Pediatric Viral Hemorrhagic Fevers

Updated: Mar 13, 2023
  • Author: Nizar F Maraqa, MD, FAAP, FPIDS; Chief Editor: Russell W Steele, MD  more...
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Practice Essentials

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.

Infectious agents that are arthropod-borne (usually mosquitoes) cause many viral hemorrhagic fevers that share many common features. 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 that cause VHFs have been identified. [6, 7]

Discussing protective measures with prospective travelers is of utmost importance for avoidance of VHFs and many other infections.

For patient education resources, see the patient education article Ticks.



Although common themes occur, the different viruses causing VHF 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 renal tubular necrosis and microvascular thrombosis may also be observed. The inflammatory response is usually minimal.



South American HF and Lassa fever arise from inhalation of aerosolized fecal matter or urine of infected rodents and from rodent bites, usually during harvest, with work on small farms, or in newly developed areas. Interhuman transmission usually does not occur but is possible.

HFRS is caused by hantaviruses, which are carried and transmitted through aerosolized excrement of rodents.

Rift Valley fever (RVF) is acquired from mosquito bites or contact with the blood of infected domestic livestock. No interhuman transmission has been observed.

Crimean-Congo HF (CCHF) results from tick bites, [8]  squashing ticks, or exposure to aerosols or fomites from slaughtered infected sheep and cattle. Nosocomial epidemics have been observed a number of times.

Ebola and Marburg infections occur from direct contact with bat excreta or saliva or with body fluids of infected non-human primates, such as monkeys, chimpanzees, and gorillas. Person to person transmission can occur from direct contact with body fluid or objects contaminated with the body fluids of an infected person.



United States statistics

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 that have been reported among rat fanciers, the only viral hemorrhagic fever cases to occur in the United States are imported cases, most frequently due to Lassa fever. The first imported case of Lassa fever in more than 20 years occurred in New Jersey in 2004. [9] More recently, imported Marburg virus disease was identified in a Colorado woman who traveled to Uganda. [10] Lassa fever was confirmed in the death of a US traveler returning from Liberia in 2015. [11] Overall, since 1969, there have been six cases reported to the CDC of documented Lassa fever in travelers coming back to the United States.

International statistics

Arenaviridae is categorized into two groups, New World and Old World arenaviruses. These viruses are generally spread by rodents. New World arenaviruses, including Guanarito (Venezuelan HF), Junin (Argentine HF), Machupo (Bolivian HF), and Sabia (Brazilian HF), 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 and resulted in two documented outbreaks in 2003 and 2019. [12]  The Old World arenaviruses include Lassa virus, the cause of Lassa fever, which is endemic in parts of West Africa (Nigeria, Sierra Leone, Guinea, Liberia, and Mali) [13] and Lujo virus, the cause of Lujo hemorrhagic fever (LUHF), which was identified in a nosocomial cluster of 5 patients in South Africa in 2008. [14] 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. Lassa fever is estimated to be the cause of up to 10-15% of annual hospitalizations in certain regions in West Africa.

Viruses belonging to the family Bunyaviridae can spread by arthropods or rodents and cause Crimean-Congo HF (CCHF), Rift Valley fever (RVF), and hantavirus infections (eg, hemorrhagic fever with renal syndrome [HFRS]). CCHF is caused by Nairovirus and has the widest geographic distribution of the tickborne infections. CCHF is seen throughout Africa, [15] the Middle East, the Balkans, [16, 17, 18] southern Russia, and western China [19, 20] and is increasingly reported in Europe, [21, 22, 23] and Turkey, as well. [24] RVF outbreaks have been reported throughout sub-Saharan Africa, Egypt, Saudi Arabia, and Yemen. In early 2019, 129 confirmed human RVF cases and 109 animal foci were reported in an epizootic that occurred in the French Mayotte Island in Africa. [25] The virus can be transmitted to humans through contact with blood, body fluids, or tissues of infected domestic livestock, or through mosquito bites (mostly the Aedes and Culex mosquitos). [26] HFRS is caused by hantaviruses (Hantaan, Seoul, Dobrava, and Puumala viruses). HFRS is found throughout the world and widely seen in Europe and Asia. In the United States and Canada, an outbreak of Seoul virus infection was reported in 2017 and potentially transmitted through infected pet rats. [27]

Filoviridae (Ebola, Marburg viruses) are found in Africa. Fruit bats are probable reservoirs. The virus spreads to humans through direct contact with bat excreta or saliva. Nonhuman primates, particularly chimpanzees and gorillas, may contract filoviruses from contact with bats and act as intermediate hosts that spread the viruses to people by coming into touch with their blood and bodily fluids. Human-to-human transmission can occur. [28] Outbreaks of Ebola in Congo, [29] Guinea, [30] and Uganda [31, 32, 33] have been recently identified, as have outbreaks of Marburg in Uganda, Ghana, and Guinea. [34]

Flaviviridae include Alkhurma HF virus, Kyasanur Forest disease (KFD) virus, [35] and Omsk HF virus. 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. [36, 2, 37] Recent reports describe the infection in travelers returning from Egypt, suggesting that the geographic range of the virus may be increasing. [3, 38] 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.

Race-, sex-, and age-related demographics

No racial predilection has been reported.

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

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



Individuals who survive and do not experience specific sequelae typically return to their premorbid state.


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.

For the other viral hemorrhagic fevers, rates of infection and mortality are as follows:

  • The South American HFs have a case-infection ratio of more than 50% of those exposed and 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 approaches 50%

  • CCHF has an infection rate of 20-100% and a fatality rate of 15-30%.

  • Fatal outcome is seen in 1-15% of HFRS cases.


Hearing deficits have been reported in up to one third of patients with severe Lassa fever.

Uveitis, orchitis, transverse myelitis, and recurrent hepatitis are late complications of Ebola and Marburg infections.

Acute liver failure, multiorgan failure, and cerebral edema may complicate Marburg infection. [39]

Infection with RVF may lead to blindness in as many as 20% of patients.

CCHF may be complicated by cardiac involvement [40]  or pleural effusions and ascites. [41]

Nosocomial transmission of CCHF with fatal outcome has been reported. [42]