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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 -
Scientific Reports Feb 2024Rift Valley Fever (RVF) is a zoonosis transmitted by Aedes and Culex mosquitoes, and is considered a priority pathogen by the WHO. RVF epidemics mostly occur in Africa...
Rift Valley Fever (RVF) is a zoonosis transmitted by Aedes and Culex mosquitoes, and is considered a priority pathogen by the WHO. RVF epidemics mostly occur in Africa and can decimate livestock herds, causing significant economic losses and posing health risks for humans. RVF transmission is associated with the occurrence of El Niño events that cause floods in eastern Africa and favour the emergence of mosquitoes in wetlands. Different risk models have been developed to forecast RVF transmission risk but very few studies have validated models at pan-African scale. This study aims to validate the skill of the Liverpool Rift Valley Fever model (LRVF) in reproducing RVF epidemics over Africa and to explore the relationship between simulated climatic suitability for RVF transmission and large-scale climate modes of variability such as the El Niño Southern Oscillation (ENSO) and the Dipole Mode Index (DMI). Our results show that the LRVF model correctly simulates RVF transmission hotspots and reproduces large epidemics that affected African countries. LRVF was able to correctly reproduce major RVF epidemics in Somalia, Kenya, Zambia and to a lesser extent for Mauritania and Senegal. The positive phases of ENSO and DMI are associated with an increased risk of RVF over the Horn of Africa, with important time lags. Following research activities should focus on the development of predictive modelling systems at different time scales.
Topics: Animals; Humans; Rift Valley Fever; Disease Outbreaks; Zoonoses; Kenya; Aedes; Rift Valley fever virus
PubMed: 38365824
DOI: 10.1038/s41598-024-53774-x -
Journal of Comparative Pathology Feb 2024Phlebotomine sand flies (Diptera: Phlebotominae) are vectors of human and animal pathogens, including Leishmania species protozoan parasites and viruses of the genus... (Review)
Review
Phlebotomine sand flies (Diptera: Phlebotominae) are vectors of human and animal pathogens, including Leishmania species protozoan parasites and viruses of the genus Phlebovirus. In Europe, visceral zoonotic leishmaniasis caused by Leishmania infantum, a deadly disease when left untreated, is endemic in southern countries, and dogs are the main reservoir hosts for human infection. Most phleboviruses cause asymptomatic infections or flu-like syndromes in humans, but Toscana phlebovirus can cause meningitis and encephalitis. These diseases are likely to re-emerge, posing a growing threat to public and animal health. Potential triggers include the movement of humans and dogs, increasing numbers of immunosuppressive conditions, climate change and other human-mediated environmental changes. An overview of the main epidemiological characteristics of the pathogens transmitted by sand flies in Europe and the potential triggers involved in their emergence and re-emergence are reviewed here. There is a need to implement mandatory notification of human and canine leishmaniases and human phleboviruses and coordinated epidemiological surveillance programmes at a European level, and to raise awareness among healthcare professionals and citizens about sand fly-borne diseases, following a One Health approach.
Topics: Animals; Dogs; Humans; Psychodidae; Europe; Leishmaniasis, Visceral; Encephalitis; Leishmania infantum; Dog Diseases
PubMed: 38320331
DOI: 10.1016/j.jcpa.2024.01.001 -
Archives of Virology Feb 2024Severe fever with thrombocytopenia syndrome (SFTS) is a hemorrhagic fever caused by SFTS virus (SFTSV), which is primarily found in East Asian countries. Despite its...
Severe fever with thrombocytopenia syndrome (SFTS) is a hemorrhagic fever caused by SFTS virus (SFTSV), which is primarily found in East Asian countries. Despite its high mortality rate and increasing incidence, no vaccines or therapeutics have yet been approved for use against SFTS. Antibody drugs have shown promise in treating lethal infectious diseases that currently have no established treatments. In the case of SFTS, however, only a limited amount of research has been done on SFTSV-neutralizing antibodies targeting the transmembrane proteins Gn and Gc, which play critical roles in viral infection. This study focuses on the production and characterization of antibodies targeting the SFTSV Gc protein. Monoclonal antibodies against Gc were generated through immunization of mice, and their antiviral activity was evaluated. Three out of four anti-Gc antibody clones from this study demonstrated dose-dependent SFTSV neutralization activity, two of which exhibited a synergistic effect on the neutralization activity of the anti-Gn antibody clone Mab4-5. Further studies are necessary to identify key sites on the SFTSV glycoprotein and to develop novel agents as well as antibodies with diverse mechanisms of action against SFTSV.
Topics: Animals; Mice; Severe Fever with Thrombocytopenia Syndrome; Glycoproteins; Phlebovirus; Hemorrhagic Fevers, Viral; Bunyaviridae Infections
PubMed: 38308735
DOI: 10.1007/s00705-024-05968-x -
Journal of Clinical Microbiology Mar 2024Rift Valley Fever phlebovirus (RVFV) is a mosquito-borne zoonotic pathogen that causes major agricultural and public health problems in Africa and the Arabian Peninsula....
Rift Valley Fever virus M and L genome segment detection: a comparison of field-deployable reverse transcription insulated isothermal PCR (RT-iiPCR) and laboratory-based multiplex reverse transcription real-time PCR.
UNLABELLED
Rift Valley Fever phlebovirus (RVFV) is a mosquito-borne zoonotic pathogen that causes major agricultural and public health problems in Africa and the Arabian Peninsula. It is considered a potential agro-bioterrorism agent for which limited countermeasures are available. To address diagnostic needs, here we describe a rapid and sensitive molecular method immediately employable at sites of suspected outbreaks in animals that commonly precede outbreaks in humans. The strategy involves the concurrent detection of two of the three RVFV genome segments (large and medium) using reverse transcription insulated isothermal PCR (RT-iiPCR) performed on a portable, touch screen nucleic acid analyzer, POCKIT. The analytical sensitivity for both the RT-iiPCR and a laboratory-based L and M multiplex reverse transcription real-time PCR assay was estimated at approximately 0.1-3 copies/reaction using synthetic RNA or viral RNA. The diagnostic sensitivity and specificity of detection of RVFV on the POCKIT, determined using sera from sheep and cattle ( = 181) experimentally infected with two strains of RVFV (SA01 and Ken06), were 93.8% and 100% (kappa = 0.93), respectively. Testing of ruminant field sera ( = 193) in two locations in Africa demonstrated 100% diagnostic sensitivity and specificity. We conclude that the POCKIT dual-gene RVFV detection strategy can provide reliable, sensitive, and specific point-of-need viral RNA detection. Moreover, the field detection of RVFV in vectors or susceptible animal species can aid in the surveillance and epidemiological studies to better understand and control RVFV outbreaks.
IMPORTANCE
The content of this manuscript is of interest to the diverse readership of the , including research scientists, diagnosticians, healthcare professionals, and policymakers. Rift Valley Fever virus (RVFV) is a zoonotic mosquito-borne pathogen that causes major agricultural and public health problems. Current and most sensitive diagnostic approaches that are molecular-based are performed in highly specialized molecular diagnostic laboratories. To address diagnostic needs, we developed a novel, rapid, and sensitive molecular method using a portable PCR machine, POCKIT, capable of immediate deployment at sites of suspected outbreaks. Here, we demonstrate that field-deployable RVFV detection can provide reliable, sensitive, and specific point-of-need viral RNA detection that could be used for diagnostic investigations and epidemiological studies, and can be performed in the field.
Topics: Humans; Cattle; Sheep; Animals; Rift Valley fever virus; Real-Time Polymerase Chain Reaction; Reverse Transcription; Laboratories; RNA, Viral
PubMed: 38305205
DOI: 10.1128/jcm.00430-23 -
Molecular Pharmaceutics Mar 2024Rift Valley fever virus (RVFV) could cause an emergency illness characterized by fever, muscle pain, and even death in humans or ruminants. However, there are no...
Rift Valley fever virus (RVFV) could cause an emergency illness characterized by fever, muscle pain, and even death in humans or ruminants. However, there are no approved antiviral drugs that prevent or treat RVFV infection. While therapeutic antibodies have shown promising potential for prevention or treatment in several studies, many studies are ongoing, especially in the field of infectious diseases. Among these studies, the mRNA-LNP platform shows great potential for application, following the COVID-19 pandemic. Previously, we have obtained a neutralizing antibody against RVFV, which was named A38 protein and verified to have a high binding and neutralization ability. In this study, we aimed to identify an effectively optimized sequence and expressed the prioritized mRNA-encoded antibody . Notably, we effectively expressed mRNA-encoded protein and used the mRNA-LNP platform to generate A38-mRNA-LNP. Pharmacokinetic experiments were conducted and set up in two groups of mRNA-A38 group and A38 protein group, which were derived from mRNA-LNP and plasmid DNA-expressed proteins, respectively. A38-mRNA-LNPs were administrated by intramuscular injection, A38 proteins were administrated by intravenous administration, and their unique ability to maintain long-lasting protein concentrations by mRNA-encoded protein was demonstrated with the mRNA-encoded protein providing a longer circulating half-life compared to injection of the free A38 protein. These preclinical data on the mRNA-encoded antibody highlighted its potential to prevent infectious diseases in the future.
Topics: Animals; Humans; Rift Valley fever virus; Rift Valley Fever; Pandemics; Antibodies, Viral; Communicable Diseases; Liposomes; Nanoparticles
PubMed: 38295278
DOI: 10.1021/acs.molpharmaceut.3c01016 -
BMC Infectious Diseases Jan 2024Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis with a high fatality rate in China. Previous studies have reported that dysregulated...
BACKGROUND
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis with a high fatality rate in China. Previous studies have reported that dysregulated inflammatory response is associated with disease pathogenesis and mortality in patients with SFTS. This investigation aimed to evaluate the prevalence and characteristics of systemic inflammatory response syndrome (SIRS), and its impact on prognosis.
METHODS
Data on demographic characteristics, comorbid conditions, clinical manifestations, laboratory parameters, and survival time of patients with SFTS were collected. Patients were divided into the non-SIRS and SIRS groups according to the presence of SIRS, then their clinical data were compared.
RESULTS
A total of 290 patients diagnosed with SFTS were retrospectively enrolled, including 126(43.4%) patients with SIRS. Patients in the non-survivor group had more prevalence of SIRS than patients in the survivor group (P < 0.001), and SIRS (adjusted OR 2.885, 95% CI 1.226-6.786; P = 0.005) was shown as an independent risk factor for prognosis of patients with SFTS. Compared with patients without SIRS, patients with SIRS had lower WBC and neutrophils counts, and fibrinogen levels, but higher AST, LDH, amylase, lipase, CK, CK-MB, troponin I, APTT, thrombin time, D-dimer, CRP, IL-6, SAA levels, and viral load. The cumulative survival rate of patients with SIRS was significantly lower than that of patients without SIRS. Patients with SIRS also showed a higher incidence of bacterial or fungal infections than patients without SIRS.
CONCLUSIONS
SIRS is highly frequent in patients with SFTS, and it is associated with high mortality.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Retrospective Studies; Prevalence; Phlebovirus; Thrombocytopenia; Fever; Prognosis; Systemic Inflammatory Response Syndrome; China
PubMed: 38291390
DOI: 10.1186/s12879-024-09026-4 -
Tropical Medicine and Infectious Disease Dec 2023In the Old World, phlebotomine sand flies from the genus are implicated in the transmission of spp. parasites (Kinetoplastida: Trypanosomatidae) and viruses belonging...
In the Old World, phlebotomine sand flies from the genus are implicated in the transmission of spp. parasites (Kinetoplastida: Trypanosomatidae) and viruses belonging to the genus (Bunyavirales: Phenuiviridae). Two of the five sand fly species known to occur in Portugal, and , the former being the most ubiquitous, are recognized vectors of , which causes visceral leishmaniasis, the most prevalent form of leishmaniasis in the country. is also the vector of the neurotropic Toscana virus, which can cause aseptic meningitis. Entomological surveillance is essential to provide fundamental data about the presence of vectors and the pathogens they can carry. As such, and given the lack of data in Portugal, an entomological survey took place in the Algarve, the southernmost region of the country, from May to October 2018. Polymerase chain reaction assays were performed in order to detect the presence of the above-mentioned pathogens in sand fly pools. Not only were both parasites and phleboviruses detected during this study, but more importantly, it was the first time their co-circulation was verified in the same sand fly population collected in Portugal.
PubMed: 38276633
DOI: 10.3390/tropicalmed9010003 -
The Science of the Total Environment Mar 2024Rift valley fever (RVF) is listed as one of prioritized diseases by WHO. This study aims to describe RVF virus' landscape distribution globally, and to insight dynamics...
BACKGROUND
Rift valley fever (RVF) is listed as one of prioritized diseases by WHO. This study aims to describe RVF virus' landscape distribution globally, and to insight dynamics change of its evolution, prevalence, and outbreaks in the process of breaking geographical barriers.
METHODS
A systematic literature review and meta-analyses was conducted to estimate RVF prevalence by hosts using a random-effect model. Molecular clock-based phylogenetic analyses were performed to estimate RVF virus nucleotide substitution rates using nucleotide sequences in NCBI database. RVF virus prevalence, nucleotide substitution rates, and outbreaks were compared before and after breaking geographical barriers twice, respectively.
RESULTS
RVF virus was reported from 26 kinds of hosts covering 48 countries from 1930 to 2022. Since RVF broke geographical barriers, (1) nucleotide substitution rates significantly increased after firstly spreading out of Africa in 2000, (2) prevalence in humans significantly increased from 1.92 % (95 % CI: 0.86-3.25 %) to 3.03 % (95 % CI: 2.09-4.12 %) after it broke Sahara Desert geographical barriers in 1977, and to 5.24 % (95 % CI: 3.81-6.82 %) after 2000, (3) RVF outbreaks in humans and the number of wildlife hosts presented increasing trends. RVF virus spillover may exist between bats and humans, and accelerate viral substitution rates in humans. During outbreaks, the RVF virus substitution rates accelerated in humans. 60.00 % RVF outbreaks occurred 0-2 months after floods and (or) heavy rainfall.
CONCLUSION
RVF has the increasing risk to cause pandemics, and global collaboration on "One Health" is needed to prevent potential pandemics.
Topics: Animals; Humans; Rift Valley fever virus; Prevalence; Phylogeny; Rift Valley Fever; Disease Outbreaks; Nucleotides
PubMed: 38272089
DOI: 10.1016/j.scitotenv.2024.170302 -
Emerging Microbes & Infections Dec 2024Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with an increasing annual incidence rate. In this case report, we presented two...
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with an increasing annual incidence rate. In this case report, we presented two patients infected with the SFTS virus, suggesting a potential direct transmission route from camels to humans through blood contact. Both patients developed symptoms after engaging in the slaughtering of one sick camel, while their family members living in the same environment or co-diners remained unaffected. Subsequent detection revealed a high viral load of SFTS virus, reaching 10 viral RNA copies/ml, in the sample obtained from the sick camel. Metagenomic sequencing did not identify any other pathogens. The SFTS virus was successfully isolated from both patient and camel samples. The complete nucleotide sequences obtained from the infected patients demonstrated a remarkable 100% similarity to those found in the camel, and genetic evolution analysis classified the virus as genotype A. Additionally, partial sequences of the SFTS virus were identified in ticks captured from the camel rearing environment, however, these sequences showed only 95.9% similarity to those found in camel and humans. Furthermore, immunoglobulin M and immunoglobulin G antibodies were detected in serum samples collected from the patient. Our findings provide evidence that camel may serve as a competent reservoir for transmitting the SFTS virus to humans. Further investigations into SFTS virus infections in large animals are warranted to understand their role in viral maintenance and transmission.
Topics: Animals; Humans; Camelus; China; Immunoglobulin G; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome
PubMed: 38269573
DOI: 10.1080/22221751.2024.2309990