Viral Hemorrhagic Fevers

What are viral hemorrhagic fevers?
The term viral hemorrhagic fever (VHF) refers to a group of illnesses that are caused by several distinct families of viruses. While some types of hemorrhagic fever viruses can cause relatively mild illnesses, many of these viruses cause severe, life-threatening disease.

The Special Pathogens Branch (SPB) primarily works with hemorrhagic fever viruses that are classified as biosafety level four (BSL-4) pathogens. A listing of these viruses appears in the SPB fact sheet index. The Division of Vector-Borne Infectious Diseases, also in the National Center for Infectious Diseases, works with the non-BSL-4 viruses that cause two other hemorrhagic fevers, dengue hemorrhagic fever and yellow fever.

How are hemorrhagic fever viruses grouped?
VHFs are caused by viruses of four distinct families:  arenaviruses, filoviruses, bunyaviruses, and flaviviruses. Each of these families share a number of features:

• They are all RNA viruses, and all are covered, or enveloped, in a fatty (lipid) coating.
• Their survival is dependent on an animal or insect host, called the natural reservoir.
• The viruses are geographically restricted to the areas where their host species live.
• Humans are not the natural reservoir for any of these viruses. Humans are infected when they come into contact with infected hosts. However, with some viruses, after the accidental transmission from the host, humans can transmit the virus to one another.
• Human cases or outbreaks of hemorrhagic fevers caused by these viruses occur sporadically and irregularly. The occurrence of outbreaks cannot be easily predicted.
• With a few noteworthy exceptions, there is no cure or established drug treatment for VHFs.

In rare cases, other viral and bacterial infections can cause a hemorrhagic fever; scrub typhus is a good example.

What carries viruses that cause viral hemorrhagic fevers?
Viruses associated with most VHFs are zoonotic. This means that these viruses naturally reside in an animal reservoir host or arthropod vector. They are totally dependent on their hosts for replication and overall survival. For the most part, rodents and arthropods are the main reservoirs for viruses causing VHFs. The multimammate rat, cotton rat,  deer mouse, house mouse, and other field rodents are examples of reservoir hosts. Arthropod ticks and mosquitoes serve as vectors for some of the illnesses. However, the hosts of some viruses remain unknown -- Ebola and Marburg viruses are well-known examples.

Where are cases of viral hemorrhagic fever found?
Taken together, the viruses that cause VHFs are distributed over much of the globe. However, because each virus is associated with one or more particular host species, the virus and the disease it causes are usually seen only where the host species live(s). Some hosts, such as the rodent species carrying several of the New World arenaviruses, live in geographically restricted areas. Therefore, the risk of getting VHFs caused by these viruses is restricted to those areas. Other hosts range over continents, such as the rodents that carry viruses which cause various forms of hantavirus pulmonary syndrome (HPS) in North and South America, or the different set of rodents that carry viruses which cause hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia. A few hosts are distributed nearly worldwide, such as the common rat. It can carry Seoul virus, a cause of HFRS; therefore, humans can get HFRS anywhere where the common rat is found.

While people usually become infected only in areas where the host lives, occasionally people become infected by a host that has been exported from its native habitat. For example, the first outbreaks of Marburg hemorrhagic fever, in Marburg and Frankfurt, Germany, and in Yugoslavia, occurred when laboratory workers handled imported monkeys infected with Marburg virus. Occasionally, a person becomes infected in an area where the virus occurs naturally and then travels elsewhere. If the virus is a type that can be transmitted further by person-to-person contact, the traveler could infect other people. For instance, in 1996, a medical professional treating patients with Ebola hemorrhagic fever (Ebola HF) in Gabon unknowingly became infected. When he later traveled to South Africa and was treated for Ebola HF in a hospital, the virus was transmitted to a nurse. She became ill and died. Because more and more people travel each year, outbreaks of these diseases are becoming an increasing threat in places where they rarely, if ever, have been seen before.

How are hemorrhagic fever viruses transmitted?
Viruses causing hemorrhagic fever are initially transmitted to humans when the activities of infected reservoir hosts or vectors and humans overlap. The viruses carried in rodent reservoirs are transmitted when humans have contact with urine, fecal matter, saliva, or other body excretions from infected rodents. The viruses associated with arthropod vectors are spread most often when the vector mosquito or tick bites a human, or when a human crushes a tick. However, some of these vectors may spread virus to animals, livestock, for example. Humans then become infected when they care for or slaughter the animals.

Some viruses that cause hemorrhagic fever can spread from one person to another, once an initial person has become infected. Ebola, Marburg, Lassa and Crimean-Congo hemorrhagic fever viruses are examples. This type of secondary transmission of the virus can occur directly, through close contact with infected people or their body fluids. It can also occur indirectly, through contact with objects contaminated with infected body fluids. For example, contaminated syringes and needles have played an important role in spreading infection in outbreaks of Ebola hemorrhagic fever and Lassa fever.

What are the symptoms of viral hemorrhagic fever illnesses?
Specific signs and symptoms vary by the type of VHF, but initial signs and symptoms often include marked fever, fatigue, dizziness, muscle aches, loss of strength, and exhaustion. Patients with severe cases of VHF often show signs of bleeding under the skin, in internal organs, or from body orifices like the mouth, eyes, or ears. However, although they may bleed from many sites around the body, patients rarely die because of blood loss. Severely ill patients cases may also show shock, nervous system malfunction, coma, delirium, and seizures. Some types of VHF are associated with renal (kidney) failure.

How are patients with viral hemorrhagic fever treated?
Patients receive supportive therapy, but generally speaking, there is no other treatment or established cure for VHFs. Ribavirin, an anti-viral drug, has been effective in treating some individuals with Lassa fever or HFRS. Treatment with convalescent-phase plasma has been used with success in some patients with Argentine hemorrhagic fever.

How can cases of viral hemorrhagic fever be prevented and controlled?
With the exception of yellow fever and Argentine hemorrhagic fever, for which vaccines have been developed, no vaccines exist that can protect against these diseases. Therefore, prevention efforts must concentrate on avoiding contact with host species. If prevention methods fail and a case of VHF does occur, efforts should focus on prh-care facilities recognize cases and prevent further hospital-based disease transmission using locally available materials and few financial resources.

What needs to be done to address the threat of viral hemorrhagic fevers?
Scientists and researchers are challenged with developing containment, treatment, and vaccine strategies for these diseases. Another goal is to develop immunologic and molecular tools for more rapid disease diagnosis, and to study how the viruses are transmitted and exactly how the disease affects the body (pathogenesis). A third goal is to understand the ecology of these viruses and their hosts in order to offer preventive public health advice for avoiding infection.

Special Pathogens Branch
Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases
Centers for Disease Control and Prevention
Public Health Service, U.S. Department of Health and Human Services