nullOf Ducks, Pigs, and Men:
(with apologies to John Steinbeck)
An Arkansas disease specialty?Of Ducks, Pigs, and Men:
(with apologies to John Steinbeck)
An Arkansas disease specialty?Case Presentation - 1Case Presentation - 1May 9: 3 year old male, previously healthy, developed fever to 102, sore throat, cough
7 days later hospitalized for progressive sx
3 days later intubated for ARDS
WBC 2000, plt 187K, AST 2150
MODS
Death 5 days after admissionCase Presentation - 2Case Presentation - 2November 6: 2 year old boy with VSD had high fever, cough, sore throat
Hospitalized for presumed pneumonia
WBC 13000
Uneventful recovery; discharge after 3 daysCase Presentation - 3Case Presentation - 3November 20: previously healthy 13 year old girl had fever, sore throat and cough
Hospitalized for pneumonia 6 days later; intubated 1 day later
WBC 2500, plt 31K, PT 12.8, PTT 38.5, urea 30.6 mmol/L (6), Creat 220 umol/L (<10)
ARDS, ARF, GI bleeding, hemoptysis
Death 25 days after admissionCase Presentation - 4 Case Presentation - 4 November 24: 54 year old man with a prior MI but no CHF had fever and cough
Hospitalized for pneumonia 5 days later; vomiting, SOB, bilateral infiltrates
WBC 5800, AST 157, acute renal failure
Death 7 days after admissionCase Presentation - 5Case Presentation - 5December 4: 24 year old woman had fever, sore throat, dizziness and cough
Hospitalized for pneumonia and massive pleural effusion 2 days later; intubated
WBC 2400, AST 74, hemorrhagic effusion
Death 24 days after admissionCase Presentation - 6Case Presentation - 6December 7: 5 year old girl had fever, sore throat, rhinitis, epistaxis and cough
Hospitalized for IV fluids; vomiting
WBC 8400, AST 91
Afebrile after 24 hours
Recovered without complicationsCase Presentation - 7Case Presentation - 7December 12: 2 year old boy with G6PD def had fever, sore throat, and rhinorrhea
Hospitalized for IV fluids; cousin of pt 6
WBC 14600
Afebrile after 24 hours
Recovered without complicationsCase Presentation Case Presentation 5 more cases: 1, 3, 19, 24, 60 years
3 had ARDS, shock, renal failure with persistent and progressive MODS - all died
2 were afebrile within 48 hours and were discharged without complicationsWhat is the diagnosis?What is the diagnosis?InfluenzaInfluenzaAll 12 cases were from Hong Kong but from at least 6 different parts with no exposure to each other or in common
All 12 had isolation of influenza A subtype H5N1 - 1st known cases in humans
5 uncomplicated with no deaths; 7 severe cases with 5 deathsnullFeb 23, 1997
Vol 151 No. 7Avian Flu - New Territories, HK, 1997Avian Flu - New Territories, HK, 1997Mar 1997 - chickens in 3 farms began to die
6800 died; 100% in 2 farms; 10 of 10 inoculated died
Open Bird Markets in Hong Kong; Daily sold:
109K Chickens, 19K pigeons, 6.5K ducks, 5K geese, misc pheasant, quail, chukar
Only 2 of 11 markets had dead chickens
After cases, 11 of 11 experimental chickens died
Dec 29, 1997 - 1.5 million birds in HK destroyed
For 18 cases, was this too extreme ?Avian Flu - New Territories, HK, 1997Avian Flu - New Territories, HK, 1997After chicken culling, no futher cases occurred
A/Sydney was documented in HK within days of slaughter; reassortment would be predicted
Potential of 60 million + deaths worldwide if new pandemic had occurred
Now in China, ducks, geese, exotic fowl have to be killed and dressed before leaving marketAvian Flu - New Territories, HK, 1997Avian Flu - New Territories, HK, 1997After chicken culling, no futher cases occurred
A/Sydney was documented in HK within days of slaughter; reassortment would be predicted
Potential of 60 million + deaths worldwide if new pandemic had occurred
Now in China, ducks, geese, exotic fowl have to be killed and dressed before leaving market
March 1999, H9N2 influenza A isolated from 2 children in Hong Kong. First confirmed cases of human infection with this strain.New Cases – Avian InfluenzaNew Cases – Avian InfluenzaFebruary 2003 – family visit to mainland China, young girl died. Father and brother hospitalized – father died. H5N1 isolated
Same time, rumors of rampant influenza in China…fear of human to human avian flu…SARS
March 2003 – highly pathogenic H7N7 avian influenza outbreak in chickens in Netherlands workers involved in slaughter got conjunctivitis…veterinarian died of respiratory infection
Current outbreak in China, Vietnam, Korea, Thailand, etc…daily the list grows.Background on influenza virusesBackground on influenza viruses3 types of Influenza viruses: A, B, C
All Influenza A viruses originate in birds
All are Avian Influenza viruses
Wild birds domestic poultry
The viruses either cause mild or life-threatening disease in domestic poultryHow does a new avian influenza virus infect humans ?How does a new avian influenza virus infect humans ?2 different influenza A virus subtypes can swap genetic material and merge—usually in a “mixing vessel”
The resulting subtype can be passed to humans and then from human to human
Humans will not have immunity to this new subtype
This leads to the next global influenza pandemic
Influenza pandemicsInfluenza pandemicsnullThe current “bird flu” situation The current “bird flu” situation Dec 2003 - present: largest outbreak of highly pathogenic H5N1 Avian influenza in poultry in Asia
>100 million birds dead or killed in 9 Asian countries
Why is there so much concern about the current outbreaks? Why is there so much concern about the current outbreaks? Avian influenza viruses normally infect humans through an intermediate host, usually a pig
This current highly pathogenic avian influenza virus (H5N1) has “jumped” directly from chickens to humans in Thailand and Vietnam without the intermediate
Virus infection has also been reported in pigs and cats— what role will they play in transmission??Human cases of avian influenza Human cases of avian influenza As of October 4, 2004The next influenza pandemicThe next influenza pandemicSo far, the avian influenza virus doesn’t spread efficiently between humans (1 case in Thailand)
But, if the virus gains this ability
The next global influenza pandemic would occur
nullnullhttp://www.cdc.gov/flu/han020302.htmhttp://www.cdc.gov/flu/han020302.htmhttp://www.cdc.gov/flu/avian/facts.htmhttp://www.cdc.gov/flu/avian/facts.htmnullThe difference between reality and fiction is…
Fiction has to make some sense
Tom ClancyEmerging Zoonoses
Species - Jumping Infectious AgentsEmerging Zoonoses
Species - Jumping Infectious AgentsUnpredictable; Immediate Investigation
Microbial/Virologic determinants
Individual Host determinants
Environmental determinants
Ecologic, Climatologic
Host Population determinants
Human/Livestock closer contact
Bioterrorism by rogue govt or amateurs
Circumnavigation of globe less than incubationEmerging Zoonoses
Species - Jumping Infectious AgentsEmerging Zoonoses
Species - Jumping Infectious AgentsEquine Morbillivirus - Australia. Hemorrhagic respiratory distress in horses. Trainer and stable hand died
Ebola Hemorrhagic Fever - Africa. reservoir ?
Rabies - USA. imported raccoons to WV
Hantavirus Pulmonary Sx. USA. ‘93. 164 cases by ‘97
Bovine Spongiform Encephalopathy; new variant Creutzfeldt Jakob. UK. 170K cattle reported; prob a million. Half entered food chain in UKInfluenza - Animal virus in humanInfluenza - Animal virus in human1979 - lab worker H7N7 after seal sneeze
1996 - Homemaker with H7N7 after cleaning duck house
10% of pig farmers in China have serologic evidence of swine flu
A few documented serious infection and deathwww.cdc.gov/ncidod/diseases/flu/weekly.htmwww.cdc.gov/ncidod/diseases/flu/weekly.htmnullwww.cdc.gov/ncidod/diseases/flu/weekly.htmwww.cdc.gov/ncidod/diseases/flu/weekly.htmwww.cdc.gov/ncidod/diseases/flu/weekly.htmwww.cdc.gov/ncidod/diseases/flu/weekly.htmInfluenza Morphology
Family Orthomyxoviridae; Genus InfluenzaInfluenza Morphology
Family Orthomyxoviridae; Genus Influenza80-120nm sphere (or filamentous) enveloped virus
Covered with surface projections (peplomers) of hemagglutinin (HA) and neurominidase (NA)
Host derived lipid bilayer with inner surface Matrix (M) protein
Eight segmented pieces of nucleocapsid with single stranded RNA genome
Polymerase (PB1, PB2, PA) transcriptase proteins
Internal nonstructural proteins (NS1, NS2) Influenza morphologyInfluenza morphologynullInfluenza: Hemagglutinin (HA)Influenza: Hemagglutinin (HA)Rod-shaped spikes, trimers, bound to membrane
Site of attachment to cells by N-acetylneuraminic (sialic) acid containing glycoproteins
Site of attachment to erythrocytes used for testing
Species specificity to arrangement of sialic acid (α 2,3 Galactose or α 2,6 Galactose)
Major antigen. Large difference in AA sequence in different subtypes. Most freq involved with variation
Specific antibody prevents infectionnullInfluenza: Neuraminidase (NA)Influenza: Neuraminidase (NA)Mushroom-shaped spikes, tetramers, bound to membrane, fewer in number than HA
Cleavage site of HA activity; cleaves bond of N-acetylneuraminic (sialic) acid & D-galactose
May remove neuraminic acid from mucin in respiratory tract which inhibits HA
Major antigen of Influenza with potential variation
Activates cytokine cascade (IL-1, TNF)
Specific antibody diminishes number of newly formed virions from infected cellsINFLUENZA - ADAPTIBILITYINFLUENZA - ADAPTIBILITYAntigenic Drift - Unpredictable antigenic change in HA or NA. Occur after pandemic form established in human; ab rise. Renders an individual susceptible to new strains as drifted strain escapes neutralization
Antigenic Shift - Emergence of novel Influenza A virus. Animal virus, normally in swine or birds, are transmitted to human. Novel HA or novel NA than those in circulating in man in recent decades.
Pandemic occurs with transmission of these novel virus with disease in large and susceptible populationInfluenza: VariabilityInfluenza: VariabilitynullInfluenza: ReassortmentInfluenza: ReassortmentInfluenza: ReassortmentInfluenza: ReassortmentInfluenza: ReassortmentInfluenza: Reassortment