Search Results (1,319)

Background/Objectives: Febrile illness in returning travelers presents a diagnostic and operational challenge for emergency medicine clinicians as early symptoms of high-consequence tropical infections often overlap with common viral syndromes. This review synthesizes current evidence to guide frontline clinicians in the systematic evaluation, diagnosis, and management of internally acquired febrile illnesses with a focus on pathogen of greatest relevance to United States (US) emergency departments (ED). Methods: We conducted a narrative review of the literature addressing epidemiology, clinical presentation, diagnostic testing, and management strategies for key travel-associated infections. Special consideration was given to rapid diagnostic modalities, pediatric risk factors, and infections most frequently implicated in returning travelers, including chikungunya (CHIK), dengue virus (DENV) disease, Ebola virus (EBV) disease, malaria, Mpox, typhoid fever (TF), yellow fever (YF), and Zika virus (ZIKV) disease. Results: Effective evaluation begins with a detailed travel and exposure history, recognition of epidemiologic and clinical red flags, and targeted use of rapid diagnostic tests. Malaria remains the most common life-threatening cause of post-travel fever and the only pathogen with reliable Food and Drug Administration (FDA)-cleared rapid testing available in the ED. Arboviral infections such as DENV, CHIK, ZIKV, and YFrequire region-specific consideration and phase-appropriate molecular or serologic evaluation. Emerging and high-consequence pathogens, including Mpox and EBV, necessitate strict infection control measures and coordination with public health authorities. Pediatric travelers, particularly those visiting friends and relatives, face disproportionate risk for severe systemic infections and often require broader diagnostic testing. Conclusions: A structured approach integrating travel history, focused examination, rapid diagnostics, and early recognition of high-risk features is essential to improving outcomes for febrile returning travelers. Strengthened vector control, enhanced vaccination uptake, and global surveillance are critical to reducing future disease burden. Full article

Yersinia pestis is the etiological agent of plague, a severe and often fatal disease in humans when left untreated. Because of the high genetic clonality of Y. pestis, high-resolution genotyping assays are necessary to differentiate between individual strains. Here, we report on the development and validation of a robust and reproducible core-genome multilocus sequence typing (cgMLST) assay for Y. pestis comprising 3139 gene targets, enabling high-resolution typing at the strain level. The assay was validated using 222 publicly available Y. pestis genomes, including 45 recently sequenced outbreak isolates from Madagascar and 21 isolates from Mongolia. The cgMLST analysis revealed primary clustering aligned with known biovar-associated branches and sub-branches. Additional geographically structured sub-clusters illustrate its application for regional diversification analysis. Yersinia pestis strains from different geographic regions were clearly distinguished, consistent with spatial clustering. Within the analyzed dataset, closely related or epidemiologically linked strains differed by zero to three alleles, suggesting this range as an operational reference for identifying highly similar isolates. The cgMLST showed clustering patterns concordant with previously described single-nucleotide polymorphism (SNP) assays. It therefore provides a standardized high-resolution typing approach, with demonstrated applicability for outbreak investigations, source tracking, and comparative genomic surveillance of Y. pestis. Full article

Rice blast, caused by the fungus Magnaporthe oryzae, is one of the most devastating threatening to global rice production. The narrow genetic background of modern rice cultivars exacerbates the shortage of durable resistance resources. In contrast, the wild rice species Oryza officinalis harbors abundant stress-resistance alleles and represents a valuable gene pool for identifying novel broad blast-resistance genes. The cloned resistance gene Pid2 is encoded in a receptor-like protein kinase conferring race-specific resistance against the M. oryzae isolate ZB15. In this study, three Pid2 homologs were isolated from O. officinalis. The special allele Pid2of-MD33 was transformed into “Yunjing 37(YG37), a blast-susceptible japonica rice cultivar” via Agrobacterium-mediated transformation. Quantitative real-time PCR analysis showed that Pid2of-MD33 was consistently expressed in various tissues of O. officinalis, with the highest transcript abundance detected in leaf mesophyll cells and plasma membranes. Inoculation with the M. oryzae isolate ZB15 revealed that transgenic YG37 lines expressing Pid2of-MD33 displayed significantly reduced lesion size and pathogen proliferation, suggesting recovered race-specific resistance. These results enrich the resistance gene resources for rice blast research and provide a promising candidate gene for rice blast resistance breeding. Full article

Background/Objectives: Rapid, equipment-free molecular detection of bacterial pathogens at the point of care (POC) remains a critical challenge. Staphylococcus aureus is a leading cause of severe infections, necessitating simple and sensitive diagnostic tools. Methods: We developed an integrated assay combining helicase-dependent amplification (HDA) and rolling circle amplification (RCA) in a sequential ‘one-pot’ format. Asymmetric HDA generates short, single-stranded amplicons from S. aureus DNA, enabling specific padlock probe ligation and subsequent exponential RCA. For equipment-free visual detection, biotin-labeled nucleotides are incorporated during RCA, and products are captured on a silica membrane and detected using a streptavidin-HRP conjugate with 3,3′,5,5′-tetramethylbenzidine substrate, producing an unambiguous blue color. Results: The assay detected as few as 10¹ genome copies of S. aureus per reaction. Evaluation against a panel of nine non-target respiratory pathogens and human genomic DNA demonstrated 100% specificity, with no cross-reactivity. The entire procedure is performed isothermally at 65 °C in a single tube with a total assay time of approximately 90 min. Conclusions: This ‘one-pot’ HDA-RCA colorimetric assay combines high sensitivity and specificity for S. aureus in a user-friendly, almost equipment-free format. Its simplicity and robust visual readout make it a promising tool for POC diagnostics in resource-limited settings, enabling rapid clinical decisions without specialized instrumentation. Full article

In 2024 Kenya had a population of 4.78 million camels that contributed to the livelihoods of pastoralist communities in northern Kenya. Previous studies in Kenya, Saudi Arabia and eastern Africa demonstrated high seroprevalence of Middle East respiratory syndrome coronavirus (MERS-CoV)-specific antibodies in dromedary camels, as well as sporadic transmission of MERS-CoV from camels to humans. Based on the MERS-CoV data and the very close contact between owners and their camels in northern Kenya, we speculated that camels may also transmit other zoonotic viruses, such as Rift Valley fever virus (RVFV). In this study, 493 camel and 197 human sera were collected in Marsabit, Kenya, through a cross-sectional survey in 2018 and analyzed for the presence of RVFV IgG antibodies using a laboratory-developed indirect enzyme-linked immunosorbent assay (ELISA). Overall, 15.6% of camels and 7.6% of humans were RVFV IgG-positive; IgG-positive camels were predominantly females in large population herds and IgG-positive humans were engaged in farming-related activities and were greater than 18 years old. Of the eight location groups sampled, two had high camel (site 2 and site 6) and two had high human (site 5 and site 6) RVFV seropositivity rates. These data suggest that camelids, such as dromedary camels, may serve as amplifying hosts for vector-borne zoonotic diseases, such as RVFV, and that humans with frequent farming and camel meat, milk, or camel product contact may have increased risk for RVFV exposure or infection. Full article

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammation, synovial hyperplasia, and progressive joint destruction. Periodontitis, a chronic inflammatory disease affecting the supporting structures of teeth, has been increasingly recognized as a potential contributor to RA pathogenesis. Evidence suggests that both conditions share common immunological mechanisms and microbial triggers. This review summarizes the data linking RA with periodontitis, with particular focus on shared pathogenic pathways, microbial triggers, immune system alterations, and clinical relevance. Methods: Experimental, epidemiological, and clinical studies were evaluated to explore biological and clinical links between periodontitis and RA. Special emphasis was placed on the mucosal origins of RA, bacterial-mediated citrullination, autoantibody formation, and the role of the complement system. Results: Available epidemiological data indicate that individuals with RA present higher prevalence and greater severity of periodontitis. Periodontal pathogens, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, contribute to immune dysregulation through citrullination, and subsequent production of anti-citrullinated protein antibodies (ACPAs), a hallmark of RA. Both diseases are characterized by chronic, uncontrolled inflammation, amplified by complement activation and neutrophil hyperactivity. Clinical evidence suggests that non-surgical periodontal therapy may reduce systemic inflammatory markers and improve RA disease activity. Conclusions: The relationship between RA and periodontitis appears to be bidirectional and the recognition of this interaction supports closer collaboration between rheumatologists and dental professionals. Future studies are required to clarify causality and determine whether management strategies can influence patient outcomes. Full article

Antimicrobial resistance [AMR] is a silent yet intensifying global threat, with particularly severe consequences in tropical and subtropical ecosystems, where high ecological connectivity, extensive antimicrobial use, and inadequate sanitation create ideal conditions for the persistence and spread of antimicrobial resistance genes [ARGs]. Within the One Health framework, migratory birds warrant special attention because they traverse tropical AMR hotspots, linking contaminated aquatic, agricultural, and peri-urban environments along established flyways. Evidence from tropical and subtropical regions indicates that migratory birds frequently carry clinically relevant AMR-associated pathogens, including extended-spectrum β-lactamase-producing Escherichia coli, multidrug-resistant Salmonella enterica, and fluoroquinolone- and macrolide-resistant Campylobacter spp. These findings suggest that migratory birds primarily function as ecological sentinels and geographic redistributors of antimicrobial resistance, reflecting environmental contamination and ecological connectivity between human-dominated and natural ecosystems, while evidence for long-term reservoir status remains context-dependent. Addressing the complex interface among AMR, migratory birds, and ARGs requires integrative surveillance strategies that explicitly incorporate wildlife into existing health systems. Genomic and metagenomic monitoring of migratory bird populations, combined with cross-sectoral data sharing, can provide early warning signals of emerging resistance patterns and inform evidence-based interventions. Understanding the ecological role of migratory birds in tropical ecosystems is therefore essential for designing effective One Health strategies to mitigate transboundary AMR risks and preserve the long-term efficacy of antimicrobial therapies. Full article

Several reproductive issues in both men and women are caused by changes in the pulsatile secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). For males to sustain spermatogenesis and Leydig cell function, and for females to ensure orderly folliculogenesis, ovulation, and ovarian steroidogenesis, precise coordination of LH and FSH secretion is necessary. Pituitary responsiveness, the frequency or amplitude of gonadotropin-releasing hormone pulses, or the dysregulation of feedback signals mediated by sex steroids and inhibins all disrupt the balance between LH and FSH secretion. Oligozoospermia, luteal-phase abnormalities, anovulation, or complete spermatogenic failure are possible clinical signs of these alterations. In addition to functional neuroendocrine disturbances, emerging genetic and epigenetic evidence, including pathogenic variants in genes such as gonadotropin-releasing hormone receptor, kisspeptin, kisspeptin receptor, luteinizing hormone beta subunit, follicle-stimulating hormone beta subunit, follicle-stimulating hormone receptor, and luteinizing hormone/choriogonadotropin receptor, has highlighted the role of inherited and acquired molecular defects in disrupting gonadotropin regulation. This narrative review synthesizes contemporary mechanistic, clinical, translational, and genetic evidence elucidating how dysregulated secretion of LH and FSH contributes to reproductive dysfunction. The molecular processes that regulate gonadotropin synthesis and release, as well as neuroendocrine regulation, gene-level determinants of hypothalamic–pituitary–gonadal (HPG) axis dysfunction, and the clinical phenotypes that result from their disruption, are all given special attention. We conclude with a discussion of new treatment strategies that target local intragonadal regulators to enhance gametogenic capacity, modulate gonadotropin signaling, or restore physiological gonadotropin-releasing hormone (GnRH) pulsatility, with consideration of how genetic insights may inform personalized therapeutic approaches. Full article

Neutrophils are among the early responders of the innate immune system and play a key role in host defense against viral infections. Beyond their classical antimicrobial functions, neutrophils can engage in a specialized defense mechanism by releasing web-like extracellular DNA known as neutrophil extracellular traps (NETs). These extracellular traps are a mesh-like network of chromatin DNA decorated with cellular components, including histones, proteases, and antimicrobial enzymes, that function to contain and limit the spread of pathogens. While NET formation contributes to antiviral immunity, accumulating evidence indicates that excessive or dysregulated NET formation can significantly contribute to immunopathology during viral infections. Thus, depending on the context and outcome, NET formation may be viewed as a double-edged sword. Therefore, understanding the regulatory mechanisms governing NET formation and its harmful effects is critical for developing therapeutic strategies that enhance antiviral defense while minimizing tissue damage. In this review, we provide a comprehensive overview of the molecular mechanisms that drive NET formation and clearance, with a particular focus on how viruses modulate these processes to influence disease outcome. We also discuss the pathways underlying NET formation and subsequent neutrophil cell death (NETosis), including canonical and non-canonical pathways, and highlight key signaling axes involving SYK, MAPKs, and NF-κB. Using SARS-CoV-2 and hepatitis B virus as representative models, we examine how different viral components trigger, exploit, or evade NET targeting and how persistent accumulation of NETs can contribute to hyperinflammation, progressive tissue injury, and post-viral syndromes. We further explore emerging evidence linking impaired NET clearance and neutrophil heterogeneity, particularly low-density neutrophils (LDNs), to chronic inflammation and post-viral sequelae such as long COVID and autoimmune hepatitis. Finally, we summarize current and emerging therapeutic strategies aimed at modulating NET formation or enhancing NET clearance. Altogether, this review underscores the dual nature of NETs in viral infections, highlighting their potential roles in antiviral defense and tissue injury, and provides a framework for the development of targeted interventions to limit virus-induced immunopathology. Full article

To address the issues of operational complexity, long duration association, and reliance on specialized equipment with existing detection methods for Vibrio parahaemolyticus, this study established a rapid detection method for V. parahaemolyticus in exported aquatic products based on the domestically developed Enzymatic Recombinase Amplification (ERA) technology. To target the thermolabile hemolysin gene (tlh) and the iron-regulated virulence regulatory protein gene (irgB) of V. parahaemolyticus, highly specific ERA primers and probes were designed and screened. Two detection platforms, a colorimetric method and a fluorescent method, were developed. Method validation results showed that this detection system achieved specific amplification for all 30 tested V. parahaemolyticus strains, with no cross-reactivity observed with 30 other common foodborne pathogenic bacteria. The detection sensitivity for both the fluorescent and colorimetric methods reached 10⁻¹ ng/μL, with a minimum detection limit of 10 CFU/25 g for artificially contaminated samples. The entire detection process, including sample preparation, requires only approximately 20 min—significantly faster than traditional culture (24–72 h) or even conventional PCR methods. Collaborative validation across five independent laboratories confirmed excellent reproducibility, with inter-laboratory agreement yielding a Kappa coefficient of 0.98. The ERA method operates at a low, constant temperature (37–39 °C), eliminating the need for thermal cyclers. When combined with portable isothermal amplification devices and visual (colorimetric) readout, it offers a distinct advantage in terms of speed, cost-effectiveness, and suitability for resource-limited or field settings compared to existing PCR-based or culture-based platforms. This method is simple to operate, rapid, sensitive, and highly suitable for on-site application, providing a reliable and practical technical solution for the rapid screening and risk monitoring of V. parahaemolyticus in exported aquatic products. Full article

Background/Objectives: Thalassemia and sickle cell anemia (SCA) patients require regular blood transfusions, a necessity that increases the risk of alloimmunization and complicates subsequent transfusion management. Methods: This retrospective cohort study, conducted at King Saud Medical City (KSMC) and King Fahad Medical City (KFMC) between 2018 and 2022, evaluated the frequency and risk factors of alloimmunization among 144 transfusion-dependent patients in Riyadh, Saudi Arabia. Results: By reviewing clinical and transfusion records alongside antibody screening results, the study found an overall alloimmunization prevalence of 20.1%. Notably, females exhibited a significantly higher rate (13.2%) compared to males (6.8%; p = 0.003), and younger patients (<20 years) showed a higher prevalence than older cohorts (p = 0.004). Analysis of ABO blood groups revealed that group A patients had a significantly lower alloimmunization rate (7.5%) compared to non-A patients (23.1%; p = 0.018), a finding that raises hypotheses about differential immune responsiveness but requires confirmation in larger studies. Group B showed the highest rate (35.3%), though this did not reach statistical significance after correction for multiple comparisons. RhD status was not significantly associated with alloimmunization. The most frequent alloantibodies identified were anti-E (31.3%), anti-K (12.5%), anti-D (10.4%), and anti-C (10.4%). Logistic regression further identified gender as a significant predictor (OR = 0.270; 95% CI: 0.113–0.646). Conclusions: Given that alloimmunization rates in Riyadh are moderately high—particularly among females and specific blood groups—and that the antibody profile (anti-E, anti-K, anti-C, anti-D) mirrors patterns seen in populations with recipient–donor ethnic mismatches, implementing extended blood group phenotyping for at least Rh (C, c, E, e) and Kell antigens prior to the first transfusion, and incorporating these findings into donor selection protocols, is critical to mitigating these risks. Full article

Background/Objectives: Nosocomial outbreaks of viral respiratory infections strain healthcare systems and endanger patients and healthcare workers (HCWs). We describe two large nosocomial outbreaks with the SARS-CoV-2 Alpha variant, during its initial emergence in Germany, to assess transmission dynamics, effectiveness of control measures, and challenges in managing highly transmissible respiratory viruses. Methods: Confirmed cases were inpatients, HCWs, or their contacts testing SARS-CoV-2-positive since 1 January 2021 (Hospital A [HA])) or 21 January 2021 (Hospital B [HB])) with N501Y and delH69/V70 spike gene mutations. We conducted case interviews, reviewed medical records and shift schedules, and performed sequencing, genome reconstruction, and phylogenetic analysis. We describe cases, transmission chains, and control measures. Results: HA reported 18 patient cases, 20 HCW cases, and 33 community cases (N = 71). HB reported 48 patient cases, 43 HCW cases (13 in a COVID-19 ward), and 27 community cases (N = 118). In-hospital transmission occurred patient-to-patient, HCW-to-patient, patient-to-HCW, and HCW-to-HCW. HA halted admissions immediately after the initial cases; HB implemented measures gradually. Regular testing detected pre-symptomatic (HA = 6; HB = 18) and asymptomatic cases (HA = 3; HB = 13). Testing of agency staff was incomplete. The suspected primary case was an HCW in HA and a patient in HB who required resuscitation shortly after admission. Conclusions: Early COVID-19 outbreaks offer valuable lessons for managing emerging nosocomial outbreaks of highly transmissible respiratory viruses. Our findings provide empirical evidence for effective interventions, including rapid response, testing, HCW protection, and rigorous contact tracing in high-risk emergency situations. Managing agency staff remains a major challenge. Full article

Pseudostellaria heterophylla, an important traditional medicinal plant in China, has suffered increasing yield and quality loss due to leaf spot disease in recent years. In this study, the causal agent was conclusively identified as Sclerotiophoma versabilis through detailed morphological characteristics and multi-locus phylogenetic analyses based on the internal transcribed spacer regions (ITS), the 28S large subunit of the nrDNA (LSU), RNA polymerase II (rpb2), and ß-tubulin (tub2) sequences. Pathogenicity tests fulfilled Koch’s postulates, thereby resolving previous taxonomic inconsistencies regarding this disease. The effects of environmental and nutritional factors on mycelial growth, conidial germination, and infection were systematically evaluated. Optimal mycelial growth occurred at 20–25 °C, pH 6–8, under continuous light. Optimal mycelial growth occurred at 20–25 °C, pH 6–8, under continuous light, while conidial germination was maximized at 20–25 °C and pH 6–7 under continuous light. Starch and glycine were identified as the most favorable carbon and nitrogen sources for the fungal mycelial growth, respectively. Infection assays indicated an incubation period of approximately 3 d and maximal disease development at moderate temperatures under low-light conditions, with 6 d-old cultures exhibiting the greatest infectivity. Microscopic observations revealed that S. versabilis penetrated host tissues directly or via stomata without forming specialized infection structures. These findings integrate taxonomic resolution with ecological and infection biology analyses, providing mechanistic insight into the environmental drivers of leaf spot epidemics and a scientific basis for disease-risk assessment and management in P. heterophylla production systems. Full article

The development of beekeeping in Ecuador has generated the need to strengthen the bee health program. Research on the main pathogens responsible for diseases like nosemosis, which can severely impact bee health, is of special interest. This study aims to identify the Nosema apis and/or Nosema ceranae species infecting honey bee colonies located in the northern Andean region of Ecuador using multiplex PCR targeting the RNA polymerase II gene (RPB1), and the phylogenetic analysis of N. ceranae based on the 16 S rRNA gene sequences. Among the 164 honey bee samples collected from colonies in the provinces of Carchi, Imbabura, and Pichincha, the prevalence of Nosema apis and Nosema ceranae was 14.63% and 21.34%, respectively. Phylogenetic analysis showed that N. ceranae from Ecuador is closely related to the sequences from Argentina and Brazil. These findings provide the first molecular confirmation of N. ceranae in Ecuador and support the need for molecular monitoring of honey bee pathogens in the region. Full article

Antimicrobial resistance (AMR) poses a severe threat to global health by limiting treatment options and increasing clinical and economic burdens. This review synthesizes evidence showing that resistance evolution is strongly shaped by antibiotic pressure, leading to the accumulation of adaptive mutations, activation of efflux systems, and widespread dissemination of resistance determinants across clinical, animal, and environmental settings. We highlight recent genomic, metagenomic, and structural findings that elucidate the molecular basis of AMR, with particular emphasis on horizontal gene transfer mediated by mobile genetic elements such as plasmids, integrons, and transposons. Analyses across One Health interfaces reveal extensive sharing of antimicrobial resistance genes among humans, livestock, and environmental reservoirs, identifying Enterobacteriaceae and ESKAPE pathogens as key hubs of resistance dissemination. Special focus is placed on Acinetobacter baumannii, where phylogenetic and three-dimensional structural analyses of class D β-lactamases OXA-23 and OXA-24/40 demonstrate a conserved catalytic framework coupled with substantial sequence and conformational variability. These structural differences likely influence carbapenem specificity and resistance levels. Collectively, the findings underscore how genetic diversity, mobile elements, and structural adaptation converge to drive AMR, reinforcing the need for integrated genomic and structural approaches to guide surveillance and antimicrobial development. Full article