Search Results (184)

Background: Leptospirosis is an important zoonosis that can present as a self-limited influenza-like illness or progress to severe, including life-threatening multiorgan dysfunction. We report the epidemiology, clinical profile, and correlates of severity among adults hospitalized patients with leptospirosis diagnosed in central Romania over a period of 17 years. Methods: We conducted a retrospective, single-center cohort study of adults admitted between 1 January 2008 and 1 December 2025 with laboratory-confirmed leptospirosis. Confirmation was based on positive anti-Leptospira IgM serology, with repeat testing when the initial result was equivocal and confirmation with a microscopic agglutination test. We extracted demographic, exposure, clinical, laboratory, treatment, and outcome data from medical records. The modified Faine score was also calculated using admission data. Results: Sixty-four patients were included in this analysis, of which 53 (82.8%) were male patients. Admissions peaked in 2023–2025 (34/64, 53.1%) and in the August–September months. Reported exposures were predominantly peri-domestic (46.9%), followed by rural/animal-related occupations (20.3%) and freshwater contact (17.2%). Severe disease occurred in 26/64 (40.6%), was more frequent in men (p = 0.021), and was more common pre-pandemic than during/after the pandemic (p < 0.001). Severe cases were associated with oliguria/anuria, hematuria, and jaundice, alongside higher urea/creatinine and bilirubin, lower hemoglobin and lymphocyte percentages, and a longer hospitalization period. One in-hospital death occurred (1.6%). Serogroup identification was available for 10 patients (15.6%) (pre-pandemic only). The mean modified Faine score was 27.5 ± 6.0. Conclusions: In this temperate-region cohort study, hospitalized leptospirosis showed a marked male predominance, a late-summer peak, and a substantial burden of severe disease. Early renal and hepatobiliary manifestations with concordant laboratory abnormalities may support timely risk stratification and escalation of care, while expanded molecular diagnostics and systematic typing are needed to clarify temporal trends and guide prevention. Full article

Background: Children and adolescents are pivotal in the transmission of influenza, and vaccination remains the most effective preventive measure. Cell-based influenza vaccines offer advantages over traditional egg-based vaccines by reducing egg-adapted mutations and improving antigenic match. SKYCellflu^® quadrivalent influenza vaccine (QIV; SK bioscience, Korea), the first cell-based QIV licensed in Korea for individuals aged 6 months and older, offers potential advantages; however, its real-world effectiveness in the Korean pediatric population remains limited. Objective: This study aimed to estimate the real-world effectiveness of SKYCellflu^® QIV, a cell-based QIV, in preventing laboratory-confirmed influenza among children and adolescents aged 6 months to 18 years in Korea during the 2024–2025 influenza season. Methods: A multicenter, prospective, test-negative case–control study was conducted from October 2024 to May 2025 across 25 institutions in Korea. Children and adolescents aged 6 months to 18 years who presented within 7 days of the onset of influenza-like illness (fever ≥ 38 °C and at least one respiratory symptom) were enrolled. Influenza infection was confirmed using rapid antigen tests or polymerase chain reaction; participants who tested positive were classified as cases, and those who tested negative for influenza served as controls. All participants were further categorized as vaccinated or unvaccinated based on receipt of SKYCellflu^® QIV. Those who received other influenza vaccines during the season were excluded. Vaccination status was verified through medical records and the national immunization registry. Results: A total of 1476 participants were included (751 cases, 725 controls). The overall adjusted vaccine effectiveness (aVE) was 45.57% (95% CI, 29.38–58.04). The vaccine demonstrated the highest effectiveness in children aged 6–35 months (aVE: 88.55%; 95% CI, 60.39–96.11). Effectiveness was higher against influenza B (aVE: 61.28%; 95% CI, 35.76–76.30) than influenza A (aVE: 41.63%; 95% CI, 22.55–56.01). The vaccine’s effectiveness in adolescents was not statistically significant due to the small sample size in this age group. Conclusions: This multicenter test-negative study provides the first real-world effectiveness of SKYCellflu^® QIV in a Korean pediatric population. The results suggest substantial protection in younger children, particularly against influenza B, and support the continued use of annual influenza vaccination in this population. Further studies with larger adolescent cohorts are needed to confirm these findings in older age groups. Full article

Background: Promoting seasonal influenza vaccination among parents may help increase the coverage of seasonal influenza vaccination among both parents and children. This study aims to investigate determinants of behavioral intention to receive a seasonal influenza vaccination among parents of children aged 0–15 years to protect themselves. Methods: A cross-sectional survey was conducted among parents of children aged 0 to 15 years with administrative health records in Shenzhen, China, between September and October 2024. Participants were recruited through multistage random sampling. First, 10 community health centers were randomly selected in Shenzhen. Within each selected center, 200 parents were randomly selected. Multivariate logistic regression models were fitted. Results: Among 1504 parents, 47.6% intended to receive a seasonal influenza vaccination in the next year. After adjusting for significant background characteristics, parents’ intention to receive a seasonal influenza vaccination was associated with a higher intention to vaccinate their children against seasonal influenza (AOR: 20.39). At the individual level, eight items measuring illness representations of seasonal influenza were associated with higher odds of intending to receive such a vaccine (AOR: 1.15–1.25), including identity (identifying symptoms), timeline, negative consequences, personal and treatment control, concern, negative emotions, and coherence. At the interpersonal level, parents who had higher levels of general and family-oriented altruism (AOR: 1.10–2.47), better family harmony (AOR: 1.07), higher exposure to information related to seasonal influenza on social media (AOR: 1.24–1.38), and thoughtful consideration of information veracity (AOR: 1.33) were more likely to report an intention. Conclusions: There are strong needs to promote seasonal influenza vaccination among parents in China. Full article

We characterized influenza A(H1N1)pdm09, A(H3N2), and B/Victoria viruses circulating in Japan during 2023–2024, focusing on lineage placement relative to WHO-recommended vaccine strains and on baloxavir resistance (PA/I38T substitutions). We enrolled 210 outpatients with influenza-like illness across eight clinics in six prefectures (October 2023–September 2024). Of these, 209 had an analyzable pre-treatment respiratory specimen for RT-PCR; hemagglutinin (HA) and neuraminidase (NA) genes were sequenced by next-generation sequencing (NGS). PA/I38T substitutions that confer baloxavir resistance were assessed by cycling-probe RT-PCR, Sanger sequencing, and NGS. HA phylogenies were constructed with global datasets and WHO vaccine reference strains. Of 209 pre-treatment specimens, 181 were influenza-positive (A(H1N1)pdm09 44.2%, A(H3N2) 37.6%, B/Victoria 18.2%); 51 follow-up specimens were collected ≈4–5 days after baloxavir or neuraminidase inhibitor therapy. HA phylogeny placed A(H1N1)pdm09 in clades 5a.2a/5a.2a.1 with predominance of subclade D.2. A(H3N2) clustered exclusively in clade 2a.3a.1 (J lineage, mostly J.1), indicating a mismatch with the season’s A/Darwin/9/2021 vaccine component and supporting the subsequent J-lineage update. All B/Victoria genomes fell within V1A.3a.2 on a C.5 backbone (C.5.1 and C.5.7). No PA/I38T variant was detected in any pre-treatment specimen. Post-baloxavir, PA/I38T emerged in one A(H3N2) case (confirmed by all three methods) and in one B/Victoria case detected by NGS only (minority variant in a low-load sample). NA genes showed no substitutions associated with reduced susceptibility to laninamivir (e.g., E119A, G147E). During 2023–2024, A(H1N1)pdm09 and B/Victoria remained genetically aligned with their vaccine components, whereas A(H3N2) shifted to the J lineage, consistent with the 2024–2025 vaccine update. Although pre-treatment PA/I38T was absent, low-frequency on-therapy selection was observed, including a rare PA/I38T in influenza B/Victoria detected by NGS, suggesting the value of deep sequencing when viral loads are low. These integrated genomic–clinical data support vaccine strain realignment for H3N2 and continued monitoring of baloxavir resistance in outpatient care. Full article

Background: In the post-pandemic era, respiratory viruses continue to cause substantial morbidity and mortality among hospitalized adults. SARS-CoV-2 and influenza remain the most common pathogens, while RSV and rhinovirus have re-emerged as relevant causes of severe illness. This study compared the characteristics and outcomes of virus-specific infections detected by multiplex real-time PCR over two consecutive seasons. Methods: This retrospective cohort study was conducted at a 1010-bed tertiary-care hospital in Türkiye between June 2022 and June 2024. Adults hospitalized with at least one respiratory virus detected by MRT-PCR were included. Demographic, clinical, and laboratory data were analyzed. Pathogen-specific comparisons were limited to monoinfections, and predictors of in-hospital mortality were identified using multivariable logistic regression. Results: Among 518 admissions, influenza (33.6%) and SARS-CoV-2 (29.3%) were the predominant pathogens, followed by rhinovirus (11.2%), RSV (6.6%), and other respiratory viruses (19.6%). Overall in-hospital mortality was 26.6%. Mortality differed across virus groups in unadjusted analyses, being highest in SARS-CoV-2 and RSV and lowest in rhinovirus. Non-survivors were older, more comorbid, more often immunosuppressed, and more likely to require oxygen therapy or ICU care at sampling. In multivariable analysis, independent predictors of mortality were ICU location at sampling (aOR 5.52), oxygen requirement (aOR 3.39), immunosuppression (aOR 3.67), older age (per 10-year increase: aOR 1.25), and secondary bacterial infection (aOR 7.00). Viral etiology, including SARS-CoV-2, was not independently associated with mortality after adjustment. Conclusions: Among hospitalized adults, mortality was driven primarily by host-related factors and secondary bacterial infection rather than by viral etiology. These findings highlight the need for strengthened adult immunization programs, reliable respiratory virus surveillance, the prevention of bacterial superinfection, and the development of and equitable access to effective vaccines and antiviral therapies to reduce severe outcomes in high-risk adults. Full article

Influenza B viruses (IBV) belong to the family of Orthomyxoviridae and circulate annually in humans causing respiratory illness. Although they are considered an exclusively human pathogen, there is evidence of IBV infections in animals, including wildlife, companion animals and livestock. In addition, metagenomic studies have identified novel orthomyxoviruses in amphibians and fish that appear related to IBV, suggesting influenza viruses, including IBV, have been associated with vertebrates across their evolutionary history. In this review, we summarise our current knowledge of potential IBV and IBV-like infections in animals. These collectively suggest that the ecology of IBV extends beyond humans and warrants further investigations. Full article

Viral respiratory infections (VRIs) remain a leading cause of global morbidity and mortality. In Djibouti, diagnostic capacity for respiratory viruses is extremely limited, and little is known about the epidemiology of VRIs in the country. To address this gap, we conducted a prospective study aimed at monitoring and describing the epidemiological and virological features of VRIs over a two-year period in Djibouti. The study was carried out between January 2023 and December 2024 in seven healthcare centers. Nasopharyngeal and/or oropharyngeal swabs were collected from consenting patients presenting with influenza-like illness (ILI) or acute respiratory infections (ARI). VRIs were diagnosed using a multiplex real-time reverse transcription polymerase chain reaction (rRT-PCR) assay targeting 16 respiratory viruses. Among the 647 samples tested, at least one respiratory virus was detected in 133 (20.6%). Influenza (6.6%), rhinovirus (5.9%), and SARS-CoV-2 (3.4%) were the most frequently detected pathogens. Adult aged 26–50 years (40.8%) were the most affected, followed by those aged 15–25 years (30.4%). None of the respiratory viruses displayed a clear seasonal pattern. These findings demonstrate the co-circulation of multiple respiratory viruses among ILI/ARI patients in Djibouti and provide the first baseline data to inform national surveillance strategies. The results underscore the need to strengthen routine laboratory-based surveillance, enhance diagnostic capacity, and integrate molecular monitoring into national public health policies for better preparedness against emerging respiratory threats. Full article

Background: Little is known about morbidity patterns and healthcare utilization among specific Hajj pilgrim groups. This study examined influenza vaccination coverage, disease spectrum and healthcare utilization outcomes among Sudanese pilgrims during Hajj 2025. Methods: A cross-sectional analysis was conducted using de-identified patient records from the Saudi Health Electronic Surveillance Network for Sudanese Hajj pilgrims in 1–9 June 2025. Data included demographics, influenza vaccination status, healthcare utilization metrics, morbidities and temporal distribution of visits. Comparisons between hospital and primary healthcare center (PHC) attendees were performed using appropriate statistical tests. Results: A total of 1130 pilgrims sought care, with 88.6% (n = 1001) attending PHCs and 11.4% (n = 129) hospitals. Their mean age was 49.7 ± 12.9 years, and 67.9% (n = 767) were male. Influenza vaccination coverage was 79% (893/1130); vaccinated pilgrims had lower incidence of influenza-like illness (ILI) compared to unvaccinated pilgrims (5.2% vs. 15.2%, p < 0.01). Respiratory illnesses were the most frequent diagnoses (40.8% in PHCs and 24.8% in hospitals), followed by musculoskeletal disorders (24.5% and 16.3%, respectively). Compared to PHCs, presentation rate for chronic diseases was higher in hospitals (19.4% vs. 8.7%, p < 0.001), so was the median clinic time (14.1 vs. 8.6 min, p < 0.001). Healthcare utilization peaked on days 3–5 coinciding with the ‘Arafat Day’. Conclusions: Sudanese pilgrims most commonly presented with acute respiratory conditions, with PHCs managing the majority of cases, and influenza vaccination was protective against ILI. Findings emphasize the need for strong primary care, efficient resource allocation, and targeted preventive strategies to safeguard pilgrims’ health in the future. Full article

Background/Objectives: Influenza A virus undergoes continuous antigenic drift, necessitating annual vaccine reformulation. Saudi Arabia faces unique epidemiological challenges owing to mass gatherings during religious pilgrimages and the dynamic movement of foreign workers. This study aimed to characterize the genetic diversity of hemagglutinin (HA) and neuraminidase (NA) genes of influenza A viruses circulating in Riyadh and to assess their match with vaccine strains during the 2024–2025 period. Methods: Nasopharyngeal samples (n = 363) were collected from patients presenting with influenza-like illness. RT-PCR was used for detection and subtyping. Sequence and phylogenetic analysis of the complete HA and NA gene sequences from A/H1N1pdm09 strains (n = 7) were then performed. Results: Of the 363 samples, 110 (30.3%) were positive for influenza A; among these, 68 (61.8%) were A/H1N1pdm09, and 42 (38.2%) were H3N2. Phylogenetic analysis revealed that all A/H1N1pdm09 strains belonged to clade 5a.1, distinct from vaccine strains. In comparison with the vaccine strain A/Wisconsin/67/2022, seven amino acid substitutions in the HA gene and eight in the NA gene were recorded in Saudi circulating strains. The significant genetic divergence between circulating A/H1N1pdm09 strains and current vaccine strains indicates potential vaccine mismatch. Conclusions: The significant genetic divergence between circulating A/H1N1pdm09 strains and current vaccine strains suggests potential vaccine mismatch. Continuous surveillance programs along with vaccination plans are necessary to tackle the changing influenza A virus strains in the special epidemiological context of Saudi Arabia. Full article

Background: Influenza cases have surged earlier than usual during the 2024–2025 season, with A/H1N1 (pdm09) being the dominant strain. We aimed to investigate early estimates of influenza vaccine effectiveness (VE) for the 2024–2025 season to enhance our influenza response strategies. Methods: From November 1 to December 31, 2024, we enrolled 990 individuals with influenza-like illness from the hospital-based influenza surveillance network (Hospital-Based Influenza Morbidity and Mortality, HIMM), which consists of eight hospitals. Results: The overall adjusted VE was estimated to be −0.5% (95% confidence interval [CI], −34.0 to 24.6), with 0.4% (95% CI, −33.2 to 25.5) for influenza A. Analyses by influenza subtype were exploratory, given the limited number of subtyped cases. Although ineffective in preventing laboratory-confirmed influenza, influenza vaccination reduced influenza-related hospitalizations by 31.9% (95% CI, 3.5 to 51.9). Conclusions: It is necessary to enhance influenza vaccine effectiveness by selecting better-matched vaccine strains and introducing immune-enhanced vaccines. Full article

Human rhinovirus (HRV) is the most common cause of upper respiratory tract infections and can cause substantial morbidity in children. Because its clinical features are nonspecific, differentiation from influenza virus and respiratory syncytial virus is often difficult, underscoring the diagnostic importance of real-time reverse transcriptase polymerase chain reaction (Real-Time RT-PCR)-based detection. This study aimed to characterize long-term epidemiological patterns of HRV in the Republic of Korea and assess their clinical and public health implications. We retrospectively analyzed 23,284 nasopharyngeal swab specimens collected between 2007 and 2024 from outpatients and inpatients presenting with influenza-like illness at a tertiary care hospital. HRV RNA was detected by Real-Time RT-PCR, and positivity rates were compared by year, month, and age group. Annual detection peaked in 2015 (31.3%) and 2016 (28.6%), then dropped sharply during the COVID-19 pandemic (2020–2021, 4.2–11.0%) and remained low through 2024. Seasonally, rates were highest in July (24.4%) and September (24.1%) and lowest in January (6.9%). Age-specific analysis showed peak positivity in children (26.1%) and infants (20.3%), with lower rates in adults (3.9%) and older adults (3.3%). These findings underscore the diagnostic value of HRV detection and provide evidence for pediatric-focused prevention, outbreak preparedness, and climate-informed surveillance strategies. Full article

Legionella pneumophila (L. pneumophila) infection is characterized by a wide spectrum of manifestations, from influenza-like illness to life-threatening atypical pneumonia with multiorgan failure. The aim of our study was the assessment of in vitro and ex vivo neutrophil activation in L. pneumophila infections, as well as the role of neutrophils’ peptides such as LL-37 in infection. The ability of neutrophils to form ex vivo extracellular traps (NETs) in response to bacterial infection was examined by immunofluorescence. In parallel, patients’ sera, as well as opsonized standard L. pneumophila strains, were used for in vitro activation of neutrophils from healthy individuals. The serum levels of interleukins were assessed using the LEGENDplexTM Multi-Analyte Flow Assay Kit. Furthermore, citrullinated cf-DNA as a marker of neutrophil extracellular traps (NETs) was detected in the serum of patients with acute infection. It was demonstrated that neutrophils released NETs in vitro and ex vivo upon L. pneumophila (interaction in an autophagy-independent manner. Notably, IL-1b was detected on NETs, but an antimicrobial peptide LL-37 was absent. The lack of antimicrobial activity failed to inhibit bacterial proliferation. In addition, in vitro and ex vivo NETs formation was observed during the Clarithromycin treatment. Those NETs were decorated with bioactive antimicrobial peptide LL-37, which inhibits bacterial proliferation. The findings provide evidence that neutrophils release NETs in vitro and ex vivo by expressing the IL1β protein in them. The lack of expression of the antimicrobial peptide LL-37 on the NETs demonstrates the inability of the cells to inhibit proliferation, and consequently the elimination of L. pneumophila. Clarithromycin plays a dual role in the elimination. Full article

Background: Cervical artery dissection (CAD) is a leading cause of acute ischemic stroke among young and middle-aged patients. Currently, the growing availability of high-resolution magnetic resonance imaging (MRI), particularly fat-saturated T1-weighted black-blood SPACE sequences, allows the non-invasive, rapid, and reliable diagnosis of multiple arterial dissections. Methods: We reported our experience from two tertiary stroke centers of patients diagnosed with spontaneous multiple cervical artery dissections, detected with high-resolution MRI, during a three-year period (2022–2025). Results: Among 95 consecutive patients with CAD, 11 patients (mean age: 48 ± 9 years, 6 (55%) females) were diagnosed with multiple symptomatic or asymptomatic CADs, whereas in 84 patients (mean age: 49 ± 11 years, 32 (38%) females) a single CAD was detected. In all patients, high-resolution MRI and MR-angiography were performed, whereas digital subtraction angiography (DSA) with simultaneous evaluation of renal arteries was conducted in nine patients. A history of trauma or chiropractic manipulations, intense physical exercise prior to symptom onset, recent influenza-like illness, and recent childbirth in a young female patient were reported as predisposing risk factors. Cervicocranial pain, cerebral infarctions leading to focal neurological signs, and Horner’s syndrome were among the most commonly documented symptoms. Characteristic findings in the high-resolution 3D T1 SPACE sequence were detected in all patients. Fibromuscular dysplasia and Eagle syndrome were detected in four patients and one patient, respectively. Eight patients were treated with antiplatelets, whereas three patients received anticoagulation with low-molecular-weight heparin. There was only one case of stroke recurrence during a mean follow-up period of 9 ± 4 months. Conclusions: This case series highlights the utility of specific high-resolution MRI sequences as a very promising method for detecting multiple CADs in young patients. The systematic use of these sequences could enhance the sensitivity of detecting multiple cervical CADs, affecting also the thorough investigation for underlying connective tissue vasculopathies, stratifying the risk for first-ever or recurrent ischemic stroke, and influencing acute reperfusion and secondary prevention therapeutic strategies. Full article

Antigenicity and immunogenicity define a potent immunogen in vaccinology. Nowadays, there are simplified platforms to produce nanocarriers for small-peptide antigen delivery, derived from various infectious agents for the treatment of a variety of diseases, based on virus-like particles (VLPs). They have good cell-penetrating properties and protective action for target molecules from degradation. Human papillomavirus (HPV) causes anogenital warts and six types of cancer in infected women, men, or children, posing a challenge to global public health. The HPV capsid is composed of viral type-specific L1 and evolutionarily conserved L2 proteins. Produced in heterologous systems, the L1 protein can self-assemble into VLPs, nanoparticles sized around 50–60 nm, used as prophylactic vaccines. Devoid of the viral genome, they are safe for users, offering no risk of infection because VLPs do not replicate. The immune response induced by HPV VLPs is promoted by conformational viral epitopes, generating effective T- and B-cell responses. Produced in different cell systems, HPV16 L1 VLPs can be obtained on a large scale for use in mass immunization programs, which are well established nowadays. The expression of heterologous proteins was evaluated at various transfection times by transfecting cells with vectors encoding codon-optimized HPV16L1 and HPV16L2 genes. Immunological response induced by chimeric HPV16 L1/L2 VLP was evaluated through preclinical assays by antibody production, suggesting the potential of broad-spectrum protection against HPV as a prophylactic nanovaccine. These platforms can also offer promising therapeutic strategies, covering the various possibilities for complementary studies to develop potential preventive and therapeutic vaccines with broad-spectrum protection, using in silico new epitope selection and innovative nanotechnologies to obtain more effective immunobiologicals in combating HPV-associated cancers, influenza, hepatitis B and C, tuberculosis, human immunodeficiency virus (HIV), and many other illnesses. Full article

Limited surveillance and laboratory testing for non-influenza viruses remains a challenge in Uganda. The World Health Organization (WHO) designated National Influenza Center (NIC) tested samples from patients with influenza-like illness (ILI) and severe acute respiratory infections (SARIs) during August 2022–February 2023. We leveraged the influenza sentinel surveillance system to detect other respiratory viruses (ORVs). Samples were tested using the US Centers for Disease Control and Prevention (CDC) influenza and SARS-CoV-2 multiplex and the FTD^TM Respiratory Pathogens 21 assays using real-time reverse transcription polymerase chain reaction (RT-qPCR). A total of 687 (ILI = 471 (68.6%) and SARI = 216 (31.4%) samples were tested. The median age was 2 years (IQR: 1–25) for ILI and 6 years (IQR: 1–18) for SARI case definitions (p-value = 0.045). One or more respiratory pathogens were detected in 38.7% (n = 266) of all samples; 33 (12.4%) were selected for metagenomics sequencing and 8 (3%) for SARS-CoV-2 targeted sequencing. Respiratory pathogens were detected by sequencing in 23 of 33 (69.7%) samples. Our study provides insight into the usefulness of this surveillance system in conducting virological testing for other viruses and provides tools and evidence to monitor patterns and characteristics of viruses causing ILI/SARI, which will guide public health decisions and interventions in Uganda. Full article