Direct and indirect effects of Puumala hantavirus on platelet function.

Thrombocytopenia is a cardinal symptom of hantavirus-induced diseases including Puumala virus (PUUV)-induced hemorrhagic fever with renal syndrome (HFRS), which is associated with impaired platelet function, bleeding manifestations and augmented thrombotic risk. However, the underlying mechanisms causing thrombocytopenia and platelet hypo-responsiveness are unknown. Thus, we investigated the direct and indirect impact of PUUV on platelet production, function and degradation. Analysis of PUUV-HFRS patient blood revealed that platelet hypo-responsiveness in PUUV infection was cell-intrinsic and accompanied by reduced platelet-leukocyte aggregates (PLAs) and upregulation of monocyte tissue factor (TF), whereas platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation was comparable to healthy controls. Plasma CXCL4 levels followed platelet count dynamics throughout disease course. PUUV activated both neutrophils and monocytes in vitro, but platelet desialylation, degranulation and GPIIb/IIIa activation as well as PLA formation and endothelial adhesion under flow remained unaltered in the presence of PUUV. Further, MEG-01 megakaryocytes infected with PUUV displayed unaltered polyploidization, expression of surface receptors and platelet production. However, infection of endothelial cells with PUUV significantly increased platelet sequestration. Our data thus demonstrate that although platelet production, activation or degradation are not directly modulated, PUUV indirectly fosters thrombocytopenia by sequestration of platelets to infected endothelium. Upregulation of immunothrombotic processes in PUUV-HFRS may further contribute to platelet dysfunction and consumption. Given the pathophysiologic similarities of hantavirus infections, our findings thus provide important insights into the mechanisms underlying thrombocytopenia and highlight immune-mediated coagulopathy as potential therapeutic target.

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.

Continuous renal replacement therapy rescues severe haemorrhagic fever with renal syndrome in pregnancy: a case report.

BACKGROUND: Haemorrhagic fever with renal syndrome (HFRS) is a natural epidemic disease caused by various types of viruses of the genus Hantavirus, which are mainly transmitted by contact with the infected rodents and their droppings. Pregnancy complicated with HFRS is rare; however, adverse maternal and foetal outcomes may be noted. In this report, we describe a case involving a pregnant woman with HFRS who was in a state of multiple organ dysfunction syndrome (MODS) and was successfully treated with continuous renal replacement therapy (CRRT). CASE PRESENTATION: A 32-year-old pregnant woman at 29 weeks of gestation was hospitalised for a fever and upper respiratory tract infection due to HFRS in winter. Persistent fever, coagulation disorder, thrombocytopenia, electrolyte imbalance, abnormal liver function, and renal failure were noted during the progression of the disease. The patient was treated with CRRT. She recovered after 21 days, and delivered a live infant by caesarean section at 38 weeks of gestation. Furthermore, obvious abnormalities were not detected during the follow-up of the mother and infant at 42 days, 3 months, 6 months, and 1 year after the delivery. CONCLUSIONS: Early diagnosis, timely application of CRRT, and comprehensive treatment may be essential for the successful treatment of patients with HFRS during pregnancy.

HTNV Sensitizes Host Toward TRAIL-Mediated Apoptosis-A Pivotal Anti-hantaviral Role of TRAIL.

Hantaviruses can cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and have led to public health threat in China. The pathogenesis of HFRS is complex and involves capillary leakage due to the infection of vascular endothelial cells. Accumulating evidence has demonstrated that hantavirus can induce apoptosis in many cells, but the mechanism remains unclear. Our studies showed that Hantaan virus (HTNV) infection could induce TNF-related apoptosis-inducing ligand (TRAIL) expression in primary human umbilical vein endothelial cells (HUVECs) and sensitize host cells toward TRAIL-mediated apoptosis. Furthermore, TRAIL interference could inhibit apoptosis and enhance the production of HTNV as well as reduce IFN-ß production, while exogenous TRAIL treatment showed reverse outcome: enhanced apoptosis and IFN-ß production as well as a lower level of viral replication. We also observed that nucleocapsid protein (NP) and glycoprotein (GP) of HTNV could promote the transcriptions of TRAIL and its receptors. Thus, TRAIL was upregulated by HTNV infection and then exhibited significant antiviral activities in vitro, and it was further confirmed in the HTNV-infected suckling mice model that TRAIL treatment significantly reduced viral load, alleviated virus-induced tissue lesions, increased apoptotic cells, and decreased the mortality. In conclusion, these results demonstrate that TRAIL-dependent apoptosis and IFN-ß production could suppress HTNV replication and TRAIL treatment might be a novel therapeutic target for HTNV infection.

Innate and adaptive immune responses against human Puumala virus infection: immunopathogenesis and suggestions for novel treatment strategies for severe hantavirus-associated syndromes.

Two related hyperinflammatory syndromes are distinguished following infection of humans with hantaviruses: haemorrhagic fever with renal syndrome (HFRS) seen in Eurasia and hantavirus pulmonary syndrome (HPS) seen in the Americas. Fatality rates are high, up to 10% for HFRS and around 35%-40% for HPS. Puumala virus (PUUV) is the most common HFRS-causing hantavirus in Europe. Here, we describe recent insights into the generation of innate and adaptive cell-mediated immune responses following clinical infection with PUUV. First described are studies demonstrating a marked redistribution of peripheral blood mononuclear phagocytes (MNP) to the airways, a process that may underlie local immune activation at the site of primary infection. We then describe observations of an excessive natural killer (NK) cell activation and the persistence of highly elevated numbers of NK cells in peripheral blood following PUUV infection. A similar vigorous CD8 Tcell response is also described, though Tcell responses decline with viraemia. Like MNPs, many NK cells and CD8 T cells also localize to the lung upon acute PUUV infection. Following this, findings demonstrating the ability of hantaviruses, including PUUV, to cause apoptosis resistance in infected target cells, are described. These observations, and associated inflammatory cytokine responses, may provide new insights into HFRS and HPS disease pathogenesis. Based on similarities between inflammatory responses in severe hantavirus infections and other hyperinflammatory disease syndromes, we speculate whether some therapeutic interventions that have been successful in the latter conditions may also be applicable in severe hantavirus infections.

Two cases of imported hemorrhagic fever with renal syndrome and systematic review of literature.

Many factors are involved in the epidemiology of hemorrhagic fever with renal syndrome (HFRS). Imported cases, as well as those by emigrants, have been reported in literature worldwide. Our goal is to document two cases of HFRS, imported by two immigrants from two countries, and to make a review of the imported HFRS literature data. We performed a systematic literature review (PRISMA guidelines) of imported cases of HFRS and herein describe our two clinical cases. We found 20 published papers, with 16 of them in English and 4 in other languages. Twenty-three patients with travel- or immigration-associated HFRS, including our two cases, were identified. We included only papers that were in English. The average age of the patients was 35.9 ±â€¯15.13 years, and the ratio of male to female was 8:1. Imported disease from Europe to Europe occurred in seven cases, America to Europe occurred in four cases, Europe to America occurred in two cases, America to America occurred in two cases, Asia to Asia in one case, Asia to Europe in one case, and Europe to Asia in one case. The results of the two cited cases are based on the clinical-laboratory, anamnestic, and serologic data for both the patients who tested positive for HFRS. Our systematic analysis shows that international travelers are important sources of infectious diseases. HFRS related to travel and immigration is a rare event. Principal risk factors for travelers and immigrants are camping outside recommended areas or under unsuitable conditions. In recent years, various publications have shown that international travelers and immigrants have expanded the spectrum of imported infectious diseases. The literature data show that the actual reported numbers of imported case of HFRS are limited.

Acute hantavirus infection presenting as haemolytic-uraemic syndrome (HUS): the importance of early clinical diagnosis.

The European prototype of hantavirus, Puumala virus (PUUV), isolated from a common wild rodent, the bank vole (Myodes glareolus), causes nephropathia epidemica (NE). NE can perfectly mimic haemolytic-uraemic syndrome (HUS), progressing from an aspecific flu-like syndrome to acute kidney injury with thrombocytopaenia, and presenting with some signs of haemolytic anaemia and/or coagulopathy. Moreover, both NE and HUS can occur in local outbreaks. We report an isolated case of NE, initially referred for plasmapheresis for suspected HUS, although signs of overt haemolysis were lacking. Early suspicion of hantavirus infection, later confirmed by serology and reverse transcription polymerase chain reaction (RT-PCR), prevented subsequent excessive treatment modalities.

Testing Experimental Therapies in a Guinea Pig Model for Hemorrhagic Fever.

Hemorrhagic fever viruses are among the deadliest pathogens known to humans, and often, licensed medical countermeasures are unavailable to prevent or treat infections. Guinea pigs are a commonly used animal for the preclinical development of any experimental candidates, typically to confirm data generated in mice and as a way to validate and support further testing in nonhuman primates. In this chapter, we use Sudan virus (SUDV), a lethal filovirus closely related to Ebola virus, as an example of the steps required for generating a guinea pig-adapted isolate that is used to test a monoclonal antibody-based therapy against viral hemorrhagic fevers.

Clinical aspects of hantavirus infections in Bulgaria.

BACKGROUND: Hantaviruses cause two distinct human diseases: hemorrhagic fever with renal syndrome (HFRS) in Asia and Europe and hantavirus pulmonary syndrome (HPS) in America. In Europe, mainly Puumala, Dobrava and Seoul viruses cause HFRS. A total of 23 cases of HFRS were detected in Bulgaria over a 2­year period 2013-2014. The aim of the study was to present epidemiology, clinical manifestations and laboratory findings of these patients. METHODS: Patients with HFRS were diagnosed using PCR, ELISA and immunoblotting tests. RESULTS: Dobrava-Belgrade virus (DOBV) was revealed as etiological agent in 16 (69.6%) patients and Puumala virus (PUUV) in 7 (30.4%) patients. All 23 patients were men aged 22-66 years of which 6 (26.1%) patients originated from regions in northern and western Bulgaria previously thought to be non-endemic. Patients with HFRS, despite the infecting hantavirus, manifested acute renal failure, asthenia and less pronounced hemorrhagic syndrome. Patients with DOBV infection were much more likely to present with arthromyalgia, severe headache, severe to moderately severe asthenoadynamia, abdominal pain, vomiting, hypotension, nervous system disorders as well as kidney enlargement, leucopenia and higher levels of blood creatinine, requiring hemodialysis procedures more often and for a longer period of time than patients with PUUV infection. CONCLUSIONS: The present report describes for the first time comparative analysis of epidemiological features, clinical manifestations and laboratory findings of DOBV and PUUV infections in Bulgaria.

Specific interference shRNA-expressing plasmids inhibit Hantaan virus infection in vitro and in vivo.

AIM: To investigate the antiviral effects of vectors expressing specific short hairpin RNAs (shRNAs) against Hantaan virus (HTNV) infection in vitro and in vivo. METHODS: Based on the effects of 4 shRNAs targeting different regions of HTNV genomic RNA on viral replication, the most effective RNA interference fragments of the S and M genes were constructed in pSilencer-3.0-H1 vectors, and designated pSilencer-S and pSilencer-M, respectively. The antiviral effect of pSilencer-S/M against HTNV was evaluated in both HTNV-infected Vero-E6 cells and mice. RESULTS: In HTNV-infected Vero-E6 cells, pSilencer-S and pSilencer-M targeted the viral nucleocapsid proteins and envelope glycoproteins, respectively, as revealed in the immunofluorescence assay. Transfection with pSilencer-S or pSilencer-M (1, 2, 4 µg) markedly inhibited the viral antigen expression in dose- and time-dependent manners. Transfection with either plasmid (2 µg) significantly decreased HTNV-RNA level at 3 day postinfectin (dpi) and the progeny virus titer at 5 dpi. In mice infected with lethal doses of HTNV, intraperitoneal injection of pSilencer-S or pSilencer-M (30 µg) considerably increased the survival rates and mean time to death, and significantly reduced the mean virus yields and viral RNA level, and alleviated virus-induced pathological lesions in lungs, brains and kidneys. CONCLUSION: Plasmid-based shRNAs potently inhibit HTNV replication in vitro and in vivo. Our results provide a basis for development of shRNA as therapeutics for HTNV infections in humans.

Treatment of a patient with severe hemorrhagic fever accompanied by infection with methicillinresistant Staphylococcus aureus, Acinetobacter baumannii, aspergillus and mucor: a case report.

A 40-year-old Korean man developed hemorrhagic fever in Xi'an, which is one of the main endemic areas for this illness in China. According to the local epidemiological situation, his condition could have been due to hantavirus infection, but this was not confirmed. He presented with the typical symptoms of hemorrhagic fever and rapidly progressed to a severe multisystem illness. The clinical situation deteriorated rapidly after admission, and he became coinfected with methicillin-resistant Staphylococcus aureus, Acinetobacter baumannii, aspergillus, and mucor. The patient was successfully treated with appropriate fluid infusion, hemodynamic support, continuous renal replacement therapy, liver protectants, and antibacterials. This case indicates that the choice of antimicrobials and the required dose are crucial issues, and that the vaccination campaign for hemorrhagic fever in Xi'an needs greater attention.

Community Acquired Severe Acute Kidney Injury Caused by Hantavirus-Induced Hemorrhagic Fever with Renal Syndrome Has a Favorable Outcome.

BACKGROUND: Puumala hantavirus (PUUV) induces an acute tubulointerstitial nephritis and acute kidney injury (AKI). Our aim was to evaluate the prognosis of severe AKI associated with PUUV infection. METHODS: We examined 556 patients who were treated at Tampere University Hospital during 1982-2013 for acute, serologically confirmed PUUV infection. Plasma creatinine was measured during hospitalization, convalescence, and 1, 2, and 5 years after the acute infection. RESULTS: Plasma creatinine concentration was elevated (>100 µmol/l) in 459 (83%) patients, while altogether 189 patients (34%) had severe AKI defined as Kidney Disease: Improving Global Outcomes (KDIGO) stage 3, that is, plasma creatinine ≥353.6 µmol/l (4.0 mg/dl) or need of dialysis. There were no fatal cases during the hospitalization or the following 3 months. Fatality rate during the years following PUUV infection did not differ between patients who had suffered from severe AKI versus those without severe AKI. Post-hospitalization plasma creatinine values were available for 188 (34%) patients. One month after the acute infection, patients with prior severe AKI had higher median plasma creatinine concentration (82 µmol/l, range 54-184) than patients without severe AKI (74 µmol/l, range 55-109, p = 0.005). After 1 year, no significant difference existed in median plasma creatinine concentrations between patients with (71 µmol/l, range 36-123) and without prior severe AKI (72 µmol/l, range 34-116, p = 0.711). After 5 years all but 1 patient had normal creatinine levels. CONCLUSIONS: In contrast to the worldwide well-accepted KDIGO criteria, severe AKI associated with PUUV infection is not associated with excess fatality but has a very good prognosis, both in the short and long terms.

Seoul hantavirus in brown rats in the Netherlands: implications for physicians--Epidemiology, clinical aspects, treatment and diagnostics.

The recent discovery of Seoul hantavirus (SEOV) presence in wild rat populations in the Netherlands has direct implications for Dutch clinicians and hantavirus diagnostics. SEOV is amongst the Old World hantaviruses which cause haemorrhagic fever and renal syndrome (HFRS) in humans. HFRS is characterised by a classical triad of fever, acute kidney injury and haemorrhage, but can show different signs and symptoms in specific cases. SEOV is transmitted from infected rats to humans by inhalation of aerosolised excreta. When compared with the known circulating hantaviruses in the Netherlands, Puumala (PUUV) and Tula (TULV), SEOV causes a more severe form of HFRS. Data from cohort studies undertaken in China and Northern Europe show differences in signs and symptoms at onset of disease, (haemorrhagic) complications and mortality. Furthermore, routine diagnostics currently available for hantavirus diagnosis in the Netherlands are not optimised for SEOV detection. The clinical outcome of an SEOV and PUUV infection will greatly benefit from an early diagnosis which will reduce the costs of unnecessary tests and treatments as well. The discovery of SEOV circulation in the Netherlands follows recent findings of SEOV infections in both rodents and humans in England, Wales, France, Belgium and Sweden, indicating the emerging character of SEOV and a high importance of this hantavirus for Public Health in large areas of Europe. Here, we review the current knowledge on the clinical manifestation of SEOV versus PUUV infections in humans, the treatment of clinical cases and diagnostics.

[Clinical characteristics of pediatric hemorrhagic fever with renal syndrome].

OBJECTIVE: To study the clinical characteristics of pediatric hemorrhagic fever with renal syndrome (HFRS), and to improve its understanding so as to reduce the misdiagnosis. METHODS: A retrospective analysis was performed on the clinical data of 26 children with HFRS between January 2009 and December 2012. RESULTS: The age of disease onset was mainly distributed between 7 and 14 years (23 cases, 88%), and the male-to-female ratio was 1.89:l. The clinical manifestations of pediatric HFRS varied. The early symptoms resembled those of a cold, and in the course of HFRS, most patients developed digestive symptoms such as vomiting and abdominal pain. The laboratory examinations usually implicated platelet changes, and the imaging examinations revealed polyserous effusions. The prominent complication was myocardial injury. CONCLUSIONS: Pediatric HFRS mainly occurs in school-age children, more commonly in males. HFRS does not have typical clinical manifestations or symptoms, so it should be distinguished from cold or appendicitis at the early stage. When applying the fluid replacement therapy, the cardiac function should be carefully monitored in case of heart failure.

Clinical characteristics and outcomes in critical patients with hemorrhagic fever with renal syndrome.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) has become an important public health concern because of the high incidence and mortality rates, and limited treatment and vaccination. Until now, clinical studies on characteristics and outcomes in critical patients with HFRS have been limited. The aim of this study was to observe the clinical characteristics and cumulative proportions surviving and explore the predictive effects and risk factors for prognosis. METHODS: A detailed retrospective analysis of clinical records for critical HFRS patients was conducted. The patients enrolled were treated in the centre for infectious diseases, Tangdu Hospital, between January 2008 and August 2012. The clinical characteristics between the survivors and non-survivors were compared by Student's t-test or Chi-square test. The risk clinical factors for prognosis were explored by logistic regression analysis. The predictive effects of prognosis in clinical and laboratory parameters were analyzed by receiver operating characteristic (ROC) curves. The cumulative proportions surviving at certain intervals in the critical patients were observed by Kaplan-Meier survival analysis. RESULTS: Of the 75 patients enrolled, the cumulative proportion surviving was 70.7% at the second week interval, with a 28-day mortality rate of 36.3%. The non-survivors tended to have higher frequencies of agitation, dyspnea, conjunctival hemorrhage, coma, cardiac failure, acute respiratory distress syndrome (ARDS) and encephalopathy (P < .05). ARDS, conjunctival hemorrhage and coma were risk factors for death in the critical patients with HFRS. The non-survivors were found to have lower serum creatinine (Scr) levels (P < .001) and higher incidences of prolonged prothrombin time (PT) (P = .006), activated partial thromboplastin time (APTT) (P = .003) and elevated white blood cells (WBC) levels (P = .005), and the laboratory parameters mentioned above reached statistical significance for predicting prognosis (P < .05). CONCLUSION: The high fatality in critical patients with HFRS underscores the importance of clinicians' alertness to the occurrence of potentially fatal complications and changes in biochemical status to ensure that timely and systematically supportive treatment can be initiated when necessary.

Clinical study of critical patients with hemorrhagic fever with renal syndrome complicated by acute respiratory distress syndrome.

OBJECTIVES: The aim of this study was to investigate the clinical characteristics and outcomes of critical patients with hemorrhagic fever with renal syndrome (HFRS) complicated by acute respiratory distress syndrome (ARDS). MATERIALS AND METHODS: To observe the demographic, epidemiological and clinical characteristics, and to explore the predictive effects for prognosis in laboratory findings, we conducted a detailed retrospective analysis of clinical records for critical patients with HFRS complicated by ARDS, treated at the center for infectious diseases, Tangdu Hospital, between January 2008 and December 2012. RESULTS: A total of 48 critical patients with laboratory confirmed HFRS accompanied by ARDS were enrolled in the study, including 27 survivors and 21 non-survivors, with a fatality rate of 43.75%. Thirty-one individuals (64.6%) contracted HFRS between the months of September and December. The non-survivors tended to have lower incidence of overlapping phase (P = 0.025). There were no obvious differences in the needs for mechanical ventilation (MV) and renal replacement therapy (RRT), except for the need for vasoactive drugs between the survivors and non-survivors (P = 0.001). The non-survivors were found to have higher frequencies of encephalopathy, refractory shock and multiple organ dysfunction syndrome (MODS), lower incidences of acute renal failure (ARF) and secondary hypertension (P<0.05). The non-survivors tended to have lower levels of serum creatinine (Scr) (P<0.001) and fibrinogen (Fib) (P = 0.003), higher incidences of prolonged prothrombin time (PT) (P = 0.006) and activated partial thromboplastin time (APTT) (P = 0.020) and higher levels of aspartate aminotransferase (AST) (P = 0.015), and the laboratory parameters mentioned above reached statistical significance for predicting prognosis (P<0.05). CONCLUSION: The high mortality rate of critical patients with HFRS complicated by ARDS emphasizes the importance of clinicians' alertness and timely initiation of systemic supportive therapy.

Viral load and humoral immune response in association with disease severity in Puumala hantavirus-infected patients--implications for treatment.

Hantaviruses are the causative agents of haemorrhagic fever with renal syndrome (HFRS) in Eurasia and of hantavirus cardiopulmonary syndrome (HCPS) in the Americas. The case fatality rate varies between different hantaviruses and can be up to 40%. At present, there is no specific treatment available. The hantavirus pathogenesis is not well understood, but most likely, both virus-mediated and host-mediated mechanisms are involved. The aim of the present study was to investigate the association among Puumala hantavirus (PUUV) viral RNA load, humoral immune response and disease severity in patients with HFRS. We performed a study of 105 PUUV-infected patients that were followed during the acute phase of disease and for up to 1-3 months later. Fifteen of the 105 patients (14%) were classified as having moderate/severe disease. A low PUUV-specific IgG response (p <0.05) and also a higher white blood cell count (p <0.001) were significantly associated with more severe disease. The PUUV RNA was detected in a majority of patient plasma samples up to 9 days after disease onset; however, PUUV RNA load or longevity of viraemia were not significantly associated with disease severity. We conclude that a low specific IgG response was associated with disease severity in patients with HFRS, whereas PUUV RNA load did not seem to affect the severity of HFRS. Our results raise the possibility of passive immunotherapy as a useful treatment for hantavirus-infected patients.

The pathogenesis of nephropathia epidemica: new knowledge and unanswered questions.

Puumala virus (PUUV) causes an acute hemorrhagic fever with renal syndrome (HFRS), a zoonosis also called nephropathia epidemica (NE). The reservoir host of PUUV is the bank vole (Myodes glareolus). Herein we review the main clinical manifestations of NE, acute kidney injury, increased vascular permeability, coagulation abnormalities as well as pulmonary, cardiac, central nervous system and ocular manifestations of the disease. Several biomarkers of disease severity have recently been discovered: interleukin-6, pentraxin-3, C-reactive protein, indoleamine 2,3-dioxygenase, cell-free DNA, soluble urokinase-type plasminogen activator, GATA-3 and Mac-2 binding protein. The role of cytokines, vascular endothelial growth hormone, complement, bradykinin, cellular immune response and other mechanisms in the pathogenesis of NE as well as host genetic factors will be discussed. Finally therapeutic aspects and directions for further research will be handled.

Acute pancreatitis associated with hemorrhagic fever with renal syndrome: clinical analysis of 12 cases.

BACKGROUND: Acute pancreatitis is one of the rare complications of hemorrhagic fever with renal syndrome (HFRS), which easy to be misdiagnosed as acute abdomen, usually critically ill, poor treatment effect, highly mortality. In this study, we retrospectively analyzed to explore the clinical characteristics, 12 cases of hemorrhagic fever with renal syndrome complicated with acute pancreatitis treatment methods and prognosis. METHODS: We conducted a retrospective study of HFRS in patients complicated with acute pancreatitis. 12 cases were collected from Ningbo first hospital between January 2001 and December 2012. Clinical information and laboratory parameters were obtained by reviewing literature and records. RESULTS: Twelve from 156 cases (7.69%) HFRS complicated with acute pancreatitis. Men comprised more than half (75%) of the sample population, the mean age was (38 ± 19) years. Abdominal pain was the main clinical manifestations in all the patients, all of their serum amylase and serum lipase were increased, 10 patients were given the total abdomen CT examination, eight cases showed enlargement of the pancreas and surrounding leakage, two cases showed pancreatic necrosis and hemorrhage. Three cases complicated with pulmonary edema. In 12 cases, four of them received hemodialysis treatment, one gives surgical intervention. Eight cases were complete remission, three cases were partial remission and one case was death. CONCLUSIONS: Acute pancreatitis is one of rare of the serious complications of HFRS, whereas the correct diagnosis and clear the cause of disease is critical for improve the quality of life of patients and reduce the mortality, timely hemodialysis treatment is effective, early intervention can improve the prognosis.

[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.