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