Hantavirus infection-related acute inflammatory demyelinative polyradiculoneuropathy: A case report and literature review.

RATIONALE: Hemorrhagic fever with renal syndrome (HFRS) is a common infectious disease in China. As a complication of post-Hantavirus infection, Guillain-Barre syndrome (GBS) was rarely previously reported. Here, we described a case of acute inflammatory demyelinative polyradiculoneuropathy secondary to Hantavirus infection in spring of 2023. We also made a summary of the clinical features from previous reported cases. PATIENT CONCERNS: A young male patient complained a fever with headache, who was subsequently diagnosed with HFRS with positive serum Hantavirus antibody IgM. Two weeks later, he presented sustained back pain, obvious numbness located in 4 extremities, chest and abdomen, facial dyskinesia and 4 extremities muscle weakness. DIAGNOSIS, INTERVENTIONS, AND OUTCOMES: He was rapidly diagnosed with GBS by typical cerebrospinal fluid change and the electromyography examination presentation, which was verified associated with hantavirus infection. He was treated with intravenous immunoglobulin infusion followed by rehabilitation treatment. He got a complete recovery within 4 months after disease onset. LESSONS: GBS was an uncommon manifestation of Hantavirus infection. GBS should be considered when acute limb weakness happens in cases with HFRS. A multidisciplinary team could make a rapid diagnosis and optimal treatment when nervous system disorders occurred.

[Acute interstitial nephritis and hantavirus infection]. / Tubulointerstitielle Nephritis und Hantavirus-Infektion.

Acute interstitial nephritis (AIN) is a cause of acute kidney injury and characterized by an inflammation of the tubulointerstitial space, leading to a decline in kidney function. Multiple etiologies can cause AIN including medications, autoimmune diseases and infections. A multiplicity of drugs is associated with AIN, while antibiotics (especially beta-lactams), proton-pump inhibitors (PPI) and non-steroidal anti-inflammatory agents (NSAIDs) are the most common. The pathognomonic triad of exanthema, fever and eosinophilia is rarely present in AIN patients. Treatment of medication-associated AIN is based upon the discontinuation of the provoking drug. Glucocorticoids can be considered in severe cases.Nephropathia epidemica (NE) is a disease caused by an infection with the Puumula-virus (PUUV) in northern and central Europe. Small rodents (mostly mice) are the host of the virus accountable for a rising number of infections during spring and summer. It is causing a syndrome consisting of AIN, fever and often thrombocytopenia. There is a good chance of complete recovery of kidney function following NE.

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.

External quality assessment of orthohantavirus and lymphocytic choriomeningitis virus molecular detection and serology in Europe, 2021.

BackgroundRodent-borne viruses such as orthohantaviruses and arenaviruses cause considerable disease burden with regional and temporal differences in incidence and clinical awareness. Therefore, it is important to regularly evaluate laboratory diagnostic capabilities, e.g. by external quality assessments (EQA).AimWe wished to evaluate the performance and diagnostic capability of European expert laboratories to detect orthohantaviruses and lymphocytic choriomeningitis virus (LCMV) and human antibody response towards orthohantaviruses.MethodsWe conducted an EQA in 2021; molecular panels consisted of 12 samples, including different orthohantaviruses (Seoul, Dobrava-Belgrade (DOBV), Puumala (PUUV) and Hantaan orthohantavirus), LCMV and negative controls. Serological panels consisted of six human serum samples reactive to PUUV, DOBV or negative to orthohantaviruses. The EQA was sent to 25 laboratories in 20 countries.ResultsThe accuracy of molecular detection of orthohantaviruses varied (50‒67%, average 62%) among 16 participating laboratories, while LCMV samples were successfully detected in all 11 participating laboratories (91-100%, average 96%). The accuracy of serological diagnosis of acute and past orthohantavirus infections was on average 95% among 20 participating laboratories and 82% in 19 laboratories, respectively. A variety of methods was used, with predominance of in-house assays for molecular tests, and commercial assays for serological ones.ConclusionSerology, the most common tool to diagnose acute orthohantavirus infections, had a high accuracy in this EQA. The molecular detection of orthohantaviruses needs improvement while LCMV detection (performed in fewer laboratories) had 95% accuracy. Further EQAs are recommended to be performed periodically to monitor improvements and challenges in the diagnostics of rodent-borne diseases.

Detection of Hantavirus during the COVID-19 Pandemic, Arizona, USA, 2020.

We identified 2 fatal cases of persons infected with hantavirus in Arizona, USA, 2020; 1 person was co-infected with SARS-CoV-2. Delayed identification of the cause of death led to a public health investigation that lasted ≈9 months after their deaths, which complicated the identification of a vector or exposure.

Favorable course of leptospirosis and hantavirus-induced acute tubulointerstitial nephritis under corticosteroid treatment.

BACKGROUND: We present two children with acute tubulointerstitial nephritis (ATIN) caused by leptospirosis in a 12-year-old boy and hantavirus in a 10-year-old girl. The role of glucocorticoids in the management of ATIN triggered by infectious agents is unclear. CASE-DIAGNOSIS/TREATMENT: Both children were hospitalized with jaundice, elevated serum creatinine, and thrombocytopenia. There was no oliguria or hypertension. Urine analysis revealed tubular proteinuria. Kidney biopsy was performed on one patient and showed tubulointerstitial inflammation with mild mesangial proliferation. Both patients were treated with glucocorticoids in view of deteriorating kidney function with respective serum creatinine values of 5.2 and 4.1 mg/dl. Both children exhibited an excellent clinical and biochemical response to treatment. Neither of the patients required dialysis. Positive serology test results indicated a recent leptospirosis and hantavirus infection. CONCLUSIONS: Leptospirosis and hantavirus associated ATIN share common clinical and biochemical features. Due to the low incidence in Europe these infectious causes of kidney dysfunction may be overlooked. Glucocorticoids may be considered in the management of ATIN.

Differential Cytokine Responses and the Clinical Severity of Adult and Pediatric Nephropathia Epidemica.

Nephropathia epidemica (NE), caused by the hantavirus infection, is endemic in Tatarstan Russia. The majority of patients are adults, with infection rarely diagnosed in children. This limited number of pediatric NE cases means there is an inadequate understanding of disease pathogenesis in this age category. Here, we have analyzed clinical and laboratory data in adults and children with NE to establish whether and how the disease severity differs between the two age groups. Serum cytokines were analyzed in samples collected from 11 children and 129 adult NE patients during an outbreak in 2019. A kidney toxicity panel was also used to analyze urine samples from these patients. Additionally, serum and urine samples were analyzed from 11 control children and 26 control adults. Analysis of clinical and laboratory data revealed that NE was milder in children than in adults. A variation in serum cytokine activation could explain the differences in clinical presentation. Cytokines associated with activation of Th1 lymphocytes were prominent in adults, while they were obscured in sera from pediatric NE patients. In addition, a prolonged activation of kidney injury markers was found in adults with NE, whilst only a short-lasting activation of these markers was observed in children with NE. These findings support previous observations of age differences in NE severity, which should be considered when diagnosing the disease in children.

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 Infection in Children-A Pilot Study of Single Regional Center.

BACKGROUND: Hantaviruses are infectious etiological agents of a group of rodent-borne hemorrhagic fevers, with two types of clinical manifestations in humans: hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS). According to available statistics, the disease occurs mainly in adults, but the lower incidence in the pediatric population might also be related to a lack of diagnosis possibilities or even unsatisfactory knowledge about the disease. MATERIALS AND METHODS: The purpose of this study was to evaluate the cases of hemorrhagic fever with renal syndrome diagnosed and treated in the Department of Nephrology at St. Mary's Emergency Hospital for Children in Iasi, Romania, representative of the North-East of Romania. We also reviewed the specialized literature on the topic. RESULTS: Between January 2017 and January 2022, eight cases of HFRS, all men, and seven from rural areas, aged 11-18 years old, were referred to our clinic because of an acute kidney injury (AKI). Seven cases were identified as Dobrava serotype while one case was determined by Haantan serotype. CONCLUSIONS: HFRS should always be considered as a differential diagnosis when faced with a patient with AKI and thrombocytopenia. Dobrava serotype is the most common hantavirus subtype in the Balkans. For the specific prevention of human infections, mainly in high-risk groups, vaccines are needed. As far as we know, this is the first study on HFRS in Romanian children.

Characterization of a Panel of Cross-Reactive Hantavirus Nucleocapsid Protein-Specific Monoclonal Antibodies.

Hantaviruses are emerging pathogens with a worldwide distribution that can cause life-threatening diseases in humans. Monoclonal antibodies (MAbs) against hantavirus nucleocapsid (N) proteins are important tools in virus diagnostics, epidemiological studies and basic research studies on virus replication and pathogenesis. Here, we extend the collection of previously generated MAbs raised against a segment of Puumala orthohantavirus (PUUV) N protein harbored on virus-like particles (VLPs) and MAbs against N proteins of Sin Nombre orthohantavirus/Andes orthohantavirus by generating nine novel MAbs against N proteins of Dobrava-Belgrade orthohantavirus (DOBV), Tula orthohantavirus (TULV), Thottapalayam thottimvirus (TPMV) and PUUV. In order to have a wide collection of well-described hantavirus-specific MAbs, the cross-reactivity of novel and previously generated MAbs was determined against N proteins of 15 rodent- and shrew-borne hantaviruses by different immunological methods. We found that all MAbs, excluding TPMV-specific MAbs, demonstrated different cross-reactivity patterns with N proteins of hantaviruses and recognized native viral antigens in infected mammalian cells. This well-characterized collection of cross-reactive hantavirus-specific MAbs has a potential application in various fields of hantavirus research, diagnostics and therapy.

Características e diagnóstico laboratorial das infecções causadas pelo hantavírus: revisão integrativa / Characteristics and laboratory diagnosis of infections caused by hantavirus: integrative review

A hantavirose é uma zoonose de distribuição mundial que utiliza como vetores roedores, musaranhos, toupeiras e morcegos. Os sintomas da infecção pelo hantavírus assemelham-se aos de diversas doenças, por isso o diagnóstico laboratorial é crucial para o tratamento precoce. Objetivo: Realizar uma revisão da literatura sobre as características e diagnóstico laboratorial da hantavirose. Métodos: Trata-se de uma revisão integrativa da literatura com base no modelo PRISMA, com seleção de estudos nas bases de dados Portal de Periódicos da Capes, PubMed/Medline, SciELO, ScienceDirect e Biblioteca Virtual em Saúde (BVS). Foram empregados os descritores: hantavírus, diagnóstico laboratorial, exames e zoonose, em português e inglês, no período de 2015 a 2022, sendo selecionados 19 artigos científicos em atendimento aos critérios de inclusão. Resultados e Discussão: Diversas técnicas diagnósticas podem ser empregadas em casos de hantavirose, sendo a biologia molecular a mais empregada, conjuntamente com a imunologia. Há outros recursos utilizados para monitoramento e evolução da doença, como a bioquímica, a hematologia e a imagenologia. Para a ocorrência de hantavirose é necessário um ambiente propício, clima específico e contato com hospedeiro suscetível, podendo evoluir para quadros assintomáticos ou sintomáticos com complicações graves. Conclusão: O diagnóstico dessa doença é desafiador e requer investigação detalhada que inclua a sintomatologia do paciente, o histórico de exposição a animais reservatórios e os resultados de exames laboratoriais. Como desfechos negativos da hantavirose incluem-se a febre hemorrágica com síndrome renal, a síndrome pulmonar por hantavírus e o óbito

Hantavirus is a worldwide distributed zoonosis that uses rodents, shrews, moles and bats as vectors. The symptoms of hantavirus infection resemble those of many diseases, so laboratory diagnosis is crucial for early treatment. Objective: The present study aimed to conduct a literature review on the characteristics and laboratory diagnosis of hantavirus. Methods: This is an integrative literature review based on the PRISMA model, with a selection of studies in the Capes Portal de Periódicos, PubMed/Medline, SciELO, ScienceDirect and Virtual Health Library databases, using the descriptors: hantavirus, laboratory diagnosis, exams, and zoonosis, in portuguese and english, from 2015 to 2022, and nineteen scientific articles that met the inclusion criteria were selected. Results and Discussion: Several techniques can be used in cases of hantavirus, with molecular biology being the most evidenced along with immunology. There are other parameters that are used for monitoring and evolution of the disease, such as biochemistry, hematology, and imaging. For the hantavirus disease, an adequate environment, specific climate and contact with a susceptible host are necessary, which may lead to asymptomatic conditions or symptoms with more serious complications. Conclusion: The diagnosis of this disease is challenging and requires detailed investigation that includes the patient's symptoms, the history of exposure to reservoir animals and the results of laboratory tests. Negative outcomes of hantavirus infection include hemorrhagic fever with renal syndrome, hantavirus pulmonary syndrome, and death

[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.

A rare case of acute acalculous cholecystitis secondary to hantavirus infection with renal syndrome.

Hantaviruses are single-stranded RNA viruses. They are transmitted to humans by rodents and insectivore hosts. Some Hantavirus subtypes are the causative agents of haemorrhagic fever with renal syndrome (HFRS), which is characterized by fever, thrombocytopenia, and acute kidney injury. Hantavirus infection is difficult to diagnose due to its non-specific clinical symptoms. Causes of acalculous cholecystitis are severe trauma or burn, surgery, long-term starvation and some viral infections. It is very rare for Hantavirus to cause acute acalculous cholecystitis. The treatment of acute acalculous cholecystitis is usually directed towards its symptoms. A 22-year-old male forest worker was admitted to our emergency outpatient clinic with the complaints of fatigue, oliguria, fever, abdominal pain and vomiting. After the clinical and laboratory examinations, HFRS and acute cholecystitis secondary to Hantavirus infection were diagnosed. The patient's condition and clinical findings improved after supportive treatment. Hantavirus infection should be considered in patients with acute kidney injury, cholecystitis and thrombocytopenia (Fig. 2, Ref. 10). Keywords: Hantavirus, acute kidney injury, acalculous cholecystitis, thrombocytopeni.

[Infection outbreak among German and Finish troups in Eastern Lapland during World War II - First description of hantavirus disease in the German language area]. / Infektionsausbruch bei deutschen und finnischen Soldaten während des 2. Weltkriegs im Östlichen Lappland ­ Erstbeschreibung der Hantavirus-Erkrankung im deutschen Sprachraum.

Eight decades ago, a report on "a swamp fever-like disease in German troups in Lapland" was published in this journal. The disease outbreak had occurred in 1942 and affected more than 1000 soldiers at the Finish front. The published, precise analysis of the clinical picture was obviously the first description of hantavirus disease in the German language area. Nowadays, hantavirus disease - in Central and Northern Europe also known as Nephropathia epidemica - is one of the most frequent notifiable virus diseases in Germany and Finland.

Hantavirus Hemorrhagic Fever with Renal Syndrome - Suspected Cases in Sri Lanka: Clinical Picture and Epidemiology from 2013-2021.

Hantavirus hemorrhagic fever with renal syndrome (HFRS) is an emerging zoonotic disease in Europe and Asia, which is clinically indistinguishable from leptospirosis. A total of 1,032 patients with clinical suspicion of HFRS-like illness were included in the analysis from March 2013 to March 2021. Of these, 168 were positive for hantavirus immunoglobulin M (IgM) antibodies. Thirty-one of 35 patients had a 4-fold increase in IgG antibody titer with paired serum, confirming acute hantavirus infections. The detected antibodies showed a diverse pattern, strongly cross-reacting with the Seoul, Hantaan, and Puumala virus antigens. All the IgM-positive patients had no serological evidence of acute dengue or leptospirosis and had classical features of HFRS, including fever, thrombocytopenia, and renal involvement. More than 90% of patients had a history of rodent exposure 2-3 weeks prior to the onset of the fever. The highest number of positive cases was diagnosed in the Western and North Central Provinces of Sri Lanka during the paddy harvesting seasons. A significant number of patients develop severe complications with high mortality rates. Therefore, hantavirus infection should be considered as a differential diagnosis for leptospirosis-like illnesses in Sri Lanka.

Use of a Novel Detection Tool to Survey Orthohantaviruses in Wild-Caught Rodent Populations.

Orthohantaviruses are negative-stranded RNA viruses with trisegmented genomes that can cause severe disease in humans and are carried by several host reservoirs throughout the world. Old World orthohantaviruses are primarily located throughout Europe and Asia, causing hemorrhagic fever with renal syndrome, and New World orthohantaviruses are found in North, Central, and South America, causing hantavirus cardiopulmonary syndrome (HCPS). In the United States, Sin Nombre orthohantavirus (SNV) is the primary cause of HCPS with a fatality rate of ~36%. The primary SNV host reservoir is thought to be the North American deer mouse, Peromyscus maniculatus. However, it has been shown that other species of Peromyscus can carry different orthohantaviruses. Few studies have systemically surveyed which orthohantaviruses may exist in wild-caught rodents or monitored spillover events into additional rodent reservoirs. A method for the rapid detection of orthohantaviruses is needed to screen large collections of rodent samples. Here, we report a pan-orthohantavirus, two-step reverse-transcription quantitative real-time PCR (RT-qPCR) tool designed to detect both Old and New World pathogenic orthohantavirus sequences of the S segment of the genome and validated them using plasmids and authentic viruses. We then performed a screening of wild-caught rodents and identified orthohantaviruses in lung tissue, and we confirmed the findings by Sanger sequencing. Furthermore, we identified new rodent reservoirs that have not been previously reported as orthohantavirus carriers. This novel tool can be used for the efficient and rapid detection of various orthohantaviruses, while uncovering potential new orthohantaviruses and host reservoirs that may otherwise go undetected.

[Hantavirus Disease: An Update]. / Hantavirus-Erkrankungen: Ein Update.

In addition to the well-known clinical early symptoms of hantavirus disease (fever, flank and abdominal pain as well as arthralgia), unusual neurological changes in the context of infection come into focus. The spectrum of neurological symptoms ranges from transient myopia to severe pareses in the context of Guillain-Barré syndrome. In endemic areas, rapid IgM tests for initial assessment are of certain value for differential diagnosis. For therapeutic approaches, only supportive measures up to transient dialysis are available.Molecular genetic analysis and comparison of hantavirus strains of patients and mice from the same geographical area allowed molecular characterization of different outbreak regions. In the meantime, the Puumala viruses of the main outbreak regions in Germany are molecularly well characterized; therefore, the nucleotide sequence of the virus strain detected in a patient makes it possible to draw conclusions about the geographic region where the patient's infection took place.The human pathogenic hantaviruses being prevalent in Germany are the Puumala virus (reservoir: bank vole) and the Dobrava-Belgrade virus, genotype Kurkino (reservoir: striped field mouse). Recently, the molecular detection of further hantaviruses in patients with hantavirus disease was achieved. It can be concluded that also the Seoul virus (reservoir: rats) and the Tulavirus (reservoir: field mouse and related species) occasionally cause hantavirus disease in Germany.New results revealed that human infections can occur not only by the generally accepted route of inhalation of virus-containing aerosols, but also by ingestion of virus-containing materials.For patients with hantavirus infection or disease, it can be assumed that they are not infectious for their environment. A new systematic review could not confirm a human-to-human transmission previously postulated for South American hantaviruses.While all known human pathogenic hantaviruses are transmitted by rodents, other hantaviruses have been recently detected in shrews, moles, and bats. The clinical significance of these new viruses is quite unclear as yet.

Global Comprehensive Outlook of Hantavirus Contagion on Humans: A Review.

Hantaviruses are rodent viruses that have been identified as etiologic agents of 2 diseases in humans: Hemorrhagic Fever with Renal Syndrome (HFRS) and Nephropathiaepidemica (NE) in the Old World and Hantavirus Pulmonary Syndrome (HPS) in the New World. Orthohantavirus is a genus of single-stranded, enveloped, negative-sense RNA viruses in the family Hantaviridae of the order Bunyavirales. The important reservoir of Hantaviruses is rodents. Each virus serotype has its unique rodent host species and is transmitted to human beings with the aid of aerosolized virus, which is shed in urine, faeces and saliva and hardly by a bite of the contaminated host. Andes virus is the only Hantavirus identified to be transmitted from human-to-human and its major signs and symptoms include fever, headache, muscle aches, lungs filled with fluid, etc. In early 1993, this viral syndrome appeared in the Four Corner location in the southwestern United States. The only accepted therapeutics for this virus is Ribavirin. Recently, serological examinations to identify Hantavirus antibodies have become most popular for investigation among humans and rodent reservoirs.