Hantavirus Pulmonary Syndrome Research Articles

Orthohantaviruses belonging to three phylogroups all inhibit apoptosis in infected target cells

Orthohantaviruses, previously known as hantaviruses, are zoonotic viruses that can cause hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS) in humans. The HPS-causing Andes virus (ANDV) and the HFRS-causing Hantaan virus (HTNV) have anti-apoptotic effects. To investigate if this represents a general feature of orthohantaviruses, we analysed the capacity of six different orthohantaviruses – belonging to three distinct phylogroups and representing both pathogenic and non-pathogenic viruses – to inhibit apoptosis in infected cells. Primary human endothelial cells were infected with ANDV, HTNV, the HFRS-causing Puumala virus (PUUV) and Seoul virus, as well as the putative non-pathogenic Prospect Hill virus and Tula virus. Infected cells were then exposed to the apoptosis-inducing chemical staurosporine or to activated human NK cells exhibiting a high cytotoxic potential. Strikingly, all orthohantaviruses inhibited apoptosis in both settings. Moreover, we show that the nucleocapsid (N) protein from all examined orthohantaviruses are potential targets for caspase-3 and granzyme B. Recombinant N protein from ANDV, PUUV and the HFRS-causing Dobrava virus strongly inhibited granzyme B activity and also, to certain extent, caspase-3 activity. Taken together, this study demonstrates that six different orthohantaviruses inhibit apoptosis, suggesting this to be a general feature of orthohantaviruses likely serving as a mechanism of viral immune evasion.

Two Point Mutations in Old World Hantavirus Glycoproteins Afford the Generation of Highly Infectious Recombinant Vesicular Stomatitis Virus Vectors.

Rodent-to-human transmission of hantaviruses is associated with severe disease. Currently, no FDA-approved, specific antivirals or vaccines are available, and the requirement for high biocontainment (biosafety level 3 [BSL-3]) laboratories limits hantavirus research. To study hantavirus entry in a BSL-2 laboratory, we set out to generate replication-competent, recombinant vesicular stomatitis viruses (rVSVs) bearing the Gn and Gc (Gn/Gc) entry glycoproteins. As previously reported, rVSVs bearing New World hantavirus Gn/Gc were readily rescued from cDNAs, but their counterparts bearing Gn/Gc from the Old World hantaviruses, Hantaan virus (HTNV) or Dobrava-Belgrade virus (DOBV), were refractory to rescue. However, serial passage of the rescued rVSV-HTNV Gn/Gc virus markedly increased its infectivity and capacity for cell-to-cell spread. This gain in viral fitness was associated with the acquisition of two point mutations: I532K in the cytoplasmic tail of Gn and S1094L in the membrane-proximal stem of Gc. Follow-up experiments with rVSVs and single-cycle VSV pseudotypes confirmed these results. Mechanistic studies revealed that both mutations were determinative and contributed to viral infectivity in a synergistic manner. Our findings indicate that the primary mode of action of these mutations is to relocalize HTNV Gn/Gc from the Golgi complex to the cell surface, thereby affording significantly enhanced Gn/Gc incorporation into budding VSV particles. Finally, I532K/S1094L mutations in DOBV Gn/Gc permitted the rescue of rVSV-DOBV Gn/Gc, demonstrating that incorporation of cognate mutations into other hantaviral Gn/Gc proteins could afford the generation of rVSVs that are otherwise challenging to rescue. The robust replication-competent rVSVs, bearing HTNV and DOBV Gn/Gc, reported herein may also have utility as vaccines.IMPORTANCE Human hantavirus infections cause hantavirus pulmonary syndrome in the Americas and hemorrhagic fever with renal syndrome (HFRS) in Eurasia. No FDA-approved vaccines and therapeutics exist for these deadly viruses, and their development is limited by the requirement for high biocontainment. In this study, we identified and characterized key amino acid changes in the surface glycoproteins of HFRS-causing Hantaan virus that enhance their incorporation into recombinant vesicular stomatitis virus (rVSV) particles. The replication-competent rVSVs encoding Hantaan virus and Dobrava-Belgrade virus glycoproteins described in this work provide a powerful and facile system to study hantavirus entry under lower biocontainment and may have utility as hantavirus vaccines.

Clinical and anatomopathological aspects of patients with hantavirus cardiopulmonary syndrome in Uberaba, Minas Gerais, Brazil.

ABSTRACTThe hantavirus cardiopulmonary syndrome is considered an emerging disease in the Americas. Since 1993, thousands of cases have been reported from different countries, but mainly from Brazil. This study aims to describe some epidemiological, clinical and anatomopathological aspects of patients with hantavirus who presented poor outcome and were autopsied in a teaching hospital in Brazil, from 2000 to 2014. Of the 10 patients included, nine were male (mean age 43.5 years) and seven reported previous contact with rodents. Fever was present in eight of ten patients, dyspnea in nine of ten and myalgia in seven of ten patients; hemoconcentration, leukocytosis, thrombocytopenia and renal involvement were evidenced in all the 10 cases. At autopsy, the main alterations were seen in the lungs: pleural effusion (8/10 cases), increased weight 2.5 to 3 times, congestion/edema (10/10), interstitial mononuclear inflammation (10/10), alveolar hemorrhage (7/10), pulmonary collapse (7/10), hyaline membranes (7/10) and alveolar neutrophilic infiltrate (2/10). Pericardial effusion (2/10), mild myocardium inflammation (4/10), right ventricle dilation (1/10), polyploidy nuclei (3/10) and pericardial diffuse petechial (1/10) were also observed. The other organs exhibited discrete and non-specific alterations. Currently, this syndrome continues to be associated with high mortality directly linked to a late diagnosis and/or a misdiagnosis in the medical centers where these patients were seen for the first time. The anatomopathological findings at autopsy revealed the final phase of the process with pulmonary alterations, allowing a direct correlation with the severity of respiratory distress observed in these patients at admission.

CLIMATE CHANGE AND HUMAN INFECTIOUS DISEASES (REVIEW)

The Intergovernmental Panel on Climate (IPCC) has concluded that climate change has significant effects on human health. In order to understand how climate change impacts infectious diseases; it is essential to understand the pathways of disease transmission. Diseases transmitted directly from source of infection to the affected individual are least affected by environmental factors. If diseases are transmitted indirectly through a physical vehicle or a biological vector, climate change will have significant effect on disease transmission through the effect on the vehicle or the vector and the pathogen. The effect of climate change varies from one region to the other. Moreover, vulnerability to the effects of climate change varies from one individual to the other, from one group to the other and from one country to the other. Disease transmission is also affected by socio-economic factors, globalization of travel and trade, land use, unplanned urbanization, population growth, and cultural attitudes, among other factors.Diseases transmitted via direct pathways include air-borne diseases like influenza, tuberculosis, measles or sexually transmitted diseases. Food-borne diseases and water-borne diseases like cholera and diarrhoeal diseases are transmitted indirectly, via physical vehicle.Mosquitoes are the best known biological disease vectors. Diseases transmitted indirectly through mosquitoes can be transmitted either by mosquito-human-mosquito pathway such as malaria, dengue, yellow fever, chicungunia, zika and lymphatic filariasis; or by mosquito-animal-mosquito pathway such as west Nile virus disease, Rift valley fever and Saint Louis encephalitis.Diseases transmitted indirectly via biological vectors also include tick-borne diseases such as lyme disease, tick-borne relapsing fever, typhus, Q fever and Rocky Mountain spotted fever; sandfly-borne diseases such as leishmaniasis; and rodent-borne diseases such as leptospirosis, hantavirus pulmonary syndrome, tularemia and plague through fleas. Diseases can also be transmitted indirectly through other vectors like tse-tse fly, black fly, triatomine bug and aquatic snails.Beginning in mid-1970s, there has been worldwide emergence, resurgence and redistribution of infectious diseases. Definitions of emerging diseases were given as well as examples of climate change impacts on emerging diseases. Examples given included west Nile virus disease, hantavirus pulmonary syndrome, Saint Louis encephalitis, Murray valley fever and Zika.

Hantavirus pulmonary syndrome in children: case report and case series from an endemic area of Brazil.

ABSTRACTHantavirus Cardiopulmonary Syndrome (HCPS) is an important emergent zoonosis associated with wild rodents in Brazil, where this viral infection in children is generally rare. We present HCPS in a child from the Pantanal Biome and a review of all reported pediatric cases in Mato Grosso State, an endemic area for HCPS in Brazil. The investigation used the Information System for Notifiable Diseases database (SINAN). A 12-year-old boy was hospitalized with fever and respiratory failure and hantavirus IgM and IgG antibodies were detected by ELISA in serum samples. During the period of 1999 to 2016, 32 HCPS pediatric cases confirmed by serology were reported to SINAN with a mortality rate of 34.4%. The possibility of hantavirus infection in children with acute febrile illness associated with respiratory failure should be considered mainly in recognized endemic areas as Mato Grosso State, contradicting a hypothesis that children are more protected from lung involvement.

Hantavirus entry: Perspectives and recent advances.

Hantaviruses are important zoonotic pathogens of public health importance that are found on all continents except Antarctica and are associated with hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. Despite the significant disease burden they cause, no FDA-approved specific therapeutics or vaccines exist against these lethal viruses. The lack of available interventions is largely due to an incomplete understanding of hantavirus pathogenesis and molecular mechanisms of virus replication, including cellular entry. Hantavirus Gn/Gc glycoproteins are the only viral proteins exposed on the surface of virions and are necessary and sufficient to orchestrate virus attachment and entry. In vitro studies have implicated integrins (β1-3), DAF/CD55, and gC1qR as candidate receptors that mediate viral attachment for both Old World and New World hantaviruses. Recently, protocadherin-1 (PCDH1) was demonstrated as a requirement for cellular attachment and entry of New World hantaviruses in vitro and lethal HPS in vivo, making it the first clade-specific host factor to be identified. Attachment of hantavirus particles to cellular receptors induces their internalization by clathrin-mediated, dynamin-independent, or macropinocytosis-like mechanisms, followed by particle trafficking to an endosomal compartment where the fusion of viral and endosomal membranes can occur. Following membrane fusion, which requires cholesterol and acid pH, viral nucleocapsids escape into the cytoplasm and launch genome replication. In this review, we discuss the current mechanistic understanding of hantavirus entry, highlight gaps in our existing knowledge, and suggest areas for future inquiry.

2502. Host Susceptibility to Andes Hantavirus Infection Associates to a Single Nucleotide Polymorphism at the αVβ3 Integrin

BackgroundANDV is etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in Chile. Transmission occurs mainly by exposure to aerosolized excretes of infected rodents, person-to-person transmission has also been reported. ANDV infected endothelial cell through αV,β3 integrin at plexin-semaphorin-integrin (PSI) domain. In vitro assays establish that the change from leucine to proline, at residues 33 in PSI-domain inhibits ANDV recognition of integrin. Here we assessed the risk that represents a polymorphism leucine to proline (L33P) and the association to susceptibility to ANDV.MethodsFor risk assessment, 74 cases and 105 controls (exposed but not infected) were genotyped by Taqman assay, epidemiological and demographic data were recorded. We also evaluated SNP distribution at general population, infected population (serum collection) and 11 prospectively diagnosed ANDV cases. A regression logistic model was used to assess environmental or person to person risks factors of hantavirus infection either in presence or absence of the “susceptible” or “protective” genotypes.ResultsIn cases and controls the susceptible (TT) genotype (Leucine) was distributed in an 89.2 and 60%, respectively (Figure 1). The protective genotype (CC) was absent among cases but present at 11.4% in exposed controls. We estimated the Odds ratio (OR), through a logistic model, first using only previously described risk activities and after adding the genotype TT; the OR increased from 6.2 to 12.6. Cases and control at same exposure (access to abandoned place) showed that controls have a 57% of TT genotype, meanwhile in cases was 91%, with an OR of 7.3. For a second common exposure activities (handle woods) the controls had a 59.4% of TT genotype, meanwhile for cases 85%. For general and infected population both did not show statistical differences in allele distribution, and we detected a 1.7% of CC genotype in the infected population (Figure 2). We did not detected CC genotypes in the eleven prospective ANDV cases.ConclusionThere was association between this particular SNP and infection susceptibility to ANDV. We highlight the relevance of genetic background in host-virus interaction. Nevertheless, other factors such as innate immune system or viral variability must be explored to fully understand the disease pathogenesis.Disclosures C. Martinez-Valdebenito, FONDECYT1161197: Grant Investigator, Educational grant. ACT1408: Grant Investigator, Research grant. M. Ferres, FONDECYT1161197: Grant Investigator, Research grant. ACT1408: Grant Investigator, Research grant. N. Le Corre, FONDECYT1161197: Grant Investigator, Research grant. ACT1408: Grant Investigator, Research grant. J. Angulo, FONDECYT1161197: Grant Investigator, Research grant. ACT1408: Grant Investigator, Research grant.

Antibodies to abrogate Andes hantavirus

Emerging Infections Andes hantavirus circulates in rodent reservoirs and can cause hantavirus cardiopulmonary syndrome in humans. This results in a potentially lethal disease for which no vaccines or targeted treatments exist. Garrido et al. screened memory B cells from people that had been infected with Andes hantavirus. Antibodies were isolated from one individual with a high viral neutralization capacity. Two of these antibodies were fully protective against disease in a hamster model, even when given several days after infection. These antibodies target distinct epitopes on the viral glycoprotein and could be developed for use alone or as a combination therapy. Sci. Transl. Med. 10 , eaat6420 (2018).

Two recombinant human monoclonal antibodies that protect against lethal Andes hantavirus infection in vivo.

Andes hantavirus (ANDV) is an etiologic agent of hantavirus cardiopulmonary syndrome (HCPS), a severe disease characterized by fever, headache, and gastrointestinal symptoms that may progress to hypotension, pulmonary failure, and cardiac shock that results in a 25 to 40% case-fatality rate. Currently, there is no specific treatment or vaccine; however, several studies have shown that the generation of neutralizing antibody (Ab) responses strongly correlates with survival from HCPS in humans. In this study, we screened 27 ANDV convalescent HCPS patient sera for their capacity to bind and neutralize ANDV in vitro. One patient who showed high neutralizing titer was selected to isolate ANDV-glycoprotein (GP) Abs. ANDV-GP-specific memory B cells were single cell sorted, and recombinant immunoglobulin G antibodies were cloned and produced. Two monoclonal Abs (mAbs), JL16 and MIB22, potently recognized ANDV-GPs and neutralized ANDV. We examined the post-exposure efficacy of these two mAbs as a monotherapy or in combination therapy in a Syrian hamster model of ANDV-induced HCPS, and both mAbs protected 100% of animals from a lethal challenge dose. These data suggest that monotherapy with mAb JL16 or MIB22, or a cocktail of both, could be an effective post-exposure treatment for patients infected with ANDV-induced HCPS.

Protocadherin-1 is essential for cell entry by New World hantaviruses.

The zoonotic transmission of hantaviruses from their rodent hosts to humans in North and South America is associated with a severe and frequently fatal respiratory disease, hantavirus pulmonary syndrome (HPS)1,2. No specific antiviral treatments for HPS are available, and no molecular determinants of in vivo susceptibility to hantavirus infection and HPS are known. Here we identify the human asthma-associated gene protocadherin-1 (PCDH1)3-6 as an essential determinant of entry and infection in pulmonary endothelial cells by two hantavirusesthat cause HPS, Andes virus (ANDV) and Sin Nombre virus (SNV). In vitro, we show that the surface glycoproteins of ANDV and SNV directly recognize the outermost extracellular repeat domain of PCDH1-a member of the cadherin superfamily7,8-to exploit PCDH1 for entry. In vivo, genetic ablation of PCDH1 renders Syrian golden hamsters highly resistant to a usually lethal ANDV challenge. Targeting PCDH1 could provide strategies to reduce infection and disease caused by New World hantaviruses.

Hantavirus Pulmonary Syndrome—The 25th Anniversary of the Four Corners Outbreak

During the spring of 1993, a mysterious respiratory disease struck the Four Corners region of the southwestern United States. Persons who became ill were generally young and previously healthy before succumbing to an acute febrile illness that began with simple influenza-like symptoms and often culminated in death by pulmonary edema and cardiovascular collapse. With astonishing speed and efficiency, a collaborative team of federal, state, and local healthcare workers, including clinicians, epidemiologists, and laboratory scientists, identified a newly discovered species of hantavirus as the causative agent of the outbreak. In the ensuing 25 years, the epidemiology, virology, pathophysiology, clinical course, and treatment of hantavirus pulmonary syndrome have been the focus of ongoing research. Because of its rarity, and because of the need for early acute intervention in the face of precipitous decline, recognition of the unique laboratory profile of hantavirus pulmonary syndrome in the setting of a predisposing exposure history is of paramount importance.

Complete Genome Sequences of Monongahela Hantavirus from Pennsylvania, USA.

Monongahela hantavirus was first identified in deer mice and was later found responsible for hantavirus pulmonary syndrome cases in Pennsylvania and West Virginia in the United States. Here, we report the complete sequences of Monongahela virus S, M, and L genomic segments obtained from a fatal clinical case reported in 1997.

Neutrophil Activation in Acute Hemorrhagic Fever With Renal Syndrome Is Mediated by Hantavirus-Infected Microvascular Endothelial Cells.

Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) in humans. Both diseases are considered to be immunologically mediated but the exact pathological mechanisms are still poorly understood. Neutrophils are considered the first line of defense against invading microbes but little is still known of their role in virus infections. We wanted to study the role of neutrophils in HFRS using blood and tissue samples obtained from Puumala hantavirus (PUUV)-infected patients. We found that neutrophil activation products myeloperoxidase and neutrophil elastase, together with interleukin-8 (the major neutrophil chemotactic factor in humans), are strongly elevated in blood of acute PUUV-HFRS and positively correlate with kidney dysfunction, the hallmark clinical finding of HFRS. These markers localized mainly in the tubulointerstitial space in the kidneys of PUUV-HFRS patients suggesting neutrophil activation to be a likely component of the general immune response toward hantaviruses. We also observed increased levels of circulating extracellular histones at the acute stage of the disease supporting previous findings of neutrophil extracellular trap formation in PUUV-HFRS. Mechanistically, we did not find evidence for direct PUUV-mediated activation of neutrophils but instead primary blood microvascular endothelial cells acquired a pro-inflammatory phenotype and promoted neutrophil degranulation in response to PUUV infection in vitro. These results suggest that neutrophils are activated by hantavirus-infected endothelial cells and may contribute to the kidney pathology which determines the severity of HFRS.

Expansion of the range of Necromys lasiurus (Lund, 1841) into open areas of the Atlantic Forest biome in Rio de Janeiro state, Brazil, and the role of the species as a host of the hantavirus

Necromys lasiurus is a generalist rodent that is thought to be the main reservoir of the Araraquara hantavirus, which causes Hantavirus Pulmonary Syndrome, in the Brazilian Cerrado savanna. This species occurs naturally in the open habitats of the Cerrado, Pantanal and Caatinga biomes, where it often occurs at high densities, although the distribution of the species has recently been observed expanding into the Brazilian state of Rio de Janeiro. This study aimed to map the occurrence of N. lasiurus within the Atlantic Forest of Rio de Janeiro state and discuss the potential role of the species as a reservoir of the Araraquara hantavirus in these areas. The study was based on a comprehensive literature search and four expeditions for the collection of specimens in the state of Rio de Janeiro. The data were used to predict the distribution of N. lasiurus, confirm the distribution of the species in the state, and detect the rates of hantavirus infection in these rodents. Necromys lasiurus has been recorded at 16 localities in 10 municipalities of Rio de Janeiro state. The relative abundance of N. lasiurus was low at all localities, except for the REBIO Poço das Antas and APA-BRSJ, two protected areas. Necromys lasiurus was associated primarily with landscapes dominated by farmland (plantations or pasture) at relatively low altitudes in the vicinity of bodies of water. A total of 204 serum samples were collected, but none were reactive for hantavirus. The distribution of N. lasiurus is expanding into many areas of the anthropogenic matrix, but it is not usually either abundant or dominant in these areas. The relatively reduced abundance of N. lasiurus in Rio de Janeiro and the lack of infection in all the areas investigated indicate that it is unlikely to be a reservoir of hantavirus in this region in the near future.

Silent Orthohantavirus Circulation Among Humans and Small Mammals from Central Minas Gerais, Brazil.

New World orthohantaviruses are emerging RNA viruses that cause hantavirus cardiopulmonary syndrome (HCPS). These viruses are a burden to public health around the world with a lethality rate of around 60%. In South America, rodents of Sigmodontinae subfamily are the main reservoirs of orthohantaviruses. We described a serosurvey for orthohantaviruses circulation in an apparently healthy human population and small mammals from rural areas in Central Minas Gerais State, Brazil. A total of 240 individuals and 50 small mammals (26 rodents belonging to 10 different species and 24 marsupials from 4 different species) were sampled during 2012-2013. The seroprevalence rates of IgG/IgM antibodies in humans were 7.1 and 1.6%, respectively. Only one rodent, an Oligoryzomys nigripes captured in peridomestic area, tested positive for IgG antibodies and viral RNA. Our findings suggest a silent circulation of orthohantaviruses in a region of intensive agriculture production. The detection of seropositive humans in an area with a lack of previous HCPS reports highlights potential oligosymptomatic cases and the need for surveillance strategies that could reduce the risk of future outbreaks.

In All Things There is a Law of Cycles; Pathogen-host Interactions in Hantavirus Infections.

Hantaviruses are carried by rodents, insectivores and bats. Some serotypes are able to cause disease in humans, i.e. hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia, and hantavirus cardio-pulmonary syndrome (HCPS) on the American continent. We examine the multiple factors that drive hantavirus outbreak occurrence in Europe like rodent population structure, habitat suitability and its changes, general climatic and local/temporal meteorological conditions, food availability in its various facets (hard, soft mast), predators, biodiversity and anthropogenic factors.

A High-Throughput Flow Cytometry Screen Identifies Molecules That Inhibit Hantavirus Cell Entry

Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS), which infects more than 200,000 people worldwide. Sin Nombre virus (SNV) and Andes virus (ANDV) cause the most severe form of HCPS, with case fatality ratios of 30%–40%. There are no specific therapies or vaccines for SNV. Using high-throughput flow cytometry, we screened the Prestwick Chemical Library for small-molecule inhibitors of the binding interaction between UV-inactivated and fluorescently labeled SNVR18 particles, and decay-accelerating factor (DAF) expressed on Tanoue B cells. Eight confirmed hit compounds from the primary screen were investigated further in secondary screens that included infection inhibition, cytotoxicity, and probe interference. Antimycin emerged as a bona fide hit compound that inhibited cellular infection of the major HCPS (SNV)- and HCPS (Hantaan)-causing viruses. Confirming our assay’s ability to detect active compounds, orthogonal testing of the hit compound showed that antimycin binds directly to the virus particle and blocks recapitulation of physiologic integrin activation caused by SNV binding to the integrin PSI domain.

Innate immune responses elicited by Sin Nombre virus or type I IFN agonists protect hamsters from lethal Andes virus infections.

Sin Nombre virus (SNV) and Andes virus (ANDV) cause hantavirus pulmonary syndrome (HPS) in humans. Both SNV and ANDV infect Syrian hamsters, but only ANDV causes lethal disease. A co-infection study was performed to determine which virus, SNV or ANDV, would dominate the survival outcome in hamsters. Infection of hamsters with SNV 1 day before ANDV challenge did not result in disease characteristic of the latter virus, and all animals survived challenge. Control animals infected solely with ANDV all succumbed by day 14. In contrast, when viruses were injected at the same site concurrently, all hamsters succumbed to HPS disease. Hantaviruses are segmented viruses; therefore we investigated which segment might be responsible for the protective phenotype of SNV by using two SNV/ANDV reassortant viruses, both with reciprocal M-segments from the other virus (denoted ASA and SAS). Both reassortants asymptomatically infect hamsters, similar to SNV. However, unlike SNV, 1 day prior preinfection with the reassortant virus did not prevent ANDV lethality. The ASA reassortant virus, but not SAS, protected hamsters from lethal ANDV infection when administered 3 days prior to ANDV challenge. Similar to SNV preinfection, the potent innate immune stimulator poly I:C administered to hamsters 1 day before ANDV challenge prevented lethal ANDV disease. Combined, these results suggest that the difference in pathogenicity of SNV and ANDV in hamsters involves differences in early host-pathogen interactions and resultant anti-viral immune responses of both the innate and adaptive immune system.

Habitat, species richness and hantaviruses of sigmodontine rodents within the Interior Atlantic Forest, Paraguay.

Four of the nine sigmodontine tribes have species that serve as reservoirs of rodent-borne hantaviruses (RBO-HV), few have been studied in any depth. Several viruses have been associated with human cases of hantavirus pulmonary syndrome often through peridomestic exposure. Jabora (JABV) and Juquitiba (JUQV), harbored by Akodon montensis and Oligoryzomys nigripes, respectively, are endemic and sympatric in the Reserva Natural de Bosque Mbaracayú (RNBM), Paraguay, a protected area of the Interior Atlantic Forest. Rodent communities were surveyed along a 30 km stretch of the RNBM in eight vegetation classifications (Low, High, Bamboo, Riparian and Liana Forests, Bamboo Understory, Cerrado, and Meadow/Grasslands). We collected 417 rodents from which 11 species were identified; Akodon montensis was the predominant species (72%; 95%CI: 64.7%-76.3%), followed by Hylaeamys megacephalus (15% (11.2%-18.2%)) and Oligoryzomys nigripes (9% (6.6%-12.4%)). We examined the statistical associations among habitat (vegetation class) type, rodent species diversity, population structure (age, sex, and weight), and prevalence of RBO-HV antibody and/or viral RNA (Ab/RNA) or characteristic Leishmania tail lesions. Ab/RNA positive rodents were not observed in Cerrado and Low Forest. A. montensis had an overall Ab/RNA prevalence of 7.7% (4.9%-11.3%) and O. nigripes had an overall prevalence of 8.6% (1.8%-23.1%). For A. montensis, the odds of being Ab/RNA positive in High Forest was 3.73 times of the other habitats combined. There was no significant difference among age classes in the proportion of Ab/RNA positive rodents overall (p = 0.66), however, all 11 RNA-positive individuals were adult. Sex and habitat had independent prognostic value for hantaviral Ab/RNA in the study population; age, presence of tail scar/lesion (19% of the rodents) and weight did not. Adjusting for habitat, female rodents had less risk of becoming infected. Importantly, these data suggest habitat preferences of two sympatric rodent reservoirs for two endemic hantaviruses and the importance of including habitat in models of species diversity and habitat fragmentation.

Hantavirus pulmonary syndrome in the central endemic region of argentina. Clinical-epidemiological characteristics of patients assisted in a Reference Center for Infectious Diseases

Background: Introduction: Hantavirus pulmonary syndrome (HPS) is an emerging zoonotic disease in our country, transmitted to humans by infected rodents. The endemic areas are 4: Northwest, Central, Northeast and Southwest area. Infection rates in wild reservoirs are variable, with seasonal fluctuations. In recent years there has been an increase in cases attributed to biological factors due to changes in the environment. Objective: To describe the epidemiological profile of assisted cases in a specialized center Methods & Materials: A descriptive and observational study. We analyzed the medical records of patients with confirmed diagnosis of HPS assisted in a referral center in the city of Buenos Aires, since January, 1999 till October, 2017. Demographic variables were tabulated, (such as age and sex), place and risk of exposure, clinical characteristics and evolution of the disease. Diagnostic confirmation was based on detection of IgM/IgG ELISA Test specific against nucleoproteins of Hantavirus spp. Results: In the study period, 32 patients with confirmed diagnosis of HPS were discharged. The average age was 39.8 years, ratio of masculinity 1.8. The risk of exposure was due to work activity in 16 cases, recreational in 7, probable interhuman contagion in 5, and causes were not identified in 4 patients. Areas of frequent exposures: X sanitary zone (Navarro, Lobos, Chivilcoy) in 5 cases, XI sanitary zone (La Plata, Cañuelas, San Vicente) in 5 cases. The average from the beginning of symptoms until the consultation was of 5.9 days. The prevalent clinical features: hyperthermia, generalized myalgias, headache and acute respiratory symptoms. Complementary studies: thrombocytopenia (<100,000) in 95% of the patients and bilateral interstitial infiltrates in the 32 cases. Mechanical ventilation required 16 of the 32 patients. The average stay was 17 days and the case fatality rate was 21.8% (7/32). Conclusion: HPS is a disease of low incidence and high lethality. The initial clinical features are a barrier in the early diagnosis, being important the epidemiological antecedent of exposure for an opportune medical assistance. Noticing changes in rodent population dynamics is a priority to prevent exposure of the community and provide a timely epidemiological alert.