Severe Rickettsia typhi Infections, Costa Rica.

Murine typhus is a febrile, fleaborne disease caused by infection with Rickettsia typhi bacteria. Cases can range from mild and nonspecific to fatal. We report 2 cases of murine typhus in Costa Rica, confirming the presence and circulation of R. typhi causing severe disease in the country.

Increased Seroprevalence of Typhus Group Rickettsiosis, Galveston County, Texas, USA.

Whether increases in typhus group rickettsiosis in Galveston County, Texas, USA, are caused by increased recognition or true reemergence is unclear. We conducted a serosurvey that demonstrated Rickettsia typhi antibodies increased from 1.2% in 2013 to 7.8% in 2021 (p<0.001). These findings support pathogen reemergence rather than enhanced recognition alone.

Rise in Murine Typhus in Galveston County, Texas, USA, 2018.

Murine typhus, an undifferentiated febrile illness caused by Rickettsia typhi, is increasing in prevalence and distribution throughout Texas. In 2018, a total of 40 cases of murine typhus were reported in Galveston County. This increase, unprecedented since the 1940s, highlights the importance of awareness by physicians and public health officials.

Rickettsia typhi as Cause of Fatal Encephalitic Typhus in Hospitalized Patients, Hamburg, Germany, 1940-1944.

We evaluated formalin-fixed paraffin-embedded tissue specimens from 7 patients who died with encephalitic typhus in Hamburg, Germany, during World War II. The archived specimens included only central nervous system tissues >70 years old that had been stored at room temperature. We demonstrated successful detection of Rickettsia typhi DNA by a nested qPCR specific to prsA in 2 patients. These results indicate that R. typhi infections contributed to typhus outbreaks during World War II. Immunohistochemical analyses of brain tissue specimens of R. typhi DNA-positive and -negative specimens showed perivascular B-cell accumulation. Around blood vessels, nodular cell accumulations consisted of CD4-positive and CD8-positive T cells and CD68-positive microglia and macrophages; neutrophils were found rarely. These findings are similar to those of previously reported R. prowazekii tissue specimen testing. Because R. typhi and R. prowazekii infections can be clinically and histopathologically similar, molecular analyses should be performed to distinguish the 2 pathogens.

Comparative evaluation of two Rickettsia typhi-specific quantitative real-time PCRs for research and diagnostic purposes.

Rickettsioses are caused by intracellular bacteria of the family of Rickettsiaceae. Rickettsia (R.) typhi is the causative agent of endemic typhus. The disease occurs worldwide and is one of the most prevalent rickettsioses. Rickettsial diseases, however, are generally underdiagnosed which is mainly due to the lack of sensitive and specific methods. In addition, methods for quantitative detection of the bacteria for research purposes are rare. We established two qPCRs for the detection of R. typhi by amplification of the outer membrane protein B (ompB) and parvulin-type PPIase (prsA) genes. Both qPCRs are specific and exclusively recognize R. typhi but no other rickettsiae including the closest relative, R. prowazekii. The prsA-based qPCR revealed to be much more sensitive than the amplification of ompB and provided highly reproducible results in the detection of R. typhi in organs of infected mice. Furthermore, as a nested PCR the prsA qPCR was applicable for the detection of R. typhi in human blood samples. Collectively, the prsA-based qPCR represents a reliable method for the quantitative detection of R. typhi for research purposes and is a promising candidate for differential diagnosis.

Murine typhus in elderly patients: a prospective study of 49 patients.

BACKGROUND: The characteristics of Rickettsia typhi infection in elderly patients have not been extensively described in the literature. METHODS: We conducted a prospective study on murine typhus in patients > 65 years old in two endemic areas of Greece. RESULTS: Forty-nine elderly patients were analyzed, including 30 (61.2%) males. The clinical triad of fever (100% of patients), headache (83.7%), and rash (73.5%), occurred in 63% of patients, whereas malaise (85.7%), anorexia (65.3%), and myalgia (59.2%) were also common. Frequent laboratory findings were transaminasemia (89.8%), lactate dehydrogenase elevation (65.3%), hematuria (55.1%), thrombocytopenia (53.1%), anemia (51%), leucopenia (40.8%), and mild hyponatremia (23.5%). Complications developed in 16 patients (32.7%); no deaths were recorded. CONCLUSIONS: The main clinical and laboratory characteristics of murine typhus are similar in elderly and younger adults. However, elderly patients have a more severe clinical picture, evidenced by a higher complication rate and longer duration of fever, even with appropriate treatment. To our knowledge, this is the first study to focus on murine typhus in a geriatric population.

Murine Typhus: A Review of a Reemerging Flea-Borne Rickettsiosis with Potential for Neurologic Manifestations and Sequalae.

Murine typhus is an acute febrile illness caused by Rickettsia typhi, an obligately intracellular Gram-negative coccobacillus. Rats (Rattus species) and their fleas (Xenopsylla cheopis) serve as the reservoir and vector of R. typhi, respectively. Humans become infected when R. typhi-infected flea feces are rubbed into flea bite wounds or onto mucous membranes. The disease is endemic throughout much of the world, especially in tropical and subtropical seaboard regions where rats are common. Murine typhus is reemerging as an important cause of febrile illness in Texas and Southern California, where an alternate transmission cycle likely involves opossums (Didelphis virginiana) and cat fleas (Ctenocephalides felis). Although primarily an undifferentiated febrile illness, a range of neurologic manifestations may occur, especially when treatment is delayed. Serology is the mainstay of diagnostic testing, but confirmation usually requires demonstrating seroconversion or a fourfold increase in antibody titer from acute- and convalescent-phase sera (antibodies are seldom detectable in the first week of illness). Thus, early empiric treatment with doxycycline, the drug of choice, is imperative. The purpose of this review is to highlight murine typhus as an important emerging and reemerging infectious disease, review its neurologic manifestations, and discuss areas in need of further study.

Murine Typhus Presenting With Mucosal Involvement.

Lipschutz ulcers (LU) present as painful genital ulcers in nonsexually active females. Associated infections include Epstein Barr virus, Mycoplasma pneumoniae, Cytomegalovirus, and influenza. To our knowledge, this is the first report of LU occurring with murine typhus. Murine typhus is caused by Rickettsia typhi, a Gram-negative, obligate intracellular organism. Rat fleas (Xenopsylla cheopis) are the classic vector, although cat fleas (Ctenocephalides felis) found on cats, dogs, and opossums have been implicated in maintaining the life cycle of R. typhi in suburban areas. Murine typhus can have a nonspecific presentation making a strong index of suspicion crucial to its diagnosis. The most common presenting signs include fever, poor appetite, malaise, and headache. Laboratory abnormalities may include elevated C-reactive protein, elevated erythrocyte sedimentation rate, hypoalbuminemia, elevated transaminases, elevated neutrophil band count, and thrombocytopenia. The treatment of choice for R. typhi is doxycycline.

Murine Typhus Infection in Pregnancy: Case Series and Literature Review.

Murine typhus is a flea-borne disease of worldwide distribution with a recent reemergence in the United States of America. There are limited data about the presentation, treatment, and outcomes in the pregnant population. We report on two cases of murine typhus during pregnancy and review the literature to compile previously reported cases. A comprehensive search was performed via the PubMed database for published articles between 1990 and 2020. Seven articles met the criteria of symptomatic pregnant murine typhus infection. A total of 37 patients were identified. Patients frequently presented with a prolonged duration of fevers prior to presentation, headache, and elevated hepatic transaminases. The diagnosis was predominantly based on serology. Treatment varied. Overall, the pregnancy outcome was favorable. Murine typhus can mimic other pregnancy-related pathologies. More exclusive and large-scale studies are needed to learn more of murine typhus during pregnancy.

Manifestations and Management of Flea-Borne Rickettsioses.

Murine typhus and flea-borne spotted fever are undifferentiated febrile illnesses caused by Rickettsia typhi and Rickettsia felis, respectively. These organisms are small obligately intracellular bacteria and are transmitted to humans by fleas. Murine typhus is endemic to coastal areas of the tropics and subtropics (especially port cities), where rats are the primary mammalian host and rat fleas (Xenopsylla cheopis) are the vector. In the United States, a cycle of transmission involving opossums and cat fleas (Ctenocephalides felis) are the presumed reservoir and vector, respectively. The incidence and distribution of murine typhus appear to be increasing in endemic areas of the US. Rickettsia felis has also been reported throughout the world and is found within the ubiquitous cat flea. Flea-borne rickettsioses manifest as an undifferentiated febrile illness. Headache, malaise, and myalgia are frequent symptoms that accompany fever. The incidence of rash is variable, so its absence should not dissuade the clinician to consider a rickettsial illness as part of the differential diagnosis. When present, the rash is usually macular or papular. Although not a feature of murine typhus, eschar has been found in 12% of those with flea-borne spotted fever. Confirmatory laboratory diagnosis is usually obtained by serology; the indirect immunofluorescence assay is the serologic test of choice. Antibodies are seldom present during the first few days of illness. Thus, the diagnosis requires acute- and convalescent-phase specimens to document seroconversion or a four-fold increase in antibody titer. Since laboratory diagnosis is usually retrospective, when a flea-borne rickettsiosis is considered, empiric treatment should be initiated. The treatment of choice for both children and adults is doxycycline, which results in a swift and effective response. The following review is aimed to summarize the key clinical, epidemiological, ecological, diagnostic, and treatment aspects of flea-borne rickettsioses.

Murine typhus. How does it affect us in the 21st century? The epidemiology of inpatients in Spain (1997-2015).

OBJECTIVE: The aim of this study was to analyze the epidemiological impact of murine typhus in patients who required hospitalization in the National Health System (SNS) in Spain between 1997 and 2015. BACKGROUND: Murine typhus (MT) is a zoonosis caused by Rickettsia typhi. MT is transmitted from rats, cats, dogs, and opossums to humans by their fleas. The clinical picture is characterized by headache, fever, rash, and liver function alteration. The prevalence of MT is considered underestimated since most cases are mild and self-limited. However, up to 10% of patients develop serious complications such as pneumonia or acute kidney injury and may even need admission to intensive care units. METHODS: This was a retrospective longitudinal descriptive study of inpatients diagnosed with Rickettsia typhi infection (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM], 081.0) in Spanish public hospitals between January 1, 1997, and December 31, 2015. Data were obtained from the Minimum Basic Data Set (MBDS, CMBD in Spanish), which includes information about inpatients admitted to the National Health System (NHS) hospitals provided by the Health Information Institute of the Ministry of Health and Equality. RESULTS: Ninety-nine inpatients were included. The incidence rate of MT was 0.12 (95% CI, 0.09-0.14) cases per one million person-years. Cases were irregularly distributed throughout the period of study, with a slight upward trend between 2013 and 2015. The Canary Islands had the highest incidence rate: 2.17 (95% CI, 1.69-2.64) cases per one million person-years (80 cases). Most patients were men (63.6%). The mean age (±SD) was 46.4 years (±19). Five patients were under 15 years old. Approximately 85.9% of cases required urgent hospital admissions. The average hospital stay was 11 days (±9.9). Only 1 patient died. CONCLUSIONS: Although considered uncommon, the incidence of MT seems to be increasing slowly. Most cases occurred in middle-aged men between late summer and early autumn in Spain. The Canary Islands and Andalusia registered the highest number of cases. The MBDS is an appropriate approach to study MT hospital management.

Emergence of murine typhus in La Réunion, France, 2012-2017.

OBJECTIVE: Murine typhus (MT) is an acute zoonosis caused by Rickettsia typhi, a flea-borne rickettsiosis. The first autochthonous case was reported in 2012. Once autochthonous transmission of Rickettsia typhi was proven, we performed a prospective study to describe and raise awareness of this often-misdiagnosed disease among physicians. PATIENTS AND METHODS: We performed a prospective observational study of MT cases in La Réunion from 2012 to 2017. MT cases were defined as clinically compatible illnesses with a specific positive serology and/or PCR. RESULTS: Sixty-one confirmed cases were collected. The main clinical features were prolonged fever (90%), asthenia (87%), and headaches (79%). The main biological abnormalities were elevated liver enzymes (84%) and thrombopenia (75%). Renal function was normal in 90% of cases; it was an important feature because leptospirosis is a frequent cause of acute renal failure. A seasonal factor was observed with 79% of cases reported in the warm season and most of them in the west and south of the island (i.e., the dry areas). CONCLUSION: MT is an emerging disease in La Réunion, and local conditions could lead to an endemic situation. Cases of acute undifferentiated fever with headaches should guide to the diagnosis of MT especially in the warm season and dry areas. Leptospirosis is an alternative diagnosis, which differs from MT by its epidemiological characteristics and by the associated frequent renal dysfunction.

Rickettsiae Within the Fleas of Feral Cats in Galveston, Texas.

Murine typhus is a flea-borne typhus group rickettsiosis caused by Rickettsia typhi. Once a prevalent disease in the United States, the use of dichlorodiphenyltrichloroethane in the 1940s broke the classic rat-rat flea cycle of transmission, and the remaining endemic foci are now believed to be associated with opossums and the cat flea (Ctenocephalides felis). In Galveston, Texas murine typhus has re-emerged as a cause of febrile illness, and 7% of fleas collected from opossums are infected with R. typhi. In this study, we sought to explore the prevalence of rickettsiae associated with fleas on cats, as these animals have been speculated to play a role in the epidemiology of murine typhus. Fleas were collected from feral cats entering a local veterinary clinic as part of a trap, spay, neuter, and release program. Fleas were identified and subjected to analysis by PCR and sequencing. An estimation of the minimum infection rate (MIR) of pooled samples was performed. Three hundred fourteen fleas (all C. felis) were collected from 24 cats. Sequences for the outer membrane protein B gene revealed R. typhi in one pool (MIR 0.3%), Rickettsia felis in four pools (MIR 1.3%), Rickettsia asembonensis in one pool (MIR 0.3%), and "Candidatus R. senegalensis" in six pools (MIR 2.0%). Results were confirmed by sequencing portions of the rickettsial citrate synthase and 17-kD protein gene. In this study, the presence of R. typhi in fleas from cats suggests that in Galveston, there exists a small but measurable risk to humans who come into contact with flea-infested cats. Despite this, we believe that the low prevalence from cat-collected fleas, compared with that previously detected from opossums, makes cats less likely to play a role in the maintenance of R. typhi in this region. The significance of other identified flea-borne rickettsiae is yet to be elucidated.

Clinical and laboratory characteristics, epidemiology, and outcomes of murine typhus: A systematic review.

Murine or endemic typhus, a febrile disease caused by Rickettsia typhi, is often misdiagnosed due to its non-specific presentation. We sought to evaluate all available evidence in the literature regarding the clinical and laboratory manifestations, epidemiological characteristics, and outcomes of murine typhus. Pubmed was searched for all articles providing available data. In an effort to incorporate contemporary data, only studies from 1980 were included. Thirty-three case series including 2074 patients were included in final analysis. Available evidence suggests that the classic triad of fever, headache and rash is encountered in only one-third of patients. Other frequent symptoms were chills, malaise, myalgia, and anorexia. A tetrad of reported laboratory abnormalities consisting of elevated liver enzymes, lactate dehydrogenase, erythrocyte sedimentation rate and hypoalbuminemia was detected. Complications were observed in one-fourth of patients, reported mortality was extremely low, but untreated patients had notably longer duration of fever. Among epidemiological characteristics, a seasonal distribution with most cases reported during warmer months, was the most prominent finding. Murine typhus in children exhibits several different characteristics, with abdominal pain, diarrhea, and sore throat reported more commonly, higher frequency of anemia, lower frequency of hypoalbuminemia, hematuria and proteinuria and a much lower rate of complications. This systematic review of published evidence provides a thorough description of the clinical and laboratory features of murine typhus and highlights important differences in children.

An outbreak of endemic typhus in Baoshan city, Yunnan province / 中华流行病学杂志

Objective To understand the epidemiologic characteristics of endemic typhus in Baoshan city. Methods Epidemiological data were collected and characteristics were analyzed. IgG antibody(Ab) of Rickettsia mooseri and Orientia tsutsuganushi in serum of patients were tested using both Weil-Felix and IFA method. The Rickettsia mooseri gltA gene, Rickettsia prowazekii gltA gene,Orientia tsutsugamushi 56 kDa protein gene, SFGR ompA gene, Ehrlichia sp. 16S rRNA gene and Anaplasma sp. 16S rRNA gene in spleen of mice were examined by PCR. Results Fifty- eight endemic typhus cases were found in Longyang district of Baoshan city, during July to August, 2009.Among them, 48 cases were confirmed by clinical diagnosis and 10 cases by laboratory tests. The Ab of Orientia tsutsugamushi Karp serotype was detected in 3 cases from laboratory diagnosis. The spleen samples from 85 Rattns flavipectus were tested using PCR. Of them, 3 samples for Rickettsia mooseri gltA gene showed positive (positive rate was 3.5% ), and the homology of 3 Rickettsia mooseri and Rickettsia mooseri Wilmington strain (GenBank U59714.1) was 100% through comparing gene sequence. The results of PCR for detecting Rickettsia prowazekii, Orientia tsutsugamushi, SFGR,Anaplasma sp. and Ehrlichia. sp were all negative. Conclusion The outbreak of endemic typhus was confirmed in Longyang district of Baoshan city through epidemiological data, clinical diagnosis and laboratory tests. Rickettsia mooseri DNA was detected in the dominant Raw flavipectus, suggesting that endemic typhus did exist in the local areas.

Two Cases of Murine Typhus / 대한피부과학회지

We report two cases of murine typhus diagnosed by indirect immunofluorescent test. The patients showed cardinal symptoms and signs such as fever and chill, general myalgia, intractable headache and typical rash. Laboratory values and histopathologic findings were compatible with murine typhus. The oral administration of doxycycline improved dramatically the clinical manifestations of the two CCLSPS.