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BioRxiv : the Preprint Server For... May 2024Some arthropod-borne obligate intracellular rickettsiae are among the most virulent human pathogens. Upon entry, species modulate immune (e.g., macrophages; MΦ) and...
UNLABELLED
Some arthropod-borne obligate intracellular rickettsiae are among the most virulent human pathogens. Upon entry, species modulate immune (e.g., macrophages; MΦ) and non-immune cell (e.g., endothelial cells) responses to create a habitable environment for host colonization. In particular, MΦ play a crucial role in either terminating an infection at an early stage or succumbing to bacterial replication and colonization. However, our understanding on how species modulate crucial cellular processes within MΦ, including phagocytosis, and host cell defenses, to establish an intracytosolic replication niche, remain poorly defined. In this study, we describe a previously unappreciated mechanism, in which pathogenic rickettsiae infection is mediated by the phosphatidylserine (PS)-binding receptor, CD300f. We found that CD300f mice but not wild-type (WT) C57BL/6J mice were protected against - or [ ]-induced fatal rickettsiosis. Adoptative transfer studies further revealed that CD300f-expressing bone marrow-derived macrophages (BMDMΦ) are important mediators to control rickettsiosis in WT mice. Mechanistical analysis, using WT or CD300f BMDMΦ, showed that CD300f facilitates the engulfment of both pathogenic and species, likely via a PS-mediated mechanism. Furthermore, CD300f was involved in the intracytosolic replication of both pathogenic rickettsiae by differentially modulating the anti-inflammatory Interleukin (IL)-10 and anti-rickettsial IL-1α and IL-1β cytokine responses. Collectively, our findings describe a previously unappreciated role for the efferocytic receptor, CD300f, to facilitate engulfment and the intracellular survival of pathogenic rickettsiae within the host.
SIGNIFICANCE STATEMENT
Vector-borne diseases, which are transmitted by hematophagous arthropods, like ticks and fleas, present a perilous threat to public health. In fact, tick- and flea-borne rickettsial diseases are on the rise globally and our current inadequate understanding on how interacts with their mammalian host has significantly impaired the development of effective interventions against pathogenic rickettsial infections. Here, we identified the phosphatidylserine (PS)-receptor, CD300f, as an important mediator of pathogenic rickettsiae infection and . Specifically, we showed that CD300f-expressing macrophages facilitate rickettsial infection by differentially modulating anti-inflammatory Interleukin (IL)-10 and anti-rickettsial IL-1α and IL-1β cytokine responses. In sum, our data described CD300f as an important regulator of rickettsial infection and may present a target for therapeutic intervention.
PubMed: 38766217
DOI: 10.1101/2024.05.10.593542 -
Therapeutic Advances in Infectious... 2024Metagenomic next-generation sequencing (mNGS) is a novel diagnostic tool increasingly used in the field of infectious diseases. Little guidance is available regarding...
BACKGROUND
Metagenomic next-generation sequencing (mNGS) is a novel diagnostic tool increasingly used in the field of infectious diseases. Little guidance is available regarding its appropriate use in different patient populations and clinical syndromes. We aimed to review the clinical utility of mNGS in patients with a specific clinical syndrome and identify factors that may increase its utility.
METHODS
We retrospectively reviewed charts of 72 non-immunocompromised adults hospitalized with the clinical syndrome of 'fever of undetermined origin' and underwent mNGS testing. Standardized criteria from a previously published study were used to determine the clinical impact of mNGS testing. We applied logistic regression to identify factors associated with a positive clinical impact.
RESULTS
Of the 72 patients identified, 62.5% were males with a median age of 56. All patients had a fever at the time of evaluation. At least one organism was identified in 65.3% of cases; most commonly were Epstein-Barr virus (13.9%), cytomegalovirus (12.5%), and (11.1%). Of those determined to have an infectious etiology of their febrile syndrome, 89.5% ( = 34/38) had a positive mNGS. Consistency between the organism(s) on mNGS and the clinically determined infectious etiology was 82.4%. mNGS had a positive clinical impact in 40.3% of cases, a negative impact in 2.8%, and no impact in 56.9% of cases. Besides age, we did not identify other factors associated with a higher likelihood of positive clinical impact.
CONCLUSION
In our review, mNGS had a positive clinical impact in a large proportion of adults with fever of undetermined origin, with minimal negative impact. However, mNGS results should be interpreted carefully given the high rate of detection of pathogens of unclear clinical significance. Randomized clinical trials are needed to assess the clinical utility of this novel diagnostic tool.
PubMed: 38645300
DOI: 10.1177/20499361241244969 -
PLoS Neglected Tropical Diseases Apr 2024Fever is the most frequent symptom in patients seeking care in South and Southeast Asia. The introduction of rapid diagnostic tests (RDTs) for malaria continues to drive...
BACKGROUND
Fever is the most frequent symptom in patients seeking care in South and Southeast Asia. The introduction of rapid diagnostic tests (RDTs) for malaria continues to drive patient management and care. Malaria-negative cases are commonly treated with antibiotics without confirmation of bacteraemia. Conventional laboratory tests for differential diagnosis require skilled staff and appropriate access to healthcare facilities. In addition, introducing single-disease RDTs instead of conventional laboratory tests remains costly. To overcome some of the delivery challenges of multiple separate tests, a multiplexed RDT with the capacity to diagnose a diverse range of tropical fevers would be a cost-effective solution. In this study, a multiplex lateral flow immunoassay (DPP Fever Panel II Assay) that can detect serum immunoglobulin M (IgM) and specific microbial antigens of common fever agents in Asia (Orientia tsutsugamushi, Rickettsia typhi, Leptospira spp., Burkholderia pseudomallei, Dengue virus, Chikungunya virus, and Zika virus), was evaluated.
METHODOLOGY/PRINCIPAL FINDINGS
Whole blood (WB) and serum samples from 300 patients with undefined febrile illness (UFI) recruited in Vientiane, Laos PDR were tested using the DPP Fever Panel II, which consists of an Antibody panel and Antigen panel. To compare reader performance, results were recorded using two DPP readers, DPP Micro Reader (Micro Reader 1) and DPP Micro Reader Next Generation (Micro Reader 2). WB and serum samples were run on the same fever panel and read on both micro readers in order to compare results. ROC analysis and equal variance analysis were performed to inform the diagnostic validity of the test compared against the respective reference standards of each fever agent (S1 Table). Overall better AUC values were observed in whole blood results. No significant difference in AUC performance was observed when comparing whole blood and serum sample testing, except for when testing for R. typhi IgM (p = 0.04), Leptospira IgM (p = 0.02), and Dengue IgG (p = 0.03). Linear regression depicted R2 values had ~70% agreement across WB and serum samples, except when testing for leptospirosis and Zika, where the R2 values were 0.37 and 0.47, respectively. No significant difference was observed between the performance of Micro Reader 1 and Micro Reader 2, except when testing for the following pathogens: Zika IgM, Zika IgG, and B pseudomallei CPS Ag.
CONCLUSIONS/SIGNIFICANCE
These results demonstrate that the diagnostic accuracy of the DPP Fever Panel II is comparable to that of commonly used RDTs. The optimal cut-off would depend on the use of the test and the desired sensitivity and specificity. Further studies are required to authenticate the use of these cut-offs in other endemic regions. This multiplex RDT offers diagnostic benefits in areas with limited access to healthcare and has the potential to improve field testing capacities. This could improve tropical fever management and reduce the public health burden in endemic low-resource areas.
Topics: Humans; Sensitivity and Specificity; Immunoglobulin M; Female; Male; Laos; Adult; Fever; Antibodies, Bacterial; Diagnostic Tests, Routine; Middle Aged; Adolescent; Young Adult; Antibodies, Viral; Antigens, Bacterial; Immunoassay
PubMed: 38598549
DOI: 10.1371/journal.pntd.0012077 -
Caspian Journal of Internal Medicine 2024Rickettsioses are infectious diseases which are caused by intracellular bacteria which belong to the family Rickettsiaceae. This zoonosis endemically prefers tropical...
BACKGROUND
Rickettsioses are infectious diseases which are caused by intracellular bacteria which belong to the family Rickettsiaceae. This zoonosis endemically prefers tropical and subtropical regions of which the Mediterranean is included. Murine typhus is a type of rickettsial disease that commonly presents with undulating fever, headache rash, chills, malaise, and myalgias. It can lead to complications such as multi-organ failure and has a lethality rate of <5% in such cases.
CASE PRESENTATION
A 70-year-old male was hospitalized at the Unit of Infectious Diseases, Mother Teresa Hospital, Tirana, Albania in a comatose condition. He had a seven-day history of fever up to 39-40°C, headache, fatigue, anorexia, vomiting, cough, and myalgia. He was a farmer and had contact with animals. Upon admission, he had scleral hemorrhages, hepatosplenomegaly, jaundice, maculopapular rash over the trunk, abdomen, and palms of his hands as well as severe acidosis, depressed bicarbonate levels, alteration in liver, kidney, and pancreas function tests. He was urgently transferred to the Intensive care unit of the Infectious Diseases Department. He was hemodynamically unstable and was put immediately on vasoactive agents and mechanical ventilation. ELISA IgM resulted positive. Supportive treatment along with antibiotics Levofloxacin and Ceftriaxone was initiated. However, the patient died on the 4 day of hospitalization and the 11 of the disease onset.
CONCLUSION
Murine typhus should be included in the investigation of possible causes when dealing with patients presenting with fever and maculopapular rash complicated by multi-organ failure and coming from a typhus-endemic area, especially in the summer season.
PubMed: 38463928
DOI: 10.22088/cjim.15.1.23 -
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 -
Vector Borne and Zoonotic Diseases... Apr 2024Flea-borne rickettsioses, collectively referred to as a term for etiological agents , , and RFLOs (-like organisms), has become a public health concern around the...
Flea-borne rickettsioses, collectively referred to as a term for etiological agents , , and RFLOs (-like organisms), has become a public health concern around the world, specifically in the United States. Due to a shared arthropod vector (the cat flea) and clinical signs, discriminating between species has proven difficult. While the effects of microbial coinfections in the vector can result in antagonistic or synergistic interrelationships, subsequently altering potential human exposure and disease, the impact of bacterial interactions within flea populations remains poorly defined. In this study, and systems were utilized to assess rickettsial interactions in arthropods. Coinfection of both and within a tick-derived cell line indicated that the two species could infect the same cell, but distinct growth kinetics led to reduced growth over time, regardless of infection order. Sequential flea coinfections revealed the vector could acquire both spp. and sustain coinfection for up to 2 weeks, but rickettsial loads in coinfected fleas and feces were altered during coinfection. Altered rickettsial loads during coinfection suggest and interactions may enhance the transmission potential of either agent. Thus, this study provides a functional foundation to disentangle transmission events propelled by complex interspecies relationships during vector coinfections.
Topics: Animals; Humans; Cats; Rickettsia typhi; Rickettsia felis; Ctenocephalides; Coinfection; Rickettsia; Siphonaptera; Flea Infestations; Felis; Cat Diseases
PubMed: 38422214
DOI: 10.1089/vbz.2023.0122 -
Case Reports in Infectious Diseases 2024Flea-borne typhus (FBT), due to and , is an infection causing fever, headache, rash, hepatitis, thrombocytopenia, and diverse organ manifestations. Cough occurs in...
Flea-borne typhus (FBT), due to and , is an infection causing fever, headache, rash, hepatitis, thrombocytopenia, and diverse organ manifestations. Cough occurs in about 30% of patients with FBT, and chest X-ray abnormalities are seen in 17%. Severe pulmonary manifestations have also been reported in FBT, including adult respiratory distress syndrome and pulmonary embolism. Because of these pulmonary manifestations, FBT can mimic Coronavirus Illness 2019 (COVID-19), a febrile illness with prominent respiratory involvement. Flea-borne typhus and COVID-19 may also have similar laboratory abnormalities, including elevated ferritin, C-reactive protein, and D-dimer. However, elevated transaminase levels, rash, and thrombocytopenia are more common in FBT. Herein, we present four cases of patients with FBT who were initially suspected to have COVID-19. These cases illustrate the problem of availability bias, in which the clinician thinks a particular common condition (COVID-19 in this case) is more prevalent than it actually is.
PubMed: 38384261
DOI: 10.1155/2024/9914306 -
Travel Medicine and Infectious Disease 2024Rickettsia is a zoonotic bacterial pathogen transmitted by vectors and has extensive reservoirs in animal and human populations. Rickettsiosis is a public health problem... (Review)
Review
SUBJECT
Rickettsia is a zoonotic bacterial pathogen transmitted by vectors and has extensive reservoirs in animal and human populations. Rickettsiosis is a public health problem all over the world. However, comprehensive information on the geographical distribution of different Rickettsia species, infection status of reservoirs, vectors, and human cases is lacking in most parts of the world. Therefore, this study aimed to investigate the geographical distribution of different Rickettsia species and their vectors in countries of the WHO-EMRO region.
METHODS
In this review study, a search was conducted for reports and published studies on Rickettsia species from WHO-EMRO region countries in various databases from 1995 to 2022. Finally, the reported status of human cases, reservoirs, and vectors associated with each species in different countries was documented.
RESULTS
Reports of infections related to the detection of Rickettsia species were only available for 15 out of 22 WHO-EMRO member countries. A total of twenty-four Rickettsia species, including R. sibrica, R. lusitaniae, R. africae, R. prowazekii, R. felis, R. typhi, R. rickettsii, R. aeschlimannii, R. conorii, R. massiliae, R. helvetica, R. monacensis, R. rhipicephali, R. bellii, R. asembonensis, R. hoogstraalii, R. andeanae, R. raoultii, R. asiatica, R. slovaca, R. australis, R. barbariae, Candidatus R. amblyommii, and Candidatus R. goldwasserii, were reported from WHO-EMRO member countries. Furthermore, human cases infected with six different Rickettsia species, including R. sibrica, R. prowazekii, R. felis, R. typhi, R. rickettsii, R. aeschlimannii, R. conorii, R. massiliae, and R. helvetica, were reported from these countries.
CONCLUSION
The vast diversity of Rickettsia vectors has contributed to the ongoing discovery of new Rickettsia species. Therefore, further research on the reservoir hosts of Rickettsia infections in the understudied WHO-EMRO region is crucial. This research sheds light on Rickettsia disease's epidemiology and transmission dynamics in this region.
Topics: Animals; Humans; Rickettsia; Rickettsia Infections; World Health Organization
PubMed: 38360158
DOI: 10.1016/j.tmaid.2024.102695 -
Emerging Infectious Diseases Feb 2024
Topics: Mice; Animals; Japan; Typhus, Endemic Flea-Borne; Seroepidemiologic Studies
PubMed: 38270544
DOI: 10.3201/eid3002.230827 -
Emerging Infectious Diseases Feb 2024
Topics: Mice; Animals; Japan; Typhus, Endemic Flea-Borne; Seroepidemiologic Studies
PubMed: 38270143
DOI: 10.3201/eid3002.231465