There are five known families of RNA viruses which causes VHFs: Arenaviridae, Filoviridae, Flaviviridae, Hantaviridae, and Rhabdoviridae.

In most VHFs, several mechanisms likely contribute to symptoms, including liver damage, disseminated intravascular coagulation (DIC), and bone marrow dysfunction.

The fourth mechanism is when infected macrophages interact with toxic cytokines, leading to diapedesis and coagulation deficiency.

The gaps lead to increased endothelial permeability and allow blood to escape from the vascular circulatory system.

[citation needed] The reasons for variation among patients infected with the same virus are unknown but stem from a complex system of virus-host interactions.

[citation needed] Definitive diagnosis is usually made at a reference laboratory with advanced biocontainment capabilities.

The findings of laboratory investigation vary somewhat between the viruses but in general, there is a decrease in the total white cell count (particularly the lymphocytes), a decrease in the platelet count, an increase in the blood serum liver enzymes, and reduced blood clotting ability measured as an increase in both the prothrombin (PT) and activated partial thromboplastin times (PTT).

The precautions include hand hygiene, double gloves, gowns, shoe and leg coverings, and face shields or goggles.

Antiviral therapy with intravenous ribavirin may be useful in Bunyaviridae and Arenaviridae infections (specifically Lassa fever, RVF, CCHF, and HFRS due to Old World Hantavirus infection) and can be used only under an experimental protocol as IND approved by the U.S. Food and Drug Administration (FDA).

[citation needed] A potential novel treatment, the NMT inhibitor, has been shown to completely inhibit lassa (LAS) and Junín (JUN) viral infections in cells based assays.