Project description:The first fatal Rickettsia rickettsii infection was diagnosed in the southwest of Mexico. The patient had fever, erythematous rash, abdominal pain, and severe central nervous system involvement with convulsive crisis. The diagnosis of R. rickettsii infection was established by immunohistochemistry and specific polymerase chain reaction.
Project description:A 39 year-old male was residing along the south coast of Texas, the USA, presented with fever, myalgias, headaches, and weight loss for ten days. Symptoms and manifestations progressed to include nuchal rigidity, photophobia, hyponatremia, thrombocytopenia, and transaminitis despite the intravenous administration of ceftriaxone and azithromycin. A lumbar puncture performed in the Emergency Department yielded pleocytosis and glucose cerebrospinal fluid/serum ratio of 0.35, suggestive of meningoencephalitis. Conglomerate data raised the suspicion of meningitis secondary to a zoonotic acquired infection, which was later confirmed to be Rickettsia typhi. Doxycycline is the drug of choice for the suspected Rickettsia disease. After doxycycline administration, the patient improved and was discharged home asymptomatic.
Project description:Patients with rickettsial infection may present with encephalitis or meningitis but neurologic involvement is rare in murine typhus. Here, we report two patients with Rickettsia typhi meningitis who presented with cranial neuropathy, presumably caused by two distinct disease processes. Recognition of the disease manifestations is important because rickettsial infections are potentially associated with significant morbidity. Simple effective treatments are available.
Project description:Rickettsioses are emerging febrile diseases caused by obligate intracellular bacteria belonging to the family Rickettsiaceae. Rickettsia typhi belongs to the typhus group (TG) of this family and is the causative agent of endemic typhus, a disease that can be fatal. In the present study, we analyzed the course of R. typhi infection in C57BL/6 RAG1(-/-) mice. Although these mice lack adaptive immunity, they developed only mild and temporary symptoms of disease and survived R. typhi infection for a long period of time. To our surprise, 3 to 4 months after infection, C57BL/6 RAG1(-/-) mice suddenly developed lethal neurological disorders. Analysis of these mice at the time of death revealed high bacterial loads, predominantly in the brain. This was accompanied by a massive expansion of microglia and by neuronal cell death. Furthermore, high numbers of infiltrating CD11b(+) macrophages were detectable in the brain. In contrast to the microglia, these cells harbored R. typhi and showed an inflammatory phenotype, as indicated by inducible nitric oxide synthase (iNOS) expression, which was not observed in the periphery. Having shown that R. typhi persists in immunocompromised mice, we finally asked whether the bacteria are also able to persist in resistant C57BL/6 and BALB/c wild-type mice. Indeed, R. typhi could be recultivated from lung, spleen, and brain tissues from both strains even up to 1 year after infection. This is the first report demonstrating persistence and reappearance of R. typhi, mainly restricted to the central nervous system in immunocompromised mice.
Project description:BACKGROUND: Rickettsiatyphi is the etiological agent of murine typhus (MT), a disease transmitted by two cycles: rat-flea-rat, and peridomestic cycle. Murine typhus is often misdiagnosed and underreported. A correct diagnosis is important because MT can cause severe illness and death. Our previous seroprevalence results pointed to presence of human R. typhi infection in our region; however, no clinical case has been reported. Although cats have been related to MT, no naturally infected cat has been described. The aim of the study is to confirm the existence of R. typhi in our location analyzing its presence in cats and fleas. METHODOLOGY/PRINCIPAL FINDINGS: 221 cats and 80 fleas were collected from Veterinary clinics, shelters, and the street (2001-2009). Variables surveyed were: date of collection, age, sex, municipality, living place, outdoor activities, demographic area, healthy status, contact with animals, and ectoparasite infestation. IgG against R. typhi were evaluated by indirect immunofluorescence assay. Molecular detection in cats and fleas was performed by real-time PCR. Cultures were performed in those cats with positive molecular detection. Statistical analysis was carried out using SPSS. A p < 0.05 was considered significant. Thirty-five (15.8%) cats were seropositive. There were no significant associations among seropositivity and any variables. R. typhi was detected in 5 blood and 2 cultures. High titres and molecular detection were observed in stray cats and pets, as well as in spring and winter. All fleas were Ctenocephalides felis. R. typhi was detected in 44 fleas (55%), from shelters and pets. Co-infection with R. felis was observed. CONCLUSIONS: Although no clinical case has been described in this area, the presence of R. typhi in cats and fleas is demonstrated. Moreover, a considerable percentage of those animals lived in households. To our knowledge, this is the first time R. typhi is detected in naturally infected cats.
Project description:Rickettsia felis infection usually is a mild-to-moderate illness characterized by general signs and symptoms. Generally, patients do not require hospitalization. However, we detected 2 severe infections with R. felis. Our findings support the importance of R. felis infection as a potentially severe illness in humans.
Project description:Fleas collected from rats during a three-year period (2000-2003) in 51 areas of all provinces of Cyprus were tested by molecular analysis to characterize the prevalence and identity of fleaborne rickettsiae. Rickettsia typhi, the causative agent of murine typhus, was detected in Xenopsylla cheopis (4%) and in Leptopsylla segnis (6.6%). Rickettsia felis was detected in X. cheopis (1%). This is the first report of R. typhi in X. cheopis and L. segnis from rats, in Cyprus, and the first report of R. felis in X. cheopis in Europe. The role of fleas (mainly X. cheopis) was confirmed in the epidemiologic cycle of murine typhus in Cyprus by interrelation of current results with those of previous studies. The geographic distribution of fleas coincided with the geographic distribution of the pathogen they can harbor, which emphasizes the potential risk of flea-transmitted infections in Cyprus.
Project description:As obligate intracellular, vector-borne bacteria, rickettsiae must adapt to both mammalian and arthropod host cell environments. Deciphering the molecular mechanisms of the interactions between rickettsiae and their host cells has largely been hindered by the genetic intractability of these organisms; however, research in other gram-negative pathogens has demonstrated that many bacterial determinants of attachment, entry, and pathogenesis are extracytoplasmic proteins. The annotations of several rickettsial genomes indicate the presence of homologs of the Sec translocon, the major route for bacterial protein secretion from the cytoplasm. For Rickettsia typhi, the etiologic agent of murine typhus, homologs of the Sec-translocon-associated proteins LepB, SecA, and LspA have been functionally characterized; therefore, the R. typhi Sec apparatus represents a mechanism for the secretion of rickettsial proteins, including virulence factors, into the extracytoplasmic environment. Our objective was to characterize such Sec-dependent R. typhi proteins in the context of a mammalian host cell infection. By using the web-based programs LipoP, SignalP, and Phobius, a total of 191 R. typhi proteins were predicted to contain signal peptides targeting them to the Sec translocon. Of these putative signal peptides, 102 were tested in an Escherichia coli-based alkaline phosphatase (PhoA) gene fusion system. Eighty-four of these candidates exhibited signal peptide activity in E. coli, and transcriptional analysis indicated that at least 54 of the R. typhi extracytoplasmic proteins undergo active gene expression during infections of HeLa cells. This work highlights a number of interesting proteins possibly involved in rickettsial growth and virulence in mammalian cells.