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Clinical Course and Long-Term Outcome of Hantavirus-Associated Nephropathia Epidemica, Germany - Volume 21, Number 1—January 2015 - Emerging Infectious Disease journal - CDC

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Clinical Course and Long-Term Outcome of Hantavirus-Associated Nephropathia Epidemica, Germany - Volume 21, Number 1—January 2015 - Emerging Infectious Disease journal - CDC



Volume 21, Number 1—January 2015

CME ACTIVITY - Research

Clinical Course and Long-Term Outcome of Hantavirus-Associated Nephropathia Epidemica, Germany

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Joerg Latus, Matthias Schwab, Evelina Tacconelli, Friedrich-Michael Pieper, Daniel Wegener, Juergen Dippon, Simon Müller, David Zakim, Stephan Segerer, Daniel Kitterer, Martin Priwitzer, Barbara Mezger, Birgit Walter-Frank, Angela Corea, Albrecht Wiedenmann, Stefan Brockmann, Christoph Pöhlmann, M. Dominik Alscher, and Niko BraunComments to Author 
Author affiliations: Robert-Bosch-Hospital, Stuttgart, Germany (J. Latus, F.-M. Pieper, D. Wegener, D. Zakim, D. Kitterer, C. Pöhlmann, M.D. Alscher, N. Braun); Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart (M. Schwab); University Hospital Tübingen, Germany (M. Schwab, E. Tacconelli); University of Stuttgart, Stuttgart (J. Dippon, S. Müller); University Hospital Zurich, Zurich, Switzerland (S. Segerer); Local Health Authority, Stuttgart (M. Priwitzer, B. Mezger); Local Health Authority, Böblingen, Germany (B. Walter-Frank); Local Health Authority, Esslingen, Germany (A. Corea, A. Wiedenmann); Local Health Authority, Reutlingen, Germany (S. Brockmann)

Abstract

Human infection with Puumala virus (PUUV), the most common hantavirus in Central Europe, causes nephropathia epidemica (NE), a disease characterized by acute kidney injury and thrombocytopenia. To determine the clinical phenotype of hantavirus-infected patients and their long-term outcome and humoral immunity to PUUV, we conducted a cross-sectional prospective survey of 456 patients in Germany with clinically and serologically confirmed hantavirus-associated NE during 2001–2012. Prominent clinical findings during acute NE were fever and back/limb pain, and 88% of the patients had acute kidney injury. At follow-up (7–35 mo), all patients had detectable hantavirus-specific IgG; 8.5% had persistent IgM; 25% had hematuria; 23% had hypertension (new diagnosis for 67%); and 7% had proteinuria. NE-associated hypertension and proteinuria do not appear to have long-term consequences, but NE-associated hematuria may. All patients in this study had hantavirus-specific IgG up to years after the infection.
Hantaviruses, enveloped RNA viruses of the family Bunyaviridae, are transmitted to humans by rodents, the natural reservoir of these viruses (1). In North America, hantavirus infection can lead to hantavirus cardiopulmonary syndrome and to case–fatality rates of up to 35% (2,3), and in Asia and Europe, infection can lead to hemorrhagic fever with renal syndrome (HFRS) (4).
In Germany, the incidence of HFRS increased from 0.09 cases/100,000 persons in 2001 to 2.47 cases/100,000 persons in 2010 (5). During October 2011–April 2012, a total of 852 HFRS cases were reported in Germany, of which 580 (68%) originated in the southern federal state of Baden-Wurttemberg (6). Puumala virus (PUUV), by far the most frequent cause of hantavirus disease in Germany (7), causes a milder form of HFRS (8) called nephropathia epidemica (NE). Hantavirus infections are one of the 5 most common notifiable viral diseases in Germany, along with norovirus infections, hepatitis C, influenza, and rotavirus infections (7).
NE is characterized by acute kidney injury associated with thrombocytopenia and, frequently, with proteinuria (9). Severe and often prolonged gastrointestinal symptoms and severe back and abdominal pain also occur (10). The severity of infection with PUUV varies from subclinical disease to severe acute kidney injury, including a fatal outcome (11,12). Renal replacement therapy is required in ≈5% of hospitalized patients with acute NE (8,10,13,14), although some studies report rates of up to 25% (15,16).
Despite the high and increasing incidence of hantavirus infection, long-term follow-up data have not been reported for a large, representative cohort of patients. Moreover, it remains unclear whether NE has long-term consequences, such as hypertension, proteinuria (17), and alteration of kidney function (18,19). Two previous studies that followed up 36 Finnish patients 5 and 10 years after they experienced PUUV-associated NE, reported that the patients had increased urinary protein excretion, glomerular hyperfiltration, and elevated blood pressure at a 5-year but not a 10-year follow-up (18,19). Other reports support an association between previous hantavirus infection and subsequent hypertension (20–23).
Data on humoral immunity years after PUUV infection are not available for a representative cohort of German patients. Thus, we conducted this study in such a cohort to describe the detailed clinical phenotype of patients with clinical manifestations of PUUV infection and their long-term outcomes and humoral immunity to PUUV.

Dr. Latus is a resident in the Nephrology department at the Robert-Bosch-Hospital, Stuttgart, Germany. His primary research interests are zoonoses, especially the clinical course of hantavirus infections.

Acknowledgment

This study was supported by the Robert-Bosch Foundation.

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Tables

Technical Appendix

Suggested citation for this article: Latus J, Schwab M, Tacconelli E, Pieper F-M, Wegener D, Dippon J, et al. Clinical course and long-term outcome of hantavirus-associated nephropathia epidemica, Germany. Emerg Infect Dis. 2015 Jan [date cited]. http://dx.doi.org/10.3201/eid2101.140861
DOI: 10.3201/eid2101.140861

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