Economia dei Paesi Emergenti Fabrizio Coricelli Università di Siena 2009.
INFEZIONI VIRALI EMERGENTI E RIEMERGENTI DEGLI …...1997: Avian influenza 2002: SARS 2012: MERS...
Transcript of INFEZIONI VIRALI EMERGENTI E RIEMERGENTI DEGLI …...1997: Avian influenza 2002: SARS 2012: MERS...
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INFEZIONI VIRALI EMERGENTI E RIEMERGENTIDEGLI ANIMALI DA COMPAGNIA
Vito Martella,Department of Veterinary Medicine
University of Bari, Italye-mail: [email protected]
GIORNATA DI STUDIOL’AQUILA, 25 marzo 2017
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A disease that has appeared in a population for the first time, or that may have existed previously but is rapidly increasing
in terms of incidence or geographic range
EMERGING DISEASE (WHO)
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“...NOTHING IN BIOLOGY
MAKES SENSE
EXCEPT IN THE LIGHT OF EVOLUTION…”
Theodosius Dobzhansky
(1900-1975)
Charles Darwin
“...NOTHING IN VIROLOGY
MAKES SENSE
EXCEPT IN THE LIGHT OF EVOLUTION…”
Marian C. Horzinek
(1936-2016)
VIRUS EVOLUTION
http://upload.wikimedia.org/wikipedia/commons/9/9c/Darwin_ape.jpghttp://upload.wikimedia.org/wikipedia/commons/9/9c/Darwin_ape.jpg
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VIRUS EVOLUTION
PROLIFERATE FASTER THAN
is the constant changeof a viral population in the face of selection pressures
EVOLUTION
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RATES OF MUTATION OF VIRUSES
RNA viruses are the masters of mutation….
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VIRUS EVOLUTIONresponsible for the emergence of most emerging and reemerging
infectious diseases faster in RNA viruses than in bacteria and DNA viruses due to the lack
of proof-reading activity of the RdRpthe same mechanisms as in higher organisms: variation (mutation) and
fixation (selection)mutants arise spontaneously and stochastically (deletions, insertions,
recombinations, reassortments)each infection represents a population bottleneck (casual selection of
mutants) and has to face the host immunity (direct selection)
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Any disease or infection that is naturally transmissible from vertebrate animals to humans
ZOONOSIS (WHO)
1997: Avian influenza
2002: SARS
2012: MERS
2014: REEMERGENCE OF EBOLA
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MAJOR ZOONOSES OF DOGS AND CATS
http://www.upenn.edu/regulatoryaffairs/Documents/iacuc/guidelines/zoonoses_dogs_and_cats.doc
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VIRAL ZOONOSES OF DOGS AND CATSRABIES: the most common canine zoonosis
2015, second semester; www.oie.it
The virus is present in 2/3 of the world countries Half of the world population live in an endemic area
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VIRAL ZOONOSES OF DOGS AND CATSRABIES: the most deadly canine zoonosis
70,000 human deaths/year>95% human cases caused by dog bites
Cave canem First century Roman mosaicHouse of the Tragic Poet, Pompeii
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VIRAL ZOONOSES OF DOGS AND CATS
RABIES: the oldest known canine zoonosis
Mesopotamia, 2300 bc, Eshnunna Code
• First attempt to prevent virustransmission from dogs to humans
• The dog owner was heavily fined incase of death of the bitten person
“If a dog is mad and the authorities have brought the fact to the knowledge of its owners; if he does not keep it in, if it bites a man and causes his death, then the owner shall pay two thirds of a mina (40 shekels) in silver. If it bites a slave and causes his death he shall pay fifteen shekels of silver”
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VIRUS DISCOVERY Datta et al., 2015, World J. Virology
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NGS IN VIRUS DISCOVERY
Mokili et al., 2011, CurrentOpinion in Virology
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EMERGING VIRUSES OF DOGS AND CATS
INFLUENZA VIRUSESROTAVIRUSESCALICIVIRUSESASTROVIRUSESOTHERS
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INFLUENZA VIRUSES
ANTIBODIES AGAINST HUMAN INFLUENZA A VIRUSES
DETECTED IN DOGS AND CATS (Nikitin et al., 1972; Fison et al., 1975;
Houser at al., 1980; Buonavoglia et al., 1983)
CATS SUCCESSFULLY INFECTED WITH A/H3N2/Hong Kong/1968
(Paniker and Nair, 1970)
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2002: BIRD FLU HPAI H5N1
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Host range of HPAI H5N1
Natural infection Experimental infection
BirdsHumansDomestic catWild felidsStone martenSwinePalm civetDog
BirdsMonkeys (C. macaque)Domestic catFerretMiceRabbitsRatsCattle
INFLUENZA VIRUSES
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H5N1 in carnivores
Date Species Outcome
Dec 2003
Feb-Mar 2004
Feb 2004
Oct 2004
Jul 2005, Vietnam
Leopard, Tiger
Clouded leopard, Tiger
Domestic cats
Tiger
Owstone palm civet
Rapid death
Rapid death
3/15 dead
147/441 dead/euthanased
3 dead
INFLUENZA VIRUSES
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Date and country Species Outcome
2005
Mar 2006, Germany (Rügen)
Mar 2006, Austria
Cats, dogs
Domestic cat
Domestic cat
Seropositives Cats 8/111Dogs 160/609
dead
3 dead
H5N1 in carnivores
INFLUENZA VIRUSES
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Cat with H5N1 natural infection, Thailand
Lung: oedema and congestion Liver: multifocal necrosisSongserm et al., 2006, Emerg. Infect. Dis.
Brain (IHC): viral antigens Heart (IHC): viral antigens
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H5N1 experimental infection of cats
• Different routes of infection:– Intratracheal– Direct contact– Administration of infected chickens
• Disease (respiratory and systemic signs)– Lung lesions– Multifocal petechiae in the lymphatic
tissue of the respiratory tract– Virus detected in internal organs– Early death
• Virus shedding• Virus transmission to contact cats
Thiry et al., 2007, Vet. Microbiol.
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Songserm et al., 2006, Em. Infect. Dis.
HPAI H5N1 in dogs
• Species not highly susceptible to HPAI H5N1
• Serological positivity
• Sporadic clinical cases
• Dogs infected by consumption of contaminated ducks
• Area with high H5N1 prevalence
• After 5 days: fever, lethargy, respiratory distress, rapid death
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Lung congestionLung: oedema and heamorrhegs (haemosiderin)
Liver: necrotic areas IHC : viral antigens in hepatocyte nuclei
Songserm et al., 2006, Em. Infect. Dis.
HPAI H5N1 natural infection in dogs
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• Infection with different routes:– Oculo-nasopharyngeal – Direct contact with infected cats
• Subclinical infection– Mild fever (39,2-39,7°C)– Conjunctivitis– Mild increase of hepatic enzyme (AST, CPK)– Periportal lymphocytic infiltration
• Viral shedding • Seroconversion (low Ab titres)• No transmission to contact cats
Giese et al., 2008, Emerg. Infect. Dis.
H5N1 experimental infection of dogs
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Equine H3N8 in dogs
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January 2004 - FLORIDA
OUTBREAK OF RESPIRATORY DISEASE IN GREYHOUNDS
8/22 DEAD DOGS (36%)
CLINICAL SAMPLES TESTED NEGATIVE TO COMMON PATHOGENS
CYNDA CRAWFORD, EL DUBOVI et al., Science, 2005
Equine H3N8 in dogs
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HAEMORRAGES IN THE RESPIRATORY TRACT
VIROLOGICAL INVESTIGATIONScanine/Fl/04
Equine H3N8 in dogs
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2 GENETIC LINEAGES
EUROPEAN
NORTHERN AMERICAN
Equine H3N8 in dogs
3 SUBLINEAGES
SUB-LINEAGE FLORIDA
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CANINE/FL/O4
96-98% NT IDENTITY TO EQUINE H3N8 FLORIDA SUBLINEAGE
ALL GENOMIC SEGMENTSOF EQUINE ORIGIN
Equine H3N8 in dogs
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FL
ALTX
AR
WVKS
AR
IA
CO
WI
Equine H3N8 in dogs
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• RESPIRATORY DISEASE IN FOXHOUNDS
• SUBSEQUENT IDENTIFICATION OF H3N8
SEROLOGICAL INVESTIGATIONS IN FOXHOUNDS
• SEROPREVALENCE OF 37,5%
• LACK OF Ab IN DOGS BORN AFTER APR 2003
• HIGH SEROPREVALENCE (
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• CIRD IN DOGS IN CONTACT WITH INFECTED HORSES
• IDENTIFICATION OF H3N8
Equine H3N8 in dogs
AUSTRALIA, 2007
Kirkland et al., Emerg Infect Dis., 2008
HA
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LARGE H3N8 EPIDEMICS IN HORSES
CROSS-SPECIES TRANSMISSION OF EQUINE H3N8 NORTHERN AMERICAN LINEAGE
Equine H3N8 in dogs
UK, 2002 AUSTRALIA, 2007
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SUBSEQUENT SEROLOGICAL INVESTIGATIONS HAVE SHOWN:
VIRUS PRESENT IN DOGS SINCE 1998
HIGH SEROPREVALENCE IN DOGS IN CONTACT WITH ILL DOGS
HIGH FREQUENCY OF SUBCLINICAL INFECTIONS
Equine H3N8 in dogs
(Larson et al., Clin Vaccine Immunol. 2011)
MOST SEVERE FORMS IN COINFECTIONS WITH S. equi subsp. zooepidemicus
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SOUTH KOREA, 2006
CHINA, 2006-2007
DIRECT TRANSMISSION FROM BIRDS TO DOGS IN LIVE-ANIMAL MARKETS
INDIA, 2011 THAILAND, 2012
Avian-like H3N2 in dogs
Bunpapong et al., Virus Genes 2014
Song et al., Emerg Infect Dis. 2008
Li et al., Infect Genet Evol. 2010
www.avma.org
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NA
HA
Avian-like H3N2 in dogs
Li et al., Infect Genet Evol. 2010
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USA (CHICAGO), APR 2015
• Fever, inappetance, lethargy
• Cough, nasal discharge
• Limited viral shedding (H3N2 1-2 d, H3N8 7-10 d)
99% IDENTITY TO THE ASIAN VIRUS
Avian-like H3N2 in dogs
http://www.cdc.gov/flu/news/canine-influenza-update.htm
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5/23/2016 -7/11/2016 (H3N2)
Avian-like H3N2 in dogs
https://ahdc.vet.cornell.edu/news/civchicago.cfm
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Avian-like H3N2 in cats
Zhou et al., Vet Microbiol. 2015CHINA, 2006-2007
AVIAN-LIKE H3N2 Ab IN STRAY CATS IN POULTRY LIVE MARKETS
SOUTH KOREA, 2009-2010 Song et al., J Gen Virol. 2011
LARGE OUTBREAK OF AVIAN-LIKE H3N2 IN DOGS AND CATS OF AN ANIMAL SHELTER IN SEOUL
• Dogs (200): 25% mortality; ? Morbidity• Cats (50): 40% mortality; 100% morbidity
USA, 2009-2010 http://www.uwsheltermedicine.comCATS WITH URD IN AN ANIMAL SHELTER IN NW INDIANAWITH DOGS WITH CIV
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http://www.doginfluenza.com/professionals/#
NO EVIDENCE FOR ZOONOTIC ACTIVITY
Equine H3N8 and avian-like H3N2
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2009: SWINE FLU
pdm09 H1N1
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pdm09 H1N1 in cats
USA (IA), Dec 2009A 13-YEAR-OLD CAT BECAME ILL AFTER ITS OWNERSDISPLAYED SEVERE DYSPNOEA AND PNEUMONIA
Sponseller et al., Emerg Infect Dis. 2010
ITALY, Dec 2009 Dundon et al., Emerg Infect Dis. 2010
FRANCE, Dec 2009 www.avma.org
A 5-YEAR-OLD CAT BECAME ILL AFTER TWO CHILDREN
SEVERE OUTBREAK OF RESPIRATORY AND GI DISEASE
25/90 CATS
50% MORTALITY
COINFECTION WITH FPLV?
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THE NETHERLANDS, 2010van den Brand et al., Emerg Infect Dis. 2010
EXPERIMENTAL INFECTION
pdm09 H1N1 in cats
MILD-MODERATE DISEASE
POSITIVE PCR RESULTS
NO VIRUS ISOLATION
8 intratracheallyinfected cats
4 contact catsNO DISEASE
VIRAL SHEDDING
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CHINA, Nov 2009NATURAL INFECTION IN TWO DOGS WITH RESPIRATORY DISEASE
Lin et al., J Gen Virol. 2012
USA (NY), Dec 2009A 13-YEAR-OLD DOG BECAME ILL AFTER ITS OWNER
www.avma.org
ITALY, OCT-DEC 2009
SEROLOGICAL EVIDENCE FOR CIRCULATION OF pdmH1N1
Dundon et al., Emerg Infect Dis. 2010
pdm09 H1N1 in dogs
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CHINA, Nov 2012 Lin et al., J Gen Virol. 2012
EXPERIMENTAL INFECTION
pdm09 H1N1 in dogs
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Song et al., J Gen Virol. 2015
LIMITED ROLE IN pdmH1N1 SPREADING
TO HUMANS
pdm09 H1N1 in dogs
VIRUS TRANSMISSIONFROM HUMANS TO PETS
SOUTH KOREA, 2014
EXPERIMENTAL INFECTION
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Roberts (2004). Science, 305: 1890-1893.ONE DOT=1000 DEATHS
Rotaviruses in humans
SEVERE ACUTE GASTROENTERITIS IN CHILDREN WORLDWIDE OVER A HALF MILLION DEATHS ANNUALLY IN DEVELOPING COUNTRIES
Rotavirusof group/species A
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Rotaviruses in animals
ENTERITIS IN FOALS (VACCINES)
ENTERITIS IN DOGS AND CATS
ENTERITIS IN CHICKENS
ENTERO-COLITIS/ENTERITISCOMPLEX OF RABBITS
NEONATAL ENTERITIS IN CALVES (VACCINES)
WEANING AND POST-WEANING DIARRHEA IN PIGLETS (VACCINES)
Rotavirusof group/species A
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MAY ANIMAL ROTAVIRUSES BE TRANSMITTED TO HUMANS
ARE THERE MOLECULAR MECHANISMSCONTROLLING INTER-SPECIES TRANSMISSION
DO HETEROLOGOUS INFECTIONS GENERATE VIRUSES OF EPIDEMIOLOGICAL RELEVANCE FOR HUMANS
Rotaviruses in animals
BUT NOT DETERMINED
Rotavirusof group/species A
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(Doro et al., Expert Rev Anti Infect Ther. 2015)
PREVALENCE OF ROTAVIRUS G AND P TYPES IN THE POST-VACCINAL ERA (2007-2012)
G1P[8]G2P[4]G3P[8]G4P[8]G9P[8]G12P[8]
Rotaviruses in humans Rotavirusof group/species A
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PREVALENCE OF ROTAVIRUS G AND P TYPES (2007-12)
OTHER ROTAVIRUS STRAINS (UNUSUAL COMBINATIONS OF G/PTYPES, RARE OR ANIMAL-LIKE TYPES)
AFRICA 8224 2323 (28.0) 1040 (12.6)
AMERICAS 6756 686 (10.1) 639 (8.2)
REGION TOTAL OTHERS (%) NT (%)
WPR 9480 638 (6.7) 907 (9.5)
SEAR 5728 911 (15.9) 1180 (20.6)
EMR 2341 276 (11.7) 336 (14.3)
EUROPE 14138 403 (2.8) 760 (5.3)
TOT 46667 5237 (11.2) 4862 (10.4)
Rotaviruses in humans Rotavirusof group/species A
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ROTAVIRUS-LIKE PARTICLES DETECTED AT LOW FREQUENCY FROM BOTH SYMPTOMATIC AND ASYMPTOMATIC DOMESTIC CARNIVORES (MARSHALL ET AL., 1984, 1987).
DIARRHEA HAS BEEN REPRODUCED IN NEONATAL GNOTOBIOTIC DOGS INFECTED EXPERIMENTALLY WITH A CANINE RV (Johnson et al., 1983).
NOT REGARDED AS A MAJOR ENTERIC PATHOGENS IN PETS
Rotaviruses in pets Rotavirusof group/species A
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PETS ROTAVIRUS ARE FREQUENTLY TRASMITTED TO HUMANS
EITHER G3P[3] OR G3P[9] RVs OF CANINE/FELINEORIGIN ARE REPORTED IN HOSPITALIZED CHILDREN
SOCIAL INTERACTIONS INCREASE THE RISKOF INFECTION OF HUMANS WITH PETS RVs
GENOME SEQUENCING OF CANINE AND FELINERVs HAS PROVIDED INTERESTING CLUES TO UNDERSTAND THIS ZOONOTIC EXPOSURE
Rotaviruses in petsRotavirus
of group/species A
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VP7
VP4
Rotaviruses in pets
Rotavirusof group/species A
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Rotaviruses in pets
Rotavirusof group/species A
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Rotaviruses in pets
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Rotaviruses in pets
DISCOVERY OF NON-A ROTAVIRUSES IN DOGS
Rotavirusof group/species C
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Rotaviruses in pets
DISCOVERY OF NON-A ROTAVIRUSES IN DOGS
Rotavirusof group/species I
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Rotaviruses in pets
DISCOVERY OF NON-A ROTAVIRUSES IN DOGS
Rotavirusof group/species I
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Vesiviruses in cats
ULCERATIVE STOMATITIS
SYSTEMIC DISEASE
OCCASIONALLY REPORTED IN DOGSMartella et al., Vet Microbiol. 2002
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Vesiviruses in dogs
NOT REGARDED AS MAJOR PATHOGENS
NOT INCLUDED IN THE DIAGNOSTIC ALGORITHMS
(Schaffer et al., 1985; Mochizuki et al., 1993)
ENTERIC DISEASE
Germany, 2003
A CALICIVIRUS (STRAIN 2117) CONTAMINATES CHO CELLS USED FOR PRODUCTION OF BIOLOGICAL PRODUCTS