Young male patients are at elevated risk of developing serious central nervous system complications during acute Puumala hantavirus infection

Abstract

BackgroundOur aim was to characterize clinical properties and laboratory parameters in patients with or without cerebrospinal fluid (CSF) findings suggestive of central nervous system (CNS) involvement, and especially those who developed serious CNS complications during acute nephropathia epidemica (NE) caused by Puumala hantavirus (PUUV) infection.MethodsA prospective cohort of 40 patients with acute NE and no signs of major CNS complications was analyzed. In addition, 8 patients with major CNS complications associated with NE were characterized. We collected data of CNS symptoms, CSF analysis, brain magnetic resonance imaging (MRI) results, electroencephalography (EEG) recordings, kidney function, and a number of laboratory parameters. Selected patients were evaluated by an ophthalmologist.ResultsPatients with a positive CSF PUUV IgM finding or major CNS complications were more often males (p < 0.05) and they had higher plasma creatinine values (p < 0.001) compared to those with negative CSF PUUV IgM. The degree of tissue edema did not explain the CSF findings. Patients with major CNS complications were younger than those with negative CSF PUUV IgM finding (52.9 vs. 38.5 years, p < 0.05). Some patients developed permanent neurological and ophthalmological impairments.ConclusionsCNS and ocular involvement during and after acute NE can cause permanent damage and these symptoms seem to be attributable to true infection of the CNS rather than increased tissue permeability. The possibility of this condition should be borne in mind especially in young male patients.

Clinical and virological characteristics of hantavirus infections in a 2014 Croatian outbreak

“…In Sweden and Finland, gender-specific differences in symptoms as well as mortality rates were identified for epidemic nephropathy [27,28]. A similar observation was reported for HFRS in China [29].…”

Clinical characterization of two severe cases of hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses Puumala and Dobrava-Belgrade genotype Sochi

“…In addition to severe courses that are linked to specific virus species or genotypes, several serious cases were reported for infection with PUUV that usually causes a milder form of hantavirus disease [14, 15]. These infections often involve extrarenal manifestations [16, 17]. Severe cases caused by various hantavirus species are not well characterized with regard to their differences and similarities in symptoms, organ involvement, laboratory parameters, and clinical course.…”

Hantaviruses Induce Antiviral and Pro-Inflammatory Innate Immune Responses in Astrocytic Cells and the Brain

“…While renal insufficiency is the principal target-organ manifestations of HFRS, viral antigens can be found in the brains of animal models (59) and CNS-associated clinical signs and symptoms have been reported in some HFRS patients (10,(19)(20)(21)(22)24,55). Our data demonstrate that HTNV and MJNV efficiently replicate and induce N protein synthesis in human astrocytic cells and similarly cause the induction of innate immune responsive genes.…”

“…The mechanisms of hantavirus-induced pathogenesis are not fully understood, but both HFRS and HCPS share several clinical and pathologic features, including high fever, thrombocytopenia, increased capillary permeability and upregulation of tumor necrosis factor-a (TNF-a). Recent reports indicate less wellstudied complications of HFRS and HCPS, such as central nervous system (CNS) dysfunction (10,(19)(20)(21)(22)24,55). However, hantaviral antigens have not been detected in the brains of patients, so the mechanisms by which hantavirus infection might lead to neurological and neuropsychological complications are almost entirely unknown.…”