Hantavirus Research Articles

Monitoring and analysis on host animals of hemorrhagic fever with renal syndrome in Henan Province from 2019 to 2022

Objective: To investigate the distribution and hantavirus (HV) carrying state in host animals of hemorrhagic fever with renal syndrome (HFRS) in Henan Province from 2019 to 2022. Methods: Host animal monitoring was carried out at the monitoring sites of HFRS in Henan Province. The real-time fluorescence quantitative PCR was used to detect hantavirus in rat lungs. The types of hantavirus were analyzed. The positive samples were sequenced and then sequence homology and variation were analyzed. Results: A total of 1 308 rodents were captured from 2019 to 2022, 16 specimens of rat lungs tested positive for hantavirus nucleic acid. The positive rate of HV was 1.22% (16/1 308). According to type, the positive rate of HV in Apodius agrarius was the highest (68.75%, 11/16). According to distribution, the positive rate of HV in field samples was the highest (2.50%, 12/480), and the positive rate of HV in residential samples was 0.53% (4/759). The typing results of 16 positive samples showed that all viruses were hantavirus type Ⅰ (hantaan virus). The positive samples were sequenced and eight S gene fragments (GenBank number: OQ681444-OQ681451) and six M gene fragments (OQ681438-OQ681443) were obtained. The S and M gene fragments were similar to the Shaanxi 84FLi strain and Sichuan SN7 strain. Phylogenetic analysis of S and M gene fragments showed that they all belonged to the hantaan virus-H5 subtype. Amino acid sequence analysis revealed that, compared with the hantaan virus vaccine strain 84FLi, the 74th amino acid encoded by eight S fragments was replaced by aspartamide with serine. Tryptophan was replaced by glycine at the 14th position of Gn region in XC2022047, and isoleucine was replaced by alanine at the 359 position of XC2022022 and XC2022024. Conclusion: The hantavirus carried by host animals in Henan Province from 2019 to 2022 belongs to the type Ⅰ (hantaan virus), and Apodemus agrarius is still the dominant host animal of the hantaan virus. Compared with the vaccine strains, amino acid sites are replaced in the immune epitopes of the S and M gene fragments.

Long‐ and Short‐Run Asymmetric Effects of Meteorological Parameters on Hemorrhagic Fever with Renal Syndrome in Heilongjiang: A Population‐Based Retrospective Study

Examining both long‐term and short‐term effects can enhance the precision and reliability of time series analysis. This study aimed to delve into the asymmetric effects of weather conditions on hemorrhagic fever with renal syndrome (HFRS) in the long and short terms and build a forecasting system. Data comprising monthly HFRS incidents and weather factors in Heilongjiang from January 2004 to December 2019 were extracted. Subsequently, the long‐ and short‐term asymmetric impacts were examined using the autoregressive distributed lag (ARDL) and nonlinear ARDL (NARDL) models. Next, the samples were partitioned into training and testing subsets to evaluate the predictive potential of both models. From 2004 to 2019, HFRS exhibited a declining trend (average annual percentage change = −6.744%, 95% CI: −13.52%–0.563%) and a dual seasonal pattern, with a prominent peak in June and a secondary one in October–December. This study identified long‐term asymmetric effects of rainfall (Wald long‐run asymmetry (WLR) = 3.292, p = 0.001), wind velocity (WLR = −3.271, p = 0.001), and air pressure (WLR = −6.453, p < 0.001) on HFRS. Additionally, this study observed short‐term asymmetric impacts of relative humidity (Wald short‐run symmetry (WSR) = −1.547, p = 0.001), rainfall (WSR = −1.984, p = 0.049), and air pressure (WSR = −2.33, p = 0.021) on HFRS. A unit increase in relative humidity, sunshine hours, and air pressure resulted in about 10.9%, 1.9%, and 13.6% decreases in HFRS, respectively; a unit decrease in relative humidity, rainfall, and sunshine hours led to about 6.7%, 1.8%, and 2% decreases in HFRS, respectively. When temperature increased and decreased by one unit, the HFRS incidence increased by 11.6% and 22.5%, respectively. HFRS also varied significantly with the positive and negative changes in differenced (D) temperature, D (relative humidity), D (wind velocity), D (rainfall), D (air pressure), and D (sunshine hours) at 0−3‐month delays over the short term. The NARDL model exhibited notably lower error rates in forecasting compared to the ARDL model. Meteorological parameters affect HFRS in both the long and short term, often showing asymmetric effects. The NARDL model, capable of incorporating various weather parameters, proves to be valuable in predicting HFRS epidemic and guiding strategies for prevention and control.

Circulating mucosal-like IgA responses increase with severity of Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome.

Old World Orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS) characterized by increased vascular permeability and acute kidney injury (AKI). Despite the systemic nature of the disease, the virus enters humans through inhalation and therefore initially encounters the immunoglobulin class A (IgA) dominated mucosal immune system. Herein, we characterized systemic IgA responses and their potential relationship to the mucosal immune activation by examining blood samples obtained from patients hospitalized due to acute Puumala orthohantavirus infection. Our findings reveal increased frequencies of putative IgA-expressing circulating mucosal-associated B1 cells and plasmablasts, as well as elevated levels of polyreactive, polymeric, virus-specific and secretory IgA in the acute stage of the disease. Importantly, the levels of circulating virus-specific and secretory IgA, as well as the putative IgA+ B1 cells, increased with the severity of AKI. Furthermore, circulating polymeric IgA displayed enhanced effector functions by forming stable complexes with the IgA receptor CD89 and induced pro-inflammatory neutrophil responses. These results suggest that excessive levels of circulating mucosal-like IgA might serve as a biomarker for HFRS disease progression.

Infections and Influencing Factors of Pathogens in Rattus norvegicus along the Zengjiang River in Guangzhou, China.

Background: Rattus norvegicus can carry and transmit various zoonotic pathogens. Some studies were conducted to investigate a few zoonotic pathogens in Guangzhou, China, but no coinfections were investigated or specifically mentioned. Studies on the infections and the influencing factors of various zoonotic pathogens in R. norvegicus along the Zengjiang River in Guangzhou have not been carried out. Materials and Methods: In this study, R. norvegicus was captured in November 2020 and September 2021 along the Zengjiang River, and was tested for Bartonella spp., Leptospira spp., Orientia tsutsugamushi, Borrelia burgdorferi, Hantavirus (HV), Ehrlichia spp., and severe fever with thrombocytopenia syndrome virus (SFTSV) by the RT-PCR. Logistic regression analysis was used to determine the impact of habitat and demographic factors on the infections and coinfections of the surveyed pathogens. Results: In 119 R. norvegicus, the detection rates of Bartonella spp., Leptospira spp., O. tsutsugamushi, B. burgdorferi, and HV were 46.2%, 31.9%, 5%, 0.8%, and 18.5%, respectively. Ehrlichia spp. and SFTSV were negative. The triple coinfection rate of Bartonella spp., Leptospira spp., and HV was 11.8%. In addition, the coinfection of Bartonella spp., Leptospira spp., and B. burgdorferi was 0.8%. Dual coinfection of Bartonella spp. and Leptospira spp., Leptospira spp. and HV, Bartonella spp. and O. tsutsugamushi, Leptospira spp. and O. tsutsugamushi, and HV and O. tsutsugamushi was 9.2%, 3.4%, 1.7%, 1.7%, and 0.8%, respectively. Infections of these pathogens in R. norvegicus were found in habitats of banana plantation, grassland, and bush. Weight affected the infection of Bartonella spp., Leptospira spp., or HV in R. norvegicus. Conclusions: R. norvegicus along the Zengjiang River not only carried various potentially zoonotic pathogens but also had a variety of coinfections. Surveillance of the density and pathogens in R. norvegicus should be strengthened to reduce the incidence of relevant zoonotic diseases.

A simple clinical score to reduce unnecessary testing for Puumala hantavirus.

Puumala hantavirus (PUUV) causes nephropathia epidemica (NE), an endemic form of transient acute renal injury (AKI). Serological testing is the mainstay of diagnosis. It was the aim of the present study to assist decision-making for serological testing by constructing a simple tool that predicts the likelihood of PUUV positivity. We conducted a comparative cohort study of all PUUV-tested cases at Aachen University tertiary care center in Germany between mid-2013 and mid-2021. N = 293 qualified for inclusion; N = 30 had a positive test result and clinical NE; N = 263 were negative. Two predictive point scores, the Aachen PUUV Score (APS) 1 and 2, respectively, were derived with the aid of logistic regression and receiver operating characteristic (ROC) analysis by determining the presence of four admission parameters. For internal validation, the internal Monte Carlo method was applied. In addition, partial external validation was performed using an independent historic cohort of N = 41 positive cases of NE. APS1 is recommended for clinical use as it estimated the probability of PUUV positivity in the entire medical population tested. With a range from 0 to 6 points, it yielded an area under the curve of 0.94 by allotting 2 points each for fever or headache and 1 point each for AKI or LDH>300 U/L. A point sum of 0-2 safely predicted negativity for PUUV, as was confirmed in the NE validation cohort. Here, we present a novel, easy-to-use tool to guide the diagnostic management of suspected PUUV infection/NE and to safely avoid unnecessary serological testing, as indicated by point sum class 0-2. Since 67% of the cohort fell into this stratum, half of the testing should be avoidable in the future.

The Role of Long Noncoding RNA Negative Regulator of Interferon Response in the Regulation of Hantaan Virus Infection.

Hantaan virus (HTNV) is prevalent in Eurasia. It causes hemorrhagic fever with renal syndrome (HFRS). Long noncoding RNAs (lncRNAs) play key roles in regulating innate immunity. Among these, lncRNA negative regulator of interferon response (NRIR) was reported as an inhibitor of several interferon (IFN)-stimulated genes. Our results showed that: NRIR expression was upregulated by HTNV infection in a type I IFN-dependent manner. The expression of NRIR in CD14+ monocytes from HFRS patients in acute phase was significantly higher than that in convalescent phase and healthy controls. HTNV infection in some HTNV-compatible cells was promoted by NRIR. NRIR negatively regulated innate immunity, especially IFITM3 expression. Localized in the nucleus, NRIR bound with HNRNPC, and knockdown of HNRNPC significantly weakened the effect of NRIR in promoting HTNV infection and restored IFITM3 expression. These results indicated that NRIR regulates the innate immune response against HTNV infection possibly through its interaction with HNRNPC and its influence on IFITM3.

High-resolution phylogeographical surveillance of Hantaan orthohantavirus using rapid amplicon-based Flongle sequencing, Republic of Korea.

Orthohantaviruses, etiological agents of hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome, pose a critical public health threat worldwide. Hantaan orthohantavirus (HTNV) outbreaks are particularly endemic in Gyeonggi Province in northern area of the Republic of Korea (ROK). Small mammals were collected from three regions in the Gyeonggi Province during 2017 and 2018. Serological and molecular prevalence of HTNV was 25/201 (12.4%) and 10/25 (40%), respectively. A novel nanopore-based diagnostic assay using a cost-efficient Flongle chip was developed to rapidly and sensitively detect HTNV infection in rodent specimens within 3 h. A rapid phylogeographical surveillance of HTNV at high-resolution phylogeny was established using the amplicon-based Flongle sequencing. In total, seven whole-genome sequences of HTNV were newly obtained from wild rodents collected in Paju-si (Gaekhyeon-ri) and Yeoncheon-gun (Hyeonga-ri and Wangnim-ri), Gyeonggi Province. Phylogenetic analyses revealed well-supported evolutionary divergence and genetic diversity, enhancing the resolution of the phylogeographic map of orthohantaviruses in the ROK. Incongruences in phylogenetic patterns were identified among HTNV tripartite genomes, suggesting differential evolution for each segment. These findings provide crucial insights into on-site diagnostics, genome-based surveillance, and the evolutionary dynamics of orthohantaviruses to mitigate hantaviral outbreaks in HFRS-endemic areas in the ROK.

Epidemiological profile of Hantavirus in the Ñuble region period 2002-2018, Chile.

Hantavirus infection is an endemic zoonosis in Chile, with an average lethality of around 36%. The highest lethality (60%) was recorded in 1997. Prevention strategies have been applied since then. Early diagnosis and technologies, such as the use of ECMO (Extracorporeal Membrane Oxygenation) and Hantavirus immune plasma, have contributed to increasing the survival of people due to this disease at the national level. In the newly created Region of Ñuble in Chile, the incidence and lethality of Hantavirus cases are unknown; therefore, the objective of this research is to describe the epidemiological profile of Hantavirus cases in the Region of Ñuble, Chile from 2002 to 2018. This knowledge contributes to substantiating and justifies the need to invest in technology and reinforce interventions related to the early diagnosis and prevention of this disease in the region. Cases reported in the Ñuble region during the period 2002-2018, extracted from the Epidemiological Survey of Environmental Research of Hantavirus cases of the Ministry of Health of Chile, were analyzed retrospectively. The epidemiological profile of the Ñuble region is very similar to the national one in terms of characterizing the individual suffering from the disease. The most affected population is young men, residents in rural areas, and mainly from a low socioeconomic segment. The regional profile of Hantavirus cases makes it possible to identify three communes with the highest number of cases: El Carmen, Coihueco, and San Carlos. A political-administrative response is expected to focus on and optimize strategies and resources to reduce the incidence and lethality of this pathology in the Ñuble region.

Hantavirus Disease Cluster Caused by Seoul Virus, Germany.

A cluster of 3 persons in Germany experienced hantavirus disease with renal insufficiency. Reverse transcription PCR-based genotyping revealed infection by Seoul hantavirus transmitted from pet rats. Seoul virus could be responsible for disease clusters in Europe, and infected pet rats should be considered a health threat.

Serological Evidence of Hantavirus Infection in Suspected Cases of Viral Haemorrhagic Fever in Conakry, Guinea

Serological Evidence of Hantavirus Infection in Suspected Cases of Viral Haemorrhagic Fever in Conakry, Guinea

Hantavirus Pulmonary Syndrome Caused by Puumala Orthohantavirus-A Case Report and Literature Review.

In this article, we report on a rare case of acute respiratory distress syndrome (ARDS) caused by the Puumala orthohantavirus (PUUV), which is typically associated with hemorrhagic fever with renal syndrome (HFRS). This is the first documented case of PUUV-associated ARDS in Southeast Europe. The diagnosis was confirmed by serum RT-PCR and serology and corroborated by phylogenetic analysis and chemokine profiling. The patient was a 23-year-old male from Zagreb, Croatia, who had recently traveled throughout Europe. He presented with fever, headache, abdominal pain, and sudden onset of ARDS. Treatment involved high-flow nasal cannula oxygen therapy and glucocorticoids, which resulted in a full recovery. A systematic literature review identified 10 cases of hantavirus pulmonary syndrome (HPS) caused by PUUV in various European countries and Turkey between 2002 and 2023. The median age of patients was 53 years (range 24-73), and six of the patients were male. Most patients were treated in intensive care units, but none received antiviral therapy targeting PUUV. Eight patients survived hospitalization. The presented case highlights the importance of considering HPS in the differential diagnosis of ARDS, even in areas where HFRS is the dominant form of hantavirus infection.

HANTAVIRUS INFECTION - EPIDEMIOLOGICAL CHARACTERISTICS IN THE AREA OF THE REPUBLIC OF CROATIA DURING THE COVID-19 PANDEMIC

Introduction: Hantaviruses are the causative agents of hemorrhagic fever with renal syndrome (HGBS). People are most often infected by inhaling a contaminated aerosol, but infection can also occur through contaminated food or water. On average, eighteen people fall ill with HGBS per year outside of epidemics. Men between the ages of 20 and 40, especially farmers, soldiers, foresters and hikers, are most often affected. Famous hotspots in Croatia are Lika, Gorski kotar and Medvednica. Objective: To analyze the frequency and epidemiological characteristics of hantavirus infections in the Republic of Croatia during the COVID-19 pandemic. Materials and methods: Data on the incidence of HGBS according to counties, seasonal occurrence, age groups and gender were analyzed, as well as the connection of recommendations for being in nature as part of the suppression of the Covid-19 pandemic to a potential increase in the number of HGBS patients. Retrospective analysis was used to process the data collected at the Croatian Institute of Public Health, and descriptive methods were used to perform statistical analyzes in the Microsoft Excel software system. Results: In the period from 2019 to 2021, there were 547 patients with HGBS, with men suffering more often than women (78.0% vs. 22.0%). The highest activity was recorded in Primorje-Gorski Kotar and Lika-Senj counties from March to August in the age groups of 30 to 39 years. In 2021, 332 patients were reported, which is more than the average, and this can be connected to the more frequent stay of people in nature due to recommendations to reduce the number of patients with the COVID-19 disease. Conclusion: The study of the epidemiological features of hantavirus infections is important for public health because it enables the identification of areas with a higher risk of infection, the recognition of epidemics and the adoption of appropriate control and prevention measures. Keywords: Hantavirus, Epidemiology, COVID-19, Croatia

Hantaan virus inhibits type I interferon response by targeting RLR signaling pathways through TRIM25

Hantaan virus (HTNV) is responsible for hemorrhagic fever with renal syndrome (HFRS), primarily due to its ability to inhibit host innate immune responses, such as type I interferon (IFN-I). In this study, we conducted a transcriptome analysis to identify host factors regulated by HTNV nucleocapsid protein (NP) and glycoprotein. Our findings demonstrate that NP and Gc proteins inhibit host IFN-I production by manipulating the retinoic acid-induced gene I (RIG-I)-like receptor (RLR) pathways. Further analysis reveals that HTNV NP and Gc proteins target upstream molecules of MAVS, such as RIG-I and MDA-5, with Gc exhibiting stronger inhibition of IFN-I responses than NP. Mechanistically, NP and Gc proteins interact with tripartite motif protein 25 (TRIM25) to competitively inhibit its interaction with RIG-I/MDA5, suppressing RLR signaling pathways. Our study unveils a cross-talk between HTNV NP/Gc proteins and host immune response, providing valuable insights into the pathogenic mechanism of HTNV.

Direct and indirect effects of Puumala hantavirus on platelet function

Thrombocytopenia is a cardinal symptom of hantavirus-induced diseases including Puumala virus (PUUV)-induced hemorrhagic fever with renal syndrome (HFRS), which is associated with impaired platelet function, bleeding manifestations and augmented thrombotic risk. However, the underlying mechanisms causing thrombocytopenia and platelet hypo-responsiveness are unknown. Thus, we investigated the direct and indirect impact of PUUV on platelet production, function and degradation.Analysis of PUUV-HFRS patient blood revealed that platelet hypo-responsiveness in PUUV infection was cell-intrinsic and accompanied by reduced platelet-leukocyte aggregates (PLAs) and upregulation of monocyte tissue factor (TF), whereas platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation was comparable to healthy controls. Plasma CXCL4 levels followed platelet count dynamics throughout disease course. PUUV activated both neutrophils and monocytes in vitro, but platelet desialylation, degranulation and GPIIb/IIIa activation as well as PLA formation and endothelial adhesion under flow remained unaltered in the presence of PUUV. Further, MEG-01 megakaryocytes infected with PUUV displayed unaltered polyploidization, expression of surface receptors and platelet production. However, infection of endothelial cells with PUUV significantly increased platelet sequestration.Our data thus demonstrate that although platelet production, activation or degradation are not directly modulated, PUUV indirectly fosters thrombocytopenia by sequestration of platelets to infected endothelium. Upregulation of immunothrombotic processes in PUUV-HFRS may further contribute to platelet dysfunction and consumption. Given the pathophysiologic similarities of hantavirus infections, our findings thus provide important insights into the mechanisms underlying thrombocytopenia and highlight immune-mediated coagulopathy as potential therapeutic target.

Development and validation of a novel death risk stratification scale in patients with hemorrhagic fever with renal syndrome: a 14-year ambispective cohort study

ObjectivesTo develop and validate a simple and effective death risk stratification scale for hemorrhagic fever with renal syndrome (HFRS). MethodsIn this ambispective cohort study, we investigated the epidemiological and clinical data of 2245 patients with HFRS (1873 enrolled retrospectively and constituting the training cohort, 372 prospectively recruited as the validation cohort) from September 2008 to December 2021, and identified independent risk factors for 30-day death of HFRS. Using logistic regression analysis, a nomogram prediction model was established and was further simplified into a novel scoring scale. Calibration plot, receiver operating characteristic curve, net reclassification index, integrated discrimination index, and decision curve analysis were used to assess the calibration, discrimination, precision, and clinical utility in both training and validation cohorts. ResultsOf 2245 patients with HFRS, 132 (5.9%) died during hospitalization. The nomogram prediction model and scoring scale were developed using six predictors: comorbid hypertension, hypotensive shock, hypoxemia, neutrophils, aspartate aminotransferase, and activated partial thromboplastin time. Both the scale and nomogram were well calibrated (near-diagonal calibration curves) and demonstrated significant predictive values (areas under receiver operating characteristic curves >0.9, sensitivity and specificity >90% in the training cohort and >84% in the validation cohort). The simplified scoring scale demonstrated equivalent discriminative ability to the nomogram, with net reclassification index and integrated discrimination index of 0.022 and 0.007 in the training cohort, 0.126 and 0.022 in the validation cohort. Decision curve analysis graphically represented significant clinical utility and comparable net benefits of the nomogram and scoring scale across a range of threshold probabilities. DiscussionThis evidence-based, factor-weighted, accurate score could help clinicians swiftly stratify HFRS mortality risk and facilitate the implementation of patient triage and tiered medical services during epidemic peaks.

Genetic variants associated with hantavirus infection in a reservoir host are related to regulation of inflammation and immune surveillance

The immunogenetics of wildlife populations influence the epidemiology and evolutionary dynamic of the host-pathogen system. Profiling immune gene diversity present in wildlife may be especially important for those species that, while not at risk of disease or extinction themselves, are host to diseases that are a threat to humans, other wildlife, or livestock. Hantaviruses (genus: Orthohantavirus) are globally distributed zoonotic RNA viruses with pathogenic strains carried by a diverse group of rodent hosts. The marsh rice rat (Oryzomys palustris) is the reservoir host of Orthohantavirus bayoui, a hantavirus that causes fatal cases of hantavirus cardiopulmonary syndrome in humans. We performed a genome wide association study (GWAS) using the rice rat “immunome” (i.e., all exons related to the immune response) to identify genetic variants associated with infection status in wild-caught rice rats naturally infected with their endemic strain of hantavirus. First, we created an annotated reference genome using 10× Chromium Linked Reads sequencing technology. This reference genome was used to create custom baits which were then used to target enrich prepared rice rat libraries (n = 128) and isolate their immunomes prior to sequencing. Top SNPs in the association test were present in four genes (Socs5, Eprs, Mrc1, and Il1f8) which have not been previously implicated in hantavirus infections. However, these genes correspond with other loci or pathways with established importance in hantavirus susceptibility or infection tolerance in reservoir hosts: the JAK/STAT, MHC, and NFκB. These results serve as informative markers for future exploration and highlight the importance of immune pathways that repeatedly emerge across hantavirus systems. Our work aids in creating cross-species comparisons for better understanding mechanisms of genetic susceptibility and host-pathogen coevolution in hantavirus systems.

Hemorrhagic Fever with Renal Syndrome Patients Exhibit Increased Levels of Lipocalin-2, Endothelin-1 and NT-proBNP.

Hemorrhagic fever with renal syndrome (HFRS) is an acute zoonotic disease caused by viruses of the Orthohantavirus genus. This syndrome is characterized by renal and cardiopulmonary implications detectable with different biomarkers. Here, we explored the role of serum and urine levels of lipocalin-2, endothelin-1 and N-terminal pro-brain natriuretic peptide (NT-proBNP) in HFRS pathology. A total of twenty-eight patients hospitalized due to a Puumala orthohantavirus infection were included, with serum and urine samples collected on patient admission (acute phase) and discharge (convalescent phase). In comparison to healthy individuals, patients exhibited significantly higher acute-phase serum and urine levels of lipocalin-2, serum levels of endothelin-1 and serum and urine levels of NT-proBNP. Patients in the convalescent phase showed a significant decrease in urine lipocalin-2, serum endothelin-1 and serum and urine NT-proBNP levels. We recorded a strong correlation between serum levels of lipocalin-2 and endothelin-1 and urine levels of lipocalin-2 with several kidney injury markers, such as serum creatinine, urea, urine white blood cell count and proteinuria. We also demonstrated an independent correlation of serum and urine lipocalin-2 levels with acute kidney injury in HFRS. All in all, our results show an involvement of NT-proBNP, lipocalin-2 and endothelin-1 in the renal and cardiac pathology of HFRS.

Seroprevalence of Hantavirus among Manual Cane Cutters and Epidemiological Aspects of HPS in Central Brazil.

Hantavirus pulmonary syndrome (HPS) is a rodent-borne zoonotic disease that is endemic throughout the Americas. Agricultural activities increase exposure to wild rodents, especially for sugarcane cutters. We carried out a survey of the epidemiological aspects of HPS and investigated the prevalence of hantavirus infection in the sugarcane cutter population from different localities in the Brazilian Midwest region. We conducted a retrospective study of all confirmed HPS cases in the state of Goiás reported to the National HPS surveillance system between 2007 and 2017, along with a seroepidemiological study in a population of sugarcane cutters working in Goiás state in 2016, using the anti-hantavirus (Andes) ELISA IgG. A total of 634 serum samples from cane cutters were tested for hantavirus antibodies, with 44 (6.9%) being IgG-reactive according to ELISA. The destination of garbage was the only statistically significant variable (p = 0.03) related to the detection of hantavirus IgG (p < 0.05). We described the epidemiological profile of reported hantavirus cases in Goiás-a highly endemic area for HPS, and where the seroepidemiological study was conducted. Our results increase our knowledge about hantavirus infections in Brazil and highlight the vulnerability of sugarcane cutters to a highly lethal disease that, to date, has no specific treatment or vaccination.

Pathogenicity of novel hantavirus isolate and antigenicity and immunogenicity of novel strain-based inactivated vaccine

BackgroundHantaan virus (HTNV, Orthohantavirus hantanensae species, Hantaviridae family) is the main etiological agent responsible for hemorrhagic fever with renal syndrome (HFRS). The novel HTNV may pose a potential danger to the control and prevention of HFRS in China, which highlights the importance of vaccine development in public health management. In previous studies, our laboratory discovered and successfully isolated a new HTNV strain, HV004 strain, from Apodemus agrarius captured in an epidemic area in Hubei, China. MethodsAn initial biological and pathogenicity characterization of HTNV 76–118 (standard train), HV114 strain (a clinical isolate from Hubei province in 1986), and the novel isolate HV004 strain from the epidemic areas of Hubei province were performed in susceptible cells and in vivo. An experimental HV004 strain inactivated vaccine was prepared, and its corresponding immunogenicity was analyzed in BALB/c mice. ResultsHV004 strain had a similar but higher pathogenicity than HTNV 76–118 and HV114 in suckling mice. A subcutaneous vaccination (s.c.) with the inactivated HTNV vaccine adjuvanted with aluminum, followed by a challenge intraperitoneally with 106 FFU/ml HTNV, afforded full protection against an HTNV challenge. All immunized mice in every group elicited serum neutralizing antibodies with increasing dosages, which may protect mice from HTNV infection. A dose-dependent stimulation index of splenocytes was also observed in immunized mice. The percentage of IFN-γ-producing CD3+CD8+ T cells was significantly higher in the spleens of immunized mice than in those of control mice. ConclusionsThese findings suggest that the inactivated HTNV vaccine may stimulate mice to produce high levels of antibodies with neutralization activity and elicit specific anti-HTNV humoral and cellular immune responses in BALB/c mice against the prevalent strain of HTNV in south central China.

Outbreak economic analysis of six imported hemorrhagic fevers following detection at 24 hours

Abstract A ten-language search found no economic analysis of symptomatic hemorrhagic fever importation for Crimean Congo (CCHF), Hantavirus (HV), Lassa (LV), Marburg (MARV), Middle East Respiratory Syndrome (MERS) or Nipah (NV) into the USA/EU/UK. This study used available literature to calculate the cost of importation of the six selected fevers with each outbreak detected at 24 hours. A PRISMA search of Pubmed and grey literature was undertaken to uncover respective R0, case fatality ratios, average hospital stay, time to death, frontline casualty frequency and contact histories. A simulated breakout, t24 intervention, Borel distribution contact model, with R0 determined infection (0-1.59) and death rate (CFR: 0.01-0.5) was formed. Treatment inc. plasma therapy, and PPE best prices were determined. ICU median operational costs were factored with contact tracing. Indirect admin costs, based on national mean values, frontline replacement, GNI per capita productivity losses through isolation (21 days as standard), hospitalisation and death were factored. Mean patient discharge ranged 4.4 - 28 days (CCHF to MERS). Time to death ranged 2 - 15 days (HV, NV). The number infected at t48 ranged 1 - 9.59 (CCHF/HV to MARV). Contacts ranged 27 - 169 (CCHF to MARV/NV/MERS). Direct costs of outbreak care, labour, and tracing ranged €424707 - €2850083.07 (CCHF - MARV). Indirect costs, attributed to administrative burdens ranged €5264 -€32800.02 (CCHF to MARV). Productivity losses, attributed separately to the isolated, treated, and dead totaled €2042613 - €26198606 (CCHF - MARV). The total outbreak cost ranged €2488512.78 - €29081489.72 (EU, CCHF - MARV). Significant direct, indirect and productivity costs were attributed to the importation of a single case of six hemorrhagic fevers when detected at t24. The significant societal cost of MARV in particular highlights the importance of continued hemorrhagic fever research and preparedness to healthcare systems in protecting future budgets. Key messages • The importation of hemorrhagic fevers has significant direct and indirect budgetary, and productivity, impacts. • Besides human cost, financial costs demand public health enhanced surveillance and response plans for hemorrhagic fever importation.