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Viral Hemorrhagic fever: The viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses that are caused by four different families of RNA viruses: 1- Arenaviridae. 2- Filoviridae. 3- Bunyaviridae. 4- Flaviviridae. All types of VHF are characterized by fever and bleeding disorders and all can progress to high fever, shock and death in many cases. Arenaviridae : Lassa virus , Junin virus, and Machupo virus (MACV) are associated with hemorrhagic fever. Epidemiology: Lassa virus: West Africa. Junin virus: Argentina. Machupo virus: Bolivia. Virology: -These are round, pleomorphic, and enveloped with a diameter of 120 nm. - Nucleocapsid with two single-stranded RNA circular segments. N Viral reservoir: Some Arenaviruses are zoonotic pathogens and are generally associated with rodents transmitted disease. Transmission: Humans could be infected through mucosal exposure to aerosols, or by direct contact of broken skin with the infectious material, derived from infected rodents. Ingestion of contaminated food, person-to-person contact is incriminated with transmission of the virus in some cases. n Pathogenesis and clinical picture: Incubation period: 10-14 days. The viruses infect macrophages, carried to blood vessels ; endothelial cells infection, T-cell mediated response, vascular damage. - Visceral hemorrhage. - Liver and spleen necrosis. - hemorrhage shock and cardiac damage. Death in 50% of cases. Filoviridae: Marburg virus and Ebola virus : Epidemiology : Endemic in Africa. 1-Marburg virus (Zimbabwe and Kenya). 2-Ebola virus (Sudan and Zaire). Reservoir: African green Monkeys and Wild Monkeys. Transmission: - Monkeys-Human contact, human-human contact, and unknown routes of transmission. -The first infection was first detected among Laboratory workers in Marburg, who had been exposed to tissue culture of cell line prepared from Monkeys. Virology: - Filoviruses have a Single stranded RNA, which encodes seven proteins Enveloped filamentous virus with Helical nucleocapsid measuring 800 to as long as 14000 nm. Pathogenesis and clinical picture: -Eosinophilic cytoplasmic inclusions are seen in cells infected with the virus. -These virus infection disseminated with blood stream to parenchymal cells of liver, spleen, lymph nodes, and lung. -Widespread hemorrhage causes edema and hypovolemic shock. -Liver function tests: SGPT, and alkaline phosphatase elevated. - Spleen destruction and lymph node enlargements. Bunyaviridae: -Super-group of at least 200 different viruses. -Most are Arboviruses. Virology: - Enveloped, spherical virion with a diameter of 90-100 nm. Single-stranded RNA nucleocapsids virus. N Transmission: Vector-born infection 1-Phlebovirus: 2-Nairovirus: 3-Bunyavirus: Sandfly , genus : Phlebotomus. Ticks. Mosquito. Vertebrate host: 1-Phlebovirus: 2-Nairovirus: 3-Bunyavirus: Sheep, cattle, others cattle, goats Rodents, small mammals, and birds. Disease: 1-Rift Valley fever ; hemorrhagic fever, encephalitis. 2-Crimean-Congo -Hemorrhagic fever. 3-California encephalitis. Pathogenesis and clinical picture: -Primary viremia; flu-like symptoms, infection of vascular endothelium and Macrophage of Reticuloendothelial system ; secondary viremia. 1-Vascular endothelial damage; leakage of plasma and erythrocytes, hemorrhagic fever. 2- Cerebral edema and encephalitis. 3- Kidney hemorrhagic necrosis. Crimean-Congo -Hemorrhagic fever caused by Nairovirus: N Flaviviridae: Flaviviruses are Arboviruses transmitted to man by vector (flavus (Latin term) means yellow). Two types of Flaviviridae cause Hemorrhagic fever (H.F), and Yellow fever: 1-Dengue virus: DHF: dengue H.F, and DSS: dengue shock syndrome. 2-Yellow fever virus: Yellow fever and Hepatitis. Vector: Mosquito of the genus Aedes. Host: Human and Monkeys.(Zoonosis). Distribution: Dengue fever: Worldwide, especially tropics. Yellow fever: Africa, and South America. Virology: - Positive Single-stranded RNA viruses. - Enveloped, Icosahedral nucleocapsid. - Size: 40-65 nm. - Glycoprotein spikes (adhesion of virus to tissue). -All Flaviviruses are serologically related: So Anti-Virus serotype antibodies could be used as prophylactic vaccine for others. Pathogenesis and clinical picture: - Biting of the host skin by vector ( Female Mosquito). , inoculation of small capillaries bloodstream by virus in Saliva. -The virus will be carried by dendritic cells throughout small capillaries to the target tissue. -Target tissue: 1-The endothelial cells of Capillaries. 2-The blood Macrophage and monocytes. -Blood phagocytes will transfer the microbe to the Reticuloendothelial system(RES). N - This will initiate Primary Viremia (fever, chill, headaches, and flu-like symptoms within 3-7 days). Secondary Viremia is associated with efficient replication of virus in RES. -This viremia can produce sufficient virus to infect: 1-Liver: Hepatitis, and Jaundice; yellow fever. 2-Brain: Encephalitis. 3-Vasculature and skin: Hemorrhage and shock. Pathogenesis of Flaviviruses: N