Search Results (323)

Objectives: This study investigated the associations of biochemical and body water distribution parameters with dengue status, as well as their discriminatory ability, among hospitalized adults with febrile illnesses and evaluated whether dynamic changes in body water volumes were associated with length of hospital stay (LOS) in dengue patients. Methods: A prospective observational cohort study was conducted at a tertiary care hospital involving 186 hospitalized adults (age ≥ 18 years) with fever onset ≤ 5 days and suspected dengue. Body water parameters were assessed by bioelectrical impedance analysis (BIA) using the InBody S10 body composition analyzer at admission (T1), defervescence (T2), and discharge (T3) in dengue patients and at admission only in other febrile illness (OFI) cases. Laboratory data and LOS were retrieved from the hospital information system. Linear and logistic regression models were used to examine the associations and interactions. Discriminative performance was assessed using a receiver operating characteristic (ROC) curve analysis. Results: The proportion of dengue cases was 55.9% (n = 104). Higher levels of lymphocytes, hematocrit, hemoglobin, AST, and ALT were associated with an increased likelihood of dengue, whereas elevated WBC counts, neutrophils, platelets, CRP, sodium, chloride, and the extracellular water-to-total body water ratio (ECW/TBW) were associated with a reduced likelihood of dengue. ROC analysis indicated that WBC showed the best diagnostic performance. In dengue patients, a greater increase in ECW volume from admission to defervescence was associated with a longer LOS in males, and ratio-based body water parameters showed longitudinal variation across dengue phases. Conclusions: Several hematologic, biochemical, and BIA-derived body water parameters were associated with dengue status. Among dengue patients, dynamic ECW changes were associated with longer LOS in males, and ratio-based fluid indices were more sensitive than absolute water volumes in reflecting fluid redistribution throughout the dengue course. Full article

Background: Malaria remains hyperendemic in the Democratic Republic of the Congo, while arboviral infections are increasingly reported but remain under-surveilled, particularly in remote regions. Overlapping ecological niches and non-specific clinical presentations complicate case management and surveillance. Methods: A cross-sectional door-to-door survey was conducted in December 2023 in Inkanamongo village (Lokolia Health Area, Boende Health Zone, Tshuapa Province). Blood samples were collected from 379 adults; malaria infection was assessed by using HRP2-based rapid diagnostic tests, and arboviral IgG antibodies were measured on dried blood spots using Luminex^® multiplex immunoassay. Sociodemographic data were collected via standardized questionnaires. Results: Malaria prevalence was 51.7% (95%CI: 46.7–56.7). Overall arboviral seroprevalence reached 78.4% (95%CI: 73.1–81.5), dominated by O’nyong-nyong virus, 42.8% (95%CI: 37.6–47.5), Rift Valley fever virus, 32.0% (95%CI: 26.9–36.2), and chikungunya virus, 23.4% (95%CI: 19.0–27.4). Concurrent malaria infection and arboviral exposure were observed in 40.4% (95%CI: 35.6–45.4) of participants. No sociodemographic factors were significantly associated with co-exposure in the multivariable analysis. Conclusions: Substantial co-exposure of malaria and multiple arboviruses occurs in this remote Congo Basin setting. Integrated surveillance and improved diagnostics are urgently needed to guide febrile illness management and preparedness in under-resourced regions. Full article

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

Background: Early differentiation of mosquito-borne viral infections from other causes of acute febrile illness remains challenging, particularly in endemic and resource-limited settings. Artificial intelligence (AI) models have been proposed to improve early diagnosis, but their incremental value over conventional approaches is unclear. Methods: We conducted a systematic review and meta-analysis of comparative studies evaluating AI/machine learning models versus conventional approaches (clinical assessment, laboratory-based pathways, or traditional statistical models) for early detection of mosquito-borne viral infections. PubMed, Embase, and Scopus were searched through August 2025. Paired performance metrics were synthesized using fixed- and random-effects models. Outcomes included AUC, sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV). Risk of bias was assessed using PROBAST. Results: Thirteen studies met inclusion criteria. Under random-effects models, AI improved sensitivity (ES = 2.64, p = 0.028), specificity (ES = 5.55, p < 0.001), accuracy (ES = 3.19, p < 0.001), and NPV (ES = 13.84, p < 0.001). No consistent advantage was observed for AUC, and PPV findings were inconsistent. Substantial heterogeneity was present across outcomes (I² = 100%). Most studies relied on internal validation, and PROBAST identified high risk of bias in the analysis domain in over half. Conclusions: AI-based models may enhance threshold-dependent performance metrics, supporting their use as adjunctive decision-support tools for early triage and case exclusion, while external validation and implementation-focused research remain essential. Full article

Background: Human granulocytic anaplasmosis (HGA) is a tick-borne zoonotic infection caused by Anaplasma phagocytophilum and transmitted by Ixodes species. In temperate regions, HGA is considered seasonal, with most cases occurring during late spring and summer. We describe two cases of HGA diagnosed in January during a winter period with episodic temperatures exceeding thresholds for tick activity, highlighting atypical seasonal presentation and diagnostic challenges. Methods: This report details the clinical course, diagnostic reasoning, and management of two patients evaluated at a tertiary care hospital in Suffolk County, New York. Data were derived from direct clinical care and the electronic health record. The institutional review board determined this work did not constitute human subject research. Written informed consent was obtained from both patients. Results: Both patients presented with acute febrile illness and characteristic laboratory abnormalities. Due to winter season, tick-borne infection was not initially suspected, resulting in delayed consideration. PCR testing confirmed A. phagocytophilum infection in Case 1, meeting CDC criteria for confirmed HGA. Case 2 met CDC criteria for probable HGA based on serologic testing showing elevated IgG (1:320) in the appropriate clinical context. Treatment with doxycycline led to rapid clinical improvement and complete recovery. Conclusions: These cases demonstrate that HGA can be diagnosed during winter months in endemic regions. Although the precise timing of infection cannot be determined, these observations occurred during a period when episodic temperatures exceeded thresholds for tick activity. The cases highlight limitations of season-based diagnostic assumptions and suggest maintaining clinical suspicion for anaplasmosis year-round in endemic areas. Full article

Background/Objectives: Fever can develop from several causes, including infectious diseases, noninfectious inflammatory diseases (NIID), malignancies, and other medical conditions. Although serum ferritin (SF) level can help differentiate infectious from non-infectious diseases, its discriminative ability (specificity) is far from satisfactory. The aim of this study was to develop a diagnostic prediction model to distinguish infectious diseases from other febrile illnesses using only common blood tests available on admission, in addition to SF level, in patients with undiagnosed fever. Methods: This single-center retrospective observational study included patients with fever of unidentified origin aged ≥18 years admitted to a Japanese acute care hospital between 1 January 2013, and 31 December 2022. They were divided into infectious and non-infectious disease groups based on their final diagnosis. Machine learning and multivariable logistic regression analysis were used to develop a model to differentiate infectious diseases from non-infectious diseases. Model performance was evaluated using area under the curve (AUC), shrinkage coefficient, and stratified likelihood ratio. Results: Among the 143 patients included, 73 had infectious diseases. A prediction model consisting of five factors—serum white blood cell count, neutrophil percentage, platelet count, lactate dehydrogenase level, and log-transformed SF level—was developed. The AUC of the model was 0.794 (95% confidence interval: 0.721–0.867) with a sensitivity of 77.1%, specificity of 68.5%, shrinkage coefficient of 0.876, and stratified likelihood ratio of 0.13–5.04. Conclusions: We developed a prediction model consisting of only five high-performing indicators, which would help differentiate infectious diseases from other fever causes early after admission. Full article

Dengue is the leading mosquito-borne viral cause of human illness and death. More than four billion people globally are at risk of dengue virus (DENV) infection, and most infections are asymptomatic or present with a non-specific febrile illness. We characterise the first complete DENV-2 genome from Sierra Leone, recovered from a febrile adult who tested RT-PCR–positive. The sequence was identified as DENV-2 genotype II, lineage F.1.1. Phylogenetically, the Sierra Leone genome formed a well-supported sister lineage with a 2024 USA DENV-2 genome; both were nested within but clearly diverged from Indian DENV-2 sequences (2021–2022) and were distinct from the Réunion DENV-2 clade. The degree of genetic divergence was incompatible with a recent or direct import of a South Asian lineage and was more consistent with diversification in an under-sampled Indian Ocean/South Asia network or outside this region in Africa. With a single Sierra Leone genome, the source and extent of local transmission remain unresolved. These findings underscore the benefits of integrating differential diagnostics and genomics into routine care for febrile illness and sustaining regional arboviral surveillance. Full article

Toscana virus (TOSV), a negative-sense RNA phlebovirus transmitted by Phlebotomus sandflies and endemic in Mediterranean regions, is an emerging pathogen capable of causing diseases ranging from mild febrile illness to severe central nervous system involvement. With no licensed vaccines or specific antiviral therapies available, the identification of novel therapeutic approaches is urgently needed. Microbial secondary metabolites have recently attracted attention for their broad-spectrum antiviral activities. Among them, monensin and brefeldin A have shown antiviral efficacy against a variety of viruses, often by disrupting viral protein trafficking and inducing Golgi-associated stress responses. However, their potential activity in the context of TOSV infection has not yet been explored. This study aimed to evaluate the in vitro antiviral activity of monensin and brefeldin A against TOSV and to gain mechanistic insights into their effects at the cellular level. Vero cells were infected with TOSV and treated with monensin (1.5–25 µM) or brefeldin A (10.9–175 nM) at different time points (4, 6, 12, 24 h). Cytotoxicity was assessed using MTT and hemolysis assays. Antiviral activity was measured via plaque reduction assays and quantitative real-time PCR targeting the viral L gene. Western blot analysis was performed to assess TFE3 expression, a transcription factor associated with the Golgi stress response. Monensin exhibited rapid antiviral activity, achieving IC₅₀ values of 2.7 µM and 2.5 µM at 4 and 6 h post-treatment, respectively, with dose-dependent suppression of viral L gene expression. Brefeldin A displayed a delayed effect, with maximal inhibition after 12 h (IC₅₀ = 66.9 nM). Monensin treatment induced a concentration-dependent upregulation of TFE3, while brefeldin A caused only a modest increase, suggesting differential activation of the Golgi stress response during TOSV infection. These findings support the potential of microbial metabolites as therapeutic candidates for emerging arboviral infections in the Mediterranean region. Full article

Objectives: Procalcitonin (PCT) is used increasingly in emergency settings to guide evaluation of febrile illnesses, but its role in pediatric infectious diarrhea, particularly as a marker of severity, remains unclear. The study objective evaluates whether PCT correlates with clinical severity and outcomes in pediatric infectious diarrhea presenting to the emergency department (ED). Methods: This prospective study enrolled 105 children with infectious diarrhea presenting to a tertiary pediatric ED. Serum PCT, C-reactive protein, clinical features, hydration status, treatment decisions (including hospitalization and antibiotic use), and outcomes were analyzed. PCT cutoffs (<0.25, <0.5, and <1.0 ng/mL) were evaluated for their associations with Salmonella infection and severity measures, including dehydration, hospitalization, length of stay, and antibiotic use. Results: Thirty-five patients (33.3%) had Salmonella enteritidis. PCT levels did not differ significantly between Salmonella-positive and negative cases (median 0.49 vs. 0.46 ng/mL; p = 0.84), and PCT demonstrated poor diagnostic performance (AUC 0.49). In contrast, PCT was strongly associated with markers of severity. Compared with lower PCT levels, children with PCT ≥ 0.25 ng/mL were more frequently hospitalized (92.1% vs. 52.6%; p < 0.001) and had longer hospital stays (4.41 vs. 3.00 days; p < 0.001). Higher PCT levels were also associated with more dehydration, higher CRP (all p < 0.001), and greater antibiotic use (66.7% vs. 23.7%; p < 0.001). PCT thresholds of 0.25–0.5 ng/mL consistently identified children at increased risk for admission and higher treatment intensity. Conclusions: PCT should not be used as a diagnostic marker for Salmonella enteritidis. Instead, it reflects the host inflammatory response and is strongly associated with clinical severity in children with acute infectious diarrhea evaluated in the ED. The incorporation of PCT thresholds into ED assessment may support early severity-based risk stratification and inform decisions regarding admission and treatment intensity. Full article

Background: Rickettsioses disproportionately affect vulnerable populations and are frequently misdiagnosed as other febrile illnesses in Yucatan, the Mexican state with the greatest diversity of Rickettsia spp. Although significant seroprevalence has been reported in rural communities, the last population-based study was conducted over two decades ago, despite environmental and social changes that have likely increased transmission risk. This study aimed to estimate the seroprevalence of spotted fever group (SFG) and typhus group (TG) of Rickettsia in an endemic area of southeastern Mexico. Methods: A cross-sectional analytical study was conducted among 390 participants. Indirect immunofluorescence was used to detect IgG antibodies against SFG and TG of Rickettsia. Sociodemographic characteristics of participants, along with environmental and community-level variables from their regions of residence, were analyzed. Results: The overall seroprevalence of both Rickettsia groups was 31.2%. Higher maximum temperatures were associated with an increase in Rickettsia seroprevalence (PR = 4.18; 95% CI: 3.40–5.14), while higher population density was associated with a decrease in seroprevalence (PR = 0.97; 95% CI: 0.96–0.98). Conclusions: Rickettsia seroprevalence in Yucatan remains high and is shaped by both environmental and demographic factors. These findings highlight the need to strengthen surveillance and prevention strategies that integrate ecological and social determinants within a One Health framework. Full article

Murine typhus (also called flea-borne or endemic typhus) is an undifferentiated febrile illness caused by the bacterium Rickettsia typhi. The disease, transmitted by rat and cat fleas, is endemic to seaboard regions worldwide. Recently, murine typhus has reemerged as an increasingly recognized cause of febrile illness in the United States, especially in Texas and Southern California. In addition to fever, manifestations often include headache, malaise, myalgias, and a maculopapular rash in approximately half of cases. Although usually considered a mild illness, when untreated, symptoms can last up to 3 weeks. Severe manifestations such as pneumonitis, acute kidney injury, and meningoencephalitis may occur. Historically, death has occurred in 0.4%, but in Southern California, the case fatality rate has been recently recorded at 1.8%. As murine typhus has reemerged, there have been growing reports that this infection has triggered hemophagocytic lymphohistiocytosis, a life-threatening hyperinflammatory syndrome. We herein report two fatal cases of hemophagocytic lymphohistiocytosis secondary to murine typhus. Autopsy revealed typhus group rickettsial antigen in tissues via immunohistochemistry, along with hemophagocytosis. Interestingly, the classic vascular and perivascular histopathologic findings associated with disseminated rickettsial infection were absent. These findings highlight an aberrant inflammatory cascade leading to hemophagocytic lymphohistiocytosis. Full article

Purpose: Kawasaki disease (KD) is an acute systemic vasculitis that can result in coronary artery lesions (CALs). This study aims to explore the expression levels of serum Ninjurin-1 (NINJ1) and high-mobility group box 1 (HMGB1) in the acute phase of KD and evaluate their clinical significance. Methods: A total of 180 children were enrolled, comprising 113 KD patients, 35 healthy controls (HCs), and 32 febrile controls whose clinical data were collected. Serum levels of NINJ1, HMGB1, Lactate Dehydrogenase (LDH), and routine inflammatory markers were compared across groups. Serum levels of NINJ1 and HMGB1 were measured via ELISA. Correlations were analyzed using Spearman tests. The diagnostic and predictive performance of biomarkers was assessed using Receiver Operating Characteristic (ROC) curve analyses. Results: Serum levels of NINJ1 and HMGB1 were significantly elevated in the KD group compared with both the HC and FC groups (all p < 0.001). NINJ1 levels were positively correlated with the z-scores of coronary arteries and were significantly higher in the CAL subgroup than in the non-CAL subgroup (p = 0.004). A strong positive correlation was observed between serum NINJ1 and HMGB1 levels in the KD group (p < 0.001). Conclusions: Elevated serum NINJ1 levels during the acute phase of KD were associated with the presence of CALs, while HMGB1 shows promise in differentiating KD from other febrile illnesses. These findings collectively suggest that the NINJ1-HMGB1 axis may offer novel insights into the mechanisms underlying KD vasculitis, supporting further investigation into its potential clinical relevance. Full article

Viral hemorrhagic fevers (VHFs) are highly lethal diseases that often present non-specific, influenza-like symptoms in their early stages, making clinical recognition and differentiation from other febrile illnesses difficult. This overlap underscores the critical need for diagnostic tests that are both sensitive and specific. Point-of-care (POC) diagnostic tests are an invaluable tool for detecting and controlling the spread of pathogens that threaten public health, such as VHFs, as these require fast, accurate diagnostics to ensure biosafety and appropriate mobilization of resources during outbreaks. Current molecular and serological diagnostic tests, while efficient and effective, lack the characteristics required of a POC test (POCT) to quickly and easily respond to a VHF outbreak while maintaining a low cost. Clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostic tests have gained popularity as POCTs due to their inherent attractive qualities, including high sensitivity and specificity, adaptability, low cost, quick turnaround time, and ease of use. However, studies on the development of CRISPR-based POC diagnostic tests for VHFs are limited. This review summarizes the current CRISPR-based POCTs for VHFs, including Ebola virus (EBOV), Lassa virus (LASV), Dengue virus (DENV), and Crimean–Congo hemorrhagic fever virus (CCHF). The isothermal pre-amplification methods commonly paired with CRISPR-based tests, such as loop-mediated isothermal amplification (LAMP) and recombinase polymerase amplification (RPA), are also discussed. Full article

Scrub typhus, caused by Orientia tsutsugamushi, remains a neglected cause of acute febrile illness. Molecular testing of blood supports early diagnosis, yet once doxycycline is started, blood qPCR positivity can drop rapidly, complicating short-term follow-up and relapse surveillance. We compared detection across multiple clinical specimens and evaluated nasopharyngeal swabs (NPSs) as noninvasive supplementary specimens during treatment initiation. In a prospective single-center cohort from Hainan, China, we enrolled 20 patients with scrub typhus. Blood, NPS, urine, and stool were collected before doxycycline administration 24 h after the first dose and on day 5. qPCR was performed for the analysis of Orientia tsutsugamushi. qPCR-positive specimens were subjected to nested PCR targeting TSA56, and nested PCR-positive amplicons were Sanger sequenced for genotyping. Before treatment, O. tsutsugamushi DNA was detected in 15/20 blood samples (75.00%) and 5/20 NPS samples (25.00%), but 0/20 urine samples (0%) and 0/20 stool samples (0%). At 24 h after treatment, detection in blood was 0/20 (0%) while NPS samples were positive in 3/20 (15.00%). All specimens were negative by day 5 after treatment. Across sequenced NPS positives (n = 3), Karp 2/3 (66.77%) and Gilliam 1/3 (33.33%) predominated. In paired blood–NPS positives, inter-specimen homology was high (percentage nucleotide identity 100% for Karp and 100% for Gilliam). NPS is not sensitive enough for primary diagnosis; however, within the first 24 h after doxycycline it offers a practical, noninvasive supplementary specimen to support short-term follow-up and community-based sampling when venipuncture or transport are constrained. Larger, multi-center studies are warranted to refine sampling windows and diagnostic performance. Full article

Background: Bilateral facial nerve palsy (BFNP) is a rare clinical entity in children and is more often associated with systemic or infectious diseases than unilateral facial palsy. Epstein–Barr virus (EBV) infection is an uncommon but recognized cause of facial nerve palsy and may present with bilateral involvement. Case presentation: We report the case of a 3-year-old boy who presented with progressive bilateral facial weakness following a febrile illness with pharyngitis and cervical lymphadenopathy. Neurological examination revealed complete bilateral facial paralysis (House–Brackmann grade VI). Laboratory investigations showed lymphocytosis and confirmed acute EBV infection through positive viral capsid antigen IgM and detectable EBV DNA in peripheral blood. Cerebrospinal fluid analysis demonstrated mild pleocytosis with negative EBV DNA. Brain magnetic resonance imaging revealed unilateral enhancement of the left facial nerve. Audiologic evaluation supported peripheral facial nerve dysfunction. The patient was treated with systemic corticosteroids, vitamin B complex supplementation, artificial tears, and speech therapy, resulting in gradual and substantial clinical improvement over five months. Discussion: A review of the pediatric literature identified only six previously reported cases of EBV-associated BFNP. The pathogenesis may involve either direct viral neurotropism or a post-infectious immune-mediated mechanism. Diagnostic evaluation is essential to exclude other serious causes of BFNP, particularly Lyme disease and Guillain–Barré syndrome. Conclusions: EBV infection should be considered in the differential diagnosis of BFNP in children. Prognosis is generally favorable, although recovery may be prolonged. Further studies are needed to clarify optimal diagnostic and therapeutic approaches. Full article