Acute Hantavirus Infection Research Articles

Neutrophil-to-lymphocyte ratio is elevated in acute hantavirus infection and correlates with markers of disease severity.

Pathogenic Eurasian hantaviruses cause hemorrhagic fever with renal syndrome (HFRS), which is characterized by acute kidney injury. The clinical course shows a broad range of severity and is influenced by direct and immune-mediated effects. The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation and predicts severity and outcome in various diseases. Therefore, we examined the role of NLR in HFRS caused by hantavirus Puumala (PUUV) and its association with disease severity and kidney injury. We detected elevated NLR levels on admission (NLRadm: median 3.82, range 1.75-7.59), which increased during acute HFRS. Maximum NLR levels (NLRmax: median 4.19, range 1.75-13.16) were 2.38-fold higher compared to the reference NLR level of 1.76 in the general population. NLR levels on admission correlate with markers of severity (length of hospital stay, serum creatinine) but not with other markers of severity (leukocytes, platelets, C-reactive protein, lactate dehydrogenase, serum albumin, proteinuria). Interestingly, levels of nephrin, which is a specific marker of podocyte damage in kidney injury, are highest on admission and correlate with NLRmax, but not with NLRadm. Together, we observed a correlation between systemic inflammation and the severity of HFRS, but our results also revealed that podocyte damage precedes these inflammatory processes.

Viral shedding and viraemia of Andes virus during acute hantavirus infection: a prospective study

Andes virus (ANDV) is a zoonotic Orthohantavirus leading to hantavirus cardiopulmonary syndrome. Although most transmissions occur through environmental exposure to rodent faeces and urine, rare person-to-person transmission has been documented, mainly for close contacts. This study investigates the presence and infectivity of ANDV in body fluids from confirmed cases and the duration of viraemia. In this prospective study, 131 participants with confirmed ANDV infection were enrolled in Chile in a prospective study between 2008 and 2022. Clinical samples (buffy coat, plasma, gingival crevicular fluid [GCF], saliva, nasopharyngeal swabs [NPS], and urine) were collected weekly for 3 weeks together with clinical and epidemiological data. Samples were categorised as acute or convalescent (up to and after 16 days following onset of symptoms). Infectivity of positive fluids was assessed after the culture of samples on Vero E6 cells and use of flow cytometry assays to determine the production of ANDV nucleoprotein. ANDV RNA was detected in 100% of buffy coats during acute phase, declining to 95% by day 17, and to 93% between days 23-29. ANDV RNA in GCF and saliva decreased from 30% and 12%, respectively, during the acute phase, to 12% and 11% during the convalescent phase. Successful infectivity assays of RT-qPCR-positive fluids, including GCF, saliva, NPS, and urine, were observed in 18 (42%) of 43 samples obtained during the acute phase of infection. After re-culture, the capacity to infect Vero E6 cells was maintained in 16 (89%) of 18 samples. Severity was associated with the presence of ANDV RNA in one or more fluids besides blood (odds ratio 2·58 [95% CI 1·42-5·18]). ANDV infection is a systemic and viraemic infection, that affects various organs. The presence of infectious particles in body fluids contributes to our understanding of potential mechanisms for person-to-person transmission, supporting the development of preventive strategies. Detection of ANDV RNA in additional fluids at hospital admission is a predictor of disease severity. National Institutes of Health and Agencia de Investigación y Desarrollo. For the Spanish translation of the abstract see Supplementary Materials section.

Molecular Detection of Orthohantavirus puumalaense in Plasma and Urine Samples from Hospitalized Patients Presenting with a Serologically Confirmed Acute Hantavirus Infection in France.

Molecular detection of Orthohantavirus puumalaense (PUUV) RNA during the course of the disease has been studied in blood of patients in Sweden and Slovenia. The use of urine has been poorly investigated. The aims of this work were to study PUUV RNA detection in plasma from a cohort of patients in France where a different PUUV lineage circulates and to assess the use of urine instead of plasma. Matched plasma and urine samples were collected daily from hospitalized patients presenting with fever, pain, and thrombocytopenia within the last 8 days and testing positive for IgM and IgG against PUUV in serum collected at inclusion and/or approximately 1 month after release. RNA was extracted from samples, and PUUV RNA was detected using real-time reverse transcription-PCR for plasma and urine samples. Sixty-seven patients presented a serologically confirmed acute hantavirus infection. At inclusion, PUUV RNA was detected in plasma from 55 of 62 patients (88.7%) sampled within the first week after disease onset, whereas it was detected in 15 of 60 (25.0%) of matched urine samples. It was then detected from 33 (71.7%) and 2 (4.4%) of 46 patients discharged from the hospital during the second week after disease onset, in plasma and urine, respectively. When PUUV RNA was detected in urine it was also detected in plasma, and not vice versa. Detection of PUUV RNA in plasma from hospitalized patients in France is similar to that observed in Sweden and Slovenia. Urine is not an appropriate sample for this detection.

Acute Hantavirus Infection Presenting With Fever and Altered Mentation in the Absence of Pulmonary or Renal Manifestations.

Illness caused by hantaviruses is often severe and is typically characterized by diffuse pulmonary disease or renal insufficiency depending on the type of hantavirus. Here we report 2 cases of hantavirus infection that resulted in severe cognitive impairment but did not have any pulmonary or renal manifestations. These 2 cases may be indicative of previously underreported symptoms of hantavirus infection and might represent examples of hantavirus-related encephalopathy.

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.

Hormonal Defects Are Common during Puumala Hantavirus Infection and Associate with Disease Severity and Biomarkers of Altered Haemostasis.

Central and peripheral hormone deficiencies have been documented during and after acute hantavirus infection. Thrombocytopenia and coagulation abnormalities are common findings in haemorrhagic fever with renal syndrome (HFRS). The associations between coagulation and hormonal abnormalities in HFRS have not been studied yet. Forty-two patients diagnosed with Puumala virus (PUUV) infection were examined during the acute phase and on a follow-up visit approximately one month later. Hormonal defects were common during acute PUUV infection. Overt (clinical) hypogonadism was identified in 80% of the men and approximately 20% of the patients had overt hypothyroidism. At the one-month follow-up visit, six patients had central hormone deficits. Acute peripheral hormone deficits associated with a more severe acute kidney injury (AKI), longer hospital stay and more severe thrombocytopenia. Half of the patients with bleeding symptoms had also peripheral hormonal deficiencies. Patients with free thyroxine levels below the reference range had higher D-dimer level than patients with normal thyroid function, but no thromboembolic events occurred. Acute phase hormonal abnormalities associate with severe disease and altered haemostasis in PUUV infection.

MAIT cell activation is associated with disease severity markers in acute hantavirus infection

SummaryHantaviruses are zoonotic RNA viruses that cause severe acute disease in humans. Infected individuals have strong inflammatory responses that likely cause immunopathology. Here, we studied the response of mucosal-associated invariant T (MAIT) cells in peripheral blood of individuals with hemorrhagic fever with renal syndrome (HFRS) caused by Puumala orthohantavirus, a hantavirus endemic in Europe. We show that MAIT cell levels decrease in the blood during HFRS and that residual MAIT cells are highly activated. This activation correlates with HFRS severity markers. In vitro activation of MAIT cells by hantavirus-exposed antigen-presenting cells is dependent on type I interferons (IFNs) and independent of interleukin-18 (IL-18). These findings highlight the role of type I IFNs in virus-driven MAIT cell activation and suggest a potential role of MAIT cells in the disease pathogenesis of viral infections.

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

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

Dynamics of Puumala hantavirus outbreak in Black Sea Region, Turkey.

Some of the hantavirus species in Euro-Asia cause haemorrhagic fever with renal syndrome (HFRS) in humans. The first documented human hantavirus infection in Turkey was diagnosed in 2009. This report describes the dynamics of the first hantavirus outbreak that emerged in humans in the Western Black Sea Region of Turkey. All the suspected cases of hantavirus infection were admitted to the Infectious Diseases and Clinical Microbiology Department at the Zonguldak Bülent Ecevit University Hospital in Zonguldak, Turkey. The patients were carefully interviewed, examined and evaluated using routine laboratory tests and hantavirus diagnostic tools. Hantavirus-reactive antibodies (IgM and IgG) in serum samples were detected via enzyme immune assay (EIA) and immunofluorescence assay (IFA) in the acute and convalescence stages of the disease. The presence of hantavirus ribonucleic acid (RNA) was analysed via reverse transcription polymerase chain reaction (RT-PCR) in serum and urine samples. A focus reduction neutralization test (FRNT) was performed to confirm specific hantavirus serotypes. In addition, a case-control study was conducted to identify possible risk factors for hantavirus transmission in the outbreak area. A control group was composed of asymptomatic individuals who were seronegative for hantavirus IgM and IgG and living in the outbreak area. A total of 55 suspected cases of hantavirus infection were admitted to the inpatient clinic between February and June of 2009. Twenty-four patients were diagnosed with acute HFRS via EIA or IFA. In 22 of the 24 infected patients, Puumala virus (PUUV) was identified as the causative hantavirus type by detecting IgM in the acute stage and an increase in the IgG level in follow-up serum samples. PUUV was also verified as the infecting agent by FRNT in two of the 24 cases. Among the 24 laboratory-confirmed HFRS cases, 21 (87.5%) were males and 3 (12.5%) were females, and the mean age was 45.92years (standard deviation±16.90years). Almost all these individuals were living in villages or rural areas. The 24 HFRS cases were matched with 26 healthy controls for statistical analyses and according to binary logistic regression analysis, and dealing with rodent control activities in gardens or in annexes of their homes (p=0.021 and Odds ratio [OR]=17.11) and being male (p=0.019 and OR=22.37) were detected as statistically significant risk factors for hantavirus infection. The most commonly observed clinical complaints were fatigue (95.8%), shivering (91.7%), fever (87.1%), headache (70.8%) and nausea (70.8%). Haemodialysis was required for four patients (16.7%). Except for the first case diagnosed with acute hantavirus infection, no patient died. The mean delay time to hospital admission from initiation of symptoms was 5.3days, the mean duration of febrile days was 2.6days, and the mean duration of hospital stay was 8.5days. Hantaviruses are circulating in Turkey and causing sporadic or epidemic infection in humans. Additional investigations are needed to better understand the dynamics of hantaviruses in this country.

Young patient with hantavirus-induced myocarditis detected by comprehensive cardiac magnetic resonance assessment

BackgroundWe report a case of hantavirus-induced myocarditis in a young adult. Hantavirus showed a rapid increase of infections in the year 2017. Only scarce data is available about potential myocardial involvement in hantavirus infections. With ECG and echocardiography providing often inconclusive results, a multiparametric cardiac magnetic resonance protocol with distinct myocardial tissue characterization seems to be the adequate tool for detecting even slight myocardial alterations.Case presentationThis case started with the presentation of young adult suffering from headache and abdominal pain. Thrombocytes were decreased, creatinine was elevated, and there was massive proteinuria. Puumala virus IgG ELISA turned out to be positive, and specific antibodies (IgG and IgM) could be detected in the serum, and confirmed by immunoassay. The patient was admitted to the nephrology department for supportive therapy. Few days later, the patient reported chest pain and dyspnea. High sensitivity troponin I rose up to 0.32 μg/l (normal range below 0.04 μg/l) with an increase of the creatinkinase to 319 U/l (normal max. 190 U/l), no dynamic ECG changes could be observed. Echocardiography revealed a normal left ventricular function without regional wall motion abnormalities, no pericardial effusion or valve abnormalities, coronary artery disease could be excluded by computed tomography. A multiparametric cardiac magnetic resonance protocol including recent mapping techniques confirmed myocardial involvement induced by acute hantavirus infection. In the next few weeks, the patient’s state of health rapidly improved and symptoms of chest pain and dyspnea disappeared. Follow up multiparametric CMR exam showed substantial decrease of the previously observed myocardial alterations during acute hantavirus infection suggesting myocardial healing.ConclusionsThis case demonstrates that a CMR protocol including recent mapping techniques and established late gadolinium enhancement technique is an adequate non-invasive tool for both 1) initial detection, and 2) follow up of patients with hantavirus-induced myocarditis, which might be more common than previously known.

Falsely positive anti-glomerular basement membrane antibodies in a patient with hantavirus induced acute kidney injury - a case report

BackgroundHantavirus infection is an uncommon cause of acute renal failure with massive proteinuria. Serology tests to support a presumptive diagnosis usually take a few days. During the initial work-up, autoimmune causes including anti-glomerular basement membrane (GBM) glomerulonephritis need to be excluded, because these require urgent therapy. In this case the delay in serological testing caused a dilemma in treatment initiation.Case presentationAn 18-year-old patient was admitted to the hospital with acute renal failure, erythrocyturia and massive proteinuria. Routine blood analysis showed leucocytosis (40,5 × 109/l) and a serum creatinine of 233 μmol/l. Infectious causes, e.g. leptospirosis or hantavirus infection, or an autoimmune disease, e.g., AAV or anti-GBM glomerulonephritis was the most feasible underlying diagnosis.Before hantavirus serology results were known, anti-GBM antibodies were positive. Treatment for anti-GBM glomerulonephritis was withheld, because of the absence of other signs and symptoms of the disease and slight improvement of renal function.The diagnosis of acute hantavirus infection was later on confirmed, by seroconversion of a follow-up serum sample. Without further intervention renal function recovered and anti-GBM antibodies disappeared.ConclusionHantavirus infection may induce anti-GBM antibodies, falsely suggestive of anti-GBM glomerulonephritis.Anti-GBM antibodies are supposed to be 100% specific. No earlier reports of false positive anti-GBM titers were reported. Nevertheless, the anti-GBM antibodies in this case were seen as an innocent bystander effect.Considering the need of urgent initiation of plasmapheresis and administration of immunosuppressants it may lead to diagnostic dilemmas with crucial therapeutic consequences. Knowledge of this anomaly when diagnosing acute renal failure, is very important.

Epidemiological and clinical characteristics of hantavirus infections detected in three geographically close natural foci during the 2014 Croatian outbreak

Purpose: The aim of this study was to analyze epidemiological and clinical characteristics of hantavirus infections detected in Croatia during the 2014 outbreak. Methods and Materials: From January to December 2014, a total of 122 patients from three geographically close natural foci in the central mountainous Croatian region (Ogulin, Slunj and Plitvice Lakes surroundings) with clinical symptoms suggestive of hantavirus infection were tested for the presence of IgM/IgG antibodies to hantaviruses. Serologic tests were performed using a commercial IFA for the simultaneous detection of Puumala (PUUV), Dobrava (DOBV), Hantaan (HTNV), Seoul (SEOV) and Saaremaa (SAAV) (Euroimmun, Lubeck Germany). Cross-reactive samples were additionally tested using a western blot (Euroimmun, Lubeck Germany). For hospitalized patients clinical symptoms and laboratory parameters were analyzed. Results: Acute hantavirus infection was confirmed by detection of IgM/IgG antibodies in 57/46.7% patients, while 10/8.2% patients were IgG seropositive (previous exposure to hantaviruses). PUUV infection was detected in 88.1% and DOBV infection in 11.9% patients. Among acute cases, 75.4% were hospitalized. Males were infected more commonly than females (75.4%). The mean patient’s age was 37.9 (range 15- 69) years. Contact with rodents was noted in 59.3% patients. The outbreak started in winter months with majority patients (80.7%) reported from May to July. According to disease severity, mild clinical form was noted in 66.7%, moderate in 18.5% and severe in 14.8% patients. The most common clinical symptoms on admission were high fever (96.3%), chills/shivering (62.9%) and lumbal pain (48.1%). In 11.1% patients, respiratory symptoms with interstitial inflammatory infiltrates on X-ray were reported. Acute renal failure was noted in 74.1% patients but only 3.7% required hemodialysis. Laboratory abnormalities included albuminuria (96.3%), thrombocytopenia (81.5%, elevated urea and/or creatinine levels (70.4%) and elevated transaminases (25.9%). The mean duration of hospitalization was 9.6 (range 4-19) days. Only one PUUV infected patient developed multiorgan failure and died. Conclusion: Our results indicate that central mountainous Croatian regions are still endemic areas for hantavirus infections with circulation of both PUUV and DOBV. Compared to previous Croatian outbreaks, respiratory symptoms that are frequently detected in PUUV infection were reported less frequent.

Evaluation of lipase levels in patients with nephropathia epidemica--no evidence for acute pancreatitis.

BackgroundThe most common causative agent for hemorrhagic fever with renal syndrome in Germany is Puumala virus (PUUV) and a high percentage of patients with PUUV infection have gastrointestinal (GI) symptoms. The aim of the present study was to determine the prevalence of increased lipase levels and acute pancreatitis during nephropathia epidemica (NE) in 166 patients from Germany.MethodsClinical and laboratory data during the acute phase of the disease were obtained from medical reports and files from 456 patients during acute hantavirus infection. Patients in whom serum lipase levels were determined during acute course of the disease were included in the study.ResultsLipase levels at the time of diagnosis were determined in 166 of the 456 NE patients (36 %). Of the 166 patients, 25 (15 %) had elevated lipase levels at the time of admission to hospital or first contact with general practitioner/nephrologist. In total 7 patients had a threefold increased serum lipase above the normal range. Abdominal pain was not more often present in the group of patients with elevated serum lipase compared to the lipase-negative group (9/25 vs 58/141). Abdominal ultrasound and CT scans revealed no signs of pancreatitis in any of the patients. Patients with elevated serum lipase had higher serum creatinine peak levels (p = 0.03) during the course of the disease.ConclusionsElevated lipase levels were common in our patient cohort and might reflect a more severe form of NE. NE does not lead to acute pancreatitis.

Association of low serum TGF-β level in hantavirus infected patients with severe disease.

BackgroundHantaviruses are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome, an immune-mediated pathogenesis is discussed. The aim of the present study was to investigate the role of TGF-β expression in acute hantavirus infection.ResultsWe retrospectively studied 77 patients hospitalised with acute Puumala infection during a hantavirus epidemic in Germany in 2012. Hantavirus infection was confirmed by positive anti-Puumala hantavirus IgG and IgM. Plasma levels of transforming growth factor (TGF)-β1 and TGF-β2 were analysed. Based on glomerular filtration rate on admission, patients were divided in mild and severe course of disease. Puumala virus RNA was detected by PCR amplification of the viral L segment gene. Out of 77 Puumala virus infected patients, 52 (68%) were male. A seasonal distribution was detected in our cohort with a peak in summer 2012, the highest incidence was observed in the age group of 30–39 years. Puumala virus RNA was detectable in 4/77 cases. Patients with severe disease had a significant longer hospital stay than patients with mild disease (6.2 vs 3.6 days). Thrombocyte count (186 vs 225 per nl), serum TGF-β1 (74 vs 118 ng/l) and TGF-β2 (479 vs 586 pg/l) were significantly lower in severe compared to mild disease. However, C-reactive protein (CRP) was significantly higher in patients with severe disease (62 vs 40 mg/l). TGF-β1/Cr was the most sensitive and specific marker associated with renal dysfunction.ConclusionHigh serum CRP and low serum TGF-β in the early phase of hantavirus infection is associated with a severe course of disease. Our results support the hypothesis of an immune-mediated pathogenesis in hantavirus infection.

Polyuria in Hantavirus Infection Reflects Disease Severity and Is Associated with Prolonged Hospital Stay: A Systematic Analysis of 335 Patients from Southern Germany

Background/Aims: Puumala virus (PUUV) infection leads to nephropathia epidemica (NE), especially in endemic areas in Central Europe. The clinical course of NE is characterized by acute kidney injury (AKI) with thrombocytopenia followed by polyuria to a different degree. The prevalence of polyuria and its associated risk factors have not been reported in a large cohort of NE patients. Methods: Clinical and laboratory data during the acute phase of the disease were obtained from the medical reports and files of 335 patients who received in-hospital treatment during acute hantavirus infection. Comprehensive statistical models were developed to estimate the probability of polyuria. Results: The median age at diagnosis was 47 years (interquartile range, IQR 40-59) and 48% of the patients developed polyuria with a urinary output of 5,100 ml/day (IQR 4,200-7,300). The hospital stay was significantly longer in the polyuric group compared to the nonpolyuric group [8 days (IQR 6-10) vs. 6 days (IQR 5-8); p = 0.04]. Using logistic regression analysis, male gender (odds ratio, OR = 1.6; 95% confidence interval, CI 1.05-2.58; p = 0.03), oliguria/anuria during NE (OR = 2.56; 95% CI 1.65-4.01; p < 0.001), severe AKI (OR = 1.87; 95% CI 1.22-2.9; p < 0.001), and hematuria (OR = 1.78; 95% CI 1.02-3.15; p = 0.04) were significantly associated with the development of polyuria. In a multivariate model, the probability of polyuria was 0.19 (SEM ± 0.05) in female patients presenting with mild/moderate AKI without anuria/oliguria. Conclusions: Almost 50% of hospitalized NE patients developed polyuria, which was associated with a prolonged hospital stay. The probability of the development of polyuria was lowest in female patients with mild/moderate, non-oliguric/anuric AKI.

Acute hantavirus infection induces galectin-3-binding protein.

Hantaviruses are zoonotic viruses that cause life-threatening diseases when transmitted to humans. Severe hantavirus infection is manifested by impairment of renal function, pulmonary oedema and capillary leakage. Both innate and adaptive immune responses contribute to the pathogenesis, but the underlying mechanisms are not fully understood. Here, we showed that galectin-3-binding protein (Gal-3BP) was upregulated as a result of hantavirus infection both in vitro and in vivo. Gal-3BP is a secreted glycoprotein found in human serum, and increased Gal-3BP levels have been reported in chronic viral infections and in several types of cancer. Our in vitro experiments showed that, whilst Vero E6 cells (an African green monkey kidney cell line) constitutively expressed and secreted Gal-3BP, this protein was detected in primary human cells only as a result of hantavirus infection. Analysis of Gal-3BP levels in serum samples of cynomolgus macaques infected experimentally with hantavirus indicated that hantavirus infection induced Gal-3BP also in vivo. Finally, analysis of plasma samples collected from patients hospitalized because of acute hantavirus infection showed higher Gal-3BP levels during the acute than the convalescent phase. Furthermore, the Gal-3BP levels in patients with haemorrhagic fever with renal syndrome correlated with increased complement activation and with clinical variables reflecting the severity of acute hantavirus infection.

Tula Hantavirus Infection in Immunocompromised Host, Czech Republic

We report molecular evidence of Tula hantavirus as an etiologic agent of pulmonary-renal syndrome in an immunocompromised patient. Acute hantavirus infection was confirmed by using serologic and molecular methods. Sequencing revealed Tula virus genome RNA in the patient’s blood. This case shows that Tula virus can cause serious disease in humans.

Hantavirus Fever without Pulmonary Syndrome in Panama

In Panama, hantavirus pulmonary syndrome (HPS) is caused by Choclo virus, a species phylogenetically related to Andes and Maporal viruses. Up to 60% of the population has been positive for specific serum antibody in community-based surveys, but mortality is very uncommon. In four western Panama clinics, we tested individuals presenting with a severe febrile prodrome for acute hantavirus (HV) infection by immunoglobulin M enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction as well as clinically similar infections, such as dengue and leptospirosis. From 2006 to 2009, at least 21% of 117 patients diagnosed with HV infection had HV Fever (HF) with no evidence of pulmonary edema (no respiratory distress or radiographic lung infiltrates), and 44% of patients had very mild HPS (radiographic pulmonary edema but no respiratory insufficiency). HV infection caused by Choclo virus in Panama presents often as HF, which contrasts with HV in the Americas but is consistent with the high seroprevalence in endemic regions.

Signs of general inflammation and kidney function are associated with the ocular features of acute Puumala hantavirus infection

Puumala hantavirus (PUUV) causes nephropathia epidemica (NE), a type of viral haemorrhagic fever with renal syndrome (HFRS). This febrile infection may affect the kidneys, central nervous system (CNS), and the eye. Acute illness is associated with increased tissue permeability and tissue oedema, and many patients experience reduced vision. The aim of this study was to explore the physiological events associated with the ocular features of acute NE. This was a prospective study of 46 NE patients who were examined during the acute infection and 1 month after hospitalization. Visual acuity, refraction, intraocular pressure (IOP), and ocular dimensions were evaluated. Cerebrospinal fluid and blood samples were collected, brain magnetic resonance imaging and electroencephalography were recorded, and HLA haplotype was analyzed. The degrees of tissue oedema and fluid imbalance were evaluated. CNS examinations did not reveal the source of the ocular changes in acute NE. The plasma C-reactive protein concentration correlated with the lens thickness and the IOP. The plasma creatinine level was associated with the change in anterior chamber depth. However, oliguric and polyuric patients displayed similar ocular findings. Patients positive for the DR3-DQ2 haplotype experienced the least diminished visual acuity. The level of systemic inflammation rather than CNS involvement appears to account for the ocular changes during acute PUUV infection, and the severity of kidney dysfunction may also have a significant role. In addition, the genetic properties of the host may well explain the ocular features of acute hantavirus infection.

Occurrence of Immunoglobulin M Antibodies against Several Bacterial and Viral Pathogens in Acute Hantavirus Infection

Elevated levels of immunoglobulin M antibodies against various pathogens, most frequently Epstein-Barr-virus and Coxiella burnetii, were detected by immunoassay in 15 of 48 patients (31.3%) with acute Puumala virus infections. Although the mechanisms leading to this IgM response are not clear yet, polyspecific immunoglobulin M antibodies have to be taken into account to avoid misinterpretation of serological results in acute hantavirus infection.