Background

Hantaviruses belong to the family Bunyaviridae and have a tri-segmented negative-sense single-stranded RNA genome. The virus reservoir was found to be rodents and transmission occurs by aerosol of rodent droppings. The different types of hantavirus have co-evolved with their specific rodent host through evolutionary time spans.

Korean haemorragic fever, that later was found to be caused by a hantavirus infection, attracted attention during, and after, the Korean war (1951–1953), when more than 3000 American and Korean soldiers fell severely ill with an infectious disease characterized by renal failure, generalized haemorrhage and shock with a letality of >10%. The causative agent was first isolated 1976 from the lungs of the striped field mouse Apodemus agrarius, and designated Hantaan virus (HTN) [1,2]. Seroepidemiological studies revealed that HTN virus is only one example of a complex of related viruses that can be found worldwide. An anti-genetically related virus (Seoul) isolated from the brown rat (Rattus norvegicus and Rattus rattus) has been implicated in a milder urban form of haemorrhagic fever with renal syndrome (HFRS) [3]. Further studies revealed another antigenetically related virus (Puumala-PUU), which was isolated from the bank vole (Clethrionomys glareolus) [4]. This hantavirus subtype causes nephropathia epidemica (NE) and is the main serotype found in Europe. Historical sources show that an epidemic of `trench nephritis' during World War I may have been hantavirus induced and that during World War II, >10 000 cases of a rodent borne leptospirosis-like disease were noted among German troops in Finnish Lappland [5].

The main hantavirus serotype known in the US is the serotype Prospect Hill that seems to be apathogenic for men. However, in 1993 a highly pathogenic form of hantavirus was detected in the south-western US, causing a severe pulmonary disease (Hantavirus pulmonary syndrome (HPS)) with a letality of >50%. The aetiologic agent was isolated from the deer mouse (Peromyscus maniculatus) and named Sin Nombre virus (SNV) [6]. In the meantime, a variety of hantaviruses were isolated from other rodent hosts in the US and named after the geographic region of their isolation, e.g. New York virus, El Moro Canyon virus, Black Creek Canal virus and Bayou virus. These isolates showed minor genetic differences to SNV. Shortly thereafter, hantaviruses causing HPS-like disease with high lethality of >50% were detected in South America, particularly in Argentina, Chile and Paraguay. In some of these cases human-to-human transmission was reported [7].

Hantavirus strains and hantavirus infections in the Balkan countries

In the Balkan region at least four serotypes are present simultaneously: PUU, SEO, HTN, HTN-like types, and a new serotype called Dobrava (DOB), that causes a mortality rate of up to 20%. In the former Yugoslavia, epidemic nephropathia outbreaks have been recorded since the early 1950s [8]. The elevated rates of illness and death in early reports suggested the spread of HTN like hantaviral strains (Plitvice and Fojnica), in addition to the mild PUU serotype prevalent in the rest of Europe. In 1987, a HTN-like virus (Porogia) was isolated from the urine of a Greek soldier who developed acute renal failure and severe pulmonary oedema after a military exercise near the border in northern Greece. The Porogia isolate showed extensive serological cross-reactivity with HTN [9]. Moreover, a hantavirus genetically very similar to HTN that caused a mortality rate of up to 20% was first described as a human isolate (Belgrade) in Serbia [10]. The aetiologic agent was confirmed in 1992 as a new hantavirus serotype called Dobrava (DOB) after isolation from its rodent vector, an Apodemus flavicollis (yellow-necked field mouse) captured in Dobrava, Slovenia [11]. The first genetic evidence for the association between DOB and severe hantavirus disease was obtained by RT–PCR from whole blood of a Greek and an Albanian patient [12]. In 1994 another hantavirus was isolated in Slovenia that was indistinguishable from the prototype Korean strain HTN by RT–PCR genotyping [13]. In the time period 1995–1996, a HFRS epidemic was recorded in the republic of Yugoslavia with more than 2000 cases of severe haemorrhagic fever [14]. During the recent military conflict in Bosnia, more than 300 individuals, most of them soldiers exposed in the field, were hospitalized in the Tuzla region (Northeast Bosnia) with acute hantavirus symptoms [15]. Most of the Balkan cases were detected in active duty military personnel and exposure to rodents seemed to be the most important risk factor for developing hantavirus disease. An outbreak of hantavirus disease in Americans abroad was reported in US soldiers camping in a mice-infested area in January 1990 in southern Germany. In a short period of 2 weeks, 24 acute PUU infections occurred, and 14 soldiers had to be hospitalized with acute renal failure of varying severity [16].

The current epidemical situation

The war in Yugoslavia caused massive streams of refugees out of the Kosovo region of Yugoslavia that end up in refugee camps in Macedonia, Albania and Montenegro. They are exposed under these conditions to rodent droppings and therefore at risk to acquire hantavirus infections. The same situation applies to deployed ground troops in the area. Recently, human-to-human transmission of hantavirus was reported in South America [7]. Given the known propensity of hantaviruses for genetic drift and major rearrangements by homologous recombination [17], a possibility of DOB virus distribution to the host countries in Europe and US through the infected refugees and soldiers cannot be excluded. This fact requires particular attention on the part of the health authorities involved in the war. The authorities are advised to initiate seroepidemiological screening of the refugees and to be aware of this potential hazard.

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