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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 -
Journal of Neuro-ophthalmology : the... Sep 2023
Topics: Humans; Typhus, Endemic Flea-Borne; Retinal Diseases; Macula Lutea; White Dot Syndromes
PubMed: 34629398
DOI: 10.1097/WNO.0000000000001360 -
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 -
Acta Tropica Jan 2024Rickettsia species are obligate intracellular bacteria that can cause mild to severe human disease. Based on phylogeny, clinical symptoms, and antigenic properties,...
Rickettsia species are obligate intracellular bacteria that can cause mild to severe human disease. Based on phylogeny, clinical symptoms, and antigenic properties, rickettsiae are classified into four groups. Infections by these agents are characterized by clinical symptoms ranging from self-limited to severe and even fatal febrile illnesses, depending on the Rickettsia spp. involved, the patient's predisposition, and timely medical care. The present study aimed to characterize rickettsial diseases in Yucatan according to clinical and laboratory features appearing in medical records corresponding to 427 samples taken between 2015 and 2018. A study was conducted over the period 2015-2018 on 427 samples. Clinical and laboratory features were documented from the patients' medical records. For molecular diagnosis, blood was collected in 3.8 % sodium citrate as anticoagulant, and DNA was extracted. Single-step and nested PCR amplification was performed using genus-specific primers for the rickettsial 17kDa and ompB genes. The amplicons obtained were purified and sequenced. A total of 22.7 % (97/427) positive cases of Rickettsia spp. were identified by PCR from 14.15 % (15/106) of the municipalities in Yucatan. 75.2 % (73/97) of the cases were from the city of Merida during the autumn (September-December). The age groups with the highest frequency of confirmed cases were pediatric (5-14 years) (57.7 %) and adults (25-49 years) (42.2 %). There were six fatal cases in children, one associated with R. typhi and five with R. rickettsii. In non-fatal cases, 32.9 % (32/97) corresponded to the spotted fever group (SFG), and 60.8 % (59/97) to the typhus group (TG). Significant differences in signs, and laboratory data, were observed between the pediatric and adult populations. For the treatment of patients, oral and intravenous doxycycline was used in severe hospitalized cases. Typhus group and spotted fever group Rickettsiae are endemic pathological agents found in urban and rural areas of our region. Molecular identification allows for greater diagnostic accuracy and timely treatment and consequently a better prognosis. It is necessary to implement or reinforce measures focused on the dissemination of knowledge regarding rickettsial diseases and their prevention.
Topics: Adult; Humans; Child; Child, Preschool; Adolescent; Mexico; Typhus, Epidemic Louse-Borne; Rickettsia Infections; Rickettsia; Spotted Fever Group Rickettsiosis
PubMed: 37931342
DOI: 10.1016/j.actatropica.2023.107048 -
The American Journal of Tropical... Jan 2024Flea-borne typhus is a vector-borne disease caused by Rickettsia typhi that occurs worldwide, except in Antarctica. In the United States, most cases are restricted to... (Review)
Review
Flea-borne typhus is a vector-borne disease caused by Rickettsia typhi that occurs worldwide, except in Antarctica. In the United States, most cases are restricted to California, Hawaii, and Texas. The syndrome is characterized by nonspecific signs and symptoms: fever, headache, rash, arthralgia, cough, hepatosplenomegaly, diarrhea, and abdominal pain. Although flea-borne typhus can cause pulmonary, neurological, and renal complications, the cardiovascular system is rarely affected. We present a case of endocarditis resulting from flea-borne typhus diagnosed by blood microbial cell-free DNA testing that required valve replacement and antibiotic therapy for 6 months. In addition, we review 20 cases of presumed and confirmed cardiovascular manifestations resulting from flea-borne typhus in the literature.
Topics: Humans; Animals; Typhus, Epidemic Louse-Borne; Typhus, Endemic Flea-Borne; Rickettsia typhi; Anti-Bacterial Agents; Siphonaptera
PubMed: 38052087
DOI: 10.4269/ajtmh.22-0794 -
BMC Ophthalmology Mar 2024To report a case of unusual presentation of retinochoroiditis caused by Rickettsia typhi in a patient without prior uveitis.
BACKGROUND
To report a case of unusual presentation of retinochoroiditis caused by Rickettsia typhi in a patient without prior uveitis.
CASE PRESENTATION
In this case, we describe a 24-year-old male soldier with no previous eye disease, who was referred to our ophthalmology department due to bilateral retinochoroiditis and vitritis. The patient initially presented with a paracentral scotoma in his right eye persisting for 7 days and scattered dark spots in his left eye for 2 days in June 2023. Preceding these ocular symptoms, he experienced a two-week episode of fever, headaches, night sweats, and rapid weight loss of 10 kg. A transient rash covered his body briefly. His mother had a history of recurrent eye inflammation. Physical examination revealed bilateral keratic precipitates on the lower corneal periphery, 1 + anterior vitreous cells, small retinal lesions and mild optic discs elevation. Fluorescein angiography indicated mild discs hyperfluorescence, and the clinically visible round punctate lesions on OCT showed inner retinal hyper-reflective lesion with a depth till outer plexiform layer possibly suggestive of a retinitis lesion. Laboratory tests were normal except thrombocytosis, elevated ESR, liver enzymes and ACE levels, with positive Rickettsia typhi serology tests. Rheumatology and infectious disease consultations ruled out autoimmune diseases, confirming Rickettsia typhi infection. Treatment included systemic doxycycline and prednisone, with improvement of visual acuity, ocular symptoms, OCT abnormalities and resolution of inflammation. Prednisone was discontinued, and after two months, additional improvement was seen clinically, with preserved retinal structures on OCT.
CONCLUSION
This study explores retinochoroiditis as a rare ocular presentation of Rickettsia typhi, an unusual infection in the Middle East. Previously reported ocular manifestations include conjunctivitis, vitritis, post infectious optic neuropathy and a few cases of uveitis. Ocular symptoms followed systemic illness, highlighting the need for awareness among clinicians. Diagnosis relies on seroconversion, with fluorescein angiography and OCT aiding in assessment. Empiric doxycycline and systemic corticosteroid therapy is recommended. Ocular symptoms resolved in two months. Awareness of these ocular manifestations is essential for timely diagnosis and management. Further research is needed to fully understand this aspect of murine typhus.
Topics: Humans; Male; Young Adult; Chorioretinitis; Doxycycline; Inflammation; Prednisone; Typhus, Endemic Flea-Borne
PubMed: 38454387
DOI: 10.1186/s12886-024-03329-5 -
Microbiology Spectrum Dec 2023spp. are intracellular bacterial parasites of a wide range of arthropod and vertebrate hosts. Some rickettsiae are responsible for several severe human diseases...
Autophagy facilitates intracellular survival of pathogenic rickettsiae in macrophages via evasion of autophagosomal maturation and reduction of microbicidal pro-inflammatory IL-1 cytokine responses.
spp. are intracellular bacterial parasites of a wide range of arthropod and vertebrate hosts. Some rickettsiae are responsible for several severe human diseases globally. One interesting feature of these pathogens is their ability to exploit host cytosolic defense responses to their benefits. However, the precise mechanism by which pathogenic spp. elude host defense responses remains unclear. Here, we observed that pathogenic and (Sheila Smith [SS]), but not non-pathogenic , become ubiquitinated and induce autophagy upon entry into macrophages. Moreover, unlike , and (SS) colocalized with LC3B but not with Lamp2 upon host cell entry. Finally, we observed that both and (SS), but not , reduce pro-inflammatory interleukin-1 (IL-1) responses, likely via an autophagy-mediated mechanism. In summary, we identified a previously unappreciated pathway by which both pathogenic and (SS) become ubiquitinated, induce autophagy, avoid autolysosomal destruction, and reduce microbicidal IL-1 cytokine responses to establish an intracytosolic niche in macrophages.
Topics: Humans; Interleukin-1; Cytokines; Rickettsia; Macrophages; Autophagy
PubMed: 37819111
DOI: 10.1128/spectrum.02791-23 -
Veterinary Parasitology Jun 2024In Europe, tick-borne diseases (TBDs) cause significant morbidity and mortality, affecting both human and animal health. Ticks can transmit a wide variety of pathogens... (Review)
Review
In Europe, tick-borne diseases (TBDs) cause significant morbidity and mortality, affecting both human and animal health. Ticks can transmit a wide variety of pathogens (bacteria, viruses, and parasites) and feed on many vertebrate hosts. The incidence and public health burden of TBDs are tending to intensify in Europe due to various factors, mainly anthropogenic and often combined. Early detection of tick-borne pathogens (TBPs), preventive measures and treatment are of great importance to control TBDs and their expansion. However, there are various limitations in terms of the sensitivity and/or specificity of detection and prevention methods, and even in terms of feasibility. Aptamers are single-stranded DNA or RNA that could address these issues as they are able to bind with high affinity and specificity to a wide range of targets (e.g., proteins, small compounds, and cells) due to their unique three-dimensional structure. To date, aptamers have been selected against TBPs such as tick-borne encephalitis virus, Francisella tularensis, and Rickettsia typhi. These studies have demonstrated the benefits of aptamer-based assays for pathogen detection and medical diagnosis. In this review, we address the applications of aptamers to TBDs and discuss their potential for improving prevention measures (use of chemical acaricides, vaccination), diagnosis and therapeutic strategies to control TBDs.
Topics: Tick-Borne Diseases; Animals; Aptamers, Nucleotide; Humans; Europe; Ticks; Tick Control
PubMed: 38714064
DOI: 10.1016/j.vetpar.2024.110190 -
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 Feb 2024
Topics: Mice; Animals; Japan; Typhus, Endemic Flea-Borne; Seroepidemiologic Studies
PubMed: 38270544
DOI: 10.3201/eid3002.230827