Influenza Research Articles

Role of Biosecurity Measures in Controlling Infectious Diseases in Poultry Farms in Thailand

Purpose: To aim of the study was to analyze the role of biosecurity measures in controlling infectious diseases in poultry farms in Thailand. Methodology: This study adopted a desk methodology. A desk study research design is commonly known as secondary data collection. This is basically collecting data from existing resources preferably because of its low cost advantage as compared to a field research. Our current study looked into already published studies and reports as the data was easily accessed through online journals and libraries. Findings: In Thailand, stringent biosecurity measures are pivotal in curbing infectious diseases in poultry farms. These measures, including controlled farm access, equipment disinfection, waste management, and quarantine protocols for new birds, effectively reduce the incidence and transmission of diseases like avian influenza and Newcastle disease. Government regulations and industry support bolster these efforts, emphasizing collaboration to ensure robust disease prevention. Challenges such as cost constraints and varying compliance levels underscore the ongoing need for innovation and improved practices to safeguard the poultry industry and ensure sustainable production. Unique Contribution to Theory, Practice and Policy: Health belief model (HBM), systems theory & social cognitive theory (SCT) may be used to anchor future studies on role of biosecurity measures in controlling infectious diseases in poultry farms in Thailand. Practice-oriented contributions emphasize ongoing training programs for farm workers and stakeholders to ensure effective implementation and compliance with biosecurity protocols. Biosecurity practices contribute to policy development by informing the formulation of regulatory standards and guidelines that mandate minimum biosecurity requirements for poultry farms.

Host Innate Antiviral Response to Influenza A Virus Infection: From Viral Sensing to Antagonism and Escape.

Influenza virus possesses an RNA genome of single-stranded, negative-sensed, and segmented configuration. Influenza virus causes an acute respiratory disease, commonly known as the "flu" in humans. In some individuals, flu can lead to pneumonia and acute respiratory distress syndrome. Influenza A virus (IAV) is the most significant because it causes recurring seasonal epidemics, occasional pandemics, and zoonotic outbreaks in human populations, globally. The host innate immune response to IAV infection plays a critical role in sensing, preventing, and clearing the infection as well as in flu disease pathology. Host cells sense IAV infection through multiple receptors and mechanisms, which culminate in the induction of a concerted innate antiviral response and the creation of an antiviral state, which inhibits and clears the infection from host cells. However, IAV antagonizes and escapes many steps of the innate antiviral response by different mechanisms. Herein, we review those host and viral mechanisms. This review covers most aspects of the host innate immune response, i.e., (1) the sensing of incoming virus particles, (2) the activation of downstream innate antiviral signaling pathways, (3) the expression of interferon-stimulated genes, (4) and viral antagonism and escape.

Combatting Antibiotic Resistance: Identifying Gaps in Knowledge, Attitude, and Practice Among Medical Interns.

Antibiotic resistance presents a significant global health threat to modern medicine. The awareness and attitude of future doctors undergoing training may play a crucial role in addressing this important issue, influencing the control of resistance and promoting responsible antibiotic stewardship. This study aimed to estimate knowledge, attitudes, and practices regarding antibiotic usage and antimicrobial resistance among tertiary care teaching hospital medical interns. The questionnaire-based cross-sectional study was conducted on 123 MBBS interns from multiple medical institutions. Intern's knowledge, attitudes, and self-reported practices regarding antibiotic use were recorded. Based on survey responses from 123 participants, 116 (94.31%) were aware of the adverse effects of indiscriminate antibiotic use, recognizing the risks of ineffective treatment, increased adverse effects, prolonged illness, bacterial resistance, and higher medical costs. Most (106, 86.18%) acknowledged the challenges of treating antibiotic-resistant infections, and 69 (56.10%) correctly identified that bacteria are not a cause of the common cold and flu. Most (115, 93.5%) recognized antibiotic resistance as a significant global health problem. In attitude, 90 (73%) believed antibiotics should be avoided for colds, but 80 (65%) thought they hastened fever recovery. Only 48 (39%) recognized that antibiotics contribute to resistance, while 102 (83%) agreed skipping doses fosters resistance. Most support hospital policies (118, 96%) and curriculum courses (112, 91%) for rational antibiotic use.Regarding practice, 12 (9.76%) interns admitted to overusing antibiotics, 68 (55.28%) consulted a doctor before starting antibiotics, and 87 (70.73%) checked expiry dates. Additionally, 62 (50.41%) preferred antibiotics for cough and sore throat symptoms. The study highlights that while interns have a good knowledge and awareness of the harms of antibiotic misuse, they are not translating this knowledge into practice. This indicates a disconnect between understanding and application. Therefore, there is a need to add a rational antibiotic prescription and stewardship module to the medical curriculum to ensure that knowledge is effectively translated into changing beliefs and practices.

Supplementation of Azolla microphylla Flour in Broiler Feed Increases Antibody Titers against Avian Influenza and Newcastle Disease

This study aimed to determine the level of protection provided by supplementation of Azolla microphylla flour in broiler feed against the antibody titers profile of Avian Influenza and Newcastle Disease. The research was conducted over two months (July-August 2021) at the broiler unit of the Integrated Field Laboratory, Faculty of Agriculture, University of Lampung. The experimental design was a Completely Randomized Design with four treatments and five replications. Each replication consisted of five Cobb CP707 strain broilers, resulting in 100 broilers. Azolla microphylla flour supplementation in the feed was administered at different doses: P0=100% commercial feed (control); P1=97.5% commercial feed + 2.5% Azolla microphylla flour; P2=95% commercial feed + 5% Azolla microphylla flour; P3=92.5% commercial feed + 7.5% Azolla microphylla flour. Serum samples were collected from 30-day-old broilers, with one sample taken from each replication, totalling 20 samples. The samples were analyzed for Avian Influenza and Newcastle Disease antibody titers at AGRILab Vaksindo Laboratory using the Hemagglutination Inhibition test. Each treatment's antibody titer data for Avian Influenza and Newcastle Disease were tabulated and presented in histograms to facilitate descriptive analysis. Antibody titers (log2 X) of Avian Influenza 4.00±0.71 and Newcastle Disease 4.60±2.07 from P2 were included in the protection level based on the WOAH Standard. The study concluded that supplementing 5% Azolla microphylla flour in broiler feed increases the antibody titers against Avian Influenza and Newcastle Disease to protective levels.

Anti-Influenza A Potential of Tagetes erecta Linn. Extract Based on Bioinformatics Analysis and In Vitro Assays.

Tagetes erecta Linn. (TE) is traditionally used to treat cardiovascular, renal, and gastrointestinal diseases. In this study, we investigated the active compounds and targets of TE extract that may exert antiviral effects against influenza A. Active compounds and targets of TE extract were identified using the Traditional Chinese Medicine Systems Pharmacology database (TCSMP). The influenza A-related gene set was screened using GeneCards and the Kyoto Encyclopedia of Genes and Genomes (KEGG). A protein-protein interaction (PPI) network was built to establish the hub targets. Pathway and target studies were conducted using Gene Expression Omnibus (GEO). The interactions between active compounds and potential targets were assessed by molecular docking. An in vitro study was performed using antiviral and plaque reduction assays. From the compound and target search, we identified 6 active compounds and 95 potential targets. We retrieved 887 influenza-associated target genes and determined 14 intersecting core targets between TE and influenza. After constructing a compound-target network, we discovered lutein and beta-carotene to be the key compounds. Next, PPI network analysis identified the top three hub genes associated with influenza (IL-6, HIF1A, and IL-1β). Similarly, GEO analysis revealed IL-6, TGFB1, and CXCL8 to be the top three target genes. In our docking study, we identified that lutein and IL-6 had the strongest bindings. Our in vitro experimental results revealed that the TE extract exhibited therapeutic rather than prophylactic effects on influenza disease. We identified lutein as a main active compound in TE extract, and IL-6 as an important target associated with influenza, by using data mining and bioinformatics. Our in vitro findings indicated that TE extract exerted protective properties against the influenza A virus. We speculated that lutein, as a key active component in TE extract, is largely responsible for its antiviral effects. Therefore, we suggest TE extract as an alternative in the treatment of influenza.

Vaccinations, cardiovascular drugs, hospitalization, and mortality in COVID-19 and Long COVID

ObjectiveTo identify highest-risk subgroups for COVID-19 and Long COVID(LC), particularly in contexts of influenza and cardiovascular disease(CVD). MethodsUsing national, linked electronic health records for England (NHS England Secure Data Environment via CVD-COVID-UK/COVID-IMPACT Consortium), we studied individuals (of all ages) with COVID-19 and LC (2020-2023). We compared all-cause hospitalization and mortality by prior CVD, high CV risk, vaccination status (COVID-19/influenza), and CVD drugs, investigating impact of vaccination and CVD prevention using population preventable fractions. ResultsHospitalization and mortality were 15.3% and 2.0% among 17,373,850 individuals with COVID-19 (LC rate 1.3%), and 16.8% and 1.4% among 301,115 with LC. Adjusted risk of mortality and hospitalization were reduced with COVID-19 vaccination ≥ 2 doses(COVID-19:HR 0.36 and 0.69; LC:0.44 and 0.90). With influenza vaccination, mortality was reduced, but not hospitalization (COVID-19:0.86 and 1.01, and LC:0.72 and 1.05). Mortality and hospitalization were reduced by CVD prevention in those with CVD, e.g., anticoagulants- COVID:19:0.69 and 0.92; LC:0.59 and 0.88; lipid lowering- COVID-19:0.69 and 0.86; LC:0.68 and 0.90. COVID-19 vaccination averted 245044 of 321383 and 7586 of 8738 preventable deaths after COVID-19 and LC, respectively. InterpretationPrior CVD and high CV risk are associated with increased hospitalization and mortality in COVID-19 and LC. Targeted COVID-19 vaccination and CVD prevention are priority interventions. FundingNIHR. HDR UK.

Assessing population-level target product profiles of universal human influenza A vaccines

Influenza A has two hemagglutinin groups, with stronger cross-immunity to reinfection within than between groups. Here, we explore the implications of this heterogeneity for proposed cross-protective influenza vaccines that may offer broad, but not universal, protection. While the development goal for the breadth of human influenza A vaccine is to provide cross-group protection, vaccines in current development stages may provide better protection against target groups than non-target groups. To evaluate vaccine formulation and strategies, we propose a novel perspective: a vaccine population-level target product profile (PTPP). Under this perspective, we use dynamical models to quantify the epidemiological impacts of future influenza A vaccines as a function of their properties. Our results show that the interplay of natural and vaccine-induced immunity could strongly affect seasonal subtype dynamics. A broadly protective bivalent vaccine could lower the incidence of both groups and achieve elimination with sufficient vaccination coverage. However, a univalent vaccine at low vaccination rates could permit a resurgence of the non-target group when the vaccine provides weaker immunity than natural infection. Moreover, as a proxy for pandemic simulation, we analyze the invasion of a variant that evades natural immunity. We find that a future vaccine providing sufficiently broad and long-lived cross-group protection at a sufficiently high vaccination rate, could prevent pandemic emergence and lower the pandemic burden. This study highlights that as well as effectiveness, breadth and duration should be considered in epidemiologically informed TPPs for future human influenza A vaccines.

Efficiency of Recycled Plastic Bedding Material and Gender in Improvement of Productive Traits, Physiological, and Immunological Parameters of Hybrid Broiler Chickens

Litter management is important for poultry housing husbandry and affects chicken performance. The present study evaluated the effect of bedding material and gender on the productive, physiological, and immunological performance of a new hybrid chicken (WINZY Line 105) under cold stress for 56 days of age. A total of 540 one-day-old broiler chicks were divided into two groups. The groups, including 270 males (M) and 270 females (F) were further divided into two sub-groups, including sawdust litter (SL) and plastic slatted floor (PSF), three replicates, and 45 chickens each. Broiler chickens were raised during the winter with an average temperature of 10oC for 56 days. Productive, physiological, and immunological performance parameters were measured. The obtained results indicated that M reared on PSF (M x PSF) recorded the highest values in body weight (BW), body weight gain (BWG), carcass characteristics, and the best values in feed conversion compared with other interaction groups during all experimental periods. In addition, F reared on PSF had higher BW, carcass, and thigh percentages, low feed intake (FI), and best feed conversion compared to females reared on SL. The M reared on PSF had the highest hepatic enzymes except AST which was higher in F reared on PSF than other treatments. However, renal function biomarkers (Creatine, Uric acid, Urea) were higher in both M and F that were reared on SL than those reared on PSF. Moreover, there was a significant interaction detected for antibody titters against avian influenza (H5) and Newcastle disease at 21 days of age suggesting that the highest values observed for M reared on PSF (M x PSF) compared with other interaction groups during the experimental period, and it was higher in F that reared on PSF than F reared on SL at 21 days of age. It can be concluded that plastic slatted floors could be an alternative to substitute wood shavings to raise broiler chickens since it was efficient from the perspective of environmental conditions and production rates.

Brain region-specific alterations in gene expression trajectories in the offspring born from influenza A virus infected mice

Influenza A virus (IAV) infection during pregnancy can increase the risk for neurodevelopmental disorders in the offspring, however, the underlying neurobiological mechanisms are largely unknown. To recapitulate viral infection, preclinical studies have traditionally focused on using synthetic viral mimetics, rather than live IAV, to examine consequences of maternal immune activation (MIA)-dependent processes on offspring. In contrast, few studies have used live IAV to assess effects on global gene expression, and none to date have addressed whether moderate IAV, mimicking seasonal influenza disease, alters normal gene expression trajectories in different brain regions across different stages of development. Herein, we show that moderate IAV infection during pregnancy, which causes mild maternal disease and no overt foetal complications in utero, induces lasting effects on the offspring into adulthood. We observed behavioural changes in adult offspring, including disrupted prepulse inhibition, dopaminergic hyper-responsiveness, and spatial recognition memory deficits. Gene profiling in the offspring brain from neonate to adolescence revealed persistent alterations to normal gene expression trajectories in the prefronal cortex, hippocampus, hypothalamus and cerebellum. Alterations were found in genes involved in inflammation and neurogenesis, which were predominately dysregulated in neonatal and early adolescent offspring. Notably, late adolescent offspring born from IAV infected mice displayed altered microglial morphology in the hippocampus. In conclusion, we show that moderate IAV during pregnancy perturbs neurodevelopmental trajectories in the offspring, including alterations in the neuroinflammatory gene expression profile and microglial number and morphology in the hippocampus, resulting in behavioural changes in adult offspring. Such early perturbations may underlie the vulnerability in human offspring for the later development of neurodevelopmental disorders, including schizophrenia. Our work highlights the importance of using live IAV in developing novel preclinical models that better recapitulate the real-world impact of inflammatory insults during pregnancy on offspring neurodevelopmental trajectories and disease susceptibility later in life.

Influenza virus infection exacerbates gene expression related to neurocognitive dysfunction in brains of old mice

BackgroundAge > 65 years is a key risk factor for poor outcomes after human influenza infection. Specifically, in addition to respiratory disease, non-neurotropic influenza A virus (IAV) causes neuro-cognitive complications, e.g. new onset depression and increases the risk of dementia after hospitalization. This study aimed to identify potential mechanisms of these effects by determining differences between young and old mice in brain gene expression in a mouse model of non-neurotropic IAV infection.MethodsYoung (12 weeks) and old (70 weeks) C57Bl/6J mice were inoculated intranasally with 200 PFU H1N1 A/PR/34/8 (PR8) or sterile PBS (mock). Gene expression in lung and brain was measured by qRT-PCR and normalized to β-actin. Findings were confirmed using the nCounter Mouse Neuroinflammation Array (NanoString) and analyzed with nSolver 4.0 and Ingenuity Pathway Analysis (IPA, Qiagen).ResultsIAV PR8 did not invade the central nervous system. Young and old mice differed significantly in brain gene expression at baseline and during non-neurotropic IAV infection. Expression of brain Ifnl, Irf7, and Tnf mRNAs was upregulated over baseline control at 3 days post-infection (p.i.) only in young mice, but old mice expressed more Ifnl than young mice 7 days p.i. Gene arrays showed down-regulation of the Epigenetic Regulation, Insulin Signaling, and Neurons and Neurotransmission pathways in old mice 3 days p.i. while young mice demonstrated no change or induction of these pathways at the same time point. IPA revealed marked baseline differences between old and young mice. Gene expression related to Cognitive Impairment, Memory Deficits and Learning worsened in old mice relative to young mice during IAV infection. Aged mice demonstrate more severe changes in gene expression related to memory loss and cognitive dysfunction by IPA.ConclusionsThese data suggest the genes and pathways related to learning and cognitive performance that were worse at baseline in old mice were further worsened by IAV infection, similar to old patients. Early events in the brain triggered by IAV infection portend downstream neurocognitive pathology in old adults.

Sustained release system from PLGA particles co-encapsulated with inactivated influenza virus with natural killer T cell agonist α-galactosylceramide

Vaccines against influenza and many other infectious diseases require multiple boosters in addition to the primary dose to improve efficacy, but this approach is not ideal for compliance. The multiple doses could potentially be replaced by sustained or pulsatile release of antigens encapsulated in degradable microparticles (MPs). The efficacy of a vaccine is improved by adding an adjuvant, which can be co-delivered from the particles to enhance immunogenicity. Here, we developed degradable poly-lactic-co-glycolic acid (PLGA) (7–17 kDa) MPs capable of sustained release of ultraviolet killed influenza virus (A/PR/8/34) (kPR8) vaccine and the natural killer T (NKT) cell agonist alpha-galactosylceramide (α-GalCer) and tested their effectiveness at providing long-term protection against influenza virus infection in mice. Multiple formulations were developed for encapsulating the virus and adjuvant separately, and in combination. The MPs exhibited sustained release of both the virus and the adjuvant lasting more than a month. Co-encapsulation significantly increased the encapsulation efficiency (EE) of the vaccine but reduced the release duration. On the other hand, co-encapsulation led to a reduction in EE for the α-GalCer and a change in release profile to a higher initial burst followed by a linear release compared to a low initial burst and slower linear release. The α-GalCer also had considerably longer release duration compared to the vaccine. Mice injected with particle formulations co-encapsulating kPR8 and α-GalCer were protected from a lethal influenza virus infection 30 weeks after vaccination. This study demonstrates that PLGA MP based vaccines are promising for providing effective vaccination and possibly for replacing multiple doses with a single injection.

Large-Scale Serological Survey of Influenza A Virus in South Korean Wild Boar (Sus scrofa).

In this comprehensive large-scale study, conducted from 2015 to 2019, 7,209 wild boars across South Korea were sampled to assess their exposure to influenza A viruses (IAVs). Of these, 250 (3.5%) were found to be IAV-positive by ELISA, and 150 (2.1%) by the hemagglutination inhibition test. Detected subtypes included 23 cases of pandemic 2009 H1N1, six of human seasonal H3N2, three of classical swine H1N1, 13 of triple-reassortant swine H1N2, seven of triple-reassortant swine H3N2, and seven of swine-origin H3N2 variant. Notably, none of the serum samples tested positive for avian IAV subtypes H3N8, H5N3, H7N7, and H9N2 or canine IAV subtype H3N2. This serologic analysis confirmed the exposure of Korean wild boars to various subtypes of swine and human influenza viruses, with some serum samples cross-reacting between swine and human strains, indicating potential infections with multiple IAVs. The results highlight the potential of wild boar as a novel mixing vessel, facilitating the adaptation of IAVs and their spillover to other hosts, including humans. In light of these findings, we recommend regular and frequent surveillance of circulating influenza viruses in the wild boar population as a proactive measure to prevent potential human influenza pandemics and wild boar influenza epizootics.

Effects of Allicin on the Immune Performance and Expression of Immune-related Genes in Muchuan Black-bone Chickens

Background: In response to China’s ban on medicinal feed additives with growth-promoting functions in livestock and poultry feed, there is an urgent need in modern animal husbandry for alternatives to antibiotics to sustain livestock health and improve feed conversion efficiency. Allicin, known for its safety, efficiency, lack of drug resistance and absence of residue, regulates the intestinal flora structure; inhibits the growth of harmful bacteria; improves intestinal health, immunity and stress resistance; and improves animal production. Methods: To investigate the impact of allicin on immune performance and immune-related gene expression in Muchuan black-bone chickens, diets were supplemented with varying allicin levels (50, 100, 200 mg/kg), designated as test groups A, B and C, respectively. Initially, growth performance was assessed. Subsequently, immunoglobulins were measured via enzyme-linked immunosorbent assay (ELISA) and colorimetry; immune titers for avian influenza and Newcastle disease were evaluated using hemagglutination and hemagglutination inhibition tests and the expression of immune genes was analyzed via real-time quantitative PCR. Finally, serum biochemical indices in each group were determined. Result: Compared to the control group, allicin supplementation resulted in increased average fasting body weight in the experimental group and significantly (P less than 0.05) higher thymus and musogastric indices in groups A and C, respectively. Serum levels of immunoglobulin M in groups A and B and immunoglobulin G levels were significantly higher in all experimental groups than in controls. Antibody titers against avian influenza H5 and H7 strains were higher in all test groups, with Newcastle disease antibody titers in groups B and C significantly higher than those in controls. The mRNA expression levels of IFN-ã were lower across all experimental groups, whereas the expression levels of TLR3 in groups B and C and TLR15 in group B were higher. Serum levels of triglycerides in group A were significantly higher and blood urea nitrogen levels were significantly lower in groups B and C than in controls. These findings indicate that dietary allicin (50-200 mg/kg) significantly improves growth performance, immunity and protein and lipid metabolism in Muchuan black-bone chickens, offering valuable data for the development and use of allicin as an antibiotic alternative.

Predictors of parental acceptance to live attenuated influenza vaccine for children

ABSTRACT To determine the influencing factors of Chinese parents' intention and behavior for children to receive live attenuated influenza vaccine during the 2022–2023 influenza season. A theoretical model was developed and included seven constructs, and structural equation modeling was used to test 11 hypotheses. From October 2022 to December 2023, a survey was conducted across 38 medical institutions in four Chinese cities and their subordinate districts, counties, and rural areas. Parents who accompanied their children for vaccinations were selected through a randomization process based on their child’s medical card numbers. Measures were taken to minimize method bias, including a diverse geographical representation and random sampling. The survey resulted in the collection of 936 valid responses, exceeding the recommended sample size for structural equation model analysis and providing robust statistical inferences. During the study period, 936 respondents were included in the study. Perceived ease of use was verified to be a predictor of perceived usefulness and perceived value. Perceived usefulness was verified as a predictor of perceived value and behavioral intention. Knowledge was a significant antecedent of perceived value and risk perception of influenza disease. Risk perception of influenza disease was proved to be a significant predictor of perceived value and self-reported vaccination behavior. Perceived value significantly affected behavioral intention, and behavioral intention significantly affected self-reported vaccination behavior. Six demographic variables significantly moderate the theoretical models. The low vaccination coverage of live attenuated influenza vaccine (LAIV) among children in China suggests a need for a deeper understanding of the factors that influence vaccination rates. Particularly, effective strategies are necessary from policymakers and practitioners to elevate childhood LAIV coverage.

Review of Application YOLOv8 in Medical Imaging

Deep learning has revolutionized medical imaging analysis, with YOLOv8 emerging as a promising tool forvarious tasks like lesion detection, organ segmentation and disease classification. This review investigates YOLOv8’sapplications across diverse medical imaging modalities (X-Ray, CT-Scan and MRI). We conducted a systematic literaturesearch across databases like Pubmed, ScienceDirect and IEEE to identify relevant studies evaluating YOLOv8’sperformance in medical imaging analysis. YOLOv8 achieved high performance for meningioma and pituitary tumorswith and without data augmentation (precision >0.92, recall >0.90, mAP >0.93). Glioma detection showed lowerperformance but still promising results (precision >0.86, recall >0.81, mAP >0.86). Breast cancer detection with SGDoptimizer yielded best performance with an average mAP of 0.87 for mass detection. The model achieved high accuracyin detecting normal (mAP 0.939) and malignant lesions (mAP 0.911). YOLO v8 on Dental radiograph successfullydetected cavities, impacted teeth, fillings and implants (precision of >0.82, recall of >0.78 and F1-Score of >0.80). Lastly,for lung disease classification, YOLOv8 achieved high accuracy (99.8% training and 90% validation) in classifyingnormal, COVID-19, influenza and lung cancer disease. With the importance to improve clinical decision-making andpatient outcomes in healthcare, the YOLOv8 algorthm underscores the importance of pre-processing, augmentation andoptimization of key hyperparameters.

IBM Pemberdayaan Masyarakat dalam Penanganan Demam pada Anak dengan Water Tepid Sponge

Children under 5 years of age have an immune system that is still developing, not perfect and not yet strong. This is what causes children to be susceptible to disease. The diseases most frequently experienced by toddlers in Indonesia are flu, diarrhea, rotavirus, allergies, asthma, hand, foot and mouth disease and Fever. Fever is condition when the body temperature rises or is above normal. Efforts to treat fever by providing pharmacological and non-pharmacological therapy. Pharmacological therapy can be carried out by administering antipyretics, while non-pharmacological therapy includes Water Tepid Sponge. Increase knowledge is urgently needed to strengthen awareness in increasing knowledge and behavior in handling fever. One of the efforts made is health education activities about treating fever with Water Tepid Sponge. The result of this community service activity is that there is an increase in knowledge and skills regarding treating fever with Water Tepid Sponge before and after providing Health Education.

Isolation of human antibodies against influenza B neuraminidase and mechanisms of protection at the airway interface

Influenza B viruses (IBVs) comprise a substantial portion of the circulating seasonal human influenza viruses. Here, we describe the isolation of human monoclonal antibodies (mAbs) that recognized the IBV neuraminidase (NA) glycoprotein from an individual following seasonal vaccination. Competition-binding experiments suggested the antibodies recognized two major antigenic sites. One group, which included mAb FluB-393, broadly inhibited IBV NA sialidase activity, protected prophylactically invivo, and bound to the lateral corner of NA. The second group contained an active site mAb, FluB-400, that broadly inhibited IBV NA sialidase activity and virus replication invitro in primary human respiratory epithelial cell cultures and protected against IBV invivo when administered systemically or intranasally. Overall, the findings described here shape our mechanistic understanding of the human immune response to the IBV NA glycoprotein through the demonstration of two mAb delivery routes for protection against IBV and the identification of potential IBV therapeutic candidates.

EPIDEMIOLOGICAL ANALYSIS OF MORTALITY FROM INFLUENZA IN THE REPUBLIC OF CROATIA

Introduction: Influenza is an acute infectious disease of the respiratory system caused by one of the influenza viruses A, B or C, which inevitably appears every year in the form of larger or smaller epidemics, with a pronounced rapid spread within the population. A higher number of deaths occurs in the months when the epidemic lasts and is associated with an increased number of pneumonia, especially in older people.Objective: Analyze the mortality from influenza inthe Republic of Croatia and consider the connection of mortality with vaccination status.Subjects and methods: A retrospective cross -sectional epidemiological study was conducted between January and April 2024. Data on deaths from influenza between January 2014 and December 2023 were analyzedin the Republic of Croatia collected at the Service for Epidemiology of Infectious Diseases of the Croatian Institute of Public Health.Results: In the observed period in the Republic of Croatia, 65321 people fell ill with the flu, of which 227 reports had a fatal outcome caused by the flu infection. Among the deceased, 70 % are people aged 65 and older, and 20 % are people aged 30 to 65. On average, more male persons died, and 63 % of respondents were not vaccinated, 32 % of respondents did not know their vaccination status, and 5 % of them were vaccinated against influenza. Conclusion: In all flu seasons, we record the highest number of deaths in people aged 65 and older. Most of the deceased persons were not vaccinated against influenza.Keywords: Human Influenza, Mortality Rate, Epidemiology, Vaccination, Croatia, Prevention

MUC5AC: A potential biomarker of severity in pediatric patients infected with influenza.

Numerous factors can increase the risk of severe influenza; however, a majority of severe cases occur in previously healthy children. Identification of high-risk children is important for targeted preventive interventions and prompt treatment. The aim of this study was to evaluate MUC5AC as a biomarker for influenza disease severity in children. For this, aprospective cohort study was conducted in 2019. Children hospitalized with acute respiratory infection (ARI) with confirmed positive influenza infection were enrolled. Influenza cases were identified by reverse transcriptase-polymerase chain reaction. Life-threatening disease (LTD) was defined by the need for intensive care and ventilatory support. MUC5AC, epidemiologic, and clinical risk factors were assessed. Three hundred and forty-two patients were hospitalized with ARI, of which 49 (14%) had confirmed influenza infection and 6 (12%) of them developed LTD. MUC5AC levels were higher in those patients with mild diseasecompared to cases with poorer outcomes. Our results show that the severity of influenza infection in children is significantly associated with low levels of MUC5AC. These findings suggest its potential as a suitable biomarker for predicting disease severity.

The antigenic landscape of human influenza N2 neuraminidases from 2009 until 2017.

Human H3N2 influenza viruses are subject to rapid antigenic evolution which translates into frequent updates of the composition of seasonal influenza vaccines. Despite these updates, the effectiveness of influenza vaccines against H3N2-associated disease is suboptimal. Seasonal influenza vaccines primarily induce hemagglutinin-specific antibody responses. However, antibodies directed against influenza neuraminidase (NA) also contribute to protection. Here, we analysed the antigenic diversity of a panel of N2 NAs derived from human H3N2 viruses that circulated between 2009 and 2017. The antigenic breadth of these NAs was determined based on the NA inhibition (NAI) of a broad panel of ferret and mouse immune sera that were raised by infection and recombinant N2 NA immunisation. This assessment allowed us to distinguish at least four antigenic groups in the N2 NAs derived from human H3N2 viruses that circulated between 2009 and 2017. Computational analysis further revealed that the amino acid residues in N2 NA that have a major impact on susceptibility to NAI by immune sera are in proximity of the catalytic site. Finally, a machine learning method was developed that allowed to accurately predict the impact of mutations that are present in our N2 NA panel on NAI. These findings have important implications for the renewed interest to develop improved influenza vaccines based on the inclusion of a protective NA antigen formulation.