The term viral hemorrhagic fever (VHF) refers to the illness
with a number of geographically restricted viruses. This illness is
characterized by fever and, in the most severe cases, shock and
(1). Although a number of other febrile viral infections may
hemorrhage, only the agents of Lassa, Marburg, Ebola, and
hemorrhagic fevers are known to have caused significant outbreaks
disease with person-to-person transmission. Therefore, the
recommendations specifically address these four agents.
The increasing volume of international travel, including visits
rural areas of the tropical world, provides opportunity for the
of these infections into countries with no endemic VHF, such As the
States. Since most physicians have little or no experience with
viruses, uncertainty often arises when VHF is a diagnostic
Lassa, Marburg, and Ebola viruses are restricted to sub-Saharan
the differential diagnosis of VHF will most often be made for
travelers to this region. Since 1976, no imported cases of VHF have
confirmed in the United States, but every year there are
to 10 suspected cases.
These guidelines review the clinical and epidemiologic features
these diseases; provide recommendations on diagnosis,
care of patients; and suggest measures to prevent secondary
This document updates earlier recommendations, issued in 1983 (2),
management of suspected and confirmed cases of VHF. Accumulated
shows that transmission of these viruses does not occur through
contact; thus, some earlier recommendations for preventing
transmission have been relaxed. Similarly, therapy recommendations
taken into account recent knowledge of the effects of antiviral
Further information on investigating and managing patients with
suspected VHF, collecting and shipping diagnostic specimens, and
instituting control measures is available on request from the
persons at CDC in Atlanta, Georgia. For all telephone numbers, dial
Epidemic Intelligence Service (EIS) Officer, Special
Branch, Division of Viral Diseases, Center for Infectious
Chief, Special Pathogens Branch, Division of Viral
for Infectious Diseases: Joseph B. McCormick, M.D. (ext.
Senior Medical Officer, Special Pathogens Branch, Division
Diseases, Center for Infectious Diseases: Susan P.
M.D. (ext. 3308).
Director, Division of Viral Diseases, Center for Infectious
Diseases (ext. 3574).
After regular office hours and on weekends, the persons
may be contacted through the CDC duty officer (ext. 2888).
Lassa virus, named after a small town in northeastern Nigeria,
enveloped, single-stranded, bisegmented ribonucleic acid (RNA)
classified in the family Arenaviridae. Its natural host is the
rat Mastomys natalensis. This ubiquitous African rodent lives in
association with humans and is commonly found in and around houses
areas. The rats are infected throughout life and shed high levels
in their urine. Although the rodent reservoir exists across wide
Africa, Lassa virus appears to be restricted to the continent's
part. Closely related viruses are found in other areas, but their
for causing human disease is poorly understood.
Lassa fever was first recognized in 1969 in northern Nigeria
two of three nurses infected in a rural hospital died. Two persons
in a U.S. laboratory with material from the original outbreak
became infected, one fatally. One person had worked with animals
with live virus, but it is uncertain how the other person acquired
infection (4,5). Naturally occurring infections, often associated
subsequent nosocomial outbreaks, have been recognized in Nigeria,
Leone, and Liberia (6). On the basis of historical information, as
serologic testing, sporadic Lassa infection may have occurred also
Guinea, Senegal, Mali, and the Central African Republic (6,7). In
10 instances, Lassa fever has been imported into countries outside
Africa (3,8-15). In the United States, the last imported case
1976 (15). No secondary transmission from these imported infections
been documented, despite intensive surveillance of many potentially
Under natural circumstances, infection with Lassa virus occurs
contact with M. natalensis or its excreta, probably within the
Subsequent person-to-person transmission occurs, although it is
to distinguish epidemiologically between these two modes of
(17,18). Person-to-person spread requires close personal contact or
with blood or excreta. Careful follow-up of household and other
contacts of cases imported into western Europe and North America
shown any evidence of secondary transmission from casual contact.
reports of Lassa fever stressed the high infectivity of the
the risks of nosocomial transmission. Recent evidence shows that
direct contact with infected tissue, blood, secretions, and
even in poorly equipped rural African hospitals, virtually
risk of infection (19,20).
In areas where it is endemic, Lassa fever occurs more
frequently in the
dry than in the rainy season. The clinical spectrum of disease is
the ratio of illness to infection is 9%-26% (18). After an
period of 1-3 weeks, illness begins insidiously, with early
fever, sore throat, weakness, and malaise (21). Pains in the joints
lower back, headache, and nonproductive cough commonly follow.
or epigastric pain, vomiting, diarrhea, and abdominal discomfort
common. Frequent physical signs include fever, exudative
conjunctival injection. Jaundice and skin rash are rare. Diffuse
be heard by auscultating the chest, and pleural and pericardial
rubs may sometimes be detected. Edema of the face and neck,
hemorrhages, mucosal bleeding, central cyanosis, encephalopathy,
characterize the most severe cases. Some patients experience adult
respiratory distress syndrome.
After the first week of illness, the patient begins to recover
milder cases, but starts to deteriorate clinically in more serious
The mortality rate for patients hospitalized with Lassa fever is
(21), despite higher earlier estimates. The prognosis is
for women in the third trimester of pregnancy, and a high rate of
wastage occurs. Overall, the case-fatality rate is about 1%-2%
Various degrees of permanent, sensorineural deafness result in
Specific diagnosis of Lassa fever can be made in three ways: by
isolating the virus from blood, urine, or throat washings; by
the presence of immunoglobulin M (IgM) antibody to Lassa virus; or
showing a fourfold rise in titer of IgG antibody between acute- and
convalescent-phase serum specimens. Antibodies are measured with
indirect fluorescent antibody technique (IFA), which remains the
method of choice. Nonspecific laboratory abnormalities include
uria and elevated liver, enzymes, with aspartate aminotransferase
levels exceeding those of alanine aminotransferase (ALT).
Adverse prognostic factors are AST elevation above 150
units/liter, and high levels of viremia during hospitalization
Treatment is supportive and may require all the modern
facilities, including renal dialysis and mechanical ventilation. It
essential to pay attention to fluid and electrolyte balance,
blood pressure and circulatory volume, and control of seizures.
A controlled clinical trial has shown an increased survival
Lassa fever patients treated with ribavirin (22). All patients with
disease should now receive this drug. Side effects are largely
to reversible hemolysis. Severely ill patients should receive
parenterally. Lassa fever convalescent plasma has not been shown to
beneficial (22) and currently cannot be recommended, particularly
potential for transmitting other viruses such as human
virus, hepatitis B virus, and the agent(s) of non-A, non-B
Prevention of Lassa virus infection requires an understanding
disease and its modes of transmission. Persons who intend to work
with endemic disease should be briefed about Lassa fever (20).
no vaccine is available for use in humans.
EBOLA HEMORRHAGIC FEVER
Ebola virus is a single-stranded, unsegmented, enveloped RNA
a characteristic filamentous structure. Classification of the virus
new family Filoviridae has been accepted. The virus is named after
river in northwest Zaire. It is morphologically similar to, but
ically distinct from Marburg virus. The reservoir of the virus in
Ebola hemorrhagic fever was first recognized in 1976. Two
occurred within a short time of each other, the first in southern
(24) and the second in northwest Zaire (25). The index case in the
epidemic occurred in a worker in a cotton factory, who subsequently
source of hospital transmission. The mortality rate among the 284
recognized cases was 53%. In the Zaire outbreak, which from the
centered around a hospital, 88% of the 318 affected persons died.
close contact with a case and receiving injections at the hospital
strong risk factors for acquiring infection.
Two cases were identified elsewhere in northwest Zaire in 1977
1978. Retrospectively, another case was diagnosed in a physician in
same area, who cut himself while performing an autopsy in 1972 and
contracted an Ebola-like illness 12 days later (26).
In 1979 another small outbreak occurred in the same area as the
outbreak in Sudan. The index case involved a worker in the same
factory (27). The case-fatality rate was 65%. Evidence from
studies suggested that Ebola virus may be endemic in certain areas
and Zaire, as well as in other parts of East and Central Africa
The mode of acquiring natural infection with Ebola virus is
Secondary person-to-person transmission results from close personal
contact, which, in the epidemics described above, frequently
nursing of sick patients. Nosocomial transmission depends on
blood, secretions, and excretions. Transmission of infection has
documented in the case of a laboratory worker who experienced a
not suggest that spread occurred through casual contact or by
The incubation period ranges from 2 to 21 days; the average is
approximately 1 week. In the cases resulting from a needle stick
the incubation period was 6 days; however, this may not
natural illness. The illness-to-infection ratio for Ebola virus is
but seroepidemiologic investigations suggest that mild or
infections can occur.
The onset of illness is abrupt, and initial symptoms resemble
an influenza-like syndrome. Fever, headache, general malaise,
joint pain, and sore throat are commonly followed by diarrhea and
pain. A transient morbilliform skin rash, which subsequently
often appears at the end of the first week of illness. Other
findings include pharyngitis, which is frequently exudative, and
occasionally conjunctivitis, jaundice, and edema. After the third
illness, hemorrhagic manifestations are common and include
well as frank bleeding, which can arise from any part of the
gastrointestinal tract and from multiple other sites.
Specific diagnosis requires isolating the virus from blood or
demonstrating IgM or rising IgG antibodies by IFA. Proteinuria
early, and elevation of liver enzymes, AST more than ALT, is
Experimental infections in primates have shown that neutrophilia,
phopenia, and thrombocytopenia occur early in the illness (30).
Treatment is supportive and may require intensive care. Limited
information exists on the efficacy of antiviral drugs or immune
prevent or ameliorate Ebola hemorrhagic fever. Ribavirin shows no
activity. Since the Zaire and the Sudan strains of the virus are
(31), if immune plasma is considered for therapeutic use, it must
specific. The dangers of transmitting other viral infections
should be remembered. No vaccine exists against Ebola virus.
MARBURG HEMORRHAGIC FEVER
Marburg virus is a single-stranded, unsegmented, enveloped RNA
that is morphologically identical to, but antigenically distinct
virus. Classification of the virus in the new family Filoviridae
accepted. Marburg virus is named after the town in Germany where
the first cases were described (32). Its reservoir in nature
In 1967, 25 people in Europe became ill after handling material
infected African green monkeys, Cercopithecus aethiops, imported
Uganda (32). The case-fatality rate was 23% for the primary cases,
deaths were reported for the six secondary cases.
An Australian traveler died of Marburg virus disease in South
1975, after apparently acquiring his infection in Zimbabwe (33).
persons with secondary cases -- a female companion and a nurse of
patient -- survived. The third recognized outbreak of Marburg virus
occurred in Kenya in 1980 (34). A French engineer contracted the
in western Kenya, and a physician in a Nairobi hospital became
while trying to resuscitate the engineer from a terminal bout of
temesis. The physician survived. Despite extensive contact with
before his illness was diagnosed, the infected physician did not
disease further. Another case of Marburg virus disease occurred in
Africa in 1982, with no secondary cases identified (35). The most
case of Marburg virus disease occurred in Kenya in 1987; it
involved a boy
visiting a park in the western part of the country near where the
had acquired the infection in 1980. The boy died, but no secondary
The mode of acquiring natural infection with Marburg virus is
Secondary spread results from close contact with infected persons
contact with blood or body secretions or excretions. In the
epidemic (32), the only persons primarily infected had direct
animal blood or tissues, without taking precautions to prevent
Sexual transmission apparently occurred in one instance in Germany
and virus has been isolated from seminal fluid up to 2 months after
(34). Marburg virus was also isolated from the anterior chamber of
in a patient who developed uveitis 2 months after the acute illness
Although the geographic distribution of Marburg virus is
Central and East Africa should be considered endemic areas.
The illness-to-infection ratio is unknown but seems high for
infections, judging from experience with the original 1967
incubation period ranges from 3 to 10 days, but was typically 5-7
the original outbreak (32). The physician infected in the Nairobi
had a 9-day incubation period.
Clinical and laboratory features of Marburg virus disease are
essentially similar to those described for Ebola virus disease.
is confirmed by isolating the virus or demonstrating IgM or rising
antibodies by IFA. The treatment is the same as for Ebola virus
and the same comments about antiviral drugs and the use of immune
CRIMEAN-CONGO HEMORRHAGIC FEVER
Crimean-Congo hemorrhagic fever (CCHF) virus is an enveloped,
Bunyaviridae. A hemorrhagic fever that had long been recognized in
came to international attention after a disease outbreak in the
peninsula in 1944 and 1945 (36). The causative agent was later
to be identical to the Congo virus (37,38), isolated in Zaire,
name CCHF. Many wild and domestic animals act as reservoirs for the
including cattle, sheep, goats, and hares. Ixodid (hard) ticks,
particularly those of the genus Hyalomma, act both as a reservoir
vector for CCHF virus. Ground-feeding birds may disseminate
vectors. Twenty-seven species of ticks are known to harbor the CCHF
CCHF is endemic in eastern Europe, particularly in the Soviet
However, it may occur in other parts of Europe, especially around
Mediterranean. CCHF has been recognized in northwest China (39),
Asia, and the Indian subcontinent and may occur in the Middle East
throughout much of Africa. Humans become infected by being bitten
or by crushing ticks, often while working with domestic animals or
livestock. Contact with blood, secretions, or excretions of
animals or humans may also transmit infection. In areas with
the disease may occur most often in the spring or summer.
Nosocomial transmission is well described in recent reports
Pakistan (40), Iraq (41), Dubai (42), and South Africa (43-48).
evidence, including recently unpublished experiences, suggests that
and other body fluids are highly infectious, but simple
as barrier nursing, effectively prevent secondary transmission
Concern has been raised about two nosocomial cases in South Africa
occurred without documented evidence of direct exposure to
material (43-47). However, all other evidence rules out airborne
The incubation period for CCHF is about 2-9 days. Initial
nonspecific and sometimes occur suddenly. They include fever,
myalgia, arthralgia, abdominal pain, and vomiting. Sore throat,
conjunctivitis, jaundice, photophobia, and various sensory and mood
alterations may develop. A petechial rash is common and may precede
and obvious hemorrhagic diathesis, manifested by large ecchymoses,
from needle-puncture sites, and hemorrhage from multiple other
case-fatality rate has been estimated to range from 15% to 70% (2),
mild or inapparent infections occur. One study suggested an
Diagnosis requires isolating the virus from blood during the
of illness or detecting rising antibody titer by IFA, complement
or one of several other methods. No data are available on the
IgM antibody response. Nonspecific laboratory abnormalities include
progressive neutropenia, lymphopenia, thrombocytopenia, and anemia.
Hyperbilirubinemia and elevated liver enzymes are common.
Treatment is supportive and may require intensive care.
inhibits CCHF virus in vitro, but its efficacy in clinical practice
unconfirmed. Although immune plasma has been used its effectiveness
APPROACH TO A SUSPECTED CASE OF VHF
The patient's travel history, symptoms, and physical signs
most important clues to the potential diagnosis of VHF. Under
circumstances, infection is most often acquired in rural areas, and
most visitors and tourists to areas with endemic VHF, exposure to
causative agents is extremely unlikely. If the patient has visited
exclusively urban zones, a diagnosis of VHF is improbable. The
realistically excluded if the interval between the onset of
the last possible exposure exceeds 3 weeks. A careful history must
about the patient's possible exposure to ill persons or traveling
companions in an area with endemic VHF.
Initial symptoms may include fever, headache, sore throat,
abdominal pain, and diarrhea. Diagnosis at this stage is difficult,
these symptoms are nonspecific. The differential diagnosis is wide
includes other viral infections -- particularly arbovirus
bacterial infections such as typhoid fever, rickettsial diseases,
parasitic infections such as malaria. Symptoms and signs supporting
diagnosis of VHF are pharyngitis and conjunctivitis, a skin rash
(particularly for Marburg and Ebola virus diseases), and later,
Two critical studies should be done for any patient who has
returned from the tropics and has fever; these are a blood-film
for malaria and blood cultures. An experienced technician may need
examine several blood smears to identify malarial parasites,
for patients who have taken prophylactic antimalarial chemotherapy.
VHF is a diagnostic possibility, blood cultures must be done in a
system. These initial specimens should be handled with the same
used for samples infected with hepatitis B virus or human
virus. An experienced technician should be briefed about the safe
of such material. All of the patient's body fluids, secretions, and
If clinicians feel that VHF is a likely diagnosis, they should
immediate steps: 1) isolate the patient, and 2) notify local and
health departments and CDC.
The aim of management is to provide optimal care to the patient
the least hazard to staff. A mobile laboratory capable of
routine laboratory tests is available on request from CDC (see
Laboratory tests essential for the patient's immediate care must be
trained staff using the precautions outlined in this document.
adherence to barrier-nursing procedures and precautions to prevent
with blood or other body fluids are fundamental to the effective
of patients with possible VHF and to the protection of the staff.
ISOLATION OF PATIENTS WITH SUSPECTED AND CONFIRMED VHF
Extensive experience in West Africa has shown that the ordinary
patients infected with hepatitis B virus or human immunodeficiency
combined with barrier nursing, effectively prevent Lassa virus
in hospitals (19). Ideally, patients should be cared for at the
where they are first seen, since patients ill with VHF tolerate the
stress of transfer poorly, and a move only increases the potential
secondary transmission. If care at the hospital where the patient
is not possible, transfer to another local facility is preferable
to a more distant center. Personnel involved in the transfer of
with suspected VHF must follow the same precautions recommended for
and nursing staff.
The patient should be isolated in a single room with an
anteroom serving as its only entrance. The anteroom should contain
for routine patient care, as well as gloves, gowns, and masks for
staff. The Appendix lists suggested supplies for the anteroom.
facilities should be available in the anteroom, as well as
decontaminating solutions. If possible, the patient's room should
negative air pressure compared with the anteroom and the outside
the air should not be recirculated. However, this is not absolutely
required, and does not constitute a reason to transfer the patient.
room such as described is not available, use adjacent rooms to
and adequate space.
Strict barrier-nursing techniques should be enforced: all
entering the patient's room should wear disposable gloves, gowns,
and shoe covers. Protective eye wear should be worn by persons
disoriented or uncooperative patients or performing procedures that
involve the patient's vomiting or bleeding (for example, inserting
nasogastric tube or an intravenous or arterial line). Protective
should be donned and removed in the anteroom. Only essential
nursing personnel should enter the patient's room and anteroom.
signs listing necessary precautions should be posted outside the
The patient should use a chemical toilet. All secretions,
and other body fluids (other than laboratory specimens) should be
with disinfectant solution. All material used for patients, such as
disposable linen and pajamas, should be double-bagged in airtight
outside bags should be sponged with disinfectant solution and later
incinerated or autoclaved. Disposable items worn by staff, such as
gloves, etc., should be similarly treated. Disposable items used in
care (suction catheters, dressings, etc.) should be placed in a
plastic container of disinfectant solution. The outside of the
should be sponged with disinfectant, and the container should be
claved, incinerated, or otherwise safely discarded.
If surgery is required, surgical staff should wear protective
and double gloves. Advice should be sought from CDC.
Lipid-containing viruses, including the enveloped viruses, are
the most readily inactivated of all viral agents (50). Suitable
disinfectant solutions include 0.5% sodium hypochlorite (10%
solution of household bleach), as well as fresh, correctly prepared
solutions of glutaraldehyde (2% or as recommended by the
phenolic disinfectants (0.5%-3%) (50,51). Soaps and detergents can
inactivate these viruses and should be used liberally.
CONFIRMATION OF THE DIAGNOSIS
The diagnosis of VHF is confirmed by isolating the virus or by
demonstrating IgM antibody or a fourfold rise in IgG antibody in
described earlier. Antibody may not appear in blood until the
of illness. Virus is usually recovered from blood, although Lassa
also be isolated from the throat or urine. Liver tissue collected
death may also be a rich source of virus.
Virus isolation must only be attempted in Biosafety Level 4
(52), such as are available at CDC. Serologic tests can be
at CDC or in the mobile laboratory (see below). Serologic tests for
antibodies are done with gamma-irradiated antigens and serum
have been inactivated with heat or gamma irradiation.
Handling Laboratory Specimens
Recommendations for safely collecting and transporting
unchanged. The essential specimens to be submitted for virus
a sample of venous blood, a midstream ("clean catch") specimen of
and a throat swab. If postmortem specimens are available, serum,
spleen, and kidney tissue are desirable. The following procedures
Glass containers should not be used. Disposable sharp
as scalpel blades, also should not be handled unnecessarily after
should be autoclaved or incinerated.
2. Venous blood samples must be collected with extreme care to
self-inoculation. Ten milliliters of clotted blood should be placed
sealed plastic container. Needles should not be recapped, bent,
removed from disposable syringes, or otherwise handled.
equipment should be put in a rigid plastic container filled with
disinfectant solution and autoclaved or incinerated.
3. Midstream urine specimens should be collected by clean
milliliters of urine should be put in a plastic screw-cap container
one of the following: rabbit serum albumin diluted to a final
of 25%, human serum albumin diluted to a 1% concentration, or
albumin at a final concentration of 10%.
4. Throat swabs should be placed in plastic screw-cap
containers in 1
ml of sterile, phosphate-buffered neutral saline containing 25%
serum, 1% human serum albumin, or 10% bovine serum albumin.
The outside of each specimen container should be swabbed with
disinfectant, and a label should be attached bearing the patient's
hospital identification, the date of collection, and the nature of
suspected infection. Then, the specimens should be double-bagged in
airtight and watertight bags, which have been similarly labeled.
containing specimens should be sponged with disinfectant before
removed from the patient's room.
Packaging and Transporting Specimens
The Office of Biosafety at CDC (ext. 3883), the persons listed
Introduction, or the state health department should be contacted
instructions on packaging, labeling, and shipping diagnostic
specimens since shipment of specimens is subject to the applicable
provisions of the Federal interstate quarantine regulations (53).
general, the specimens should be packaged as follows:
Place the specimens for transport in a tightly sealed,
container, such as a screw-cap plastic tube or vial, and seal the
tape. Make sure plastic containers are resistant to temperatures as
-80 degrees C. If the specimen is in a glass or other unsuitable
it should be carefully transferred using the laboratory precautions
2. Wrap the primary container in sufficient absorbent material
example, tissue) to absorb the entire contents in case the
3. Place the wrapped, sealed primary container in a durable,
watertight screw-cap mailing tube or metal can. This secondary
should be sealed with tape. Several primary containers of
individually wrapped in absorbent material, may be placed in one
container, to a maximum of 50 ml of specimen material.
4. On the outside of the secondary container, attach the
labels and other relevant information.
5. Place the secondary container in a secure box or mailing
addressed to one of the individuals listed in the Introduction.
6. Transport the specimen for virus isolation on dry ice.
7. Since individual commercial and noncommercial carriers or
services may apply different regulations for transporting biologic
specimens, contact a representative of the chosen carrier
ensure that all necessary formalities are fulfilled. One person
the Introduction must be contacted by telephone about the
nature, the method of shipment, and the expected date and time of
Exposure of Laboratory Personnel to Specimens
Laboratory tests should be kept to the minimum required for the
immediate care of the patient until the mobile laboratory arrives.
investigations, such as examination of a blood smear for malaria
inoculation of blood cultures, must not, however, be postponed.
staff dealing with specimens from patients who might have a VHF
the same personal precautions as patient-care staff. Surgical
gowns, shoe covers, and masks should be worn. When possible,
tests should be performed in biological safety cabinets. Blood
should be prepared in a closed system. Every effort should be made
creating an aerosol or splashing, and protective eye wear should be
possible. A full-face respirator with an HEPA (high efficiency
air) filter is an acceptable, but cumbersome alternative to masks
protective eye wear. Nonessential tests should not be performed,
routine automated equipment be used unless the specimen has been
ivated. Abundant supplies of disinfectant solutions should be
available. Safe laboratory work has been done with use of these
precautions for many years in VHF-endemic areas with poorly
Laboratory personnel accidentally exposed to
material (for example, through injections or cuts or abrasions on
hands) should immediately wash the infected part, apply a
solution such as hypochlorite solution, and notify the patient's
The person should then be considered as a high-risk contact and
under surveillance (see below).
Accidental spills of potentially contaminated material should
liberally covered with disinfectant solution, left to soak for 30
and wiped up with absorbent material soaked in disinfectant.
CLINICAL CARE OF PATIENTS WITH SUSPECTED VHF
The challenge of managing patients with VHF is to provide the
quality of care with the least risk of transmitting infection.
discussion about therapy is beyond the scope of this document.
require close supervision, and some will need modern intensive-care
facilities. Since pathogenesis is not entirely understood and
therapy is limited, treatment is largely supportive. It is
give careful attention to fluid and electrolyte balance. In severe
therapy will be required for shock and blood loss. The supportive
patients critically ill with VHF is the same as the conventional
provided to patients with other causes of multisystem failure.
respiratory distress syndrome, renal failure, seizures, and coma
require specific interventions, such as mechanical ventilation,
and neurologic intensive care. If surgery is required (for example,
obstetric intervention), it should be done.
The prognosis for patients with Lassa fever has been shown to
with levels of viremia, but not with the development of IgM or IgG
virus. Experimental infections with Lassa and Ebola viruses in
monkeys suggest that shock results from platelet and endothelial
dysfunction, with subsequent leakage of fluid from the
and hemorrhage. To date, therapeutic use of heparin or
not proven effective and is probably contraindicated.
Patients with Lassa fever should receive ribavirin (see box).
severely ill persons, treatment may begin while confirmation of the
diagnosis is pending. Ribavirin is recommended both therapeutically
patients with Lassa fever and prophylactically for high-risk
such patients. Its use for patients with CCHF and their high-risk
may be justified but is unstudied.
Ribavirin 30 mg/kg intravenously (IV) loading dose,
mg/kg IV every 6 hours for 4 days, and then 8 mg/kg IV
hours for 6 days (total treatment time 10 days).
Ribavirin 500 mg by mouth every 6 hours for 7 days.
Use of convalescent plasma for Lassa fever Is not currently
recommended. Analogues of prostacyclin are being evaluated as to
efficacy in restoring the endothelial cell defect (20). Therapy can
discussed with persons listed in the Introduction.
Clinical experience with Ebola and Marburg virus diseases is
and individual judgment must determine whether convalescent plasma
antiviral drugs should be used. Interferon and ribavirin show no in
effect against these agents.
Ribavirin has been shown effective against some of the
vitro, and its use in patients with CCHF seems reasonable, although
clinical experience is available.
CDC has adapted a mobile isolator that can be used as a
laboratory to investigate cases of suspected or confirmed VHF
This facility can be transported immediately to any part of the
States, with an accompanying technician and physician experienced
dealing with hemorrhagic fevers. The mobile laboratory has
routine hematologic and biochemical studies, as well as for basic
iologic and coagulation investigations. Serodiagnostic tests for
VHF can be
performed in this facility, but cultures for virus isolation
Electrolyte measurements on inactivated serum specimens are also
but blood gas analysis is not. Early use of this facility is
delays in investigating the suspected case because of concern about
hazards of handling specimens. Further information about the mobile
laboratory and its use can be obtained from the persons listed in
AUTOPSY AND HANDLING OF A CORPSE
Before an autopsy is done on a patient suspected to have died
the possible risks and benefits must be carefully considered.
have been conducted safely on these patients, sometimes without
knowledge of the diagnosis (34), but under some circumstances it
wiser to forego this procedure. Limited autopsy or postmortem
blood and percutaneous liver biopsy material may be appropriate.
The same precautions recommended for clinicians and laboratory
working with infected patients and specimens must be followed.
gloves, caps and gowns, waterproof aprons, shoe covers, and
wear are required. Aerosol formation must be avoided (for example,
electrical cutting instruments must not be used). All solid and
waste should be decontaminated with disinfectant solution or by
1 hour at 60 degrees C. Liquid waste can then be washed down the
solid waste should be incinerated.
All unnecessary handling of the body, including embalming,
avoided. Persons who dispose of the corpse must take the same
outlined for medical and laboratory staff. The corpse should be
an airtight bag and cremated or buried immediately.
Disposable items, such as pipette tips, specimen containers,
etc., should be placed in a container filled with disinfectant
incinerated. Clothes and blankets that were used by the patient
washed in a disinfectant, such as hypochlorite solution.
Nondisposable items such as endoscopes used in patient care
cleaned with decontaminating fluids (for example, gluteraldehyde or
hypochlorite). Laboratory equipment must be treated similarly. All
disposable materials that withstand autoclaving should be
they have been soaked in disinfectant solution. The patient's bed
exposed surfaces in the hospital room, or in vehicles used to
patient, should be decontaminated with disinfectant solution.
IDENTIFICATION, SURVEILLANCE, AND MANAGEMENT OF PATIENT CONTACTS
A contact is defined as a person who has been exposed to an
person or to an infected person's secretions, excretions, or
3 weeks of the patient's onset of illness. Contacts may be
three levels of risk.
Casual contacts are persons who had remote contact with the
patient. These include persons on the same airplane, in the same
etc. Since the agents of VHF are not spread by such contact, no
surveillance is indicated.
2. Close contacts are persons who had more than casual contact
the patient. They include persons living with the patient, nursing
serving the patient when he or she was ill, shaking hands with or
the patient, handling the patient's laboratory specimens, etc.
contact persons should be identified by state and local health
in collaboration with CDC, as soon as VHF is considered a likely
for the index case. Once the diagnosis is confirmed, close contacts
should be placed under surveillance. This requires these
record their temperatures twice daily and report any temperature of
degrees F (38.3 degrees C) or above or any symptom of illness to
health officer responsible for surveillance. Surveillance should be
continued for 3 weeks after the person's last contact with the
3. High-risk contacts are persons who have had mucous membrane
with the patient, such as kissing or sexual intercourse, or have
needle stick or other penetrating injury involving contact with the
patient's secretions, excretions, blood, tissues, or other body
These individuals should be placed under surveillance as soon as
considered a likely diagnosis in the index case.
Any contact who develops a temperature of 101 degrees F (38.3
C) or higher or any other symptoms of illness should be immediately
isolated and treated as a VHF patient. Ribavirin should be
postexposure prophylaxis for high-risk contacts of patients with
fever. Dosage schedules are given in the box on page 11. Although
experience is more limited, postexposure prophylaxis with ribavirin
recommended for high-risk contacts of patients with CCHF.
Convalescent patients and their contacts should be warned that
the causative agents of VHF may continue to be excreted for many
semen, as demonstrated with Marburg (32,34) and Ebola (29) viruses,
urine, as occurs sometimes with Lassa virus (13). It is recommended
the persons listed in the Introduction be contacted about arranging
shipment to CDC of seminal fluid and urine specimens from patients
convalescent period for virus isolation. Convalescent patients must
meticulous about personal hygiene. While data are limited
infectivity in the convalescent period, abstinence from sexual
is advised until genital fluids have been shown to be free of the
the patient does engage in sexual intercourse before tests are
use of condoms is advised.
Fisher-Hoch SP, Simpson DIH. Dangerous pathogens. Br Med Bull
CDC. Viral hemorrhagic fever: initial management of suspected
firmed cases. MMWR 1983;32(2S):27S-39S.
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disease of man from West Africa: I. Clinical description and
pathological findings. Am J Trop Med Hyg 1970;19:670-6.
Leifer E, Gocke DJ, Bourne H. Lassa fever, a new virus disease
from West Africa: II. Report of a laboratory-acquired infection
with plasma from a person recently recovered from the disease.
Trop Med Hyg 1970;19:677-9.
CDC. Lassa virus infection -- Pennsylvania. MMWR
Monath TP. Lassa fever: review of epidemiology and
Frame JD. Surveillance of Lassa fever in missionaries stationed
Africa. Bull WHO 1975;52:593-8.
Woodruff AW, Monath TP, Mahmoud AAF, Pain AK, Morris CA. Lassa
Britain: an imported case. Br Med J 1973;3:616-7.
Gilles HM, Kent JC. Lassa fever: retrospective diagnosis of two
patients seen in Great Britain in 1971. Br Med J 1976;2:1173.
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fever: clinical and virological findings. Br Med J
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experience at St Thomas's Hospital. Br Med J 1982;285:1003-5.
Zweighaft RM, Fraser DW, Hattwick MAW, et al. Lassa fever:
an imported case. N Engl J Med 1977;297:803-7.
Keenlyside RA, McCormick JB, Webb PA, Smith E, Elliott L,
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study of the epidemiology and ecology of Lassa fever. J Infect
Helmick CG, Webb PA, Scribner CL, Krebs JW, McCormick JB. No
for increased risk of Lassa fever infection in hospital staff.
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management of a severe case of Lassa fever with simple barrier
techniques. Lancet 1985;2:1227-9.
McCormick JB, King IJ, Webb PA, et al. A case-control study of
clinical diagnosis and course of Lassa fever. J Infect Dis
McCormick JB, King IJ, Webb PA, et al. Lassa fever. Effective
with ribavirin. N Engl J Med 1986;314:20-6.
Johnson KM, McCormick JB, Webb PA, Smith ES, Elliott LH, King
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Heymann DL, Weisfeld JS, Webb PA, Johnson KM, Cairns T,
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Baron RC, McCormick JB, Zubeir OA. Ebola virus disease in
Sudan: hospital dissemination and intrafamilial spread. Bull
Teepe RGC, Johnson BK, Ocheng D, et al. A probable case of
haemorrhagic fever in Kenya. East Afr Med J 1983;60:718-22.
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infection. Br Med J 1977;2:541-4.
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Smith DH, Johnson BK, Isaacson M, et al. Marburg-virus disease
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Casais J. Antigenic similarity between the virus causing
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Chumakov MP, Smirnova SE, Tkachenko EA. Relationship between
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Appendix: Suggested Equipment and Supplies for Anteroom Adjoining
Prescribed medications (analgesics, Containers with solution
antipyretics, antibiotics, etc.) swabs and urine specimens
Resuscitation equipment text)
Material for physical examination Labels
Portable X-ray machine Marker pens
Electrocardiogram machine Plastic airtight bags
Intravenous equipment and supplies sizes)
Tourniquets Plastic trash bags
Dry gauze Disinfectant solutions (see
Alcohol swabs Chemical toilet
Needles (various sizes) Urinals
Syringes (various sizes) Nursing supplies
Plastic container for disposal of Disposable linen, towels,
pajamas, needles and other sharp equipment etc.
Tubes for hematologic and biochemical investigations.
Blood-culture bottles covers, and protective
eye wear .