Hemorrhagic fevers, sometimes called viral hemorrhagic fevers or VHFs, are caused by viruses that exist throughout the world. However, they are most common in tropical areas. Early symptoms, such as muscle aches and fever, can progress to a mild illness or to a more debilitating, potentially fatal disease. In severe cases, the vascular system is compromised. A prominent symptom is bleeding, or hemorrhaging, from orifices and internal organs.
Although hemorrhagic fevers are regarded as emerging diseases, they probably have existed for many years. This designation is not meant to imply that they are newly developing, but rather that human exposure to the causative viruses is increasing to the point of concern.
Hemorrhagic viruses are maintained in nature in arthropod (insects, spiders, and other invertebrates with external hard skeletons) or in certain rodent populations, which serve as disease reservoirs. Individuals within these populations become infected with a virus but do not die from it. In many cases, they do not even develop symptoms. The viruses are then transmitted from a reservoir population to humans by vectors, either members of the reservoir population or an intervening species, such as mosquitoes.
Hemorrhagic fevers are generally either endemic or linked to specific locations. If many people reside in an endemic area, the number of cases may soar. For example, dengue fever, a type of hemorrhagic fever, is found in 122 countries and as of 2012 affected between 50 and 100 million people annually. A large percentage of those infected live in densely populated Southeast Asia, an area in which the disease vector, the mosquito, thrives. Some hemorrhagic fevers are exceedingly rare because people infrequently encounter the virus. Marburg hemorrhagic fever, which has affected fewer than 100 people since its discovery in 1967, provides one such example. Fatality rates are also variable. In cases of dengue hemorrhagic fever, fewer than 1% of treated individuals and 2%–5% of untreated individuals die. On the other end of the spectrum is Ebola, an African hemorrhagic fever, that kills 30%–90% of those infected.
The onset of hemorrhagic fevers may be sudden or gradual, but all of them are linked to damage to the blood vessels and the potential for hemorrhaging. However, not all cases progress to serious bleeding. Hemorrhaging may be attributable to the destruction of blood coagulating factors or to increased permeability of body tissues. The severity of bleeding ranges from petechiae, which are pinpoint hemorrhages under the skin surface, to distinct bleeding from such body orifices as the nose or vagina.
The viruses that cause hemorrhagic fevers are found most commonly in tropical locations; however, a few are found in cooler climates. Typical disease vectors include rodents, ticks, and mosquitoes, but person-to-person transmission in healthcare settings or through sexual contact can also occur.
Ebola is the most famous of the Filoviridae, a virus family that also includes the Marburg virus. Ebola is endemic to Africa, particularly the Republic of the Congo and Sudan; the Marburg virus is found in sub-Saharan Africa. The natural reservoir of filoviruses is unknown. The incubation period, or time between infection and appearance of symptoms, is thought to be between three and eight days, possibly longer.
Symptoms appear suddenly and include severe headache, fever, chills, muscle aches, malaise, and appetite loss. These symptoms may be accompanied by nausea, vomiting, diarrhea, and abdominal pain. Victims become apathetic and disoriented. Severe bleeding commonly occurs from the gastrointestinal tract, nose, throat, and vagina. Other bleeding symptoms include petechiae and oozing from injection sites.
Viruses of the Arenaviridae family cause Argentinean, Brazilian, Bolivian, and Venezuelan hemorrhagic fevers. Lassa fever, which occurs in west Africa, also arises from an arenavirus. Infected rodents, the natural reservoir, shed virus particles in their urine and saliva, which humans may inhale or otherwise come in contact with.
Fever, muscle aches, malaise, and appetite loss gradually appear one to two weeks after infection with the South American viruses. Initial symptoms are followed by headache, back pain, dizziness, and gastrointestinal upset. The face and chest appear flushed and the gums begin to bleed. In about 30% of cases, the disease progresses to bleeding under the skin and from the mucous membranes and/or to effects on the nervous system, such as delirium, coma, and convulsions. Untreated, South American hemorrhagic fevers have a 10%–30% fatality rate.
Lassa fever also begins gradually, following an 8–14-day incubation. Initial symptoms resemble those of the South American hemorrhagic fevers, followed by a sore throat, muscle and joint pain, severe headache, pain above the stomach, and a dry cough. The face and neck become swollen, and fluid may accumulate in the lungs. Bleeding occurs in 15%–20% of infected individuals, mostly from the gums and nose. Overall, the fatality rate is lower than 2%, but hospitals may encounter 20% fatality rates, treating typically the most serious of cases.
The Flaviviridae family includes the viruses that cause yellow and dengue fevers. Yellow fever occurs in tropical areas of the Americas and Africa and is transmitted from monkeys to humans by mosquitoes. The virus may produce a mild, possibly unnoticed illness, but some individuals are suddenly stricken with a fever, weakness, low back pain, muscle pain, nausea, and vomiting. This phase lasts one to seven days, after which the symptoms recede for one to two days. Symptoms then return with greater intensity, along with jaundice, delirium, seizures, stupor, and coma. Bleeding occurs from the mucous membranes and under the skin surface, and dark blood appears in stools and vomit.
Mosquitoes also transmit the dengue virus. Dengue fever is endemic in Southeast Asia and areas of the Americas. Cases have also been reported in southern Florida, the Caribbean, Saudi Arabia, and northern Australia. In 2001–2002, an outbreak of dengue fever occurred in Hawaii, and in 2004 several cases were reported along the border between Texas and Mexico in the southwestern United States. Mosquitoes that can transmit dengue fever are also found in the U.S. Gulf Coast states. Dengue fever was common in this area before mosquito abatement programs were instituted. This virus causes either the mild dengue fever or the more serious dengue hemorrhagic fever–dengue shock syndrome (DHF-DSS).
In children, dengue fever is characterized by a sore throat, runny nose, slight cough, and a fever lasting for a week or less. Older children and adults experience more severe symptoms: fever, headache, muscle and joint pain, loss of appetite, and a rash. The skin appears flushed, and intense pain occurs in the bones and limbs. After nearly a week, the fever subsides for one to two days before returning. Minor hemorrhaging, such as from the gums or more serious gastrointestinal bleeding may occur.
DHF-DSS primarily affects children younger than 15 years. The symptoms initially resemble those of dengue fever in adults, without the bone and limb pain. As the fever begins to abate, the individual's condition worsens and hemorrhaging occurs from the nose, gums, and injection sites. Bleeding is also seen from the gastrointestinal, genitourinary, and respiratory tracts.
The Bunyaviridae family includes several hundred viruses, but only a few are responsible for hemorrhagic fevers in humans.
Rift Valley fever is caused by the phlebovirus, found in sub-Saharan Africa and the Nile Delta. Natural reservoirs are wild and domestic animals, and transmission occurs through contact with infected animals or through mosquito bites. The incubation period lasts 3–12 days. Most cases of Rift Valley fever are mild and may be symptomless. If symptoms develop, they include fever, backache, muscle and joint pain, and headache. Hemorrhagic symptoms occur rarely, whereas death, which occurs in fewer than 3% of cases, is attributable to massive liver damage.
Crimean-Congo hemorrhagic fever is caused by nairovirus and occurs in central and southern Africa, Asia, Eurasia, and the Middle East. The virus is found in hares, birds, ticks, and domestic animals and may be transmitted by ticks or by contact with infected animals. The nairovirus incubation period is 3–12 days, after which an individual experiences fever, chills, headache, severe muscle pain, pain above the stomach, nausea, vomiting, and appetite loss. Bleeding under the skin and gastrointestinal and vaginal bleeding may develop in the most severe cases. Death rates range from 10% in southern Russia to 50% in parts of Asia.
There are many hantaviruses, but only about 15 cause illness in humans. The virus was first identified in Korea in the 1950s. Hemorrhagic fever with renal (kidney) syndrome is caused by the hantaviruses: Hantaan, Seoul, Puumala, Dobrava, and sin nombre virus (SNV). Hantaan virus occurs in northern Asia, the Far East, the Balkans; Seoul virus is found worldwide; Puumala virus is found in Scandinavia and northern Europe; and Dobrava virus occurs in the Balkans. SNV is found in the United States primarily in the Southwest and California. Wild rodents are the natural reservoirs and transmit the virus via their excrement or body fluids or through direct contact. Initial symptoms develop within 10–40 days and include fever, headache, muscle pain, and dizziness. Other symptoms are blurry vision, abdominal and back pain, nausea, and vomiting. High levels of protein in the urine signal kidney damage; hemorrhaging may also occur. Death rates from hantavirus infection range up to 25%. In 2012, an outbreak of hantavirus infections occurred in people who had stayed in tent-cabins at Yosemite National Park in California. As of 2012, several people had died of the infection.
Since the hemorrhagic fevers share symptoms with many other diseases, positive identification of the disease relies on evidence of the viruses in the bloodstream such as detection of antigens and antibodies or isolation of the virus from the body. Disruptions in the normal levels of bloodstream components may be helpful in determining some, but not all, hemorrhagic fevers.
In 2006, researchers at Columbia University in New York adapted a test to detect respiratory viruses to quickly and accurately detect ten viruses that cause hemorrhagic fevers, including Marburg and Ebola.
Some researchers have investigated the possibility of targeting tissue factor (TF) as a way of treating viral hemorrhagic fevers. TF is a protein that activates the coagulation process in these illnesses, and experimental models suggest that a blockade of tissue factor assists the body's immune response to hemorrhagic fever viruses.
Recovery from some hemorrhagic fevers is more certain than from others. The filoviruses are among the most lethal; fatality rates for Ebola range from 30%–90%, whereas DHF-DSS cases result in a 1%–5% fatality rate. Whether a case occurs during an epidemic or as an isolated case and the available of medical care also has a bearing on the outcome. For example, isolated cases of yellow fever have a 5% mortality rate, but 20%–50% of epidemic cases may be fatal.
Permanent disability can occur with some types of hemorrhagic fever. About 10% of severely ill Rift Valley fever victims suffer retina damage and may be permanently blind, and 25% of South American hemorrhagic fever victims suffer potentially permanent deafness.
Proper treatment is vital. In cases of DHF-DSS, fatality can be reduced from 40%–50% to less than 2% with adequate medical care. For individuals who survive hemorrhagic fevers, prolonged convalescence usually is inevitable. However, survivors seem to gain lifelong immunity against the virus that made them ill.
Hemorrhagic fevers can be prevented through vector control and personal protection measures. Attempts have been made in urban and settled areas to destroy mosquito and rodent populations. In areas where such measures are impossible, individuals can use insect repellents, mosquito netting, and other methods to minimize exposure. Individuals who plan to travel to Africa, Asia, and other parts of the world where hemorrhagic fever viruses are common, should check the Centers for Disease Control (CDC) Travelers' health pages online for up-to-date information on outbreaks, preventive measures, and treatments.
Vaccines have been developed against yellow fever, Argentinean hemorrhagic fever, and Crimean-Congo hemorrhagic fever. Vaccines against other hemorrhagic fevers have been researched. Another possible preventive measure is increasing the number of natural killer (NK) cells in the body. These cells appear to be an important innate source of protection against Ebola and other filoviruses.
Prevention of epidemics of hemorrhagic fevers acquired a new importance in the early 2000s from concern that the causative viruses might be used as weapons of bioterrorism. These viruses can be transmitted in aerosol form, require a low dose to cause infection, and can have a high mortality rate.
See also Communicable diseases ; Ebola virus disease ; Endemic ; Viruses .
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Rebecca J. Frey, PhD
Revised by Tish Davidson, AM