Viral Hemorrhagic

Fevers

• All types of Viral hemorrhagic fevers (VHF) are characterized by fever and bleeding disorders and can progress to shock and death in many cases.

• Viral hemorrhagic fevers (VHFs) are group of animal and human illnesses that are caused by four different RNA viral families:

oArenaviridae.

oBunyaviridae.

oFiloviridae.

oFlaviviridae.

• There is no specific treatment or vaccine for these viruses, except for yellow fever live attenuated vaccine.

Arenaviridae• Epidemiology:oLassa virus: West Africa.oJunin virus: Argentina.oMachupo virus: Bolivia.

• Virology: Round, enveloped viruses. Two segments SS RNA.

• Viral reservoir: some are zoonotic transmitted by rodents.

NTransmission:

Arenaviruses are shed in the urine and saliva of the infected rodents.

• Mucosal exposure to the aerosols e.g. inhalation.

• By direct contact of broken skin with the infectious material, from infected rodents.

• Ingestion of contaminated food.

• Person to person contact.

nPathogenesis and clinical picture:

The viruses infect the macrophages and the endothelial cells of the blood vessels, T-cell mediated response lead to vascular damage.o Visceral hemorrhages.o Liver and spleen necrosis.o Shock and cardiac damage. o Death in 50% of cases.

Bunyaviridae:• Large group of at least 200 different viruses.

• Most are Arboviruses: transmitted by arthropods.

• Virology: o Enveloped, spherical, segmented Ss RNA.o The most important specie are Rift Valley

Fever Virus (RVF) & Crimean Congo Hemorrhagic virus (CCHF).

o RVF was first reported in livestock in Kenya’s Rift Valley in the 1910s.

N

& Transmission: Vector-born infection

• Rift valley fever virus is transmitted by mosquitos, direct contact with infected animals and rarely between humans.

• CCHF is transmitted by Ticks from animals to human and from human to humans.

o Vertebrate host: domestic animals such as cattle, buffalo, sheep, goats, and camels.

o Outbreaks of RVF and CCHF were confirmed in southern & western borders of Saudi Arabia and both viruses are now endemic in KSA.

Pathogenesis and clinical picture: • Primary viremia: infection of vascular endothelium

and macrophages of RES. Multiply within the RES.• Secondary viremia:– Vascular endothelial damage; leakage of plasma

and erythrocytes, hemorrhagic fever. – Cerebral edema and encephalitis.– Renal hemorrhagic necrosis.

• Most rift valley fever cases are mild & self-limiting, febrile illness. However, some patients develop meningoencephalitis, vision loss or hemorrhagic fever

• CCHF cause more sever hemorrhages with mortality rate ≈ 30%.

RVF

Crimean-Congo -Hemorrhagic fever caused by Nairovirus: N

Filoviridae • Genus: Marburg virus and Ebola virus.• Virology: filamentous helical enveloped Ss RNA

viruses, encodes seven proteins. From the Latin "filum," meaning thread-like, based on their filamentous structure.

• Epidemiology: Endemic in Africa.

• Marburg virus (Kenya and Zimbabwe).

• Ebola virus (Sudan and Zaire).• Reservoir:

• They are zoonotic diseases (fruit bats??)*.

Transmission:

• The first infection was first detected among laboratory workers in Marburg, who had been exposed to tissue culture of cell line prepared from African green monkeys.

• Highly transmissible: the virus is present in the blood and all body fluids including urine, saliva, sweat, feces, vomit, breast milk, and semen.

• Bats-human contact, monkeys-human contact, human-human contact and unknown routes of transmission.

Pathogenesis and clinical picture: Vascular endothelial damage lead to widespread

hemorrhages, edema and hypovolemic shock. The virus is disseminated through blood stream to

the liver, spleen, lymph nodes (RES), and lungs. Eosinophilic cytoplasmic inclusions are seen in

the infected cells. Liver function tests: SGPT (ALT) and AST are

elevated*, and alkaline phosphatase is mildly elevated.

Spleen destruction and lymph node enlargements. Mortality rate: 50% up to 90%.

Hemorrhagic rash

Ebola Outbreak in Africa (March 2014-2015)• The largest outbreak of Ebola virus. On17th

October/2014, the cumulative number of suspected cases was 9216, including 4555 deaths (case-fatality rate 55 percent).

• On 4th March 2015 24000 cases and 10000 deaths.• On 26th of April: 26312 cases and 10900 deaths.• A Saudi citizen was suspected to suffer from

Ebola infection but postmortem samples were negative.

Flaviviridae:o Flaviviruses are Arboviruses (transmitted to

man by arthropods). o Flavus means yellow (jaundice).o Three genera cause hemorrhagic fever:

• Dengue virus: Dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS).

• Yellow fever virus: yellow fever and hepatic dysfunction.

• Alkhumra virus*: alkhumra hemorrhagic fever. Was first isolated in KSA in 1995.

Virology:• Enveloped, icosahedral nucleocapsid, positive Ss RNA

viruses. Has glycoprotein spikes (adhesion of virus to tissue). All Flaviviruses are serologically related.

• Vector: Aedes aegypti female mosquito : Yellow Fever virus & Dengue virus. Tick: Alkhumra virus.

• Host: Human and monkeys (Zoonosis).• Distribution:

• Dengue fever: Worldwide, especially tropics. Outbreaks had occurred in KSA.

• Yellow fever: Africa, and South America.

• Alkhumra virus: KSA and Egypt.

Aedes aegypti

Aedes aegypti

Pathogenesis and clinical picture:• The target tissues:• The endothelial cells of the capillaries.• The macrophage and monocytes which will

transfer the virus to the reticuloendothelial system (RES).

• The vector bite host skin and inoculate the virus with the saliva into the small capillaries.

• Adhesion to the cells by the glycoprotein spikes.

• The virus is then carried through the small capillaries by the dendritic cells to other organs.

N• This will initiate primary viremia (fever, chill, headaches, and flu-like symptoms within 3-7 days).

• Secondary viremia: after efficient replication of the virus in RES these viruses will infect:o Liver: hepatitis, and jaundice (yellow fever).o Brain: encephalitis.o Vasculature and skin: hemorrhage and

shock. o Kidneys: oliguria and albuminuria.

Pathogenesis of Flaviviruses:N

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