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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 -
MBio Feb 2021species (spp.) are strict obligate intracellular bacteria, some of which are pathogenic in their mammalian host, including humans. One critical feature of these...
species (spp.) are strict obligate intracellular bacteria, some of which are pathogenic in their mammalian host, including humans. One critical feature of these stealthy group of pathogens is their ability to manipulate hostile cytosolic environments to their benefits. Although our understanding of cell biology and pathogenesis is evolving, the mechanisms by which pathogenic spp. evade host innate immune detection remain elusive. Here, we show that disease severity in wild-type (WT) C57BL/6J mice infected with Rickettsia typhi (the etiologic agent of murine typhus) and Rickettsia rickettsii (the etiologic agent of Rocky Mountain spotted fever), but not with the nonpathogenic species Rickettsia montanensis, correlated with levels of bacterial burden as detected in the spleens of mice, as well as the serum concentrations of proinflammatory cytokine interleukin-1α (IL-1α) and, to a lesser extent, IL-1β. Antibody-mediated neutralization of IL-1α confirmed a key role in controlling mortality rates and bacterial burdens of rickettsia-infected WT mice. As macrophages are a primary source of both IL-1α and IL-1β cytokines, we determined the mechanism of the antirickettsial activities using bone marrow-derived macrophages. We found that pathogenic R. typhi and R. rickettsii, but not nonpathogenic R. montanensis, eluded pro-IL-1α induction and benefited predominantly from the reduced IL-1α secretion, via a caspase-11-gasdermin D (Gsdmd)-dependent pathway, to facilitate intracytosolic replication. Adoptive transfer experiments identified that IL-1α secretion by macrophages was critical for controlling rickettsiosis in WT mice. In sum, we identified a previously unappreciated pathway by which pathogenic, unlike nonpathogenic, rickettsiae preferentially target the caspase-11-Gsdmd-IL-1α signaling axis in macrophages, thus supporting their replication within the host. Currently, no vaccines are available to prevent rickettsioses, while vector-borne rickettsial infections in humans are on the rise globally. In fact, the insufficient understanding of how pathogenic species circumvent host immune defense mechanisms has significantly hindered the development of more effective therapeutics. Here, we identified a previously unappreciated role for the caspase-11-Gsdmd-IL-1α signaling axis in limiting the replication of pathogenic and R. typhi species in murine macrophages and wild-type (WT) C57BL/6J mice. Adoptive transfer studies further identified IL-1α-secreting macrophages as critical mediators in controlling rickettsial infection in WT mice. Collectively, these findings provide insight into the potential mechanism of how pathogenic, but not nonpathogenic, spp. benefit from a reduction in the caspase-11-Gsdmd-mediated release of IL-1α to support host colonization.
Topics: Humans; Animals; Mice; Inflammasomes; Interleukin-1alpha; Mice, Inbred C57BL; Rickettsia; Caspases; Mammals
PubMed: 35130729
DOI: 10.1128/mbio.02918-21 -
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 -
BMC Infectious Diseases May 2020Reports of human rickettsial infection in Indonesia are limited. This study sought to characterize the epidemiology of human rickettsioses amongst patients hospitalized... (Observational Study)
Observational Study
BACKGROUND
Reports of human rickettsial infection in Indonesia are limited. This study sought to characterize the epidemiology of human rickettsioses amongst patients hospitalized with fever at 8 tertiary hospitals in Indonesia.
METHODS
Acute and convalescent blood from 975 hospitalized non-dengue patients was tested for Rickettsia IgM and IgG by ELISA. Specimens from cases with seroconversion or increasing IgM and/or IgG titers were tested for Rickettsia IgM and IgG by IFA and Rickettsia genomes using primers for Rickettsia (R.) sp, R. typhi, and Orientia tsutsugamushi. Testing was performed retrospectively on stored specimens; results did not inform patient management.
RESULTS
R. typhi, R. rickettsii, and O. tsutsugamushi IgG antibodies were identified in 269/872 (30.8%), 36/634 (5.7%), and 19/504 (3.8%) of samples, respectively. For the 103/975 (10.6%) non-dengue patients diagnosed with acute rickettsial infection, presenting symptoms included nausea (72%), headache (69%), vomiting (43%), lethargy (33%), anorexia (32%), arthralgia (30%), myalgia (28%), chills (28%), epigastric pain (28%), and rash (17%). No acute rickettsioses cases were suspected during hospitalization. Discharge diagnoses included typhoid fever (44), dengue fever (20), respiratory infections (7), leptospirosis (6), unknown fever (6), sepsis (5), hepatobiliary infections (3), UTI (3), and others (9). Fatalities occurred in 7 (6.8%) patients, mostly with co-morbidities.
CONCLUSIONS
Rickettsial infections are consistently misdiagnosed, often as leptospirosis, dengue, or Salmonella typhi infection. Clinicians should include rickettsioses in their differential diagnosis of fever to guide empiric management; laboratories should support evaluation for rickettsial etiologies; and public policy should be implemented to reduce burden of disease.
Topics: Acute Disease; Adolescent; Adult; Aged; Antibodies, Bacterial; Child; Child, Preschool; Dengue; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; Fever; Hospitalization; Humans; Immunoglobulin G; Indonesia; Infant; Leptospirosis; Male; Middle Aged; Orientia tsutsugamushi; Retrospective Studies; Rickettsia Infections; Rickettsia rickettsii; Rickettsia typhi; Scrub Typhus; Typhoid Fever; Young Adult
PubMed: 32448167
DOI: 10.1186/s12879-020-05057-9 -
The Journal of Biological Chemistry Mar 2014Methylation of rickettsial OmpB (outer membrane protein B) has been implicated in bacterial virulence. Rickettsial methyltransferases RP789 and RP027-028 are the first...
Methylation of rickettsial OmpB (outer membrane protein B) has been implicated in bacterial virulence. Rickettsial methyltransferases RP789 and RP027-028 are the first biochemically characterized methyltransferases to catalyze methylation of outer membrane protein (OMP). Methylation in OMP remains poorly understood. Using semiquantitative integrated liquid chromatography-tandem mass spectroscopy, we characterize methylation of (i) recombinantly expressed fragments of Rickettsia typhi OmpB exposed in vitro to trimethyltransferases of Rickettsia prowazekii RP027-028 and of R. typhi RT0101 and to monomethyltransferases of R. prowazekii RP789 and of R. typhi RT0776, and (ii) native OmpBs purified from R. typhi and R. prowazekii strains Breinl, RP22, and Madrid E. We found that in vitro trimethylation occurs at relatively specific locations in OmpB with consensus motifs, KX(G/A/V/I)N and KT(I/L/F), whereas monomethylation is pervasive throughout OmpB. Native OmpB from virulent R. typhi contains mono- and trimethyllysines at locations well correlated with methylation in recombinant OmpB catalyzed by methyltransferases in vitro. Native OmpBs from highly virulent R. prowazekii strains Breinl and RP22 contain multiple clusters of trimethyllysine in contrast to a single cluster in OmpB from mildly virulent R. typhi. Furthermore, OmpB from the avirulent strain Madrid E contains mostly monomethyllysine and no trimethyllysine. The native OmpB from Madrid E was minimally trimethylated by RT0101 or RP027-028, consistent with a processive mechanism of trimethylation. This study provides the first in-depth characterization of methylation of an OMP at the molecular level and may lead to uncovering the link between OmpB methylation and rickettsial virulence.
Topics: Amino Acid Motifs; Bacterial Outer Membrane Proteins; Cell Membrane; Chromatography, Liquid; Kinetics; Lysine; Methylation; Methyltransferases; Plasmids; Protein Structure, Tertiary; Rickettsia prowazekii; Rickettsia typhi; Tandem Mass Spectrometry; Virulence
PubMed: 24497633
DOI: 10.1074/jbc.M113.535567 -
Microbiology and Immunology 1995Cross-reactivity between Rickettsia japonica and R. typhi was observed by immunofluorescence tests using sera from patients with Oriental spotted fever (OSF), from whom... (Comparative Study)
Comparative Study
Cross-reactivity between Rickettsia japonica and R. typhi was observed by immunofluorescence tests using sera from patients with Oriental spotted fever (OSF), from whom the causative agent was isolated and identified as R. japonica. Western immunoblotting with these sera revealed that only the 120-kilodalton surface polypeptide, i.e., rickettsial outer membrane protein (rOmp) B, has a common antigenicity with the 105-kilodalton surface polypeptide of R. typhi. In some cases, antibodies specifically reactive with R. typhi were detected in acute-phase sera followed by a significant rise in titers, possibly because of an anamnestic response to a previous infection with an R. typhi-like agent; the sera retained reactivity to R. typhi even after absorption by a homologous strain. A lipopolysaccharide (LPS)-like antigen of R. typhi was found to be reactive with some sera of OSF patients. The ladder bands on Western immunoblot of rickettsial organisms were confirmed to be polysaccharide in nature, which was demonstrated by comparing them with the pattern of silver-stained gel of proteinase K-treated rickettsial specimens after sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
Topics: Antibodies, Bacterial; Antibody Specificity; Antigens, Bacterial; Bacterial Outer Membrane Proteins; Blotting, Western; Cross Reactions; Fluorescent Antibody Technique; Humans; Lipopolysaccharides; Rickettsia; Rickettsia Infections; Rickettsia typhi; Species Specificity
PubMed: 8789054
DOI: 10.1111/j.1348-0421.1995.tb03298.x -
Journal of Bacteriology Oct 2018Members of the genus are obligate intracellular, Gram-negative coccobacilli that infect mammalian and arthropod hosts. Several rickettsial species are human pathogens...
Members of the genus are obligate intracellular, Gram-negative coccobacilli that infect mammalian and arthropod hosts. Several rickettsial species are human pathogens and are transmitted by blood-feeding arthropods. In Gram-negative parasites, the outer membrane (OM) sits at the nexus of the host-pathogen interaction and is rich in lipopolysaccharide (LPS). The lipid A component of LPS anchors the molecule to the bacterial surface and is an endotoxic agonist of Toll-like receptor 4 (TLR4). Despite the apparent importance of lipid A in maintaining OM integrity, as well as its inflammatory potential during infection, this molecule is poorly characterized in pathogens. In this work, we have identified and characterized new members of the recently discovered LpxJ family of lipid A acyltransferases in both and , the etiological agents of murine typhus and Rocky Mountain spotted fever, respectively. Our results demonstrate that these enzymes catalyze the addition of a secondary acyl chain (C/C) to the 3'-linked primary acyl chain of the lipid A moiety in the final steps of the Raetz pathway of lipid A biosynthesis. Since lipid A architecture is fundamental to bacterial OM integrity, we believe that rickettsial LpxJ may be important in maintaining membrane dynamics to facilitate molecular interactions at the host-pathogen interface that are required for adhesion and invasion of mammalian cells. This work contributes to our understanding of rickettsial outer membrane physiology and sets a foundation for further exploration of the envelope and its role in pathogenesis. Lipopolysaccharide (LPS) triggers an inflammatory response through the TLR4-MD2 receptor complex and inflammatory caspases, a process mediated by the lipid A moiety of LPS. Species of directly engage both extracellular and intracellular immunosurveillance, yet little is known about rickettsial lipid A. Here, we demonstrate that the alternative lipid A acyltransferase, LpxJ, from and catalyzes the addition of C fatty acid chains into the lipid A 3'-linked primary acyl chain, accounting for major structural differences relative to the highly inflammatory lipid A of .
Topics: Acyltransferases; Bacterial Proteins; Fatty Acids; Genome, Bacterial; Host-Pathogen Interactions; Lipid A; Rickettsia rickettsii; Rickettsia typhi
PubMed: 30012728
DOI: 10.1128/JB.00334-18 -
PloS One 2012An increasing use of point of care diagnostic tests that exclude malaria, coupled with a declining malaria burden in many endemic countries, is highlighting the lack of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
An increasing use of point of care diagnostic tests that exclude malaria, coupled with a declining malaria burden in many endemic countries, is highlighting the lack of ability of many health systems to manage other causes of febrile disease. A lack of knowledge of distribution of these pathogens, and a lack of screening and point-of-care diagnostics to identify them, prevents effective management of these generally treatable contributors to disease burden. While prospective data collection is vital, an untapped body of knowledge already exists in the published health literature.
METHODS
Focusing on the Mekong region of Southeast Asia, published data from 1986 to 2011 was screened to for frequency of isolation of pathogens implicated in aetiology of non-malarial febrile illness. Eligibility criteria included English-language peer-reviewed studies recording major pathogens for which specific management is likely to be warranted. Of 1,252 identified papers, 146 met inclusion criteria and were analyzed and data mapped.
RESULTS
Data tended to be clustered around specific areas where research institutions operate, and where resources to conduct studies are greater. The most frequently reported pathogen was dengue virus (n = 70), followed by Orientia tsutsugamushi and Rickettsia species (scrub typhus/murine typhus/spotted fever group n = 58), Leptospira spp. (n = 35), Salmonella enterica serovar Typhi and Paratyphi (enteric fever n = 24), Burkholderia pseudomallei (melioidosis n = 14), and Japanese encephalitis virus (n = 18). Wide tracts with very little published data on aetiology of fever are apparent.
DISCUSSION AND CONCLUSIONS
This mapping demonstrates a very heterogeneous distribution of information on the causes of fever in the Mekong countries. Further directed data collection to address gaps in the evidence-base, and expansion to a global database of pathogen distribution, is readily achievable, and would help define wider priorities for research and development to improve syndromic management of fever, prioritize diagnostic development, and guide empirical therapy.
Topics: Asia, Southeastern; Fever; Geography; Humans
PubMed: 22970193
DOI: 10.1371/journal.pone.0044269 -
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 -
Clinical Microbiology and Infection :... Dec 2009
Topics: Animals; Antibodies, Bacterial; Dog Diseases; Dogs; Female; Fluorescent Antibody Technique, Indirect; Immunoglobulin G; Male; Rickettsia Infections; Rickettsia felis; Rickettsia typhi; Seroepidemiologic Studies; Spain
PubMed: 19392898
DOI: 10.1111/j.1469-0691.2008.02156.x