Management of Hantavirus Cardiopulmonary Syndrome in Critical Care Transport: A Review.

In 1993, the Southwest found itself staring down a disease then known as "unexplained adult respiratory syndrome." During the outbreak, 12 of 23 known patients died. What we now recognize as hantavirus cardiopulmonary syndrome still remains a rare and deadly disease. Although no cure exists, modern supportive techniques such as extracorporeal membrane oxygenation have increased survival among these patients. Early diagnosis has become the primary factor in patient survival. The initial presentation of hantavirus is similar to acute respiratory distress syndrome, necessitating a high index of suspicion to afford the patient the best chance of survival. Diagnosis is further complicated by prolonged and nonspecific incubation periods making it difficult to pinpoint an exposure. Familiarizing oneself with common clinical presentations, diagnostic strategies, and testing is the best way to increase patient survival. Because hantavirus has a predilection for rural areas, transport to a tertiary facility is paramount to provide the resources necessary to care for these complex patients. Rapid sequence intubation, although common in airway-compromised patients, could prove fatal in the setting of the severe hemodynamic instability found in hantavirus cardiopulmonary syndrome. Anticipation of significant pressor use and fluid administration could likely mean the difference in patient mortality during transport.

Hantavirus in humans: a review of clinical aspects and management.

Hantavirus infections are part of the broad group of viral haemorrhagic fevers. They are also recognised as a distinct model of an emergent zoonotic infection with a global distribution. Many factors influence their epidemiology and transmission, such as climate, environment, social development, ecology of rodent hosts, and human behaviour in endemic regions. Transmission to humans occurs by exposure to infected rodents in endemic areas; however, Andes hantavirus is unique in that it can be transmitted from person to person. As hantaviruses target endothelial cells, they can affect diverse organ systems; increased vascular permeability is central to pathogenesis. The main clinical syndromes associated with hantaviruses are haemorrhagic fever with renal syndrome (HFRS), which is endemic in Europe and Asia, and hantavirus cardiopulmonary syndrome (HCPS), which is endemic in the Americas. HCPS and HFRS are separate clinical entities, but they share several features and have many overlapping symptoms, signs, and pathogenic alterations. For HCPS in particular, clinical outcomes are highly associated with early clinical suspicion, access to rapid diagnostic testing or algorithms for presumptive diagnosis, and prompt transfer to a facility with critical care units. No specific effective antiviral treatment is available.

[Hantavirus infections]. / Infections à hantavirus.

Hantaviruses are enveloped zoonotic RNA viruses hosted by rodents and responsible in the Americas for hantavirus pulmonary syndrome. In Europe, they cause hemorrhagic fever with renal syndrome and its milder form, nephropathia epidemica. The disease begins abruptly with high fever, chills, headache, back pain and abdominal pain associated with nausea and vomiting. Diagnosis is primarily made by serology. There is currently no specific medication or preventive available in Europe. Treatment is symptomatic.

Les hantavirus sont des virus zoonotiques à ARN enveloppés hébergés principalement par des rongeurs et responsables, aux Amériques, du syndrome pulmonaire à hantavirus. En Europe, ils provoquent la fièvre hémorragique avec syndrome rénal et sa forme plus légère appelée néphropathie épidémique. La maladie se présente de manière aiguë avec une forte fièvre, des frissons, des céphalées, des dorsalgies ainsi que des douleurs abdominales associées à des nausées et vomissements. Le diagnostic se fait principalement par sérologie. Il n'existe actuellement pas de médication spécifique, ni de vaccination disponible en Europe. Le traitement repose sur un soutien symptomatique.

Hantavirus.

Hantaviruses are tri-segmented lipid-enveloped RNA viruses belonging to the Bunyaviridae family. Human infection corresponds to a zoonosis associated with two different clinical syndromes: hemorrhagic fever with renal syndrome that occurs in Asia and Europe and hantavirus cardiopulmonary syndrome (HCPS) that occurs in the North America, Central America and South America. The major pathogenic mechanisms in HCPS include (1) direct microvascular endothelial injury leading to increased capillary permeability and the development of noncardiogenic pulmonary edema and acute respiratory distress syndrome, and (2) exaggerated host immune response leading to secondary organ damage. The incubation period for this disease is quite long (6-39 days, median: 18 days); however, rapid progression to respiratory failure and shock can occur highlighting the importance of high index of clinical suspicion. Management revolves around high-quality supportive care. Various management and preventative strategies are currently being explored and warrant further examination to improve the overall outlook following infection with hantavirus.

Two patients, two viruses and multiple sites of injury in the kidney.

Viral nephropathy is a term defines glomerular, tubular and/or vascular injury in kidney caused by viruses itself or virus-induced immune mechanisms. It is difficult to prove causality between the renal disease and the viral infection, however, renal biopsy findings can help in this regard. Several viruses such as hepatitis B and C, Human immun deficiciency virus (HIV), Hantavirus, Cytomegalovirus (CMV), an recently Coronavirus are shown to affect the kidney. Treatment of viral nephropathies are unique regarding the diagnosis which can be made only with renal biopsy in most of the situations. We present two patients presented with acute kidney injury and thrombocytopenia caused by different viruses (Hantavirus and HIV) that affect multiple areas in kidney that revealed with kidney biopsy. Supportive treatment in the patient with Hantavirus nephropathy and HIV treatment along with eculizumab and supportive treatment in the patient with HIVAN were successfully implemented.

Atypical case of hantavirus infection in Sri Lanka mimicking leptospirosis: a case report.

BACKGROUND: Hantavirus infection is an emerging zoonotic infection which has two characteristic patterns of presentation: hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome. The clinical presentation of hantavirus infection closely mimics leptospirosis. CASE PRESENTATION: This case report describes a previously apparently well 36-year-old Sri Lankan Sinhalese man who presented with an acute febrile illness with myalgia, with liver involvement in the form of transaminitis, cardiac involvement in the form of myocarditis, acute kidney injury, and pulmonary involvement. He was initially managed as severe leptospirosis with multiorgan dysfunction with antibiotics, steroids, and N-acetyl cysteine. A diagnosis of acute hantavirus infection was made subsequently. He made an uneventful recovery. CONCLUSION: Hantavirus infections need to considered in the differential diagnosis of patients presenting with acute febrile illness with multiorgan involvement. Larger studies are needed to evaluate the seroprevalence of hantavirus in Sri Lanka because it could be an emerging serious public health problem.

Meeting report: Eleventh International Conference on Hantaviruses.

The 2019 11th International Conference on Hantaviruses (ICH 2019) was organized by the International Society for Hantaviruses (ISH), and held on September 1-4, 2019, at the Irish College, in Leuven, Belgium. These ICHs have been held every three years since 1989. ICH 2019 was attended by 158 participants from 33 countries. The current report summarizes research presented on all aspects of hantavirology: ecology; pathogenesis and immune responses; virus phylogeny, replication and morphogenesis; epidemiology; vaccines, therapeutics and prevention; and clinical aspects and diagnosis.

Kidney Diseases Associated With Parvovirus B19, Hanta, Ebola, and Dengue Virus Infection: A Brief Review.

Viral infection-associated kidney diseases are an emerging public health issue in both developing and developed countries. Many new viruses have emerged with new paradigms of kidney injury, either directly through their cytopathic effect or indirectly through immune-mediated glomerulopathy, tubulointerstitial disease, and acute kidney injury as part of multiorgan failure. Herein, we will discuss Parvovirus, which causes glomerulopathy, and Hanta, Ebola, and Dengue viruses, which cause viral hemorrhagic fever and acute kidney injury. Clinical manifestations also depend on extrarenal organ systems involved. Diagnosis of these viral infections is mainly based on a high index of suspicion, serologic testing, and isolation of viral DNA/RNA. Management is largely conservative, as specific antiviral agents are unavailable.

Síndrome cardiopulmonar por Hantavirus luego del brote de Epuyén, Argentina: la necesidad de investigar nuevas formas de intervención terapéutica / Cardiopulmonary syndrome due to Hantavirus after the outbreak in Epuyén, Argentina: the need to investigate new forms of therapeutic intervention / Síndrome cardiopulmonar por Hantavírus depois do surto de Epuyén, Argentina: a necessidade de investigar novas formas de intervenção terapêutica

Los Hantavirus son virus con ARN de cadena simple pertenecientes a la familia Bunyaviridae. A diferencia de otros virus de la familia, no tienen artrópodos como vectores; sus hospederos en la naturaleza son roedores y algunos mamíferos pequeños. La transmisión al hombre ocurre por la inhalación de excretas de los animales infectados, rara vez por mordeduras y se ha documentado la posibilidad de transmisión persona a persona. Existen dos formas clínicas de la enfermedad: fiebre hemorrágica con síndrome renal (FHSR) distribuida en Europa y Asia, y síndrome cardiopulmonar por Hantavirus (SCPH), en las Américas. El SCPH se presenta clinicamente en cuatro fases: incubación, prodrómica, cardiopulmonar y convalescencia. En el laboratorio es frecuente el hallazgo de trombocitopenia, junto con otros cambios hematológicos y bioquímicos. El diagnóstico se realiza por la detección de anticuerpos o PCR. Recientemente en Epuyén, Provincia de Chubut, Argentina, ocurrió un brote que afectó a 34 personas con 12 muertes asociado a la transmisión interpersonal. Se revisa la situación actual con respecto al tratamiento y las posibilidades futuras de intervención. Aunque se trate de una enfermedad con una baja prevalencia, la alta tasa de letalidad y el alto impacto emocional y económico que sufren las localidades afectadas hacen necesario seguir investigando la búsqueda de nuevas alternativas de tratamiento.

Hantaviruses are single-stranded RNA viruses that belong to the Bunyaviridae family. Unlike other viruses in the family, they do not have arthropods as vectors; their hosts in the wild are rodents and some small mammals. Human transmission takes place through inhalation of excreta from infected animals, rarely from bites, and the possibility of person-to-person transmission has been documented. There are two clinical forms of the disease: hemorrhagic fever with renal syndrome (HFRS) distributed in Europe and Asia, and cardiopulmonary Hantavirus syndrome (HCPS) distributed in the Americas. The HCPS presents clinically in four phases: incubation, prodromal, cardiopulmonary and convalescence. In the laboratory, a thrombocytopenia is common, together with other hematological and biochemical changes. Diagnosis is made through the detection of antibodies or PCR. Recently, in Epuyén, Province of Chubut, Argentina, an outbreak occurred, affecting 34 people with 12 deaths associated with interpersonal transmission. The current situation is reviewed with respect to the treatment and the future possibilities of intervention. Although it is a disease with a low prevalence, the high rate of lethality and the high emotional and economic impact suffered by the affected areas make it necessary to continue investigating in search of new treatment alternatives.

Os Hantavírus são vírus RNA de cadeia simples pertencentes à família Bunyaviridae. Diferente de outros vírus da família, não têm artrópodes como vetores; seus anfitrões na natureza são roedores e alguns mamíferos pequenos. A transmissão para o homem acontece através da inalação de excrementos dos animais infectados, raras vezes por mordeduras e foi documentada a possibilidade de transmissão de pessoa para pessoa. Existem duas formas clínicas da doença: febre hemorrágica com síndrome renal (FHSR) distribuída na Europa e Ásia, e síndrome cardiopulmonar por Hantavírus (SCPH), nas Américas. O SCPH apresenta-se clinicamente em quatro fases: incubação, prodrômica, cardiopulmonar e convalescença. No laboratório é frequente o achado de trombocitopenia, junto a outras mudanças hematológicas e bioquímicas. O diagnóstico é realizado pela detecção de anticorpos ou PCR. Recentemente em Epuyén, Província de Chubut, Argentina, houve um surto que afetou 34 pessoas com 12 mortes associado à transmissão interpessoal. Revê-se a situação atual relativa ao tratamento e às possibilidades futuras de intervenção. Embora se trate de uma doença com uma baixa prevalência, a alta taxa de letalidade e o alto impacto emocional e econômico que sofrem as localidades afetadas tornam necessário continuar investigando em busca de novas alternativas de tratamento.

Hemorrhagic fever of bunyavirus etiology: disease models and progress towards new therapies.

A growing number of bunyaviruses are known to cause viral hemorrhagic fever (VHF), a severe febrile illness which can progress to hypovolemic shock and multi-organ failure and is characterized by hematologic abnormalities and vascular leak. At present, there are no approved vaccines or antiviral therapies to effectively prevent or treat VHF caused by pathogenic bunyaviruses. Advances in the modeling of bunyaviral infections have facilitated efforts towards the development of novel post-exposure prophylactic and therapeutic countermeasures, several of which may some day be approved for human use. Here, we review recent progress in animal models of severe bunyaviral infections essential to this mission, as well as promising antivirals and biologicals that are at various stages of the development process.

Rodent-borne infectious disease outbreaks after flooding disasters: Epidemiology, management, and prevention.

OBJECTIVE: To alert clinicians to the climatic conditions that can precipitate outbreaks of the rodent-borne infectious diseases most often associated with flooding disasters, leptospirosis (LS), and the Hantavirus-caused diseases, hemorrhagic fever with renal syndrome (HFRS) and Hantavirus pulmonary syndrome (HPS); to describe the epidemiology and presenting clinical manifestations and outcomes of these rodent-borne infectious diseases; and to recommend both prophylactic therapies and effective control and prevention strategies for rodent-borne infectious diseases. DESIGN: Internet search engines, including Google®, Google Scholar®, Pub Med, Medline, and Ovid, were queried with the key words as search terms to examine the latest scientific articles on rodent-borne infectious disease outbreaks in the United States and worldwide to describe the epidemiology and presenting clinical manifestations and outcomes of LS and Hantavirus outbreaks. SETTING: Not applicable. PARTICIPANTS: Not applicable. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Rodent-borne infectious disease outbreaks following heavy rainfall and flooding disasters. RESULTS: Heavy rainfall encourages excessive wild grass seed production that supports increased outdoor rodent population densities; and flooding forces rodents from their burrows near water sources into the built environment and closer to humans. CONCLUSIONS: Healthcare providers should maintain high levels of suspicion for LS in patients developing febrile illnesses after contaminated freshwater exposures following heavy rainfall, flooding, and even freshwater recreational events; and for Hantavirus-caused infectious diseases in patients with hemorrhagic fevers that progress rapidly to respiratory or renal failure following rodent exposures.

A non-randomized multicentre trial of human immune plasma for treatment of hantavirus cardiopulmonary syndrome caused by Andes virus.

BACKGROUND: In Chile, Andes virus (ANDV) is the sole aetiological agent of hantavirus cardiopulmonary syndrome (HCPS) with mean annual incidence of 55 cases, 32% case fatality rate (CFR) and no specific treatment. Neutralizing antibody (NAb) titres at hospital admission correlate inversely with HCPS severity. We designed an open trial to explore safety and efficacy and evaluate pharmacokinetics of immune plasma as a treatment strategy for this disease. METHODS: We performed plasmapheresis on donors at least 6 months after HCPS and measured NAb titres through a focus-reduction neutralization test. Subjects admitted to 10 study sites with suspected/confirmed HCPS were eligible for treatment with immune plasma by intravenous infusion at an ANDV NAb dose of 5,000 U/kg. HCPS was confirmed through immunoglobulin M serology or reverse transcriptase-PCR. The main outcome was mortality within 30 days. RESULTS: From 2008-2012, we enrolled and treated 32 cases and confirmed HCPS in 29. CFR of hantavirus plasma-treated cases was 4/29 (14%); CFR of non-treated cases in the same period in Chile was 63/199 (32%; P=0.049, OR=0.35, CI=0.12, 0.99); CFR of non-treated cases at the same study sites between 2005-2012 was 18/66 (27%; (P=0.15, OR=0.43, CI=0.14, 1.34) and CFR in a previous methylprednisolone treatment study was 20/60 (33%; P=0.052, OR=0.32, CI=0.10, 1.00). We detected no serious adverse events associated to plasma infusion. Plasma NAb titres reached in recipients were variable and viral load remained stable. CONCLUSIONS: Human ANDV immune plasma infusion appears safe for HCPS. We observed a decrease in CFR in treated cases with borderline significance that will require further studies for confirmation.

[Prognostic factors in hantavirus infections]. / Hantavirus enfeksiyonlarinda prognostik faktörler.

The hantaviruses classified in Hantavirus genus of Bunyaviridae family, may cause two different types of clinical conditions, namely hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Mortality may reach up to 40% in these infections. Hantavirus subtypes (Sin Nombre, Hantaan, Seoul, Puumala, Dobrava, etc) with different virulences represent one of the most significant factors affecting the mortality. Additionally, many other factors including age, gender, humoral immune response, genetic factors, patient's clinical and laboratory findings, transfusion, mechanical ventilation requirement, antiviral treatment and immunotherapy administered to the patient are prognostically important. Increasing age had an unfavorable effect on mortality. While the disease is commonly observed in the male gender, mortality rate is higher in the female gender. The higher the emergent neutralizing antibody response, the virus spread, the number of the infected cells and the cytotoxic T lymphocyte-mediated injury will be lower. The requirement for dialysis is reported to be higher with a poorer prognosis in individuals with HLA-B8, -DR3, -DQ2 alleles, and those with HLA-B27 allele usually experience a milder clinical course. Clinically, the risk of mortality increases in patients with multiple, central nervous system hemorrhage, sepsis, disseminated intravascular coagulation (DIC) and secondary infection. The presence of adult respiratory distress syndrome (ARDS), the requirement for mechanical ventilation, the presence of dyspnea and hemoconcentration in HPS are reported to be the most important prognostic factors associated with death. The correlation of severity and the transfusion requirement with mortality was demonstrated. High serum levels of white blood cells, blood urea nitrogen (BUN), creatinine phophokinase (CPK), C-reactive protein (CRP), prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer and INR (International normalized ratio) are prognostic factors that increase the mortality risk. Hemodialysis support is particularly important in cases infected with Hantaan and Dobrava viruses. Respiratory support and mechanical ventilation can be life-saving in HPS cases. Extracorporeal membrane oxygenation support has been demonstrated to have a favorable contribution to the patient survival in HPS. While there are some human and animal trials showing that ribavirin reduces the severity of HFRS, hemodialysis requirement and mortality, its efficacy for HPS has not yet been demonstrated. As a result, a proper evaluation of the prognostic factors will provide physicians a perspective with respect to the disease course and the necessary treatment approach.

Other viral pneumonias: coronavirus, respiratory syncytial virus, adenovirus, hantavirus.

Severe viral pneumonia is an increasing problem among adults. The incidence and number of viruses known to cause pneumonia and respiratory failure have also expanded in recent years. This article provides an overview of severe respiratory disease caused by coronavirus, respiratory syncytial virus, adenovirus, and hantavirus. These emerging pathogens are easily overlooked and timely diagnosis requires a high index of suspicion and confirmation by molecular testing. Management of individual cases is mainly supportive and requires institution of appropriate infection control measures. Vaccines and effective therapeutics for these potentially devastating respiratory viruses are urgently required.

Hantavirus infection in North America: a clinical review.

The recent outbreak of hantavirus in Yosemite National Park has attracted national attention, with 10 confirmed cases of hantavirus cardiopulmonary syndrome and thousands of more people exposed. This article will review the epidemiology, presentation, workup, and treatment for this rare but potentially lethal illness. The possibility of infection with hantavirus deserves consideration in patients with severe respiratory symptoms with rodent exposure or rural/wilderness travel. Accurate diagnosis requires a high index of suspicion. Hantavirus cardiopulmonary syndrome presents as a vague prodrome of fever, cough, myalgias, chills, and nausea followed by a rapidly worsening respiratory phase. Presumptive diagnosis can be made based on pulmonary interstitial edema on chest radiographs in association with leukocytosis, thrombocytopenia, and hemoconcentration. Suspected cases should be confirmed with a reference laboratory and reported to the appropriate public health authorities. Although treatment is primarily supportive, aggressive fluid administration should be avoided due to the risk of pulmonary edema. The cardiopulmonary phase of the disease can progress rapidly with catastrophic decompensation in as little as a few hours. Patients require rapid intensive care unit admission for monitoring, mechanical ventilation, vasoactive agents, and possibly extracorporeal mechanical ventilation. Emergency physicians should be aware of outbreaks and vigilant for hantavirus exposures, especially during the summer and early fall months.

[Hantavirus infection as the cause of haemorrhagic fever with renal syndrome]. / Hantavirus-infektion som årsag til hæmoragisk feber med renalt syndrom.

Hantavirus is an RNA virus that can cause potentially fatal pulmonary and renal diseases in humans. Infections with Hantaviruses occur through inhalation of aerosol from rodent faeces, urine or saliva. The predominant virus type in Denmark is the Puumala virus, which causes the mildest form of haemorrhagic fever with renal syndrome, the so-called nephropathia epidemica (NE) with good prognosis (mortality 0.1-0.4%). The incidence of Hantavirus-infection in Denmark is about ten cases a year. The diagnosis of Hantavirus-infection is based on serology and/or polymerase chain reaction in blood or urine.

[Hantavirus diseases]. / Malattie da Hantavirus.

Hantaviruses are emerging viruses that cause persistent chronic infections in their small mammal hosts. When these viruses are transmitted to humans, they can cause two clinical syndromes, hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). The understanding of the epidemiology, pathogenesis and natural history of these viruses has improved in recent years. The number of reported hantavirus infections is increasing worldwide and new hantaviruses are being discovered in many countries, so they now represent a public health problem of global concern. It is believed that hantavirus infections might be underestimated due to the frequently asymptomatic and nonspecific mild infections they cause as well as the lack of simple standardized diagnostic laboratory methods. In this review the current concepts regarding the epidemiology, ecology, clinical presentation, pathogenesis, diagnosis, and treatment of the infections associated with these emerging human pathogens are presented.

Hantavirus infections for the clinician: from case presentation to diagnosis and treatment.

Hantaviruses cause Hantavirus Pulmonary Syndrome (HPS; also called Hantavirus Cardiopulmonary Syndrome) in the Americas and Hemorrhagic Fever with Renal Syndrome (HFRS) in Asia and Europe. In Scandinavia and northern Europe, a milder form of HFRS is prevalent, termed nephropathica epidemica (NE). HPS presents with acute respiratory failure, mild-moderate renal failure, thrombocytopenia, and reactive lymphocytosis. HFRS has pronounced renal dysfunction and less prominent respiratory involvement, with thrombocytopenia and hemorrhagic findings. Both syndromes have long-term sequelae. Common symptomatology is due to underlying pathophysiology, mainly increased vascular permeability and immune activation. Laboratory and imaging markers predicting disease severity are under research, allowing for more efficient patient management. Diagnosis is presumptive, based on typical clinical findings and patient history of likely rodent exposure. Confirmation of diagnosis is by serological testing and/or RT-PCR. Treatment is mainly comprised of cardiovascular, respiratory, and renal function support, with fluid and electrolyte homeostasis being crucial components of care. In HPS, the use of extracorporeal membrane oxygenation in decompensated patients has also shown to be beneficial.