Disease in animals caused by Filoviridae _Nabaraj.pptx

Disease in animals caused by Filoviridae

1. Filoviridae and Bunyaviridae Nabaraj Shrestha

2. Filoviridae

3. Filoviridae The family Filoviridae  is the taxonomic home which consists of two genus (Ebola virus and Marburg virus). Both viruses, and some of their lesser known relatives, cause severe disease in humans and nonhuman primates in the form of  Viral Hemorrhagic Fevers. Both genus are serologically, biochemically, and genetically distinct.  All filoviruses are WHO Risk Group 4 Pathogens ( requiring Biosafety Level 4 equivalent containment).

4. Filoviridae History 1967: Marburg virus European laboratory workers 1976: Ebola virus Ebola Zaire Ebola Sudan 1989 and 1992: Ebola Reston USA and Italy Imported macaques from Philippines 1994: Ebola Côte d'Ivoire

5. Filoviridae Taxonomy Species: Lake Victoria Marburg Virus Genus Species: Ivory Coast Ebola Virus Reston Ebola Virus Sudan Ebola Virus Zaire Virus

6. Filoviridae Properties Virions are pleomorphic, appearing as long filamentous forms and other shapes. Virions have a uniform diameter of 80 nm and vary greatly in length (unit nucleocapsid lengths of about 800 nm for Marburg and 1000 nm for Ebola virus ) Virions are composed of a lipid envelope covered with peplomers surrounding a helically wound nucleocapsid The genome is composed of a single molecule of negative-sense single-stranded RNA, 19.1 kb in size, the largest of all negative-sense RNA viruses.

7. Filoviridae Properties (Summary) Genome Linear Single stranded RNA Non-segmented Negative sense Capsid Enveloped Helical symmetry Long, filamentous shape (hence “filo”)

8. Filoviridae Transmission These viruses may be endemic in bats or wild monkeys and can be spread to humans and between humans. Contact with the animal reservoir or direct contact with infected blood or secretions can spread the disease. These viruses have been transmitted by accidental injection and through the use of contaminated syringes. Health care workers tending the sick and monkey handlers may be at risk.

9. Filoviridae Transmission (Summary) Reservoir is UNKNOWN Bats implicated with Marburg Intimate contact Nosicomial transmission Reuse of needles and syringes Exposure to infectious tissues, excretions, and hospital wastes Aerosol transmission Primates

10. Filoviridae Epidemiology Marburg – Africa Case fatality – 23-33% Ebola - Sudan, Zaire and Côte d'Ivoire – Africa Case fatality – 53-88% Ebola – Reston – Philippines Pattern of disease is UNKOWN

11. Filoviridae Humans (Clinical Features) Incubation period: 4–10 days (Extreme range 2-21 days) Abrupt onset Fever, chills, frontal headache, malaise, and myalgia Profound leukopenia, bradycardia, conjunctivitis and macropapular rash. Following 2-3 days: pharyngitis, nausea, vomiting, prostration and bleeding ( petechiae , ecchymoses , uncontrolled bleeding from venipuncture sites and melena - Most severe hemorrhagic fever) Abortion in pregnant women. Death around day 6–9 days after onset of clinical disease. Case Fatality Rate: 80-90%.

12. Susceptible to non human primates (Gorillas, monkeys). Incubation period is 3-6 days. Hemorrhagic fever Same clinical course as humans Filoviridae Animals (Clinical Features)

13. 2014 Ebola Virus Disease (EVD) outbreak in West Africa More than 28,000 people were affected, with more than 11,000 deaths. I ncubation period of Ebola virus disease (EVD) varies from 2 to 21 days. Contact with blood or bodily fluids of a person infected with the Ebola virus. Contact with or handling of wild animals, alive or dead or their raw or undercooked meat. Having sexual intercourse with a sick person or a person recovering from EVD for at least 7 weeks. Having contact with any object, such as needles, that has been contaminated with blood or bodily fluids.

14. Pathogenesis Filovirus replicate in macrophages, dendritic cells and endothelium. Macrophages are a principal site of virus replication and produce a host of pro-inflammatory cytokines that exacerbate systemic disease.

15. Pathogenesis Viral proteins VP35, VP24 (for ebolaviruses ), and VP40 (for marburgviruses ) are strong antagonists of the type I interferon response, directly targeting RIG-I and interferon signaling, an effect that cancels the host response that would normally limit virus replication. Lymphocytes are not sites of virus replication. But infection is associated with extensive lymphoid depletion and profound peripheral lymphopenia . Filovirus infection of macrophages, monocytes, and dendrititc cells leads to dissemination of virus throughout the body.

16. Pathogenesis Also filovirus infection causes secretion of a variety of inflammatory mediators such as tissue necrosis factor and interlukin-8 , nitric oxide that have potentially profound effects on vascular permeability and coagulation. These vascular effects contribute to hypovolemic shock and multiorgan failure. Inravascular coagulation will cause hepatic necrosis and reduced synthesis of clotting factors.

17. Model of Ebolavirus pathogenesis

18. Pathology Causes extensive necrosis within target organs, especially the liver. Focal hepatic necrosis is accompanied by the formation of eosinophilic bodies—resembling the Councilman bodies of yellow fever—and smaller, basophilic inclusions; both types can also be seen in most other tissues. Fatty changes within hepatocytes, so characteristic of yellow fever, are, however, slight. Mononuclear cells accumulate in the peripheral spaces.

19. Pathology High concentrations of virus are seen by electron microscopy in the zones of necrosis. Necrotic lesions are also found in the pancreas, gonads, adrenals, hypophysis , thyroid, kidney and skin. Severe congestion and stasis are obvious in the spleen . Early and profound leukopenia, followed by a dramatic neutrophilia with a left shift.

20. Diagnosis Detection of viral antigen in tissues through Immunofluorescence or antigen capture ELISA or RT-PCR. Lateral flow rapid diagnostic tests. Immunoglobulin M capture ELISA and G ELISA.

21. Immunity, Prevention and Control Recombinant, vectored vaccines (But lacks cross protection between Marburg and Ebola viruses and between different species of Ebolavirus ). Restriction in consumption of bush meat, including bats and diseased or dead nonhuman primates. Stop importation of wild monkeys (Basically for medical research and vaccine production). Screening for the presence of filovirus infection in workers.

22. Conclusion Wild monkeys are an important source for the introduction of filoviruses . Quarantine of imported nonhuman primates and professional handling of animals are essential to prevent introduction of these agents into humans. Although the transmission of filoviruses occurred through monkeys, they are not considered to be the natural reservoir of the virus. Aerosal transmission cycle in bats or other mammals plays some role in the natural history of filoviruses .

23. Conclusion Several factors allowing the emergence/reemergence of hemorrhagic fever caused by filoviruses : international commerce and jet travel; interhuman spread during normal social transactions or sexual intercourse; limited experience in diagnosis and case management; the import of nonhuman primates ; an unknown reservoir; and finally

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