Japanese B Encephalitis

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Japanese B Encephalitis

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Japanese B Encephalitis

  1. 1. Dr.T.V.Rao MDDr.T.V.Rao MD 1
  2. 2.  Flaviviridae ◦ Flavivirus The name is derived from the Latin „flavus‟ ◦ Flavus means “yellow”  Refers to yellow fever virus Enveloped Single stranded RNA virus Morphology not well defined Center for Food Security and Public Health Iowa State University - 2007
  3. 3.  Japanese B encephalitis virus is Spherical, 40 – 60 nm in diameter Contain a positive sense Single stranded RNA, 11 kb in size RNA genome is infectious Several viruses in this group are related. Dr.T.V.Rao MD 3
  4. 4.  Japanese encephalitis ( previously known as Japanese B encephalitis is a disease caused by the mosquito- borne Japanese encephalitis virus. The Japanese encephalitis virus is a virus from the family Flaviviridae. Domestic pigs and wild birds are reservoirs of the virus; transmission to humans may occur Dr.T.V.Rao MD 4
  5. 5.  The outer envelope is formed by envelope (E) protein and is the protective antigen. It aids in entry of the virus to the inside of the cell. The genome also encodes several non-structural proteins also (NS1,NS2a,NS2b,NS3,N 4a,NS4b,NS5). NS1 is produced as secretary form also. NS3 is a putative helicase, and NS5 is the viral Dr.T.V.Rao MD 5
  6. 6.  1870s: Japan ◦ “Summer encephalitis” epidemics 1924: Great epidemic in Japan ◦ 6,125 human cases; 3,797 deaths 1935: First isolated ◦ From a fatal human encephalitis case 1938: Isolated from Culex tritaeniorhynchus Center for Food Security and Public Health Iowa State University - 2007
  7. 7.  1940-1978 ◦ Disease spread with epidemics in China, Korea, and India 1983: Immunization in South Korea ◦ Started as early as age 3 ◦ Endemic areas started earlier 1983-1987: Vaccine available in U.S. on investigational basis Center for Food Security and Public Health Iowa State University - 2007
  8. 8.  Viruses (most common) ◦ More than 100 different viruses can cause acute encephalitis ◦ Seasonal and geographic distribution can help narrow differential diagnosis ◦ Examples of common viruses:  Arbovirus  Enter viruses  Mumps, Varicella  Herpes simplex virus  Influenza Rabies *Note: A large number of reported cases of encephalitis are due to an unspecified cause
  9. 9.  First discovered and originally restricted to Japan. Now large scale epidemics occur in China, India and other parts of Asia. Flavivirus, transmitted by culex mosquitoes. The virus is maintained in nature in a transmission cycle involving mosquitoes, birds and pigs. Most human infections are subclinical: the in apparent to clinical cases is 300:1 In clinical cases, a life-threatening encephalitis occurs. The disease is usually diagnosed by serology. No specific therapy is available. Since Culex has a flight range of 20km, all local control measures will fail. An effective vaccine is available.
  10. 10. Infection is caused by a flavivirus, a single stranded RNA virus. It is transmitted by the bite of the Culex tritaeniorhynchus mosquito. The virus multiplies at the site of the bite and in regional lymph nodes before viraemia develops. Viraemia can lead to inflammatory changes in the heart, lungs, liver, and reticuloendothelial system. Dr.T.V.Rao MD 10
  11. 11.  Japanese encephalitis is the leading cause of viral encephalitis in Asia, with 30,000– 50,000 cases reported annually. Case-fatality rates range from 0.3% to 60% and depends on the population and on age. Dr.T.V.Rao MD 11
  12. 12. Dr.T.V.Rao MD 13
  13. 13.  Vector-borne disease Enzootic cycle ◦ Mosquitoes: Culex species  Culex tritaeniorhynchus ◦ Reservoir/Amplifying hosts  Pigs, bats  Ardeid (wading) birds  Possibly reptiles and amphibians ◦ Incidental hosts  Horses, humans, others Center for Food Security and Public Health Iowa State University - 2007
  14. 14.  Culex tritaeniorhynchus a rural Mosquito that breeds in rice fields, is the principle vector. In India in 1955 the virus were isolated from Culex vishnui mosquitoes in Vellore region in Tamil Nadu Dr.T.V.Rao MD 15
  15. 15.  Most important global cause of arboviral encephalitis with > 50,000 cases and 15,000 deaths reported each year.  Only about 1 in 250 JE infections result in symptomatic illness.  Primarily affects children 1 to 15 years of age.• If unrecognized, mortality is up to 30% with half of  Incubation period is 5 to survivors sustain severe neurological sequelae. 14 days.
  16. 16.  Leading cause of viral encephalitis in Asia with 30-50,000 cases reported annually Fewer than 1 case/year in U.S. civilians and military personnel travelling to and living in Asia Rare outbreaks in U.S. territories in Western Pacific Dr.T.V.Rao MD 17
  17. 17. Dr.T.V.Rao MD 18
  18. 18. Dr.T.V.Rao MD 19
  19. 19.  Herons act as reservoir hosts and pigs as amplifier hosts. Human infection is a tangential „dead end‟ and infections are spread when the infected mosquitoes reach high density. Dr.T.V.Rao MD 20
  20. 20. Pathogenesis of Flavivirus Infections Subcutaneous injectionExtraneural Tissues Connective tissue Striated muscle Regional lymph nodes Pancreas Adrenal Smooth muscle Efferent lymphatics Thoracic duct Reticuloendothelial Plasma Viremia Humoral antibody cell clearance Vascular endothelium Olfactory epithelium ? ? Neural Parenchyma CNS antibody Neurons, Glia(?) lymphocytes, macrophage Cellular dysfunction Cellular lysis Fields Virology, Vol 1, Fourth Edition. Lippincott-Williams & Wilkins (Philadelphia), pp Inflammation 1057, 2001
  21. 21.  The incubation period is 6 to 16 days. There is a prodrome of fever, headache, nausea, diarrhoea, vomiting, and myalgia, which may last for several days. This may be followed by a spectrum of neurological disease ranging from mild confusion, to agitation, to overt coma. Two thirds of patients have seizures. It is more common in children, while headache and meningism are more common in adults. Dr.T.V.Rao MD 22
  22. 22. Common symptoms of encephalitis Lethargy Sudden fever Headache Change in consciousness Irritability or restlessness Tremors or Vomiting and convulsions diarrhea
  23. 23.  Tremor or other involuntary movements are common. Mutism has been described as a presenting symptom. So has a syndrome of acute flaccid paralysis. Fever resolves by the second week, and choreoathetosis or extra pyramidal symptoms develop as the other neurological Dr.T.V.Rao MD 24
  24. 24.  The isolation of virus from Blood, CSF, or tissues. Detection of Arbovirus specific RNA in blood,CSF, or Tissue However very few reference laboratories can perform the isolation in view of the biosafety considerations Dr.T.V.Rao MD 25
  25. 25.  IgM capture enzyme-linked immunoassay (ELISA) of serum or CSF is the standard diagnostic test. Sensitivity is nearly 100% when both serum and CSF are tested. False-negatives may result if the samples are tested too early, as in the first week of illness. New IgM dot enzyme immunoassays for CSF and serum are portable and simple tests that can be used in the field. Compared with ELISA as the gold standard, the sensitivity and specificity are around 98 and 99% respectively. Dr.T.V.Rao MD 26
  26. 26.  Viral RNA is extracted from serum or from suspected tissues of the patients or mosquito homogenates. The product is amplified by RTPCR and the products analyzed by restriction digestion and determined by nucleotide sequence of PCR product. The identified sequence is compared with nucleotide sequence found in Gene bank or other data bases Dr.T.V.Rao MD 27
  27. 27.  There is some cross- reactivity with other flavivirus and from Japanese encephalitis and yellow Dr.T.V.Rao MD 28
  28. 28.  Japanese Encephalitis B Vaccine has been produced since 1992. The vaccine is effective but not without risks and the substantial risks of the disease and the risks of the vaccine have to be balanced, especially for stays of brief duration. These are discussed more fully in the article on that subject. As with malaria, prophylaxis must be supplemented by techniques to avoid being bitten by mosquitoes. Dr.T.V.Rao MD 29
  29. 29.  Preventive measures include mosquito control and locating piggeries away from human dwellings A formalin inactivated mouse brain vaccine using the Nakayama strain has been employed in human immunization in Japan – Two doses at two week‟s interval followed by a booster 6 – 12 months later constitute a full course. However the immunity was short lived Dr.T.V.Rao MD 30
  30. 30.  Two vaccines are manufactured and distributed exclusively in People‟s Republic of China ◦ Inactivated vaccine grown in primary hamster kidney cells ◦ Live attenuated vaccine (SA14-14-2) grown in hamster kidney cells The third is manufactured in Japan and distributed abroad by arrangement with Sanofi-Pasteur ◦ Licensed as JE-VAXR and is the only FDA approved vaccine for use in the U.S. ◦ Has been in wide use worldwide since the 1960‟s ◦ Three subcutaneous injections over a month with
  31. 31.  Live attenuated vaccine ◦ Used in equine and swine ◦ Successful for reducing incidence Inactivated vaccine (JE-VAX)  Used for humans  Japan, Korea, Taiwan, India, Thailand  Used for endemic or epidemic areas ◦ Recommended for travelers  Visiting endemic areas for > 30 days Center for Food Security and Public Health Iowa State University - 2007
  32. 32.  A live attenuated vaccine has been developed in China from JE strain SA 14-14-2, passed through weanling mice The vaccine is produced in primary bay hamster kidney cells. Administered in two doses, one year apart, the vaccine has been reportedly effective in preventing clinical disease Dr.T.V.Rao MD 33
  33. 33.  Side effects “Generally inconsequential.” Local tenderness or mild systemic symptoms in 10- 30% - Field’s virology No neurologic events in Japanese surveillance Infrequent allergic reactions in adult travelers ◦ Urticaria, angioedema, bronchospasm, erythema nodosum and e. multiforme Incidence varies in different reports: 2/1000 to 1% 14,000 US Marines, 11 pruritus, 26 urticaria ◦ History of urticaria after hymenoptera envenomation or other provocations caused a relative risk increase of 9.1 ◦ None of the reactions were severe or life threatening Case control study in Australia identified increased reaction risk if excessive alcohol consumption in 48 hours after vaccination (p=
  34. 34.  Vector control ◦ Eliminate mosquito breeding areas ◦ Adult and larvae control Vaccination ◦ Equine and swine ◦ Humans Personal protective measures ◦ Avoid prime mosquito hours ◦ Use of repellants containing DEET Center for Food Security and Public Health Iowa State University - 2007
  35. 35.  Facilitate implementation of attenuated vaccine in unvaccinated populations in endemic areas Develop improved vaccines Identify risk factors for progression to symptomatic encephalitis and viral persistence Describe clinical features of JE in AIDS and determine its potential as an opportunistic infection Dr.T.V.Rao MD 36
  36. 36. Dr.T.V.Rao MD 37
  37. 37.  Createdby Dr.T.V.Rao MD for Medical and Paramedical Professionals in Developing World  Email  doctortvrao@gmail.com Dr.T.V.Rao MD 38

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