Viral Hemorrhagic Fevers

The term ''viral hemorrhagic fever'' (VHF) describes a variety of viral diseases which are characterized by fever and bleeding in humans. This syndrome is caused by RNA viruses belonging to the families Filoviridae (Ebola virus and Marburg virus), Arenaviridae (Lassa virus, Junin virus, Machupo virus, Guanarito virus, and Sabia virus), Bunyaviridae [CCHF virus, Rift Valley fever (RVF) virus, and Hantaviruses], and Flaviviridae (yellow fever virus and dengue virus). After transmission from their reservoir host or vector to humans, these viruses cause an acute infection and there is no evidence of chronic courses.

The clinical symptoms in the early phase of a VHF are very similar irrespective of the causative virus and resemble a flu-like illness or a common enteritis. Headache, myalgia, gastrointestinal symptoms, and symptoms of the upper respiratory tract dominate the clinical picture. Hepatitis is also common. Therefore, especially in the early phase, virological testing is of utmost importance in diagnosis. The late phase of a VHF is more specific and characterized by organ manifestations and organ failure. Hemorrhage, the hallmark of a VHF, is present only in a fraction of patients depending on the virus species or even virus strain. Mild and subclinical courses seem to occur in all hemorrhagic fevers. However, if the disease is symptomatic, the case fatality ranges between 5% and 30%, but may be as high as 80% in Ebola fever.

With a few exceptions, currently, there exists no specific and effective therapy for VHF. The drug ribavirin is effective against Lassa virus and probably against CCHF virus. Vaccines have been developed against yellow fever virus,[1] Junin virus,[2] and RVF virus.[3]

Isolation of the virus in cell culture or laboratory animals, PCR, virus antigen detection, electron microscopy, and detection of specific antibodies in the serum of the patient are common methods for laboratory diagnosis of a VHF. According to the focus of this volume, this article addresses molecular diagnostic methods only. However, diagnosing a VHF always requires combined testing with more than one method.

This article reviews published VHF RT-PCR methods. Reported analytical sensitivities are compared against virus concentrations found in patients, and primers are reevaluated based on the latest GenBank entries by multiple sequence alignment (refer to table legends).

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