Myths and truths: Hemorrhagic fevers in Greece and Europe

 

Myths Truths
Hantaan viruses are not endemic in Europe. Puumala virus (PUUV) causes nephropathia epidemica, a mild clinical presentation of HFRS, with a fatality rate <1%. It is endemic in Scandinavia, the western area of the ex-Soviet Union, and in northern Europe where it has been recognized for decades.

Dobrava-Belgrade virus (DOBV) is the cause of thousands of HFRS cases in the Balkans. In Greece almost all HFRS cases are caused by DOBV. A serologic study carried out by our laboratory in 1981 revealed that a hantavirus circulates in Greece; in 1984 the serologic investigation of a human case identified a hantavirus infection, and in 1989 we described the clinical and laboratory characteristics of the disease endemic in our country, based on a study of 27 serologically diagnosed, severe HFRS cases.

However, from the south-eastern to the western and northern countries of Europe there is a gradient of the DOBV/PUUV infection ratio ranging from 50% in Slovenia to <1% in Western Europe and Fennoscandia, where PUUV is predominant. Outdoor activities are a risk factor as infection may occur during any civil or military intervention in forest areas, making farmers, shepherds, forestry workers, and military personnel high-risk groups. The male to female ration is 3:1; the age distribution shows a higher incidence in the age group 35–50. Person-to-person spread has not been identified.

The exact incidence of hantavirus infections cannot be estimated, especially for the mild Puumala virus-induced HFRS (nephropathia epidemica) for which the number of infections is underestimated. In Greece, there are about five cases admitted to hospitals on a yearly basis, two of which are reported to the Hellenic Center for Disease Control and Prevention (HCDCP), Athens, Greece (unpublished data). Since 2004 the Department of Surveillance of the HCDCP has been notified of 18 human cases (none fatal), 12 Greek nationals and six foreigners. Of those, 13 did not report any travel history (12 were residents of northern Greece), one had travelled to Bulgaria, and four could not be reached on reporting their infection.

Crimean-Congo hemorrhagic fever (CCHF) is not endemic in Europe. Crimean-Congo hemorrhagic fever virus infection (CCHFV infection), caused by the Crimean-Congo hemorrhagic fever virus (CCHFV), genus Nairovirus, family Bunyaviridae, is a tick-borne viral zoonosis with the potential of human-to-human transmission. It affects wide areas of Asia, south-eastern Europe, and Africa. Serologic data suggest CCHFV is not clinically evident in France, Portugal, Hungary, Egypt, and India, but clinical cases have been reported from Balkan countries.

In Greece, a serosurvey in 1982 revealed human infections of CCHF without a history of severe disease. Α more recent serosurvey in the rural, mountainous, sparsely-populated north-western prefecture of Greece revealed a 14.4% CCHF IgG antibody seroprevalence even though CCHF cases have never been reported in this area and none of the participants recalled any symptoms resembling CCHF.

Only one case has ever been reported in Greece, close to the north-eastern border in 2008. It was fatal, and caused by a strain different from the AP92 strain, but similar to those identified in the Balkan Peninsula, Russia and Turkey. However, in the same area of Greece, a considerable increase in the prevalence of antibodies against CCHFV has been detected during the past 20 years. This could be attributed to climatic changes and infested livestock movements (legal or illegal) in a habitat suitable for ticks.

Hemorrhagic fever viruses (VHFs) are found primarily in African and in tropical countries. They do not affect Europe. Different hemorrhagic fever viruses circulate in different continents, in all types of climate. Visitors, workers, or tourists traveling to endemic areas may contract VHF viruses and import them into a country. VHFs can also be introduced to a country by importing animals infected with VHF viruses.
We are Europeans, and on returning to our countries, we will be promptly diagnosed and effectively treated in European hospitals. All VHFs have insidious onset with non-specific symptoms, thus a diagnosis is not easily reached. Valuable time may elapse and close contacts or health care workers may be infected if a VHF is not suspected promptly. Furthermore, for Marburg and Ebola the serodiagnosis is not reliable. There is no specific treatment apart from ribavirin (not effective against Ebola and Marburg filoviruses) and supportive therapy. The earlier the ribavirin is administered, the more benign the course of the disease. The case fatality rates are high.
Visitors to rural or suburban areas in Africa can avoid contact with VHF viruses by collecting information about ongoing outbreaks in the area. This is not true as the native populations are not a reliable indicator as to whether VHFs circulate in rural or suburban areas. The native populations appear commonly seropositive with IgG antibodies against VHF viruses, and they have a high incidence of asymptomatic or mild disease. In contrast, according to the literature, incoming foreigners to the area suffer a higher incidence of severe disease, hospitalization, and death.
The filoviruses Marburg and Ebola, are similar to other VHFs. This is not true. They have higher case fatality rates, from 25% to 83%. They produce up to five generations of cases within household contexts. They are very stable and highly infective via the skin and skin-attached structures. Only Marburg and Ebola cause a maculopapular rash, prominent on the trunk at around Day 5. They follow a severe progressive course with abdominal pain and diarrhea, and the IgG serologic detection may be unreliable with many false positives. Viral isolation is used to confirm the diagnosis. Reverse transcription of the RNA of these viruses and its subsequent PCR is a sensitive diagnostic method. Last but not least, ribavirin is not effective for filoviruses.
Lassa virus is similar to other VHF viruses. There are important differences between Lassa and other VHF viruses. Endemic Lassa may be transmitted by aerosol or by direct contact with infected rodents in households and by person-to-person contact. Attempts to control the disease by controlling rodents in households have failed. Viral aerosol transmission has occurred in the laboratory.

 

Professor Antonios Antoniadis,
Medical School, University of Thessaloniki, President of the Hellenic Pasteur Institute