Hemorrhagic fever viruses

ByDr. Marwa Salah

Hemorrhagic fever viruses

Arboviruses:• Dengue fever virus (Flaviviridae)• Rift Valley fever virus (Bunyaviridae)• Yellow fever virus (Flaviviridae)

Roboviruses:• Hantaan virus (Bunyaviridae)• Marburg & Ebola viruses (Filoviridae)• Lassa fever virus (Arenaviridae)• Junin & Muchupo (Arenaviridae)

• OHF virus (OMSK hemorrhagic fever) (Flaviviridae)

• KFD virus (Kyasanur forest disease) (Flaviviridae)

• CCHF virus (Crimean-Congohemorragic fever) (Bunyaviridae

Arboviruses & Roboviruses• “Arbo” is derived from arthropod-born viruses

• they do not cause disease in arthropods.

• They are enveloped (sensitive) viruses, they need intimate contact or insect bite to be transmitted.

• No man to man transmission except in yellow fever and dengue.

• Various animal, rodents and birds are reservoirs of infection.

• Roboviruses are not transmitted by arthropods but maintained within the rodent reservoir.

• Man to man transmission occurs.

Dengue feverFlaviviridae, Arbovirus,

icosahedral enveloped (+) ss RNA

Replication

• In the cytoplasm

• Released by budding

Replication of Dengue virus

Transmission & Pathogenesis of Dengue fever• Four serotypes

• Reservoir

probably monkey

• Vector

mosquito; Aedes egypti

• High Viremia, so man to man transmission occurs

Female Aedes aegypti mosquito

• I.P.: 5-6 daysEpidemiology• Dengue fever 1st reported epidemics in 1779-80• In Africa, South East Asia & South America• KSA in 2006, 1544 cases (461 children <14 yrs.)

Clinical forms1. Asymptomatic2. Classic Dengue Fever (Break bone fever ): fever,

headache, myalgia, arthralgia, nausea, vomiting, macular rash

3. Dengue Hemorrhagic fever4. Dengue Shock Syndrome

Dengue hemorrhagic fever• Mainly in children• Acute onset of fever, hematemesis, melena

renal involvement and shock with 50% mortality

• It needs biosafety level 2

A large subcutaneous hemorrhage on upper arm in Patient with dengue hemorrhagic fever

Hemorrhagic conjunctivitis

Pathogenesis of Dengue HF

• Primary infection with one serotype produces antibodies specific to that serotype.

• Secondary infection with another serotype is followed by formation of immune complexes between the second serotype and antibodies to the first one.

• These antibodies not only fail to neutralize the virus but also enhances its ability to infect higher number of monocytes & release of cytokines, & vasoactive mediators leading to DIC, Hemorrhage, shock & death.

Pathogenesis of Dengue HF

Rift Valley fever• Bunyaviridae: Helical

enveloped (-) ss RNA segmented

• Single serotype• Replication• Transmission:1. mosquito bite2. contact with tissues,

blood or body fluids of infected animals

Epidemiology• In Africa, Yemen & KSA• 1st reported in Kenya 1931• KSA in 2000-01, 77 died• Epizootics in sheep & cattle in Sudan, Egypt &

South Africa. • In 1977, an outbreak occurred in Egypt with

many deaths in animals and 600 human deaths

Pathogenesis of RFV infection• Virus spreads to regional lymph nodes, liver and

spleen & infects tissue macrophages • Soluble mediators & cytokines recruit more cells , to

be infected leading to virus amplification Infection of hepatocytes impairs synthesis of

clotting factors Reduced synthesis of albumin by hepatocytes

reduced plasma osmotic pressure causing edema. Infected adrenal cortical cells impairs secretion of

steroid-synthesizing enzymes leading to hypotension and hypovolemia.

C/P: 1. Mild: most cases, inapparent or flu-like e.g.

fever, headache, myalgia, nausea, vomiting. Recovery in 4-7 days

2. Severe:• i. Ocular retinopathy• ii. Meningoencephalitis• iii. Hemorrhagic fever It requires Biosafety level 3

Laboratory Diagnosis of HFVs

• Direct virus isolation on tissue culture.• Detection of viral antigens or antibody by

immunofluorescence.• Detection of viral nucleic acid by PCR.