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Maria A Caravedo Martinez,1 Alejandro Ramírez-Hernández,2 Lucas S Blanton1 1Department of Internal Medicine – Division of Infectious Diseases, University of Texas Medical Branch, Galveston, TX, USA; 2Department of Pathology, University of Texas Medical Branch, Galveston, TX, USACorrespondence: Lucas S Blanton 301 University Boulevard, Galveston, TX, 77555-0435, USATel +1 (409) 747-0236Fax +1 (409) 772-6527Email lsblanto@utmb.eduAbstract: 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.Keywords: Rickettsia typhi, murine typhus, endemic typhus, flea-borne typhus, Rickettsia felis, flea-borne spotted fever, rickettsiosis

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.

Persons experiencing homelessness in São Paulo, Brazil, were seropositive for Bartonella spp. (79/109, 72.5%) and typhus group rickettsiae (40/109, 36.7%). Bartonella quintana DNA was detected in 17.1% (14/82) body louse pools and 0.9% (1/114) blood samples. Clinicians should consider vectorborne agents as potential causes of febrile syndromes in this population.

Outbreaks of life-threatening Rocky Mountain spotted fever in humans and dogs associated with a canine-tick maintenance cycle constitute an important One Health opportunity. The reality of the problem has been observed strikingly in Mexico, Brazil, Colombia, and Native American tribal lands in Arizona. The brown dog tick, Rhipicephalus sanguineus sensu lato , acquires the rickettsia from bacteremic dogs and can maintain the bacterium transtadially to the next tick stage. The subsequent adult tick can then transmit infection to a new host, as shown by guinea pig models. These brown dog ticks maintain spotted fever group rickettsiae transovarially through many generations, thus serving as both vector and reservoir. Vaccine containing whole-killed R. rickettsii does not stimulate sufficient immunity. Studies of Rickettsia subunit antigens have demonstrated that conformationally preserved outer-membrane autotransporter proteins A and B are the leading vaccine candidates. The possibility of a potentially safe and effective live attenuated vaccine has only begun to be explored as gene knockout methods are applied to these obligately intracellular pathogens.

Ehrlichia chaffeensis is the causative agent of human monocytotropic ehrlichiosis (HME), a disease that ranges in severity from mild to fatal infection. Ehrlichia chaffeensis is maintained in a zoonotic cycle involving white-tailed deer (Odocoileus virginianus) as the main vertebrate reservoir and lone star ticks (Amblyomma americanum) as its principal vector. Through complete genomic analysis from human ehrlichial isolates and DNA sequences obtained from deer and tick specimens, nine strains of E. chaffeensis have been characterized. Few studies have examined the genetic diversity of E. chaffeensis in ticks, and some of these investigations have identified that the genetic sequences coincide with the circulating strains reported so far. Here, we report the first evidence of E. chaffeensis DNA from an unfed Amblyomma tenellum (formerly Amblyomma imitator) collected in South Texas. We characterized the genetic variation of this E. chaffeensis genotype using conserved gene markers such as rRNA, dsb, and groEL. We also used gene targets useful to distinguish genotypes, such as the variable length PCR target gene (VLPT) and 120-kDa gene, encoding the tandem-repeat proteins TRP32 and TRP120, respectively. Our results suggest a novel E. chaffeensis genotype that exhibited greater variability than other genotypes of E. chaffeensis and highlights the role for A. tenellum as a potential vector of E. chaffeensis., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Murine typhus is an undifferentiated febrile illness. Historically recognized throughout Latin America, it has been seldom reported in recent decades. When clinicians and researchers are attuned, endemic foci have reemerged. The demonstrable seroprevalence in areas devoid of reported cases indicates murine typhus is an underappreciated infectious disease in Latin America.

Murine typhus is an acute undifferentiated febrile illness caused by Rickettsia typhi. In the United States, its reemergence appears to be driven by a shift from the classic rat-rat flea cycle of transmission to one involving opossums (Didelphis virginiana) and cat fleas. Little is known of the ability of opossums to act as a reservoir and amplifying host for R. typhi. Here, we use Monodelphis domestica (the laboratory opossum) as a surrogate for D. virginiana. Opossums were inoculated via the intraperitoneal (IP) or intradermal (ID) route with 1 × 106 viable R. typhi. Blood and tissues were collected on days 6, 13, 20, and 27 or if moribund. Although one ID-infected opossum died, the remainder did not appear ill, whereas half of the IP-inoculated animals succumbed to infection. Rickettsemia was demonstrated in all animals through week 2 of infection and sporadically in weeks 3 and 4. Rickettsia typhi DNA was detected in all tissues, with most animals demonstrating the presence of bacteria into weeks 3 and 4. Histopathology and immunohistochemistry demonstrated typical findings of rickettsial infection. Akin to infection in rats, the demonstration of disseminated infection, typical inflammation, and prolonged rickettsemia with relatively few clinical effects (especially in the more natural route of ID inoculation) supports the potential of opossums to act as a competent mammalian reservoir and component of the zoonotic maintenance cycle of R. typhi. Understanding the dynamics of infection within opossums may have implications for the prevention and control of murine typhus.

Tick-borne rickettsial infections are serious, common, and difficult to diagnose. Among the most important factors leading to failure to diagnose and treat tick-borne rickettsioses effectively is a lack of consideration of the potential diagnosis by primary caregivers and emergency department physicians in patients presenting with undifferentiated acute febrile illness during tick season. This situation exists because of insufficient primary and continuing medical education of medical students, primary care and emergency medicine residents, and practicing physicians regarding tick-borne rickettsioses specific to the region where they practice. Delayed initiation of treatment with an appropriate antibiotic is associated with adverse outcomes including increased rates of hospitalization, admission to an intensive care unit, and mortality. The earliest symptoms are nonspecific, consisting of fever, headache, myalgias, and nausea and/or vomiting. Laboratory abnormalities are typically absent at this time when the therapeutic response to an appropriate antibiotic would be optimal. There is a mistaken idea among a substantial portion of physicians that the best antibiotic available, doxycycline, should not be administered to children 8 years of age or younger or during pregnancy. For all of the above reasons, there is unnecessary morbidity and mortality caused by tick-borne rickettsioses. This report proposes measures to address these critical issues regarding tick-borne rickettsioses., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.

The current COVID-19 pandemic has presented unprecedented challenges to the world community. No effective therapies or vaccines have yet been established. Upon the basis of homologies to similar coronaviruses, several potential drug targets have been identified and are the focus of both laboratory and clinical investigation. The rationale for several of these drug candidates is presented in this review. Emerging clinical data has revealed that severe COVID-19 disease is associated with heightened inflammatory responses and a procoagulant state, suggesting that patient treatment strategies must extend beyond antiviral agents. Effective approaches to the treatment of vulnerable patients with comorbidities will render COVID-19 substantially more manageable., Competing Interests: Conflicts of interest The authors declare no conflicts of interest.

Introduction: Rickettsioses are zoonotic diseases caused by pathogenic bacteria of the genus Rickettsia and transmitted to man by means of arthropod vectors such as ticks, fleas, mites and lice. Historically, Caldas Department has reported a significant number of cases of murine typhus to the Colombian national health surveillance system, and consequent studies of flea-borne rickettsiosis identified the circulation of Rickettsia typhi and Rickettsia felis in multiple municipalities. Our aim was to genotype species of Rickettsia detected in fleas collected from domestic and wild mammals in Caldas., Methodology: Flea samples were taken by convenience sampling from dogs, cats and wild mammals (rodents and marsupials) in 26 municipalities. Specimens were classified by current taxonomic keys and pooled for DNA extraction and molecular screening for Rickettsia spp. by PCR amplification of gltA, htrA and sca5 genes. Positive samples were genotyped by enzyme digestion (htrA) and sequencing., Results: A total of 1388 flea samples were collected. Rickettsia DNA was amplified in 818 (gltA), 883 (htrA) and 424 (sca5) flea pools. Alignment analysis with available Rickettsia DNA sequences showed greater similarity with R. asembonensis (gltA) and with R. felis (sca5 and htrA). Restriction pattern was compatible with R. felis. R. typhi was not identified., Conclusion: The present study confirms the presence and high prevalence of R. asembonensis and R. felis in fleas from domestic and wild animals in different municipalities from Caldas Department., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2020 Carol B Colonia, Alejandro Ramirez-Hernandez, Juliana Gil-Mora, Juan C Agudelo, Gabriel Jaime Castano Villa, Camilo Pino, Paola Betancourt-Ruiz, Jorge E Perez Cardenas, Lucas S Blanton, Marylin Hidalgo.)

Murine typhus is a flea-borne rickettsiosis caused by Rickettsia typhi . When severe, endothelial dysfunction can lead to acute kidney injury secondary to prerenal azotemia or acute tubular necrosis. Here, we describe an unusual cause of kidney injury during the course of murine typhus-focal segmental glomerulosclerosis.

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.

Rocky Mountain spotted fever (RMSF), caused by Rickettsia rickettsii , is a severe tick-borne infection endemic to the Americas. Oral doxycycline is effective, but during severe life-threatening disease, intravenous therapy is recommended. Unfortunately, intravenous formulations of doxycycline are not always available. Therefore, we aimed to determine the susceptibility of R. rickettsii to an alternative parenteral agent, tigecycline, in vitro and in vivo. To determine the minimum inhibitory concentration of tigecycline, R. rickettsii -inoculated Vero cells were incubated with medium containing tigecycline. At various time points, monolayers were collected and R. rickettsii was quantified via real-time polymerase chain reaction (PCR). The growth of R. rickettsii was inhibited in the presence of ≥ 0.5 µg/mL of tigecycline. To determine the effectiveness of tigecycline in vivo, guinea pigs were inoculated with R. rickettsii. Five days after inoculation, they were treated twice daily with subcutaneous tigecycline 3.75 mg/kg or subcutaneous doxycycline 5 mg/kg. Treated animals improved, whereas untreated controls remained ill. Tissues were collected for quantitative PCR-determined bacterial loads on day 8. Median bacterial loads in the tigecycline group were less than those in untreated animals: liver (0 versus 2.9 × 10 4 copies/mg), lung (0 versus 8.3 × 10 3 copies/mg), skin (2.6 × 10 2 versus 2.2 × 10 5 copies/mg), spleen (0 versus 1.3 × 10 4 copies/mg), and testes (0 versus 1.0 × 10 5 copies/mg, respectively). There were no significant differences in the bacterial loads between doxycycline-treated versus tigecycline-treated guinea pigs. These data indicate that tigecycline is effective against R. rickettsii in cell culture and in an animal model of RMSF.

Cases of tick-borne diseases, including spotted fever rickettsioses, borreliosis, babesiosis, anaplasmosis and ehrlichiosis, in the United States and territories have more than doubled from 2004 to 2016 and account for 77% of all vector-borne disease reports. In an effort to inform control efforts, the presence of tick-borne pathogens and their vectors was assessed in a recreational park in Walker County, Texas. Here we report data from questing ticks collected on three dates from June 2017 to June 2018. The majority of ticks collected were Amblyomma americanum (96.69%) followed by three additional tick species: Dermacentor variabilis (2.59%), Ixodes scapularis (0.52%), and A. maculatum (0.21%). Ticks were pooled and tested for molecular evidence of bacterial and viral pathogens, respectively. All of the 68 pools of A. americanum had molecular evidence of the spotted fever group rickettsia, Rickettsia amblyommatis. Additionally, six (8.82%) of the A. americanum pools contained sequences matching Ehrlichia chaffeensis , the pathogen responsible for human monocytotropic ehrlichiosis, and 11 (16.18%) for E. ewingii . Three of the A. americanum pools demonstrated evidence of Borrelia lonestari . The presence of etiologic agents of known human disease in this study merits the continued surveillance efforts of ticks and their pathogens in areas where they could pose risks to public health.

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.

Rickettsia typhi and Rickettsia felis are flea-borne pathogens, which cause murine typhus and flea-borne spotted fever, respectively. Recently, two other flea-borne rickettsiae (phylogenetically similar to R. felis ) have been discovered- Rickettsia asembonensis and Candidatus Rickettsia senegalensis. Currently, species-specific identification of detected organisms requires sequencing- or probe-based PCR assays. Our aim was to develop an efficient and inexpensive method to differentiate R. felis and R. felis -like organisms through restriction fragment length polymorphism (RFLP) analysis. Outer membrane protein B sequences of the aforementioned flea-borne rickettsiae were analyzed using DNASTAR Lasergene Core software to focus on the region amplified by the primers 120.2788 and 120.3599. Restriction enzyme digestion sites were identified, and in silico digestions of each species were compared through simulated agarose gels. The enzyme Nla IV was determined to be the most effective at creating a unique banding pattern within the area of interest. To confirm the predicted performance of Nla IV digestion, we tested the DNA of known PCR positive Ctenocephalides felis fleas collected from cats and opossums within Galveston, Texas. DNA from these fleas was amplified using the sca5 primer set 120.2788 and 120.3599. The PCR products were then digested with Nla IV, subjected to polyacrylamide gel electrophoresis, and visualized through ethidium bromide staining. The banding patterns were then compared with the computer-generated digestion patterns. All samples demonstrated a banding pattern consistent with the predicted pattern for the known species, as confirmed by previous sequencing. This RFLP assay was developed to be an efficient and cost-effective method to screen samples for R. felis, R. asembonensis , and Candidatus R. senegalensis. We believe this assay can aid in the epidemiological and ecological studies of flea-borne rickettsiae.

Rickettsia are small, obligately intracellular, gram-negative bacilli. They are distributed among a variety of hematophagous arthropod vectors and cause illness throughout the world. Rickettsioses present as an acute undifferentiated febrile illness and are often accompanied by headache, myalgias, and malaise. Cutaneous manifestations include rash and eschar, which both occur at varying incidence depending on the infecting species. Serology is the mainstay of diagnosis, and the indirect immunofluorescence assay is the test of choice. Reactive antibodies are seldom present during early illness, so testing should be performed on both acute-phase and convalescent-phase sera. Doxycycline is the treatment of choice., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Murine typhus, caused by Rickettsia typhi , is an undifferentiated febrile illness with no available rapid and sensitive diagnostic assay for use during early disease. We aimed to compare the health-care charges in those diagnosed with murine typhus to those with influenza, a febrile illness with an available rapid diagnostic test. A comparison of health-care-associated charges at the University of Texas Medical Branch at Galveston demonstrated a median of $817 for influenza versus $16,760 for murine typhus ( P < 0.0001). Median laboratory ($184 versus $3,254 [ P < 0.0001]) and imaging charges ($0 versus $514 [ P < 0.0001]) were also higher in those with murine typhus. Those receiving at least one imaging study during their illness were greater in the murine typhus group (91.3% versus 20.3%) ( P < 0.0001). The median time needed to establish a confirmed or presumptive diagnosis was 2 days for influenza compared with 9 days for murine typhus ( P < 0.0001). The median number of health-care encounters was greater for those with murine typhus (2 versus 1) ( P < 0.0001). Eleven patients (15.9%) with influenza were hospitalized as a result of their illness compared with 16 (69.6%) with murine typhus ( P < 0.0001). The estimated mortality based on disease severity at presentation by Acute Physiology and Chronic Health Evaluation II scoring was similar in the two groups-both had a median 4% mortality risk ( P = 0.0893). These results highlight the need for improved clinical recognition and diagnostics for acute rickettsioses such as murine typhus.

With advances in molecular genetics, more pathogenic rickettsial species have been identified. Pathogenic rickettsiae are transmitted by vectors, such as arthropods, into the patient's skin and then spread into the microvascular endothelial cells. Clinical manifestations are characterized by fever with headache and myalgias, followed by rash 3 to 5 days later. The undifferentiated nature of clinical symptoms, knowledge of the epidemiology, and the patient's history of travel and exposure to arthropod vectors are critical to the empiric administration of antimicrobial therapy. Doxycycline is currently the most effective antibiotic for treatment of all spotted fever group and typhus group rickettsioses., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: To date more than 20 antigenically distinct strains of Orientia tsutsugamushi (OT) reported within the tsutsugamushi triangle that cause an undifferentiated acute febrile illness in humans. Genotypic characterization of OT in different geographic regions or within the same country, is important in order to establish effective diagnostics, clinical management and to develop effective vaccines. Genetic and antigenic characterization of OT causing human disease in OT-endemic regions is not known for Sri Lanka., Methods: Adult patients and children who were admitted with an acute febrile illness and presumed to having acute scrub typhus based on presence of an eschar and other supporting clinical features were recruited. Eschar biopsies and buffy coat samples collected from patients who were confirmed having OT by IFA were further studied by real time PCR (Orientia 47 kD) and nested PCR (Orientia 56 kD) amplification. DNA sequences were obtained for 56 kD gene amplicons and phylogenetic comparisons were analyzed using currently available data in GenBank [Neucleotide substitution per 100 residues, 1000 Bootstrap Trials]., Results: Twenty eschar biopsies (Location1,19, Location 2,1) and eight buffy coat samples (Location1,6, Location2,2) examined by real time PCR revealed Orientia amplicons in 16 samples. DNA sequences were obtained for the 56 kD gene amplicons in 12 eschars and 4 buffy coat samples. The genotypes of the Location1 samples revealed that, 7 exhibiting close homology with JP1 [distantly related to UT177 Thai (Karp related)], five had close homology with Kato strain, two had close homology with JGv and JG AF [Distantly related to Kawasaki M63383] and one had close homology with Gilliam strain. The Location 2 strain was closely related to Kuroki-Boryong L04956, the genotype which is distributed in far eastern Asia. Similar to other patients in the cohort this patient also had never travelled out of Sri Lanka., Conclusions: We observed all three main OT genotypes in Sri Lanka, and the majority fell into Thai Karp related clade. These results demonstrate great antigenic diversity of OT in the studied areas of Sri Lanka.

Rickettsia typhi and Rickettsia felis are flea-borne rickettsiae that are distributed throughout the world. This mini-review outlines the ecology and epidemiology of flea-borne rickettsioses; highlights important clinical, diagnostic, and therapeutic considerations; and discusses areas of uncertainty regarding Rickettsia felis and other rickettsiae harbored by fleas., (© The American Society of Tropical Medicine and Hygiene.)

Murine typhus is an acute undifferentiated febrile illness caused by Rickettsia typhi The classic reservoir (Rattus spp.) and flea vector (Xenopsylla cheopis) were once culprits of murine typhus in the United States. Vector and rodent control efforts have drastically decreased the prevalence of disease, except in a few endemic foci where opossums and cat fleas play a role in transmission. Since 2012, there has been a reemergence of murine typhus in Galveston, TX. We hypothesize that opossums and cat fleas are involved in the transmission of R. typhi in Galveston. To explore this, we sought to find the seroprevalence of typhus group antibodies from opossums. We also sought to find the prevalence of R. typhi in fleas parasitizing these animals. We collected blood from 12 opossums and found that eight (66.7%) had the presence of anti-R. typhi antibodies. All opossums were infested with fleas; a total of 250 Ctenocephalides felis fleas were collected from these animals. Seven opossums (53.8%) were infested with fleas that had molecular evidence of R. typhi infection, while six (46.2%) were infested with fleas that contained Candidatus Rickettsia senegalensis, an organism closely related to R. felis The minimum flea infection rate for R. typhi was 7.0%. The minimum infection rate for Candidatus R. senegalensis was 6.1%. Our study demonstrates that fleas infected with R. typhi parasitize opossums in Galveston. It is therefore likely that opossums and their fleas play a role in the city's recent reemergence of murine typhus., (© The American Society of Tropical Medicine and Hygiene.)

Fungal infections are infrequent causes of brain abscesses. Fonsecaea monophora is a dematiaceous fungus that appears to be neurotropic. We report a case of Fonsecaea monophora infection in a patient with acquired immunodeficiency syndrome, and review previous reports of brain abscesses by this organism.

Malassezia pachydermatis is a relatively rare agent of bloodstream infections. We describe an unusual case of Malassezia fungemia in an adult patient hospitalized for Staphylococcus aureus bacteremia who was also found to have multibacillary leprosy. Treatment of the patient required extensive medical management but resulted in a good outcome.

Murine typhus is a flea-borne febrile illness caused by Rickettsia typhi. Although often accompanied by rash, an inoculation lesion has not been observed as it is with many tick- and mite-transmitted rickettsioses. We describe a patient with murine typhus and an unusual cutaneous manifestation at the site of rickettsial inoculation., (© The American Society of Tropical Medicine and Hygiene.)

Twelve patients with murine typhus were identified in Galveston, Texas, USA, in 2013. An isolate from 1 patient was confirmed to be Rickettsia typhi. Reemergence of murine typhus in Galveston emphasizes the importance of vector control and awareness of this disease by physicians and public health officials.

Rocky Mountain spotted fever (RMSF) is a severe illness caused by Rickettsia rickettsii for which there is no available vaccine. We hypothesize that exposure to the highly prevalent, relatively nonpathogenic "Rickettsia amblyommii" protects against R. rickettsii challenge. To test this hypothesis, guinea pigs were inoculated with "R. amblyommii." After inoculation, the animals showed no signs of illness. When later challenged with lethal doses of R. rickettsii, those previously exposed to "R. amblyommii" remained well, whereas unimmunized controls developed severe illness and died. We conclude that "R. amblyommii" induces an immune response that protects from illness and death in the guinea pig model of RMSF. These results provide a basis for exploring the use of low-virulence rickettsiae as a platform to develop live attenuated vaccine candidates to prevent severe rickettsioses.

Background: Anaplasmosis, caused by Anaplasma phagocytophilum and Anaplasma platys, and ehrlichiosis, caused by Ehrlichia chaffeensis, Ehrlichia ewingii, the "Panola Mountain Ehrlichia" and Ehrlichia muris-like pathogens have been identified as emerging tick borne infectious diseases in dogs and human patients. Persistent intravascular infection with these bacteria is well documented in dogs, but is less well documented in human beings., Methods: Serology and PCR targeting multiple microbial genes, followed by DNA sequencing, was used to test sequential blood samples. Tissue culture isolation was attempted in two laboratories., Results: A. platys, E. chaffeensis, and E. ewingii DNA was amplified from two Anaplasma and Ehrlichia seronegative family members and their dog, all lacking typical symptoms of anaplasmosis or ehrlichiosis. Following treatment with doxycycline, the dog and mother were Anaplasma and Ehrlichia spp. PCR negative., Conclusions: Sequential PCR testing provided molecular evidence supporting intravascular persistence of A. platys and Ehrlichia spp. in two humans and their dog. Diagnosticians and clinicians should consider the potential for co-infections due to these tick borne organisms.

Tick-borne diseases, such as spotted fever rickettsioses and ehrlichioses, are potentially severe and life-threatening infections. The incidences of these infections increase during warm weather months as ticks become active. Clinicians often consider outdoor activities in rural areas to be a risk factor for exposure to ticks and the pathogens they carry, but are those who live, work, and play within an urban environment excluded from this risk? In this study, we collected ticks from two urban parks in Little Rock, AR, to assess the presence of rickettsiae and ehrlichiae within an urban setting. A total of 273 ticks were collected during July, 2011. Amblyomma americanum was the predominant tick species, with 255 (93%) of those collected. The remaining 18 (7%) were Dermacentor variabilis. Ticks were separated and pooled into groups for further testing. Forty-two of the 43 (98%) A. americanum pools demonstrated molecular evidence for the presence of rickettsiae. None of the D. variabilis contained rickettsiae. Restriction enzyme fragment length polymorphism analysis and DNA sequencing revealed Rickettsia amblyommii to be the species present. One A. americanum pool from park A demonstrated the presence of Ehrlichia chaffeensis, the pathogen responsible for human monocytotropic ehrlichiosis. These results indicate that tick-borne pathogens are not limited to rural or suburban areas.

Purpose of Review: The purpose of this review is to describe recent advances in our understanding of the pathogenesis, epidemiology, and clinical features of rickettsial diseases with emphasis placed on those relating to travel and tropical medicine., Recent Findings: Rickettsioses are becoming increasingly recognized as causes of febrile illness in travelers and in those residing in the tropics. In South and Central America, infection with Rickettsia rickettsii continues to have severe consequences. Resurgence of Mediterranean spotted fever in Bulgaria highlights the threat of rickettsial infections when there is a lapse in vector and reservoir control. Similar to African tick-bite fever, Rickettsia parkeri is an emerging cause of eschar-associated infection in Brazil, Argentina, and Uruguay. Several reports of murine typhus requiring hospitalization demonstrate the risk of this infection to the traveler. The use of fluoroquinolones for milder spotted fevers may fall out of favor with evidence of deleterious effects in those treated with ciprofloxacin., Summary: With globalization and increased access to travel, clinical awareness of rickettsial diseases is of increasing importance. Although the growing number of rickettsial species may be daunting to the clinician, recognition of the patterns of rickettsial disease will ensure prompt and effective therapy.

The antiretroviral agent atazanavir is associated with mild asymptomatic hyperbilirubinemia. We report two cases of symptomatic hyperbilirubinemia attributed to atazanavir in conjunction with the Pneumocystis jirovecii pneumonia prophylaxis agent dapsone. Symptoms and laboratory evidence of hemolysis resolved upon discontinuation of dapsone, enabling successful antiretroviral therapy. Symptomatic hyperbilirubinemia due to hemolytic anemia is a potential adverse event when using the combination of atazanavir and dapsone in the treatment of patients with the human immunodeficiency virus.

Murine typhus is a widely distributed flea-borne infection caused by Rickettsia typhi. Symptoms of murine typhus are nonspecific and mimic a variety of other infectious diseases. We herein report a case of murine typhus in an area where the broad use of DDT in the mid-20th century has now made it a rare disease. The patient described presented with headache, fever, and a faint macular rash. Initial laboratory studies revealed a slight transaminase elevation. Further questioning revealed exposure to opossums, prompting the consideration of murine typhus as a diagnosis. Although typhus group antibodies were not present during the patient's acute illness, empiric therapy with doxycycline was initiated, and the patient defervesced. One month after convalescence, the patient returned to clinic with serum that contained typhus group antibodies with an IgG titer of 1 : 1024. Murine typhus is an important consideration during the workup of a patient with a nonspecific febrile illness. Exposure to reservoir hosts and the flea vector place humans at risk for this disease. Clinician recognition of this entity is required for diagnosis and effective therapy.