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141 Cards in this Set
- Front
- Back
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What are the other viruses of FLAVIVIRIDAE
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HEPACIVIUS - hep C(bloodborne - parenteral)
PESTIVIRUS - virus of swine and cattle - contact transmission |
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FLAVIVIRUS CHARACTERISITICS
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1.+stranded, non-segmented, RNA ~9-13kb ~50nm diammeter
2. ICOSAHEDRAL nucleocapsid 3. Enveloped thru maturation of intracytoplasmic membranes 4. GlycoP lie flat along env surface 5. single ORF translated into long polyP cleaved to make numerous polyP |
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Secondary characteristics of FLAVIVIRUS
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Capped genomes with cap-dependent translation
Genera Pestivirus and Hepacivirus - non-capped genomes with IRES Stem-loop structure req for replication and structural stability Receptor for genus Flavivirus - GLYCOSAMINOGLYCAN? Tick-borne viruses generally more environmentally resistant than mosq born |
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What is the disease manifestation of Flavivirus
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1. no known ass with human ds - many
2. Systemic febrile illness/hem fever - YP, DF, OMSK HF, KYASANUR FOREST DS 3. fever, arthritis, rash - DF, WNF 4. ENCEPH/HF - JE, STLE, Murray valley E, WNE, Omsk HF, Tick-borne E, Kysanur Forest DS |
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FLAVIVIRUS DX
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1. CULTURE- cell lines: Variety of insect, mam, avia
a.cell lines - CPE usually dramatic in vertebrate cell lines b. WHOLE ANIMALS - chick embryo, suckling mouse brain, mosq 2. SEROLOGY a. serology - lots x rsns b. X neutraliziton testing |
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describe Aedes Aegypti (vector for DF)
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Lives around human habitation
Lays eggs & produces larvae preferentially in arti containers Primarily DAYTIME BITERS Only females are blood feedsers Nervous feeders Inc interupted feeding = inc spread |
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What has happened with Aedes infestation since 70's
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Huge reinfestation
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What is Yellow Fever
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Classic hemmorhagic fever know fosince 1648
Old world virus & vector imported to new world via slave trade 18th -early 20th C epidemis in Americas(philly in 1792/NOLA in 1905) |
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Who first recognized virus - mosq relationship and recognized arbovirus?
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Walter Reed in early 1900
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Who was able to control YF in Cuba and Panama and what happened
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Panama Canal build - oil on top of H2o to keep Mosq out.
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Talk about YF Epidemiology
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YF in africa and SA:
distinct topotypes in E and W Africa only one topotype in circulation since 1974 ~5000 cases/year but under-reported Urban epidemics inc in AFrica recently Last urban ep in Americas was 1954 BUT a. A Aegypti recoloization i n recent decades b. Increasing urbanization c. Inc rainforest entry and destruction |
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Describe seasonal fluctuations of YF
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1. Afric - transmission beings during rainy season and peaks in dry
2. Americas - peaks in rainy 3. Urban YF - can extend thru out year |
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What can be a signal of YF
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Monkey die off (African monkeys are asymptomatic but may see die offs in America)
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Talk about Amplification Cycles in YF
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Sylvanic cycle with monkeys. Urban Cycle can occur with humans via A Aegypti
Zone of Emergence with those living in Forrest |
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What can cause cyclic appearance of YF in Monkey
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depletion of vertebrate hosts
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What is extrinsic incubation period for YF virus
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7-17 days
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How does YF persist thru dry season?
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Transovarian vertical transmission
Savannah(zone of emergence) transmission from sylvanic mosquitos |
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Is there human-human transmission of YF
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NO
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what are clinical symptoms of YF
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Liver is prom target - yellow jaundice (direct viral damage)
non-spec febrile to life-threatening Hem disease |
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How long is intrinsic incubation
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3-6 days
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What is infection case ratio
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HIGH! 20:1
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What are the classic periods of YF
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1. infection
2. intoxication 3 recovery |
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What is case fatality rate of YF
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20%
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What is differential dx
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malaria, typhoid fever, hepB, lepto, WNV, DF, all over viral HF(Congo-crimean, Rift valley, Ebola, Marburg, Lassa, Boivian and Argen HF)
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How is YF controlled and prevented?
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Reduce Mosq vectors (elim breeding sites)
Larva reduction(most effective) via larvivorous fish, copopods, other larvivor insects. Need full participation Insecticides PPmeasures |
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DESCRIBE YF VACCINE - 17D
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live attenuated, 95% w/1 injection/ prob lifetime protection tho rec boosters q 10 years.
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Who should get YF vaccine
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all healthy travelers to areas of risk in SA and Africa. Some exception for elderly
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What is safety record of YF vaccine
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v good. rare encephalitis. Rarely see: egg allergy, elderly, pregos, immunos
Contra in kiddos <9 |
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What about Dengue
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Refer to Dengue notes
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when was last previous report of dengue in US and latest new cases
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1945 then cases again in 80's and ongoing.
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Reasons for DF expansion in Americas
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Extensive vector infestation
Declining vector control'' Inc non-biodegradable containers and poor solid waste disposal Inc Air travel Inc population density in urban areas. |
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How many are at risk WW for dengue
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2.5 billion
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What is story on DHF in Americas
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50 fold increase in reported cases 89-93 compared to 84-88 Widespread abundance of A aegypti
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dengue clinical syndromes
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1. undif fever - DF
2. classic DF 3. DHF 4. DSS |
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DF clinical characteristics
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fever
headache mm joint pain nausea/vomiting rash Hem manifestation(no nec sign of DHF!) |
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What is four criteria necessary of DHF!!!
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1. fever
2. Hem manifestations(hi cell#s due to low fluid) 3. low platelet count (100,000/mm3 or less) Objective evidence of 'leaky caps"(elev hematocrit(20% over baseline), low albumin, pleural or other effusions |
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Hemorrhagic manifestations of Dengue
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Petechiae, purpura, ecchymoses
Gingival bleeding Nasal bleeding GI bleeding - hematemesis, melena, hematochezia HEMaturia INC Menstrual flow |
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What are two symptoms to cause thinking about Dengue
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rash and fever
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What does hyperendemicity cause
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increased probability of DHF
(one explanation) |
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Describe tourniquet test
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BP cuff, come off 1/2 for 5 minutes. Positive test 20+ petechiae per 1 inch2
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What is the Pleural Effusion Inde
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PEI = A/B x 100
(A is not darkened area of rib/B is distance from sternum to outside ribs) |
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Describe vector control methods - chem control for Dengue
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1. larvicides may be used to kill immature aquatic stages
2. Ultr-low volum fumigation ineffective against adult mosq(breeding sites still present) 3. Mosq may have resistance to aerosol sprays |
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What are biological and environmental controls for Dengue
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BIO - largely experimental - place fish in containers to eat larve
ENV - elimination of larval habitats - most likely effective long term. |
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What is control challenge of Dengue
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1. active community involvement
2. Solicit input from earliest planning stages 3. encourage comm ownership 4. programs that emphasize communites - know what to do without TRUE COMMUNITY PARTICIPATION ISKEY |
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IS THERE A DENGUE VACCINE
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No licensed vaccine
Must be tetravalent Field testing of an attenuated tetra planned No immediate future plans. |
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What families cause VHFs
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Flaviviridae, Arenaviridae, Bunyaviridae adnd Filoviridae
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What is restrictive factor on VHF and why
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Vector abundance because primarily zoonotic
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What makes VHFs make them of concern
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high intl travel and high communicability, case fatality and nosocomidial ampliphication
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Which VHFs are endemic to Americas?
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Flavividae - Dengue and YF, Arenavirus - South American or 'new world' fevers and Hanta with renal complications
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What is structure of VHF viruses
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small, single stranded RNa, enveloped
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What is greatest risk for epidemic YF
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infected individual from forrest who enters urban area where A Aegypti are present and transmission between humans occurs
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What are common containers
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old tires and flower pots
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What is significance of vertical transmission in 'yF
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transmits during dry season
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What is endemic area for YF
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Amazon and coniguous areas and island of Trinidad
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Who is most exposed for YF
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young males in forest clearing areas
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What causes more infection and death than any other arbovirus`
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Dengue
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What happened to bring Dengue back
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ceased A Aegypti eratication following eradicaton in 70s
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What are Flaviviru Agnic group ass with Encephalitis
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two types - mosquito born and tick borne
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What are Mosquito borne Flavivius
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JE
ST E WEST NILE E MURRAY VALLEY E -AUSSIE KUNJUN- AUSSIE |
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Which causes more mortality - flavi mosq or tick
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mosquito borne
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what are flavivirus tick borne ds
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CEE
RSSE Louping Ill Powassan Omsk HF Kyasanur Forest fever |
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Where and by whom are arboviral enceph maintained
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bird-mosq cycle with Culex species mosquito
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What else can Arboviral E infect
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pigs, humans, other mammals
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Are humans important amplifying host of arboviral enceph
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NO
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What is the season for Arboviral Enceph
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late summer/early fall for temperate zone
Year round in tropix |
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What other families can cause arboviral enceph
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Togaviridae and Bunyaviridae
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What is encephalitis
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brain inflammation
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habitat and location for JE
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E africa - rice paddy, pigs
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What is habitat and location for St louis E
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Americas
sewers, waste water |
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what is loc and habitat for West Nile
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Africa, ME, Americas
Irrigation waste water |
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What is hab and location for Murry Valley and Kunjin
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Australia in irrigation
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What does Culex mosquito prefer and when
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BAD WATER - rice paddies, irrigiated fileds and floodplains durin rainy season
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What is difference between enzootic and epizootic transmission
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enzootic - virus maintained in animals
epizootic - virus breaks out to cause epidemic which may die out over time. |
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Alphavirus name coems from where
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once known as group A arboviruses
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characteristix of alphavirus
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Pos stranded, non-segmented RNA
Icosahedral nucleocapsid replic in cytoplasm enveloped thru plasma membrane single orf with post translat cleavage to make four pp produce hemagglutinins often induce apoptosis |
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possible consequences of alphavirus
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1. asymp
2. fever arthritis, rash(old world) 3. enceph(new world) |
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What is polyarthritis syndrome
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maculopapular rash 4-8 days after initial symp - itchy or irritating
may be accomp by increase in fever joint pains may reoccur w/o rash or fever for many months rare fatalitites or long term sequaliae |
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What are antiviral influenza treatments
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For A: Amantadine, Rimantadine.
For A and B: neuraminidase inhibitors - Oseltamivir (Tamiflu) oral and Zaimivir inhaled |
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Differences between Seasonal, Avian and Pandemic flu
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Seasonal - conragious resp illness caused by influenza virus
Avian - bird flu, naturally occuring in birds, caused by avian influenza viruses Pandemic- global outb reak when new Influenza A causes serious human illness and spreads p - p. |
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Pandemic in 1918 was where and aused how many deaths
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Ft riley, Ks, >50 mil globally, 2 mil in USA. Ended WWI
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What made 1918 virus so deadly
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HA from avian HA, not this alone, but related to host range(young healthy adults)
Polymerase P were more avian than human - control replication and may relate to transmissability. |
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What H1N1 pandemic was from where?
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A/California
triple reassortant of swine, avian ad human flu |
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What are three subtypes of Avian Infuenza infecting both bird and peopel
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Inf AH5
Inf AH7 Inf A H9 |
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What was Avian Influenza that affected humans in 1996 in HKong
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H5N1
killed most wild, domestic and exoctic birds in Hong Kong in 2002 |
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Describe H5N1 influenza
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precursor of "Z genotype" mpwe dominant in SE Asia. as of 8/09 killed 262/440 cases humans = CFR=60%
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What has caused the spread of this H5N1 strain
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1. mvmt of poultry for food or sport
2. migration of wild waterfowl 3. movement of infected humans?? |
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What is control of Avian Influenza
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1. dev of surveillance systems and dx capacity
2. Culling poultry 3. Limiting contact btw wild and domestic fowl 4. Vaccination of poultry(must prevent ds AND virus shedding) |
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Describe qualities in Influenza vaccine
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1. grown in chick embryos
2. infected fluids harvested 3. Slow and hard to QC 4. new tri-valent vac each year (based on 2 A's and 1 B virus 5. best = 70% protection 6.may not be effective on newly evolved strains |
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How is vaccine inactivated
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formalin inactivated
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describe nasal spray vaccine and who it is used for
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LIVE ATTENUATED!
nasal delivery 2-49 years age, healthy not pg |
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who should not get vaccinated??
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severe allergy to eggs
previous rx to vaccine, including GB dynftomr. kifd<6 months people with fever live not for pg |
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What happens in Pandemic alert period
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ph 3 - human inf with new subtype but no hum-hum spread
ph4 - small clusters hum-hum, highly localized ph 5 - larger clusters, still localized (virus being better adapted to humans) |
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What are only ways presently to control arboviruses
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1. eradication of vector
2. immunization |
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How does large urban development create problems with arbovirus?
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deforestation, irrigation, and resettlement programs disrupt the sylvan cycle of the virus and contribute to outbreaks.
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describe Adenovirus
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dlb DNA, Icosahedral capsid, multiple splicing of late genes
small DNA tumor virus used for cancer tx, vaccine dev, gene therapy |
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Where did adenovirus come from
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adenoid tissue. military recruits with acute resp distress syn(ARDS)
rarely fatal, hi morbidity bad for transplant recpts. |
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What are 1sts about Adenovirus
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1st pathogenic human virus to cause cancer
1st eukaryotic genome synth in vitro 1st evidence for disontinuous genes 1st means of introducing naked DNA into cells |
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What is classification of Adenovirus
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Family Adenoviridae
Genera Aviadenovirus (birds only) Mastadenovirus - humans + |
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Sub groups of Adenovirus
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A - F
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How transmitted for adenovirus
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person - person. Kids can harbor for up to 10 years (in lymphoid tissue)
pink eye |
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who is at risk for adeno
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v young, v old, v sick
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what is ad-mediated epidemic keratoconjunctivitis?
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EKC "shipyard eye". seen in opthamalogy settings with muiltidose bottles - long lived outside the body
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What is risk in adenovirus
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BMT patients have hi risk of dying
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What is Ad36 and what is it linked to?
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Linked to obesity in children. Adenovirus 36. no mechanism yet.
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What is adenovirus used for in research
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Oncolytic adenoviruses(cancer killing) - 1st tested in humans. Onyx-015
Gene therapy vectors Vaccine vector |
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What happened to Onyx 015
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tested in humans as first oncolytic virus. Approved by Chinese FDA in 2005
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What does Onyx-015 do in oncology?
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significantly reduce tumor size in baby mice
delivery of genes to tumor cells |
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talk about replicating and non-replicating vectors
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replic "armed" vectors increase cell killing by viral and gene-mediated means.
non-repl - deliver genes to promote tumor cell death |
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What is application of adenoviruses and vaccines
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multiple agns cloned into Ad vector
Ad5 is vector of choice, best in respiratory route. Challenges due to vector immunity. Liver toxicity seen |
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What is Ro?
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Reproductive number - ave number of secondary cases generated by one primary case in a suscepticle community.q
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What are CPE's
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Cytopathic effects - many viruses kill cells in which they replicate sometimes with characteristic appearances i.e. CPEs!
Can give clues to the sort of immne respon to be expected. |
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what are 'bursters' vs ' creepers'
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Bursters burst the host cell to release new virions. Creepers - viruses that create synctia - multinucleated giant cells and pass from cell to cell rather than burst.
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what causes the formation of mnucleated giant cells? what else did it cause
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Fusion proteins, which also mediated the entry of virus through plasma membrane.
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What are viral inclusions
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intracytoplasmic, intranuclear or both. Bodies appear within cells as a result of infection viruses.
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Describe cardiac ionotropy - shock
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1st blood vessels(bv) dilate, dec BP. cell junctions open up and liquid leaks out. Pericaridal hydropy=impaired heart pumping leads to shock.
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What are characteristics of JE
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East asia,
50K cases/year 10K deaths/year. children and elderly at highest risk perm neurological seq 45-70% resev - birds and pigs vector - Culex, esp C. tritaeniorhynchus |
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How is JE dx?
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IgM usually in serum and CSF
virus and viral agns present in brain, but only isolated in severe cases. CSF - WBCs, sugar us normal CT and MRI may be norm or show diffuse edema. occ focal abn |
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what is DD for JE
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brain abscess, bact meningitis, neurosyphillis, leptospirosis, herpes enceph
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What are clinical sym of JE
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Intrinsic incu 3-6 days
present: febrile, enceph, maybe hem ds Initial viremia from lymphoid sys. onset may be mild or abrupt |
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JE clinical II
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CNS invasion thru viremia or direct thru olfactory nerves(H/A, photophobia, vomit, leth, convul, coma)
Diffuse brain damage - viral destruction or inflammatory response case fat - <.05-75% Duration - few days to 2-3 wks prolonged convalescense and residual possible. |
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Describe JE vaccine
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v expensive
Formalin inact - JE VAX not in use IXIARO - inactivated cell culture derived vaccine. Live atten in use in China |
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What are phases of clinical trials for vaccine?
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I clinical trials
II Prove safety-dosing III Efficacy IV post makting |
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Where is risk for JE
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Asian countries
Rural areas, rice growing, summer pattern, duration of stay |
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WEST NILE VIRUS - history?
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part of JE agn complex
first found in Uganda 1937 one of most widespread FLAVIVIRUS 1st epi in Israel in 50's pretty much ww distribution. Recently into americas |
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What is bird role in WNV
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wild birds - primary amplifier hosts
Migratory birds role in distrib and re-intro |
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which birds have WNV in US
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american crow
blue jay magpie sparrow red-tailed hawk others |
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What is usual VECTOR IN WnV
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Culex - some from Aedes, anopheles, etc, also from ticks, both hard and soft
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describe WNF
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incub 5-15 d
febrile, influena like illness with abrupt onset mod - hi fever ha, sore throat, backache, myalgia, arthraligia, fatigue RASH WNND - acute aseptic mem or enceph case fatality 3-15% |
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WNV in US possible pathways of intro
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Infected human host
Human-transported vertebrate host (legal or illegal) Human-transp vector storm-transport vertebrate host(bird) Intentional intro - bioterror |
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Other issues with WNV
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placental transmission - project @ Tulane wtih CDC
Breast milk transmission organ/tissue donor infections(blood supply) Lab infections WNV in reptiles(gators in LA & FL) |
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StLE transmission cycle
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reservoir - wild birds
vector - culex Urban(epi) vector - C quinquefasciatus |
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SLE Ds
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Incub 5-15 d
Asym febrile - aseptic men-enceph inf:disease ratio = 85-800;1 MORT 3-20% IN EASTERN US tx - supportive |
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SLE RISK GROUP
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elderly
low SES - outside risk outdoor occupation |
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SLE - HOW dx?
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Must be specifically requested. Not normally looked for.
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Control of SLE
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vector
bahavioral modification No vaccine availale |
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What about Murray Valley and Kunjin viruses
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Endemic in Australia
Epis after heavy rainfall consecutive summers Resevr - lg water birds and mammals vector - Culex annlirostris |
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What about Tick born encephalitis
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Eu, Asia, NA
distinct gp w/in Flavivirus 40% aa homogeneity with mosq flaviviruses - not much Ticks - Ixodes and Dermacentor also - raw goat milk Inacti vaccine in Central Eu |
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Why tick borne not more widely spread
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a. vector not present
b. viremias short, don't usually travel w viremia. |
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What is Togaviridae
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refers to "cloak" enveloped
two genera - Alpha: > 26 viruses, all arboviruses Rubi(Rubella, not studied) |
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Characteristics of Alpha
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+ stranded, non-seg RNA
Icosahedral nucleocapsid repl in cyto enveloped single ORF prod HA Induce apoptosis |
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Alphavirus dx
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Culture:
cell lines or whole animal Serology: Elisa, HI some members of New World AlphaV pm CDC select agent list of concern |
