Viral hemorrhagic fevers

Signs and Symptoms

Clinical signs/symptomsb of Ebola Hemorrhagic Fever

—Maculopapular rash (predominantly on trunk) occurs about 5 days after illness onset
—Jaundice and pancreatitis often occur
—As disease progresses, bleeding manifestations may develop (eg, mucous membrane hemorrhages, hematemesis, bloody diarrhea, petechiae, ecchymoses, oozing of blood at puncture sites)
—In 1995 DRC outbreak, some form of bleeding was reported in 37% of 219 patients
—CNS findings include psychosis, delirium, coma, seizures
—Shock (with DIC and end-organ failure) often ensues during second week of illness
—Signs and symptoms recorded for 219 patients in 1995 DRC outbreak (recorded at time of admission or during clinical course) included:
    ~Asthenia (78%)
    ~Diarrhea (74%)
    ~Headache (73%)
    ~Anorexia (73%)
    ~Nausea/vomiting (70%)
    ~Abdominal pain (56%)
    ~Myalgias/arthralgias (51%)
    ~Dysphagia (41%)
    ~Conjunctival inflammation/hemorrhage (34%)
    ~Dyspnea (25%)
    ~Gingival hemorrhage (21%)
    ~Petechiae (15%)
    ~Melena (14%)
    ~Hiccups (14%)
    ~Hematemesis (13%)
—Asymptomatic infections can occur
—Recovery may take up to several weeks

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CNS, central nervous system; DIC, disseminated intravascular coagulation; DRC, Democratic Republic of the Congo.

aSee References: Borio 2002; Peters 2005: Marburg and Ebola Virus Hemorrhagic Fevers.
bSee References: Borio 2002; Bwaka 1999; Khan 1999; Leroy 2000: Human asymptomatic Ebola infection; Peters 2005: Marburg and Ebola virus hemorrhagic fevers.
cSee References: WHO 1985: Viral haemorrhagic fevers: report of a WHO expert committee, 1984.
dSee References: Bwaka 1999, Kibadi 1999.
eSee References: Kahn 1999; WHO 2007: Ebola hemorrhagic fever; Zaki 1997.


Clinical Signs/Symptomsa of Marburg Hemorrhagic Fever

—Maculopapular rash occurs on the 5th to 7th day (trunk, face, neck, proximal regions of extremities) and is nonpruritic.
—Jaundice and pancreatitis usually occur.
—As disease progresses, bleeding manifestations may develop (eg, mucous membrane hemorrhages, hematemesis, bloody diarrhea, melena, bleeding from gums, petechiae, ecchymoses, hematuria).
—In one report of 23 patients, bleeding manifestations occurred in 7 (30%).
—CNS findings include restlessness, confusion, apathy, somnolence, meningismus.
—Shock (with DIC and end-organ failure) may ensue during 2nd week of illness
—Recovery may take up to several weeks.

Abbreviations: ALT, alanine aminotransferase; CNS, central nervous system; AST, aspartate aminotransferase; DIC, disseminated intravascular coagulation.

aSee References: Gear 1975; Martini 1971; Peters 2005: Marburg and Ebola virus hemorrhagic fevers.
bSee References: Martini 1971; WHO: Marburg haemorrhagic fever: situation updates.


Clinical Signs/Symptomsa of Lassa Fever

—Severe exudative pharyngitis may occur (40% in one series of 306 patients).b
—Macolopapular rash may be noted on some fair-skinned patients.
—Severe prostration may occur by 6th to 8th day.
—As disease progresses, bleeding manifestations may develop (eg, mucous membrane hemorrhages, hematemesis, bloody diarrhea, petechiae, ecchymoses).
—In one outbreak in Sierra Leone, bleeding manifestations occurred in 17% of 306 patients.b
—Other findings that may occur include:
    ~Edema of head and neck
    ~Pleural, pericardial effusions
    ~Neurologic involvement (encephalopathy, coma, meningeal signs, cerebellar syndromes, tremors, seizures, eighth cranial nerve involvement)
    ~Capillary leak syndrome
    ~Shock with end-organ failure
—For those with less severe disease, recovery begins at about 10 days, although weakness and fatigue may persist for several weeks.
—Most infections are thought to be mild or subclinical; severe disease occurs in 5%-10% of cases.

Abbreviations: ALT, alanine aminotransferase; AST: aspartate aminotransferase; BUN, blood urea nitrogen; CPK, creatine phosphokinase; WBC, white blood cell.

aSee References: Borio 2002; Peters 2005: Lymphocytic choriomeningitis virus, Lassa virus, and the South American hemorrhagic fevers.
bSee References: McCormick 1987: A case-control study.
cSee References: McCormick 1987: A case-control study; Peters 2005: Lymphocytic choriomeningitis virus, Lassa virus, and the South American hemorrhagic fevers.
dSee References: McCormick 1987: A prospective study.
eSee References: Peters 2005: Lymphocytic choriomeningitis virus, Lassa virus, and the South American hemorrhagic fevers.
fSee References: Frame 1989.


Clinical Signs/Symptomsa of New World Hemorrhagic Fever

—Common early findings include:
    ~Conjunctival injection
    ~Flushing of face, upper body
    ~Enanthem (petechiae and/or small vesicles)
    ~Skin petechiae
    ~Generalized lymphadenopathy
—As disease progresses, vascular or neurologic manifestations may occur (5-7 days after illness onset).
—Vascular manifestations include:
    ~Capillary leak syndrome
    ~Proteinuria
    ~Bleeding manifestations (eg, mucous membrane hemorrhages, hematemesis, bloody diarrhea, petechiae, ecchymoses)
    ~In one series of 14 patients with Venezuelan hemorrhagic fever, bleeding manifestations in 13 (92%)
    ~Vasoconstriction, shock
—Neurologic manifestations include:
    ~Tremors
    ~Myoclonic movements
    ~Seizures
    ~Dysarthria
    ~Coma
—Clinical findings on admission for 14 patients with Venezuelan hemorrhagic fever includedb:
    ~Dehydration (71%)
    ~Pharyngitis (71%)
    ~Somnolence (64%)
    ~Conjunctivitis (50%)
    ~Crackles (43%)
    ~Petechiae (29%)
    ~Cervical adenopathy (21%)
    ~Facial edema (14%)
    ~Tonsillar exudates (14%)
    ~Hand tremors (7%)
    ~Rash (7%)
—Recovery occurs over 2-3 wk.

aSee References: Borio 2002; Peters 2005: Lymphocytic choriomeningitis virus, Lassa virus, and the South American hemorrhagic fevers.
bSee References: Salas 1991.
cSee References: WHO1985: Viral haemorrhagic fevers: report of a WHO expert committee.
dSee References: Peters 2005: Lymphocytic choriomeningitis virus, Lassa virus, and the South American hemorrhagic fevers.
eSee References: CDC 2000: Fatal illnesses associated with a New World arenavirus; CDC 1994: Bolivian hemorrhagic fever; Peters 2005: Lymphocytic choriomeningitis virus, Lassa virus, and the South American hemorrhagic fevers; Salas 1991.


Clinical Signs/Symptomsb of Rift Valley Fever

—Subclinical infection is common.
—Four clinical patterns occur:
    ~Undifferentiated fever lasting 2-7 days (>90% of cases; often associated with nausea, vomiting, and abdominal pain)
    ~Hemorrhagic fever with marked hepatitis and bleeding manifestations (<1% of cases; occurs 2-4 days after onset of fever)
    ~Encephalitis (<1% of cases; occurs 1-4 wk after onset of fever)
    ~Retinitis (up to 10% of cases; occurs 1-4 wk after onset of fever; often bilateral; hemorrhages, exudates, and cotton wool spots may be visible on macula; retinal detachment may occur)
—Common bleeding manifestations include gastrointestinal bleeding and epistaxis.
—Neurologic symptoms include confusion, lethargy, tremors, ataxia, coma, seizures, meningismus, vertigo, and choreiform movements.
—Hepatitis, hepatic failure, and renal failure may occur.
—A report of the 2001 outbreak in Saudi Arabia identiied the following clinical features for 683 laboratory-confirmed cases:
    ~Fever: 92.6%
    ~Nausea: 59.4%
    ~Vomiting: 52.6%
    ~Abdominal pain: 38.0%
    ~Diarrhea: 22.1%
    ~Jaundice: 18.1%
    ~Neurologic manifestations: 17.1%
    ~Hemorrhagic manifestations: 7.1%

Abbreviations: ALT, alanine aminotransferase; AST: aspartate aminotransferase; DIC, disseminated intravascular coagulation; RVF, Rift Valley fever.

aSee References: Borio 2002.
bSee References: Al-Hazmi 2003; Borio 2002; CDC 2000: Outbreak of Rift Valley fever--Yemen; CDC: Rift Valley fever fact sheet; Madani 2003; WHO 1984: Viral hemorrhagic fevers: report of a WHO expert committee.
cSee References: Lacy 1996.
dSee References: WHO 1985: Viral haemorrhagic fevers: report of a WHO expert committee.
eSee References: Al-Hazmi 2003, Borio 2002, Madani 2003, Morrill 1996.


Clinical Signs/Symptomsb of Yellow Fever

—Subclinical infection is common (5%-50%).
—Five clinical patterns occur:
    ~Very mild (transient fever, mild headache; illness lasting about 1 day)
    ~Mild (more pronounced fever and headache; nausea, vomiting, epigastric pain, myalgias, epistaxis, photophobia, asthenia [may be present]; illness lasting 2-3 days).
    ~Moderately severe (high fever; severe headache/backache; biphasic course with jaundice, albuminuria, oliguria, protracted vomiting, and bleeding manifestations in second phase; illness lasting about 1 wk)
    ~Malignant (fulminant infection with severe hepatic involvement, bleeding manifestations, renal failure, shock, and death [usually 7-10 days after illness onset])
    ~Fever accompanied by only meningeal signs and symptoms
—Bleeding manifestations include hematemesis, bloody diarrhea, epistaxis, gum bleeding, petechial and purpuric hemorrhages.
—Severe disease develops in about 15% of patients; of these, about 50% go on to the malignant form and die.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase.

aSee References: Tsai 2000.
bSee References: Lacy 1996; Tsai 2000; WHO 2001: Yellow fever; WHO 1985: Viral haemorrhagic fevers: report of a WHO expert committee, 1984.
cSee References: Lacy 1996.
dSee References: Borio 2002; Lacy 1996; WHO 2001: Yellow fever.


Clinical Signs/Symptomsa of Kyasanur Forest Disease

—Diarrhea and vomiting occur by the 3rd or 4th day.
—Enanthem with papulovesicular lesions occurs on soft palate.
—Ocular findings include conjunctival congestion, subconjunctival hemorrhage, superficial punctate keratitis, mild iritis, and retinal and vitreous hemorrhage.b
—Cervical and axillary lymphadenopathy are usually present.
—Bleeding manifestations are seen as early as third day (bleeding from nose, gums, gastrointestinal tract).
—In one series of 152 patients, bleeding occurred in 26 patients (17%).b
—The initial illness phase lasts 6 days to 2 wk.
—Illness may be biphasic for up to 50% of cases; after initial illness, afebrile period of 9-21 days occurs, followed by meningoencephalitis.
—Findings associated with meningoencephalitis include tremors, headache, mental status changes, and abnormal reflexes.
—Hemorrhagic pulmonary edema and renal failure occur in severe cases.
—Recovery takes up to 4 wk.

aSee References: Borio 2002, Pavri 1989, Pattnaik 2006.
bSee References: Nayak 1983.
cSee References: Pavri 1989.


Clinical Signs/Symptomsa,b of Omsk Hemorrhagic Fever

—Initial febrile illness lasting 5-12 days occurs, followed by second phase several days later in 30%-50% of patients that is often more severe.
—Generalized lymphadenopathy and splenomegaly commonly occur.
—During second phase, pneumonia occurs in about 30% of patients and meningeal symptoms are common.

—Diffuse encephalitis may occur.
—Recovery may take several weeks.

aSee References: Borio 2002.
bSee References: WHO 1985: Viral haemorrhagic fevers: report of a WHO expert committee.

Center for Infectious Disease Research & Policy Website. 2007. University of Minnesota. 21 Feb, 2011<http://www.cidrap.umn.edu>.
Viral hemorrhagic fevers (VHF) are illnesses characterized by fever and bleeding diathesis. Manifestations of VHF often include flushing of the face and chest, petechiae, frank bleeding, edema, hypotension, and shock. Malaise, myalgias, headache, vomiting, and diarrhea occur frequently.
USAMRIID's Medical Management of Biological Casualities Handbook. Sixth ed. Fort Dietrich, Maryland: U.S. Army Medical Research Institute of Infectious Diseases, 2005. 74.
  • Fever
  • Muscular Pain
  • Headaches
  • Hemorrhage
  • Hypotension
  • Shock
WMD Response Guidebook. Third ed. Louisiana: Louisiana State University and A&M College, National Center for Biomedical Research and Training, Academy of Counter-Terrorist Education, 2006. 17.
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