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Arboviral Diseases

Arboviral Diseases. Stephen J. Thomas, MD Director, Viral Diseases Branch Walter Reed Army Institute of Research JUL 2013 Paul B. Keiser, Feb 2014. UNCLASSIFIED. What is a virus?.

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Arboviral Diseases

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  1. Arboviral Diseases Stephen J. Thomas, MD Director, Viral Diseases Branch Walter Reed Army Institute of Research JUL 2013 Paul B. Keiser, Feb 2014 UNCLASSIFIED

  2. What is a virus? • Defined: A sub-cellular agent consisting of a core of nucleic acid surrounded by a protein coat that must use the metabolic machinery of a living host to replicate and produce more viral particles. • Viruses are known to infect almost all organisms, including bacteria, fungi, plants, insects, and vertebrates. • 20-300 nm in diameter; a “filterable” agent.

  3. What is an arbovirus? • Arboviruses are Arthropod-borne. • They are transmitted to vertebrates by hematophagous (blood feeding) arthropod vectors • mosquitoes • other biting flies • ticks

  4. Arboviruses • Occur in nearly all parts of the world. • Over 500 distinct viruses, ~100 causing human infections • Nearly all arboviruses fall into one of 4 families: • Flaviviridae • Togaviridae • Bunyaviridae • Reoviridae

  5. Classification Scheme Source: Flint et al. 2000. Principles of virology Introduction to Virology

  6. Classification Scheme Nucleic acid----------------- Symmetry of capsid------- Naked or enveloped------ Genome architecture---- Baltimore class------------ Family name--------------- Virion polymerase-------- Virion diam. (nm)--------- Genome size (total in kb)- Properties Classification criteria Source: Flint et al. 2000. Principles of virology

  7. Factors in Arboviral Disease Virus Vector Ecology Host Reservoir Ecology

  8. Arbovirus Features • Able to replicate in both the arthropod vector and the vertebrate (bird or animal) host. • Transmission to vertebrate occurs as the vector regurgitates while taking its blood meal. • Viremia must reach high enough levels in the host to continue the cycle before reduced by the host immune system. • Able to infect multiple species of animals and birds, but usually limited to a specific arthropod vector.

  9. Arbovirus Features • In the tropics, transmission is year-round. • In temperate climates, transmission to vertebrates is seasonal and the virus requires an overwintering strategy. • Transovarial transmission in the vector. • Migration with avian host. • Disease is usually more severe in newly exposed hosts and species. • Deforestation • Irrigation • Urbanizatiom • Travel

  10. How do you determine if a vector is involved? • Four criteria establish vector competence: • Isolation of the disease-producing agent from wild-caught specimens • Demonstration of its ability to become infected by feeding upon a viremic host • Demonstration of its ability to transmit by bite • Field evidence confirming association of the infected arthropod with the vertebrate population in which the infection is occurring.

  11. Systemic Febrile Illness Chikungunya, O’nyong-nyong, Ross River, Dengue, Zika Fever with Arthritis Chikungunya, Ross River, O’nyong-nyong Encephalitis JE, WNV, TBE, EEE, WEE Hemorrhagic Fever Yellow Fever, Dengue, Rift Valley Fever, Chikungunya, CCHF Arboviral diseases: clinical syndromes

  12. Arboviruses • Family Flaviviridae • Genus Flavivirus • Tick-borne viruses • Mammalian tick-borne virus group • Kyasanur forest disease virus (KFDV) • Tick-borne encephalitis virus (TBEV) • Mosquito-borne viruses • Dengue virus group • Dengue virus (DENV) • Japanese encephalitis virus group • Japanese encephalitis virus (JEV) • Murray Valley encephalitis virus (MVEV) • St. Louis encephalitis virus (SLEV) • West Nile virus (WNV) • Yellow fever virus group • Yellow fever virus (YFV) • Zika Virus Dengue

  13. Threat Assessment – ID Risk

  14. Japanese Encephalitis (JEV) • Most common cause of viral encephalitis worldwide • 160,000 reported cases 1966 • 16,000 reported in 1996, decline is due to • Large-scale vaccination programs in Thailand • Urbanization in Japan, Taiwan, ROK • Annual est> 50K • 2.5 cases/10,000 population at risk • Primarily a disease of children • Naïve adults at risk -- i.e., travelers • Most infections are subclinical/self-limited • Clinical cases have high mortality, morbidity • CFR ~25 -30% • Long-term disability 45 - 50%

  15. JEV - Clinical Findings • Incubation period 4 – 14 days • Sudden onset fever, chills and aches • Lethargy, HA, meningismus, N/V • Acute Flaccid Paralysis • Rapid onset paralysis despite normal consciousness • Weakness legs > arms, asymmetric • Flaccid paralysis also occurs in 5%-20% of comatose patients with "classic" JE • Course • Occasionally fulminant • Short prodrome, deep coma, respiratory depression, posturing, death • Usually, improvement over ~ 1 week • Neuropsychiatric sequelae resolves over years or is permanent

  16. Vector: Culex mosquitoes Culex tritaeniorhynchus Breeds in marshes, rice paddies Night-biting Zoonotic amplification Domestic pigs Migratory waterfowl Domestic waterfowl? Ducks Seasonal/climate factors Summertime / post-rainy season Increased vector number, feeding behaviors Increased viral replication JEV - Transmission

  17. Vector control – difficult in endemic regions Impractical, historically ineffective Twilight-biting, marsh-breeding mosquitoes Reservoir control – difficult in endemic regions Swine Segregation impractical vaccination expensive Other potential reservoirs Vaccination Mass pediatric vaccinations Apparently highly effective JEV - Prevention

  18. West Nile Virus • Widely distributed; • Infects >300 bird species • Infects >60 mosquito species • Transmission by blood product transfusion documented before routine screening. • Most infections are sub-clinical/self-limited. • 1:5 develop fever • 1:150 develop CNS disease • Incidence increases with age.

  19. Yellow Fever

  20. Yellow Fever Virus • Molecular sequencing • 1 serotype, 5 genotypes • Phylogenetic analyses • Evolved over 3000 yrs • YF virus originated in Africa • Divided into West and East African lineages • West African lineage • Imported into S. America and New World

  21. Urban, sylvatic and savannah cycles Non-human primates can be a reservoir. Aedes spp.Haemagogus spp. (Africa) (Americas) Vertical transmission, infected ova survival Yellow Fever Transmission

  22. Yellow Fever – South America

  23. Yellow Fever - Africa

  24. Incubation of 3 to 6 days Clinical spectrum of disease Mild, febrile illness → Fatal VHF Severe YF Fever, Chills, Headache Lumbosacral pain, Myalgia Anorexia, Nausea, Vomiting Gingival hemorrhages, Epistaxes Bradycardia despite ↑ temperature (Faget's sign) Yellow Fever: Acute Period

  25. Symptoms for ~ 3 days (period of viremia) Defervescence and improvement (~ 24 hours) Fever and symptoms return Vomiting, Epigastric pain, Prostration, Jaundice Yellow Fever: Acute Period

  26. Hemorrhage “Coffee-ground” hematemesis (vomito negro) Melena, Petechiae, Ecchymoses Intravascular volume depletion Liver damage/jaundice Renal failure ↑ Albuminuria ↓ Urine output (UO) Yellow Fever: Hemorrhagic Phase

  27. Death (in 20% to 50% of severe cases) 7th to 10th day of illness ↑ jaundice, hemorrhages, ↑ HR, ↓ BP, ↓ UO, ↓ Temp. Agitated delirium, Intractable hiccups, Stupor, Coma Laboratory findings ↓ WBC, ↓Plts ↑ Bilirubin, ↑ Serum transaminase levels ↑ PT and PTT < synthesis of clotting factors + > consumption ST-T wave changes in the electrocardiogram. Yellow Fever: Hemorrhagic Phase

  28. Prolonged convalescence Profound asthenia lasting 1 to 2 weeks Late death End of convalescence Weeks after recovery from the acute illness Rare phenomenon Attributed to cardiac complications or renal failure Elevations of serum transaminase levels Persist for at least 2 months after onset of acute illness Yellow Fever: Convalescent Phase

  29. 20-50%

  30. Yellow Fever: Diagnosis • Clinical Diagnosis • Exposure history • Advanced Diagnostics: • Virus Isolation (culture) • Rapid Diagnostics • PCR • may not be positive late in disease • Antibody or Antigen detection (ELISA) • IgM for acute phase, coupled with convalescent antibodies (IgM/IgG) • Neutralization Ab are more specific for YF

  31. Yellow Fever: Treatment Overview • Supportive Care -- no specific therapy • Maintain nutrition and prevent hypoglycemia • NG tube to prevent gastric distention • Treatment of hypotension (IVF, pressors) • Supplemental oxygen • Correction of bleeding abnormalities • Dialysis • Treatment of secondary infections • Treatment of DIC • PROTECT FROM FURTHER MOSQUITO EXPOSURE Certain medications should be avoided, such as aspirin or other non-steroidal anti-inflammatory drugs (such as ibuprofen and naproxen), because these may increase the risk for bleeding.

  32. Zika virus is an emerging arboviral infection. Like other flaviviruses it has the capacity to mutate, adapt and infect urban mosquitoes in particular Aedesaegytpi. Like dengue, we are observing an emerging human infection influenced by human migration and urban transmission. It is the first Flaviviridae of the genera flavivirus that has demonstrated sexual transmission. Zika virus

  33. Figure 1 Approximate known distribution of Zika virus, 1947–2007. Red circle represents Yap Island. Yellow indicates human serologic evidence; red indicates virus isolated from humans; green represents mosquito isolates.

  34. Arboviruses • Family Togaviridae • Genus Alphavirus • Eastern equine encephalitis virus (EEE) • Ross River Virus (RRV) • Venezuelan equine encephalitis virus (VEE) • Western equine encephalitis virus (WEE) • Chikungunya

  35. Ross River Virus • Ross River virus (RRV) is a mosquito-transmitted Alphavirusthat is endemic and enzootic in Australia and Papua New Guinea • RRV causes the most common arboviral disease in Australia • Asymptomatic infections occur in ~30% • Symptomatic infections typically include constitutional effects, rash, and rheumatic manifestations • Symptoms may last for months, longer in those with co-morbidities

  36. Ross River Virus Disease • RRV usually incubates for 7 to 9 days • Constitutional • Fever affects from one third to one half of patients • Rash, fever, and arthralgia occur in any sequence • Myalgia is common • Lymphadenopathy occurs quite often • Sore throat and coryza less frequently • Diarrhea is rare • Fatigue typically affects over 50% of patients

  37. Ross River Virus Disease • Joint manifestations • Symmetrical and acute in onset • Variable tenderness, effusions are common • Peripheral joints are predominantly involved: • Ankles, fingers, wrists, and knees • Rash • Usually lasts 5 to 10 days • May be the sole manifestation of infection • Mainly on the limbs and trunk • Maculopapular, vesicular, or purpuric

  38. Ross River Virus Disease • Diagnosis • Serology: 4x rise in IgG over 14 days • Treatment • No known treatment will alter the disease course • Treat symptoms • NSAIDS • Physical therapy, hydrotherapy, etc. • Reassurance

  39. Chikungunya

  40. Threat Assessment – ID Risk

  41. Chikungunya - Threat Assessment • Travelers • Historically South and Southeast Asia, Africa. • Transmission in the Caribbean confirmed in Dec 2013. • Military • Lethality low, 1-7 LDD expected, • Prolonged convalescence due to arthritis. • Viet Nam : 15% of FUO caused by dengue or CHIK • Reunion Island outbreak (French) • Attack rate (~33%) • Lingering clinical manifestations • French troops in Gabon: outbreaks in 2006-7.

  42. Chikungunya distribution

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