Rickettsia typhi-induced murine typhus is underrecognized in southern U.S. regions such as Texas. While typical symptoms include fever, rash, and mild pulmonary involvement, severe presentations such as pneumonia or acute respiratory distress syndrome (ARDS) can occur. The radiographic "crazy-paving" pattern is nonspecific and can be seen in a variety of infectious and inflammatory pulmonary conditions, creating diagnostic uncertainty. Because pulmonary alveolar proteinosis (PAP) typically prompts consideration of invasive diagnostic evaluation, recognizing infectious mimics has important clinical implications. A 46-year-old man with alcohol use disorder develops fatigue, cough, dysuria, dyspnea, and fever. CT imaging revealed bilateral perihilar ground-glass opacities with interlobular septal thickening ("crazy-paving"). Laboratory studies showed leukocytosis, thrombocytopenia, acute kidney injury, transaminitis, and elevated inflammatory markers. Broad-spectrum antibiotics did not provide symptom relief. Serologic testing confirmed murine typhus; doxycycline led to rapid clinical and radiographic improvement. Four-week follow-up imaging showed near-complete resolution. This is, to our knowledge, the first reported case of murine typhus presenting with radiological and clinical features that closely mimic pulmonary alveolar proteinosis. In endemic regions, murine typhus should be included in the differential diagnosis of diffuse alveolar disease with a crazy-paving pattern, as this overlap may lead to diagnostic uncertainty and potentially unnecessary invasive evaluation. Early recognition and treatment with doxycycline can result in rapid clinical and radiographic resolution.

Rickettsial diseases are a group of vector-borne, zoonotic infections caused by obligate, gram-negative, intracellular coccobacilli within the order Rickettsiales and the genera Rickettsia, Orientia, Ehrlichia, and Anaplasma. These infections are transmitted by hematophagous arthropod vectors, including ticks, mites, fleas, and lice, and occur worldwide among humans who are accidental hosts. Clinical manifestations range from mild febrile illness to severe, life-threatening multisystem disease. Although these infections commonly present with acute fever, headache, myalgias, and rash, the clinical features, severity, and pattern of organ involvement vary according to the infecting species. Murine typhus and epidemic typhus are acute febrile illnesses caused by Rickettsia typhi and R prowazekii, respectively. Together, these organisms comprise the typhus group of the rickettsioses. Both are obligate intracellular, gram-negative coccobacilli transmitted to humans by arthropod vectors. Murine typhus is a flea-borne zoonosis maintained primarily in rodents, although other mammals such as opossums and cats may also contribute to transmission in some regions. Murine typhus has a global distribution and is endemic in warm coastal, tropical, and subtropical areas. Epidemic typhus is spread by the human body louse and occurs mainly in settings where louse infestations are common, including areas affected by war, natural disasters, homelessness, refugee camps, overcrowding, and poor sanitation. Early manifestations of epidemic and murine typhus are nonspecific, with sudden onset of fever, severe headache, and myalgias. A rash, when present, usually begins on the trunk and spreads to the extremities, although it is less common and often less prominent in murine typhus. Murine typhus is usually a mild to moderate illness, but severe disease can occur, particularly in older adults and patients with underlying medical conditions. Epidemic typhus is more severe and may be accompanied by confusion, delirium, hypotension, and multiorgan involvement. Untreated epidemic typhus carries a high mortality rate. As a result, diagnosis is based largely on the clinical presentation together with a history of compatible exposures. With international travel, migration, and population displacement due to war and humanitarian crises, rickettsial diseases are being encountered more frequently outside their traditional endemic regions. Murine and epidemic typhus should be considered in patients presenting with an acute undifferentiated febrile illness, particularly when there is a history of travel to or residence in endemic areas, exposure to fleas or body lice, homelessness, overcrowding, refugee camps, or other conditions associated with poor sanitation. Early recognition and prompt initiation of treatment, usually doxycycline, are critical, as delays in treatment are associated with substantially increased morbidity and mortality. Treatment with doxycycline should be started as soon as typhus is suspected and should not be delayed while awaiting laboratory confirmation.

Murine typhus is a flea-borne disease caused by the bacteria Rickettsia typhi that occurs worldwide, but predominantly in endemic areas. The clinical presentation of typhus is often nonspecific, leading to delays in diagnosis and treatment. The severity of the disease varies widely. Most cases are relatively mild, but some patients develop a very severe form and may die. We report a case of severe murine typhus complicated by septic shock, alveolar hemorrhage, and acute respiratory distress syndrome in a teenager who was born in Somalia and had immigrated from Kenya to Switzerland. Diagnosis was suspected upon admission in the pediatric intensive care unit and was confirmed by PCR. The patient improved with doxycycline treatment. Rickettsial disease should be considered in the differential diagnosis of patients returning from endemic areas, and anti-rickettsial treatment should be started without delay to ensure rapid recovery and avoid severe complications.

Fleaborne typhus (FBT) is reemerging as a significant cause of febrile illness in southern California, USA. We performed enhanced testing on low-titer Rickettsia typhi antibody-positive specimens from patients with FBT-compatible illness reported in Los Angeles County, California, during 2022-2024. We tested 114 specimens by repeat serology and 113 by real-time PCR; 81 (71%) were PCR-positive, and 95 (83%) had higher antibody titers by repeat serology. Most PCR-positive specimens were collected 8-10 days after illness onset, but some were collected up to 15 days after illness onset. All PCR-positive specimens were R. typhi-specific. After additional testing, 113 (99%) suspected cases were reclassified as probable or confirmed FBT cases. Our findings indicate that many low-titer seropositive results represent true infections and that use of minimum serology thresholds for public health investigation underestimates surveillance case counts. Expanding commercial molecular testing capacity will improve clinical FBT diagnosis and enhance surveillance accuracy.

Murine typhus, caused by Rickettsia typhi, is a flea-borne zoonosis that typically presents with fever, headache, myalgias, and rash. Central nervous system involvement is uncommon, and neuroimaging findings that mimic posterior reversible encephalopathy syndrome (PRES) are rarely reported. This case highlights a rare neuroinfectious presentation of murine typhus with PRES-like imaging findings in a young woman. A previously healthy woman in her 30s presented with persistent retro-orbital headaches, intermittent fevers, tremors, dysarthria, photophobia, myalgias, progressive weakness, and recurrent syncopal episodes. Initial computed tomography of the head demonstrated age-advanced microvascular ischemic changes versus possible PRES. Brain magnetic resonance imaging later revealed bilateral parietal-predominant fluid-attenuated inversion recovery (FLAIR) hyperintensities in the white matter, concerning for PRES. Cerebrospinal fluid (CSF) analysis was unremarkable, and extensive infectious and autoimmune evaluation was unrevealing. Despite nondiagnostic testing, persistent fevers and neurologic symptoms prompted empiric doxycycline therapy for suspected atypical infection. Within 48 hours, the patient experienced marked clinical improvement with resolution of fever, dysarthria, tremors, photophobia, and severe headache. Post-discharge serology showed a positive Rickettsia typhi IgM with a negative IgG. While these findings were consistent with possible early murine typhus, the absence of convalescent serologic testing limited definitive confirmation. Murine typhus is increasingly recognized as a cause of severe neurologic disease due to endothelial injury and systemic vasculitis. This case is notable for PRES-like neuroimaging abnormalities, normal CSF studies, and severe neurologic manifestations occurring in an otherwise healthy host without traditional risk factors for severe disease. The patient's rapid clinical improvement following doxycycline therapy was consistent with a rickettsial infection but was not diagnostic of murine typhus. This case highlights the importance of early empiric treatment when rickettsial disease is suspected while awaiting confirmatory testing. This case expands the recognized neurologic spectrum of murine typhus and emphasizes the importance of considering rickettsial infections in patients presenting with unexplained febrile neurologic syndromes and nonspecific MRI abnormalities, particularly in endemic regions.

The Rickettsia genus comprises obligate intracellular bacteria transmitted by arthropods and responsible for clinically relevant zoonoses, rickettsioses, such as spotted fever and typhus. The difficulty of cultivating these bacteria in vitro reinforces the importance of in silico approaches, such as pangenomic and genomic plasticity analyses. This study analyzed 165 genomes from 31 Rickettsia species available in the REFSEQ (NCBI) database. Tools such as Orthofinder, ANIclustermap, Gegenees, and Mauve were used to classify genes into core, shared, and singletons, assess genomic similarity, and identify structural rearrangements. The results indicate that the genus has an open pangenome (α = 0,842), suggesting high genetic variability and adaptive and expansion potential. Species such as R. typhi exhibited a nearly closed pangenome (α = 0,999), with high genomic conservation, whereas R. rhipicephali showed an open pangenome (α = 0,876), reflecting greater plasticity and intraspecies diversity. Functional categorization of genes revealed that the core genome is associated with vital functions, while singletons include genes related to genetic mobility, indicating possible acquisition through horizontal transfer. Synteny analysis demonstrated high gene conservation in R. typhi and extensive structural reorganization in R. rhipicephali. Statistical correlation reinforced the stability of the core genome regardless of pangenome expansion and revealed an inverse relationship between the number of singletons and the value of α. The findings demonstrate the existence of contrasting evolutionary trajectories within the Rickettsia genus, with conserved, specialized species coexisting alongside genetically dynamic species that are more adaptable to different niches. Thus, this study expands the understanding of clonality, genomic plasticity, and functional diversity within the genus, providing support for future investigations into virulence factors, vaccine targets, and bacterial evolution.

Typhus (FBT), caused by Rickettsia typhi, rarely causes neurological disease. Herein, we describe neurological involvement in two cases of FBT. In the first case, an adult presented with persistent fever which deteriorated into status epilepticus. He was successfully treated with doxycycline and made a complete recovery. In the second case, a patient suffered an ischemic stroke and had a protracted clinical course but ultimately made a near complete recovery. In addition to these cases, we conducted a comprehensive narrative review of 43 cases of neurologic involvement in FBT reported from 1989 to 2025. Cases were excluded if there were pathologic discrepancies with typical cases of FBT. Presentations ranged from cranial nerve palsies to meningitis and fulminant encephalitis. This review highlights the spectrum of CNS complications associated with FBT and underscores the importance of early recognition and treatment with doxycycline to improve outcomes. Given the potential severity of neurologic involvement, clinicians in endemic areas should maintain a high index of suspicion for FBT in patients presenting with a febrile illness and neurologic symptoms.

Murine typhus is a reemerging infectious disease with the potential for severe manifestations. We conducted a retrospective study to examine severe illness in those hospitalized with murine typhus in Galveston, Texas. We identified 149 cases, of which 119 (79.8%) were hospitalized and 33 (28%) required admission to the intensive care unit (ICU). ICU patients were older than non-ICU patients (54.9 vs. 47.2 years; p<0.02). Thrombocytopenia was more severe in the ICU group (101 × 10[3] µ/L) compared to the non-ICU group (137 × 10[3] µ/L) (p<0.01). The median time from healthcare contact in the emergency department to initiation of appropriate antibiotics was similar for the ICU group (1 day) and non-ICU group (2 days) (p = 0.26). Two deaths (1.7%) in the ICU group were attributed to multiorgan failure and hemophagocytic lymphohistiocytosis. In murine typhus-endemic regions, early recognition and prompt treatment is imperative to mitigate adverse outcomes.

Rickettsial diseases present ongoing diagnostic challenges due to antigenic diversity, serological cross-reactivity, and the lack of reliable standardised control reagents. Current serodiagnostic assays frequently rely on convalescent human sera as positive controls, which are inherently variable, limited in supply, and poorly suited to assay standardisation and quality assurance. In this study, we developed and validated human-mouse chimeric monoclonal antibodies targeting the conserved outer membrane protein B (OmpB) of Rickettsia typhi as defined, renewable, positive-control calibrators for existing rickettsial serological platforms. Murine monoclonal antibodies were generated and engineered into chimeric IgG antibodies, which were expressed in HEK293T cells. The chimeric antibodies demonstrated high antigen specificity, bound native OmpB on the surface of R. typhi, and showed no detectable cross-reactivity within the tested antigen panel when evaluated using dot blot, immunofluorescence microscopy, and Luminex-based multiplex assays. Compared with patient-derived positive control sera, the chimeric antibodies demonstrated improved specificity and consistent performance within the evaluated assay conditions. These findings support the potential use of chimeric monoclonal antibodies as standardised positive controls for rickettsial serodiagnostics, with potential applications in assay validation, quality assurance, and inter-laboratory harmonisation.

BACKGROUND: This study aimed to evaluate the seroprevalence of anti-IgG antibodies against Rickettsia typhi among patients with unexplained acute fever (UAF) at the Sourô Sanou University Hospital (CHUSS) in Bobo-Dioulasso, Burkina Faso. METHODS: A prospective study was conducted from July to October 2025. A total of 87 patients with UAF were enrolled. The diagnostic protocol systematically included blood cultures and ELISA for the detection of anti-R. typhi IgG antibody. The diagnostic protocol included routine screening for malaria and dengue fever, as well as blood cultures. ELISA was performed only if the initial tests were negative. RESULTS: The overall anti-R. typhi IgG antibody seroprevalence was 12.64% (12/87). The 30–45-year age group was the most represented (25.29%). Farmers and housemaids were the most exposed (18.2%). Clinically, chills and headaches were the most frequent symptoms (18.2%). Regarding risk factors, 54.5% of seropositive patients were reported living in proximity to animals or arthropod habitats. While 92% of blood cultures were negative, a statistically significant association was observed between serological and blood culture results (p < 0.001). CONCLUSION: These findings confirm the circulation of Rickettsia typhi in Bobo-Dioulasso, highlighting murine typhus as a potential cause of unexplained acute fever. However, the detection of anti- R. typhi IgG antibody can indicate past exposure; further studies using molecular technique or paired-sera analysis are essential to confirm acute cases and accurately assess the disease burden in Burkina Faso. CLINICAL TRIAL NUMBER: Not applicable.