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

BMC Infectious Diseases

Heikki Kauma¹  Olli Vapalahti³  Antti Vaheri³  Alexander Plyusnin³  Seppo Rytky⁴  Olli Vainio⁵  Pasi I Salmela¹  Ari Karttunen⁷  Eija Pääkkö⁷  Tarja Sironen³  Saara-Mari Mähönen⁶  Nina Hautala²  Timo Hautala¹ 

[1] Department of Internal Medicine, Oulu University Hospital, Oulu, Finland;Department of Ophthalmology, Oulu University Hospital, Oulu, Finland;Department of Virology, Infection Biology Research Program, Haartman Institute, University of Helsinki, Helsinki, Finland;Department of Clinical Neurophysiology, Oulu University Hospital, Oulu, Finland;Clinical Microbiology Laboratory, Oulu University Hospital, Oulu, Finland;Institute of Diagnostics, Department of Medical Microbiology and Immunology, University of Oulu, Oulu, Finland;Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland

关键词: hypopituitarism;    encephalitis;    hantavirus;   

Others  :  1175632
DOI  :  10.1186/1471-2334-11-217

 received in 2011-02-08, accepted in 2011-08-14,  发布年份 2011

【 摘 要 】

Background

Our 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.

Methods

A 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.

Results

Patients 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.

Conclusions

CNS 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.

【 授权许可】

   
2011 Hautala et al; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Vapalahti O, Mustonen J, Lundkvist A, Henttonen H, Plyusnin A, Vaheri A: Hantavirus infections in Europe. Lancet Infect Dis 2003, 3:653-661.
• [2]Piechotowski I, Brockmann SO, Schwarz C, Winter CH, Ranft U, Pfaff G: Emergence of hantavirus in South Germany: rodents, climate and human infections. Parasitol Res 2008, 103(Suppl 1):S131-S137.
• [3]Tersago K, Verhagen R, Servais A, Heyman P, Ducoffre G, Leirs H: Hantavirus disease (nephropathia epidemica) in Belgium: effects of tree seed production and climate. Epidemiol Infect 2009, 137:250-256.
• [4]Ahlm C, Linden C, Linderholm M, Alexeyev OA, Billheden J, Elgh F, Fagerlund M, Zetterlund B, Settergren B: Central nervous system and ophthalmic involvement in nephropathia epidemica (European type of haemorrhagic fever with renal syndrome). J Infect 1998, 36:149-155.
• [5]Alexeyev OA, Morozov VG: Neurological manifestations of hemorrhagic fever with renal syndrome caused by Puumala virus: review of 811 cases. Clin Infect Dis 1995, 20:255-258.
• [6]Toivanen AL, Valanne L, Tatlisumak T: Acute disseminated encephalomyelitis following nephropathia epidemica. Acta Neurol Scand 2002, 105:333-336.
• [7]Hautala T, Mähonen SM, Sironen T, Hautala N, Pääkkö E, Karttunen A, Salmela PI, Ilonen J, Vainio O, Glumoff V, Rytky S, Plyusnin A, Vaheri A, Vapalahti O, Kauma H: Central nervous system-related symptoms and findings are common in acute Puumala hantavirus infection. Ann Med 2010, 42:344-351.
• [8]Hautala T, Sironen T, Vapalahti O, Pääkko E, Särkioja T, Salmela PI, Vaheri A, Plyusnin A, Kauma H: Hypophyseal hemorrhage and panhypopituitarism during Puumala Virus Infection: Magnetic Resonance Imaging and detection of viral antigen in the hypophysis. Clin Infect Dis 2002, 35:96-101.
• [9]Mähönen SM, Sironen T, Vapalahti O, Pääkkö E, Hautala N, Ilonen J, Glumoff V, Vainio O, Kauma H, Vaheri A, Plyusnin A, Hautala T: Puumala virus RNA in cerebrospinal fluid in a patient with uncomplicated nephropathia epidemica. J Clin Virol 2007, 40:248-251.
• [10]Settergren B, Juto P, Trollfors B, Wadell G, Norrby SR: Clinical characteristics of nephropathia epidemica in Sweden: prospective study of 74 cases. Rev Infect Dis 1989, 11:921-927.
• [11]Forslund T, Saltevo J, Anttinen J, Auvinen S, Brummer-Korvenkontio M, Korhonen A, Poutiainen M: Complications of nephropathia epidemica: three cases. J Intern Med 1992, 232:87-90.
• [12]Launes J, Hautanen A: Nephropathia epidemica encephalitis. Acta Neurol Scand 1988, 78:234-235.
• [13]Bergmann F, Krone B, Bleich S, Prange H, Paulus W: Encephalitis due to a hantavirus infection. J Infect 2002, 45:58-59.
• [14]Horan TC, Andrus M, Dudeck MA: CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008, 36:309-332.
• [15]Hautala N, Kauma H, Vapalahti O, Mähonen SM, Vainio O, Vaheri A, Hautala T: Prospective study on ocular findings in acute Puumala hantavirus infection in hospitalised patients. Br J Ophthalmol 2010.
• [16]Vaheri A, Vapalahti O, Plyusnin A: How to diagnose hantavirus infections and detect them in rodents and insectivores. Rev Med Virol 2008, 18:277-288.
• [17]Mäkela S, Jaatinen P, Miettinen M, Salmi J, Ala-Houhala I, Huhtala H, Hurme M, Pörsti I, Vaheri A, Mustonen J: Hormonal deficiencies during and after Puumala hantavirus infection. Eur J Clin Microbiol Infect Dis 2010, 29:705-713.
• [18]Pekic S, Cvijovic G, Stojanovic M, Kendereski A, Micic D, Popovic V: Hypopituitarism as a late complication of hemorrhagic fever. Endocrine 2005, 26:79-82.
• [19]Mustonen J, Huttunen NP, Brummer-Korvenkontio M, Vaheri A: Clinical picture of nephropathia epidemica in children. Acta Paediatr 1994, 83:526-529.
• [20]Ahlm C, Settergren B, Gothefors L, Juto P: Nephropathia epidemica (hemorrhagic fever with renal syndrome) in children: clinical characteristics. Pediatr Infect Dis J 1994, 13:45-49.
• [21]Easterbrook JD, Kaplan JB, Glass GE, Pletnikov MV, Klein SL: Elevated testosterone and reduced 5-HIAA concentrations are associated with wounding and hantavirus infection in male Norway rats. Horm Behav 2007, 52:474-481.