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Virology Journal Nov 2022Tick-borne diseases (TBDs) are bacterial, viral, and parasitic diseases transmitted by ticks. Viral TBDs have increased in prevalence over the last decade with many new... (Review)
Review
Tick-borne diseases (TBDs) are bacterial, viral, and parasitic diseases transmitted by ticks. Viral TBDs have increased in prevalence over the last decade with many new pathogenic viruses being discovered. Doxycycline is often empirically prescribed by clinicians to treat symptomatic patients following tick bites due to suspicions of bacterial TBDs such as Rocky Mountain spotted fever, anaplasmosis, and ehrlichiosis. However, viral TBDs are included in the differential diagnosis if patients do not clinically improve following antibiotic therapy. Several viral TBDs present with dermatological manifestations. Recognizing the differences in clinical presentations of TBDs, particularly of newly emerging viral TBDs in the United States, can help physicians identify the viral TBD, and possibly rule out viral illnesses with different clinical presentations. Therefore, this review discusses clinical manifestations, with an emphasis on dermatologic manifestations of Heartland Virus, Bourbon Virus, Powassan Virus, Deer Tick Virus and Colorado Tick Fever Virus. KEY POINTS: Viral tick-borne diseases have increased in prevalence over the last decade and often have similar clinical manifestations to other tick-borne diseases, including bacterial infections. Here, we review the dermatologic manifestations of Heartland Virus (HRTV), Bourbon Virus (BRBV), Powassan Virus (POWV), Deer Tick Virus (DTV) and Colorado Tick Fever Virus (CTFV) that are important for clinicians.
Topics: Animals; Humans; United States; Tick-Borne Diseases; Phlebovirus; Doxycycline; Encephalitis Viruses, Tick-Borne; Bacteriophages; Ticks
PubMed: 36443864
DOI: 10.1186/s12985-022-01924-w -
EMBO Molecular Medicine Mar 2024Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening disease caused by a novel bunyavirus (SFTSV), mainly transmitted by ticks. With no effective...
Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening disease caused by a novel bunyavirus (SFTSV), mainly transmitted by ticks. With no effective therapies or vaccines available, understanding the disease's mechanisms is crucial. Recent studies found increased expression of programmed cell death-1 (PD-1) on dysfunctional T cells in SFTS patients. However, the role of the PD-1/programmed cell death-ligand 1 (PD-L1) pathway in SFTS progression remains unclear. We investigated PD-1 blockade as a potential therapeutic strategy against SFTSV replication. Our study analyzed clinical samples and performed in vitro experiments, revealing elevated PD-1/PD-L1 expression in various immune cells following SFTSV infection. An anti-PD-1 nanobody, NbP45, effectively inhibited SFTSV infection in peripheral blood mononuclear cells (PBMCs), potentially achieved through the mitigation of apoptosis and the augmentation of T lymphocyte proliferation. Intriguingly, subcutaneous administration of NbP45 showed superior efficacy compared to a licensed anti-PD-1 antibody in an SFTSV-infected humanized mouse model. These findings highlight the involvement of the PD-1/PD-L1 pathway during acute SFTSV infection and suggest its potential as a host target for immunotherapy interventions against SFTSV infection.
Topics: Animals; Humans; Mice; Bunyaviridae Infections; Phlebovirus; B7-H1 Antigen; Severe Fever with Thrombocytopenia Syndrome; Leukocytes, Mononuclear; Programmed Cell Death 1 Receptor
PubMed: 38366162
DOI: 10.1038/s44321-024-00026-0 -
The American Journal of Tropical... Dec 2023Severe fever with thrombocytopenia syndrome virus (SFTSV), Heartland virus (HRTV) and Guertu virus (GTV) belong to the severe fever with thrombocytopenia...
Severe fever with thrombocytopenia syndrome virus (SFTSV), Heartland virus (HRTV) and Guertu virus (GTV) belong to the severe fever with thrombocytopenia syndrome/Heartland group of genus Bandavirus in the family Phenuiviridae of order Bunyavirales. Severe fever with thrombocytopenia syndrome virus and HRTV, identified from ticks from Asia and America, respectively, are important pathogens causing severe febrile diseases in humans. Guertu virus, closely related to these two viruses, is a potential pathogen, but no confirmed infection has been identified. So far, human-derived neutralizing monoclonal antibodies (mAbs) against SFTSV have been identified as having a great potential to be developed as antivirals; however, there is still a lack of neutralizing mAbs to GTV and HRTV. In this study, five neutralizing the mAbs against GTV and HRTV were obtained by hybridoma screening technology, four of which (14B4, 14D8, and 20D4 derived from GTV, and 27C8 derived from HRTV) showed cross reactivity and neutralization to all three viruses, and one derived from HRTV (10D6) neutralized HRTV specifically. The possible mechanisms of mAbs cross neutralization among the three viruses are discussed by analyzing their glycoprotein (GP) sequences and structures. Generating these neutralizing mAbs provides important antiviral candidates against GTV, HRTV, and SFTSV despite their differential activities, and their protective effect could be further evaluated in virus-infected mice. Their differential neutralizing efficiency and specificity further suggested that the three viruses share common mechanisms on the basis of GP functioning, and that HRTV poses a unique mechanism that differs from the other viruses. These findings shed light on developing broad-spectrum antiviral strategies against bandaviruses and promoting an understanding of the bandavirus infection process.
Topics: Animals; Humans; Mice; Antibodies, Neutralizing; Phlebovirus; Antibodies, Monoclonal; Severe Fever with Thrombocytopenia Syndrome; Glycoproteins; RNA Viruses; Antiviral Agents
PubMed: 37931293
DOI: 10.4269/ajtmh.23-0073 -
PLoS Neglected Tropical Diseases Aug 2022SFTSV, a tick-borne bunyavirus causing a severe hemorrhagic fever termed as severe fever with thrombocytopenia syndrome (SFTS). To evaluate the potential role of rodents...
SFTSV, a tick-borne bunyavirus causing a severe hemorrhagic fever termed as severe fever with thrombocytopenia syndrome (SFTS). To evaluate the potential role of rodents and its ectoparasitic chiggers in the transmission of SFTSV, we collected wild rodents and chiggers on their bodies from a rural area in Qingdao City, Shandong Province, China in September 2020. PCR amplification of the M and L segments of SFTSV showed that 32.3% (10/31) of rodents and 0.2% (1/564) of chiggers (Leptotrombidium deliense) from the rodents were positive to SFTSV. Our results suggested that rodents and chiggers may play an important role in the transmission of SFTSV, although the efficiency of chiggers to transmit SFTSV needs to be further investigated experimentally.
Topics: Animals; Bunyaviridae Infections; China; Fever; Mite Infestations; Phlebovirus; Rodentia; Ticks; Trombiculidae
PubMed: 36037170
DOI: 10.1371/journal.pntd.0010698 -
International Journal of Infectious... Dec 2022Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with a high case fatality rate. Key gaps remained as to the assessment of...
OBJECTIVES
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with a high case fatality rate. Key gaps remained as to the assessment of the clinical picture in fatal cases.
METHODS
A retrospective study was performed on 496 patients with fatal SFTS. The dynamic pattern of clinical manifestations and laboratory indicators were delineated.
RESULTS
The mean age of the fatal cases was 69.0 years (standard deviation: 9.3), and 52.8% were male. The median clinical course from disease onset to death was 11 (interquartile range: 10-13) days. A total of 11 laboratory indicators (neutrophil %, platelet, aspartate aminotransferase, aspartate aminotransferase/alanine transaminase, lactate dehydrogenase, creatine kinase, cystatin C, D-dimer, activated partial thromboplastin time, thrombin time, glucose) persistently deviated from normality across hospitalization. The critical time points when the rapid worsening of the indicators was at 6-9 days after disease onset. Alanine transaminase, AST, lactate dehydrogenase, total bile acid, gamma-glutamyl transpeptidase, and glucose were all elevated to a more pronounced level in fatal cases of those aged ≤70 years.
CONCLUSION
The fatal outcome was developed in rather a short course after the disease onset of SFTS. High vigilance should be put on the key time points when the severe worsening and severe complications occur.
Topics: Humans; Male; Aged; Female; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Retrospective Studies; Alanine Transaminase; China; Glucose; Lactate Dehydrogenases
PubMed: 36241165
DOI: 10.1016/j.ijid.2022.10.008 -
Frontiers in Public Health 2021Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease, and the number of cases has increased in recent years in Zhejiang Province, China....
INTRODUCTION
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease, and the number of cases has increased in recent years in Zhejiang Province, China. However, whether the seasonal distribution, geographic distribution, and demographic characteristics of SFTS have changed with the increase of incidence was unclear.
MATERIALS AND METHODS
Data on SFTS cases in Zhejiang Province and tick density in Daishan County from 2011 to 2019 were collected. The changing epidemiological characteristics of SFTS including seasonal distribution, geographical distribution, and demographic features were analyzed using descriptive statistical methods, Global Moran's I, local Getis-Ord * statistic, and spatial scan statistic.
RESULTS
A total of 463 SFTS cases including 53 (11.45%) deaths were reported from 2011 to 2019 in Zhejiang Province, and the annual number of cases showed increasing tendency. SFTS cases were reported in almost half of the counties (40/89) of Zhejiang Province. Elderly farmers accounted for most cases and the proportion of farmers has increased. Most cases (81.21%) occurred during April and August. The interval from illness onset to confirmation was significantly shortened ( = 5.194, < 0.001). The majority of cases were reported in Zhoushan City from 2011 to 2016, but most cases were reported in Taizhou City since 2017.
DISCUSSION
We observed dynamic changes in the seasonal distribution, geographical distribution, and demographic features of SFTS, and comprehensive intervention measures, such as clearance of breeding sites, killing of tick adults, and health education should be strengthened in farmers of the key areas according to the changed epidemiological characteristics.
Topics: Adult; Aged; Bunyaviridae Infections; China; Humans; Incidence; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome
PubMed: 35223761
DOI: 10.3389/fpubh.2021.803660 -
Journal of Medical Entomology Nov 2023Heartland (HRTV) and Bourbon (BRBV) viruses are newly identified tick-borne viruses, isolated from serious clinical cases in 2009 and 2014, respectively. Both viruses... (Review)
Review
Heartland (HRTV) and Bourbon (BRBV) viruses are newly identified tick-borne viruses, isolated from serious clinical cases in 2009 and 2014, respectively. Both viruses originated in the lower Midwest United States near the border of Missouri and Kansas, cause similar disease manifestations, and are presumably vectored by the same tick species, Amblyomma americanum Linnaeus (Ixodida: Ixodidae). In this article, we provide a current review of HRTV and BRBV, including the virology, epidemiology, and ecology of the viruses with an emphasis on the tick vector. We touch on current challenges of vector control and surveillance, and we discuss future directions in the study of these emergent pathogens.
Topics: United States; Animals; Ixodidae; Ticks; Amblyomma; Phlebovirus; Missouri
PubMed: 37862097
DOI: 10.1093/jme/tjad060 -
Journal of Clinical Virology : the... Jan 2021Heartland virus (HRTV), a recently reclassified member of the genus Bandavirus, family Phenuiviridae, was first isolated in 2009 from a Missouri farmer exhibiting...
BACKGROUND
Heartland virus (HRTV), a recently reclassified member of the genus Bandavirus, family Phenuiviridae, was first isolated in 2009 from a Missouri farmer exhibiting leukopenia and thrombocytopenia with suspected ehrlichiosis. Since then, more HRTV cases have been diagnosed, and firstline laboratory diagnostic assays are needed to identify future infections Objectives. We sought to develop rapid and reliable IgM and IgG microsphere immunoassays (MIAs) to test sera of patients suspected of having HRTV infection, and to distinguish between recent and past infections.
STUDY DESIGN
Heartland virus antigen was captured by an anti-HRTV monoclonal antibody covalently bound to microspheres. Antibodies in human sera from confirmed HRTV-positive and negative cases were reacted with the microsphere complexes and detected using a BioPlex® 200 instrument. Assay cutoffs were determined by receiver operator characteristic analysis of the normalized test output values, equivocal zones for each assay were defined, and sensitivities, specificities, accuracies, and imprecision values were calculated.
RESULTS
Sensitivities, specificities and accuracies of the IgM and IgG MIAs were all >95 %. Both tests were precise within and between assay plates, and cross-reactivity with other arboviruses was not observed.
CONCLUSIONS
HRTV IgM and IgG MIAs are accurate and rapid first-line methods to serologically identify recent and past HRTV infections.
Topics: Antibodies, Viral; Antigens, Viral; Cross Reactions; Humans; Immunoassay; Immunoglobulin M; Microspheres; Phlebovirus
PubMed: 33248359
DOI: 10.1016/j.jcv.2020.104693 -
Journal of Medical Virology Feb 2023Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening infectious disease caused by the SFTS virus (SFTSV). This study aimed to evaluate the predictive...
Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening infectious disease caused by the SFTS virus (SFTSV). This study aimed to evaluate the predictive power of C-reactive protein to lymphocyte ratio (CLR) and establish an early-warning model for SFTS mortality. We retrospectively analyzed hospitalized SFTS patients in six clinical centers from May 2011 to 2022. The efficacy of CLR prediction was evaluated by the receiver operating characteristic (ROC) analysis. A nomogram was established and validated. Eight hundred and eighty-two SFTS patients (median age 64 years, 48.5% male) were enrolled in this study, with a mortality rate of 17.8%. The area under the ROC curve (AUC) of CLR was 0.878 (95% confidence interval [CI]: 0.850-0.903, p < 0.001), which demonstrates high predictive strength. The least absolute shrinkage and selection operator regression selected seven potential predictors. Multivariate logistic regression analysis determined three independent risk factors, including CLR, to construct the nomogram. The performance of the nomogram displayed excellent discrimination and calibration, with significant net benefits in clinical uses. CLR is a brand-new predictor for SFTS mortality. The nomogram based on CLR can serve as a convenient tool for physicians to identify critical SFTS cases in clinical practice.
Topics: Humans; Male; Middle Aged; Female; Severe Fever with Thrombocytopenia Syndrome; C-Reactive Protein; Bunyaviridae Infections; Retrospective Studies; Phlebovirus; Risk Factors; China
PubMed: 36734063
DOI: 10.1002/jmv.28546 -
Journal of Infection in Developing... May 2022Rift Valley fever (RVF) is a zoonotic disease caused by RVF virus (RVFV) and transmitted primarily by mosquitoes and contact with fluids and tissues of infected animals....
INTRODUCTION
Rift Valley fever (RVF) is a zoonotic disease caused by RVF virus (RVFV) and transmitted primarily by mosquitoes and contact with fluids and tissues of infected animals. First described in Kenya, it has spread to many African countries and beyond. In humans, it is sometimes misdiagnosed because the symptoms resemble those of influenza and/or malaria. Butchers, abattoir workers, and livestock keepers have the highest risk of infection.
METHODOLOGY
In this study, serum samples collected between February and September 2019 from 196 individuals comprising of butchers (n = 121), abattoir/slaughterhouse workers (n = 55), and livestock keepers (n = 20) in Benue, Sokoto, and Borno States of northern Nigeria were screened using a commercial ELISA that detected anti-RVFV IgM and IgG alike (i.e., without discrimination). Data from administered questionnaires and the ELISA results were statistically analyzed.
RESULTS
Thirty-nine (19.9%) of the 196 samples were positive for RVFV antibodies. The distribution by states showed that 17.4% (8/46), 21.7% (15/69), and 19.8% (16/81) of samples from Benue, Sokoto, and Borno States were seropositive, respectively. Additionally, 21.5% (26/121) butchers, 16.4% (9/55) abattoir workers, and 20% (4/20) livestock keepers were seropositive.
CONCLUSIONS
These findings provide serological evidence for exposure of occupationally at-risk individuals in northern Nigeria to RVFV. The higher seropositivity obtained in Sokoto and Borno states could be due to contact of these individuals with infected animal blood/tissues, aborted fetuses, and unhindered transboundary movement of animals and animal products into these states which share international borders with Niger, Chad, and Cameroon where evidences of RVFV infections were recently reported.
Topics: Animals; Humans; Kenya; Livestock; Nigeria; Rift Valley fever virus; Zoonoses
PubMed: 35656961
DOI: 10.3855/jidc.15367