Hemorrhagic Fevers

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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.