Hemorrhagic fevers

Synonyms

2

Overview

Hemorrhagic fevers also called Viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses in which fever and hemorrhage are caused by a viral infection. VHFs may be caused by five distinct families of RNA viruses: the families Arenaviridae, Filoviridae, Bunyaviridae, Flaviviridae, and Rhabdoviridae. All types of VHF are characterized by fever and bleeding disorders and all can progress to high fever, shock and death in many cases. Some of the VHF agents cause relatively mild illnesses, such as the Scandinavian nephropathia epidemica (a Hantavirus), while others, such as Ebola virus, can cause severe, life-threatening disease.

Symptoms

Signs and symptoms of VHFs include (by definition) fever and increased susceptibility to bleeding (bleeding diathesis). Manifestations of VHF often also include flushing of the face and chest, small red or purple spots (petechiae), bleeding, swelling caused by edema, low blood pressure (hypotension), and shock. Malaise, muscle pain, headache, vomiting, and diarrhea occur frequently. The severity of symptoms varies with the type of virus. The “VHF syndrome” (capillary leak, bleeding diathesis, and circulatory compromise leading to shock) appears in a majority of people with filovirus hemorrhagic fevers (e.g., Ebola and Marburg virus), Crimean–Congo hemorrhagic fever (CCHF), and the South American hemorrhagic fevers caused by arenaviruses, but only in a small minority of patients with dengue, Rift Valley fever, and Lassa fever.

Causes

Five families of RNA viruses have been recognised as being able to cause hemorrhagic fevers.

  • The family Arenaviridae include the viruses responsible for Lassa fever (Lassa virus), Lujo virus, Argentine (Junin virus), Bolivian (Machupo virus), Brazilian (Sabiá virus) and Venezuelan (Guanarito virus) hemorrhagic fevers.
  • The family Bunyaviridae include the members of the Hantavirus genus that cause hemorrhagic fever with renal syndrome (HFRS), the Crimean-Congo hemorrhagic fever (CCHF) virus from the Nairovirus genus, Garissa virus and Ilesha virus from the Orthobunyavirus and the Rift Valley fever (RVF) virus from the Phlebovirus genus.
  • The family Filoviridae include Ebola virus and Marburg virus.
  • The family Flaviviridae include dengue, yellow fever, and two viruses in the tick-borne encephalitis group that cause VHF: Omsk hemorrhagic fever virus and Kyasanur Forest disease virus.
  • In September 2012 scientists writing in the journal PLOS Pathogens reported the isolation of a member of the Rhabdoviridae responsible for 2 fatal and 2 non-fatal cases of hemorrhagic fever in the Bas-Congo district of the Democratic Republic of Congo. The non-fatal cases occurred in healthcare workers involved in the treatment of the other two, suggesting the possibility of person-to-person transmission. This virus appears to be unrelated to previously known Rhabdoviruses.

Diagnosis

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 hematocrit may be elevated. The serum urea and creatine may be raised but this is dependent on the hydration status of the patient. The bleeding time tends to be prolonged.

Treatment

Medical management of HF patients may require intensive supportive care. 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 investigational new drug (IND) approved by the U.S. Food and Drug Administration (FDA). Interferon may be effective in Argentine or Bolivian hemorrhagic fevers (also available only as IND).