Viral Hemorrhagic Fevers
Description
Viral hemorrhagic fevers are a group of febrile illnesses
caused by several distinct families of viruses, all of which are
enveloped and have RNA genomes. These groups include Ebola and Marburg
viruses; Lassa fever virus, and the New World arenaviruses (Guaranito,
Machupo, Junin, Sabia); and Rift Valley fever and Crimean Congo hemorrhagic
fever viruses. Although some types cause relatively mild illnesses,
many of these viruses can cause severe, life-threatening disease.
Severe illness is characterized by vascular damage and increased
permeability, multiorgan failure, and shock. (See also Dengue,
and Yellow
Fever.)
Ebola and Marburg:
Filoviral Diseases
Ebola and Marburg are
filoviruses that belong to the family Filoviridae and can cause severe
hemorrhagic fever in humans and nonhuman primates. Four species of
Ebola virus have been identified: Côte d'Ivoire, Sudan, Zaire,
and Reston. Ebola-Reston infection is fatal in monkeys but does not
cause severe disease in humans. Confirmed cases of Ebola hemorrhagic
fever have been reported in the Congo, Côte d'Ivoire, Democratic
Republic of Congo, Gabon, Sudan, and Uganda. Occupational infection
of a laboratory worker resulting from a needle-stick injury has been
documented in England. Marburg virus also is indigenous to Africa.
Although the precise geographic range for Marburg virus is unknown,
it includes at least parts of Uganda and western Kenya, Democratic
Republic of Congo, and possibly Zimbabwe. The reservoir host(s) for
Ebola and Marburg viruses are not known. Outbreaks can occur when
an index case-patient that has been exposed to that unknown reservoir
species returns to a community. Within that community, the outbreak
often becomes amplified in the health-care setting.
Lassa Fever: Arenaviral
Diseases
Lassa fever is a severe,
often fatal, hemorrhagic fever that is caused by a virus transmitted
from asymptomatically infected rodents to humans.The virus, a member
of the virus family Arenaviridae, is a single-stranded RNA virus.
Arenaviruses are transmitted by animal hosts and can be divided into
two groups: the New World or Tacaribe complex and the Old World or
lymphocytic choriomeningitis virus (LCMV)/Lassa complex, including
Flexal virus. Viruses causing human illness are Lassa virus, Lassa
fever; Junin virus, Argentine hemorrhagic fever; Machupo virus, Bolivian
hemorrhagic fever; Guanarito virus, Venezuelan hemorrhagic fever;
Sabia virus, Brazilian hemorrhagic fever; LCMV, meningitis, encephalitis,
meningoencephalitis; and Flexal virus, an influenzalike illness that
has been reported among laboratory personnel handling rodents in
Brazil.
Each virus is associated
with one or more closely related rodent species that constitute its
natural reservoir. Tacaribe complex viruses are generally associated
with the New World rats and mice (family Muridae, subfamily Sigmodontinae).
The LCM/Lassa complex viruses are associated with the Old World rats
and mice (family Muridae, subfamily Murinae). Taken together, these
types of rodents are located across most of the earth's landmass,
including Europe, Asia, Africa, and the Americas. An exception is
Tacaribe virus, found in Trinidad, which was isolated from bats.
Lassa fever is limited
to rural areas of West Africa, with areas of hyperendemicity in eastern
Sierra Leone, Guinea, Liberia, and Nigeria. Peridomestic exposure
to infected rodents is the most likely source of human infection.
Transmission of arenaviruses to humans can occur via inhalation of
primary aerosols from rodent urine, by ingestion of contaminated
food, or by direct contact of broken skin with rodent excreta. Rodent
infestation and inappropriate food storage increase the risk of human
infection. Person-to-person spread of Lassa and Machupo viruses has
also been described, most notably by contact transmission in the
hospital setting. Despite one anecdotal report of possible airborne
transmission, this is not believed to be an important route of infection
from person to person. Laboratory handling of infectious specimens
and contact with contaminated medical equipment are also associated
with transmission.
Rift Valley Fever
and Related Bunyaviral Diseases
Rift Valley fever (RVF)
is caused by a member of the Bunyaviridae family; it affects primarily
livestock and may also infect humans. It is transmitted by several
means, including the bites of mosquitoes, percutaneous inoculation,
or inhalation of aerosols from contaminated blood or fluids of infected
animals. Other diseases caused by viruses of the family Bunyaviridae
include hantavirus pulmonary syndrome (HPS), hemorrhagic fever with
renal syndrome (HFRS), and Crimean-Congo hemorrhagic fever. Both
HPS and HFRS are transmitted to humans through contact with urine,
feces, or saliva of infected rodents. Crimean-Congo virus is transmitted
to humans by infected ticks or direct contact with fresh carcasses
or blood of infected animals, usually domestic livestock. Nosocomial
transmission of Crimean-Congo virus has also been reported.
RVF virus is endemic to
sub-Saharan Africa, where sporadic outbreaks occur in humans, for
example, in the Nile Delta, Egypt (1978 and 1993), and the lower
Senegal River basin of Mauritania (1987). A large epidemic also occurred
in Kenya and Tanzania during 1997–1998. A recent outbreak (2000)
of RVF occurred in southwestern Saudi Arabia and Yemen with a strain
of RVF closely related to that of the 1997–1998 East African
strain. This outbreak represented the first spread of the virus outside
Africa, demonstrating its potential for spread to unaffected regions
elsewhere in the tropics. Crimean-Congo hemorrhagic fever (CCHF)
is endemic where ticks of the genus Hyalomma are found, including
Africa, the Balkans, the Middle East, and western China. Recent cases
of CCHF have been confirmed in Oman (1995), United Arab Emirates
(1979 and 1994), and Saudi Arabia (1990) and antibody to CCHF has
been reported in Kuwait. The viruses that cause HPS are present in
the New World; whereas those that cause HFRS
occur worldwide.
Occurrence
Taken together, the viruses that cause VHF are distributed
over much of the globe. Each virus is associated with one or more
nonhuman host or vector species, restricting the virus and the disease
it causes to the areas inhabited by these species. Viruses causing
hemorrhagic fever are initially transmitted to humans when the habitats
of infected reservoir hosts or vectors and humans overlap. Risk of
VHF is associated with human incursion into such areas. In general,
these are enzootic diseases for which humans are incidental, “dead-end” hosts.
Risk for Travelers
The risk for international travelers is generally
considered to be low. The viruses carried in rodent reservoirs are
transmitted when humans have contact with urine, fecal matter, saliva,
or other excreta of infected rodents. The viruses associated with
arthropod vectors are usually spread when the vector mosquito or
tick bites a human or when a human crushes an infected tick. Some
of these vectors may spread the virus to animals, including livestock.
Humans may become infected through contact with infected animals
(e.g., during birthing, veterinary care, or slaughter).
During recorded outbreaks of hemorrhagic fever caused
by filovirus infections (e.g., Ebola), persons who cared for (fed,
washed, or medicated) or worked very closely with infected persons
were at highest risk for infection. Health care-associated transmission
through contact with infectious body fluids has been an important
factor in the spread of this disease.
Several cases of Lassa fever have been confirmed
in international travelers. These travelers were staying or living
in traditional dwellings in the countryside or in small villages;
no risk has been associated with travelers who stay in hotels. Travel
involving patient contact or rodent exposure is associated with increased
risk. Medical personnel, researchers, and relief workers involved
in the management of patients or working in disease-endemic areas
should be aware of their risk and should minimize rodent exposure
and use personal protective equipment to prevent health care-associated
exposure.
Travelers exposed to the blood or tissues of sick
animals, or to infected mosquitoes in RVF-endemic areas are at risk
for infection. Among travelers to Bunyavirus-endemic regions, those
staying in rodent-infested dwellings may be at increased risk for
HPS and HFRS.
Prevention
Prevention efforts should concentrate on avoiding
contact with host or vector species. Investigational vaccines have
been developed for Argentine hemorrhagic fever and Rift Valley fever
but have not been approved by the FDA. For the other viruses that
cause VHF, no vaccine is available. If prevention methods fail and
a traveler becomes ill with VHF, efforts should focus on preventing
further transmission from person to person, e.g., through occupational
injury among health-care personnel, by re-use of injection needles
or syringes, or splashes of infectious body fluids reaching unprotected
mucous membranes.
Travelers should not visit locations where an outbreak
is occurring. Contact with rodents should be avoided, particularly
in Lassa or Bunyavirus-endemic areas. Where RVF is endemic, travelers
should avoid direct contact with livestock and minimize their exposure
to arthropod bites by using permethrin-impregnated bed nets and insect
repellents.
Strict compliance with infection control precautions
(i.e., use of disposable gloves, face shields, and disposable gowns
to prevent direct contact with body fluids and splashes to mucous
membranes when caring for patients or handling clinical specimens;
and appropriate use and disposal of sharp instruments) is recommended
to avoid health care-associated infections.
Direct contact with the remains of anyone suspected
of having died of Ebola or Marburg infection should be avoided. Remains
should be buried promptly by trained, specially organized teams using
appropriate safety equipment.
Treatment
Patients should receive supportive care, including
balancing fluids and electrolytes, maintaining oxygenation status
and blood pressure, and preventing or providing treatment for any
secondary infections. In general, no specific treatments or established
cures have proven benefit for patients with VHF. Ribavirin, an antiviral
drug, has been effective in treating some patients with Lassa fever,
New World arenaviruses, and Crimean-Congo hemorrhagic fever; however,
it is not FDA licensed for these indications. Treatment with convalescent-phase
plasma has been used with success in some patients with Argentine
hemorrhagic fever. In addition, studies have suggested that interferon,
immune modulators, or convalescent-phase plasma may be of benefit
to patients with Rift Valley fever; however, these treatments are
not currently available.
— Michael
Bell, Abbigail Tumpey
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