Hantavirus

To investigate the distribution of hantaviruses among animals in Southern and Central Highland area of Vietnam, a total of 1311 serum samples were obtained from rats and Asian house shrews (Suncus murinus) captured at 11 locations between 2006 and 2009. A total of 1066 serum samples from rats were examined for IgG antibodies against Hantaan virus, and there were 30 antibody-positive serum samples from rats that had been captured mainly in a port area and urban area in Ho Chi Minh City (HCMC) (2.8%). All of the antibody-positive rats were Rattus norvegicus, and they had Seoul virus (SEOV) genome in their lungs. SEOV sequences detected from rats captured in Southern Vietnam belonged to the same lineage as those from rats captured at Haiphong Port and a market area in Hanoi City. SEOV strain CSG5 was isolated from a rat captured at Saigon Harbor. Strain CSG5 showed a cross-neutralization pattern almost the same as that of a representative strain of SEOV. A total of 245 Asian house shrews were captured in the Central Highland area and near HCMC. Sera were examined for IgG antibodies against Thottapalayam virus (TPMV), and 32 (13.1%) of the antibody-positive shrews were mainly from the Central Highland area and showed a neutralizing antibody against TPMV. These results indicated that SEOV is distributed among R. norvegicus inhabiting harbor and urban areas of Southern Vietnam and that TPMV or an antigenically related virus is distributed among Asian house shrews in Central Highland area.

We study the spread of Hantavirus over a host population of deer mice using a population dynamics model. We show that taking into account the internal fluctuations in the mouse population due to its discrete character strongly alters the behaviour of the system. In addition to the familiar transition present in the deterministic model, the inclusion of internal fluctuations leads to the emergence of an additional deterministically hidden transition. We determine parameter values that lead to maximal propagation of the disease, and discuss some implications for disease prevention policies.

Using a model for rodent population dynamics, we study outbreaks of Hantavirus infection induced by the alternation of seasons. Neither season by itself satisfies the environmental requirements for propagation of the disease. This result can be explained in terms of the seasonal interruption of the relaxation process of the mouse population toward equilibrium, and may shed light on the reported connection between climate variations and outbreaks of the disease.

The connection between nephropathia epidemica (NE) and vegetation dynamics has been emphasized in recent studies. Changing climate has been suggested as a triggering factor of recently observed epidemiologic peaks in reported NE cases. We have investigated whether there is a connection between the NE occurrence pattern in Belgium and specific trends in remotely sensed phenology parameters of broad-leaved forests. The analysis of time series of the MODIS Enhanced Vegetation Index revealed that changes in forest phenology, considered in literature as an effect of climate change, may affect the mechanics of NE transmission.

Introduction One of the challenges in managing patients with hantavirus infection is accurately identifying individuals who are at risk of developing severe disease. Prompt identification of these patients can facilitate critical decisions, such as early referral to an intensive care unit. The identified prognostic factors could be incorporated into predictive models to enhance the management of hantavirus infection. Objective: To identify and evaluate prognostic factors associated with mortality in hantavirus infection, providing a basis for a risk assessment model for hantavirus mortality Methods We conducted a systematic review following the 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' (PRISMA) guidelines. We conducted a comprehensive search in PubMed/MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase from their inception to January 2024. Furthermore, we included studies evaluating individual prognostic factors or risk assessment models of hantavirus infections, with no restrictions on study design, publication status, or language. When feasible, we conducted meta-analyses for prognostic factors using the inverse variance-based method with random effect model. We assessed the certainty of the evidence using the GRADE approach, Results: We included 30 studies with a total of 92,183 participants. We identified the following key prognostic factors which predicted and increased mortality and disease severity: over 15 years, female gender, 1 .

In Panama, hantavirus pulmonary syndrome (HPS) is caused by Choclo virus, a species phylogenetically related to Andes and Maporal viruses. Up to 60% of the population has been positive for specific serum antibody in community-based surveys, but mortality is very uncommon. In four western Panama clinics, we tested individuals presenting with a severe febrile prodrome for acute hantavirus (HV) infection by immunoglobulin M enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction as well as clinically similar infections, such as dengue and leptospirosis. From 2006 to 2009, at least 21% of 117 patients diagnosed with HV infection had HV Fever (HF) with no evidence of pulmonary edema (no respiratory distress or radiographic lung infiltrates), and 44% of patients had very mild HPS (radiographic pulmonary edema but no respiratory insufficiency). HV infection caused by Choclo virus in Panama presents often as HF, which contrasts with HV in the Americas but is consistent with the high seroprevalence in endemic regions.

In Canada, hantavirus infected deer mice (Peromyscus maniculatus) have been collected from British Columbia to Newfoundland. Partial sequencing of G1 and N protein encoding regions from Canadian Peromyscus maniculatusborne hantaviruses demonstrated the existence of significant genotypic divergence among strains. Phylogenetic analysis showed that Sin Nombre (SN)-like viruses from eastern and western Canadian deer mice can be divided into at least two broad-based genogroups. Sequencing of mitochondrial DNA from infected deer mice originating from various eastern and western provinces showed that SN-like virus genogroups appeared to be associated with distinct haplotypes of mice. Sera from deer mice infected with eastern and western viral genotypes neutralized the Sin Nombre virus strain, Convict Creek 107, but not the New York 1 hantavirus. Despite the genetic heterogeneity of Canadian SN-like strains these hantaviruses do not appear to define unique hantavirus serotypes.

Determining toxicity of experimental compounds is an important step in the antiviral screening process. While bone marrow clonogenic assays are considered the most predictive for drug induced bone marrow suppression, they are expensive and not

In Egypt, the etiology of chronic renal failure (CRF) is not well defined. A hospital-based case-control study was initiated in February 1998, to determine whether hantavirus infection is involved in chronic renal disease (CRD) in Egypt. The study enrolled 350 study patients with a history of CRF and 695 matched controls with CRD due to renal calculus or renal cancer, but with normal renal functions. Sera from cases and controls were tested for anti-hantavirus IgG using ELISA with a cell-lysate antigen from Hantaan virus prototype strain 76-118. A demographic questionnaire was completed for each study participant. Five of the 350 cases (1.4%), and seven of the 695 controls (1.0%) were antibody-positive to hantavirus, with a titer ≥1:400. The difference in antibody prevalence between the study cases and the control cases was not statistically significant (P = 0.48). All antibody-positive study cases and controls had been exposed to rodents. Data indicated that in Egypt, hantavirus seroprevalence in CRD patients is low, and hantavirus infections do not appear to be a significant cause of CRF.

Hantavirus pulmonary syndrome (HPS) with high mortality rate has been reported in five countries in South America. Rapid accurate methods are important both for monitoring acute infections and for epidemiological studies. The Andes virus nucleoprotein amino acid sequence has a high identity percentage compared with other sequences of this region and has been chosen for the development of diagnostic reagents. Andes nucleoprotein expressed in Escherichia coli was applied as antigen in IgG, IgA and mu-capture IgM enzyme-linked inmunosorbent assays (ELISAs). An evaluation of this reagent was conducted to establish its usefulness for differential diagnosis of HPS and seroprevalence studies. Samples from 135 reverse transcription (RT)-PCR-confirmed HPS cases, 77 individuals with other respiratory infections and 957 healthy inhabitants from endemic and non-endemic areas were analysed. The hantavirus-infected patients had an early and strong IgM, IgG and IgA serum antibody response, in most...

An increase of Hantavirus Pulmonary Syndrome (HPS) cases around a southwestern Argentina town and in persons living 1400 km away but in contact with those cases was detected during the spring of 1996. In order to evaluate person-to-person transmission we compared the homology of PCR-amplified viral sequences of 26 Argentine and Chilean cases. Sixteen of them were epidemiologically linked cases and had the same sequence (Epilink/96) in the S segment 3Ј noncoding region and in the M segment partial G1 and G2 region (a total of 1075 nucleotides). Contrarily, two geographical and contemporary but nonepidemiologically related cases differed from Epilink/96 in the compared regions. No significant differences, such as glycosylation or hydrophilic pattern, were found between Epilink/96 and the other sequences. Nucleotide and deduced amino acid sequence homologies between samples from southern Argentina and Chile ranged from 90.9 to 100% and 96.4 to 100%, respectively. Phylogenetic analysis revealed that all the analyzed southwestern viruses belong to the Andes lineage. Although human infection principally occurs via inhalation of contaminated rodent excreta, our results with Andes virus show the first direct genetic evidence of person-to-person transmission of a hantavirus.

Hantaviruses (genus Hantavirus, family Bunyaviridae) are enveloped tri-segmented negative-stranded RNA viruses each carried by a specific rodent or insectivore host species. Several different hantaviruses known to infect humans circulate in Europe. The most common is Puumala (PUUV) carried by the bank vole; another two important, genetically closely related ones are Dobrava-Belgrade (DOBV) and Saaremaa viruses (SAAV) carried by Apodemus mice (species names follow the International Committee on Taxonomy of Viruses nomenclature). Of the two hantaviral diseases, hemorrhagic fever with renal syndrome (HFRS) and hantaviral cardiopulmonary syndrome, the European viruses cause only HFRS: DOBV with often severe symptoms and a high case fatality rate, and PUUV and SAAV more often mild disease. More than 10,000 HFRS cases are diagnosed annually in Europe and in increasing numbers. Whether this is because of increasing recognition by the medical community or due to environmental factors such as climate change, or both, is not known. Nevertheless, in large areas of Europe, the population has a considerable seroprevalence but only relatively few HFRS cases are reported. Moreover, no epidemiological data are available from many countries. We know now that cardiac, pulmonary, ocular and hormonal disorders are, besides renal changes, common during the acute stage of PUUV and DOBV infection. About 5% of hospitalized PUUV and 16%-48% of DOBV patients require dialysis and some prolonged intensive-care treatment. Although PUUV-HFRS has a low case fatality rate, complications and long-term hormonal, renal, and cardiovascular consequences commonly occur. No vaccine or specific therapy is in general use in Europe. We conclude that hantaviruses have a significant impact on public health in Europe.

This paper reports the establishment of a model for hantavirus host adaptation. Wild-type (wt) (bank vole-passaged) and Vero E6 cell-cultured variants of Puumala virus strain Kazan were analyzed for their virologic and genetic properties. The wt variant was well adapted for reproduction in bank voles but not in cell culture, while the Vero E6 strains replicated to much higher efficiency in cell culture but did not reproducibly infect bank voles. Comparison of the consensus sequences of the respective viral genomes revealed no differences in the coding region of the S gene. However, the noncoding regions of the S gene were found to be different at positions 26 and 1577. In one additional and independent adaptation experiment, all analyzed cDNA clones from the Vero E6-adapted variant were found to carry substitutions at position 1580 of the S segment, just 3 nucleotides downstream of the mutation observed in the first adaptation. No differences were found in the consensus sequences of the entire M segments from the wt and the Vero E6-adapted variants. The results indicated different impacts of the S and the M genomic segments for the adaptation process and selective advantages for the variants that carried altered noncoding sequences of the S segment. We conclude that the isolation in cell culture resulted in a phenotypically and genotypically altered hantavirus.

Background. Puumala virus (PUUV) induced hemorrhagic fever with renal syndrome is common in many European countries. The typical renal histologic lesion is acute tubulointerstitial nephritis. We examined the type and kinetics of urine protein excretion, and prognostic significance of proteinuria for the severity of acute kidney injury (AKI) in acute PUUV infection. Methods. The amount of dipstick albuminuria at hospital admission was analyzed in 205 patients with acute PUUV infection. Dipstick albuminuria at admission was graded into three categories: 0-1+, 2+, 3+. In 70 patients also 24-hour urinary excretion of protein, and overnight urinary excretion of albumin, immunoglobulin(Ig)G, and α1-microglobulin were measured over three consecutive days during the hospital stay. Results. Maximum median daily proteinuria, overnight albuminuria, and IgG excretion was observed five days, while that of creatinine values was observed nine days after the onset of the disease. The medians of maximum plasma creatinine levels during hospital stay were different in the 3 categories of dipstick albuminuria: 0-1+ 98 µmol/L (58-1499), 2+ 139 µmol/L (71-829), and 3+ 363 µmol/L (51-1285) (p<0.001). Dipstick albuminuria ≥2+ at admission could detect 89% of the patients who subsequently developed severe AKI. Glomerular proteinuria, but not tubular proteinuria (α1-microglobulin), correlated with the severity of the emerging AKI. Conclusion. In acute PUUV infection, maximum median proteinuria values preceded the most severe phase of AKI by a few days. A highly useful finding for clinical work was that a quick and simple albuminuria dipstick test at hospital admission predicted the severity of the upcoming AKI.

Coagulation abnormalities are associated with Puumala virus-induced hemorrhagic fever with renal syndrome (PUUV-HFRS). We evaluated the coagulation capacity of plasma during acute PUUV-HFRS by measuring thrombin generation using calibrated automated thrombography (CAT®). Material and Methods The study cohort comprised of 27 prospectively collected, consecutive, hospital-treated patients with acute PUUV infection. Blood samples were drawn in the acute phase and at the control visit approximately 5 weeks later. To evaluate thrombin generation, the lag time of initiation, endogenous thrombin potential (ETP), and peak and time to peak thrombin concentration were assessed by CAT® in platelet poor plasma without corn trypsin inhibitor. Plasma levels of D-dimer, fibrinogen and prothrombin fragments (F1+2) were also evaluated. Results When the acute phase was compared with the control phase, ETP was decreased (median 1154 nM/min, range 67-1785 vs. median 1385 nM/min, range 670-1970; p<0.001), while the lag time was prolonged (median 3.8 minutes, range 2.1-7.7 vs. median 2.9 minutes, range 2.0-4.1; p<0.001). Low ETP correlated with low peak thrombin concentration (r=0.833, p<0.001). Prolonged time to peak associated with the lag time (r=0.78, p<0.001). ETP was associated with thrombocytopenia (r=0.472, p=0.015) and weakly with fibrinogen level (r=0.386, p=0.047). The measured CAT® parameters did not associate with D-dimer and F1+2 levels. Conclusions Decreased ETP together with low peak and prolonged lag time indicate decreased plasma potential for thrombin generation in vitro. Together with low platelet count and enhanced fibrinolysis this further refers to altered blood coagulation and increased propensity toward bleeding in acute PUUV-HFRS.

Background: The emergence and re-emergence of zoonotic and vector-borne diseases are increasing in Europe. Prominent rodent-borne zoonotic viruses include Puumala hantavirus (PUUV; the causative agent of nephropathia epidemica, NE), lymphocytic choriomeningitis virus (LCMV), and orthopoxviruses (OPV). In addition, Ljungan virus (LV) is considered a potentially zoonotic virus. Objective: The aim of this study was to compare clinical picture between acute PUUV patients with and without additional rodent-borne viral infections, to investigate if concurrent infections influence disease severity. Study design: We evaluated seroprevalence of and seroconversions to LCMV, LV and OPV in 116 patients hospitalized for NE. Clinical and laboratory variables were closely monitored during hospital care. Results: A total of five LCMV, 15 LV, and one OPV seroconversions occurred. NE patients with LCMV seroconversions were younger, and had lower plasma creatinine concentrations and platelet counts than patients without LCMV seroconversions. No differences occurred in clinical or laboratory findings between patients with and without seroconversions to LV and OPV. We report, for the first time, LCMV seroprevalence in Finland, with 8.5% of NE patients seropositive for this virus. Seroprevalences for LV and OPV were 47.8% and 32.4%, respectively. Conclusion: Cases with LCMV seroconversions were statistically younger, had milder acute kidney injury and more severe thrombocytopenia than patients without LCMV. However, the low number of seroconversion cases precludes firm conclusions. Concurrent LV or OPV infections do not appear to influence clinical picture for NE patients.

We evaluated the mechanisms of thrombocytopenia and procoagulant changes in relation with clinical variables in a cohort of patients with acute hantavirus disease. Blood samples of 33 prospectively recruited, consecutive, hospitalized patients with acute Puumala virus-induced hemorrhagic fever with renal syndrome (HFRS) were collected acutely and at the recovery visit (control). Serum thrombopoietin (TPO) and activity of plasma microparticles (MPs) from various cell sources were measured with enzyme-linked immunosorbent assay-based methods. The results were related to data on platelet indices and functions, coagulation variables, and clinical disease. Serum TPO was nearly 4-fold higher acutely compared with the control (median 207 pg/mL, range 56-1258 pg/mL vs. median 58 pg/mL, range 11-241 pg/mL, P < 0.001) and coincided with high mean platelet volume (MPV) and immature platelet fraction (IPF%). Prothrombin fragments and D-dimer were high acutely compared with the control (F1 + 2 median 704 pmol/L, range 284-1875 pmol/ L vs. median 249 pmol/L, range 118-556 pmol/L, P < 0.001; D-dimer median 2.8 mg/L, range 0.6-34.0 mg/L vs. median 0.4 mg/L, range 0.2-1.1 mg/L, P < 0.001), and associated with low platelet count and severe acute kidney injury (AKI). MPs' procoagulant activity was high acutely only among patients with mild AKI (plasma creatinine below the median at the time of the measurement). Upregulated TPO together with high MPV and IPF% confirm active thrombopoiesis, but do not predict severity of HFRS. Simultaneously, elevated prothrombin fragments and D-dimer suggest increased consumption of platelets in patients with severe AKI. Activity of platelet-derived MPs in HFRS should be studied with flow cytometry in a larger cohort of patients.

Hantaviruses have co-existed with their hosts for millions of years. Seewis virus (SWSV), a soricomorph-borne hantavirus, is widespread in Eurasia, ranging from Central Siberia to Western Europe. To gain insight into the phylogeography and evolutionary history of SWSV in Finland, lung tissue samples of 225 common shrews (Sorex araneus) trapped from different parts of Finland were screened for the presence of SWSV RNA. Forty-two of the samples were positive. Partial small (S), medium (M) and large (L) segments of the virus were sequenced, and analyzed together with all SWSV sequences available in Genbank. The phylogenetic analysis of the partial Ssegment sequences suggested that all Finnish SWSV strains shared their most recent common ancestor with the Eastern European strains, while the L-segment suggested multiple introductions. The difference between the Land S-segment phylogenies implied that reassortment events play a role in the evolution of SWSV. Of the Finnish strains, variants from Eastern Finland occupied the root position in the phylogeny, and had the highest genetic diversity, supporting the hypothesis that SWSV reached Finland first form the east. During the spread in Finland, the virus has formed three separate lineages, identified here by correlation analysis of genetic versus geographic distance combined with median-joining network analysis. These results support the hypothesis that Finnish SWSV recolonized Finland with its host, the common shrew, from east after the last ice age 12,000-8000 years ago, and then subsequently spread along emerging land bridges towards west or north with the migration and population expansion of its host.

Introduction: Puumala hantavirus (PUUV) causes a mild type of hemorrhagic fever with renal syndrome characterized by acute kidney injury (AKI), increased capillary leakage, and thrombocytopenia. Albuminuria and hematuria in dipstick urine test at hospital admission are known to predict the severity of upcoming AKI. Methods: We analyzed dipstick urine glucose in 195 patients with acute PUUV infection at hospital admission, and divided them into 2 categories according to the presence or absence of glucose in the dipstick urine test. Determinants of disease severity were analyzed in glucosuric and nonglucosuric patients. Results: Altogether, 24 of 195 patients (12%) had glucosuria. The patients with glucosuria had more severe AKI than patients without glucosuria (median maximum creatinine concentration 459 mmol/l, range 78-1041 mmol/l vs. 166 mmol/l, range 51-1499 mmol/l; P < 0.001). The glucosuric patients had more severe thrombocytopenia (median minimum platelet count 41 Â 10 9 /l, range 5-102 Â 10 9 /l vs. 62 Â 10 9 /l, range 3-249 Â 10 9 /l; P ¼ 0.006), and more pronounced signs of increased capillary leakage (change in weight, maximum plasma hematocrit, minimum plasma albumin). The glucosuric patients were more often in clinical shock at admission (20.8% vs. 1.2%; P < 0.001) and the length of hospital stay was longer (median 7.5 days, range 4-22 days vs. 6 days, range 2-30 days; P ¼ 0.009). Conclusion: Glucosuria is relatively rare, but when present it predicts a more severe disease course in patients with acute PUUV infection.

Hantaviruses are zoonotic pathogens that have severe harmful effects on humans. They belong to a completely different genus in the Bunyaviridae family as they are rodent-borne viruses. They have a persistent life cycle in their primary hosts without causing any infection, however, they can infect humans in case of any contact with rodents or inhalation of aerosolized contaminated rodent droppings or saliva. Hantavirus has a wide geographic dispersal and is found in all the continents except Antarctica. Since their first encounter in the 1950s during the Korean conflict, it has been a threat to humans. Hantavirus syndrome can result in either Hemorrhagic Fever with Renal Syndrome (HFRS), which is more prevalent in America, and Hantavirus Cardiopulmonary Syndrome (HCPS) prevalent in Eurasia. These viruses have caused approximately 2,00,000 infections worldwide in recent years. In this review, we provide a summary of the progress made in understanding the hantavirus epidemiology, different vaccines, drugs, pathogenesis, clinical features, model systems used for hantavirus studies, treatments, and preventions associated with the virus.

Since 1995 when the first case of hantavirus pulmonary syndrome (HPS) was reported in Patagonia, there have been more than 400 cases of HPS reported in five countries in South America. The first case of HPS was associated with Andes (AND) virus. In this study, we report on the genetic diversity, geographical distribution, and serological features of hantavirus infection in six countries in South America based on 87 HPS cases from Argentina, Bolivia, Chile, Paraguay, and Uruguay. An early immunoglobulin M (IgM), IgA, and IgG humoral response was observed in almost all HPS cases. The IgM response appears to peak 1 or 2 days after the onset of symptoms. Peak IgG antibody titers occur mostly after the first week. Low IgG titers or the absence of IgG was associated with higher mortality rates. The IgA response peaks around day 15 and then rapidly decreases. The results of phylogenetic analysis based on partial M-fragment G1- and G2-encoding sequences showed that HPS cases from the five c...

Andes orthohantavirus (ANDV) is a New World hantavirus that is a major cause of hantavirus cardiopulmonary syndrome (HCPS; also referred to as hantavirus pulmonary syndrome) in South America, particularly in Chile and Argentina. ANDV is one of the few hantaviruses for which there is a reliable animal model, the Syrian hamster model, which recapitulates important aspects of human disease.

Barrera et al Conclusiones: Los hallazgos demuestran exposición previa a Rickettsia sp. y a Hantavirus en la población indígena de Tuchín. Los resultados pueden ser útiles para establecer una alerta sobre estas fiebres hemorrágicas. Aunque no se hallaron seropositivos para Chikungunya, este fue el primer trabajo de vigilancia epidemiológica realizado en Colombia sobre este virus.

We report here the complete genomic sequence of the Chilean human isolate of Andes virus CHI-7913. The S, M, and L genome segment sequences of this isolate are 1,802, 3,641 and 6,466 bases in length, with an overall GC content of 38.7%. These genome segments code for a nucleocapsid protein of 428 amino acids, a glycoprotein precursor protein of 1,138 amino acids and a RNA-dependent RNA polymerase of 2,152 amino acids. In addition, the genome also has other ORFs coding for putative proteins of 34 to 103 amino acids. The encoded proteins have greater than 98% overall similarity with the proteins of Andes virus isolates AH-1 and Chile R123. Among other sequenced Hantavirus, CHI-7913 is more closely related to Sin Nombre virus, with an overall protein similarity of 92%. The characteristics of the encoded proteins of this isolate, such as hydrophobic domains, glycosylation sites, and conserved amino acid motifs shared with other Hantavirus and other members of the Bunyaviridae family, are identified and discussed.

We assessed the utility of an enzyme-linked immunosorbent assay (ELISA) for the detection of hantavirus-specific antibodies from sera of Oligoryzomys longicaudatus, the principal reservoir of Andes virus (ANDV), using an antigen previously developed for detection of antibodies to Sin Nombre virus (SNV) in sera from Peromyscus maniculatus. The assay uses a protein A/G horseradish peroxidase conjugate and can be performed in as little as 1.5 hours. Serum samples from Oligoryzomys longicaudatus collected in central-south Chile were used and the assay identified several that were antibody positive. This assay can be used for the rapid detection of antibodies to divergent hantaviruses from geographically and phylogenetically distant rodent species.

Background: Andes orthohantavirus (ANDV) is the sole etiologic agent of Hantavirus Cardiopulmonary Syndrome in Chile and, until now, the only Hantavirus known to be transmitted by person-to-person route. The main risk of person-to-person transmission is to be a sexual partner of an index case, and deep kissing the main mechanism of infection. Experimental reports suggest that ANDV infection can be inhibited by some saliva components. Therefore, some host factors like saliva quality, could help to explain why some individuals do not become infected even though their exposure to the virus is high. Aim: To compare some saliva components, such cytokines and mucins, between ANDV-infected cases (exposed-sick), their close household contacts (exposed-not sick) and healthy control not exposed. Methods: Sixty-nine confirmed ANDV-infected cases, 76 close household contacts exposed to ANDV but not infected (CHC) and 39 healthy control not exposed (HCNE). The following components were measured in saliva: secretory immunoglobulin A (sIgA) by ELISA; cytokines (IL1β, IL12p70, TNFα, INFy, IL10, IL6, VEGF, IP10, and IL8) by Multiplex Assay and mucins MUC7 and MUC5B by Western Blotting. Results: Among infected cases, CHC and HCNE analyzed 74, 45, and 33% were men, respectively (p ≤ 0.05). The average age for cases, CHC and HCNE was 37.7, 28.7, and 32 years, respectively (p ≤ 0.05). The average concentration of sIgA in infected cases was 4.846 mg/mL, higher than for CHC group, 0.333 mg/mL (p ≤ 0.05). For cytokines, significant differences were found comparing all groups for IFNy, IL12p70, and IL8. Among CHC group, there was a higher frequency of detection of MUC7 isoform (62.6%; 31/49) compared to ANDV-infected cases (40.5%; 17/42) (p < 0.05). Similarly, presence of MUC5B was higher among CHC groups (62.16%; 46/74) than in ANDV-infected cases (44.4%; 28/63) (p < 0.05). Conclusions: Three salivary components showed differences between infected cases and close household contacts (sIgA, cytokines, and mucins). These differences can be Martinez-Valdebenito et al. Oral Immunity in ANDV Cases explained by the acute state of the disease in the ANDV-infected cases group. However, the differences in MUC5B and isoforms of MUC7 are not entirely explainable by the infection itself. This work represents a novel description of salivary components in the context of ANDV infection.

Sociodemographic risk factors of hantavirus cardiopulmonary syndrome Background: Hantavirus cardiopulmonary syndrome (HCPS) is caused by new world hantaviruses, among which Andes hantavirus (ANDV) is endemic to Chile and Southern Argentina. The disease caused by ANDV produces plasma leakage leading to enhanced vascular permeability and has a high case fatality rate (35%), mainly due to respiratory failure, pulmonary edema and myocardial dysfunction, hypoperfusion and shock. Host sociodemographic and genetic factors might influence the course and outcome of the disease. Yet, they have not been thoroughly characterized. Aim: To evaluate sociodemographic factors as risk factors in severity of HCPS. Patients and Methods: Study period: 2004-20013, attending in eight collaborative centers, etiological diagnosis was performed by serology or molecular biology, mild and severe HCPS were compared.139 Chilean patients were analyzed, 64 (46%) with severe disease among which 12 (19 %) died. Results: European ethnicity had 5,1 times higher risk than Amerindian ethnic group to develop a severe HCPS, greater seriousness that was also associated with an urban residence. Conclusion: It was observed that ethnicity and type of residence were significant risk factors for HCPS severity. Hypotheses explaining these findings are discussed.

Background: Hantavirus cardiopulmonary syndrome (HCPS) has a mortality up to 35–40% and its treatment is mainly supportive. A variable to predict progression from mild to severe disease is unavailable. This study was performed in patients with documented infection by Andes orthohantavirus, and the aim was to find a simple variable to predict progression to moderate/severe HCPS in patients with mild disease at admission. Methods: We performed a retrospective analysis of 175 patients between 2001 and 2018. Patients were categorized into mild, moderate, and severe disease according to organ failure and advanced support need at hospital admission (e.g., mechanical ventilation, vasopressors). Progression to moderate/severe disease was defined accordingly. Clinical and laboratory variables associated with progression were explored. Results: Forty patients with mild disease were identified; 14 of them progressed to moderate/severe disease. Only platelet count was different between those wh...

Results. A total of 78 recruits participated in the study. The participants were male and the mean age was 21 years (SD 4.9). In the first two weeks of training, nine recruits reported to outpatient clinics for their ILI, resulting in an attack rate of 12%. Fifty-five recruits returned symptom diary cards with at least 13 days of records between visit 1 and visit 2. Among them, four trainees visited clinics for ILI while additional 14 trainees reported at least one day of ILI without seeking healthcare. The proportion of patients not seeking care was 78%. The attack rate of self-reported ILI (to health clinics or on symptom cards) was 33% (18/55). The self-reported ILI participants reported a median of 2 days of having ILI (range: 1-7 days). Conclusion. Our data showed that the majority of trainees reporting ILI did not seek healthcare. The attack rate based on clinic attendance largely underestimated the ILI burden. Understanding reasons and obstacles of trainees not seeking care would be crucial in infection control and reduction of ILI transmission among basic training recruits who are at high risk of ILI. Disclosures. All authors: No reported disclosures.

Genetic susceptibility to Andes Hantavirus: Association between severity of disease and HLA alleles in Chilean patients Andes hantavirus (ANDV) infection in Chile has a variable clinical expression, and infected individuals may present with different grades of disease severity. This study aimed to determine if clinical expression of ANDV infection in Chilean patients is associated with the HLA system. HLA alleles A, B, DRB1 and DQB1, were studied in two groups of patients with confirmed ANDV infection: 41 patients with a mild disease course (without respiratory failure and cardiovascular shock) and 46 patients with a severe disease course (with respiratory failure and shock). Molecular typing of HLA system was performed by SSP-PCR. The HLA-DRB1*15 allele, was significantly more common in the group of patients with mild disease (p = 0,007) and thus for possibly associated with a protective effect against ANDV infection. Conversely, HLA-B*08 was more common in patients with severe disease (p = 0,06). Although the association was marginally significant, allele HLA-B*08 may be linked to an increased susceptibility to the severe clinical course of HCPS by ANDV.

Andes virus (ANDV) is the predominant etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in southern South America. In Chile, serologically confirmed human hantavirus infections have occurred throughout a wide latitudinal distribution extending from the regions of Valparaíso (32 to 33°S) to Aysén (46°S) in southern Patagonia. In this study, we found seropositive rodents further north in the Coquimbo region (30°S) in Chile. Rodent seroprevalence was 1.4%, with Oligoryzomys longicaudatus displaying the highest seroprevalence (5.9%), followed by Abrothrix longipilis (1.9%) and other species exhibiting ≤0.6% seropositivity. We sequenced partial ANDV small (S) segment RNA from 6 HCPS patients and 32 rodents of four different species collected throughout the known range of hantavirus infection in Chile. Phylogenetic analyses showed two major ANDV South (ANDV Sout) clades, congruent with two major Chilean ecoregions, Mediterranean (Chilean matorral [shrubland]) and Valdivian t...

Hantavirus cardiopulmonary syndrome (HCPS) is a highly pathogenic emerging disease (40% case fatality rate) caused by New World hantaviruses. Hantavirus infections are transmitted to humans mainly by inhalation of virus-contaminated aerosol particles of rodent excreta and secretions. At present, there are no antiviral drugs or immunotherapeutic agents available for the treatment of hantaviral infection, and the survival rates for infected patients hinge largely on early virus recognition and hospital admission and aggressive pulmonary and hemodynamic support. In this study, we show that Andes virus (ANDV) interacts with human apolipoprotein H (ApoH) and that ApoH-coated magnetic beads or ApoH-coated enzyme-linked immunosorbent assay plates can be used to capture and concentrate the virus from complex biological mixtures, such as serum and urine, allowing it to be detected by both immunological and molecular approaches. In addition, we report that ANDV-antigens and infectious virus a...

See the editorial commentary by Montgomery et al., on pages 1553-5.) Background. Andes virus (ANDV) infection, which has a case fatality rate of 37% in Chile, often occurs in household clusters and may be transmitted from person to person. Methods. To determine the incidence and risk factors for additional household cases, we conducted a prospective study among recent household contacts of persons with hantavirus cardiopulmonary syndrome (HCPS) in Chile, including testing of serum for anti-hantavirus antibodies and blood cells for ANDV RNA by reversetranscription polymerase chain reaction (RT-PCR). Results. We enrolled 76 index case patients and 476 household contacts, of whom 16 (3.4%) developed HCPS; 32.6% of 92 cases occurred in household clusters. The risk of HCPS was 17.6% among sex partners of index case patients, versus 1.2% among other household contacts (). Person-to-person transmission was definite in P ! .001 3, probable in 9, and possible in 2 of the 16 additional household case patients. We detected ANDV RNA by RT-PCR in peripheral blood cells 5-15 days before the onset of symptoms or the appearance of anti-hantavirus antibodies. Conclusions. In recent household contacts of persons with HCPS in Chile, the risk of HCPS was greatest among sex partners. Among the household contacts who developed HCPS, viremia preceded the onset of symptoms and the appearance of anti-hantavirus antibodies by up to 2 weeks. Hantavirus cardiopulmonary syndrome (HCPS) occurs throughout much of the Americas [1-7]. More cases (480) have been reported in Chile, where the case fatality rate is 37%, than in the United States (451), and Andes virus (ANDV), the etiologic agent of all known cases in Chile and of most cases in Argentina, is the

Hantavirus cardiopulmonary syndrome (HCPS) is an emerging infectious disease first reported in Chile in 1995. Andes hantavirus (ANDV) is responsible for the more than 500 cases of HCPS reported in Chile. Previous work showed that ANDV is genetically differentiated in Chile across contrasting landscapes. To determine whether the reservoir rodent (Oligoryzomys longicaudatus) populations are also geographically segregated, we conducted range-wide spatial genetic analyses of O. longicaudatus in Chile using the mitochondrial DNA cytochrome b gene. Given that landscape structure influences the incidence of hantavirus infections, we also tested 772 O. longicaudatus specimens for antibodies to ANDV captured during the period 2000 − 2006. Population genetic analyses of O. longicaudatus are largely congruent with those reported for ANDV, with the host primarily differentiated according to three defined ecoregions, Mediterranean, Valdivian rain forest and North Patagonian rain forest. Significant differences in the relative prevalence of anti-ANDV antibodies in rodent samples also were found across the three ecoregions. We relate these results to the number of reported human HCPS cases in Chile, and discuss the importance of landscape differences in light of ANDV transmission to humans and among rodent populations.

Background Information on the sequential appearance, duration, and magnitude of clinical and laboratory parameters in hemorrhagic fever with renal syndrome (HFRS) is limited. Methods Analysis of clinical and laboratory parameters obtained serially in 81 patients with HFRS, of whom 15 were infected with Dobrava virus and 66 with Puumala virus. Results The initial signs/symptoms, appearing on median day 1 of illness, were fever, headache, and myalgia. These were present in 86%, 65%, and 40% of patients and had a median duration of 4, 4, and 5.5 days, respectively. The signs/symptoms were followed by myopia (appearance on day 5), insomnia (day 6), oliguria/anuria (day 6), polyuria (day 9), and sinus bradycardia (day 9.5). These were present in 35%, 30%, 28%, 91%, and 35% of patients; their median duration was 2, 2, 2, 7, and 1 day, respectively. Laboratory abnormalities, including thrombocytopenia, elevated alanine aminotransferase, CRP, procalcitonin, creatinine, diminished glomerular filtration rate, and leukocytosis, were ascertained on admission to hospital or on the following day (day 5 or 6 of illness) and were established in 95%, 87%, 99%, 91%, 94%, 87%, and 55% of patients, and had a median duration of 4, 3, 7, 3, 9, 8, and 2 days, respectively. Comparison of patients infected with Dobrava and Puumala viruses found several differences in the frequency, magnitude, and duration of abnormalities, indicating that Dobrava virus causes the more severe HFRS.

Paraná state presents the fourth highest number of accumulated cases of hantavirus pulmonary syndrome in Brazil. To map the risk areas for hantavirus transmission we carried out a study based on rodent trapping and determined the anti-hantavirus seroprevalence in these animals and in the inhabitants of these localities. Overall seroprevalence in rodents and humans were 2.5% and 2.4%, respectively. Eighty-two percent of the seropositive rodents were genetically analyzed. Phylogenetic analyses revealed that hantaviruses from rodent samples cluster with Araucá ria (Juquitiba-like) or Jaborá hantavirus genotypes. The Jaborá strain was identified in Akodon serrensis and Akodon montensis, whereas the Araucá ria strain was detected in Oligoryzomys nigripes, Oxymycterus judex, A. montensis, and Akodon paranaensis, with the latter species being identified for the first time as a natural host. These findings expose the complex relationships between virus and reservoirs in Brazil, which could have an impact on hantavirus transmission dynamics in nature and human epidemiology.

To date, only two rodent-borne hantaviruses have been detected in sub-Saharan Africa. Here, we report the detection of a yet unknown hantavirus in a Natal mastomys (Mastomys natalensis) in Méliandou, Guinea, in 2014. The phylogenetic placement of this virus suggests that it might represent a cross-order spillover event from an unknown bat or eulipotyphlan host.

Objective. To search Hantavirus and Arenavirus in small rodents and establish their spatial distribution in disturbed ecosystems in the municipality of Villavicencio, Meta, Colombia. Materials and method. A descriptive cross-sectional study was carried out from October 2018 to October 2019 in periurban and rural areas of the municipality of Villavicencio. Rodents were captured using Sherman-type traps and molecular detection of Hantavirus and Arenavirus was carried out by Polymerase chain Reaction technique. Results. A total of 50 rodents were captured belonged to 3 families and six species, the Muridae (76%) with the highest number of captured individuals, Cricetidae (22%) and Echimydae (2%). All samples were negative for the molecular markers of Hantavirus and Arenavirus. Conclusions. The study of mammalian hosts, particularly small rodents contribute to monitor diseases transmitted by these small mammals that act as reservoirs.

We studied seven cases of Hantavirus infection and renal involvement who presented at our institute in last 4 months. Their demographic profile and presenting ABSTRACT Background: Hantavirus infections are found all over world but there is paucity of information about clinical features of Hantavirus infection in India. Aim of current study was to study clinical profile and outcome of patients with Hantavirus infection and renal insufficiency who presented at our institute. Methods: All patients who were admitted in department of medicine with Hantavirus infection and renal insufficiency were included. Their basic demographic profile with relevant laboratory investigations was recorded. They were diagnosed with Hantavirus infection if they had positive IgM antibodies by ELISA test. Results: There were seven patients with mean age of 54 years. They had mean serum creatinine level of 4.37 ± 1.86 mg%. All had thrombocytopenia and hepatic dysfunction as well. Five patients had hypotension. There was need of dialysis in three patients. They also had hypoalbuminemia. No patient had features suggestive of acute respiratory distress syndrome. All patients had recovery of renal function and there was no mortality. Conclusion: Patients with Hantavirus infection presented like hemorrhagic fever with renal syndrome. Their outcome is good. We need to suspect Hantavirus infection in appropriate clinical scenario in India.

Background: Hantaviruses are a group of emerging pathogens causing hemorrhagic fever with renal syndrome and Hantavirus cardiopulmonary syndrome in human. This study was conducted to investigate Hantavirus infection among Iranian viral hemorrhagic fever suspected patients. Methods: From April 2014 to June 2016, 113 cases from 25 different provinces of Iran were analyzed for Hantavirus infection by IgM/IgG ELISA and pan-Hantavirus RT-PCR tests. Results: Although, viral genome was detected in none of the subjects, IgM and IgG antibodies were detected in 19 and 4 cases, respectively. Differentiation of the anti-Hantavirus antibodies according to virus species by EUROLINE Anti-Hantavirus Profile kit revealed 3 Puumala virus IgM positive , 1 Hantaan virus IgM positive, 1 Hantaan virus IgM borderline and 2 Puumala virus IgG borderline cases. Conclusions: This study demonstrates the circulation of Hantaviruses in Iran and calls for further investigations of these life-threatening viruses in the country.

Tag der mündlichen Prüfung: 16.02.2012 estimate the pathogenic potential of SANGV in comparison to GRW/Aa. We have found that SANGV exclusively recognizes β1 integrins as cellular entry receptors and elicits strong induction of IFN-λ1 in infected cells. Therefore, in cultivated host cells SANGV exhibits functional characteristics distinct from GRW/Aa. Whether these properties contribute to SANGV-mediated pathogenesis in humans needs to be elucidated in future studies.