to Infectious Diseases or Refugees
Hemorrhagic fevers (HFs) are found in numerous areas of the world, with variants
noted below under vectors and agents.
Agents and Vectors:
Viruses are transmitted by:
- Zoonosis or transmission
of a disease of animals directly to humans from the animal host (especially
rodents in the case of hemorrhagic fevers): HF with renal syndrome secondary
to Hantaan virus infection: Europe, East China, and Korea (In Europe includes
Puumala virus, Scandinavia; Belgrade virus, Yugoslavia; Dobrava virus, Balkan
area. These three tend to cause milder infections); Hantavirus pulmonary
syndrome: North America (especially Southern), South America (especially
Andes); Junin HF, Argentina; Machupo HF, Bolivia; Lassa HF, West Africa;
Ebola and Marburg HFs: Central Africa (vector not known).
- Tick: Omsk HF: Russia,
especially Siberia; Kyasanur Forest hemorrhagic fever: India; Crimean-Congo
HF: Africa, Middle East, Eastern Europe, Russia, Western China.
- Mosquito: Chikungunya
HF: Africa and East Asia; dengue fever: worldwide; yellow fever: tropical
Africa and South America; Rift Valley fever: Africa, especially Central,
The viral HFs are are
considered by the CDC to be Category A biological warfare (BW) agents (CDC,
2000). See bioterror box below.
the index of suspicion is increased with travel in an endemic area + hemorrhagic
manifestations occurring within the incubation period, endemic areas and incubation
periods are given in discussions of specific HFs. The range of incubation
for HFs is 3-28 days.
Findings and Treatment
Note: The most important
HFs are discussed separately in this site and summarized in this file. These
include dengue fever, yellow
fever, Lassa fever, and the Ebola
and Marburg fevers). Those of lesser importance, i.e., lower incidence
or virulence are summarized in this file. These include hemorrhagic fever
with renal syndrome caused by hantavirus, hantavirus pulmonary syndrome, South
American HFs, Kyasanur Forest HF, Omsk HF, Crimean-Congo HF, Chikungunya HF,
and Rift Valley HF. The U.S. Centers for Disease Control groups Crimean-Congo,
Lassa, Ebola, and Marburg hemorrhagic fevers together as causing viral hemorrhagic
fevers (VHFs) and in some cases, presents management as of VHF as a unified
concept (CDC, 1995). The Marburg and Ebola hemorrhagic fevers (both from Filoviruses)
are characterized by easy transmissability, high mortality, lack of effective
vaccine, and lack of effective treatment.
General Signs and
Symptoms: The viral hemorrhagic syndrome (VHS) results from widespread
increased permeability of microvasculature. Depending on the severity of vascular
instability and decrease in platelet function, presentation may range from
mild to severe illness; and hemorrhagic manifestations are not always apparent.
A common course of illness begins with an abrupt onset of fever, myalgia,
cutaneous flushing, and conjunctival suffusion. Within several days, the patient's
condition worsens to include syncope, photophobia, headache, hyperesthesia,
abdominal pain, nausea/vomiting, anorexia, and prostration.
The viral HFs (Lassa,
Junin and related) are considered by the CDC to be Category A biological
warfare agents as they pose a risk to national security because they
"can be easily disseminated or transmitted from person to person;
cause high mortality, with potential for major public health impact;
might cause public panic and social disruption; and require special
action for public health preparedness" (CDC, 2000, p. 5). Though
Iraq is not known to have produced weaponized viral HFs (Shoham, 2000),
"all are potentially infectious by the aerosol route and most are
stable as respirable aerosols (Cieslak & Eitzen, 2000, p. 28). Treatment
is supportive, hence very challenging in a mass casualty situation.
Specific Signs and
- Hemorrhagic fever
with renal syndrome caused by hantavirus (Europe, Russia, East China,
and Korea): Incubation ranges from 9-35 days. Severity of the illness varies,
with mild or subclinical infections common. More severe cases are characterized
by a febrile stage lasting 3-5 days with abrupt onset of fever, headache,
photophobia, blurred vision, facial flushing extending to neck and shoulders,
conjunctival petechiae, periorbital edema, pharyngeal injection and/or petechiae,
axillary petechiae, lumbar back pain and CVA tenderness lasting 3-5 days.
The illness may gradually resolve after this febrile stage or a hypotensive
stage may begin as the temperature falls. The hypotensive stage is characterized
by decreased blood pressure, tachycardia, and sometimes shock. Thrombocytopenia,
leukocytosis, proteinuria, and oliguria occur, as does renal failure in
some cases. Renal function returns as the oliguric phase resolves and the
polyuric phase ensues. Electrolyte imbalances and dehydration may occur
in the polyuric phase. Disseminated intravascular coagulation may occur
relatively early in the course of illness. Treatment is supportive as discussed
- Hantavirus pulmonary
syndrome (North America, especially Southern; South America, especially
Andes): Incubation ranges from 7-28 days. Hantavirus infection is thought
to occur through inhalation of infected rodent droppings dust. Hantaviruses
cause HFs as described above and in Latin America and the U.S., the hantavirus
pulmonary syndrome (HPS). HPS is characterized by a flu-like febrile illness
that rapidly progresses to shock and adult respiratory distress syndrome
with thrombocytopenia, hemoconcentration, and leukocytosis. Treatment is
supportive as discussed below. Ventilation may be necessary within 24 hours
- Junin HF (Argentina),
Machupo HF (Bolivia), and other South American HFs: Incubation in South
American HFs ranges from 7-14 days. South American HFs are characterized
by the gradual onset of fever, myalgia, and signs and symptoms as described
above under general signs and symptoms. Thrombocytopenia, bleeding, and
neurological dysfunction (confusion, tremors, and cerebellar signs) are
common in South American HFs. Treatment is supportive and also includes
ribavirin as discussed below.
- Lassa HF (West
Africa, including Nigeria) is discussed in greater detail in a full discussion
file. Incubation of Lassa fever ranges from 7-21 days. Presentation
of Lassa fever varies. Common early symptoms are gradual onset of fever,
malaise, headache, and abdominal pain. Other symptoms are conjunctivitis,
facial swelling, sore throat, non-productive cough, retrosternal pain, nausea,
vomiting, diarrhea, back pain, and myalgia. Respiratory rate, temperature,
pulse rate are increased and blood pressure decreased. Neurological symptoms
may also occur, including hearing loss, tremors, and encephalitis. Hemorrhagic
manifestations (not usually evident) may include mucosal bleeding and, less
frequently, conjunctival, gastrointestinal, or vaginal bleeding. Severe
infections produce hemorrhagic manifestations, pleural effusions, and shock.
Pregnant women are more likely to die than are others. Some degree of deafness
occurs in about 30% of patients. See full discussion. Treatment is supportive
and also includes ribavirin as discussed below.
- Ebola and Marburg
HFs: See full discussion (Central Africa): Incubation of Ebola
and Marburg HFs ranges from 3-16 days. Both Ebola and Marburg HFs are characterized
by sudden onset of fever, chills, severe headache, and myalgia. On about
the fifth day of illness, a maculopapular rash may appear - most prominently
on the trunk (the rash may eventually desquamate). Other manifestations
occurring at about the same time include sore throat/pharyngitis, chest
pain, abdominal pain, nausea, vomiting, diarrhea, and hemorrhagic symptoms,
e.g., bleeding mucosal membranes. Symptoms may increase in severity and
include jaundice, pancreatic inflammation, rapid weight loss, prostration,
delirium, shock, hepatic failure, massive hemorrhaging, and multi-organ
failure. Case fatality rates for Marburg HF are around 25% and for Ebola
HF range from 50% to 90% (in Africa). See full discussion. Treatment is
supportive as discussed below.
- Kyasanur Forest
HF (India): Incubation is 3-8 days. Kyasanur Forest HF is caused by
a tick-borne flavivirus and currently is found only in the Mysore State
of India. The illness is characterized by sudden onset fever and headache,
followed by back and extremity pain, bradycardia, lymphadenopathy, conjunctival
injection, palantine injection, petechiae, and other hemorrhagic signs.
Meningoencephalitis is relatively common. Treatment is supportive as discussed
- Omsk HF (Russia):
Except for geographic location, Omsk HF is similar to Kyasanur Forest HF.
HF (Africa, Middle East, Eastern Europe, Russia, Western China): Incubation
is 3-12 days. Crimean-Congo HF is transmitted by the bite or crushing of
infected ticks, or by contact with live or dead infected mammals. The clinical
picture is similar to that described above under General Signs and Symptoms,
except that in Crimean-Congo HF there are significant liver abnormalities
(>AST, >phosphokinase, >bilirubin, leukocytosis, and signs of disseminated
intravascular coagulation. Though treatment is not definitive, more severe
cases are often successfully treated with IV ribavirin as described below.
- Chikungunya fever
(Topical areas, especially urban, of Asia, India, and East Africa): Chikungunya
fever is an arboviral infection transmitted by the Aedes aegypti mosquito.
Incubation is 2-4 days and the illness is self-limiting with acute symptoms
(abrupt onset fever, headache, arthralgias, nausea, vomiting, abdominal
pain, sore throat, lymphadenopathy, rash at defervescence, and malaise)
lasting 3-10 days. Arthralgias remain a problem for weeks to several months
after the acute phase. Febrile convulsions may occur in young children.
Treatment is supportive for fever and pain.
- Dengue: See
full discussion (East and West Africa, Southeast and East Asia, Pacific
Islands, Eastern Australia, Central and South America, Mexico, South Texas,
Caribbean Islands - with distribution increasing, especially in urban areas)
Incubation is 7-10 days. Dengue fever and HF are transmitted by mosquitos,
and there is increasing incidence and prevalence of cocirculation of multiple
serotypes. Dengue is usually a self-limited illness characterized by abrupt
onset high (biphasic) fever, chills, headache, rash, signs of bleeding,
changes in taste, sore throat, nausea, vomiting, diarrhea, anorexia, severe
aching myalgia and arthralgia (hence "bone-break" fever), and depression.
Complications include meningoencephalitis, dengue hemorrhagic fever (DHF),
and dengue shock syndrome (DSS). Treatment is supportive and convalescence
tends to be lengthy. See full discussion.
- Rift Valley fever
(Africa, especially Central, Egypt): Incubation is 3-5 days. The Rift Valley
fever (RVF) virus is transmitted by mosquito or perhaps other blood-sucking
insect bite; and by exposure to body fluids or meat of infected animals.
Most people with RVF have no symptoms or a mild febrile illness with liver
abnormalities. Others, however, develop a classic HF with weakness, fatigue,
back pain, dizziness, and rapid weight loss. Retinal vasculitis occurs in
about 10% of cases, and encephalitis may also occur in a few patients. Though
definitive research on treatment is lacking, treatment of severe cases may
include the use of IV ribavirin as described below.
Shock, multifocal hemorrhage, encephalopathy, seizures, convulsions, and/or
coma may occur in more serious infections. Renal failure is a complication
of HF with renal syndrome. Case mortality rates vary with the causative virus
and level of care. For example, the mortality rate for patients with dengue
HF who receive supportive care is less than 1%, while the mortality rate for
patients with hantavirus pulmonary syndrome is 30-50%. The mortality rate
for patients with Ebola HF ranges from 50-90%.
Increased AST, leukopenia, proteinuria, hemoconcentration, thromboctopenia,
and at least in the case of Crimean-Congo HF, also increased creatinine phosphokinase,
bilirubin, leukocytosis, and signs of disseminated intravascular coagulation.
manifestations + travel to an endemic area. Except for the presence of the
rash, dengue fever is difficult to distinguish from other febrile illnesses
(e.g., malaria, yellow fever, influenza) or arboviral disease with dengue-like
courses (Colorado tick fever, Rift Valley fever, Ross River fever, sandfly
fever). For this reason, an initial diagnosis may be "dengue-like disease."
Serologic diagnosis is on the basis of a fourfold or greater increase in antibody
titer in paired sera by hemagglutination inhibition, complement fixation,
enzyme immunoassay, or neutralization test. Standardized immunoglobulin (Ig)
M- and IgG-capture enzyme immunoassay are used to identify acute-phase antibodies.
Samples are collected no earlier than five days, nor later than six weeks
after onset. Viral RNA can be detected by specific complementary DNA probes
or amplified first by polymerase chain reaction.
Rickettsial diseases (typhus, Q fever, trench fever, spotted fevers such as
Rocky Mountain or Boutonneuse), meningococcemia, malaria, shigellosis, leptospirosis.
is supportive with acetaminophen rather than aspirin for fever and pain relief,
bed rest, fluid replacement, and gradual convalescence. Increased capillary
permeability limits the extent of fluid replacement. Pressors may be required
to maintain blood pressure. Renal failure requires dialysis. Lassa fever,
South American HFs, and possibly Crimean-Congo HF and Rift Valley HF may be
treated with a slow infusion of IV ribavirin 32 mg/kg; followed by 16 mg/kg
qid for 4 days; and this by 8 mg/kg tid for 6 days. Dengue hemorrhagic fever
and shock syndrome are medical emergencies treated in intensive care settings.
Carlini, M.E. & Shandera,
W.X. (1999). Infectious diseases: Viral and rickettsial. In L.M. Tierney,
S.J. McPhee, & M.A. Papadakis (Eds.), Current Medical Diagnosis & Treatment
(14th ed.) (pp.1255-1290). Stamford Connecticut: Appleton & Lange.
Centers for Disease
Control (1999). Lassa fever. Available online at http://www.cdc.gov/ncidod/dvrd/spb/mnpages/lassaf.htm
Centers for Disease Control
(1998). Rift Valley fever. Available online at http://www.cdc.gov/ncidod/dvrd/spb/mnpages/rvf.htm
Centers for Disease Control
and Prevention. (2000). Biological and chemical terrorism: Strategic plan
for preparedness and response. MMWR: Morbidity and Mortality Weekly Report,
Chin, J. (Ed.) (2000).
Control of communicable diseases manual (17th ed.). Washington, DC:
American Public Health Association.
Cieslak, T.J. & Eitzen,
E.M. (2000). Bioterrorism: Agents of concern. Journal of Public Health
Management Practice. 6(4), 19-29.
Halstead, S. (1996).
Arboviruses. In W.E. Nelson, R.E. Behrman, R.M. Kliegman, A.M. Arvin (Eds.),
Nelson Textbook of Pediatrics (15th ed.) (pp. 920-929). Philadelphia:
W.B. Saunders Company.
Levin, M.J. (1999). Infections:
Viral and rickettsial. In W.W. Hay, A.R. Hatward, M.J. Levin & J.M. Sondheimer
(Eds.). Current Pediatric Diagnosis & Treatment (14th ed.) (pp. 960-994).
Stamford Connecticut: Appleton & Lange.
Peters, C.J. (1998).
Infections caused by arthropod- and rodent-borne viruses. In A.S. Fauci, E.
Braunwald, K.J. Isselbacher, J.D. Wilson, J.B. Martin, D.L Kasper, S.L. Hauser,
& D.L. Longo, (Eds.) Harrison's Principles of Internal Medicine (14th
ed.) (pp. 1132-1146). New York: McGraw-Hill.