Search Results (80)

(1) Background: Hemorrhagic fever with renal syndrome (HFRS) remains a prevalent zoonosis in Eurasia. Orthohantavirus puumalaense (PUUV), carried by bank voles (Myodes glareolus), is the principal zoonotic pathogen of HFRS in this region. Despite ongoing efforts to develop effective drugs and vaccines against PUUV, this challenge remains. (2) Aim: In this study, we aimed to express a large quantity of the PUUV recombinant N (rN) protein using E. coli. We also sought to develop a protocol for extracting the rN protein from pellets, solubilizing, and refolding it to restore its native form. This protocol is crucial for producing a large quantity of rN protein to develop vaccines and diagnostic tools for HFRS. (3) Methods; PUUV S segment open reading frame (ORF) coding for N protein was synthesized and cloned into the plasmid vector pET-28 (A+). The ORF was transformed, expressed and induced in BL21(DE3) pLysS E. coli strain. Subsequently, rN protein was purified using immobilized metal affinity and ion chromatography. Immune reactivity of rN protein was tested by employing in house and commercial VektoHanta-IgG kit ELISA methods (both in vitro and in vivo). (4) Results: The best conditions for scaling up the expression of the PUUV rN protein were an incubation temperature of 20 °C during a 20 h incubation period, followed by induction with 0.5 mM IPTG. The most significant protein yield was achieved when the pellets were incubated in denaturing buffer with 8M urea. The highest yield of refolded proteins was attained using non-denaturing buffer (50 mM Tris-HCl) supplemented with arginine. A final 50 μL of PUUV rN protein solution with a concentration of 7 mg/mL was recovered from 1 L of culture. The rN protein elicited an antibody response in vivo and reacted with serum taken from patients with HFRS by ELISA in vitro. (5) Conclusion: Therefore, the orthohantavirus N protein’s ability to elicit immune response in vivo suggests that it can be used to develop vaccines against PUUV after conducting in vitro and in vivo studies to ascertain neutralising antibodies. Full article

Zoonotic viral diseases have continued to threaten global public health in recent decades, with rodent-borne viruses being significant contributors. Infection by rodent-carried hantaviruses (HV) can result in hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans, with varying degrees of morbidity and mortality. However, no Food and Drug Administration (FDA) vaccines or therapeutics have been approved for the treatment of these diseases. In an effort to identify antiviral bioactive molecules, we isolated four oligomeric phloroglucinols from Callistemon rigidus leaves, including two new phloroglucinol trimers, callistemontrimer A and B, along with two previously characterized phloroglucinol dimers, rhodomyrtosone B and rhodomyrtone. We evaluated the anti-Hantaan virus (HTNV) activity of these compounds. Notably, callistemontrimer A demonstrated higher anti-HTNV activity compared to ribavirin. Mechanistic studies revealed that callistemontrimer A exerted its antiviral effects by inhibiting viral replication, likely through interaction with RNA-dependent RNA polymerase (RdRp) of HTNV, as supported by molecular docking analysis. These results highlight oligomeric phloroglucinols as promising lead candidates for the development of anti-HV therapeutics. Full article

This study aimed to analyze the epidemiological characteristics and incidence trends of zoonotic diseases in China from 2015 to 2022, providing evidence for zoonotic disease prevention and control strategies. Individual case data for nationally reported zoonotic diseases from the Chinese Disease Prevention and Control Information System were collected. Descriptive epidemiology and statistical methods were employed to analyze trends along with changes in their spatial, temporal, and demographic distributions. From 2015 to 2022, the annual incidence rates of leishmaniasis, Japanese encephalitis, rabies, echinococcosis, hemorrhagic fever with renal syndrome (HFRS), and schistosomiasis showed a fluctuating downward trend. The incidence rates of anthrax and leptospirosis remained relatively stable. The incidence of brucellosis declined from 2015 to 2018 but subsequently increased through 2022. Western provinces, such as Gansu, Ningxia, Qinghai, Xinjiang, and Yunnan, remain high-incidence areas for multiple zoonotic diseases, with farmers being the population at the highest risk. These findings indicate it is essential to strengthen cross-sectoral cooperation and develop region- and population-specific prevention and control strategies based on the ‘One Health’ concept, particularly in areas with high incidence rates and among high-risk populations. Full article

Chiggers (chigger mites) and gamasid mites are two groups of ectoparasites on rodents, and they can be the vectors or potential vectors of scrub typhus and hemorrhagic fever with renal syndrome (HFRS), while Bower’s white-toothed rat (Berylmys bowersi) can serve as the reservoir host of the diseases. Based on field investigations at 117 survey sites of southwest China, a total of 2512 mites were collected from 55 B. bowersi rats. Under a microscope, these mites were taxonomically identified as 56 distinct species, comprising 37 chigger mite species and 19 gamasid mite species. The mite infestation burdens on B. bowersi were heavy, with a high prevalence (P_M = 85.45%), mean abundance (MA = 45.67), and intensity (MI = 53.45). Of 56 mite species identified, 7 are vectors of scrub typhus and HFRS. Of the seven vector mite species, Leptotrombidium scutellare was one of dominant chigger species, with a higher infestation index on rats (P_M = 21.82%, MA = 7.76) than the other six vector mite species. The sex ratio of female gamasid mites was higher than that of males. The number and infestation of adult gamasid mites were higher than those of immature mites. The infestation indexes of mites on B. bowersi hosts varied with the host’s sex and age and fluctuated along different environmental gradients. The association coefficient (V) showed a slight positive association between chiggers and gamasid mites, suggesting that these two groups of mites may coexist on B. bowersi rats. Spearman correlation coefficients showed positive correlations among some dominant and vector mite species, indicating that some mite species tend to select the same hosts. A total of 69 mite species (47 chigger mite species and 22 gamasid mite species) on B. bowersi were estimated by species rarefaction and extrapolation curves. In conclusion, Berylmys bowersi has a high susceptibility to mite infestation, and it has the potential to harbor abundant mites, with heavy mite burdens. The occurrence of vector mite species, especially L. scutellare (the dominant species), increases the potential risk of transmission and the focus persistence of scrub typhus and HFRS in southwest China. Full article

Hemorrhagic fever with renal syndrome (HFRS) is the result of acute, zoonotic, natural foci hantavirus infections. It has serious social and medical importance due to its widespread distribution and the disease’s severity. There is a lack of effective etiotropic therapy and specific prophylaxis available. The aim of this review is to observe the etiological, clinical, and epidemiological features of nosologic HFRS forms in Russia, as well as differences and similarities with hantavirus pulmonary syndrome (HPS). The various clinical HFRS manifestations characterized diseases associated with Puumala, Kurkino, and Sochi hantaviruses in the Russian European part, and with Hantaan, Amur, and Seoul hantaviruses in the Russian Far East. Differences were observed for HFRS foci types based on biological characteristics and natural host population dynamics. As a result of clinical and epidemiological analysis six nosological forms were established, all of which were classified as “hemorrhagic fever with renal syndrome” according to the WHO’s expert recommendation from 1983 year. The study showed comparable taxonomic characteristics and determined the mechanism of human infection course for HFRS and HPS. The accumulated knowledge of this study allows for the combination of HFRS and HPS names into a common logical disease name “Hantavirus fever”. Full article

(1) Background: We aimed to analyze the epidemiological characteristics of hemorrhagic fever with renal syndrome (HFRS) in Longyou County and to provide a basis for the future response to this disease. (2) Methods: Data on hemorrhagic fever and host animals were collected from 2011 to 2023. Descriptive methods were used to analyze the epidemic. The R4.4.1 software was used to show how the host density relates to the virus levels, temperature, and rainfall and to predict the host density. (3) Results: We observed 58 cases of hemorrhagic fever, the majority of which occurred in farmers. There were two incidence peaks each year during the spring and winter seasons, accounting for 22.41% and 43.10% of the total cases, respectively. The outdoor rodent population density was significantly and positively correlated with the outdoor rodent virus prevalence (R² = 0.9411), serving as a robust predictor of the outdoor rodent virus prevalence. Additionally, the density of outdoor rodents exhibited a strong nonlinear relationship with the temperature and precipitation. (4) Conclusions: After hemorrhagic fever vaccination, rodent population density control, and rodent carrier rodent control from 1995 to 2000, the hemorrhagic fever epidemic was generally stable, and the epidemiological characteristics remained stable. In the future, we should continue to take active and effective comprehensive measures to intervene, further realize the effective control of HFRS, and prevent the recurrence of hemorrhagic fever epidemics. Full article

Orthohantaviruses (also known as hantaviruses) are pathogens that cause two distinct, yet related forms of severe human disease: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). These diseases pose a significant threat to global public health due to their high case fatality rates, which can range from 1% to 50%. In recent years, an increasing number of countries and regions have reported human cases, underscoring the urgent need for improved understanding, prevention, and treatment strategies. Given the severity of these diseases and the lack of specific post-exposure antiviral treatments, preventive measures are critical. For several decades, substantial efforts have been dedicated to developing orthohantavirus vaccines, leading to significant advancements. The first large-scale deployment involved inactivated vaccines, which played a crucial role in reducing HFRS incidence in South Korea and China. Subunit vaccines, viral vector vaccines, and virus-like particle (VLP) vaccines have also been extensively researched. Nucleic acid vaccines, including both mRNA and DNA vaccines, hold the greatest potential for future development due to their rapid design and production cycles, ability to elicit robust immune responses, ease of storage and transportation, and adaptable production platforms. Ongoing advancements in computer technology and artificial intelligence promise to further enhance the development of more effective orthohantavirus vaccines. Full article

Background: The fatality rate of hemorrhagic fever with renal syndrome (HFRS), due to hantavirus transmitted by rodents, ranges from 1% to 12%. This study aims to delineate the clinical and laboratory characteristics of HFRS, identify factors associated with disease severity, and construct and validate a nomogram for prognosis prediction of HFRS in the central part of China. Methods: Out of 598 HFRS patients diagnosed via serology tests from four hospitals in Hubei Province, 551 were included. Clinical data were gathered and analyzed, followed by logistic univariate and multivariate analyses to identify independent prognostic factors. A nomogram was developed and validated to forecast the patient’s prognosis. Results: Vaccination led to a notable drop in HFRS incidence from 2018 to 2019, and seasonal trends exhibited bimodal changes with peaks from May to July and November to January. The 30-day mortality rate was 4.17% (23/551). Red blood cell count (RBC), age, two-stage overlap, qSOFA ≥ 2, aspartate aminotransferase (AST), and three-stage overlap were identified as independent prognostic factors. A predictive risk classification system using a nomogram chart was developed, and Kaplan–Meier curves indicated that the new system accurately distinguished 30-day mortality among the three risk groups. Conclusions: The risk score (EASTAR) system demonstrated good predictive performance for prognostic prediction, and it can be applied to quickly screen patients who require ICU admission. Full article

Hemorrhagic fever with renal syndrome (HFRS) induced by Eurasian pathogenic orthohantaviruses is characterized by acute kidney injury (AKI) with often massive proteinuria. The mechanisms of the organ-specific manifestation are not completely understood. To analyze the role of glomerular and tubular damage in kidney injury induced by HFRS, we measured specific markers in urine samples of patients with acute Puumala virus (PUUV) infection and determined their correlation with disease severity. Levels of α1-microglobulin (α1-MG) and kidney injury molecule 1 (KIM-1), which is expressed by injured tubular epithelial cells, were measured to detect tubular dysfunction and injury. Immunoglobulin G (IgG) and the podocyte specific protein nephrin served as markers for glomerular injury. All four markers were elevated on admission. Markers of glomerular injury, IgG and nephrin, correlated with markers of disease severity such as length of hospitalization, serum creatinine, and proteinuria. In contrast, tubular injury did not correlate with these severity markers. Our results demonstrate that hantavirus infection induces both glomerular and tubular injury early in the clinical course. However, the glomerular dysfunction and podocyte injury seem to contribute directly to disease severity and to play a more central role in HFRS pathogenicity than direct damage to tubular epithelial cells. Full article

Hemorrhagic fever with renal syndrome (HFRS) and tick-borne encephalitis (TBE) are the most common viral diseases in Russia. HFRS is caused by six different types of hantaviruses: Hantaan, Amur, Seoul, Puumala, Kurkino, and Sochi, which are transmitted to humans through small mammals of the Muridae and Cricetidae families. TBE is caused by viruses belonging to five different phylogenetic subtypes. The similarities in the ecology of HFRS and TBE pathogens is presented here. Hantavirus-infected small mammals can transmit the virus to uninfected animals, and ticks can also transmit hantavirus to other ticks and mammals. Hantavirus transmission from ticks to humans is possible only hypothetically based on indirect data. Over the past 23 years, 164,582 cases of HFRS (4.9 per 10⁵ people) and 71,579 cases of TBE (2.5 per 10⁵ people) were registered in Russia. The mortality rate was 0.4% (668 cases) in HFRS and 1.6% deaths (1136 cases) in TBE. There were 4030 HFRS (2.5%) and 9414 TBE (13%) cases in children under 14 years old. HFRS and TBE cases were registered in 42 out of 85 Russian regions; in 18—only HFRS, in 13—only TBE, and 12 had no reported cases. The prospects of applying a combined vaccine for HFRS and TBE prevention are shown in this paper. Full article

Puumala orthohantavirus (PUUV) is an emerging zoonotic virus endemic to Europe and Russia that causes nephropathia epidemica, a mild form of hemorrhagic fever with renal syndrome (HFRS). There are limited options for treatment and diagnosis of orthohantavirus infection, making the search for potential immunogenic candidates crucial. In the present work, various bioinformatics tools were employed to design conserved immunogenic peptides containing multiple epitopes of PUUV nucleocapsid protein. Eleven conserved peptides (90% conservancy) of the PUUV nucleocapsid protein were identified. Three conserved peptides containing multiple T and B cell epitopes were selected using a consensus epitope prediction algorithm. Molecular docking using the HPEP dock server demonstrated strong binding interactions between the epitopes and HLA molecules (ten alleles for each class I and II HLA). Moreover, an analysis of population coverage using the IEDB database revealed that the identified peptides have over 90% average population coverage across six continents. Molecular docking and simulation analysis reveal a stable interaction with peptide constructs of chosen immunogenic peptides and Toll-like receptor-4. These computational analyses demonstrate selected peptides’ immunogenic potential, which needs to be validated in different experimental systems. Full article

While the pathology of acute hemorrhagic fever with renal syndrome (HFRS) has been widely researched, details on the chronic HFRS sequelae remain mainly unexplored. In this study, we analyzed the clinical and laboratory characteristics of 30 convalescent HFRS patients 14 years after the disease contraction, mainly emphasizing several endothelial dysfunction parameters. Convalescent HFRS patients exhibited significantly higher serum levels of erythrocyte sedimentation rate, von Willebrand factor, uric acid, C-reactive protein and immunoglobulin A when compared to healthy individuals. Furthermore, 24 h urine analyses revealed significantly lower sodium and potassium urine levels, as well as significantly higher proteinuria, microalbumin levels and β2-microglobulin levels when compared to healthy individuals. First morning urine analysis revealed significantly higher levels of hematuria in convalescent HFRS patients. None of the additional analyzed endothelium dysfunction markers were significantly different in post-HFRS patients and healthy individuals, including serum and urine P-selectin, E-selectin, soluble intercellular adhesion molecule 1, vascular intercellular adhesion molecule 1 (sVCAM-1) and vascular endothelial growth factor (VEGF). However, binary logistic regression revealed a weak association of serum sVCAM-1 and urine VEGF levels with HFRS contraction. Generally, our findings suggest mild chronic inflammation and renal dysfunction levels in convalescent HFRS patients 14 years after the disease contraction. Full article

Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease widespread in Europe and Asia. HFRS is caused by negative-sensed single-stranded RNA orthohantaviruses transmitted to humans through inhaling aerosolized excreta of infected rodents. Symptoms of HFRS include acute kidney injury, thrombocytopenia, hemorrhages, and hypotension. The immune response raised against viral antigens plays an important role in the pathogenesis of HFRS. Inhibitory co-receptors are essential in regulating immune responses, mitigating immunopathogenesis, and reducing tissue damage. Our research showed an increased soluble form of inhibitory co-receptors TIM-3, LAG-3, and PD-1 in HFRS patients associated with disease severity. Our study aimed to investigate the impact of HFRS on the concentrations of soluble forms of inhibitory receptors TIM-3, LAG-3, and PD-1 in the patient’s serum and the potential correlation with key clinical parameters. Our study aimed to investigate the impact of HFRS on the concentrations of soluble forms of inhibitory receptors TIM-3, LAG-3, and PD-1 in the patient’s serum and their possible association with relevant clinical parameters. Using multiplex immunoassay, we found elevated levels of TIM-3, LAG-3, and PD-1 proteins in the serum of HFRS patients. Furthermore, increased levels were associated with creatinine, urea, lactate dehydrogenase concentrations, and platelet count. These findings suggest that these proteins play a role in regulating the immune response and disease progression. Full article

Nephropathis epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS), is an acute zoonotic disease endemic in the Republic of Tatarstan. This study aimed to assess the impact of rosuvastatin on the clinical and laboratory results of NE. A total of 61 NE patients and 30 controls were included in this study; 22 NE patients and 7 controls received a daily dose of rosuvastatin (10 mg) for ten consecutive days. Serum samples were collected on days 1, 5, and 10 after admission to the hospital. These samples were analyzed to determine the levels of lipids, cytokines, and kidney toxicity markers. Our findings indicate that rosuvastatin reduced the duration of the second wave of fever and alleviated back pain and headache symptoms. Additionally, low-density lipoprotein cholesterol (LDL-C) serum levels were significantly decreased on days 5 and 10 upon rosuvastatin treatment. Furthermore, rosuvastatin decreased the levels of cytokines in the serum, particularly proinflammatory cytokines IL-1β and IL-8. NE patients had significantly altered levels of the kidney toxicity markers albumin and osteopontin. The data from our study provide evidence supporting the therapeutic potential of rosuvastatin in NE cases. Full article

Hemorrhagic fever with renal syndrome (HFRS) is caused by hantaviruses (HVs) and is endemic in Zhejiang Province, China. In this study, we aimed to explore the changing epidemiology of HFRS cases and the dynamics of hantavirus hosts in Zhejiang Province. Joinpoint regression was used to analyze long-term trends in the incidence of HFRS. The comparison of animal density at different stages was conducted using the Mann–Whitney Test. A comparison of HV carriage rates between stages and species was performed using the chi-square test. The incidence of HFRS shows a continuous downward trend. Cases are widely distributed in all counties of Zhejiang Province except Shengsi County. There was a high incidence belt from west to east, with low incidence in the south and north. The HFRS epidemic showed two seasonal peaks in Zhejiang Province, which were winter and summer. It showed a marked increase in the age of the incidence population. A total of 23,073 minibeasts from 21 species were captured. Positive results were detected in the lung tissues of 14 rodent species and 1 shrew species. A total of 80% of the positive results were from striped field mice and brown rats. No difference in HV carriage rates between striped field mice and brown rats was observed (χ² = 0.258, p = 0.611). Full article