CA displayed inhibition activity against the NA of H1N1 and IVB. These findings suggest that EPE and CA can suppress the infection and propagation of H1N1, IVB, and RSV-A, demonstrating their potential as preventive and therapeutic agents for viral respiratory infections or as ingredients for health functional foods.

Misuse of Antibiotics in Pediatric Patients – A Comprehensive Review .

To identify and assess the likely causes of antibiotic overuse in the Pediatric outpatient department (OPD) of a busy teaching hospital. Overuse of antibiotics has emerged as a significant global pediatric concern. Specifically, the sale of drugs without a prescription from a doctor and other circumstances may have an impact on the abuse of antibiotics. Antibiotic resistance is encouraged by the misuse of antibiotics, particularly when antibiotics are used, even when they are not the recommended course of therapy. The Centers for Disease Control and Prevention estimate that between one-third and half of all antibiotic usage in humans is unwarranted or improper. Viral pathogens are the primary cause of respiratory tract infections (RTI) in children compared to adults. Interestingly, compared to adults with RTI, very little is known regarding the usage of antibiotics in children.

Detection of Mycoplasma sp using next-generation DNA sequencing is common on nasal swabs from both healthy and unhealthy pet rabbits (Oryctolagus cuniculus).

Upper respiratory infections are a frequent problem in pet rabbits and rodents, and Mycoplasma pulmonis is 1 of the most common causes of respiratory infections in pet rats. M pulmonis was detected in 1967 in laboratory rabbits via culture of the nares and oropharynx, but overall, Mycoplasma is not commonly identified in the upper airway of rabbits. The objective of this study was to compare the prevalence of Mycoplasma sp detection via next-generation DNA sequencing on nasal swabs obtained from healthy and unhealthy rabbits. The results of nasal swabs from both healthy and unhealthy rabbits submitted for next-generation DNA sequencing from January 2022 to February 2023 were reviewed. Data gathered included signalment, whether or not Mycoplasma sp was detected, and the cell count and relative predominance of Mycoplasma sp compared to other organisms. 91 rabbits met the inclusion criteria, of which 49 were healthy and 42 were unhealthy. Overall, 52 of 91 (57.1%) rabbits were positive and 39 of 91 (42.8%) were negative for Mycoplasma sp. Mycoplasma positivity was significantly (P < .001) more common in healthy rabbits (37/49 [75.5%]) compared to unhealthy rabbits (15/42 [35.7%]). The fact that Mycoplasma positivity was common in both groups of rabbits, and particularly common in rabbits without upper respiratory signs, suggests that Mycoplasma may be normal nasal flora in rabbits. Further research is needed to determine whether Mycoplasma could function as an opportunistic pathogen in rabbits.

Establishment and evaluation of MIRA-qPCR assay for the rapid and sensitively detection of Mycoplasma pneumoniae.

Aim: Mycoplasma pneumoniae (MP) is a common cause of respiratory infections, and its incidence has increased post-COVID-19 due to "immune debt." Real-time quantitative polymerase chain reaction (qPCR) is the standard for detecting MP, but it has a lengthy detection time. This study aimed to establish a highly sensitive rapid detection method for MP.Materials & methods: We developed an integrated assay combining multienzyme isothermal rapid amplification (MIRA) with qPCR, referred to as MIRA-qPCR, for the rapid detection of MP, delivering results within approximately 40min.Results: The analytic sensitivity of the MIRA-qPCR assay was 10copies per reaction, and it exhibited no cross-reactivity with other respiratory pathogens, ensuring high specificity. Clinical sample analysis demonstrated higher sensitivity for MIRA-qPCR compared to qPCR reported in the literature, and 100% concordance with commercial qPCR kit.Conclusion: The MIRA-qPCR method established in this study is a promising tool for the clinical detection of MP, offering significant advantages for the rapid diagnosis of MP infections.

Antigenic analysis of the influenza B virus hemagglutinin protein

Influenza B viruses (IBVs) primarily infect humans and are a common cause of respiratory infections in humans. Here, to systematically analyze the antigenicity of the IBVs Hemagglutinin (HA) protein, 31 ​B/Victoria and 19 ​B/Yamagata representative circulating strains were selected from Global Initiative of Sharing All Influenza Data (GISAID), and pseudotyped viruses were constructed with the vesicular stomatitis virus system. Guinea pigs were immunized with three doses of vaccines (one dose of DNA vaccines following two doses of pseudotyped virus vaccines) of the seven IBV vaccine strains, and neutralizing antibodies against the pseudotyped viruses were tested. By comparing differences between various vaccine strains, we constructed several pseudotyped viruses that contained various mutations based on vaccine strain BV-21. The vaccine strains showed good neutralization levels against the epidemic virus strains of the same year, with neutralization titers ranging from 370 to 840, while the level of neutralization against viruses prevalent in previous years decreased 1–10-fold. Each of the high-frequency epidemic strains of B/Victoria and B/Yamagata not only induced high neutralizing titers, but also had broadly neutralizing effects against virus strains of different years, with neutralizing titers ranging from 1000 to 7200. R141G, D197 ​N, and R203K were identified as affecting the antigenicity of IBV. These mutation sites provide valuable references for the selection and design of a universal IBV vaccine strain in the future.

Patterns and Influencing Factors of Organisms and Sensitivity in Sputum at Sylhet

Background: Respiratory tract infections, especially pneumonia and tuberculosis, remain significant public health problems in Bangladesh. This information alone is critical to manage local pathogen distributions, antibiotic susceptibility, and response plans. Objectives: To evaluate the frequency of bacterial pathogens in sputum samples, test their antibacterial sensitivity, and relate them to various demographic factors among patients in Sylhet, Bangladesh. Methods: This cross-sectional study was carried out in the Chest Disease Clinic, Sylhet from January to June 2024.Sputum samples were taken from 120 patients diagnosed with lower respiratory tract infections. Colony and bacterial identification was done microbiologically, and antibiotic susceptibility was determined by using the Kirby-Bauer disk diffusion method. Results: The cocci were the most prevalent, with gram-positive bacteria constituting 75% of all isolates: Staphylococcus aureus 29. Co-amoxiclav had the highest sensitivity of 23 percent, while the highest resistance was recorded for linezolid at 50 percent. Tobacco use was described in 79. Overall, there was a significant association between TB-positive status and the isolation of Klebsiella pneumoniae (p = 0.032). Most participants were of lower SES, and this was observed in 59.32% of the study’s participants. Conclusions: This research found that gram-positive organisms are the most frequent cause of respiratory infections in Sylhet, with S. aureus being the most dominant isolate. The high tobacco use and the link to S. aureus colonization indicate that interventions could and should be targeted. Concerning antibiotic susceptibility patterns, the need to exercise reasonable use of antibiotics and constant monitoring of antimicrobial resistance cannot be overemphasized. These findings may help the local clinicians, help set up empirical antibacterial therapy, and facilitate the design of some targeted health interventions. Scholars Middle East Publishers Browse Journals Payments Publication Ethics SUBMIT ARTICLE

Identification of distinct genotypes in circulating RSV A strains based on variants in the virus replication-associated genes.

Respiratory syncytial virus (RSV) is a common cause of respiratory infection that often leads to hospitalization of infected younger children and older adults. RSV is classified into two strains, A and B, each with several subgroups or genotypes. One issue with the definition of these subgroups is the lack of a unified method of identification or genotyping. We propose that genotyping strategies based on the genes coding for replication-associated proteins could provide critical information on the replication capacity of the distinct subgroups, while clearly distinguishing genotypes. Here, we analyzed the virus replication-associated genes N, P, M2, and L from de novo assembled RSV A sequences obtained from 31 newly sequenced samples from hospitalized patients in Philadelphia and 78 additional publicly available sequences from different geographic locations within the United States. In-depth analysis and annotation of variants in the replication-associated proteins identified the polymerase protein L as a robust target for genotyping RSV subgroups. Importantly, our analysis revealed non-synonymous variations in L that were consistently accompanied by conserved changes in its co-factor P or the M2-2 protein, suggesting associations and interactions between specific domains of these proteins. Similar associations were seen among sequences of the related human metapneumovirus. These results highlight L as an alternative to other RSV genotyping targets and demonstrate the value of in-depth analyses and annotations of RSV sequences as it can serve as a foundation for subsequent in vitro and clinical studies on the efficiency of the polymerase and fitness of different virus isolates.IMPORTANCEGiven the historical heterogeneity of respiratory syncytial virus (RSV) and the disease it causes, there is a need to understand the properties of the circulating RSV strains each season. This information would benefit from an informative and consensus method of genotyping the virus. Here, we carried out a variant analysis that shows a pattern of specific variations among the replication-associated genes of RSV A across different seasons. Interestingly, these variation patterns, which were also seen in human metapneumovirus sequences, point to previously defined interactions of domains within these genes, suggesting co-variation in the replication-associated genes. Our results also suggest a genotyping strategy that can prove to be particularly important in understanding the genotype-phenotype correlation in the era of RSV vaccination, where selective pressure on the virus to evolve is anticipated. More importantly, the categorization of pneumoviruses based on these patterns may be of prognostic value.

Emerging Methods in the Identification of Bacterial Respiratory Tract Pathogens.

Here, we will review different bacterial causes of respiratory tract infections and discuss the available diagnostic methods. Moreover, we will provide some recently published patents and newer techniques, such as respiratory panels and omics approaches, and express the challenges in this path. Respiratory tract infections (RTIs) include those infections that can lead to the involvement of different respiratory parts, including the sinuses, throat, airways, and lungs. Acute respiratory tract infection is the leading cause of death from infectious illnesses worldwide. According to the World Health Organization, 1.6 to 2.2 million deaths have occurred due to acute respiratory infections in children under five years of age. About 4 million people die annually from respiratory infections, 98% of which are caused by lower respiratory infections. Depending on the type of pathogen, the severity of the infection can vary from mild to severe and even cause death. The most important pathogens involved in respiratory tract infections include Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The symptoms are often similar, but the treatment can vary greatly. Therefore, correct diagnosis is so important. There are several methods for diagnosing respiratory infections. Traditional tests include the culture of respiratory samples, considered the primary tool for diagnosing respiratory infections in laboratories, and less common standard tests include rapid and antigenic tests. It is essential to think that the culture method is reliable. In the original method of diagnosing respiratory infections, some bacteria were challenging to grow successfully, and many clinical laboratories needed to be equipped for viral cultures. Another issue is the time to get the results, which may take up to 7 days. Rapid and antigenic tests are faster but need to be more accurate. The clinical laboratories are trying to be equipped with molecular methods for detecting respiratory pathogens and identifying the genetic material of the infectious agent in these new methods as the primary method in their agenda.

Immune Response to Respiratory Syncytial Virus

Abstract Respiratory syncytial virus (RSV) is an important cause of respiratory infection among children and infants globally. The first line of the immune response against this virus is neutrophils, macrophages, and innate lymphoid cells. Antigen-presenting cells such as dendritic cells which present the viral antigen to T lymphocytes that mediate viral clearance by T cytotoxic cells and initiate systemic lymphopenia. Humoral immunity will also be stimulated through B-cell-stimulating factors derived from epithelial cells of the respiratory tract that play an important factor in antibody production and induction memory to reinfection through IgG and IgA protective antibodies that are useful in vaccine production.

Cost-Effectiveness Analysis of Maternal Respiratory Syncytial Virus Vaccine in Protecting Infants from RSV Infection in Japan.

Respiratory syncytial virus (RSV) is one of the major causes of respiratory tract infections among children. Until recently, the monoclonal antibody palivizumab was the only RSV prophylaxis available in Japan. In 2024, the bivalent RSV prefusion F protein-based (RSVpreF) vaccine was approved for the prevention of RSV infection in infants by active immunization of pregnant women. In this study, we assessed the cost-effectiveness of a combined strategy of RSVpreF vaccine and palivizumab in Japanese setting. Using a Markov model, we evaluated prevented cases and deaths of medically attended RSV infections from birth to age 11months for each of the three healthcare settings: inpatient (hospitalization), emergency department visits, and outpatient visits. Incremental cost-effectiveness ratios (ICERs) were calculated from economic outcomes (intervention costs, medication costs, and productivity losses) and quality-adjusted life years (QALYs). Further, we calculated the maximum price of RSVpreF vaccine within which the program would be cost-effective. In comparison with the current prophylaxis (palivizumab alone), a combined prophylaxis of year-round RSVpreF vaccination of pregnant women and palivizumab prescription for premature infants born in < 32weeks gestational age (wGA) and all infants with high risk prevented 14,382 medically attended cases of RSV (hospitalization, 7490 cases; emergency department, 2239 cases; outpatient, 4653 cases) and 7 deaths, respectively. From a healthcare payer perspective, when the price of RSVpreF vaccine was equal to or less than ¥23,948 (US$182), a combination prophylaxis was cost-effective under the ICER threshold of ¥5million per QALY. The other combination prophylaxis of year-round RSVpreF vaccination and palivizumab prescription of premature born in < 32wGA regardless of risk in infants was a dominant strategy (more effective and less costly). A combined prophylaxis of year-round RSVpreF vaccine and palivizumab could be a cost-effective strategy to protect neonates throughout the infant stage (< 1years old) in Japan.

Epidemiology of respiratory syncytial virus in hospitalized children over a 9-year period and preventive strategy impact.

Background: Respiratory Syncytial Virus (RSV) is the primary cause of respiratory infections and hospitalizations in young children globally, leading to substantial disease burden and mortality. The aim of the present study was to review and provide updates on how the SARS-CoV-2 pandemic have significantly influenced RSV epidemiology on hospitalized children due to RSV infection. A potential impact of the available preventive strategies on the same population were provided. Methods: All children aged 0-6years hospitalized at Meyer Children's Hospital IRCCS for RSV infection from September 2014 to March 2023 were retrospectively recorded. Seasonal trends before and after SARS-CoV-2 pandemic, age distribution, ICU admission and co-infections, comorbidities and prematurity were retrieved. Predictions on the number of hospitalizations avoided by the deployment of different preventive strategies were provided. Results: A total of 1,262 children with RSV infection were included in the study. The 70% of them had less than 1 year-of-age at the moment of hospitalization and almost 50% less than 3months. In the post-pandemic seasons, a 317% increase in the number of hospitalizations was recorded with a significant increase in older children compared to the pre-pandemic seasons. ICU support was required for 22% of children, the majority of whom were under 3months of age. Almost 16% of hospitalized children were born preterm and only 27% of hospitalized children had prior comorbidities. The rate of comorbidities among RSV hospitalized children increased with age. Nirsevimab prophylaxis could have prevented more than 46% of hospitalizations in this cohort. A preventive strategy addressing also children aged 7months to 6years of age with co-existing comorbidities would increase that rate above 57%. Discussion: The identification of RSV hospitalization-related features is informing the decision-maker for the deployment of the wisest preventive approach on a population scale.

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 β-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.

Inhalation of 2, 4-di-tert-butylphenol-Loaded micelles suppresses respiratory syncytial virus infection in mice

Human respiratory syncytial virus (RSV) is a common cause of respiratory infections in infants, young children, and elderly people. However, there are no effective treatments or vaccines available in most countries. In this study, we explored the anti-RSV potential of 2, 4-Di-tert-butylphenol (2, 4-DTBP), a compound derived from Houttuynia cordata Thunb. To overcome the poor solubility of 2, 4-DTBP, we encapsulated it in polymeric micelles and delivered it by inhalation. We found that 2, 4-DTBP-loaded micelles inhibited RSV infection in vitro and improved survival, lung pathology, and viral clearance in RSV-infected mice. Our results suggested that 2, 4-DTBP-loaded micelle is a promising novel therapeutic agent for RSV infection.

الكشف عن بعض عوامل الضراوة بين المبيضات المعزولة من المرضى وانتشار جين candidalysin ECE1

المبيضات البيضاء هي مسبب شائع لعدوى الجهاز التنفسي وداء المبيضات الفموي لدى الناس ، ومسببات أمراض الخميرة الانتهازية والأسباب الرئيسية للمرض والوفيات لدى الأشخاص الذين يعانون من نقص المناعة وتسبب التهابات سطحية على الأسطح المخاطية التي تصيب ملايين الأشخاص في جميع أنحاء العالم. كان الهدف الرئيسي من هذه الدراسة هو التحقق من انتشار بعض عوامل الضراوة التي لها القدرة على تكوين الأغشية الحيوية (Biofilm)، والبروتينيز (Proteinase)، وإنتاج الهيمولايسين( Hymolysine) بين عزلات C. albicans التي تشمل انتشار جين Candidalysin (ECE1). تم جمع العينات خلال الفترة من ايار 2022 الى اب 2022 من 280 عينة (مسحة) لمرضى عراقيين من مختلف الاعمار والاجناس غير مكررين كانوا يعانون من داء المبيضات الفموي وامراض الجهاز التنفسي في مستشفيات بغداد (مستشفى مدينه الطب و مستشفى اليرموك التعليمي ومستشفى مدينه الامامين الطبية التعليمية). تم زراعة العينات التي تم جمعها على وسط اكار السابرويد دكستروز (SDA) مضاف اليه كلورامفينيكول كمضاد للبكتيريا بتركيز 10 ميكجم / مل ، وتم حضن الاطباق الملقحة على وسط SDA عند 37 درجة مئوية لمدة تتراوح بين 24-48 ساعة.أظهرت نتائج الاستنبات أن 102 عينة كانت موجبه، منها58 (56.86%) من تجويف الفم و 44 (43.14%) من الجهاز التنفسي، بينما 178 منها كانت سالبة , تم الكشف عن عزلات المبيضات باستخدام الطرق التقليدية والتي تشمل (النمو على وسط HiCrome Candida ، إنتاج الأنبوب الجرثومي Germ tube ، تكوين الابواغ الكلاميديه Clamydospore وتم تأكيد نتئج التعريف باستخدام نضام VITEK-2 بينت النتائج ان من بين 102 عزلة C. albicans هي الاكثر شيوعا بين الانواع بنسبة 68.63 % ثم تلتها C. tropicalis بنسبة %10.78 ثم C. kruzei %5.88 وC. kefyr %5.88 C. parapsilosis % 4.9 بينما كانت C. glabrata % 3.9 وتمثل النسبة الاقل بين الانواع . تم فحص حساسية عزلات المبيضات للأدوية المضادة للفطريات بطريقة انتشار القرص ، والتي أجريت على النحو الموصى به بواسطة(CLSI) M44-A -وثيقة . أظهرت العزلات درجة عالية من الحساسية للأمفوتريسين-ب 93.14% وكلوتريمازول 90.20% ونسياتين 85.92% ،تم التحقق من انتشار جينCandidalysin (ECE1) بين 70 عزلة من C. albicans باستخدام تقنية تفاعل البلمرة المتسلسل PCR ، وأظهرت النتائج أن 41 58.57% تحتوي على جين Ece1 في تجويف الفم والجهاز التنفسي. و 34 عزلة 48.57% من C. albicans كانت منتجة قوية للغشاء الحيوي, بينما 30 عزلة 42.86% عزلة انتجت بروتيناز و 20 عزلة 28.57% عزلة لديها القدرة على تحلل الدم.