Pediatric Viral Hemorrhagic Fevers

Updated: Apr 10, 2013
  • Author: Martha L Muller, MD; Chief Editor: Russell W Steele, MD  more...
  • Print
Overview

Background

The 12 distinct enveloped RNA viruses that cause most viral hemorrhagic fever (VHF) cases are members of 4 families: Arenaviridae, Bunyaviridae, Filoviridae, and Flaviviridae. Disease severity resulting from infection by these agents varies widely, but the most extreme manifestations include circulatory instability, increased vascular permeability, and diffuse hemorrhage. In May 1995, these diseases came to worldwide attention with an outbreak of Ebola virus near the city of Kikwik, Zaire. [1] With increased international travel, these primarily tropical viruses may now be imported into nonendemic countries. Furthermore, several of these agents have been associated with nosocomial outbreaks involving health care workers and laboratory personnel.

Ebola virus. Electron micrograph courtesy of the C Ebola virus. Electron micrograph courtesy of the Centers for Disease Control and Prevention.

See Ebola: Care, Recommendations, and Protecting Practitioners, a Critical Images slideshow, to review treatment, recommendations, and safeguards for healthcare personnel.

Viral hemorrhagic fevers share many common features. Infectious agents that are arthropod-borne (usually mosquitoes) cause many viral hemorrhagic fevers. For several viral hemorrhagic fevers, person-to-person transmission may occur through direct contact with infected patients, their blood, or their secretions and excretions. Animal reservoirs are generally rats and mice, but domestic livestock, monkeys, and other primates may also serve as intermediate hosts.

Yellow fever (the prototype virus of the Flaviviridae family), dengue, Hantavirus pulmonary syndrome (HPS), and hemorrhagic fever with renal failure syndrome (HFRS) are discussed in separate chapters (see Differentials). The other flaviviral hemorrhagic fevers (HFs), Alkhurma HF virus, [2, 3, 4] Kyasanur Forest disease, [5] and Omsk HF, are described only in cursory detail because they have very limited geographic distribution and/or have virtually disappeared from the endemic zones in which they were previously found.

Novel viruses have recently been identified. [6, 7]

Next:

Pathophysiology

Although common themes occur, the different viruses display variable pathophysiology. Hemorrhage is typically present in many organs, and effusions are common in serous cavities (although they may be minimal or absent in some patients). Widespread necrosis generally occurs, may be present in any organ system, and varies from modest and focal to massive in extent. Liver and lymphoid systems are usually extensively involved, and the lung regularly demonstrates varying degrees of interstitial pneumonitis, diffuse alveolar damage, and hemorrhage. Acute tubular necrosis and microvascular thrombosis may also be observed. The inflammatory response is usually minimal.

Previous
Next:

Epidemiology

Frequency

United States

Aside from the bunyaviral HPS (Bayou, Black Creek Canal, Four Corners, Muleshoe, Sin Nombre), which appears to be associated with rodent-contaminated, abandoned, and closed buildings, and rare cases of HFRS, the only viral hemorrhagic fever to occur in the United States are imported cases, most frequently Lassa fever. The first imported case of Lassa fever in more than 20 years occurred in New Jersey in 2004. [8] More recently, imported Marburg virus disease was identified in a Colorado woman who traveled to Uganda. [9] Lassa fever imported to the US was again reported in 2010. [10]

International

Arenaviridae, including Guanarito (Venezuelan HF), Junin (Argentine HF), Machupo (Bolivian HF), Sabia (Brazilian HF), and Lassa viruses, are found throughout South America, particularly in the Argentine pampas, Bolivia, Venezuela, and rural Brazil near Sao Paulo. The Chapare virus was recently identified in Bolivia. [11] More recently, a novel arenavirus was identified in 5 patients in southern Africa. [12] Arenaviridae are also found in West Africa (eg, Lassa in Nigeria, Sierra Leone, Guinea, Liberia, and Mali). [13] Chronic infection of small field rodents makes rural residents and farmers the most frequently infected, with a strong seasonal predominance for the fall. In Argentina, agricultural workers are disproportionately infected. In Bolivia, rodents can invade towns and cause epidemics. In West Africa, Lassa fever is spread to humans when infected rodents are captured for consumption, as well as by person-to-person exposures. Currently, outbreaks of Lassa fever are occurring in West Africa.

Bunyaviridae (Crimean-Congo HF [CCHF], Rift Valley fever [RVF]) are seen throughout Africa, [14] the Middle East, the Balkans, [15, 16, 17] southern Russia, and western China. [18, 19] CCHF has the widest geographic distribution of the tickborne infections and is increasingly reported in Europe, [20, 21, 22] and Turkey, as well. [23]

Filoviridae (Ebola, Marburg viruses) are found in Africa and possibly in the Philippines. [24] The vector is unknown, but infected primates sometimes provide a link for spread to humans. Later spread among humans or primates by close contact may also occur. Aerosol transmission is suspected in some monkey infections. It appears that outbreaks of Ebola disease often follow uncommonly dry periods, when rainfall resumes and reaches unusually high levels. Outbreaks of Marburg in Angola have been recently identified, [25, 26] as have outbreaks of Ebola in Congo [27] and Uganda. [28, 29, 30]

Flaviviridae include Alkhurma HF virus, Kyasanur Forest disease [31] , and Omsk HF. Alkhurma HF virus is a variant of Kyasanur Forest disease virus found in Saudi Arabia and reported in a small number of patients since the 1990s. [32, 2, 33] Recent reports describe the infection in travelers returning from Egypt, suggesting that the geographic range of the virus may be increasing. [3, 34] Kyasanur Forest disease follows a tick bite in rural areas of the endemic zone, Karnataka, India. Monkey die-offs may accompany increased virus activity. Omsk HF was observed in western Siberia and has a poorly understood vector and reservoir cycle that involves ticks, voles, muskrats, and, possibly, water-borne and mosquito transmission. Very few cases have been reported in recent years.

Mortality/Morbidity

Ebola and Marburg are considered the most severe viral hemorrhagic fevers, with 25-100% mortality rates. The infection rate is high, particularly for the Zaire subtype of Ebola virus. During pregnancy, Ebola infection has been universally fatal. The South American HF has a case-infection ratio of more than 50% of those exposed. The mortality rate is 15-30%. Lassa fever is a milder infection, with a fatality rate of 2-15%, and is probably much more common than is recognized. Approximately 1% of individuals exposed to RVF virus become infected, but the mortality rate of persons infected is 50%. CCHF has an infection rate of 20-100% and a fatality rate of 15-30%.

Race

No racial predilection has been reported.

Sex

No known sex predilection for viral hemorrhagic fever has been noted, except as occupational exposures dictate.

Age

Persons affected are frequently those who have the most occupational exposure, although susceptibility in endemic regions is often highest for young children.

Previous