Search Results (140)

Background/Objectives: Azacitidine (AZA) is the standard of care for patients with higher-risk Myelodysplastic Syndromes (MDS). There is limited real-life data, however, characterizing its efficacy and safety profile in elderly patients. Methods: We conducted a single-center retrospective cohort chart review to compare front-line AZA therapy in patients ≥75 years (elderly) vs. <75 years (younger) with higher-risk MDS treated at our cancer center. The primary endpoint was overall survival and main secondary endpoints included response, as per the 2006 International Working Group consensus criteria, leukemia-free survival, transfusion independence, and safety outcomes. Results: In total, 55 patients were elderly (median age: 79.9 years), including 27 patients >80 years, and 41 were younger (median age: 69.4 years). Baseline demographic variables were similar between both groups. The majority of elderly patients (98%) received the full dose of AZA (75 mg/m²), compared with 90% of younger patients. The median number of AZA cycles was 8 (range: 2–69) in elderly and 7.75 (range: 1–96) in younger patients. Treatment delays occurred in 36.4% of elderly and 29.3% of younger patients, most commonly due to infection complications in both groups (p = 0.076). Disease control rates (complete remission + partial remission + stable disease) were 92.9% in the younger subgroup and 96.4% in the elderly subgroup (p = 0.154). Relapse occurred in 48.8% of younger patients and 40.0% of elderly patients. Median overall survival (OS) was 17.3 months for the younger subgroup, 15.7 months for the elderly subgroup (p = 0.771), and 11.9 months among patients >80 years (p = 0.381). Mortality rates and causes of death were similar between both subgroups. Most common causes of death included disease progression, sepsis, febrile neutropenia, and pneumonia. Conclusions: AZA monotherapy resulted in a high response rate and was well-tolerated in elderly patients with higher-risk MDS. These findings remain consistent in the real-world setting despite potential confounding factors that may contribute to inferior outcomes. Full article

Background: China’s influenza vaccine (InfV) has undergone multiple iterations and numerous technological breakthroughs, providing tremendous impetus and solid support for the development of China’s health sector. As the number of vaccinated individuals continues to rise, the importance of ongoing surveillance and evaluation of vaccine safety has become increasingly prominent, forming part of efforts to maintain public trust in the national immunization program and ensure its sustainability. Methods: From 2016 to 2025, data on suspected adverse events following immunization (AEFIs) related to InfV administration were extracted from the Chinese National Immunization Information System (CNIIS). Data on InfV vaccination doses were obtained from the Anhui Provincial Immunization Information Management System. A descriptive statistical method was used to analyze the distribution characteristics of AEFIs, and the chi-square test was applied to evaluate differences in reporting rates. Results: Between 2016 and 2025, a total of 4026 AEFI reports related to InfV were monitored through the CNIIS. The overall reporting rate was 34.40 per 100,000 doses. Specifically, common adverse reactions and rare adverse reactions accounted for 95.88% (3860 cases) and 3.38% (136 cases), with reporting rates of 32.98 per 100,000 doses and 1.16 per 100,000 doses, respectively. Among common adverse reactions, the reporting rates of fever (axillary temperature ≥ 38.6 °C), local redness and swelling at the injection site (diameter > 5.0 cm), and local induration (diameter > 5.0 cm) were 9.62 per 100,000 doses, 1.96 per 100,000 doses, and 1.20 per 100,000 doses, respectively. Among rare adverse reactions, the reporting rates of allergic rash, angioedema, anaphylactic shock, febrile convulsions, anaphylactoid purpura, thrombocytopenic purpura, epilepsy, Guillain–Barré syndrome, and aseptic abscess were 0.98, 0.05, 0.03, 0.03, 0.02, 0.02, 0.01, 0.01, and 0.01 per 100,000 doses, respectively. No cases were reported for subunit inactivated influenza vaccine (IIV, Subunit). Statistically significant differences were observed in the reporting rates of allergic rash across different types of InfV (χ² = 36.83, p < 0.05), with trivalent inactivated influenza vaccine (IIV3, Split) and trivalent live attenuated influenza virus vaccine (LAIV3) showing the highest reporting rates. Most adverse events following vaccination occurred within 24 h after inoculation. Conclusions: From 2016 to 2025, the overall reporting rate of AEFIs after InfV administration in Anhui Province was within an acceptable range. Common adverse reactions were common, while rare adverse reactions were few, mainly consisting of allergic reactions. These results indicate that InfV has a favorable safety profile, and continuous strengthening of AEFI surveillance for InfV and improvement of surveillance quality are warranted. Full article

Background: Anaplasmosis is an emerging tick-borne infection that typically presents as a non-specific febrile illness, with variable degrees of cytopenias and liver tests abnormalities. Severe complications remain atypical and uncommon. Case Report: We report a case of acute pulmonary embolism (PE) occurring during confirmed anaplasmosis in a 73-year-old male with no traditional thromboembolic risk factors. The patient presented with fever, constitutional symptoms, thrombocytopenia, leukopenia, and abnormal liver tests, raising suspicion for a tick-borne illness. Despite early clinical improvement on doxycycline, persistent tachycardia triggered further evaluation and uncovered an acute PE. Comprehensive workup at admission and repeated 14 months later excluded inherited and acquired thrombophilias, malignancies, autoimmune diseases, and alternative infectious etiologies. The patient was treated with doxycycline 100 mg orally twice daily for 10 days and anticoagulation with unfractionated heparin followed by 6 months of apixaban for a first episode of provoked PE. He attained complete clinical recovery without recurrence of thrombosis at the two-year follow-up. Discussion: Infectious diseases are increasingly recognized as contributors to thrombosis through inflammation-mediated hypercoagulability and endothelial dysfunction. Pulmonary involvement in anaplasmosis typically manifests as pneumonitis, pneumonia or acute respiratory distress syndrome, but thrombotic complications such as PE are exceedingly rare. This case highlights a rare but clinically significant vascular complication of anaplasmosis and underscores the importance of considering thromboembolic events in patients with persistent or unexplained tachycardia. Conclusions: As the incidence of anaplasmosis continues to rise, greater awareness of its potential cardiovascular manifestations is essential. Early recognition and prompt treatment with doxycycline remain critical, while further studies are needed to better define the thrombotic risk associated with this infection. Full article

Background/Objectives: Arboviral diseases transmitted by Aedes mosquitoes, including Dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV), represent a major public health challenge in tropical regions. Their clinical similarity complicates differential diagnosis, particularly in settings of viral co-circulation, and may lead to underdiagnosis. The objective was to detect acute dengue infection and assess serological evidence of Chikungunya and Zika virus exposure among patients with acute febrile syndrome and clinical suspicion of dengue in the department of Córdoba, Colombia. Methods: A prospective descriptive study was conducted between 2023 and 2024 in healthcare institutions in Montería and Sahagún. Serum samples were analyzed by ELISA to detect DENV NS1 antigen, anti-CHIKV IgM, and anti-ZIKV IgG antibodies. Sociodemographic, clinical, and laboratory variables were described, and the association between prior ZIKV infection and dengue severity was assessed. Results: Ninety patients were included. Isolated laboratory marker detection was observed for DENV NS1 antigen in 36.7% (33/90), anti-ZIKV IgG in 30.0% (27/90), and anti-CHIKV IgM in 2.2% (2/90); combined arboviral markers were identified in 22.2% (20/90), and 8.9% (8/90) had no detectable markers. Among NS1-confirmed dengue cases (n = 47), 61.7% (29/47) were classified as dengue with warning signs. Anti-ZIKV IgG detection was not associated with dengue clinical classification (p = 0.989), although platelet counts were lower in IgG-positive cases (p = 0.037). Conclusions: The findings support laboratory-supported diagnosis and integrated acute febrile illness surveillance in Córdoba, including locally adapted vector control, in a setting of arbovirus co-circulation with overlapping laboratory markers. Full article

Orthohantavirus infections are classically associated with hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus cardiopulmonary syndrome (HCPS) in the Americas. However, accumulating evidence indicates that the clinical spectrum is considerably broader, with frequent involvement of organ systems beyond the kidney and lung. Hepatic manifestations, in particular, may mimic acute viral hepatitis, leading to diagnostic challenges and underrecognition. This paper synthesizes published evidence on hepatic involvement in orthohantavirus infection, with a focus on clinical presentation, pathogenic mechanisms, differential diagnosis, biomarkers, and public health implications. Relevant literature was identified through searches of peer-reviewed articles, with emphasis on studies reporting hypertransaminasemia, hepatitis-like illness, and liver injury in confirmed hantavirus infections. Mild to moderate elevations in aminotransferases are common during acute orthohantavirus infection, and in some patients the clinical picture may be dominated by fever, thrombocytopenia, and hepatitis-like abnormalities, closely resembling dengue, leptospirosis, or classical viral hepatitis. Hepatic injury appears to result primarily from systemic endothelial dysfunction, immune-mediated inflammation, and microvascular leakage rather than direct hepatocytopathic effects. Emerging biomarkers of severity, including thrombocytopenia, neutrophil-to-lymphocyte ratio, soluble thrombomodulin, and IL-6 trans-signaling, reflect widespread vascular and inflammatory activation. Diagnostic delays are frequent, particularly in non-endemic regions, due to low clinical awareness and overlapping features with more common febrile hepatotropic syndromes. Orthohantavirus infection should be considered in the differential diagnosis of acute febrile illness with unexplained hypertransaminasemia and thrombocytopenia, especially when epidemiological clues suggest rodent exposure or compatible environmental contexts. Recognizing hepatic involvement as part of a systemic endothelial syndrome may improve diagnostic accuracy, reduce underreporting, and facilitate earlier supportive management. Increased awareness among hepatologists, infectious disease specialists, and emergency physicians is warranted. Full article

Background/Objectives: Arboviruses including dengue virus (DENV), Zika virus (ZIKV), chikungunya virus (CHIKV), yellow fever virus (YFV), and West Nile virus (WNV) co-circulate across the Americas, generating overlapping febrile syndromes that challenge etiological diagnosis based solely on clinical criteria. Cartridge-based multiplex molecular platforms offer potential for decentralized testing in hyperendemic settings, yet independent real-world evaluations of their clinical and analytical performance remain limited. Methods: A retrospective two-phase analytical study was conducted. Phase 1 assessed clinical diagnostic accuracy for dengue using 163 de-identified serum samples classified using a composite reference standard consisting of Panbio NS1 ELISA reactivity (≥11 Panbio units) combined with compatible clinical and epidemiological data, operationalized in accordance with the PAHO 2023 laboratory confirmation algorithm for dengue; RT-qPCR was not routinely available for all archived samples, and reported sensitivity should therefore be interpreted as a conservative lower-bound estimate; Phase 2 evaluated analytical sensitivity across all eight panel targets using characterized arboviral reference strains in serial dilution experiments, with reference RT-qPCR assays as the comparator; this phase was incorporated to characterize detection thresholds for targets not represented by clinical specimens. Results: In Phase 1, the M10 demonstrated sensitivity of 96.0% (96/100), specificity of 100% (63/63), overall accuracy of 97.5%, and near-perfect agreement with the reference standard (Cohen’s κ = 0.95). DENV-3 was the predominant serotype (74/96; 77.1%), followed by DENV-1 (16.7%) and DENV-4 (6.3%); DENV-2 was not detected. In Phase 2, operational LoDs (defined as the lowest concentration yielding a detectable Ct in all triplicate reactions for the RT-qPCR, and from a single cartridge per dilution point for the STANDARD M10) were equivalent or superior to reference RT-qPCR for six targets (DENV-1, DENV-3, DENV-4, ZIKV, WNV, YFV; range 1–5 PFU/mL), while DENV-2 and CHIKV showed 20-fold higher operational LoDs (20 PFU/mL vs. 1 PFU/mL for the reference RT-qPCR); formal LoD₉₅ estimates were not determined. Conclusions: The STANDARD M10 Arbovirus Panel shows high clinical accuracy for dengue and adequate analytical sensitivity for most targets, supporting its use as a complementary decentralized molecular tool. Reduced sensitivity for DENV-2 and CHIKV and the absence of formal LoD₉₅ estimates remain key limitations to be addressed in future validation studies. Full article

Self-limited focal epilepsies in childhood (SELFEs), formerly referred to as “benign epilepsies in childhood”, constitute a heterogeneous group of epileptic conditions with onset predominantly in the neonatal, infantile, and childhood periods. A defining feature of these syndromes is that seizures arise without underlying structural, metabolic, or other demonstrable cerebral pathology, and the overall clinical trajectory is expected to be favorable, with seizures resolving spontaneously over time. Current nosological frameworks divide SELFEs into two broad categories according to age at onset: (a) neonatal and infantile forms, encompassing self-limited familial and non-familial neonatal, neonatal-infantile, and infantile epilepsies, genetic epilepsy with febrile seizures plus (GEFS+), and myoclonic epilepsy of infancy (MEI); and (b) childhood-onset forms, including self-limited epilepsy with centrotemporal spikes (SeLECTS), self-limited epilepsy with autonomic seizures (SeLEAS), childhood occipital visual epilepsy (COVE), and photosensitive occipital lobe epilepsy (POLE). Despite their historically “benign” label, there is no general agreement to include GEFS + and MEI among the group of SELFEs as both these conditions have been not classified as focal epilepsy in general. Accumulating evidence shows that a subset of affected children subsequently develop additional seizure types, cognitive deterioration, and behavioral or neuropsychiatric difficulties—outcomes that the word “benign” does not adequately communicate. Advances in molecular genetics have identified pathogenic variants affecting ion channels, synaptic transmission, and neuronal excitability, reshaping current understanding of disease mechanisms and phenotypic variability across these syndromes. This review highlights clinically relevant challenges in the diagnosis and management of SELFEs, critically examines emerging genotype–phenotype correlations, and provides evidence-based recommendations for antiseizure medication initiation and withdrawal tailored to individual syndrome characteristics and risk profiles. Full article

The diagnosis of enteric fever has become difficult due to the nonspecific and overlapping clinical syndrome of typhoid and paratyphoid infections with other febrile illnesses. Moreover, the rapid emergence of fluoroquinolone-resistant typhoidal Salmonella and the lack of robust diagnostic methods highlight the urgent need for highly sensitive molecular techniques. Here, we evaluated the performance of a rapid, reliable, and cost-effective molecular diagnostic approach for detecting Salmonella Typhi, including the globally dominant haplotype H58 lineage (H58), and Salmonella Paratyphi A. An in-house-built conventional polymerase chain reaction (PCR) was performed on a collection of blood-culture-positive strains, and the sensitivity and specificity were compared with those of the standard blood culture results. H58 and non-H58 Typhi lineages with distinct resistance patterns were confirmed from the previously reported sequencing data. Our PCR result showed that target genes SSPA2308, STY2513, and STY0307 demonstrated 100% sensitivity and specificity for Salmonella Paratyphi A, Salmonella Typhi, and H58 Salmonella Typhi, respectively. The PCR assay reliably detected bacterial DNA at 5.2 × 10⁴ colony-forming units (CFUs), with consistent amplification observed up to 10⁻¹ dilution. This single-nucleotide polymorphism (SNP)-based diagnostic approach has added a new dimension to designing unique markers for multidrug-resistant (MDR)-associated H58 lineage detection and has the potential to inform local treatment algorithms. Full article

Brugada syndrome (BrS) is a rare but potentially life-threatening condition that may lead to sudden cardiac death. Among the causes, dysfunctions of ion channels involved in the cardiac action potential (specifically in SCN5A and SCN10A genes) are particularly significant. Among diagnosed Brugada patients, fever-induced episodes occur in 20–30% of cases. Fever worsens sodium channel dysfunction, as elevated temperature further reduces their conductance. First clinical manifestation of BrS occurs usually during a febrile episode, especially in young people. We performed a multiparametric examination in addition to genetic analysis. We treated a 19-year-old man presenting with subfebrility. During the patient’s subfebrile episodes, 12-lead ECG recordings revealed ST-segment elevations in leads V1–V3. Notably, the patient remained asymptomatic. Targeted genetic testing of SCN5A did not reveal any disease-causing variants as an underlying cause of the syndrome, but the temperature-inducing effect was demonstrated. The occurrence of the Brugada type 1 pattern has also been observed at subfebrile episodes, although significantly rarely. This case demonstrates that in susceptible patients, even a relatively mild elevation in body temperature can trigger ion channel dysfunctions. Timely diagnosis and follow-up are important in preserving quality of life and preventing fatal outcomes. Full article

Background: Brucellosis is a globally distributed zoonotic disease characterized by highly variable clinical manifestations that may mimic systemic autoimmune and inflammatory disorders. In Europe, where the incidence of brucellosis is relatively low, limited clinical awareness may contribute to delayed diagnosis and inappropriate management. In addition to zoonotic transmission, Brucella species are a well-recognized cause of laboratory-acquired infections (LAIs) among microbiology laboratory personnel. Methods: We report a case of laboratory-acquired Brucella abortus infection in a young woman presenting with undulant fever, arthralgia, systemic inflammation, elevated ferritin levels, and antinuclear antibody (ANA) positivity. Microbiological confirmation was achieved through serological testing (ELISA), repeat blood cultures, species-specific quantitative PCR, and whole-genome sequencing (WGS) followed by core genome multilocus sequence typing (cgMLST). Results: Initial laboratory evaluation revealed elevated C-reactive protein, mildly increased ferritin levels (146 ng/mL), abnormal liver enzyme levels, and rising ANA titers (from 1:160 to 1:320), raising suspicion of a systemic autoimmune disorder and prompting consideration of corticosteroid therapy. Although the initial blood culture was negative, subsequent molecular diagnostics and repeat cultures confirmed B. abortus infection. Epidemiological investigation suggested a possible occupational exposure in a diagnostic microbiology laboratory, consistent with a laboratory-acquired infection. Genomic analysis classified the isolate as sequence type 1 (ST1) and demonstrated zero allelic differences compared with the ST1 reference strain. Targeted antimicrobial therapy resulted in complete clinical recovery, supporting an infection-triggered immune response rather than primary autoimmunity. Conclusions: Acute brucellosis should be considered in the differential diagnosis of febrile syndromes accompanied by autoimmune-like laboratory abnormalities, even in low-incidence regions. This case highlights the diagnostic challenges posed by laboratory-acquired brucellosis and underscores the importance of early microbiological investigation and strict biosafety awareness in laboratory settings. 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

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease in which renal involvement is a major determinant of prognosis and is classically dominated by amyloid A (AA) amyloidosis. Non-amyloid renal manifestations are uncommon and poorly characterized. We report a case of clinically overt FMF associated with anti-phospholipase A2 receptor (PLA2R) antibody-positive membranous nephropathy (MN). A 46-year-old man with recurrent febrile episodes fulfilling Tel Hashomer criteria for FMF developed progressive proteinuria with detectable anti-PLA2R antibodies. Genetic testing identified a heterozygous missense MEFV variant in exon 10 (p.Lys695Arg), a mutation with variable penetrance and conflicting pathogenic classification. Kidney biopsy demonstrated PLA2R-positive MN, excluding amyloidosis. After initial conservative management, the patient progressed to nephrotic syndrome complicated by renal vein thrombosis, requiring immunosuppressive therapy according to the Ponticelli regimen in addition to colchicine and anticoagulation, resulting in clinical and immunological remission. In parallel, we performed a systematic review of the literature, identifying only isolated reports of biopsy-proven MN in FMF patients. This case highlights the diagnostic importance of kidney biopsy in FMF patients with proteinuria and illustrates that immune-mediated glomerular disease may occur even in association with non-founder or variably penetrant MEFV mutations, requiring disease-specific management beyond standard autoinflammatory control. Full article

Objectives: To access the effects of febrile seizures from coexisting neurodevelopmental conditions that are commonly associated with autism spectrum disorder. We examined whether febrile seizures are independently associated with ASD after considering neurodevelopmental comorbidities and seizure-related clinical characteristics. Methods: We conducted a nationwide population-based matched cohort study using Taiwan’s National Health Insurance Research Database. The study included 948 children with FS and 3804 age- and sex-matched controls without FS. Participants were followed longitudinally for incident ASD. Associations were evaluated using Cox proportional hazards models with additional analyses restricted to the FS cohort. Neurodevelopmental comorbidities assessed included attention-deficit/hyperactivity disorder (ADHD), epilepsy, and Tourette syndrome/tic disorder. Results: Among 4752 children followed for more than 10 years, 43 (0.9%) developed ASD. FS were not independently associated with ASD in adjusted Cox regression models. In contrast, ADHD, epilepsy, and Tourette syndrome/tic disorder were strongly and consistently associated with ASD across analytic models. Conclusions: Febrile seizures were not independently associated with autism spectrum disorder. Instead, ASD risk was largely explained by coexisting neurodevelopmental comorbidities, consistent with a shared neurodevelopmental susceptibility framework. These findings suggest that developmental surveillance should prioritize children with neurodevelopmental disorders rather than those with febrile seizures alone. Full article

West Nile virus (WNV) is a mosquito-borne flavivirus with one of the widest global distributions. Since its discovery in Uganda in 1937, it has become a major zoonotic pathogen, and after its introduction into the United States in 1999, it spread rapidly across the Americas, becoming the leading cause of neuroinvasive arboviral disease. Its expansion illustrates a remarkable ecological adaptability, further intensified by climate change. In Latin America and the Caribbean, WNV circulation has been consistently documented in birds, horses, and mosquitoes; however, confirmed human cases remain disproportionately scarce compared with North America and Europe. Reports include sporadic human cases in Brazil (>100 since 2014), Mexico (~13), Argentina (2006–2007), Puerto Rico (2007), Nicaragua, and Haiti, while animal and vector evidence extends to Guatemala, El Salvador, Belize, Costa Rica, Bolivia, Paraguay, Colombia, Venezuela, Cuba, and Ecuador. This paradox likely reflects structural limitations within regional health systems, including underdiagnosis, restricted diagnostic capacity, and significant surveillance gaps, particularly in contexts where mild febrile syndromes may be misclassified as dengue, Zika, or Chikungunya. The regional risk of emergence is further amplified by climatic variability, ecological change, and intensifying human–wildlife interactions. Experiences from Europe highlight the importance of early detection, transfusion safety, and integrated surveillance within a One Health framework. Strengthening preparedness in Latin America will require investments in diagnostic infrastructure, implementation of standardized seroepidemiological surveys, development of predictive models tailored to local ecological contexts, and robust intersectoral collaboration. 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