Hemorrhagic Fevers

Definition

Hemorrhagic fevers 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, a prominent symptom is bleeding, or hemorrhaging, from orifices and internal organs.

Description

Although hemorrhagic fevers are regarded as emerging diseases, they probably have existed for many years. This designation isn't meant to imply that they are newly developing, but rather that human exposure to the causative viruses is increasing to the point of concern.

These viruses are maintained in nature in arthropod (insects, spiders and other invertebrates with external hard skeletons) or animal populations—so-called disease reservoirs. Individuals within these populations become infected with a virus but do not die from it. In many cases, they don't even develop symptoms. Then the viruses are 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, affects approximately 100 million people annually. A large percentage of those infected live in densely populated southeast Asia; an area in which the disease vector, a mosquito, thrives. Some hemorrhagic fevers are exceedingly rare, because people very infrequently encounter the virus. Marburg hemorrhagic fever, which has affected fewer than 40 people since its discovery in 1967, provides one such example. Fatality rates are also variable. In cases of dengue hemorrhagic fever-dengue shock syndrome, 1-5% of the victims perish. 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 by the potential for hemorrhaging. However, not all cases progress to this very serious symptom. 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 pin-point hemorrhages under the skin surface, to distinct bleeding from such body orifices as the nose or vagina.

Causes and symptoms

The viruses that cause hemorrhagic fevers are found most commonly in tropical locations; however, some are found in cooler climates. Typical disease vectors include rodents, ticks, or mosquitoes, but person-to-person transmission in health care settings or through sexual contact can also occur.

Filoviruses

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 last three to 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 and throat, and vagina. Other bleeding symptoms include petechiae and oozing from injection sites. Ebola is fatal in 30-90% of cases.

Arenaviruses

Viruses of the Arenaviridae family cause the Argentinian, 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.

Flaviviruses

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 the Caribbean, Saudi Arabia, and northern Australia. In 2004 several cases were reported along the border between Texas and Mexico in the southwestern United States. 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.

Bunyaviruses

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; while 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 three to 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.

Hemorrhagic fever with renal (kidney) syndrome is caused by the hantaviruses: Hantaan, Seoul, Puumala, and Dobrava. Hantaan virus occurs in northern Asia, the Far East, and the Balkans; Seoul virus is found worldwide; Puumala virus is found in Scandinavia and northern Europe; while Dobrava virus occurs in the Balkans. 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 range from 0-10%.

Diagnosis

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.

Treatment

Lassa fever, and possibly other hemorrhagic fevers, respond to ribavirin, an antiviral medication. However, most of the hemorrhagic fever viruses can only be treated with supportive care. Interferon is not useful and may in fact complicate management. Such care centers around maintaining correct fluid and electrolyte balances in the body and protecting the patient against secondary infections. Heparin and vitamin K administration, coagulation factor replacement, and blood transfusions may be effective in lessening or stopping hemorrhage in some cases.

Some researchers are investigating 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.

Prognosis

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%, while DHF-DSS cases result in a 1-5% fatality rate. Whether a case occurs during an epidemic or as an isolated case 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 is usually inevitable. However, survivors seem to gain lifelong immunity against the virus that made them ill.

Prevention

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.

KEY TERMS

Antibody— A molecule created by the body's immune system to combat a specific infectious agent, such as a virus or bacteria.

Antigen— A specific feature, such as a protein, on an infectious agent. Antibodies use this feature as a means of identifying infectious intruders.

Coagulating factors— Components within the blood that help form clots.

Endemic— Referring to a specific geographic area in which a disease may occur.

Hemorrhage— As a noun, this refers to the point at which blood is released. As a verb, this refers to bleeding.

Incubation— The time period between exposure to an infectious agent, such as a virus or bacteria, and the appearance of symptoms of illness.

Petechiae— Pinpoint hemorrhages that appear as reddish dots beneath the surface of the skin.

Reservoir— A population in which a virus is maintained without causing serious illness to the infected individuals.

Ribavirin— A drug that is used to combat viral infections.

Tissue factor— A glycoprotein involved in blood coagulation.

Vector— A member of the reservoir population or an intervening species that can transmit a virus to a susceptible victim. Mosquitoes are common vectors, as are ticks and rodents.

Vaccines have been developed against yellow fever, Argentinian hemorrhagic fever, and Crimean-Congo hemorrhagic fever. Vaccines against other hemorrhagic fevers are being 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 has 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 as well as having a high mortality rate.

Resources

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Viral Diseases." Section 13, Chapter 162 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

PERIODICALS

Izadi, S., K. H. Naieni, S. R. Madjdzadeh, and A. Nadim. "Crimean-Congo Hemorrhagic Fever in Sistan and Baluchestan Province of Iran, A Case-Control Study on Epidemiological Characteristics." International Journal of Infectious Diseases 8 (September 2004): 299-306.

Mahanty, S., and M. Bray. "Pathogenesis of Filoviral Haemorrhagic Fevers." Lancet Infectious Diseases 4 (August 2004): 487-498.

Ruf, W. "Emerging Roles of Tissue Factor in Viral Hemorrhagic Fever." Trends in Immunology 25 (September 2004): 461-464.

Salvaggio, M. R., and J. W. Baddley. "Other Viral Bioweapons: Ebola and Marburg Hemorrhagic Fever." Dermatologic Clinics 22 (July 2004): 291-302.

Setlick, R. F., D. Ouellette, J. Morgan, et al. "Pulmonary Hemorrhage Syndrome Associated with an Autochthonous Case of Dengue Hemorrhagic Fever." Southern Medical Journal 97 (July 2004): 688-691.

Warfield, K. L., J. G. Perkins, D. L. Swenson, et al. "Role of Natural Killer Cells in Innate Protection against Lethal Ebola Virus Infection." Journal of Experimental Medicine 200 (July 19, 2004): 169-179.

ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 639-3311. 〈http://www.cdc.gov〉.

Infectious Diseases Society of America (IDSA). 66 Canal Center Plaza, Suite 600, Alexandria, VA 22314. (703) 299-0200. Fax: (703) 299-0204. 〈http://www.idsociety.org〉.

World Health Organization (WHO). 〈http://www.who.int/en/〉.

OTHER

Centers for Disease Control and Prevention, Special Pathogens Branch. "Ebola Hemorrhagic Fever," August 23, 2004. 〈http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola.htm〉.

Centers for Disease Control and Prevention, Special Pathogens Branch. "Marburg Hemorrhagic Fever," August 23, 2004. 〈http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/marburg.htm〉.

Hemorrhagic Fevers

Introduction

Disease History, Characteristics, and Transmission

Scope and Distribution

Treatment and Prevention

Impacts and Issues

BIBLIOGRAPHY

Introduction

Hemorrhagic diseases are caused by infection with certain viruses and, rarely, bacteria. Hemorrhage is severe and uncontrolled bleeding. As implied by their name, a central feature of hemorrhagic fevers is this uncontrolled bleeding, which is caused by the destruction of cells inside the body as the virus makes new copies of itself.

Hemorrhagic fevers are terrifying to those affected, to those attempting to care for the sick, and to those who read about or watch images of an outbreak. Hemorrhagic infections cause symptoms that appear and progress swiftly. Because outbreaks of hemorrhagic fevers appear and sweep through a population very rapidly before disappearing, very little is known of the details of the various viral infections.

Disease History, Characteristics, and Transmission

Hemorrhagic diseases are mainly caused by viruses. They are also known collectively as viral hemorrhagic fevers. Bacterial hemorrhagic infections are rare, but one example of such a disease is scrub typhus.

Viral hemorrhagic fevers are caused by viruses in four groups—arenaviruses, filoviruses, bunyaviruses, and the flaviviruses. Arenaviruses are a family of RNA viruses (their genetic material is not composed of DNA, only RNA) that are associated with human diseases transmitted by rodents. They cause a number of hemorrhagic fevers, including Lassa fever (caused by the Lassa virus), Argentine hemorrhagic fever (caused by the Junin virus), Bolivian hemorrhagic fever (caused by the Machupo virus), Venezuelan hemorrhagic fever (caused by the Guananto virus), and Brazilian hemorrhagic fever (caused by Sabia).

The first arenavirus was isolated in 1933 during an investigation into an outbreak of St. Louis encephalitis. The virus was found not to be the cause of the outbreak, but the severity of its health threat was revealed. The limited studies that have been done in the intervening decades (studies are limited because of the great danger in working with the viruses) have shown that arenaviruses are typically transmitted to humans via animals such as rodents. These viruses are characterized as zoonotic, which means that they reside in another host (a wild or domesticated animal) but are capable of causing disease when transmitted to humans.

Bunyaviruses are a family of RNA viruses that are associated with rodent- or insect-borne diseases in humans. Viruses in this family are known to cause Crimean-Congo hemorrhagic fever, Rift Valley fever, and Hantavirus pulmonary syndrome. Congo-Crimean fever, a disease known for many years in eastern Europe and central Asia, is caused by a virus that is transmitted to humans and a variety of domestic and wild animals by ticks. Humans can become infected when they come into close contact with infected cattle, and slaughterhouses have been involved in disease outbreaks. Rift Valley fever is generally found in areas of eastern and southern Africa where cattle and sheep are raised. The virus responsible for the disease primarily affects livestock, but humans can also contract the disease when they are bitten by mosquitoes infected with the virus or when they come into contract with the blood or body parts of infected animals. Hantavirus disease is transmitted to humans mainly through the inhalation of aerosolized virus particles from dried mouse feces. Investigation of a disease outbreak that occurred in the United States in 1993 determined that a virus called the Sin Nombre virus (a type of hantavirus) was a cause. Another virus called that Hantaan virus causes Hantavirus pulmonary syndrome. This virus was isolated during an investigation of a disease outbreak that occurred in the 1950s near the Hantan River in Korea.

Filoviruses cause severe hemorrhagic diseases in humans and other primates, including Ebola hemorrhagic fever and Marburg hemorrhagic fever. Flaviviruses cause a wide range of human diseases, including tick-borne encephalitis, yellow fever, Dengue hemorrhagic fever, Kyasanur Forest disease, and Omsk hemorrhagic fever. Depending on the virus, the disease may be transmitted to humans via rodents, ticks, and mosquitoes. In some cases, such as Ebola, the host is still not known. Bats are a suspected natural reservoir of the virus that causes Ebola, but the virus has yet to be isolated from these animals.

The various viral hemorrhagic viruses differ in structure. For example, arenaviruses are spherical, while filoviruses, such as the Marburg virus, can be U-shaped, O-shaped, or even shaped like the number 6. Although these hemorrhagic viruses differ, they do share some common features. For example, they all contain ribonucleic acid (RNA) as their genetic material. In addition, humans are not their normal host. While the viruses are able to live without severely affecting natural hosts, such as cattle, the infection caused in humans is severe. This is the primary reason that human outbreaks of hemorrhagic fever disappear so rapidly. The high death rate makes it impossible for the virus to persist in a human population for very long once an outbreak has been recognized and treatment measures, such as isolation of those who are infected, is initiated.

Most hemorrhagic viruses share another feature in common. Once a human is infected he or she can then transfer the virus to other people (person-to-person transmission), often via contaminated body fluids. Caregivers can become infected in this way. This transmission can occur in a hospital or clinic, and such hospital acquired infections are called nosocomial infections.

While the various viral hemorrhagic fevers have their own distinct symptoms, they do share some symptoms and a pattern of symptoms over time. The diseases typically begin a sudden fever, a general feeling of fatigue, myalgia, dizziness, pain and stiffness in the neck and back, diarrhea, and severe headache (which can be so bad that a person becomes nauseated and vomits, and becomes very sensitive to light). Some people do recover, and recovery can be as rapid as the onset of the disease. However, others deteriorate further, and begin to hemorrhage from the mouth, eyes, and ears. This bleeding is only the external manifestation of the massive bleeding that is occurring inside the body, as various organs become infected. In the final stages of a hemorrhagic fever, organs fail and the nervous system breaks down, leading to coma, seizures, and death.

Scope and Distribution

The filoviruses that cause Marburg hemorrhagic fever and Ebola are found in various regions of the Africa continent. Three of the four known species of Ebola are named for the regions in which they were first discovered—Ivory Coast, Sudan, and Zaire.

WORDS TO KNOW

BIOSAFETY LEVEL FOUR LABORATORY: A specially equipped, secured laboratory where scientists study the most dangerous known microbes. These labs are designed to contain infectious agents and disease-causing microbes, prevent their dissemination, and protect researchers from exposure.

HEMORRHAGE: Very severe, massive bleeding which is difficult to control.

MYALGIA: Muscular aches and pain.

ZOONOSES: Zoonoses are diseases of microbiological origin that can be transmitted from animals to people. The causes of the diseases can be bacteria, viruses, parasites, and fungi.

The occurrence of viral hemorrhagic fevers in areas as widely separated as Korea, Arizona, and Africa highlight the global distribution of the virus that cause hemorrhagic fevers. A particular virus may be more localized; for example, the viruses that cause Ebola appear to be localized to a few regions in Africa. However, because so little is still known about viral hemorrhagic fevers, it is possible that the true distribution of the various viruses is not yet known.

Treatment and Prevention

Hemorrhagic diseases are difficult to treat because outbreaks occur quickly, often in remote regions of the world. The speed and ferocity of the infection often means that patients are near death by the time they are seen by a health care provider. Vaccines are available only for yellow fever and Argentine hemorrhagic fever. For the remaining hemorrhagic fevers, the best prevention is to avoid contact with animals that are known to be hosts of the particular virus. However, in many cases, a population has little knowledge of the infections and their exposure risks, making prevention virtually impossible. One exception is hantavirus pulmonary syndrome in the United States. This disease has been well publicized and many people are aware that it is spread by rodents. When insects are involved in the transmission of a virus, spraying programs that kill insect populations, especially during their breeding season, can be helpful.

When combating an outbreak, isolating infected patients from other patients can help reduce the spread of the disease. In addition, all protective clothing and soiled material used in patient treatment should be stored in a secure container until it can be destroyed (usually by incineration).

Impacts and Issues

While relatively little is known about viral hemorrhagic fevers, they may have a serious impact on life in the areas of the world where they occur. For example, it is estimated that 100,000–300,000 Lassa fever infections occur annually in regions of West Africa where that virus is most prevalent, and about 5,000 of those infected die of the disease. But, since the rodent species that carries the virus is found much more widely, the actual range of Lassa fever may be much greater. In regions where the virus is found, about 15% of people admitted to hospital have Lassa fever; many more people never make it to a hospital, so the actual impact of the disease is difficult to determine.

As of 2007, much less is known about hemorrhagic fevers than remains to be discovered. One reason for this lack of knowledge is that the infections are very difficult to study during an outbreak. Health care providers faced with an outbreak struggle to mount a quick and efficient response that can save lives. Sometimes, cultural norms and taboos in remote regions hinder efforts to contain outbreaks and study their cause. For instance, during the 2005 Ebola outbreak in the Cuvette Ouest region of the Republic of Congo, medical workers from United Nations aid agencies arrived at the scene wearing white protective biohazard suits and were met with skepticism and hostility, as the color white is associated with evil in the remote village where the outbreak first occurred.

Viral hemorrhagic fevers can only be studied in a few specialized laboratories known as biosafety level four (BSL-4) laboratories. These laboratories are designed with safety and containment features that make it safe for researchers to work with the viruses and that prevent escape of the viruses outside of the lab. In BSL-4 laboratories, hemorrhagic fevers are studied in a high-containment environment, where incoming and outgoing airflow is controlled and where researchers wear protective clothing that includes one-piece positive pressure suits with separate ventilation systems. Protocols for studying the viruses that cause hemorrhagic fevers include restricted access to the laboratory, working under Class III biological safety cabinets, and decontamination following work with the virus. Currently, there are about 30 BSL-4 laboratories in the world, 10 of which are in the United States.

IN CONTEXT: SCIENTIFIC QUESTIONS

Ebola virus and Marburg virus are the two known members of the filovirus family that cause hemorrhagic fevers. Ebola viruses were first isolated from humans during concurrent outbreaks of VHF in northern Zaire and southern Sudan in 1976. An earlier outbreak of VHF caused by Marburg virus occurred in Marburg, Germany, in 1967 when laboratory workers were exposed to infected tissue from monkeys imported from Uganda. Two subtypes of Ebola virus—Ebola-Sudan and Ebola-Zaire—previously have been associated with disease in humans. In 1994, a single case of infection from a newly described Ebola virus occurred in a person in Cote d'Ivoire. In 1989, an outbreak among monkeys imported into the United States from the Philippines was caused by another Ebola virus but was not associated with human disease.

Initial clinical manifestations of Ebola hemorrhagic fever include fever, headache, chills, myalgia (muscle aches throughout the body), and malaise; subsequent manifestations include severe abdominal pain, vomiting, and diarrhea. In reported outbreaks, fifty percent to ninety percent of cases have been fatal.

The natural reservoirs for these viruses are not known. Although nonhuman primates were involved in the 1967 Marburg outbreak, the 1989 U.S. outbreak, and the 1994 Côte d'Ivoire case, their role as virus reservoirs is unknown. Transmission of the virus to secondary cases occurs through close personal contact with infectious blood or other body fluids or tissue. In previous outbreaks, secondary cases occurred among persons who provided medical care for patients; secondary cases also occurred among patients exposed to reused needles. Although aerosol spread has not been documented among humans, this mode of transmission has been demonstrated among nonhuman primates. Based on this information, the high fatality rate, and lack of specific treatment or a vaccine, work with this virus in the laboratory setting requires biosafety level four containment.

See AlsoEbola; Marburg Hemorrhagic Fever.

BIBLIOGRAPHY

Books

Drexler, Madeline. Secret Agents: The Menace of Emerging Infections. New York: Penguin, 2003.

Powell, Michael, and Oliver Fischer. 101 Diseases You Don't Want to Get. New York: Thunder's Mouth Press, 2005.

Zimmerman, Barry E., and David J. Zimmerman. Killer Germs. New York: McGraw-Hill, 2002.

Brian Hoyle

HEMORRHAGIC FEVERS

DEFINITION

Hemorrhagic fevers (pronounced heh-meh-RA-jik) are a group of diseases caused by viruses. They occur throughout the world, but are most common in tropical areas. Early symptoms include muscle aches and fevers. The disease can progress to a more serious condition and, in many cases, can be fatal. A prominent symptom in late stages is hemorrhaging (rapid or heavy bleeding) from body openings and internal organs.

DESCRIPTION

Hemorrhagic fevers are a growing concern throughout the world. They are not new diseases, but they are affecting much larger numbers of people every year.

The viruses that cause hemorrhagic fevers live in a great variety of animals, such as arthropods and mammals. Arthropods are insects, spiders, and other animals with hard external skeletons. These animals are called the natural reservoir for the disease. In many cases, these animals do not become ill when infected by the viruses. They do, however, carry the viruses in their body.

Viruses are transferred from these animals to humans by vectors. A vector is an organism that carries a disease from one animal to another. Mosquitoes are common vectors. When they bite an animal, they suck in some of its blood. If the animal is infected with a virus, the blood also contains that virus. When the vector bites a human, it leaves some of its saliva in the wound. Some of the virus may also be left behind. The human becomes infected with the virus.

Hemorrhagic fevers are often endemic. An endemic disease is one that affects many people in a given area over long periods of time. Dengue fever (pronounced DEN-gay) is an example. It affects about 100 million people annually. Most of these people live in southeast Asia. The area is very crowded. People often live in close contact with each other. The disease is transmitted easily from one person to another. In addition, the mosquito that carries dengue fever thrives in southeast Asia.

Hemorrhagic Fevers: Words to Know

Disease reservoir:

A population of animals in which a virus lives without causing serious illness among the animals.

Endemic:

The widespread occurrence of a disease over a given area that lasts for an extended period of time.

Hemorrhage:

Heavy or uncontrollable bleeding.

Ribavirin:

A drug used to treat viral infections.

Vector:

An animal that transmits an infectious agent, such as a virus, from one animal to another animal.

Some hemorrhagic fevers are very rare. An example is Marburg hemorrhagic fever. It was first discovered in 1967. In the next thirty years after that, fewer than forty people were diagnosed with the disease.

The rate of fatalities (deaths) varies among the different forms of hemorrhagic fever. In the case of dengue fever, the death rate is about 1 to 5 percent. At the other extreme, ebola (pronounced ee-BO-la), an African hemorrhagic fever, kills 50 to 90 percent of those infected.

The onset (beginning) of hemorrhagic fevers may be sudden or gradual. They all have one characteristic in common, however. They all have the potential to result in hemorrhaging. The seriousness of the hemorrhaging also varies. In some cases, it involves no more than tiny pinpoints of bleeding under the skin. In other cases, the patient may bleed extensively from the mouth, nose, and other body openings.

CAUSES AND SYMPTOMS

Many different kinds of hemorrhagic fevers are known. The viruses that cause these diseases are usually found in tropical locations, but some are also found in cooler climates. Typical disease vectors include rodents (mice and rats), ticks, and mosquitoes. The virus can also be passed from person to person through sexual contact or other means.

Filoviruses

Ebola (pronounced ee-BO-la) is the most famous of the filoviruses (pronounced fi-lo-VI-russ-ez). It is endemic to Africa, especially to the Republic of the Congo and to Sudan. Scientists have not discovered the natural reservoir for the filoviruses.

Symptoms of a filovirus infection appear suddenly. They include severe headache, fever, chills, muscle aches, and loss of appetite. These symptoms may be accompanied by nausea, vomiting, diarrhea, and abdominal pain. A person with the infection may become listless and disoriented. Severe bleeding occurs from the stomach and intestines, nose, throat, and vagina. Ebola is fatal in 50 to 90 percent of all cases.

Arenaviruses

Arenavirus (pronounced uh-RE-nuh-virus) infections occur most often in parts of South America and west Africa. In west Africa they cause a disease known as lassa fever. The disease is spread by rodents. The virus is transmitted when humans come in contact with the urine and saliva of rats and mice. Symptoms differ somewhat between South American and west African forms of the disease.

The first symptoms of South American arenavirus infection are fever, muscle ache, weakness, and loss of appetite. Later, patients experience dizziness, headache, back pain, and upset stomach. The face and chest become red, and the gums begin to bleed. In about 30 percent of all cases, hemorrhaging occurs. Bleeding occurs under the skin and in the mucous membranes, the moist tissues that line body openings. In late stages, the nervous system is affected. A person experiences delirium and convulsions and may go into a coma. About 10 to 30 percent of patients die of the disease.

The symptoms of lassa fever are somewhat similar to those of South American infections, but the death rate is usually much lower, about 2 percent.

Flaviviruses

The two best known diseases caused by flaviviruses (pronounced fla-vih-VI-russ-ez) are yellow fever and dengue fever.

Yellow fever occurs in tropical areas of the Americas and Africa. It is transmitted from monkeys to humans by mosquitoes. Some people experience only a mild form of the disease. They may not even realize that they

have been infected. In more serious cases, a patient experiences fever, weakness, low back pain, muscle pain, nausea, and vomiting. After about a week, these symptoms nearly disappear. Then they come back stronger than before. They develop into delirium (a form of madness), seizures, numbness, and coma. Bleeding occurs under the skin and in the mucous membranes. Blood also appears in stools and vomit.

Bunyaviruses

Bunyaviruses (pronounced BUN-yuh-vi-russ-ez) cause a number of hemorrhagic fevers, including Rift Valley fever and Crimean-Congo hemorrhagic fever. Rift Valley fever occurs in southern Africa and the Nile delta. The disease is transferred from wild and domestic animals to humans by

bites of infected animals or through mosquito bites. The death rate is less than 3 percent.

Crimean-Congo hemorrhagic fever is found throughout much of Africa, Asia, and the Middle East. It is found in rabbits, birds, ticks, and domestic animals. Humans contract the disease after being bitten by an infected animal or by infected ticks. Death rates range from 10 to 50 percent. The symptoms of both Rift Valley and Crimean-Congo fevers are similar to those of other hemorrhagic fevers.

DIAGNOSIS

The symptoms of hemorrhagic fevers are similar to those of other diseases. Diagnosis depends on blood tests that show the presence of the virus.

TREATMENT

There are few drugs for the treatment of viral infections. Ribavirin (pronounced RI-buh-vih-rin) is one such drug. It is sometimes used to treat lassa fever and other hemorrhagic fevers. Treatment of these diseases is generally aimed at making patients more comfortable. Patients are often given fluids to replace those lost by vomiting and diarrhea. They may be given antibiotics to protect against other infections. Vitamin K is sometimes given to help stop bleeding. Blood transfusions may also be used to restore blood lost during hemorrhaging.

In many parts of the world, patients with hemorrhagic fevers receive no treatment at all. There are not enough medical or financial resources to treat everyone with the disease. People are left to recover or die on their own.

PROGNOSIS

The prognosis for various forms of hemorrhagic fever vary widely. The death rate for ebola can be as high as 90 percent. For some forms of dengue fever, it can be as low as 1 percent.

Some types of hemorrhagic fever can cause permanent disability. For example, about 10 percent of those who develop Rift Valley fever will suffer eye damage. They may become permanently blind. About 25 percent of patients with South American hemorrhagic fever become permanently deaf.

Proper treatment is very important. It can reduce the death rate dramatically. In some forms of dengue fever, lack of treatment results in a death rate of 40 to 50 percent. With adequate treatment, the death rate drops to less than 2 percent.

PREVENTION

The best way to prevent hemorrhagic fevers is to eliminate the vectors that carry the diseases. For example, efforts have been made to wipe out mosquito or rodent populations in some areas. These efforts are sometimes successful in big cities in developed nations. They are less successful in large rural areas in developing nations. In these cases, the best hope may be personal protection. People should use mosquito netting, insect repellents, and other devices to protect themselves against vectors.

Vaccines have also been developed against some hemorrhagic fevers, including yellow fever, Argentinean hemorrhagic fever, and Crimean-Congo fever. People who plan to travel in areas where these diseases occur should

be vaccinated against them. The vaccines are costly, however, and many local populations cannot afford them.

FOR MORE INFORMATION

Books

Garrett, Laurie. The Coming Plague: Newly Emerging Diseases in a World Out of Balance. New York: Farrar, Strauss, and Giroux, 1994.

Henig, Robin Marantz. A Dancing Matrix: How Science Confronts Emerging Viruses. New York: Vintage Books, 1994.

Regis, Edward. Virus Ground Zero: Stalking the Killer Viruses With the Centers for Disease Control. New York: Pocket Books, 1996.

Ryan, Frank. Virus X: Tracking the New Killer Plagues Out of the Present and into the Future. Boston: Little Brown & Company, 1997.

Periodicals

LeGuenno, Bernard, "Emerging Viruses," Scientific American (October 1995): pp. 56+.

Web sites

Outbreak (An on-line information service about emerging diseases) http://www.outbreak.org (accessed October 25, 1999).

National Center for Infectious Diseases. Viral Hemorrhagic Fever. http://www.cdc.gov/ncidod/diseases/virlfvr/virlfvr.htm (accessed October 25, 1999).