Hantaviruses—Globally emerging pathogens
Introduction
Hantavirus disease is a zoonosis. The causative viruses, collectively belonging to the genus Hantavirus of the Bunyaviridae family, are harbored by small mammals as reservoir hosts and transmitted to men. In humans, they cause febrile disease, usually named “Hemorrhagic Fever with Renal Syndrome” (HFRS) for disease in Asia and Europe and “Hantavirus Cardiopulmonary Syndrome” (HCPS) in the Americas with case fatality rates of up to 35–50% [67], [48], [45], [18]. The pathogenesis of hantavirus disease is characterized by changes in blood coagulation, vasodilatation and disturbances in the barrier function of the capillaries, resulting in extravasion of blood and inflammatory processes in the affected organs. Since pathogenesis is highly similar and clinical appearance is overlapping between both syndromes, comprehensive terms as “hantavirus disease” or “hantavirus fever” have been suggested to denote the disease [12], [92].
Virus transmission to humans occurs via inhalation of aerosolized rodent urine, saliva, and feces, rarely by rodent bites. In the environment, virus particles remain infectious for several weeks – depending on factors as humidity, temperature, and association with protective proteins [22]. An overview about the risk factors of hantavirus infections was very recently compiled by Watson et al. [98]; the most prominent factors are involvement in outdoor activities, such as rural- and forest-related activities, peridomestic rodent presence, exposure to potentially infected dust, and outdoor military training. Humans are usually considered to be dead-end hosts who do not transmit the virus further. However, indubitable human-to-human transmission of Andes hantavirus was reported in Argentina and Chile [99], [63], [9], [53], [14].
According to the presence of infected animal hosts and their contacts to humans, occurrence of hantavirus disease can be observed in different climatic zones including subtropics and tropics. Hantaviruses are considered to belong to the group of emerging viruses; this has mainly to do with the frequent identification of novel hantaviruses and their role as human pathogens. There are different trends in the development of case numbers; whereas in China – the country with most HFRS cases per year worldwide – the number of patients seems to decrease because of the vaccination approaches in this country [23], the number of cases in Europe and particularly Germany shows a clear increase over the last years [70], [46].
Here, we will refer to the progress in hantavirus epidemiology and diagnostics during the previous decade (see also Box 1) with a particular focus on infections in tropical areas.
Section snippets
Africa
Africa is clearly the continent with the most recent scientific progress in terms of hantavirus epizootiology and epidemiology. Ten years ago, no indigenous African hantaviruses were known, while today, approximately 10 hantaviruses have been identified not only in rodents but also shrews and even bats in Africa.
Several seroepidemiological studies in African humans suggested the presence of hantaviruses in Africa much earlier (for a comprehensive review, see [100]). However, the first African
Laboratory methods
Usual laboratory findings in both HFRS and HCPS are thrombocytopenia, increased haematocrit, leukocytosis, and increased serum creatinine. Other laboratory markers depend on the preferentially targeted organ and its failure. Hantavirus isolation in cell culture is not a routine procedure for laboratory diagnosis because it is laborious, time-consuming and can only be performed by trained personnel in biosafety level 3 laboratories [95].
Considering that HFRS and HCPS are rapidly progressive
Treatment and prophylaxis
Treatment of disease is based on the clinical symptoms and occasionally includes hemodialysis, oxygenization, and/or shock therapy. There is no specific antiviral chemotherapy available. Ribavirin is the only established antiviral drug with some in vitro and in vivo-effects against hantavirus replication [81], [60]. However, its action is rather virus-nonspecific and its therapeutic use leads to side effects, such as anemia. The efficacy of ribavirin therapy given to HTNV-infected suckling mice
Conclusions and outlook on the next decade (see also Box 2)
In the next years, we expect an extended search for hantavirus occurrence and epidemiology in geographical “terrae incognitae” of all continents, including Africa and Australia. This includes the quest to identify the presence of (new) hantaviruses in (new) hosts and the clinical relevance of newly discovered hantaviruses. The finding of new hantaviruses requires the development of respective serodiagnostic tools to investigate their seroepidemiology and their clinical relevance in infected
Funding
Work from the laboratories of the authors was supported by various research grants. Writing of this review paper was not supported by special funding.
Competing interests
None declared.
Ethical approval
None.
Acknowledgement
We thank Jan ter Meulen (Seattle, WA) for encouragement and helpful suggestions, Ric Yanagihara (Honolulu, HI) for critical reading, and Christina Grübel (Berlin) for her help in manuscript editing.
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