Hantavirus Pulmonary Syndrome Research Articles

Hantavirus Disease and COVID-19.

Navajo Nation is disproportionately affected by hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease that can quickly progress to respiratory failure and cardiogenic shock. The initial signs and symptoms of HCPS are indistinguishable from coronavirus disease 2019 (COVID-19). However, this distinction is critical, as the disease course differs greatly, with most patients with COVID-19 experiencing mild to moderate illness. We set out to determine if the evaluation of peripheral blood smears for five hematopathologic criteria previously identified as hallmarks of hantavirus infection, or "the hantavirus 5-point screen," could distinguish between COVID-19 and HCPS. The hantavirus 5-point screen was performed on peripheral blood smears from 139 patients positive for COVID-19 seeking treatment from Tséhootsooí Medical Center and two Emory University hospitals. Of these 139 individuals, 136 (98%) received a score of 3/5 or below, indicating low suspicion for HCPS. While thrombocytopenia, one of the key signs of HCPS, was seen in the patients with COVID-19, it was generally mild and remained stable on repeat specimens collected 12 to 24 hours later. Given these findings, the 5-point screen remains a useful rapid screening tool for potential HCPS cases and may be useful to distinguish early HCPS from COVID-19 in HCPS endemic regions.

Novel infection of pericytes by Andes virus enhances endothelial cell permeability

Andes Virus (ANDV) non-lytically infects pulmonary microvascular endothelial cells (PMECs) causing a severe capillary leak syndrome termed Hantavirus Pulmonary Syndrome (HPS). Basolaterally, PMECs are in contact with pericytes which play critical roles in regulating PMEC permeability and immune cell recruitment. We discovered that ANDV persistently infects primary human vascular pericytes for up to 9 days, and that PMEC monolayer permeability was increased by supernatants from ANDV-infected pericytes. Pericyte-directed PMEC permeability was consistent with the high-level secretion of the permeability factor VEGF (vascular endothelial growth factor) elicited by ANDV-infected pericytes. These findings suggest that ANDV infection of pericytes augments PMEC permeability and reveal a novel mechanism of pericyte-directed vascular barrier dysfunction that contributes to HPS and provides new therapeutic targets.

HANTAVIRUS PULMONARY SYNDROME: A RARE CASE REPORT

TOPIC: Chest Infections TYPE: Fellow Case Reports INTRODUCTION: Hantavirus pulmonary syndrome (HPS) is a rare but potentially life-threatening viral illness transmitted to humans from the infected urine, droppings or saliva of certain species of mice and rats. 728 cases have been reported so far since surveillance in the United States began in 1993 [1]. Most cases (93%) have occurred in states west of the Mississippi River. We present a case of a young male who presented with Hantavirus pulmonary syndrome. CASE PRESENTATION: 28 year old male from rural Texas presented with 1 week of intractable nausea and vomiting. He initially presented to an outside ER where he was found to be hypoxic requiring supplemental oxygen and worsening respiratory status and was transferred to our hospital for higher level of care. Initial workup with CT angiogram of chest revealed bilateral infiltrates and bilateral pleural effusions. Patient was initially started on empiric antibiotics and placed on non-invasive ventilation. Influenza and Repeated COVID-19 tests were negative. Patient reported that he lives in rural area and recently had exposure to a dead mouse in one of his house traps. Hantavirus IgG and IgM antibodies were sent which came back positive after patient had been discharged. Patient did well with supportive therapy of gentle diuresis and non-invasive ventilation and was discharged home after 5 days. DISCUSSION: The clinical syndrome of Hantavirus pulmonary syndrome (HPS) was first recognized in 1993. Although rare, it is frequently fatal, with a case fatality rate of 36%. HPS is an acute febrile illness with a prodrome consisting of fever, chills, myalgia, headache, and gastrointestinal symptoms. One or more of the following clinical features must be present:• Bilateral diffuse interstitial edema• Clinical diagnosis of acute respiratory distress syndrome (ARDS)• Radiographic evidence of noncardiogenic pulmonary edemaLaboratory criteria for diagnosis include detection of hantavirus-specific immunoglobulin M or rising titers of hantavirus-specific immunoglobulin G. CONCLUSIONS: Patients infected with Hantavirus pulmonary syndrome do better if they are recognized early and treated in Intensive care unit. There is no specific treatment or vaccine available at this point. Supplemental oxygen and intubation and mechanical ventilation for severe respiratory failure remains the standard of care. REFERENCE #1: https://www.cdc.gov/hantavirus/hps/index.html DISCLOSURES: No relevant relationships by Anam Hassan, source=Web Response No relevant relationships by Muhammad Hasham Sarwar, source=Web Response No relevant relationships by Brian Williams, source=Web Response

Therapeutic Efficacy of Human Monoclonal Antibodies against Andes Virus Infection in Syrian Hamsters.

Andes virus, an orthohantavirus endemic to South America, causes severe hantavirus cardiopulmonary syndrome associated with human-to-human transmission. No approved treatments or vaccines against this virus are available. We show that a combined treatment with 2 monoclonal antibodies protected Syrian hamsters when administered at midstage or late-stage disease.

Viruses Run: The Evasion Mechanisms of the Antiviral Innate Immunity by Hantavirus.

Hantavirus can cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome (HPS) in America, with high mortality and unknown mechanisms. Innate immunity is the host’s first-line defense to bridge the acquired immunity against viral infections. However, hantavirus has evolved various strategies in both molecular and cellular aspects to evade the host’s natural immune surveillance. The Interferon-I (IFN-I) signaling pathway, a central link of host defense, induces various antiviral proteins to control the infection. This paper summarizes the molecular mechanisms of hantavirus evasion mechanisms of the IFN signaling pathway and cellular processes such as regulated cell death and cell stress. Besides, hantavirus could also evade immune surveillance evasion through cellular mechanisms, such as upregulating immune checkpoint molecules interfering with viral infections. Understanding hantavirus’s antiviral immune evasion mechanisms will deepen our understanding of its pathogenesis and help us develop more effective methods to control and eliminate hantavirus.

Tracing Transmission of Sin Nombre Virus and Discovery of Infection in Multiple Rodent Species.

Sin Nombre orthohantavirus (SNV), a negative-sense, single-stranded RNA virus that is carried and transmitted by the North American deer mouse Peromyscus maniculatus, can cause infection in humans through inhalation of aerosolized excreta from infected rodents. This infection can lead to hantavirus cardiopulmonary syndrome (HCPS), which has an ∼36% case-fatality rate. We used reverse transcriptase quantitative PCR (RT-qPCR) to confirm SNV infection in a patient and identified SNV in lung tissues in wild-caught rodents from potential sites of exposure. Using viral whole-genome sequencing (WGS), we identified the likely site of transmission and discovered SNV in multiple rodent species not previously known to carry the virus. Here, we report, for the first time, the use of SNV WGS to pinpoint a likely site of human infection and identify SNV simultaneously in multiple rodent species in an area of known host-to-human transmission. These results will impact epidemiology and infection control for hantaviruses by tracing zoonotic transmission and investigating possible novel host reservoirs. IMPORTANCE Orthohantaviruses cause severe disease in humans and can be lethal in up to 40% of cases. Sin Nombre orthohantavirus (SNV) is the main cause of hantavirus disease in North America. In this study, we sequenced SNV from an infected patient and wild-caught rodents to trace the location of infection. We also discovered SNV in rodent species not previously known to carry SNV. These studies demonstrate for the first time the use of virus sequencing to trace the transmission of SNV and describe infection in novel rodent species.

Polyclonal alpaca antibodies protect against hantavirus pulmonary syndrome in a lethal Syrian hamster model

The use of antibody-based therapies for the treatment of high consequence viral pathogens has gained interest over the last fifteen years. Here, we sought to evaluate the use of unique camelid-based IgG antibodies to prevent lethal hantavirus pulmonary syndrome (HPS) in Syrian hamsters. Using purified, polyclonal IgG antibodies generated in DNA-immunized alpacas, we demonstrate that post-exposure treatments reduced viral burdens and organ-specific pathology associated with lethal HPS. Antibody treated animals did not exhibit signs of disease and were completely protected. The unique structures and properties, particularly the reduced size, distinct paratope formation and increased solubility of camelid antibodies, in combination with this study support further pre-clinical evaluation of heavy-chain only antibodies for treatment of severe respiratory diseases, including HPS.

A Case of Hantavirus Infection Detected During the COVID-19 Pandemic

Hantaviruses are viruses belonging to the Bunyaviridae family, and they cause two forms of acute illness in humans: hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). HFRS form seen in our country progresses with fever, acute kidney injury, thrombocytopenia and bleeding. Therefore, hantavirus infections should be kept in mind in the differential diagnosis of patients presenting with these symptoms and signs. This report presents a case followed up with the differential diagnosis of coronavirus disease-19 (COVID-19) during the pandemic and diagnosed with HFRS due to hantavirus.

Cells of the human respiratory tract support the replication of pathogenic Old World orthohantavirus Puumala

BackgroundTransmission of all known pathogenic orthohantaviruses (family Hantaviridae) usually occurs via inhalation of aerosols contaminated with viral particles derived from infected rodents and organ manifestation of infections is characterized by lung and kidney involvement. Orthohantaviruses found in Eurasia cause hemorrhagic fever with renal syndrome (HFRS) and New World orthohantaviruses cause hantavirus cardiopulmonary syndrome (HCPS). However, cases of infection with Old World orthohantaviruses with severe pulmonary manifestations have also been observed. Therefore, human airway cells may represent initial targets for orthohantavirus infection and may also play a role in the pathogenesis of infections with Eurasian orthohantaviruses.MethodsWe analyzed the permissiveness of primary endothelial cells of the human pulmonary microvasculature and of primary human epithelial cells derived from bronchi, bronchioles and alveoli for Old World orthohantavirus Puumala virus (PUUV) in vitro. In addition, we examined the expression of orthohantaviral receptors in these cell types. To minimize donor-specific effects, cells from two different donors were tested for each cell type.ResultsProductive infection with PUUV was observed for endothelial cells of the microvasculature and for the three tested epithelial cell types derived from different sites of the respiratory tract. Interestingly, infection and particle release were also detected in bronchial and bronchiolar epithelial cells although expression of the orthohantaviral receptor integrin β3 was not detectable in these cell types. In addition, replication kinetics and viral release demonstrate enormous donor-specific variations.ConclusionsThe human respiratory epithelium is among the first targets of orthohantaviral infection and may contribute to virus replication, dissemination and pathogenesis of HFRS-causing orthohantaviruses. Differences in initial pulmonary infection due to donor-specific factors may play a role in the observed broad variance of severity and symptoms of orthohantavirus disease in patients. The absence of detectable levels of integrin αVβ3 surface expression on bronchial and small airway epithelial cells indicates an alternate mode of orthohantaviral entry in these cells that is independent from integrin β3.

Longitudinal Assessment of Cytokine Expression and Plasminogen Activation in Hantavirus Cardiopulmonary Syndrome Reveals Immune Regulatory Dysfunction in End-Stage Disease.

Pathogenic New World orthohantaviruses cause hantavirus cardiopulmonary syndrome (HCPS), a severe immunopathogenic disease in humans manifested by pulmonary edema and respiratory distress, with case fatality rates approaching 40%. High levels of inflammatory mediators are present in the lungs and systemic circulation of HCPS patients. Previous studies have provided insights into the pathophysiology of HCPS. However, the longitudinal correlations of innate and adaptive immune responses and disease outcomes remain unresolved. This study analyzed serial immune responses in 13 HCPS cases due to Sin Nombre orthohantavirus (SNV), with 11 severe cases requiring extracorporeal membrane oxygenation (ECMO) treatment and two mild cases. We measured viral load, levels of various cytokines, urokinase plasminogen activator (uPA), and plasminogen activator inhibitor-1 (PAI-1). We found significantly elevated levels of proinflammatory cytokines and PAI-1 in five end-stage cases. There was no difference between the expression of active uPA in survivors’ and decedents’ cases. However, total uPA in decedents’ cases was significantly higher compared to survivors’. In some end-stage cases, uPA was refractory to PAI-1 inhibition as measured by zymography, where uPA and PAI-1 were strongly correlated to lymphocyte counts and IFN-γ. We also found bacterial co-infection influencing the etiology and outcome of immune response in two cases. Unsupervised Principal Component Analysis and hierarchical cluster analyses resolved separate waves of correlated immune mediators expressed in one case patient due to a sequential co-infection of bacteria and SNV. Overall, a robust proinflammatory immune response, characterized by an imbalance in T helper 17 (Th17) and regulatory T-cells (Treg) subsets, was correlated with dysregulated inflammation and mortality. Our sample size is small; however, the core differences correlated to survivors and end-stage HCPS are instructive.

Hantavirus infection-induced B cell activation elevates free light chains levels in circulation.

In humans, orthohantaviruses can cause hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). An earlier study reported that acute Andes virus HPS caused a massive and transient elevation in the number of circulating plasmablasts with specificity towards both viral and host antigens suggestive of polyclonal B cell activation. Immunoglobulins (Igs), produced by different B cell populations, comprise heavy and light chains; however, a certain amount of free light chains (FLCs) is constantly present in serum. Upregulation of FLCs, especially clonal species, associates with renal pathogenesis by fibril or deposit formations affecting the glomeruli, induction of epithelial cell disorders, or cast formation in the tubular network. We report that acute orthohantavirus infection increases the level of Ig FLCs in serum of both HFRS and HPS patients, and that the increase correlates with the severity of acute kidney injury in HFRS. The fact that the kappa to lambda FLC ratio in the sera of HFRS and HPS patients remained within the normal range suggests polyclonal B cell activation rather than proliferation of a single B cell clone. HFRS patients demonstrated increased urinary excretion of FLCs, and we found plasma cell infiltration in archival patient kidney biopsies that we speculate to contribute to the observed FLC excreta. Analysis of hospitalized HFRS patients' peripheral blood mononuclear cells showed elevated plasmablast levels, a fraction of which stained positive for Puumala virus antigen. Furthermore, B cells isolated from healthy donors were susceptible to Puumala virus in vitro, and the virus infection induced increased production of Igs and FLCs. The findings propose that hantaviruses directly activate B cells, and that the ensuing intense production of polyclonal Igs and FLCs may contribute to acute hantavirus infection-associated pathological findings.

Articles of Significant Interest in This Issue

Andes virus (ANDV) selectively infects pulmonary microvascular endothelial cells (PMECs), causing a 35% fatal acute pulmonary edema termed hantavirus pulmonary syndrome (HPS). However, the mechanism of ANDV-induced vascular permeability remains an enigma. Gorbunova and Mackow (e00396-21) found that the ANDV N-protein binds to RhoGDI, the primary repressor of RhoA-directed vascular permeability. N-protein binding to S34-phosphorylated RhoGDI inhibited RhoGDI binding and repression of RhoA, revealing a novel edemagenic mechanism that permits ANDV to cause HPS. These findings rationalize targeting PKCα phosphorylation of RhoGDI to therapeutically inhibit HPS patient edema and may be broadly applicable to other causes of acute respiratory distress.

Rodent borne zoonoses: A brief review

Rodents are the most abundant and diversified order of living mammals in the world. Since the middle ages they are known to contribute to human diseases, eg. black rats associated with distribution of plague. In modern times also rodents form a threat for public health and a number of pathogens are directly or indirectly transmitted by rodents. Of 2277 extant rodent species, 217 species are reservoirs harboring 66 zoonoses caused by viruses, bacteria, fungi, helminths, and protozoa and play a major role in their transmission and spread in different ways. Among the most important diseases in terms of public health are salmonellosis, plague, leptospirosis, leishmaniasis, toxoplasmosis, rat-bit fever, taeniasis-like Capillaria hepatica, zoonotic babesiosis, Lassa fever, hemorrhagic fever with renal syndrome (HFRS), and the hantavirus cardiopulmonary syndrome (HCPS). In addition, Arenaviruses are responsible for South American Hemorrhagic Fevers (SAHF). Rodents may harbor different complex bacteria, such as Mycobacterium tuberculosis and Mycobacterium microti, Escherichia coli, agents of Tularemia, Tick-borne relapsing fever, Bartonellosis, Listeriosis, Lyme disease, Q fever, Ehrlichiosis and others. Recent changes in the global climate and ecosystem composition led to the spread of rodents and rodent-borne pathogens globally. Rodent control in rural environments relies mainly on the use of rodenticides. Other management methods which can be applied are trapping, habitat management (e.g., proofing, sanitation), and biocontrol (e.g., wild or domestic predators, rodent pathogens).

Proteinuria in Hantavirus Cardiopulmonary Syndrome: A Frequent Finding Linked To Mortality

ObjectivesTo determine the relative frequency and prognosis value of proteinuria in hantavirus cardiopulmonary syndrome (HCPS) due to Andes virus. MethodsThis observational analytical study prospectively obtained data from patients admitted to 12 health centers in nine Chilean cities between 2001 and 2018. Only patients with confirmed Andes virus HCPS and laboratory characterization that included qualitative proteinuria determination at admission were considered. ResultsThe database involved 175 patients, 95 of them had a measurement of urine protein at the time of hospital admission. They were mainly male (71%) and the median age was 35 [22-47] years. Median duration of the febrile prodromal time was 5 [4-7] days. Hospital length of stay and hospital mortality rate were 10 [7-14] days and 21.1%, respectively. Seventy-three patients (77%) were identified with proteinuria at admission, which was associated with increased mortality rate (26% versus 5%, p=0.036) and the relative risk was 1.3 [1.1-1.6], p=0.002. ConclusionsProteinuria is a frequent finding in patients with HCPS, which is associated with a higher mortality rate.

Microbiological and epidemiological review of Hantavirus: A Review

Hantaviruses are rodent viruses that have a world-wide distribution. Rodents and insectivores act as asymptomatic, chronic, persistently infected carrier hosts, whereas humans are dead end hosts and may exhibit symptoms after an incubation period of between one and six weeks. Hantaviruses infect humans and causing either hemorrhagic fever with renal syndrome (HFRS) or Hantavirus cardiopulmonary syndrome (HCPS). Due to the absence of the treatment and approved vaccine in the USA, European and Asian countries, the public awareness and precautions are the only way of minimizing the risk of Hantavirus infection. This review provides a microbiological and epidemiological summary of the Hantavirus diseases in rodents and human beings. We concluded that the disease is a serious zoonotic disease the affect animals and humans and the mortality rate is really high. A wide range of different diagnostic tests play an important role in the diagnosis of the Hantavirus.

Orthohantavirus Survey in Indigenous Lands in a Savannah-Like Biome, Brazil.

In Brazil, the first confirmed cases of hantavirus cardiopulmonary syndrome in Indigenous populations occurred in 2001. The purpose of this study was to determine the seroprevalence of orthohantavirus infections in the Utiariti Indigenous land located in the southeastern region of the Brazilian Amazon. In December 2014 and 2015, a survey was conducted using an enzyme-linked immunosorbent assay in nine villages belonging to the Haliti–Paresí Indigenous communities. A total of 301 participants were enrolled in the study. Of the two study cohorts, the one from 2014 showed a prevalence of 12.4%, whereas the one from 2015 had a serum prevalence of 13.4%. Analysis of the paired samples of 110 Indigenous people who participated in both stages of the study enabled identification of four individuals who had seroconverted during the study period. Identifying the circulation of orthohantaviruses in the Utiariti Indigenous land highlights a serious public health problem in viral expansion and highlights the need to implement preventive measures appropriate to the sociocultural reality of these communities.

Continuing Orthohantavirus Circulation in Deer Mice in Western Montana.

Hantavirus pulmonary syndrome (HPS) is an often-fatal disease caused by New World hantaviruses, such as Sin Nombre orthohantavirus (SNV). In the US, >800 cases of HPS have been confirmed since it was first discovered in 1993, of which 43 were reported from the state of Montana. The primary cause of HPS in the US is SNV, which is primarily found in the reservoir host Peromyscus maniculatus (deer mouse). The reservoir host covers most of the US, including Montana, where multiple studies found SNV in local deer mouse populations. This study aimed to check the prevalence of SNV in the deer mice at popular recreation sites throughout the Bitterroot Valley in Western Montana as compared to previous studies in western Montana. We found high prevalence (up to 20%) of deer mice positive for SNV RNA in the lungs. We were unable to obtain a SNV tissue culture isolate from the lungs but could passage SNV from lung tissue into naïve deer mice. Our findings demonstrate continuing circulation of SNV in western Montana.

Evidence of Hantavirus circulation among municipal street sweepers, southwest of Iran.

Hantaviruses are rodent-borne zoonosis pathogens that cause hemorrhagic fever with renal syndrome (HFRS) and Hantavirus cardiopulmonary syndrome (HCPS) in humans. Rodents spread the virus via their excretions. The outbreak of Hantaviruses pose a significant public health problem. The epidemiology and history of Hantaviruses in Iran is not clear and regardless of the data from the few available studies, little is known about its epidemiology in this country. Herein, we discuss the prevalence of IgG antibody against Hantavirus serotypes in 385 street sweepers from southwest of Iran. Serum samples were investigated, using Hantavirus Pool 1 "Eurasia" IgG kit and Pool 2 "America" ELISA IgG kit (Euroimmun, Germany) to detect IgG antibodies against Old and New World Hantaviruses. The results showed a specific IgG antibody in two samples (0.5%). Both of seropositive cases had specific IgG antibody against Old World Hantaviruses. The data of the current study along with the previous data, indicate the circulation of Hantaviruses in Iran. Hence, the risk of Hantavirus infection in high-risk groups should be considered as a serious health issue.

A novel genotype of Hantaan orthohantavirus harbored by Apodemus agrarius chejuensis as a potential etiologic agent of hemorrhagic fever with renal syndrome in Republic of Korea.

Orthohantaviruses, causing hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome, pose a significant public health threat worldwide. Despite the significant mortality and morbidity, effective antiviral therapeutics for orthohantavirus infections are currently unavailable. This study aimed to investigate the prevalence of HFRS-associated orthohantaviruses and identify the etiological agent of orthohantavirus outbreaks in southern Republic of Korea (ROK). We collected small mammals on Jeju Island during 2018-2020. We detected the Hantaan virus (HTNV)-specific antibodies and RNA using an indirect immunofluorescence assay test and reverse transcription-polymerase chain reaction on Apodemus agrarius chejuensis (A. chejuensis). The prevalence of anti-HTNV antibodies among rodents was 14.1%. A total of six seropositive mouse harbored HTNV RNA. The amplicon-based next-generation sequencing provided nearly full-length tripartite genomic sequences of six HTNV harbored by A. chejuensis. Phylogenetic and tanglegram analyses were conducted for inferring evolutionary relationships between orthohantaviruses with their reservoir hosts. Phylogenetic analysis showed a novel distinct HTNV genotype. The detected HTNV genomic sequences were phylogenetically related to a viral sequence derived from HFRS patient in southern ROK. Tanglegram analysis demonstrated the segregation of HTNV genotypes corresponding to Apodemus spp. divergence. Our results suggest that A. chejuensis-borne HTNV may be a potential etiological agent of HFRS in southern ROK. Ancestral HTNV may infect A. chejuensis prior to geological isolation between the Korean peninsula and Jeju Island, supporting the co-evolution of orthohantaviruses and rodents. This study arises awareness among physicians for HFRS outbreaks in southern ROK.

Serological Evidence of Human Orthohantavirus Infections in Barbados, 2008 to 2016

Background: Hantavirus pulmonary syndrome (HPS) is well-known in South and North America; however, not enough data exist for the Caribbean. The first report of clinical orthohantavirus infection was obtained in Barbados, but no other evidence of clinical orthohantavirus infections among adults in the Caribbean has been documented. Methods: Using enzyme linked immunosorbent assay (ELISA) tests followed by confirmatory testing with immunofluorescent assays (IFA), immunochromatographic (ICG) tests, and pseudotype focus reduction neutralization tests (pFRNT), we retrospectively and prospectively detected orthohantavirus-specific antibodies among patients with febrile illness in Barbados. Results: The orthohantavirus prevalence rate varied from 5.8 to 102.6 cases per 100,000 persons among febrile patients who sought medical attention annually between 2008 and 2016. Two major orthohantavirus epidemics occurred in Barbados during 2010 and 2016. Peak orthohantavis infections were observed observed during the rainy season (August) and prevalence rates were significantly higher in females than males and in patients from urban parishes than rural parishes. Conclusions: Orthohantavirus infections are still occurring in Barbados and in some patients along with multiple pathogen infections (CHIKV, ZIKV, DENV and Leptospira). Orthohantavirus infections are more prevalent during periods of high rainfall (rainy season) with peak transmission in August; females are more likely to be infected than males and infections are more likely among patients from urban rather than rural parishes in Barbados.