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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 -
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 -
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 -
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 -
Acta Crystallographica. Section D,... Feb 2024Phenuiviridae nucleoprotein is the main structural and functional component of the viral cycle, protecting the viral RNA and mediating the essential...
Phenuiviridae nucleoprotein is the main structural and functional component of the viral cycle, protecting the viral RNA and mediating the essential replication/transcription processes. The nucleoprotein (N) binds the RNA using its globular core and polymerizes through the N-terminus, which is presented as a highly flexible arm, as demonstrated in this article. The nucleoprotein exists in an `open' or a `closed' conformation. In the case of the closed conformation the flexible N-terminal arm folds over the RNA-binding cleft, preventing RNA adsorption. In the open conformation the arm is extended in such a way that both RNA adsorption and N polymerization are possible. In this article, single-crystal X-ray diffraction and small-angle X-ray scattering were used to study the N protein of Toscana virus complexed with a single-chain camelid antibody (VHH) and it is shown that in the presence of the antibody the nucleoprotein is unable to achieve a functional assembly to form a ribonucleoprotein complex.
Topics: Nucleoproteins; Sandfly fever Naples virus; Nucleocapsid Proteins; Models, Molecular; RNA, Viral
PubMed: 38265877
DOI: 10.1107/S2059798324000196 -
Viruses Jan 2024Wuxiang virus (WUXV) is the first sandfly-borne isolated from collected in China and has been established as a consistent viral presence in the local sandfly...
Wuxiang virus (WUXV) is the first sandfly-borne isolated from collected in China and has been established as a consistent viral presence in the local sandfly populations of both Wuxiang County and Yangquan City. However, its distribution in the Shanxi Province remains unclear. In this study, three novel WUXV strains were isolated from sandflies collected from Jiexiu City, Shanxi Province, China, in 2022. Subsequently, whole-genome sequences of these novel strains were generated using next-generation sequencing. The open reading frame (ORF) sequences of the WUXV strains from the three locations were subjected to gene analysis. Phylogenetic analysis revealed that WUXV belongs to two distinct clades with geographical differences. Strains from Wuxiang County and Yangquan City belonged to clade 1, whereas strains from Jiexiu City belonged to clade 2. Reassortment and recombination analyses indicated no gene reassortment or recombination between the two clades. However, four reassortments or recombination events could be detected in clade 1 strains. By aligning the amino acid sequences, eighty-seven mutation sites were identified between the two clades, with seventeen, sixty, nine, and one site(s) in the proteins RdRp, M, NSs, and N, respectively. Additionally, selection pressure analysis identified 17 positively selected sites across the entire genome of WUXV, with two, thirteen, one, and one site(s) in the proteins RdRp, M, NSs, and N, respectively. Notably, sites M-312 and M-340 in the M segment not only represented mutation sites but also showed positive selective pressure effects. These findings highlight the need for continuous nationwide surveillance of WUXV.
Topics: Animals; Phylogeny; China; Amino Acid Sequence; High-Throughput Nucleotide Sequencing; Psychodidae; RNA-Dependent RNA Polymerase
PubMed: 38257803
DOI: 10.3390/v16010103 -
Viruses Jan 2024Toscana virus (TOSV), a sandfly-borne virus, is an important etiological agent in human acute meningitis and meningoencephalitis in the Mediterranean area during the...
Toscana virus (TOSV), a sandfly-borne virus, is an important etiological agent in human acute meningitis and meningoencephalitis in the Mediterranean area during the summer. However, the actual number of TOSV infections is underestimated. Laboratory confirmation is necessary because TOSV infection has overlapping clinical features with other neuro-invasive viral infections. Nowadays, the reference test for direct diagnosis in the acute phase of TOSV infection is the PCR based method for detecting TOSV in cerebrospinal fluid and/or plasma, serum, or blood. Although poorly employed, urine is another helpful biological matrix for TOSV detection. Urine is a matrix rich in PCR inhibitors that affect PCR efficiency; consequently, false negatives could be generated. To investigate the potential effect of urine PCR inhibitors on TOSV detection, we compared undiluted and diluted urine using 10-fold series of spiked TOSV. The results showed a significant improvement in TOSV detection performance in diluted urine (1 TCID vs. 1 × 10 TCID limit of detection and 101.35% vs. 129.62% efficiency, respectively, in diluted and undiluted urine). In conclusion, our data provide preliminary important insights into the use of diluted urine to limit the impact of the inhibitory effects of urine on the detection of TOSV in RT-PCR-based approaches.
Topics: Humans; Sandfly fever Naples virus; Body Fluids; Plasma; Encephalitis, California; Laboratories
PubMed: 38257798
DOI: 10.3390/v16010098 -
Viruses Jan 2024Rift Valley fever is a zoonotic viral disease transmitted by mosquitoes, impacting both humans and livestock. Currently, there are no approved vaccines or antiviral...
Rift Valley fever is a zoonotic viral disease transmitted by mosquitoes, impacting both humans and livestock. Currently, there are no approved vaccines or antiviral treatments for humans. This study aimed to evaluate the in vitro efficacy of chemical compounds targeting the Gc fusion mechanism. These compounds were identified through virtual screening of millions of commercially available small molecules using a structure-based artificial intelligence bioactivity predictor. In our experiments, a pretreatment with small molecule compounds revealed that 3 out of 94 selected compounds effectively inhibited the replication of the Rift Valley fever virus MP-12 strain in Vero cells. As anticipated, these compounds did not impede viral RNA replication when administered three hours after infection. However, significant inhibition of viral RNA replication occurred upon viral entry when cells were pretreated with these small molecules. Furthermore, these compounds exhibited significant inhibition against Arumowot virus, another phlebovirus, while showing no antiviral effects on tick-borne bandaviruses. Our study validates AI-based virtual high throughput screening as a rational approach for identifying effective antiviral candidates for Rift Valley fever virus and other bunyaviruses.
Topics: Chlorocebus aethiops; Humans; Animals; Rift Valley fever virus; Artificial Intelligence; Vero Cells; Computers; Phlebovirus; RNA, Viral; Antiviral Agents
PubMed: 38257788
DOI: 10.3390/v16010088