A R B O V I R U S E S ( Ar thropod bo rne Viruses )

1. A R B O V I R U S E S ( Arthropod borne Viruses )

2. General Properties • Arbo viruses (Arthropod borne viruses) • Viruses of vertebrates biologically transmitted by haematophagus insect vectors. • They multiply in blood sucking insects and are transmitted to the vertebrate hosts. • Prevalent through out the world but are numerous in tropical than temperate climate. • About 500 viruses are there but in India 40 viruses have been detected. Many of them cause human disease.

3. Unaccepted taxonomically but useful biological concept. Named according to : Disease- yellow fever virus Place of isolation- Kyasanurforest disease (KFD) Local name of disease- Chikungunya Worldwide , Tropics India: > 40 Arbo viruses. Only > 10 cause disease.

4. “Hemotophagus” insect vectors . Vectors: Mosquitoes. Ticks. Phlebotomus Culicoide Less common Cimicidae

5. Placed in Toga viridae Flavi viridae. Bunya viridae Reo viridae Arena viridae. Filo viridae

6. Classification and structure A. Toga Viridae-alphavirus • Structure: Icosahedral, enveloped, 40-70 nm diameter, RNA

7. B. Flaviviridiae-Flavi virus

8. C. Bunya viridea

9. (D) Reo viridae • Structure: Helical, enveloped, RNA (ds RNA) • Members: • Colorado tick fever • African horse sickness • Palam, Kasba and Vellore viruses.

10. E)ARENA VIRIDAE Junin Machupo Lassa fever Lymphocytic choriomeningitis

11. F)FILOVIRIDAE Marburg Ebola

12. Mode of transmission: Insect Bite. Ingestion. Inhalation. Contact.

13. Pathogenicity • 3 main clinical entities • Fever with or without rashes • Hemorrhagic fevers • Encephalitis

14. Pathogenesis : Enters ‘ thru ‘ bite of insect Lymphatics Multiply RES (LN, liver, spleen , Endothelial cells of BV)  Blood stream (Viremia)  Target organs. CNSCapillary endotheliumLiver Multiplication Hemorrhagic Yellow fever Fever

15. Necrosis of Neurons, Perivascular cuffing of CBV, Sorrounded by microglia. Forms glial knots.  ( Encephalitides )

17. Laboratory diagnosis : 1. Virus isolation: Patient Insects Réservoir animal Specimens : Blood, CSF. (During first 1- 3 days of illness)

18. Identification methods in Laboratory: 1. Suckling mice: Encephalitis 2. Chick embryo: CAM , Yolk sac. 3. Tissue cultures Primary: Chick embryo fibroblasts. Continuous cell lines: Vero / HeLa. Insect tissue.

19. 4. Haemagglutination : Goose AND chick RBCs.  5. Serology : ELISA, CFT, HAI, Neutralization Test. 6. PCR technique : More sensitive. 7. Plaque reduction Neutralization Test (PRNT): More specific. “Antigenic” cross reactions among different groups.

20. Epidemiology : Zoonoses. Maintained in animals Except Dengue, O’ nyong nyong Asymptomatic in animals. Biting a viremic vertebrate . VectorsReservoir animal Human infection

21. Prevention : 1. Vector control. 2. Eradication of known reservoir. 3. Immunization : Vaccine Hyper immune Sérum

22. Togavirus : Enveloped, spherical, single stranded RNA viruses. Replicates in host cell cytoplasm. Alpha viruses All are mosquito borne HAI : Not specific Neutralisation test : More specific

23. Encephalitis Viruses :( America ) Eastern equine encephalitis Western equine encephalitis Venezuelan équine encephalitis Culex & Anophèles mosquitos. Wild birds are reservoirs.

24. Clinical manifestations: Sudden onset of fever Headache, Neck stiffness. Nausea, vomiting Disorientation Stupor or coma Convulsions in acute cases. Rigidity, weakness of limbs. Absent / irregular tendon reflexes.

25. CSF : Pleocytosis Protein, sugar levels are Normal. Identification of viral genome by PCR.

26. Febrile illness : With or without rash & arthralgia. CHIKUNGUNYA : 1952 Chikungunde = which folds up 1963 in India: As epidemics Calcutta, Madras Irregular outbreaks till 1973 in Maharashtra. Outbreak in 2006

27. Modes of transmission: 1.Transmitted exclusively by Aedes aegyptii. 2. Incubation period : 3 -12 days. 3 .Out breaks are common during the rainy season because of increased breading places for mosquito.

28. Clinical manifestations: Sudden onset of fever. Crippling Joint pains. Lymphadenopathy. Conjunctivitis. Maculopapular rash. Hemorrhagic manifestations rare.   Biphasic fever typically

29. Diagnosis: 1. Clinical history. 2. Antigen detection (by using Monovalent antisera) 3. An IgM capture ELISA more useful. 4.A rapid, micro-scale focus reduction neutralization test for rapid diagnosis. 5. RT- PCR assay developed by Malaysians.

30. No vaccine. No specific therapy.

31. O nyong, nyong: Uganda. (Africa) Anopheles mosquito Resembles Chikungunya

32. Semliki Forest virus :Uganda, Aedes mosquito. Sindbis Virus : In India since 1952. Ross river virus : Epidemic polyarthritis in Australia.

33. Flaviviruses: Mosquito borne and tick borne Encephalitis viruses : Reservoirs :Wild birds. Vector : Culex St. Louis encephalitis virus in USA West Nile virus: India (Karnataka) Dengue like disease Murray Valley encephalitis virus in Australia.

34. Japanese ‘B’ encephalitis: Japan 1871. Isolated in 1935. Summer and autumn.  Vector:Culex tritaeniorhychus Human infection is Dead-end event. Reservoir host : Herons. Amplifier Host : Pig.

35. Clinical Features: Abrupt onset of fever, Headache, Vomiting. Signs of encephalitis: Nuchal rigidity. Convulsions, confusion. Dysarthria, Tremors. Altered sensorium. Coma.

36. Pathogenesis : I phase : Viral multiplication in neuronal tissue. Seen in blood 3 days before CNS involvement. II phase: Major illness Viral multiplication in CNS Injury  Destruction  leads to

37. Lesions in basal structures & Cerebral cortex. Small hemorrhages. Perivascular cuffing. Meningeal infiltration Nerve damage. Patches of encephalomalacia. Spongiform appearance.

38. Lab diagnosis : Best infirst 1 - 3 days of illness Peripheral Smear: Neutrophilia CSF : Pleocytosis ( Lymphocytes ) Viral isolation.

39. Epidemiology : Usually Asymptomatic. 500 – 1000 unapparent infections /every case. General Mortality is 50% . In the old age 80%. Residual neurological damage : 50%

40. India : 1955 from Vellore. Children. Epidemics October and November. South India (AP ,TN ) only up to 1973. 1976 Dibrugarh. Gorakhpur Kolar

41. Prevention: 1. Mosquito control. 2. Vigilance on Piggeries. 3. Hyper immune serum: 1 - 2 days after infection. 4. Vaccine

42. Vaccines : 1.Formalin inactivated mouse Brain Vaccine. Nakayama strain Two doses : 2 weeks interval Booster : 6 – 12 months. Immunity is short lived. 2.Primary Baby Hamster kidney cell Live attenuated vaccine. JE strain SA 14-14-2 2 doses . 1 year apart 3. Vaccination of pigs

43. Hemorrhagic fevers : Dengue (Types 1 – 4) Aedes aegyptii Yellow fever Kyasanur Forest disease Ixodid ticks Omsk hemorrhagic Fever  

44. Hemorrhagic fever with systemic involvement : YELLOW FEVER : Yellow Jack in Africa Epidemics : Central America. Caribbean New York  Vector : Aedes aegyptii Extrinsic IP : 12 days Incubation period: 3 - 6 days.

45. Clinical Features:Acute fever, Chills, Backache. Nausea, Generalized malaise, Vomiting Slow pulse rate, temperature.  Jaundice, Albuminuria, Hemorrhagic manifestations on mucosa.

46. Histologically :  Liver : Fatty degeneration Mid zonal necrosis. Intracytoplasmic inclusions: Councilman bodies. Kidney :Focal Degeneration of tubular epithelium. Spleen & LN : Focal Degeneration. CNS : Intranuclear acidophilic inclusion bodies in Nerve, Glial cells-- “Torres bodies.

47. Epidemiology : Unapparent infections common. Not present in India . All ages between 15 – 45. Mild in infants than old age.   Monkey is reservoir. Wood cutters, Nut pickers, Road builders : Usual victims

48. Urban cycle and sylvatic cycle • Urban cycle • Humans – both definitive host & reservoir • Aedes aegypti – vector • Sylvatic cycle • Wild monkeys – reservoirs • Haemagogus spegazzinii & Aedes africanus

49. Control : 1. Mosquito control. 2. Vaccines : a. French neurotropic vaccine Administered : By scarification. Complication: Encephalitis.

50. B. 17D live attenuated vaccine. Chick embryo ( Yolk sac ). Asibi strain Mouse embryo. Route of Administration : Sub cutaneous 0.5 ml. Validity : 10 yrs. Administered from 9 months of age.