Invasive Pulmonary Aspergillosis in Critically Ill Patients with Hantavirus Infection, Austria.

We investigated a cohort of 370 patients in Austria with hantavirus infections (7.8% ICU admission rate) and detected 2 cases (cumulative incidence 7%) of invasive pulmonary aspergillosis; 1 patient died. Hantavirus-associated pulmonary aspergillosis may complicate the course of critically ill patients who have hemorrhagic fever with renal syndrome.

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.

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.

[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.

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.

Puumala Hantavirus Infections Show Extensive Variation in Clinical Outcome.

The clinical outcome of Puumala hantavirus (PUUV) infection shows extensive variation, ranging from inapparent subclinical infection (70-80%) to severe hemorrhagic fever with renal syndrome (HFRS), with about 0.1% of cases being fatal. Most hospitalized patients experience acute kidney injury (AKI), histologically known as acute hemorrhagic tubulointerstitial nephritis. Why this variation? There is no evidence that there would be more virulent and less virulent variants infecting humans, although this has not been extensively studied. Individuals with the human leukocyte antigen (HLA) alleles B*08 and DRB1*0301 are likely to have a severe form of the PUUV infection, and those with B*27 are likely to have a benign clinical course. Other genetic factors, related to the tumor necrosis factor (TNF) gene and the C4A component of the complement system, may be involved. Various autoimmune phenomena and Epstein-Barr virus infection are associated with PUUV infection, but hantavirus-neutralizing antibodies are not associated with lower disease severity in PUUV HFRS. Wide individual differences occur in ocular and central nervous system (CNS) manifestations and in the long-term consequences of nephropathia epidemica (NE). Numerous biomarkers have been detected, and some are clinically used to assess and predict the severity of PUUV infection. A new addition is the plasma glucose concentration associated with the severity of both capillary leakage, thrombocytopenia, inflammation, and AKI in PUUV infection. Our question, "Why this variation?" remains largely unanswered.

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.

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.

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.

Alcohol Consumption and Its Influence on the Clinical Picture of Puumala Hantavirus Infection.

Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome. Characteristic clinical findings include acute kidney injury (AKI), thrombocytopenia, and capillary leakage. Smoking increases the risk of severe AKI, but it is not known whether alcohol consumption predisposes patients to a more severe infection. Liver and pancreatic enzymes, as well as biomarkers of alcohol consumption (gamma-glutamyl transferase, GGT; carbohydrate-deficient transferrin, CDT; GGT-CDT combination; and ethyl glucuronide, EtG), were measured from 66 patients with acute PUUV infection during hospitalization and at the convalescence phase. Alcohol consumption was present in 41% of the study population, 15% showing signs of heavy drinking. Alcohol use did not affect the severity of PUUV induced AKI nor the overall clinical picture of the infection. Liver enzyme levels (GGT or alanine aminotransferase, ALT) were elevated in 64% of the patients, but the levels did not associate with the markers reflecting the severity of the disease. Serum amylase activities at the convalescent stage were higher than those at the acute phase (p < 0.001). No cases with acute pancreatitis were found. In conclusion, our findings indicate that alcohol consumption does not seem to affect the clinical course of an acute PUUV infection.

Eosinophilia during Hantavirus infection: a cohort study.

BACKGROUND: There are emerging eosinophil-related considerations concerning viral infections. The role of eosinophils has poorly been evaluated during Hantavirus infection. METHODS: The aim of this study was to determine the prevalence of eosinophilia (defined as an eosinophil count above 500 cells/mm3) during haemorrhagic fever with renal syndrome (HFRS) in a large cohort of patients, and to identify factors associated with eosinophilia. RESULTS: Among 387 patients hospitalized for HFRS, 98 (25.3%) had eosinophilia. By univariate analysis, eosinophilia was significantly associated with more severe thrombocytopenia, high C-reactive protein level, white blood cell count and neutrophil count and lower nephrotoxic drug intake. As there was a collinearity between white blood cell count and C-reactive protein level, only C-reactive protein level with platelet count and nephrotoxic drug intake were entered in the multivariable analysis. Elevated C-reactive protein concentrations remained independently associated with eosinophilia. CONCLUSION: Eosinophilia during HFRS affects one quarter of patients, and supports the role of eosinophils in antiviral immunity against hantavirus infection.

Hantavirus infection as a risk factor for chronic kidney disease of unknown aetiology (CKDu) and its prevalence in endemic areas of Sri Lanka since 2010 according to a retrospective serological analysis.

Background. Chronic kidney disease of unknown aetiology (CKDu) is a major public health problem in Sri Lanka, especially among agrarian communities. Although the cause of CKDu is still unknown, hantavirus infection has been proposed as a risk factor.Methods. This study was performed using serological samples collected from two CKDu-endemic areas, Anuradhapura (2010) and Badulla districts (2010 and 2016), and a non-endemic area, Matale (2016) district. The presence of anti-Thailand orthohantavirus IgG antibodies was investigated in serum samples. Hantavirus seroprevalence and demographic data were epidemiologically analysed.Results. Seroprevalence was higher in CKDu patients (40.6-60.0 %) and healthy individuals in CKDu-endemic areas (17.6-25.5 %) than in healthy individuals in non-endemic areas (3.0 %). Statistically significant odds ratios (ORs) for hantavirus infection in CKDu patients were detected in CKDu-endemic areas [ORs: 3.2 and 3.1; 95 % confidence interval (CI): 1.8-5.5 and 1.8-5.2 in Anuradhapura and Badulla districts in 2010; and OR: 4.4, 95 % CI: 2.3-8.5 in 2016 in Badulla district). Furthermore, the OR for hantavirus infection in Badulla district has increased in the last decade from 3.1 (95 % CI: 1.8-5.3) to 4.4 (95 % CI: 2.3-8.5).Conclusion. Hantavirus infection has been prevalent in two distant CKDu-endemic areas since 2010. The observed significant association of hantavirus seropositivity with CKDu indicates a possible role of hantavirus infection in CKDu pathogenesis.

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

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

Targeted high volume hemofiltration could avoid extracorporeal membrane oxygenation in some patients with severe Hantavirus cardiopulmonary syndrome.

BACKGROUND: Hantavirus cardiopulmonary syndrome (HCPS) has a high lethality. Severe cases may be rescued by venoarterial extracorporeal membrane oxygenation (VA ECMO), alongside substantial complications. High volume hemofiltration (HVHF) is a depurative technique that provides homeostatic balance allowing hemodynamic stabilization in some critically ill patients. METHODS: We implemented HVHF before VA ECMO consideration in the last five severe HCPS patients requiring mechanical ventilation and vasoactive drugs admitted to our intensive care unit. Patients were considered HVHF-responders if VA ECMO was avoided and HVHF-nonresponders if VA ECMO support was needed despite HVHF. A targeted-HVHF strategy compounded by aggressive hyperoncotic albumin, sodium bicarbonate, and calcium supplementation plus ultrafiltration to avoid fluid overload was implemented on three patients. RESULTS: Patients had maximum serum lactate of 8.8 (8.7-12.8) mmol/L and a lowest cardiac index of 1.8 (1.8-1.9) L/min/m2 . The first two required VA ECMO. They were connected later to HVHF, displayed progressive tachycardia and declining stroke volume. The opposite was true for HVHF-responders who received targeted-HVHF. All patients survived, but one of the VA ECMO patients suffered a vascular complication. CONCLUSION: HVHF may contribute to support severe HCPS patients avoiding the need for VA ECMO in some. Early connection and targeted-HVHF may increase the chance of success.

Case Report: Spinal Subarachnoid Hemorrhage: A Rare Complication of Hemorrhagic Fever with Renal Syndrome.

Hemorrhagic fever with renal syndrome (HFRS), caused by hantavirus, is occasionally seen in tropical areas. The virus is carried by specific rodent host species. Hemorrhagic fever with renal syndrome is characterized by renal failure and hemorrhagic manifestations, and its complications may be severe, including massive bleeding, multi-organ dysfunction, and possibly death. In this patient case, a 46-year-old woman diagnosed with HFRS initially presented with fever, impaired renal function, and thrombocytopenia. Four days after symptom onset, the patient complained of abrupt right lower abdominal pain and numbness. Magnetic resonance imaging revealed a spinal subarachnoid hemorrhage (SAH) beyond the T7 to S2 vertebrae. No cases of spinal SAH in HFRS have been reported until now. This case demonstrates that when a patient's symptoms are atypical, bleeding-related complications must be considered.

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.

Prevalence and risk factors of Hantavirus infection in patients undergoing hemodialysis in Khartoum, Sudan, in 2019: a cross-sectional study.

BACKGROUND: Hantaviruses are enveloped negative sense RNA viruses that cause hemorrhagic fever with renal syndrome. This study aimed to identify the prevalence of Hantavirus IgG antibodies and possible risk factors for Hantaviruses infections among end-stage renal disease (ESRD) patients attending the Dr Salma dialysis center in Sudan. METHODOLOGY: This was a cross-sectional study in which 91 ESRD patients and 30 healthy plasma samples were screened for Hantavirus IgG antibodies using ELISA. A questionnaire containing sociodemographics, history of rat exposure and clinical data information was filled in by each ESRD patient. RESULTS: In this study, 9 out of 91 ESRD patients (9.9%) tested positive for Hantaviruses antibodies (IgG) while none of the 30 healthy plasma samples showed seropositivity. There was no statistically significant association between age, gender, educational level and rat exposure and Hantavirus infection in ESRD patients (p>0.05). CONCLUSION: This study is the first to be conducted in Sudan regarding Hantaviruses and ESRD. The prevalence of Hantavirus antibodies among ESRD patients is high compared with findings reported in the literature from studies conducted on the same group of patients. It points to an interesting question as to whether Hantaviruses have an association with ESRD but further studies are needed before drawing any conclusions.

When polyuria does not stop: a case report on an unusual complication of hantavirus infection.

BACKGROUND: The clinical features, course and outcome of hantavirus infection is highly variable. Symptoms of the central nervous system may occur, but often present atypically and diagnostically challenging. Even though the incidence of hantavirus infection is increasing worldwide, this case is the first to describe diabetes insipidus centralis as a complication of hantavirus infection in the Western world. CASE PRESENTATION: A 49-year old male presenting with severe headache, nausea and photophobia to our neurology department was diagnosed with acute haemorrhage in the pituitary gland by magnetic resonance imaging. In the following days, the patient developed severe oliguric acute kidney failure. Diagnostic workup revealed a hantavirus infection, so that the pituitary haemorrhage resulting in hypopituitarism was seen as a consequence of hantavirus-induced hypophysitis. Under hormone replacement and symptomatic therapy, the patient's condition and kidney function improved considerably, but significant polyuria persisted, which was initially attributed to recovery from kidney injury. However, water deprivation test revealed central diabetes insipidus, indicating involvement of the posterior pituitary gland. The amount of urine production normalized with desmopressin substitution. CONCLUSION: Our case report highlights that neurological complications of hantavirus infection should be considered in patients with atypical clinical presentation.

Platelet Count in Patients with Mild Disease at Admission is Associated with Progression to Severe Hantavirus Cardiopulmonary Syndrome.

BACKGROUND: Hantavirus cardiopulmonary syndrome (HCPS) has a mortality up to 35-40% and its treatment is mainly supportive. A variable to predict progression from mild to severe disease is unavailable. This study was performed in patients with documented infection by Andes orthohantavirus, and the aim was to find a simple variable to predict progression to moderate/severe HCPS in patients with mild disease at admission. METHODS: We performed a retrospective analysis of 175 patients between 2001 and 2018. Patients were categorized into mild, moderate, and severe disease according to organ failure and advanced support need at hospital admission (e.g., mechanical ventilation, vasopressors). Progression to moderate/severe disease was defined accordingly. Clinical and laboratory variables associated with progression were explored. RESULTS: Forty patients with mild disease were identified; 14 of them progressed to moderate/severe disease. Only platelet count was different between those who progressed versus those that did not (37 (34-58) vs. 83 (64-177) K/mm3, p < 0.001). A ROC curve analysis showed an AUC = 0.889 (0.78-1.0) p < 0.001, with a platelet count greater than 115K /mm3 ruling out progression to moderate/severe disease. CONCLUSIONS: In patients with mild disease at presentation, platelet count could help to define priority of evacuation to tertiary care centers.