peste porcina africana: virus georgia 2007 y la actual
TRANSCRIPT
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Peste Porcina Africana: virus Georgia 2007 y la Actual Epidemia de la Enfermedad
Guillermo R. Risatti MV, MS, PhD.Profesor Asociado
Departemento de Patobiología y Ciencias VeterinariasDirector de Sección de Servicios de Diagnóstico
Connecticut Veterinary Medical Diagnostic LaboratoryCollege of Agriculture, Health and Natural Resources
University of ConnecticutUSA
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La Enfermedad
• La Peste Porcina Africana (PPA) es unaenfermedad viral, contagiosa y hemorrágicaque afecta a los cerdos (domésticos y salvajes).
• La PPA es una enfermedad reportable (OIE).
• Descrita en Kenya en 1920.
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Virus de la Peste Porcina Africana (vPPA)
• Virus ADN de cadena doble• Genoma de 170-190 kilobases• Codifica 180-190 genes• Esructura del virión es compleja con mas de 50
proteínas virales• Único miembro de la familia Asfarviridae• Garrapatas de la familia Argasidae, género
Ornitodoros (O. moubata) son vectores del virus (África).
• O. erraticus en España y Portugal?
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Asfarviridae
From: Viral Zone, ExPASy Bioinformatics Resource Portal
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From L.K. Dixon et al. / Virus Research 173 (2013) 3– 14
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Picture from: The Pirbright Intitute (https://www.pirbright.ac.uk/asfv)
ASFV virus particles
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Virulencia del vPPA
• Determinantes de virulecia en el vPPA: se conocen algunos genes
• Cepas de alta virulencia: Georgia 2007, genotipo II, probablemente originada enMozambique.
• Cepas de baja virulencia:
– Africa
– España y Portugal
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Historia Natural: ciclos de transmisión
• Ciclo salvaje: Africa– garrapata-cerdos salvajes-cerdos domésticos
(África; particularmente en Este y Sur de África).
– warthogs (Phacochoerus aethiopicus), red river hogs (Potamochoerus porcus).
• Ciclo doméstico: – transmisión directa entre cerdos afectados
– cerdo doméstico-cerdo doméstico.
– cerdo salvaje-cerdo salvaje
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Infecciones persistentes como reservorios del vPPA
Warthogs Red River hogs Cerdos domésticosque sobreviven la
infección???
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Ornithodorus moubata
O. moubata
Warthogs: madriguera
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PPA/PPC: Definición de CasoSu
spec
t C
ase • Rapidly
Spreading
• Highly Contagious
• High Morbidity
• Variable Mortality
• Internal Hemorrhages
Pro
bab
le C
ase • High Fever
• Depression
• Conjunctivitis
• Ocular Discharge
• Constipation
• Vomiting
• Diarrhea
• Posterior Ataxia
• Widespread Hemorrhages
• Periparturient Death of Piglets
Co
nfi
rmed
Cas
e • ASF/CSF Virus Detected by PCR-RT-PCR
• Detect Virus Using ImmunocaptureELISA
• Detect antibodies using ELISA
Sospechoso Probable Confirmado
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Historical distribution of ASFV genotypes (n=27) detected in Africa and Europe
From: FAO Empres Vol.6 September 12
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PPA fuera de Africa: origen de epidemiasrecientes
1950 2007
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Epicentro de la epidemia de PPA?
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Dispersión de la epidemia de PPA en Rusia
Domestic pigs Wild boars
From: FAO Empres Vol.6 September 12
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Pigs in low biosecurity holdings
From: FAO Empres Vol.6 September 12
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Wild boar distribution in Eurasia
From: FAO Empres Vol.6 September 12
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Epidemia de PPA 2018
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Provinces in China affected by African Swine Fever outbreaks
Hainan
Anhui
Jilin
Liaoning
Shandong
Fujian
Hubei
Hunan
GuangdongGuangxi
Shanghai
Shanxi
Inner Mongolia
Shaanxi
Ningxia
GansuQinghai
Sichuan
Xinjiang
Zhejiang
Guizhou
Chongqing
Yunnan
Heilongjiang
Jiangxi
Beijing
Tianjin*
Taiwan
Hong Kong
Tibet
Macau
JiangsuHenan
Hebei
ASF outbreaks reportedSource: OIE, 2018
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1
6
7
2 3
4
5
# Province Date
1 Liaoning 08/01/2018
2 Henan 08/14/2018
3 Jiangsu 08/15/2018
4 Zhejiang 08/17/2018
5 Anhui 08/19/2018
6 Heilongjiang 09/01/2018
7 Inner Mongolia 09/12/2018
8 Jillin 09/14/2018
9 Tianjin 10/10/2018
10 Shanxi 10/16/2018
11 Yunnan 10/19/2018
12 Hunan 09/28/2018
13 Guizhou 10/14/2018
ASF outbreaks in China: chronology
Source: OIE, 2018
8
9
10
11
1213
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Source: Gain Report #CH18016, USDA Foreign Agricultural Service
10% of pig production
26% of pig production
25% of pig production
13% of pig production
21% of pig production
Denotes Provinces reporting ASF outbreaks
Pig production in China and ASF outbreaks
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Other major pork producing countries in the region
Russia
Tajikistan
Vietnam
Pakistan
Nepal
Laos
MongoliaKyrgyzstan
Kazakhstan
North Korea
South Korea
India
Bhutan
Thailand
Myanmar
Bangladesh
Afghanistan
Kashmir
Hainan
Anhui
Jilin
Liaoning
Shandong
Fujian
Hubei
Hunan
GuangdongGuangxi
Shanghai
Shanxi
Inner Mongolia
Shaanxi
Ningxia
GansuQinghai
Sichuan
Xinjiang
Zhejiang
Guizhou
Chongqing
Yunnan
Heilongjiang
Jiangxi
Beijing
Tianjin
Taiwan
Hong Kong
Tibet
Macau
JiangsuHenan
Hebei
Yellow Sea
East China Sea
South China Sea
Bay of Bengal
Spratly Islands
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Vacunas contra vPPA
• El desarrollo de vacunas contra el vPPA se ha visto comprometido debido a conocimientosinsuficientes relacionados con:– Diversidad genética y antigénica del vPPA.
– Proteínas virales que confieren protección contra la infección.
– Naturaleza de la respuesta immune contra el vPPA.
– Infección y transmisión del vPPA.
– Determinantes de virulencia/atenuación
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From L.K. Dixon et al. / Virus Research 173 (2013) 3– 14
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Resistance to physical and chemical action
• Resistance to physical and chemical action Temperature: Highly resistant to low temperatures. Heat inactivated by 56°C/70 minutes; 60°C/20 minutes.
• pH: Inactivated by pH 11.5 in serum-free medium. Serum increases the resistance of the virus, e.g. at pH 13.4 – resistance lasts up to 21 hours without serum, and 7 days with serum.
• Chemicals/Disinfectants: Susceptible to ether and chloroform. Inactivated by 8/1000 sodium hydroxide (30 minutes), hypochlorites – 2.3% chlorine (30 minutes), 3/1000 formalin (30 minutes), 3% ortho-phenylphenol (30 minutes) and iodine compounds.
• Survival: Remains viable for long periods in blood, faeces and tissues; especially infected, uncook
Source: OIE
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Vacunas Experimentales
• Expresión de antígenos virales por medio de vectores.
• Antígenos virales (vacunas a subunidad).
• Cepas virales naturalmente atenuadas.
• Virus vivos modificados.
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J Virol. 2015 Aug; 89(16):8556-66.
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Infection with ASFV Georgia 2007/1
Transfection with p72GUSconstruct
Recombination Selection
Preparation of virus stockTest stock purity by PCR
Whole genome sequencingTest for attenuation via IM
x
Swine macrophages
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Development of recombinant ASFV-G Δ9GL virus
1 189,340
ASFV-Georgia 2007
9GL
94,952 95,308
Georgia 9GL MLHWGPKYWRSLHLYAIFFSDAPSWKEKYEAIQWILNFIESLPCTRCQHHAFSYLTKNPLTLNNSEDFQYWTFAFHNNVNNRLNKKIISWSEYKNIYEQSILKTIEYGKTDFIGAWSSL
Malawi 9GL .......F..T..........T.G.....................M.R................................K.....................N................
E75 9GL .......................................................................................................................
1 189,340p72-GUS
ASFV-Georgia 2007 Δ9GL
1 189,340
9GL
pΔ9GL-p72GUS
ASFV sequencesASFV sequences
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ASFV-G 102 HAD
IM 9.2 d
ASFV-G Δ9GL102 HAD
IM
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ASFV-G Δ9GL104 HAD
IM8.25 d
ASFV-G Δ9GL103 HAD
IM
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J Virol. 2016 Dec 16; 91(1).
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1 189340
p72-GUS
ASFV-G ΔB119L
95104 95278 184331 184621
DP96R
1 189340
DP96R ASFV sequencesASFV sequencesp72-GUS
95104 95278
1 189340
p72-GUS p72-mCherry
184331 184586
ASFV-G ΔB119L/DP96R
95104 95278
1 189340
B119L
94949 95308
1 189340
B119L ASFV sequencesASFV sequences
184331 184621
DP96R
ASFV-G
184331 184621
DP96R
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Pigs survive infections with the mutant virus even at high doses (10,000X)
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Protección es inducida a los 14 días post-vacunación
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Necesidad de obtener y comercializar vacunas contra la PPA
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Control y Erradicación de PPA
• Definición de zonas de alto riesgo (cadena de valor del cerdo).
• Definición de caso y detección/confirmacióntemprana.
• Cuarentena y eliminación del brote.
• Eliminación de animales en granjas encontacto con el brote.
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Países productores de cerdos en la región
Russia
Tajikistan
Vietnam
Pakistan
Nepal
Laos
MongoliaKyrgyzstan
Kazakhstan
North Korea
South Korea
IndiaBhutan
Thailand
Myanmar
Bangladesh
Afghanistan
Kashmir
Hainan
Anhui
Jilin
Liaoning
Shandong
Fujian
Hubei
Hunan
GuangdongGuangxi
Shanghai
Shanxi
Inner Mongolia
Shaanxi
Ningxia
GansuQinghai
Sichuan
Xinjiang
Zhejiang
Guizhou
Chongqing
Yunnan
Heilongjiang
Jiangxi
Beijing
Tianjin
Taiwan
Hong Kong
Tibet
Macau
JiangsuHenan
Hebei
Yellow Sea
East China Sea
South China Sea
Bay of Bengal
Spratly Islands
El próximo lugar afectado?
Brotes de PPA reportados, Noviembre 2018Source: OIE