Hemorrhagic fevers and diseases

Hemorrhagic diseases are caused by infection with certain viruses or bacteria . Viruses cause virtually all the hemorrhagic diseases of microbiological origin that arise with any frequency. The various viral diseases are also known as viral hemorrhagic fevers. Bacterial hemorrhagic disease does occur, but rarely. One example of a bacterial hemorrhagic disease is scrub typhus .

Copious bleeding is the hallmark of a hemorrhagic disease. The onset of a hemorrhagic fever or disease can produce mild symptoms that clear up quickly. However, most hemorrhagic diseases are infamous because of the speed that some infections take hold, and the ferocity of their symptoms. Such hemorrhagic maladies, such as Ebola, have high mortality rates.

Viral types and characteristics

Four main groups of viruses exist that cause hemorrhagic disease or fever: arenaviruses, filoviruses, bunyaviruses, and flaviviruses. Arenaviruses cause Argentine hemorrhagic fever, Bolivian hemorrhagic fever, Sabia-associated hemorrhagic fever, Lymphocytic choriomeningitis, Venezuelan hemorrhagic fever, and Lassa fever. Members of the filovirus group cause Ebola hemorrhagic fever and Marburg hemorrhagic fever. Bunyaviruses cause Crimean-Congo hemorrhagic fever, Rift Valley fever, and Hantavirus pulmonary syndrome . Lastly, Flaviviruses cause tick-borne encephalitis , yellow fever , Dengue hemorrhagic fever, Kyasanur Forest disease, and Omsk hemorrhagic fever.

These viruses differ in structure and in the severity of the symptoms they can cause. They all, however, share common features. All hemorrhagic viruses contain ribonucleic acid (RNA) as their genetic material. The RNA is protected and confined in a membrane called the viral envelope. The envelope is typically made of lipid . Another feature of hemorrhagic viruses, and indeed of all viruses, is the requirement for a host in which to live and produce new viral particles. Hemorrhagic viruses can live in some non-human mammals , such as primates , and in insects . The primates and insects are described as being natural reservoirs of the particular virus . Humans are not a natural reservoir. Epidemiologists (disease trackers) suspect that initial infections of humans occurs only accidentally when humans and the primate or insect come into close contact.

In contrast to the reservoir host, the presence of the hemorrhagic virus in humans typically produces a devastating illness. The symptoms can progress from mild to catastrophic very rapidly (i.e., in only hours). While catastrophic for the victims and difficult to treat, the rapid nature of the outbreaks has an advantage. Because victims succumb quickly, the transmission of the virus from human to human is limited. An outbreak can appear, ravage a local population, and fade away within days or a few weeks.

The viruses that cause the various hemorrhagic fevers and diseases do not survive in the host following the disease (the Human Immunodeficiency Virus, in contrast, is able be latent in the host, and survive for prolonged periods of time before symptoms of infection appear). However, people who are recovering from infections caused by Hantavirus and Argentine hemorrhagic fever can excrete infectious viruses in their urine.

The sporadic appearance of hemorrhagic outbreaks and the fact that they often occur in geographically isolated regions (e.g., interior of Africa ) has made the study of the diseases difficult. It is known that there is not any timetable to the appearance of a hemorrhagic fever, such as in one season of the year relative to another season. The only factor that is known clearly is that the viruses are passed from the natural host to humans. How this transfer occurs and why it occurs sporadically are not known.

The viruses do not damage their primate or insect hosts as much as they do a human who acquires the microorganisms . The reasons for this difference are unknown. Researchers are attempting to discover the basis of the natural resistance, as this would help in finding an effective treatment for human hemorrhagic diseases.

The speed at which hemorrhagic fevers appear and end in human populations, combined with their frequent occurrence in relatively isolated areas of the globe has made detailed study difficult. Even though some of the diseases, such as Argentine hemorrhagic fever, have been known for almost 50 years, knowledge of the molecular basis of the disease is lacking. For example, while it is apparent that some hemorrhagic viruses can be transmitted through the air as aerosols , the pathway of infection once the microorganism has been inhaled is still largely unknown.

Hemorrhagic diseases are zoonotic diseases; ones that occur by the transfer of the disease causing agent from a non-human to a human. For some of the hemorrhagic viruses, the reservoir host is known. They include the cotton rat, deer mouse , house mouse, arthropod ticks, and mosquitoes . However, for viruses such as the Ebola and Marburg viruses, the natural host still is not known. Outbreaks with these two viruses have involved transfer of the virus to human via primates. Whether the primate is the natural reservoir host, or whether primates acquire the virus as the result of contact with the true natural reservoir host, is yet another aspect of hemorrhagic diseases that is not clear.

As mentioned, hemorrhagic fevers can rapidly spread through a human population. This is due to human-to-human transmission. This transmission occurs easily, often via body fluids that accidentally contact a person who is caring for the afflicted person. Funeral practices of handling and washing the bodies of the deceased have contributed to human-to-human transmission of Ebola during outbreaks in Sub-Saharan Africa.

Hemorrhagic diseases typically begin with a fever, a feeling of tiredness, and a generalized aching of muscles. In rare instances, symptoms may not progress any further, in which case recovery is rapid. For unknown reasons, however, more serious damage often occurs. Here, symptoms include copious bleeding from the mouth, eyes, and ears. Internal bleeding also occurs, as organs are attacked and destroyed by the infection. Death is typically the result of the overwhelming damage to the organs, and from the failure of the nervous system . Often, victims have seizures and lapse into a coma prior to death.

Hemorrhagic diseases are difficult to treat. One reason is because of the rapid progression of the disease. Another reason is because vaccines exist for only a few of the diseases (i.e., yellow fever and Argentine hemorrhagic fever). For the remaining diseases, supportive care such as keeping the infected person hydrated is often the only course of action.

To prevent outbreaks, the most effective policy is to curb human interaction with the natural reservoir of the microbe. For example, in the case of hantavirus pulmonary syndrome, scientists discovered in the 1990s that the responsible virus was resident in rodent populations, and that these populations exploded in numbers after rainy periods. Thus, limiting contact with places where the rodents live (i.e., barns), particularly after a rainy period, is a wise practice. Insect vectors are controlled by a spraying and common sense steps, such as use of insect repellent, proper clothing, insect netting over sleeping areas.

Hemorrhagic fevers are significant, not only because of the human suffering they cause, but because the viral agents could be exploited as bioweapons. For these reasons, a great deal of research effort is devoted towards understanding the origins and behaviors of the viruses.

Ebola and other hemorrhagic diseases

The best-studied hemorrhagic fever is Ebola. The Ebola virus is named after a river located in the Democratic Republic of the Congo, where the virus was discovered in 1976. This outbreak occurred in the western part of the African nation of Sudan and in nearby Zaire. In 1979, another outbreak occurred in Zaire. In 1995, an outbreak that involved 316 people occurred in Kikwit, Zaire. Outbreaks have also occurred in the African regions of Gabon and the Ivory Coast.

There are four species of Ebola virus. These differ in their arrangement of their genetic material and in the severity of the infection they cause. Ebola-Zaire, Ebola-Sudan, and Ebola-Ivory Coast cause disease in humans. The fourth species, Ebola-Reston, causes disease in primates.

Ebola Reston inspired great public awareness and terror of hemorrhagic diseases. This infamous virus is named for the United States military primate research facility where the virus was isolated during a 1989 outbreak of the disease in research primates. At that time, there was fear that Ebola fever could spread to neighboring Washington, DC. Study of the cause of this outbreak determined that Ebola viruses could remain infectious after becoming dispersed in the air. Whether inhalation of the virus plays a major role in the development of the hemorrhagic fever is not clear. The current consensus is that airborne transmission is possible, but is not the principle route of infection.

Other hemorrhagic viruses can be spread by air. These include the Marburg, Lassa, Congo-Crimean, and Hantaviruses.

The Junin virus causes the hemorrhagic fever known as Argentine hemorrhagic fever. The virus was discovered in 1955, during a disease outbreak among corn harvesters in Argentina. It was later determined that the virus was spread to the workers by contact when rodent feces that had dried in the cornfields. The same route of transmission is used by the Machupo virus, which causes Bolivian hemorrhagic fever.

Congo-Crimean hemorrhagic fever is transmitted to people by ticks. The tick is likely not the natural reservoir host of the virus, but acquires the virus when it feeds on the natural reservoir host. This identity of the host is not known. This hemorrhagic fever occurs in the Crimea and in regions of Africa, Asia , and Europe .

Another hemorrhagic fever called Rift Valley fever occurs mainly in Africa. Like Ebola, it cause explosive outbreaks of disease.

Hantavirus disease was first described around the time of World War II, in Manchuria. United Nations troops stationed in Korea during the Korean War in the 1950s were sickened with the disease. A lung infection caused by the virus, which can rapidly progress to death, became prominent because of an outbreak in the southwestern region of the United States in the mid-1990s. Like some of the other hemorrhagic fevers, Hantavirus Pulmonary Syndrome is caused by inhalation of dried rodent feces.

Many of the above hemorrhagic fevers were discovered only in the past 50 to 75 years. Other hemorrhagic fevers have a longer history. For example, yellow fever was discovered in the first decade of the twentieth century, when a disease outbreak occurred among workers who were constructing the Panama Canal.

The diagnosis of hemorrhagic fevers often requires knowledge of the recent travel of the patient. This helps to clarify what natural hosts the patient may have come in contact with.

Vaccine and treatment

As of 2003, the only licensed vaccine for a hemorrhagic fever is that available for yellow fever. The vaccine consists of live virus particles that have been modified so as not to be capable of growth or of causing an infection. The virus is capable of stimulating the immune system to produce antiviral antibodies. The vaccine must be taken by those who are traveling to areas of the world where yellow fever is actively present (areas of Africa and South America ). The vaccine may have some potential in protecting people from the virus that causes Bolivian hemorrhagic fever.

Vaccines to Rift Valley fever are under development. But these are still undergoing testing and so are not publicly available. Vaccines have not been developed to the other hemorrhagic fevers. An antiviral drug called ribavirin shows potential against Lassa fever. Unfortunately, the drug has caused mutations in test animals. Thus, its use on humans carries a risk. In determining whether or not to administer ribavirin, the risk of its use is weighed against the urgency of the illness.

At the present time, the best treatments for hemorrhagic fevers are isolation of the infected patient and care when handling the patient. For example, health care workers should be dressed in protective clothing, including gloves and protective facemask. Also, any material or equipment that comes into contact with a patient should be sterilized to kill any virus that may have adhered to the items.

The devastating infection caused by the hemorrhagic viruses is remarkable given the very small amount of genetic material that the viruses contain. For example, Ebola viruses can produce less than 12 proteins . How the viruses are able to evade the host immune responses, and establish infections is unknown. The virus may commandeer the host's genetic material to produce proteins that it is unable to produce. Or, hemorrhagic viruses may be exquisitely designed infection machines, containing only the resources needed to evade the host and establish an infection. Sequencing of the genetic material of hemorrhagic viruses will help distinguish between these two possibilities.

See also Immunology; Zoonoses.

Resources

books

Specter, S.C., R.L. Hodinka, and S.A. Young. Clinical Virology, 3rd ed. Washington, DC: American Society for Microbiology Press, 2000.

Tao, H. Atlas of Hemorrhagic Fever with Renal Syndrome. Thousand Oaks, CA: Science press, 1999.

organizations

Centers for Disease Control and Prevention, Special Pathogens Branch, National Center for Infectious Diseases, MS A–26, 1600 Clifton Road, Atlanta, GA 30333. (404) 639-1510. February 8, 2002 [cited November 12, 2002] <http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/vhf.htm>.

Brian Hoyle

KEY TERMS

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Hemorrhagic

—Involving life-threatening bleeding.

Reservoir host

—The animal or organism in which the virus or parasite normally resides.

Vector

—Any agent, living or otherwise, that carries and transmits parasites and diseases.

Zoonoses

—The transmission of disease to humans from an animal.