Hemorrhagic Fevers and Diseases

█ BRIAN D. HOYLE

Hemorrhagic diseases are caused by infection with viruses or bacteria. As the name implies, a hallmark of a hemorrhagic disease is copious bleeding. The onset of a hemorrhagic fever or disease can lead to relatively mild symptoms that clear up within a short time. However, hemorrhagic diseases are most recognized because of the ferocity and lethality of their symptoms as well as the speed at which they render a person extremely ill.

High rates of infection, easy transmission, and high levels of morbidity (illness) and mortality (death) mean that some hemorrhagic viruses hold the potential for use as biological weapons. Viruses including, but not limited, Ebola, Marburg, Lassa fever, and New World arenaviruses, offer characteristics desirable in potential bioweapon agents.

Four groups of hemorrhagic viruses. The viruses that cause hemorrhagic diseases are members of four groups. These are the arenaviruses, filoviruses, bunyaviruses, and the flaviviruses. Arenaviruses are the cause of Argentine hemorrhagic fever, Bolivian hemorrhagic fever, Sabiaassociated hemorrhagic fever, Lassa fever, Lymphocytic choriomeningitis, and Venezuelan hemorrhagic fever. The bunyavirus group causes Crimean-Congo hemorrhagic fever, Rift Valley fever, and Hantavirus pulmonary syndrome. Filoviruses are the cause of Ebola hemorrhagic fever and Marburg hemorrhagic fever. Lastly, the flaviviruses cause tick-borne encephalitis, yellow fever, Dengue hemorrhagic fever, Kyasanur Forest disease, and Omsk hemorrhagic fever.

Virtually all the hemorrhagic diseases of microbiological origin that arise with any frequency are caused by viruses. The various viral diseases are also known as viral hemorrhagic fevers. Bacterial infections that lead to hemorrhagic fever are rare. One example is a bacterium known as scrub typhus.

None of the known viral hemorrhagic diseases are indigenous to the United States (i.e., none occur naturally). Accordingly, a primary risk factor of viral hemorrhagic diseases includes travel to areas where the virus is indigenous (e.g., portions of Africa, Asia, the Middle East, and South America).

Work with these viruses must only be conducted in high containment (BSL-4) laboratories. There are two such labs in the U.S.; one is located at the Centers for Disease Control and Prevention (CDC), and the other at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). All personnel at these laboratories must wear protective clothing (e.g., double-gloves, biohazard suits, shoe coverings, face shields, respirators, etc.) and often work in negative pressure rooms.

Although Ribavirin, an antiviral medication, has shown some effectiveness against arenaviridae and bunyaviridae viruses, there are currently no antiviral medications effective against filoviridae and flaviviridae viruses. A vaccine exists for only yellow fever. Insect vectors are controlled by a concerted campaign of spraying and observance of precautionary measures (e.g., use of insect repellent, proper clothing, insect netting over sleeping areas, etc.).

Molecular biology and modes of transmission. While the viruses in the groups display differences in structure and severity of the symptoms they can cause, there are some features that are shared by all the viruses. For instance, all the hemorrhagic viruses contain ribonucleic acid as their genetic material. The nucleic acid is contained within a so-called envelope that is typically made of lipids. Additionally, all the viruses require a host in which to live. The animal or insect that serves as the host is also called the natural reservoir of the particular virus. This natural reservoir does not include humans. Infection of humans occurs only incidentally upon contact with the natural reservoir.

Symptoms of hemorrhagic diseases can progress from mild to catastrophic in only hours. As a result, an outbreak of hemorrhagic disease tends to be self-limiting in a short time. In some cases, this is because the high death rate of those who are infected literally leaves the virus with no host to infect. Often the outbreak fades away as quickly as it appeared.

Hemorrhagic-fever-related illnesses appear in a geographical area where the natural reservoir and humans are both present. If the contact between the two species is close enough, then the disease-causing microorganism may be able to pass from the species that is the natural reservoir to the human.

Although little is clear about the state of the microbes in their natural hosts, it is reasonably clear now that the viruses do not damage these hosts as much as they do a human who acquires the microorganisms. Clarifying the reasons for the resistance of the natural host to the infections would be helpful 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.

The transmission of hemorrhagic viruses from the animal reservoir to humans makes the viruses the quintessential zoonotic disease. For some of the viruses, the host has been determined. Hosts include the cotton rat, deer mouse, house mouse, arthropod ticks, and mosqitoes. However, for other viruses, such as the Ebola and Marburg viruses, the natural host still remains undetermined. Outbreaks with the Ebola and Marburg viruses have involved transfer of the virus to humans via primates. Whether the primate is the natural host or acquired the virus as the result of contact with the true natural host is not clear.

Another fairly common feature of hemorrhagic diseases is that once humans are infected with the agent of the disease, human-to-human transmission can occur. Often this transmission is via body fluids that accidentally contact a person who is offering care to the afflicted person.

Hemorrhagic diseases typically begin with a fever, a feeling of tiredness, and aching muscles. These symptoms may not progress further, and recovery may occur within a short time. However, damage that is more serious often is characterized by copious bleeding, especially from orifices such as the mouth, eyes, and ears. More seriously, internal bleeding also occurs as organs are attacked by the infection. Death can result, though usually not from direct loss of blood, but from nervous system failure, coma, or seizures.

█ FURTHER READING:

BOOKS:

Andreoli, Thomas E., et al. Cecil Essentials of Medicine. Philadelphia: W. B. Saunders, 1993.

Cormican, M. G., and M. A. Pfaller. "Molecular Pathology of Infectious Diseases," in Clinical Diagnosis and Management by Laboratory Methods. 20th ed. Philadelphia: W. B. Saunders, 2001.

PERIODICALS:

Dutton, Gail. "Biotechnology Counters Bioterrorism." Genetic Engineering News no. 21 (December 2000): 1–22ff.

Peters, C. J., and J. W. LeDuc. "An Introduction to Ebola: The Virus and the Disease." The Journal of Infectious Diseases no. 179 (Supplement 1, February 1999): ix–xvi.

ELECTRONIC:

Centers for Disease Control. "Ebola Hemorrhagic Fever." 2001. < http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola.htm > (March 12, 2003).

Centers for Disease Control. "Viral Hemorrhagic Fevers." 2000. < http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/vhf.htm > (March 12, 2003).

Centers for Disease Control. "Yellow Fever: Disease and Vaccine." 2001. < http://www.cdc.gov/ncidod/dvbid/yellowfever/index.htm > (March 12, 2003).

SEE ALSO

Biological Warfare
Biological Weapons, Genetic Identification
Bioshield Project
Bioterrorism
Bioterrorism, Protective Measures
CDC (United States Centers for Disease Control and Prevention)
Chemical and Biological Detection Technologies