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.

Hantavirus Infections among Military Forces.

INTRODUCTION: Hantaviruses cause two kinds of clinical syndromes. Hemorrhagic fever with renal syndrome is caused by Hantaan virus in Asia, Puumala virus (PUUV) and Dobrava virus in Europe, and Seoul virus worldwide. Hantavirus cardiopulmonary syndrome is caused by Sin Nombre virus in North America and Andes virus and related viruses in Latin America. All hantaviruses are carried by rodents and insectivores. Humans are infected via inhaled aerosols of rodent excreta. In the history, there are several epidemics of acute infectious diseases during many wars, which have been suggested or proven to be caused by various hantaviruses. MATERIALS AND METHODS: Literature review of 41 original publications and reviews published between 1943 and 2022 was performed. Among them, 23 publications handle hantavirus infections among military forces, and the rest 17 hantavirus infections themselves. RESULTS: A large epidemic during World War II in 1942 among German and Finnish soldiers in Northern Finland with more than 1,000 patients was most probably caused by PUUV. During Korean War in 1951-1954,∼ 3,200 cases occurred among United Nations soldiers in an epidemic caused by Hantaan virus. During Balkan war from 1991 to 1995, numerous soldiers got ill because of hantavirus infection caused by PUUV and Dobrava virus. Several other reports of cases of various hantavirus infections especially among U.S. soldiers acting in South Korea, Germany, Bosnia, and Kosovo have been described in the literature. CONCLUSIONS: Military maneuvers usually include soil removal, spreading, digging with accompanied dust, and living in field and other harsh conditions, which easily expose soldiers to rodents and their excreta. Therefore, the risks of hantavirus infections in military context are obvious. All military infections have been caused by hantaviruses leading to hemorrhagic fever with renal syndrome.

Case Report: Hemorrhagic Fever with Renal Syndrome Complicated by Bilateral Subdural Hematoma.

Hemorrhagic fever with renal syndrome (HFRS) is an acute, natural focal disease worldwide. Bilateral subdural hematoma (BSH) is a rare occurrence in patients with HFRS. A 51-year-old man was admitted with fever, headache, lower back pain, and reduced urine volume. The patient was diagnosed with HFRS accompanied by BSH, as evidenced by IgM and IgG antibodies for hantavirus that were positive, and abnormal blood test results and computed tomographic head scan. He recovered and was discharged after symptomatic treatment. Hemorrhagic fever with renal syndrome might present rare clinical manifestations with BSH. The early identification of this condition is crucial to an improved prognosis.

FDG PET/CT in Hantavirus Hemorrhagic Fever With Renal Syndrome.

ABSTRACT: A 58-year-old man with fever, myalgia, and dysuria was admitted to the hospital. Because of prolonged fever, FDG PET/CT was performed. Surprisingly, bilateral kidneys were rapidly enlarged for 5 days with the renal parenchyma showing intense hypermetabolism. FDG PET/CT demonstrated physiology of Hantavirus invading kidneys and causing nephritis. This case illustrates that FDG PET/CT could be the choice of image modality for diagnosis and treatment evaluation of patients suspected of hemorrhagic fever with renal syndrome. To the best of our knowledge, this is the first report of FDG PET/CT image for a patient with hemorrhagic fever with renal syndrome.

Hemorrhagic fever with renal syndrome and reversible splenial lesion syndrome.

Hemorrhagic fever with renal syndrome (HFRS) and reversible splenial lesion syndrome are both considered uncommon conditions relatively rare. Fever, hemorrhage, and acute kidney injury are the prevailing symptoms frequently observed in cases of HFRS. We describe a case of a middle-aged man who had been hospitalized with fever and acute neurological symptoms. His main symptom was recurrent dizziness. Cranial computed tomography (CT) did not reveal any obvious lesions, such as encephalorrhagia or infarctions. The splenium of corpus callosum showed hyperintensity on brain magnetic resonance imaging (MRI), which is in line with the characteristic radiographic observations of reversible splenial lesion syndrome (RESLES). Further analyses revealed that the patient's platelet counts had decreased to 7×109/L while hemorrhagic fever antibodies were positive. Eventually, the patient was diagnosed with HFRS and exhibited clinical improvements after active treatment.

A case of pulmonary tuberculosis patient complicated with hemorrhagic fever with renal syndrome and scrub typhus in Yunnan, China: a case report.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) caused by Orthohantavirus (OHV) and scrub typhus (ST) caused by Orientia tsutsugamushi (OT) are two infectious diseases prevalent in southwest China. Rodents are the natural host and the main source of the two diseases. OT infection to humans is usually resulted from bite of an infective chigger mite on rodents, and OHV is transmitted through contact or inhalation of aerosols and secretions from infected rodent. The use of antibiotics and hormones is crucial for infectious diseases, although the clinical manifestations are not obvious and a definitive diagnosis becomes more difficult in the presence of these drugs. Clinically, fever is the first symptom of these two diseases, and most of them are accompanied by common symptoms such as chills and headaches. The clinical symptoms of these two diseases are very similar and therefore it is not easy to make a differential diagnosis. CASE PRESENTATION: In this case, a 44-year-old male famer with pulmonary tuberculosis and a history of working in coal transportation was admitted to the hospital because of respiratory symptoms accompanied by fever, headache, and skin rashes on his body. Biochemical and urinalysis revealed the hepatic and renal injury. The subsequent molecular testing confirmed he suffered from HFRS and scrub typhus simultaneously that the serological and clinical diagnosis could not identify the cause of infection before. Such case has not been reported in Yunnan Province before. CONCLUSION: The clinical diagnosis should be combined with serological and nucleic acid testing approaches for differential diagnosis in areas where HFRS and ST are endemic.

Logistic regression analysis of risk factors for hemorrhagic fever with renal syndrome complicated with acute pancreatitis.

BACKGROUND: Hantavirus infection is the main cause of hemorrhagic fever with renal syndrome (HFRS), which is common in Asia and Europe. There is a considerable risk of morbidity and mortality from the uncommon Hantavirus complication known as acute pancreatitis (AP). METHODS: Retrospective analysis of the medical records of individuals with HFRS was performed. Relevant variables were assessed by univariate analyses and the variables with a p value <.05 were entered into the multivariable regression analysis. RESULTS: In this study, 114 individuals with HFRS in total were included, and 30 of them (26.32%) had AP. The univariate analyses showed that living in Xuancheng city (Anhui Province); an alcohol consumption history; white blood cell (WBC) count; lymphocyte (lym%) and eosinophil percentages (EO%); neutrophil (neut), eosinophil (EO), and red blood cell (RBC) counts; hemoglobin (Hb); hematocrit (HCT); proteinuria; hematuria; albumin (ALB), blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA), cystatin-C (Cys-C) levels; carbon dioxide-combining power (CO2CP); fibrinogen degradation products (FDPs); and D-dimer level were significantly associated with HFRS complicated with AP (p < .05). In the multivariable regression analysis, an alcohol consumption history, lym%, proteinuria, FDPs and D-dimer level were found to be risk factors for HFRS complicated with AP (p < .05). CONCLUSION: Our findings indicate that HFRS patients with a history of consuming alcohol, a high lym%, intense proteinuria, high levels of FDPs, and a low level of D-dimer might be more prone to the development of AP.KEY MESSAGESThis is the first report employing Logistic regression analysis methods for exploring the risk factors for HFRS complicated with AP in China.Many factors (most are laboratory parameters) were significantly associated with HFRS complicated with AP.We found that HFRS patients with a history of consuming alcohol, a high lym%, intense proteinuria, high levels of FDPs, and a low level of D-dimer might be more prone to the development of AP.

Case Report: Multiple Organ Failure Caused by Hemorrhagic Fever with Renal Syndrome.

Hemorrhagic fever with renal syndrome (HFRS), a natural epidemic disease caused by hantavirus (HV), is one of the viral diseases that pose a major threat to our health. Considering the increasing number of atypical-onset cases reported in some countries, it is important to be familiar with the symptoms of HFRS and the signs of HV infection. This report describes the case of a 55-year-old man with complaints of fever, vomiting, and diarrhea. His symptoms showed no significant improvement after routine anti-infective, antipyretic, and other symptomatic supportive treatments administered at a local clinic. During these treatments, the patient had progressive oliguria; after 3 days, he also developed multiple organ failures, such as the liver and kidney, and was examined for positive serum IgM antibodies to hemorrhagic fever during treatment at our hospital. The patient was finally diagnosed with HFRS followed by multiple organ failure. After antiviral therapy, including ribavirin, piperacillin, and tazobactam, continuous renal replacement therapy, fluid metabolism adjustment, and related supportive therapy were administered, which improved his liver and kidney function. He was discharged on the 25th day after hospitalization. It is difficult to manage patients who develop multiple organ failure after HFRS. Moreover, this condition is rare in clinical settings, with fever being the initial indication. For diseases with unknown origin such as refractory fever and diarrhea, it is crucial to differentiate them from common pathogenic infection and HV infections to provide timely treatment that improves the prognosis of patients.

The role of glomerular lesions in the prognosis of patients with acute kidney injury during hemorrhagic fever with renal syndrome.

OBJECTIVE: This study aimed to explore the role of glomerular lesions in patients who suffered from acute kidney injury (AKI) during hemorrhagic fever with renal syndrome (HFRS). METHODS: The study comprised 66 patients with AKI during HFRS treated at the National Clinical Research Center of Kidney Diseases of China, Jinling Hospital, from January 2014 to December 2018. According to the kidney pathological findings, the 66 patients were divided into two groups: the tubulointerstitial injury group (HFRS-TI group, n = 43) and the tubulointerstitial injury with glomerular lesions group (HFRS-GL group, n = 23). The clinical and pathological characteristics of the 66 patients were analyzed. RESULTS: There were 9 cases of IgA nephropathy, 1 case of membranous nephropathy, 2 cases of diabetic nephropathy, and 11 cases of mesangial proliferative glomerulonephritis in the HFRS-GL group. There were more males in the HFRS-GL group than in the HFRS-TI group (92.3% vs. 69.8%, p < .05). A higher proportion of interstitial fibrosis (56.5% vs. 27.9%, p < .05) and more immunoglobulin and complement depositions (p < .001) were observed in the HFRS-GL group than in the HFRS-TI group. Rates of remission of AKI were lower in the HFRS-GL group than in the HFRS-TI group (73.9% vs. 95.3%, p < .05). The presence of glomerular lesions (HR = 5.636, 95% CI = 1.121-28.329, p = .036) and moderate tubulointerstitial injury (HR = 3.598, 95% CI = 1.278-10.125, p = .015) were found to be independent risk factors for kidney prognosis. CONCLUSIONS: Patients with AKI during HFRS can have glomerular lesions or glomerulonephritis. Patients with AKI during HFRS who have glomerular lesions or moderate renal tubulointerstitial injury proven by kidney biopsy have a relatively poor kidney prognosis. A kidney biopsy can help determine long-term prognosis in patients with AKI during HFRS.

Detection of co-infection with Orientia tsutsugamushand and hemorrhagic fever with renal syndrome by next-generation sequencing.

Purpose: The co-infection with Orientia tsutsugamushand and hemorrhagic fever with renal syndrome is rare. There are many similarities in early clinical practice between the two diseases, and sometimes it is easy to misdiagnose, especially when co-infection occurs.Methods: We describe a patient who presented with fever and headache after bitten by an insect and whose physical examination showed conjunctival hyperemia, eschar and petechiae in tongue and the soft palate. To lead to a diagnosis, the serum antibody of Hantaan virus, Weil-Felix test and  next-generation sequencing of cerebrospinal fluid was performed.Results: The Weil-Felix test was negative on the 15th day after the onset of the disease and a repeated Weil-Felix test on the 21st day showed a titer of 1:160 and the IgM against Hantaan virus was positive. The number of sequence reads identified corresponding to O. tsutsugamushi was 239 with a genomic coverage of 0.9178%. This patient was diagnosed with intracranial infection with Orientia tsutsugamushi and co-infection with epidemic hemorrhagic fever. The symptoms in our patient quickly decreased after the administration of tetracycline.Conclusion: Next-generation sequencing is helpful for the early diagnosis of scrub typhus, especially when the Weil-Felix test is negative. Clinicians need to be reminded to screen for common pathogens that may be co-infected, such as epidemic hemorrhagic fever.

The presence of intraperitoneal, retroperitoneal and pleural fluid in acute Puumala hantavirus infection.

BACKGROUND: Puumala hantavirus (PUUV) causes most cases of haemorrhagic fever with renal syndrome (HFRS) in Europe. PUUV infection is characterised by acute kidney injury, thrombocytopenia and increased capillary leakage. Typical symptoms are fever, headache, nausea, abdominal and back pain. This study aimed to evaluate the amount and distribution of intraperitoneal, retroperitoneal and pleural fluid and the association of fluid collections to the symptoms and clinical findings in patients with acute PUUV infection. METHODS: Abdominal magnetic resonance imaging (MRI) was performed on 27 hospitalised patients with acute PUUV infection. The clinical and laboratory findings and patients' symptoms were analysed in relation to the imaging findings. The thickness of the fluid collections was measured in millimetres (mm) from axial images. RESULTS: Fluid collections were found in all patients. The amount of intraperitoneal fluid correlated positively with plasma C-reactive protein (CRP) level (r = 0.586, p = .001), while it had an inverse correlation with serum creatinine concentration (r = -0.418, p = .030). Retroperitoneal fluid also correlated inversely with serum creatinine and cystatin C concentrations (r = -0.501, p = .008 and r = -0.383, p = .048, respectively). The amount of fluid was not greater in patients with abdominal or back pain. Patients with back pain had higher serum creatinine compared with patients without back pain, 452 µmol/L (range 88-1071) vs. 83 µmol/L (range 60-679), p = .004. CONCLUSIONS: Fluid collections were found in all patients. A greater amount of intraperitoneal fluid associates with higher CRP concentrations but not with higher serum creatinine levels. Back pain associates with higher creatinine level but not with the presence of fluids.

Clinical and laboratory features and factors predicting disease severity in pediatric patients with hemorrhagic fever with renal syndrome caused by Hantaan virus.

The clinical features and factors associated with disease severity in children with hemorrhagic fever with renal syndrome (HFRS) have not been well characterized. This study analyzed the clinical and laboratory factors associated with disease severity in children with HFRS caused by Hantaan virus. Data in pediatric patients with HFRS were retrospectively collected from Xi'an Children's Hospital over a 9-year period. Independent factors associated with disease severity were identified. Nomogram predicting disease severity was constructed based on variables filtered by feature selection. In total, 206 children with HFRS were studied. Fever, digestive tract symptoms, headache, backache, bleeding, and renal injury signs were the common symptoms. Elevated white blood cell, reduced platelet, hematuria, proteinuria, coagulation abnormalities, increased blood urea nitrogen (BUN) and procalcitonin (PCT), decreased estimated glomerular filtration rate and low serum Na+ , Cl- , and Ca2+ were the common laboratory findings. In the 206 patients, 21 patients had critical type disease and 4 patients (1.9%) died. Hydrothorax, hypotension and cerebral edema/cerebral herniation at hospital admission were independent clinical characteristics, and neutrophil %, prothrombin activity, PCT, BUN, and Ca2+ at hospital admission were independent laboratory factors associated with critical disease. Feature selection identified BUN, PCT and prothrombin time as independent factors related to critical disease. A nomogram integrating BUN and PCT at admission was constructed and calibration showed high accuracy for the probability prediction of critical disease. In conclusion, this study characterized the clinical and laboratory features and constructed a nomogram predicting disease severity in pediatric HFRS, providing references for disease severity evaluation in managing children HFRS.

[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.

Hyperamylasemia Caused by the Hantaan Virus: A Retrospective Study of 101 Patients with Hemorrhagic Fever with Renal Syndrome in West China.

Background: Hyperamylasemia (HA) is an inconspicuous manifestation of hemorrhagic fever with renal syndrome (HFRS) in Baoji city, West China. Hantaan virus (HTNV) is the only pathogen-caused HFRS in this region, but the knowledge about HA in the local HFRS patients has been limited. The aim of this study was to investigate the characteristics of HA and its predictive risk factors for doctors to engage in timely monitoring and dealing with the possible serious changes prewarned by HA in the early stages of the disease to improve the final outcome. Methods: All HFRS patients with and without HA (HA and nHA groups, respectively) were treated in Baoji People's Hospital. The clinical characteristics between the two groups were compared by Student's t-test or Chi-square test. The risk factors for prognosis were measured by the logistic regression analysis. The predictive effects of prognosis in clinical and laboratory parameters were analyzed by the receiver operating characteristic curves. Results: 46.53% of the patients demonstrated HA, among which 71.7% were severe and critical types of HFRS, greater than that in the nHA group (19.57%, P < 0.001). The hospitalization day and the general incidence of acute pancreatitis (AP) were longer or greater in the HA group than in the nHA group (P < 0.01). Age and the time from the onset of the first symptom to the patient being admitted to hospital (T OA) were the predictive risk factors for HA. The best cut-off values were the age of 54 years and T OA of 5.5 days. Conclusion: HTNV-induced HA is a common clinical presentation of HFRS patients in West China. It can increase the severity, the hospitalization days of patients, and the incidence of AP in HFRS. Age and T OA constituted independent risk factors for HA caused by HTNV.

Expression Profile of Human Renal Mesangial Cells Is Altered by Infection with Pathogenic Puumala Orthohantavirus.

Acute kidney injury (AKI) with proteinuria is a hallmark of infections with Eurasian orthohantaviruses. Different kidney cells are identified as target cells of hantaviruses. Mesangial cells may play a central role in the pathogenesis of AKI by regulation of inflammatory mediators and signaling cascades. Therefore, we examined the characteristics of hantavirus infection on human renal mesangial cells (HRMCs). Receptor expression and infection with pathogenic Puumala virus (PUUV) and low-pathogenic Tula virus (TULV) were explored. To analyze changes in protein expression in infected mesangial cells, we performed a proteome profiler assay analyzing 38 markers of kidney damage. We compared the proteome profile of in vitro-infected HRMCs with the profile detected in urine samples of 11 patients with acute hantavirus infection. We observed effective productive infection of HRMCs with pathogenic PUUV, but only poor abortive infection for low-pathogenic TULV. PUUV infection resulted in the deregulation of proteases, adhesion proteins, and cytokines associated with renal damage. The urinary proteome profile of hantavirus patients demonstrated also massive changes, which in part correspond to the alterations observed in the in vitro infection of HRMCs. The direct infection of mesangial cells may induce a local environment of signal mediators that contributes to AKI in hantavirus infection.

Increased Heparanase Levels in Urine during Acute Puumala Orthohantavirus Infection Are Associated with Disease Severity.

Old-world orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS), characterized by acute kidney injury (AKI) with transient proteinuria. It seems plausible that proteinuria during acute HFRS is mediated by the disruption of the glomerular filtration barrier (GFB) due to vascular leakage, a hallmark of orthohantavirus-caused diseases. However, direct infection of endothelial cells by orthohantaviruses does not result in increased endothelial permeability, and alternative explanations for vascular leakage and diminished GFB function are necessary. Vascular integrity is partly dependent on an intact endothelial glycocalyx, which is susceptible to cleavage by heparanase (HPSE). To understand the role of glycocalyx degradation in HFRS-associated proteinuria, we investigated the levels of HPSE in urine and plasma during acute, convalescent and recovery stages of HFRS caused by Puumala orthohantavirus. HPSE levels in urine during acute HFRS were significantly increased and strongly associated with the severity of AKI and other markers of disease severity. Furthermore, increased expression of HPSE was detected in vitro in orthohantavirus-infected podocytes, which line the outer surfaces of glomerular capillaries. Taken together, these findings suggest the local activation of HPSE in the kidneys of orthohantavirus-infected patients with the potential to disrupt the endothelial glycocalyx, leading to increased protein leakage through the GFB, resulting in high amounts of proteinuria.

Long-Term Consequences of Puumala Hantavirus Infection.

Several viral infections are associated with acute and long-term complications. During the past two years, there have been many reports on post-infectious symptoms of the patients suffering from COVID-19 disease. Serious complications occasionally occur during the acute phase of Puumala orthohantavirus caused nephropathia epidemica. Severe long-term consequences are rare. Fatigue for several weeks is quite common. Hormonal insufficiencies should be excluded if the patient does not recover normally.