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VIRAL HAEMORRHAGIC FEVER
•Viral hemorrhagic fevers (VHFs) are a group of febrile illnesses caused by RNA viruses from several viral families. •These highly infectious viruses lead to a potentially lethal disease syndrome characterized by fever, malaise, vomiting, mucosal and gastrointestinal (GI) bleeding, edema, and hypotension.
Virus Family Disease (Virus) Natural DistributionUsual Source of Human Infection
Incubation (Days)
Arenaviridae
Arenavirus Lassa fever Africa Rodent 5-16
Argentine HF (Junin) South America Rodent 7-14
Bolivian HF (Machupo)
South America Rodent 9-15
Brazilian HF (Sabia) South America Rodent 7-14
Venezuelan HF (Guanarito)
South America Rodent 7-14
Bunyaviridae
Phlebovirus Rift Valley fever Africa Mosquito 2-5
Nairovirus Crimean-Congo HF Europe, Asia, Africa Tick 3-12
Hantavirus Hemorrhagic fever with renal syndrome, hantavirus pulmonary syndrome
Asia, Europe, worldwide
Rodent 9-35
Filoviridae
Filovirus Marburg and Ebola Africa Unknown 3-16
Flaviviridae
Flavivirus Yellow fever Tropical Africa, South America
Mosquito 3-6
Dengue HF Asia, Americas, Africa Mosquito Unknown for dengue HF, 3-5 for dengue
Virus Family Disease (Virus)Natural Distribution
Usual Source of Human Infection
Incubation (Days)
Arenaviridae
Arenavirus Lassa fever Africa Rodent 5-16
Argentine HF (Junin)
South America Rodent 7-14
Bolivian HF (Machupo)
South America Rodent 9-15
Brazilian HF (Sabia)
South America Rodent 7-14
Venezuelan HF (Guanarito)
South America Rodent 7-14
Bunyaviridae
Phlebovirus Rift Valley fever Africa Mosquito 2-5
Nairovirus Crimean-Congo HF
Europe, Asia, Africa
Tick 3-12
Hantavirus Hemorrhagic fever with renal syndrome, hantavirus pulmonary syndrome
Asia, Europe, worldwide
Rodent 9-35
Filoviridae
Filovirus Marburg and Ebola
Africa Unknown 3-16
Flaviviridae
Flavivirus Yellow fever Tropical Africa, South America
Mosquito 3-6
Dengue HF Asia, Americas, Africa
Mosquito Unknown for dengue HF, 3-5 for dengue
ArenaviridaeJunin virus
Machupo virusGuanarito virus
Lassa virusSabia virus
Arenaviridae HistoryFirst isolated in 19331958: Junin virus - Argentina
First to cause hemorrhagic feverArgentine hemorrhagic fever
1963: Machupo virus – BoliviaBolivian hemorrhagic fever
1969: Lassa virus – NigeriaLassa fever
Arenaviridae TransmissionVirus transmission and amplification occurs in rodents
Shed virus through urine, feces, and other excreta
Human infection Contact with excretaContaminated materialsAerosol transmission
Person-to-person transmission
Arenaviridae EpidemiologyAfrica
LassaSouth America
Junin, Machupo, Guanarito, and SabiaContact with rodent excreta Case fatality: 5 – 35% Explosive nosicomial outbreaks with Lassa
and Machupo
Arenaviridae in HumansIncubation period
10–14 daysFever and malaise
2–4 daysHemorrhagic stage
Hemorrhage, leukopenia, thrombocytopeniaNeurologic signs
BunyaviridaeRift Valley Fever virus
Crimean-Congo Hemorrhagic Fever virusHantavirus
Bunyaviridae History 1930: Rift Valley Fever – Egypt
Epizootic in sheep1940s: CCHF - Crimean peninsula
Hemorrhagic fever in agricultural workers1951: Hantavirus – Korea
Hemorrhagic fever in UN troops5 genera with over 350 viruses
Bunyaviridae TransmissionArthropod vector
Exception – HantavirusesRVF – Aedes mosquito CCHF – Ixodid tickHantavirus – RodentsLess common
AerosolExposure to infected animal tissue
Bunyaviridae EpidemiologyRVF - Africa and Arabian Peninsula
1% case fatality rateCCHF - Africa, Eastern Europe, Asia
30% case fatality rateHantavirus - North and South America,
Eastern Europe, and Eastern Asia1-50% case fatality rate
Bunyaviridae HumansRVF
Incubation period – 2-5 days0.5% - Hemorrhagic Fever
CCHF Incubation period – 3-7 daysHemorrhagic Fever - 3–6 days
following clinical signsHantavirus
Incubation period – 7–21 daysHPS and HFRS
Bunyaviridae AnimalsRVF
Abortion – 100%Mortality rate
>90% in young5-60% in older animals
CCHFUnapparent infection in livestock
HantavirusesUnapparent infection in rodents
FiloviridaeMarburg virus
Ebola virus
Filoviridae History1967: Marburg virus
European laboratory workers1976: Ebola virus
Ebola ZaireEbola Sudan
1989 and 1992: Ebola RestonUSA and ItalyImported macaques from Philippines
1994: Ebola Côte d'Ivoire
Filoviridae Transmission Reservoir is UNKNOWN
Bats implicated with MarburgIntimate contactNosicomial transmission
Reuse of needles and syringesExposure to infectious tissues, excretions, and
hospital wastesAerosol transmission
Primates
Filoviridae EpidemiologyMarburg – Africa
Case fatality – 23-33%Ebola - Sudan, Zaire and Côte d'Ivoire –
AfricaCase fatality – 53-88%
Ebola – Reston – PhilippinesPattern of disease is UNKOWN
Filoviridae HumansMost severe hemorrhagic feverIncubation period: 4–10 daysAbrupt onset
Fever, chills, malaise, and myalgiaHemorrhage and DICDeath around day 7–11Painful recovery
Filoviridae AnimalsHemorrhagic fever
Same clinical course as humans
Ebola RestonHigh primate mortality -
~82%
FlaviviridaeDengue virus
Yellow Fever virusOmsk Hemorrhagic Fever virus
Kyassnur Forest Disease virus
Flaviviridae History1648 : Yellow Fever described17th–20th century
Yellow Fever and Dengue outbreaks1927: Yellow Fever virus isolated1943: Dengue virus isolated1947
Omsk Hemorrhagic Fever virus isolated1957: Kyasanur Forest virus isolated
Flaviviridae TransmissionArthropod vectorYellow Fever and Dengue viruses
Aedes aegyptiSylvatic cycleUrban cycle
Kasanur Forest VirusIxodid tick
Omsk Hemorrhagic Fever virusMuskrat urine, feces, or blood
Flaviviridae EpidemiologyYellow Fever Virus – Africa and Americas
Case fatality rate – variesDengue Virus – Asia, Africa, Australia, and
AmericasCase fatality rate – 1-10%
Kyasanur Forest virus – IndiaCase fatality rate – 3–5%
Omsk Hemorrhagic Fever virus – EuropeCase fatlity rate – 0.5–3%
Flaviviridae HumansYellow Fever
Incubation period – 3–6 daysShort remission
Dengue Hemorrhagic FeverIncubation period – 2–5 daysInfection with different serotype
Kyasanur Forest DiseaseOmsk Hemorrhagic Fever
Lasting sequela
Flaviviridae AnimalsYellow Fever virus
Non-human primates – varying clinical signsDengue virus
Non-human primates – No symptomsKyasanur Forest Disease Virus
Livestock – No symptomsOmsk Hemorrhagic Fever Virus
Rodents – No symptoms
Disease in Humans
Viral Hemorrhagic FeversInitial Symptoms
High feverHeadache Malaise WeaknessExhaustion
DizzinessMuscle achesJoint painNauseaNon-bloody
diarrhea
Prodormal illness lasting less than 1 week may include
Viral Hemorrhagic FeversClinical SignsFlushing,
conjunctival injection (“red eye”)
Pharyngitis
Rash
Edema
Hypotension
Shock
Mucous membrane bleeding
VHF Surveillance: Clinical Identification of Suspected Cases Clinical criteria:
Temperature 101 F(38.3 C) for <3 weeksSevere illness and no predisposing factors
for hemorrhagic manifestations 2 or more of the following:
Hemorrhagic or purple rash Epistaxis Hematemesis Hemoptysis Blood in stools Other hemorrhagic symptoms No established alternative diagnosis
JAMA 2002;287Adapted from WHO
DiagnosisSpecimens must be sent to
CDCU.S. Army Medical Research Institute of
Infectious Disease (USAMRIID) Serology PCR IHC Viral isolation Electron microscopy
TreatmentSupportive treatment Ribavirin
Not approved by FDAEffective in some individuals Arenaviridae and Bunyaviridae only
Convalescent-phase plasma Argentine HF, Bolivian HF and Ebola
Strict isolation of affected patients is required
Report to health authorities