-
Tropical Medicine and Infectious Disease Mar 2020Flea-borne typhus, due to and , is an infection causing fever, headache, rash, hepatitis, thrombocytopenia, and diverse organ manifestations. Although most cases are... (Review)
Review
Flea-borne typhus, due to and , is an infection causing fever, headache, rash, hepatitis, thrombocytopenia, and diverse organ manifestations. Although most cases are self-limited, 26%-28% have complications and up to one-third require intensive care. Flea-borne typhus was recognized as an illness similar to epidemic typhus, but having a milder course, in the Southeastern United States and TX from 1913 into the 1920s. Kenneth Maxcy of the US Public Health Service (USPHS) first described the illness in detail and proposed a rodent reservoir and an arthropod vector. Other investigators of the USPHS (Eugene Dyer, Adolph Rumreich, Lucius Badger, Elmer Ceder, William Workman, and George Brigham) determined that the brown and black rats were reservoirs and various species of fleas, especially the Oriental rat flea, were the vectors. The disease was recognized as a health concern in the Southern United States in the 1920s and an increasing number of cases were observed in the 1930s and 1940s, with about 42,000 cases reported between 1931-1946. Attempts to control the disease in the 1930s by fumigation and rat proofing and extermination were unsuccessful. The dramatic increase in the number of cases from 1930 through 1944 was due to: the diversification of Southern agriculture away from cotton; the displacement of the smaller black rat by the larger brown rat in many areas; poor housing conditions during the Great Depression and World War II; and shortages of effective rodenticides and insecticides during World War II.
PubMed: 32121541
DOI: 10.3390/tropicalmed5010037 -
The American Journal of Tropical... Jul 2022Murine 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...
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.
Topics: Animals; Didelphis; Mice; Monodelphis; Rats; Rickettsia; Rickettsia Infections; Rickettsia typhi; Siphonaptera; Typhus, Endemic Flea-Borne
PubMed: 35895366
DOI: 10.4269/ajtmh.21-1076 -
Vaccine Nov 2009Rickettsia prowazekii, R. rickettsii, R. conorii, and R. typhi are serious biologic weapon threats because of high infectivity of low dose aerosols, stable small... (Review)
Review
Rickettsia prowazekii, R. rickettsii, R. conorii, and R. typhi are serious biologic weapon threats because of high infectivity of low dose aerosols, stable small particle aerosol infectivity, virulence causing severe disease, difficulty in establishing a timely diagnosis, ineffectiveness of usual empiric treatments, potential for engineered complete antimicrobial resistance, lower level of immunity, availability of the agents in nature, and feasibility of propagation, stabilization, and dispersal. Infection induces long-term immunity, killed rickettsial vaccines stimulate incomplete protection, and a live attenuated mutant stimulates strong immunity but reverts to virulence. Prospects for rational development of a safe, effective live attenuated vaccine are excellent.
Topics: Animals; Biological Warfare; Biological Warfare Agents; Humans; Rickettsia; Rickettsia Infections; Rickettsial Vaccines; Vaccines, Attenuated; Virulence
PubMed: 19837287
DOI: 10.1016/j.vaccine.2009.07.045 -
Infection and Immunity Jun 2017is the causative agent of endemic typhus, a disease with increasing incidence worldwide that can be fatal. Because of its obligate intracellular life style, genetic...
is the causative agent of endemic typhus, a disease with increasing incidence worldwide that can be fatal. Because of its obligate intracellular life style, genetic manipulation of the pathogen is difficult. Nonetheless, in recent years, genetic manipulation tools have been successfully applied to rickettsiae. We describe here for the first time the transformation of with the pRAM18dRGA plasmid that originally derives from and encodes the expression of GFPuv (green fluorescent protein with maximal fluorescence when excited by UV light). Transformed () bacteria are viable, replicate with kinetics similar to those of wild-type in cell culture, and stably maintain the plasmid and GFPuv expression under antibiotic treatment and during infection of mice. CB17 SCID mice infected with succumb to the infection with kinetics similar to those for animals infected with wild-type and develop comparable pathology and bacterial loads in the organs, demonstrating that the plasmid does not influence pathogenicity. In the spleen and liver of infected CB17 SCID mice, the bacteria are detectable by immunofluorescence microscopy in neutrophils and macrophages by histological staining. Finally, we show for the first time that transformed rickettsiae can be used for the detection of CD8 T cell responses. GFP-specific restimulation of spleen cells from -infected BALB/c mice elicits gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin 2 (IL-2) secretion by CD8 T cells. Thus, bacteria are a novel, potent tool to study infection with the pathogen and and the immune response to these bacteria.
Topics: Animals; CD8-Positive T-Lymphocytes; Cytokines; Green Fluorescent Proteins; Liver; Macrophages; Mice; Mice, Inbred BALB C; Mice, SCID; Neutrophils; Plasmids; Rickettsia typhi; Spleen; Transformation, Bacterial; Typhus, Endemic Flea-Borne
PubMed: 28289147
DOI: 10.1128/IAI.00156-17 -
PloS One 2021Rickettsioses are neglected and emerging potentially fatal febrile diseases that are caused by obligate intracellular bacteria, rickettsiae. Rickettsia (R.) typhi and R....
Rickettsioses are neglected and emerging potentially fatal febrile diseases that are caused by obligate intracellular bacteria, rickettsiae. Rickettsia (R.) typhi and R. prowazekii constitute the typhus group (TG) of rickettsiae and are the causative agents of endemic and epidemic typhus, respectively. We recently generated a monoclonal antibody (BNI52) against R. typhi. Characterization of BNI52 revealed that it specifically recognizes TG rickettsiae but not the members of the spotted fever group (SFG) rickettsiae. We further show that BNI52 binds to protein fragments of ±30 kDa that are exposed on the bacterial surface and also present in the periplasmic space. These protein fragments apparently derive from the cytosolic GroEL protein of R. typhi and are also recognized by antibodies in the sera from patients and infected mice. Furthermore, BNI52 opsonizes the bacteria for the uptake by antigen presenting cells (APC), indicating a contribution of GroEL-specific antibodies to protective immunity. Finally, it is interesting that the GroEL protein belongs to 32 proteins that are differentially downregulated by R. typhi after passage through immunodeficient BALB/c CB17 SCID mice. This could be a hint that the rickettsia GroEL protein may have immunomodulatory properties as shown for the homologous protein from several other bacteria, too. Overall, the results of this study provide evidence that GroEL represents an immunodominant antigen of TG rickettsiae that is recognized by the humoral immune response against these pathogens and that may be interesting as a vaccine candidate. Apart from that, the BNI52 antibody represents a new tool for specific detection of TG rickettsiae in various diagnostic and experimental setups.
Topics: Animals; Antibodies, Bacterial; Antibodies, Monoclonal; Antigens, Bacterial; Cell Line; Chaperonin 60; HEK293 Cells; Humans; Mice, Inbred BALB C; Mice, SCID; Periplasm; Rickettsia Infections; Rickettsia typhi; Xenopus laevis; Mice
PubMed: 34111210
DOI: 10.1371/journal.pone.0253084 -
PLoS Neglected Tropical Diseases Feb 2017Endemic typhus caused by Rickettsia (R.) typhi is an emerging febrile disease that can be fatal due to multiple organ pathology. Here we analyzed the requirements for...
Cytotoxic effector functions of T cells are not required for protective immunity against fatal Rickettsia typhi infection in a murine model of infection: Role of TH1 and TH17 cytokines in protection and pathology.
Endemic typhus caused by Rickettsia (R.) typhi is an emerging febrile disease that can be fatal due to multiple organ pathology. Here we analyzed the requirements for protection against R. typhi by T cells in the CB17 SCID model of infection. BALB/c wild-type mice generate CD4+ TH1 and cytotoxic CD8+ T cells both of which are sporadically reactivated in persistent infection. Either adoptively transferred CD8+ or CD4+ T cells protected R. typhi-infected CB17 SCID mice from death and provided long-term control. CD8+ T cells lacking either IFNγ or Perforin were still protective, demonstrating that the cytotoxic function of CD8+ T cells is not essential for protection. Immune wild-type CD4+ T cells produced high amounts of IFNγ, induced the release of nitric oxide in R. typhi-infected macrophages and inhibited bacterial growth in vitro via IFNγ and TNFα. However, adoptive transfer of CD4+IFNγ-/- T cells still protected 30-90% of R. typhi-infected CB17 SCID mice. These cells acquired a TH17 phenotype, producing high amounts of IL-17A and IL-22 in addition to TNFα, and inhibited bacterial growth in vitro. Surprisingly, the neutralization of either TNFα or IL-17A in CD4+IFNγ-/- T cell recipient mice did not alter bacterial elimination by these cells in vivo, led to faster recovery and enhanced survival compared to isotype-treated animals. Thus, collectively these data show that although CD4+ TH1 cells are clearly efficient in protection against R. typhi, CD4+ TH17 cells are similarly protective if the harmful effects of combined production of TNFα and IL-17A can be inhibited.
Topics: Adoptive Transfer; Animals; Cytokines; Disease Models, Animal; Mice, Inbred BALB C; Mice, SCID; Rickettsia typhi; T-Lymphocyte Subsets; Th1 Cells; Th17 Cells; Typhus, Endemic Flea-Borne
PubMed: 28222146
DOI: 10.1371/journal.pntd.0005404 -
Infectious Disease Reports Oct 2023Murine typhus is an acute febrile illness caused by , an obligately intracellular Gram-negative coccobacillus. Rats () and their fleas () serve as the reservoir and... (Review)
Review
Murine typhus is an acute febrile illness caused by , an obligately intracellular Gram-negative coccobacillus. Rats () and their fleas () serve as the reservoir and vector of , respectively. Humans become infected when -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 () and cat fleas (). 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.
PubMed: 37987401
DOI: 10.3390/idr15060063 -
International Angiology : a Journal of... Oct 2017Rickettsia was suggested as a possible etiology of Buerger's disease (BD) in the 1980s but this suggestion was never ruled out or proven. Recently, we found evidence of...
BACKGROUND
Rickettsia was suggested as a possible etiology of Buerger's disease (BD) in the 1980s but this suggestion was never ruled out or proven. Recently, we found evidence of Rickettsia by polymerase chain reaction in 3 out of 25 biopsy samples from the amputated limb of a young man diagnosed with BD. The aim of this paper was to investigate the presence of anti-rickettsial antibodies in the sera of BD patients.
METHODS
To detect the IgG class antibody against Rickettsia rickettsii, which has cross reactions with the spotted fever group (RSFG), and Rickettsia typhi, which has cross reactions with typhus fever group, the sera of patients and controls were diluted to 1:64 and analyzed by indirect micro fluorescence immunoassay (MIF).
RESULTS
The MIF study showed that 26 of the 28 patients were positive for Rickettsia rickettsii antibodies and MIF had the same appearance as the positive control, which was provided with the kit. In all members of the healthy control group, Rickettsia rickettsii was negative and had the appearance of the negative control. Rickettsia typhi was negative for all patients and members of the control group.
CONCLUSIONS
A species of Rickettsia associated with the RSFG, which might not be pathogenic for the entire population, may induce BD in the context of a specific genetic or environmental background. RSFG infection could explain key questions about BD, including its gender and geographical distribution, clinical manifestation, angiography pattern, and pathological findings. Evaluating antibodies against RSFG in BD patients from different countries is now highly recommended.
Topics: Adult; Antibodies, Bacterial; Case-Control Studies; Cross Reactions; Diagnosis, Differential; Fluorescent Antibody Technique, Indirect; Humans; Immunoglobulin G; Iran; Male; Middle Aged; Rickettsia Infections; Rickettsia rickettsii; Thromboangiitis Obliterans
PubMed: 26344511
DOI: 10.23736/S0392-9590.17.03420-4 -
PloS One 2023The hematophagous behaviour emerged independently in several instances during arthropod evolution. Survey of salivary gland and saliva composition and its...
The hematophagous behaviour emerged independently in several instances during arthropod evolution. Survey of salivary gland and saliva composition and its pharmacological activity led to the conclusion that blood-feeding arthropods evolved a distinct salivary mixture that can interfere with host defensive response, thus facilitating blood acquisition and pathogen transmission. The cat flea, Ctenocephalides felis, is the major vector of several pathogens, including Rickettsia typhi, Rickettsia felis and Bartonella spp. and therefore, represents an important insect species from the medical and veterinary perspectives. Previously, a Sanger-based sialome of adult C. felis female salivary glands was published and reported 1,840 expressing sequence tags (ESTs) which were assembled into 896 contigs. Here, we provide a deeper insight into C. felis salivary gland composition using an Illumina-based sequencing approach. In the current dataset, we report 8,892 coding sequences (CDS) classified into 27 functional classes, which were assembled from 42,754,615 reads. Moreover, we paired our RNAseq data with a mass spectrometry analysis using the translated transcripts as a reference, confirming the presence of several putative secreted protein families in the cat flea salivary gland homogenates. Both transcriptomic and proteomic approaches confirmed that FS-H-like proteins and acid phosphatases lacking their putative catalytic residues are the two most abundant salivary proteins families of C. felis and are potentially related to blood acquisition. We also report several novel sequences similar to apyrases, odorant binding proteins, antigen 5, cholinesterases, proteases, and proteases inhibitors, in addition to putative novel sequences that presented low or no sequence identity to previously deposited sequences. Together, the data represents an extended reference for the identification and characterization of the pharmacological activity present in C. felis salivary glands.
Topics: Animals; Female; Ctenocephalides; Proteomics; Salivary Glands; Saliva; Rickettsia felis; Flea Infestations
PubMed: 36649293
DOI: 10.1371/journal.pone.0279070 -
Journal of Vector Borne Diseases 2022Fleas (Insecta, Siphonaptera) are important vectors of plague and murine typhus in many parts of the world. Currently, about 2700 flea species were described in the... (Review)
Review
Fleas (Insecta, Siphonaptera) are important vectors of plague and murine typhus in many parts of the world. Currently, about 2700 flea species were described in the world. The most common vector flea Xenopsylla cheopis is found throughout India, but X. astia, and X. brasiliensis are found less and limited in distribution associated with the domestic rats such as Rattus rattus, R. norvegicus, Mus musculus, and Bandicota bengalensis. Bubonic plague is a major flea-borne disease caused by the bacterial pathogen Yersinia pestis, transmitted from rats to humans via the rodent flea, X. cheopis. A major outbreak of plague and high mortality occurred in India. After 1966 with the 3 decadal intervals, plague cases occurred only during the year 1994 reported in 5 different states (Gujarat, Maharashtra, Karnataka, Uttar Pradesh, Madhya Pradesh and New Delhi and subsequently plague cases occurred during 2002 and 2004 after the one-decade interval in Himachal Pradesh (2002). Another outbreak of bubonic plague was reported in Dangud village, Barkhot tehsil, Uttarkashi district, Uttarakhand during October 2004. Ctenocephalides fleas are common in cats and dogs, which are the main vectors of bacteria rickettsiae, such as Rickettsia typhi, R. felis, R. conorii, and Bartonella henselae. Molecular and serological evidence also confirms the presence of R. typhi, R. conorii R. felis and B. henselae pathogens in cats and other fleas in India. Flea bites and flea-borne dermatitis are common in men and pet animals. Because of the re-emergence of the plague, updated information on fleas and flea-borne diseases are essential to control the flea vectors and flea-borne diseases in India. Hence, this comprehensive review updates the available information on fleas and fleas transmitted diseases in India.
Topics: Animals; Cats; Dogs; Flea Infestations; Humans; India; Mice; Plague; Public Health; Rats; Siphonaptera
PubMed: 35708399
DOI: 10.4103/0972-9062.328977