Elevated cerebrospinal fluid neopterin concentration is associated with disease severity in acute Puumala hantavirus infection.

Nephropathia epidemica (NE) caused by Puumala hantavirus (PUUV) is the most common hemorrhagic fever with renal syndrome (HFRS) in Europe. The infection activates immunological mechanisms that contribute to the pathogenesis and characteristics of the illness. In this study we measured cerebrospinal fluid (CSF) neopterin concentration from 23 acute-phase NE patients. We collected data on kidney function, markers of tissue permeability, haemodynamic properties, blood cell count, length of hospitalisation, inflammatory parameters, and ophthalmological properties. The neopterin levels were elevated (> 5.8 nmol/L) in 22 (96%) NE-patients (mean 45.8 nmol/L); these were especially high in patients with intrathecal PUUV-IgM production (mean 58.2 nmol/L, P = 0.01) and those with elevated CSF protein concentrations (mean 63.6 nmol/L, P < 0.05). We also observed a correlation between the neopterin and high plasma creatinine value (r = 0.66, P = 0.001), low blood thrombocyte count (r = -0.42, P < 0.05), and markedly disturbed refractory properties of an eye (r = 0.47, P < 0.05). Length of hospitalisation correlated with the neopterin (r = 0.42, P < 0.05; male patients r = 0.69, P < 0.01). Patients with signs of tissue oedema and increased permeability also had high neopterin concentrations. These results reinforce the view that PUUV-HFRS is a general infection that affects the central nervous system and the blood-brain barrier.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Plasma B-type natriuretic peptide (BNP) in acute Puumala hantavirus infection.

BACKGROUND: Nephropathia epidemica (NE) is a haemorrhagic fever with renal syndrome (HFRS) caused by Puumala hantavirus (PUUV). Acute infection causes transient kidney injury, permeability disorder, and fluid retention, for example. METHODS: B-type natriuretic peptide (BNP) and N-terminal peptide (NT-proBNP) during NE were investigated; disease severity and development of clinical symptoms were considered. RESULTS: Mean concentrations were 80.2 pg/mL and 55.2 pg/mL for BNP, and 2362.5 pg/mL and 1057.0 pg/mL for NT-proBNP in males and females, respectively. Hospitalization was 6.3 versus 5.2 days (P = 0.01) and 5.9 versus 4.4 days (P = 0.01) for patients with elevated BNP (> 100 pg/mL) or NT-proBNP (> 300 pg/mL), respectively, compared to those with normal peptide concentrations. Weight change during hospitalization was -2.8 or -0.3 kg (P <0.05) in patients with elevated or normal BNP, respectively. Heart rate (r = -0.46, P = 0.001 and r = -0.37, P = 0.01), creatinine clearance (r = -0.46, P = 0.001 and r = -0.56, P = 0.000), blood haemoglobin concentration (r = -0.55, P = 0.000 and r = -0.52, P = 0.000), and C-reactive protein (r = -0.47, P = 0.001 and r = -0.36, P = 0.01) measured when the peptide samples were collected correlated with BNP and NT-proBNP, respectively. In addition, anterior chamber depth of eye and plasma BNP (r = -0.39, P < 0.05) displayed a correlation. CONCLUSIONS: BNP and NT-proBNP levels are associated with severity of several clinical features of acute NE.