Viral hemorrhagic fever

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

The viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses that are caused by five distinct families of RNA viruses: the Arenaviridae, Filoviridae, Bunyaviridae, Togaviridae, and Flaviviridae. All types of VHF are characterized by fever and bleeding disorders and all can progress to high fever, shock and death in extreme cases. Some of the VHF agents cause relatively mild illnesses, such as the Scandinavian nephropathia epidemica, whilst others, such as the African Ebola virus, can cause severe, life-threatening disease.

In conjunction with the World Health Organization, CDC has developed practical, hospital-based guidelines, titled Infection Control for Viral Haemorrhagic Fevers In the African Health Care Setting. The manual can help health-care facilities recognize cases and prevent further hospital-based disease transmission using locally available materials and few financial resources.

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.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

• Mékambo in Gabon is the site of several outbreaks of Ebola hemorrhagic fever.
• Orientale, Congo villages of Durba and Watsa were the epicenter of the 1998–2000 outbreak of Marburg hemorrhagic fever.
• Uige Province in Angola is the site of world’s worst hemorrhagic fever epidemic, which occurred in 2005.
• The ongoing VHF outbreak in the village of Mweka, Democratic Republic of the Congo (DRC) that started in August, 2007, and that has killed 103 people (100 adults and three children), has been shown to be caused (at least partially) by the Ebola virus.
• Some experts believe that the Black Death of the Middle Ages may have been caused by a VHF and not by the bubonic plague.^[1]

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

The diversity of clinical features seen among the VHF infections probably originates from varying mechanisms of pathogenesis. An immunopathogenic mechanism, for example, has been identified for dengue hemorrhagic fever, which usually occurs among patients previously infected with a heterologous dengue serotype. An influential theory explaining this phenomenon is called “antibody-dependent enhancement.” In contrast, disseminated intravascular coagulation (DIC) is thought to underlie the hemorrhagic features of Rift Valley, Marburg and Ebola fevers. In most VHFs, however, the etiology of the coagulopathy is most likely multifactorial (e.g., hepatic damage, consumptive coagulopathy, primary marrow dysfunction, etc).

The reasons for variation among patients infected with the same virus are unknown but stem from a complex system of virus-host interactions. Moreover, why some infected persons develop full-blown VHF while others do not also remains an unresolved issue. Virulence of the infecting agent clearly plays an important role. The “VHF syndrome” (capillary leak, bleeding diathesis and hemodynamic compromise leading to shock) occurs in a majority of patients manifesting disease from filoviruses, CCHF and the South American hemorrhagic fever viruses, while it occurs in a small minority of patients with dengue, RVF and Lassa fever.

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.

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.

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.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

• The Arenaviridae include the viruses responsible for Lassa fever and Argentine, Bolivian, and Venezuelan hemorrhagic fevers.
• The Bunyaviridae include the members of the Hantavirus genus that cause hemorrhagic fever with renal syndrome (HFRS), the Crimean-Congo hemorrhagic fever (CCHF) virus from the Nairovirus genus, and the Rift Valley fever (RVF) virus from the Phlebovirus genus.
• The Filoviridae include Ebola and Marburg viruses.
• Finally, the Flaviviridae include dengue, yellow fever, and two viruses in the tick-borne encephalitis group that cause VHF: Omsk hemorrhagic fever virus and Kyasanur Forest disease virus.

Template:WH Template:WS

Please help WikiDoc by adding more content here. It’s easy! Click here to learn about editing.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Viral hemorrhagic fever has to be differentiated from other viral fevers like:

• Crimean-Congo hemorrhagic fever (CCHF)
• Ebola hemorrhagic fever
• Hantavirus Pulmonary Syndrome
• Hemorrhagic fever with renal syndrome (HFRS)
• Lassa Fever
• Marburg hemorrhagic fever

Template:WH

Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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 arena viruses, 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.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

VHF should be suspected in febrile persons who, within 3 weeks before onset of fever, have either

1) traveled in the specific local area of a country where VHF has recently occurred;

2) had direct unprotected contact with blood, other body fluids, secretions, or excretions of a person or animal with VHF; or

3) had a possible exposure when working in a laboratory that handles hemorrhagic fever viruses.

The likelihood of acquiring VHF is considered low in persons who do not meet any of these criteria. Even following travel to areas where VHF has occurred, persons with fever are more likely to have infectious diseases other than VHF (e.g., common respiratory viruses, endemic infections such as malaria or typhoid fever). Clinicians should promptly evaluate and treat patients for these more common infections while awaiting confirmation of a VHF diagnosis.

In Africa, transmission of VHF in healthcare settings has been associated with reuse of contaminated needles and syringes and with provision of patient care without appropriate barrier precautions to prevent exposure to virus-containing blood and other body fluids (including vomitus, urine, and stool). The transmission risks associated with various body fluids have not been well defined because most caregivers who have acquired infection had contacts with multiple fluids.

The risk for person-to-person transmission of hemorrhagic fever viruses is greatest during the latter stages of illness when virus loads are highest; latter stages of illness are characterized by vomiting, diarrhea, shock, and, in less than half of infected patients, hemorrhage. No VHF infection has been reported in persons whose contact with an infected person occurred only during the incubation period (i.e., before onset of fever). The incubation period for VHF ranges from 2 days to 3 weeks, depending on the viral agent. There are reports of Ebola virus transmission occurring within a few days after onset of fever; however, the presence of other symptoms in the source patients and the level of exposure to body fluids among secondary cases are unknown in these instances (CDC, unpublished data, 1995). In studies involving three monkeys experimentally infected with Ebola virus (Reston strain), fever and other systemic signs of illness preceded detection of infectious virus in the animals’ pharynx by 2-4 days, in the conjunctiva and on anal swabs by 5-6 days, and in the nares by 5-10 days.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

• Coma
• Death
• Disseminated intravascular coagulation (DIC)
• Kidney failure
• Liver failure
• Parotitis
• Secondary bacterial infections
• Shock

Template:WH Template:WS