Recent outbreaks of hantavirus disease in Germany and in the United States

Abstract

Infections are a growing cause of acute kidney injury (AKI) and have attracted attention in recent years due to outbreaks of zoonotic diseases. A rise in AKI events occurred during the outbreak of influenza in 2009 and the hemolytic uremic syndrome in 2011 in Germany.1.Abdulkader R.C. Ho Y.L. de Sousa Santos S. et al.Characteristics of acute kidney injury in patients infected with the 2009 influenza A (H1N1) virus.Clin J Am Soc Nephrol. 2010; 5: 1916-1921Crossref PubMed Scopus (36) Google Scholar,2.Buchholz U. Bernard H. Werber D. et al.German outbreak of Escherichia coli O104:H4 associated with sprouts.N Engl J Med. 2011; 365: 1763-1770Crossref PubMed Scopus (556) Google Scholar In 2012 Germany's authorities noticed a remarkable increase of hantavirus-induced AKI. Hantaviruses are zoonoses transmitted by inhalation of contaminated aerosols from small mammals. Pathogenic strains are distributed worldwide and cause different clinical entities. In Europe, the Puumala hantavirus is predominant, and the epidemic occurrence of cases has been increasing in recent years. This year, an extraordinary rise has been observed; case numbers exceed those of previous years. The problem of increasing case numbers is not limited to Germany. In September 2012 an outbreak of hantavirus occurred in the Unites States. However, the situation there differs from those in European countries. The disease-causing hantavirus, Sin Nombre, is the etiological agent of hantavirus cardiopulmonary syndrome, characterized by pulmonary involvement and high mortality. The outbreak occurred among tourists in a national park. A global alert was issued, because thousands of travelers from foreign countries were at risk of having acquired the infection during their stay in the park. The two outbreaks reported here are not epidemiologically linked but demonstrate the global emergence of hantavirus disease. Since 2001 it has been mandatory to report a hantavirus infection to the health authorities in Germany. During these years fewer than 450 cases per year were reported, with the exception of the outbreaks in 2007 and 2010, with 1688 and 2017 cases, respectively.3.SurvStat 2012http://www3.rki.de/SurvStatGoogle Scholar This year, 2182 cases of hantavirus disease were already reported from January to July (Figure 1). The number of infections started to increase from October 2011, and since spring 2012, cases have rapidly accumulated. Males are overrepresented and constitute about 70% of cases. The age group that is mostly infected ranges from 40 to 49 years. These characteristics correspond to those of previous hantaviral epidemics. In Germany, Puumala virus (PUUV) is clinically the most important hantavirus. Its natural reservoir is the bank vole, Myodes glareolus, which is found throughout the country. PUUV disease cases in Germany are concentrated in specific outbreak regions (Figure 2), each of them characterized by a particular molecular clade of PUUV strains found in local bank voles as well as patients.4.Boone I. Wagner-Wiening C. Reil D. et al.Rise in the number of notified human hantavirus infections since October 2011 in Baden-Wurttemberg, Germany.Euro Surveill. 2012; 17: pii=20180Google Scholar,5.Ettinger J. Hofmann J. Enders M. et al.Multiple synchronous Puumala hantavirus outbreaks, 2010.Emerg Infect Dis. 2012; 18: 1461-1664Crossref PubMed Scopus (62) Google Scholar The initial symptoms of hantavirus disease are sudden onset with fever, nausea, headache, and abdominal and side/back pain. About 55–65% of patients with hantavirus disease are hospitalized, for a median duration of 8 days. Patients are usually admitted with acute renal failure and thrombocytopenia. Infection is characterized by marked proteinuria, elevation of serum creatinine levels, and decreased serum albumin. Typically, hemorrhagic fever with renal syndrome is diagnosed serologically by immunofluorescence assay, immunoblot, or enzyme-linked immunosorbent assay. Because the viremic phase in the patient lasts no longer than 1 to a few weeks after the onset of symptoms, the molecular characterization of circulating virus strains by sequencing of the hantavirus genome is possible only from serum/EDTA blood specimens sampled during this period. In contrast to serological assays, molecular approaches make it possible to distinguish between infections by different representatives of a particular hantavirus species (for instance, PUUV). Efficient serotyping of the responsible hantavirus species requires the determination of neutralizing antibodies in the patient's serum, which has to be performed under biosafety level 3 conditions.6.Krüger D.H. Schonrich G. Klempa B. Human pathogenic hantaviruses and prevention of infection.Hum Vaccin. 2011; 7: 685-693Crossref PubMed Scopus (139) Google Scholar About 5% of hospitalized patients require temporary dialysis. In some cases, extrarenal manifestations such as neurological complications and pulmonary symptoms can be observed. PUUV infections may vary in severity and symptoms. The prognosis regarding renal outcome is very good, and most patients recover completely. No fatal cases were reported during the ongoing outbreak. The case fatality rate for infection with PUUV is very low in Europe (<0.1%) and Germany (<0.03%). Of the 8141 hantavirus cases reported in Germany since 2001, only two were fatal.7.Robert-Koch-Institut, Berlin,2011Google Scholar In Germany, hantavirus disease has to be reported by law.8.Robert-Koch-Institut, Berlin,2007Google Scholar There are no licensed prophylactic vaccines for use in Europe and no passive immunization or chemoprophylaxis available. Consequently, exposure prophylaxis is the most important task for prevention of hantavirus infections and disease. To reduce the risk of virus transmission from the reservoir hosts to humans, one should avoid any kind of contact with small rodents (and probably shrews) or exposure to their excreta. This includes control of mice inside and outside of human housing. Trapped or dead mice have to be disinfected and disposed of. When cleaning rooms with potential mouse infestation (such as stables, sheds, summer houses in spring), one should wear disposable gloves and, if possible, a face mask. Swirling dust particles containing mouse excreta or nesting material should be avoided. Areas frequented by rodents should be moistened before cleaning. During outdoor activities (camping, farm or forest work), contact with nests and excreta of mice should also be avoided. Further precautions include the safe storage of food inside and outside of human dwellings and the avoidance of food litter.6.Krüger D.H. Schonrich G. Klempa B. Human pathogenic hantaviruses and prevention of infection.Hum Vaccin. 2011; 7: 685-693Crossref PubMed Scopus (139) Google Scholar According to a standardized prioritization procedure for infectious diseases based on criteria such as clinical importance, epidemiology, and impact on society, hantavirus disease was classified in the highest priority group for necessary surveillance and epidemiology research.9.Balabanova Y. Gilsdorf A. Buda S. et al.Communicable diseases prioritized for surveillance and epidemiological research: results of a standardized prioritization procedure in Germany, 2011.PLoS One. 2011; 6 ([online]): e25691Crossref PubMed Scopus (88) Google Scholar More than 80,000 cases of hantavirus disease were reported in the past 10 years in Europe;10.Heyman P. Ceianu C.S. Christova I. et al.A five-year perspective on the situation of haemorrhagic fever with renal syndrome and status of the hantavirus reservoirs in Europe, 2005–2010.Euro Surveill. 2011; 16: pii=19961Google Scholar the highest case numbers were in Russia, Finland, Germany, Sweden, Belgium, and France, with annual averages ranging from about 100 (France) to more than 7000 (Russia). In 2012, increased case numbers were also observed in France and Russia. The epidemic profile of hantavirus disease in the European countries is heterogeneous and closely linked to conditions that favor growth of infected reservoir host populations (for example, climate, abundance of food, lack of predators).11.Heyman P. Thoma B.R. Marie J.L. et al.In search for factors that drive hantavirus epidemics.Front Physiol. 2012; 3 ([online]): 237Crossref PubMed Scopus (43) Google Scholar At the time of writing, an outbreak of hantavirus infections affected California. From June through 17 September 2012, nine cases of hantavirus pulmonary syndrome were reported in people who had visited Yosemite National Park, California.12.2012http://www.cdc.gov/hantavirus/outbreaks/yosemite-national-park-2012.htmlGoogle Scholar Three people died from the infection. In contrast to the outbreak of hantavirus disease in Germany, whose clinical picture is characterized by acute kidney injury and associated with a favorable outcome, people infected in Yosemite developed severe lung disease. Species circulating in the Americas cause hantavirus cardiopulmonary syndrome (HCPS).13.Duchin J.S. Koster F.T. Peters C.J. et al.Hantavirus pulmonary syndrome: a clinical description of 17 patients with a newly recognized disease. The Hantavirus Study Group.N Engl J Med. 1994; 330: 949-955Crossref PubMed Scopus (568) Google Scholar In North America, including Yosemite National Park, the Sin Nombre hantavirus carried by the deer mouse (Peromyscus maniculatus) is a predominant species. As with hantavirus species of the Old World, person-to-person transmission of Sin Nombre virus has not been reported. HCPS is characterized by a sudden onset with flu-like symptoms. After the initial phase, respiratory distress and hemodynamic alterations occur, leading to hypotension, pulmonary edema, and hypoxia. Patients often require supplemental oxygen. The mortality of HCPS is 35%. In contrast to species in the Old World, the renal involvement is minimal. Mild to moderate elevation of serum creatinine and proteinuria are observed.14.Peters C.J. Simpson G.L. Levy H. Spectrum of hantavirus infection: hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome.Annu Rev Med. 1999; 50: 531-545Crossref PubMed Scopus (213) Google Scholar,15.MacNeil A. Ksiazek T.G. Rollin P.E. Hantavirus pulmonary syndrome, United States, 1993–2009.Emerg Infect Dis. 2011; 17: 1195-1201Crossref PubMed Scopus (84) Google Scholar In addition to the modest renal dysfunction that affects some HCPS patients, potential renal sequelae have been reported.16.Pergam S.A. Schmidt D.W. Nofchissey R.A. et al.Potential renal sequelae in survivors of hantavirus cardiopulmonary syndrome.Am J Trop Med Hyg. 2009; 80: 279-285PubMed Google Scholar However, no apparent pathology of the kidney is observed. Yosemite National Park is a popular travel destination, attracting more than 4 million tourists a year from all over the world. Eight of the nine infected people stayed in so-called signature tent cabins in Curry Village. An estimated 10,000 people stayed in these cabins from 10 June through 24 August 2012. About 2500 were from outside the United States, most of them from Europe; 1923 European Union citizens were potentially exposed to the virus. The greatest numbers were from France (502), the United Kingdom (342), and Germany (250). Fortunately, despite the great number of people potentially exposed, no other infected Yosemite visitors from inside or outside the United States were reported. Import of hantavirus infection owing to travel is seldom observed. Only one case of HCPS imported from the Americas to Europe is known to have occurred, from South America in 2001.17.Murgue B. Domart Y. Coudrier D. et al.First reported case of imported hantavirus pulmonary syndrome in Europe.Emerg Infect Dis. 2002; 8: 106-107Crossref PubMed Scopus (19) Google Scholar The outbreak of HCPS among travelers calls for an awareness that imported hantavirus disease may present differently than what is expected from the endemic hantavirus strain. In contrast to the hantavirus disease in Germany and other European and Asian countries, HCPS is a rare disease, with less than 300 cases in the past 10 years in the United States. However, increasing case numbers in Europe and the outbreak of a hantavirus infection with a high mortality among travelers bring hantavirus disease into the focus of public-health interest. We thank Arnd Goppelsröder (Germany), Alexander Plyusnin (Finland), Sophie Quoilin (Belgium), and Jean Marc Reynes (France) for providing information about epidemiological data on hantavirus infections in their countries.