1. Hemorrhagic fever viruses By Dr. Marwa Salah

2. 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)

3. OHF virus (OMSK hemorrhagic fever) (Flaviviridae) KFD virus (Kyasanur forest disease) (Flaviviridae) CCHF virus (Crimean-Congohemorragic fever) (Bunyaviridae

4. 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.

6. Roboviruses are not transmitted by arthropods but maintained within the rodent reservoir. Man to man transmission occurs.

7. Dengue fever  Flaviviridae, Arbovirus, icosahedral enveloped (+) ss RNA  Replication In the cytoplasm Released by budding

8. Replication of Dengue virus

9. 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

11. I.P.: 5-6 days Epidemiology 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 forms 1.Asymptomatic 2.Classic Dengue Fever (Break bone fever ): fever, headache, myalgia, arthralgia, nausea, vomiting, macular rash 3.Dengue Hemorrhagic fever 4.Dengue Shock Syndrome

13. Dengue hemorrhagic fever Mainly in children Acute onset of fever, hematemesis, melena renal involvement and shock with 50% mortality It needs biosafety level 2

14. A large subcutaneous hemorrhage on upper arm in Patient with dengue hemorrhagic fever Hemorrhagic conjunctivitis

15. 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.

16. Pathogenesis of Dengue HF

17. Rift Valley fever Bunyaviridae: Helical enveloped (-) ss RNA segmented Single serotype Replication Transmission: 1.mosquito bite 2.contact with tissues, blood or body fluids of infected animals

18. 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

19. 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.

20. 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

21. 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.