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MMWR. Morbidity and Mortality Weekly... Aug 2023Fleaborne typhus (also known as murine typhus), a widely distributed vectorborne zoonosis caused by Rickettsia typhi, is a moderately severe, but infrequently fatal...
Fleaborne typhus (also known as murine typhus), a widely distributed vectorborne zoonosis caused by Rickettsia typhi, is a moderately severe, but infrequently fatal illness; among patients who receive doxycycline, the case-fatality rate is <1%. Fleaborne typhus is a mandated reportable condition in California. Reported fleaborne typhus cases in Los Angeles County have been increasing since 2010, with the highest number (171) reported during 2022. During June-October 2022, Los Angeles County Department of Public Health learned of three fleaborne typhus-associated deaths. This report describes the clinical presentation, illness course, and methods used to diagnose fleaborne typhus in these three cases. Severe fleaborne typhus manifestations among these cases included hemophagocytic lymphohistiocytosis, a rare immune hyperactivation syndrome that can occur in the infection setting; myocarditis; and septic shock with disseminated intravascular coagulation. Increased health care provider and public health awareness of the prevalence and severity of fleaborne typhus and of the importance of early doxycycline therapy is essential for prevention and treatment efforts.
Topics: Mice; Humans; Doxycycline; Typhus, Epidemic Louse-Borne; Los Angeles; Typhus, Endemic Flea-Borne; Rickettsia typhi; Animals
PubMed: 37535465
DOI: 10.15585/mmwr.mm7231a1 -
BioRxiv : the Preprint Server For... Jul 2023Rickettsiae are Gram-negative obligate intracellular parasites of numerous eukaryotes. Human pathogens of the Transitional Group (TRG), Typhus Group (TG), and Spotted...
UNLABELLED
Rickettsiae are Gram-negative obligate intracellular parasites of numerous eukaryotes. Human pathogens of the Transitional Group (TRG), Typhus Group (TG), and Spotted Fever Group (SFG) rickettsiae infect blood-feeding arthropods, have dissimilar clinical manifestations, and possess unique genomic and morphological attributes. Lacking glycolysis, rickettsiae pilfer numerous metabolites from host cytosol to synthesize peptidoglycan and lipopolysaccharide (LPS). For LPS, O-antigen immunogenicity varies between SFG and TG pathogens; however, lipid A proinflammatory potential is unknown. We previously demonstrated that (TRG), (TG), and (SFG) produce lipid A with long 2' secondary acyl chains (C16 or C18) compared to short 2' secondary acyl chains (C12) in (SFG) lipid A. To further probe this structural heterogeneity and estimate a time point when shorter 2' secondary acyl chains originated, we generated lipid A structures for two additional SFG rickettsiae ( and ) utilizing Fast Lipid Analysis Technique adopted for use with tandem mass spectrometry (FLAT ). FLAT allowed analysis of lipid A structure directly from host cell-purified bacteria, providing substantial improvement over lipid A chemical extraction. FLAT -derived structures indicate SFG rickettsiae diverging after evolved shorter 2' secondary acyl chains. Bioinformatics analysis of LpxL late acyltransferases revealed discrete active sites and hydrocarbon rulers for long versus short 2' secondary acyl chain addition. While the significance of different lipid A structures for diverse pathogens is unknown, our success using FLAT will facilitate determining how structural heterogeneity impacts interactions with host lipid A receptors and overall inflammatory potential.
IMPORTANCE
Deforestation, urbanization, and homelessness lead to spikes in Rickettsioses. Vector-borne human pathogens of Transitional Group (TRG), Typhus Group (TG), and Spotted Fever Group (SFG) rickettsiae differ by clinical manifestations, immunopathology, genome composition, and morphology. We previously showed that lipid A (or endotoxin), the membrane anchor of Gram-negative bacterial lipopolysaccharide (LPS), structurally differs in (later-evolving SFG) relative to (basal SFG), (TG), and (TRG). As lipid A structure influences recognition potential in vertebrate LPS sensors, further assessment of lipid A structural heterogeneity is needed. Here, we sidestepped the difficulty of lipid A chemical extraction by utilizing FLAT , a new procedure for generating lipid A structures directly from host cell-purified bacteria. These data confirm later-evolving SFG pathogens synthesize structurally distinct lipid A. Our findings impact interpreting immune responses to different pathogens and utilizing lipid A adjuvant or anti-inflammatory properties in vaccinology.
PubMed: 37461656
DOI: 10.1101/2023.07.06.547954 -
PloS One 2023Murine typhus (MT), an infection caused by the gram-negative bacteria Rickettsia typhi (R. typhi), is a significant cause of acute febrile illness (AFI) in Southeast...
Murine typhus (MT), an infection caused by the gram-negative bacteria Rickettsia typhi (R. typhi), is a significant cause of acute febrile illness (AFI) in Southeast Asia but is rarely reported in Indonesia. The current study aimed to describe the clinical characteristics of MT cases in Bandung, West Java. Non-confirmed AFI cases (n = 176) from a prospective cohort study of whom paired serum samples (acute (T1), midterm (T2), or convalescent (T3)) were available were screened using MT serology. IgG against R. typhi was detected in the T2 or T3 samples using an in-house ELISA. Positive IgG samples were further screened for the presence of IgM. If both IgM and IgG were positive, the endpoint titer of T1, T2, or T3 was determined. In cases with a fourfold increase in titer, real-time PCR of T1 samples was performed to detect R. typhi DNA. In total, 71/176 (40.3%) patients tested positive for IgG antibody, and 26 AFI cases were confirmed as MT (23 cases by PCR, 3 cases by fourfold titer increased IgG or IgM titer). The most common clinical symptoms in the confirmed cases were headache (80%), arthralgia (73%), malaise (69%), and myalgia (54%). In these cases, the presumptive clinical diagnoses were typhoid fever (43.2%), dengue (38.5%), and leptospirosis (19.2%). MT was not considered in any of the patients, and no patients received doxycycline. These findings confirmed that MT is an important cause of AFI in Indonesia. MT should be included in the differential diagnosis of AFI, and empirical treatment with doxycycline should be considered.
Topics: Mice; Animals; Humans; Typhus, Endemic Flea-Borne; Indonesia; Prospective Studies; Doxycycline; Rickettsia typhi; Fever; Immunoglobulin G; Immunoglobulin M
PubMed: 37418452
DOI: 10.1371/journal.pone.0283135 -
Emerging Infectious Diseases Jul 2023To elucidate the epidemiology of murine typhus, which is infrequently reported in Japan, we conducted a cross-sectional study involving 2,382 residents of...
To elucidate the epidemiology of murine typhus, which is infrequently reported in Japan, we conducted a cross-sectional study involving 2,382 residents of rickettsiosis-endemic areas in Honshu Island during August-November 2020. Rickettsia typhi seroprevalence rate was higher than that of Orientia tsutsugamushi, indicating that murine typhus is a neglected disease.
Topics: Animals; Mice; Humans; Typhus, Endemic Flea-Borne; Scrub Typhus; Seroepidemiologic Studies; Japan; Cross-Sectional Studies; Orientia tsutsugamushi; Rickettsia typhi
PubMed: 37347821
DOI: 10.3201/eid2907.230037 -
Infection Dec 2023The number of homeless people in Germany is steadily increasing. Due to their often precarious living conditions, this specific population may be increasingly exposed to...
PURPOSE
The number of homeless people in Germany is steadily increasing. Due to their often precarious living conditions, this specific population may be increasingly exposed to ectoparasites that can transmit various pathogens. To assess the prevalence and thus the risk of such infections, we analyzed the seropositivity of rickettsiosis, Q fever, tularemia and bartonellosis in homeless individuals.
METHODS
A total of 147 homeless adults from nine shelters in Hamburg, Germany, were included. The individuals underwent questionnaire-based interviewing, physical examination, and venous blood was drawn between May and June 2020. Blood samples were analyzed for antibodies against rickettsiae (Rickettsia typhi and R. conorii), Coxiella burnetii, Francisella tularensis and bartonellae.
RESULTS AND CONCLUSION
A very low seroprevalence of R. typhi and F. tularensis infection was found (0-1%), while antibodies against R. conorii and C. burnetii were more common (7% each), followed by a relatively high seroprevalence of 14% for bartonellosis. Q fever seroprevalence was associated with the country of origin, whereas bartonellosis seroprevalence was associated with the duration of homelessness. Preventive measures targeting ectoparasites, especially body lice, should be put in place continuously.
Topics: Adult; Animals; Humans; Q Fever; Arthropods; Seroepidemiologic Studies; Bacterial Infections; Coxiella burnetii; Bartonella Infections; Ill-Housed Persons; Antibodies, Bacterial
PubMed: 37289422
DOI: 10.1007/s15010-023-02059-y -
Emerging Infectious Diseases Jun 2023We report a case of murine typhus in China caused by Rickettsia typhi and diagnosed by nanopore targeted sequencing of a bronchoalveolar lavage fluid sample. This case...
We report a case of murine typhus in China caused by Rickettsia typhi and diagnosed by nanopore targeted sequencing of a bronchoalveolar lavage fluid sample. This case highlights that nanopore targeted sequencing can effectively detect clinically unexplained infections and be especially useful for detecting infections in patients without typical signs and symptoms.
Topics: Animals; Mice; Humans; Typhus, Endemic Flea-Borne; Nanopores; Rickettsia typhi; China; Bronchoalveolar Lavage Fluid
PubMed: 37209688
DOI: 10.3201/eid2906.221929 -
The Journal of Infection May 2023The burden of imported rickettsial infection in the UK is not previously described. This retrospective review identifies rickettsial cases diagnosed at the national...
OBJECTIVE
The burden of imported rickettsial infection in the UK is not previously described. This retrospective review identifies rickettsial cases diagnosed at the national reference laboratory between 2015 and 2022.
METHODS
Samples testing positive for spotted fever group, typhus group, and scrub typhus IgG/IgM on acute and convalescent blood samples, and/or PCR on tissue/blood were categorized as suspected, confirmed or past infection.
RESULTS
220 patients had rickettsioses, and the commonest import was acute spotted fever group infection (61%, 125/205), 54% (62/114) from South Africa. In acute typhus group cases, 60% (40/67) were from Southeast Asia. One patient with Rickettsia typhi bacteremia died. Scrub typhus group infections (5%, 10/205) were exclusively from Asia and the Western Pacific regions. Overall, 43% of confirmed cases (39/91) had not received doxycycline prior to results.
CONCLUSIONS
Rickettsial infections are important and under-recognized causes of imported fever in the UK. Thorough history, examination, and timely treatment with doxycycline should be considered if there is suspicion of Rickettsia infection before testing.
Topics: Humans; Scrub Typhus; Doxycycline; Typhus, Epidemic Louse-Borne; Rickettsia Infections; Rickettsia; Spotted Fever Group Rickettsiosis
PubMed: 36948252
DOI: 10.1016/j.jinf.2023.03.015 -
International Journal of Infectious... May 2023We examined the frequency of cross-reactions to Rickettsia typhi in patients with Japanese spotted fever (JSF) and evaluated the differences between two rickettsiae...
OBJECTIVES
We examined the frequency of cross-reactions to Rickettsia typhi in patients with Japanese spotted fever (JSF) and evaluated the differences between two rickettsiae using antibody endpoint titers.
METHODS
Patients' immunoglobulin (Ig)M and IgG titers against Rickettsia japonica and Rickettsia typhi in two phases were measured using an indirect immunoperoxidase assay at two reference centers for rickettsiosis in Japan. Cross-reaction was defined as a higher titer against R. typhi in convalescent sera than in acute sera among patients fulfilling the criteria for JSF diagnosis. The frequencies of IgM and IgG were also evaluated.
RESULTS
Approximately 20% of cases showed positive cross-reactions. A comparison of antibody titers revealed the difficulty in identifying some positive cases.
CONCLUSION
Cross-reactions of 20% in serodiagnosis may lead to the misclassification of rickettsial diseases. However, with the exception of some cases, we were able to successfully differentiate JSF from murine typhus using each endpoint titer.
Topics: Animals; Mice; Humans; Typhus, Epidemic Louse-Borne; Japan; Rickettsia Infections; Spotted Fever Group Rickettsiosis; Rickettsia; Typhus, Endemic Flea-Borne; Rickettsia typhi; Serologic Tests; Immunoglobulin M; Immunoglobulin G; Antibodies, Bacterial
PubMed: 36907548
DOI: 10.1016/j.ijid.2023.03.012 -
Infectious Disease Reports Feb 2023Infection with members of the order Rickettsiales (the genera , , , and ) is known to cause hemophagocytic lymphohistiocytosis (HLH). The literature is scant on...
Infection with members of the order Rickettsiales (the genera , , , and ) is known to cause hemophagocytic lymphohistiocytosis (HLH). The literature is scant on flea-borne typhus (FBT) being implicated in this process. We present a case of autopsy-proven HLH caused by FBT in a 71-year-old diabetic female who was initially suspected of having diabetic ketoacidosis who rapidly suffered decompensated multi-organ failure. Although she was suspected of having FBT and HLH pre-mortem, due to her rapid progression to multi-organ failure, she was transitioned to comfort care by her family five days after admission. A literature search yielded five other cases of HLH secondary to FBT, which are analyzed in this review. The literature on HLH occurring with infection due to other members of the order Rickettsiales is also surveyed.
PubMed: 36826354
DOI: 10.3390/idr15010014 -
Vaccines Jan 2023In recent years, promising vaccination strategies against rickettsiosis have been described in experimental animal models and human cells. OmpB is considered an...
In recent years, promising vaccination strategies against rickettsiosis have been described in experimental animal models and human cells. OmpB is considered an immunodominant antigen that is recognized by T and B cells. The aim of this study was to identify TCD4+INF-γ+ and TCD8+INF-γ+ lymphocytes in an autologous system with macrophages transfected with the vaccine candidate pVAX1-OmpB24. Lymphocytes and monocytes from 14 patients with Rickettsia were isolated from whole blood. Monocytes were differentiated into macrophages and transfected with the plasmid pVAX1-OmpB24 pVax1. Isolated lymphocytes were cultured with transfected macrophages. IFN-γ-producing TCD4+ and TCD8+ lymphocyte subpopulations were identified by flow cytometry, as was the percentage of macrophages expressing CD40+, CD80+, HLA-I and HLA-II. Also, we analyzed the exhausted condition of the T lymphocyte subpopulation by PD1 expression. Macrophages transfected with pVAX1-OmpB24 stimulated TCD4+INF-γ+ cells in healthy subjects and patients infected with . Macrophages stimulated TCD8+INF-γ+ cells in healthy subjects and patients infected with and . Cells from healthy donors stimulated with OmpB-24 showed a higher percentage of TCD4+PD1+. Cells from patients infected with had a higher percentage of TCD8+PD-1+, and for those infected with the larger number of cells corresponded to TCD4+PD1+. Human macrophages transfected with pVAX1-OmpB24 activated TCD4+IFN-γ+ and CD8+IFN-γ+ in patients infected with different Rickettsia species. However, PD1 expression played an important role in the inhibition of T lymphocytes with
PubMed: 36680017
DOI: 10.3390/vaccines11010173