Hantavirus Infections in Europe: From Virus Carriers to a Major Public-health Problem

Paul Heyman; Antti Vaheri; Åke Lundkvist; Tatjana Avsic-Zupanc

Disclosures

Expert Rev Anti Infect Ther. 2009;7(2):205-217. 

In This Article

Hantavirus Infections in Europe

Reliable diagnostic tools for the diagnosis of hantavirus infections only became available in the 1990s, and hantavirus infections were probably heavily under-diagnosed well into the last decade of the 20th Century. Diagnostics of hantavirus infections had been initiated before 1990 in only six European countries: Finland (1979), Belgium (1981), Sweden (1984), Slovenia (1985), France (1987) and Russia (1980). In other countries, attention was only given to hantavirus infections after 1990 (Table 2).

A survey conducted by Heyman and Vaheri, on behalf of the European Network for Diagnostics of Imported Viral Diseases (ENIVD), accounted for a total of 35,424 confirmed cases, 33,587 (94.8%) of which were detected between 1990 and 2006.[38] Of the total number of cases in the EU 24,672 (69.6%) were reported by Finland and no hantavirus cases were reported from Spain, Italy, Cyprus or Denmark. In the Russian Federation, the European region accounted for 95% of the nation's total number of cases. From 1996 to 2006, 89,162 cases were detected, the vast majority due to PUUV infection. In the Asian region of the Russian Federation, much fewer cases were noted, with DOBV, SAAV, SEOV, HTNV and AMRV as causal agents (Platonov A, Pers. Comm.). It should, however, be kept in mind that, given the unclear clinical pictures and the benign or nonexisting clinical symptoms in a large fraction of patients, at least some cases escaped the various surveillance systems. It has been estimated that only 30% of PUUV infections lead to disease with serological confirmation.[39] Hantavirus disease is notifiable (by law a disease that has to be reported to the public-health authorities, usually within 48 h after laboratory diagnosis) in most EU countries; it is not notifiable in Austria, Cyprus, France, Portugal, Romania and Spain.

In most European countries, between 10 and 20 endemic rodent species are present on average.[201] Active surveillance of carrier rodents and circulation of pathogenic hantaviruses is seldom or not maintained on a regular basis in most countries. As active surveillance involving fieldwork (rodent snap- and/or live-trapping, sampling and subsequent testing) is both expensive and time-consuming, often with no immediate result for public-health authorities. Active surveillance is often initiated on a national level as a response to a past or ongoing epidemic, which is, by definition, too little, too late.

Tula virus, PUUV, DOBV, SAAV and SEOV hantaviruses have been reported as circulating in Europe. Of these, PUUV and DOBV have caused the vast majority of human cases in Europe, with the exception of Switzerland where the only case was associated with Tula virus.[40] Recently, SAAV was also found to be responsible for human cases in Eastern Europe.[41] No confirmed cases of SEOV infection have so far been reported in Europe, although an unpublished case, confirmed by focus reduction neutralization tests, occurred in France (Lundkvist A, Pers. Comm.).[42] Imported hantavirus cases caused by DOBV in Sweden and Austria, HTNV in Austria and Sin Nombre virus[43] in France, have been rare.

In Western and Northern Europe (Fennoscandia), only PUUV infections have been reported. From West and North to East Europe, the PUUV/DOBV infection ratio varied from 3.6% in Southern Germany, to more than 50% in Slovenia and up to 100% in Greece.

The number of human cases is on the rise in almost all European countries, and record numbers of cases were noted in Finland (2603 cases in 2002 and 2526 cases in 2005[202]), Sweden (459 cases in 2004 and 2195 cases in 2007[203]), Germany (>1400 reported in September 2007[204]) and Belgium (372 cases in 2005) during the last 5 years (Table 3).[205] Mild winters and more frequent and productive mast events allow more rodents to survive over winter. Mild winters, especially, are responsible for an early start to the breeding season and, therefore, for larger rodent populations.[44–46]

Increased hantavirus activity in epidemic years occurs in nonsynchrony geographically and temporally in the EU and adjacent countries. In West Europe, especially in Belgium, a 3-year epidemic cycle occurred until 1999 (1990, 1993, 1996 and 1999). Between 1999 and 2005 a 2-year cycle was observed (1999, 2001, 2003 and 2005); 2006 was, again, an epidemic year, as was 2007 with more than 260 cases, and 2008, with more than 270 cases detected in the first 11 months, emerged as the fourth consecutive epidemic year. As this part of Europe is located in the temperate deciduous broad leaf-tree biome, rodent cycles are regulated by masting (i.e., the available food from mainly oak and beech trigger higher rodent population densities) and a simultaneous increase of virus circulation in the population. The key factor, however, is the pattern change in 1999, which is so far unexplained, but abiotic factors, such as climatic conditions, probably play their role.[47,48]

Norway, Sweden and Finland, with 1084, 3516 and 24,672 reported cases, respectively, account for most of the hantavirus cases in Europe. Located in the boreal forest biome, rodent population-density cycles depend mainly on predator–prey mechanisms. High incidences of HFRS similar to Finland occur in parts of European Russia (e.g., Bashkiria and Udmurtia regions) and parts of Northern Sweden.

The epidemiological pattern in Finland seems to be changing.[49] In Eastern Europe, the co-circulation of two or three hantaviruses, PUUV, DOBV and SAAV, could be noted. Austria represents an interesting mixture of patterns: in the low-altitude regions (West European) the mast-year pattern prevails, while at higher altitudes (northern European) the cyclic pattern is observed (Aberle S, Pers. Comm.[50]). The number of cases in Bosnia–Herzegovina peaked in 1995 with 354 cases[51] during the conflict in that region. The epidemiological pattern and the epidemic cycles are less clear than in Western or Northern Europe.

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