Emerging Virus Infections

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Emerging Viruses

  • emerging viruses are ones that until recently have not been cause for serious public or animal health concern 
  • most emerging human viruses are initially zoonoses transmitted from an animal host and undergone adaptation to be maintained in the human host 
  • emerging animal viruses often originate from an animal reservoir and undergo cross-species adaptation 
  • viruses that have shifted their geographical location are also seen as emerging viruses 
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Examples

  • West Nile Fever - Old virus new location 
  • Bluetongue/African Horse sickness - vector changes, climate change and re-emergence
  • Henipaviruses - cross-species transmission, encroachment 
  • Schmallenberg - out of the blue, importance of disease surveillance 
  • Foot and Mouth disease - old enemy, need for constant vigilance 
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West Nile Fever Virus

  • first isolated in West Nile district, Uganda, 1937 
  • 25% of human infections show mild symptoms - fever, aches, occasional rash and lymph node swelling
  • small percentage of these develop encephalitis, ~10% die 
  • severe disease in horses 
  • transmitted by Culex pipiens mosquitoes 
  • short duration, sylvatic life cycle in passerines 
  • humans and horses are incidental, dead-end hosts
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West Nile Fever Virus (2)

  • member of Japanese Encephalitis virus complex 
  • geographically restricted and originally absent from USA 
  • introduced to NY state from Middle East in 1999 - unknown source 
  • spread rapidly N>S along bird migration routes and E>W
  • naive bird popualtion highly susceptible 
  • very high attack rate in the primary wave when virus first entered a region/state 
  • subsequent years herd immunity causes incidence to fall 
  • 2002 - incidence soared - climate reasons? - adaptation of virus?
  • massive incidence in horses especially in colorado 
  • virus is now endemic - incidence of disease has fallen 
  • serological evidence that WNFV circulates in UK but no evidence of disease or isolation of live virus from screening 
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Hendra and Nipah Viruses (1)

Closely related paramoxyviruses 50% fatality in humans 

Hendra  

  • fatalaties due to pneumonia and/or encephalitis 
  • outbreak in 1994 killed 13/24 racehorses and 2/3 humans 
  • one farmer infected after PM on horse, one was a year after apparent recovery 
  • may also infect cats and dogs 
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Hendra and Nipah Viruses (2)

Nipah 

  • fatalaties due mainly to encephalitis 
  • 1999 large outbreak caused by Nipah virus occured in Malaysia 
  • 265 human cases - 105 deaths 
  • most human cases could be traced to contacts with pigs (amplifier species)
  • Nipah was found in 6% of pig farms in Malaysia 1-5% mortality pigs 40% in piglets 
  • end of outbreak pig stocks reduced by 50% - culling
  • 2004 recent outbreak in Bangladesh - no pigs involved 
  • direct transmission to humans - human-to-human transmission 
  • virus circulation in African fruit bats 
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Hendra and Nipah transmission

  • originated from fruit bats
  • nasal/oral transmission requiring direct contact 
  • virus excreted in urine and saliva 

Hendra                                                                 

  • Horse to human transmission (rare)
  • Horse to horse transmission inefficient
  • Cats susceptible - transmit to horses
  • No human-human, cat-cat, horse-cat transmission

Nipah

  • Pig to human transmission inefficient, relatively rare
  • V efficient pig-pig transmission (100% morbidity)
  • also infects dogs, cats, horses and goats
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Schmallenberg virus (1)

  • Bunyaviridae - close relative of Shamonda virus 
  • first recognised - summer 2011 on continent
  • causes diarrhoea and milk-drop in cattle 
  • also transplacental infection and abnormalities in sheep 
  • deformed lambs - arthrogryposis hydranencephaly syndrome - is what alerted APHA
  • very rapidly identified using 'next gen sequencing' and diagnostic PCR developed 
  • identical to virus in NL/Belgium and Germany
  • re-emerged Jan 2012, spread in south, 2013 all UK and Europe
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Schmallenberg virus (2)

  • bunyavirus
  • arbovirus spread by Culicoides pulicaris, dewulfi and obseletus
  • hosts - cattle, sheep and goats (and dogs) 
  • serological evidence for infection in all species of deer (and alpacas) found in UK
  • rapidly declined in subsequent years - high herd immunity 
  • in 2016 currently absent from UK - still considered a potential threat 
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Schmallenberg pathogenesis

  • little known about specific pathogenesis 
  • very high intra-herd prevalence of mild symptoms of acute infection 
  • increased temp - not necessarily fever
  • diarrhoea - not necessarily 
  • very short, pronounced viraemia 
  • sites of viral replication largely undetermined but replicates extensively in neurones 
  • vaccines now available - SBVax and Bovillis 
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FMDV

  • 7 serotypes - large number of antigenically distinct subtypes 
  • wide geographic distribution  - esp Africa, Middle East, Southern and Eastern Asia and India 
  • Pan-Asiatic type O most widely distributed and has caused most recent outbreaks in countries free from FMDV 
  • susceptible species (and others)
    • cattle
    • goats
    • sheep
    • pigs
    • buffalo
    • zebu 
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Clinical Features FMDV

  • clinically indistinguishable from other vesicular virus diseases 
  • signs in cattle include salivation, depression, anorexia, lameness, caused by painful vesicles in skin of lips, tongue, gums, nostrils, coronary bands, inter-digital spaces and teats 
  • fever and decreased milk production usually precede appearance of vesicles 
  • vesicle rupture, leaving large denuded areas prone to secondary infection 
  • in pigs, sheep and goats clinical signs are similar but milder
  • lameness is predominant sign 
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Pathogenesis FMDV

  • respiratory infection results in initial asymptomatic replication in the pharynx
  • virus detected in the soft palette and tonsils 
  • virus spreads systemically to many tissues and organs before the onset of clinical disease
  • replication in stratum spinosum at multiple eplithelial sites leads to vesicle formation 
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Transmission of FMDV

  • one of the most infectious viruses known 
  • lots of virus in breath, saliva, faeces, urine, and milk - up to 4 days before clinical signs 
  • pigs shed a particularly large amount of virus 
  • cattle infection usually respiratory 
  • pigs via ingestion of infected foods - need higher dose
  • other routes - insemination with infected sem en; contact with contaminated clothing, instruments, vehicles and people 
  • inadequately activated vaccine caused 1981 outbreak (France) - major factor or ceasing use of vaccine in Europe 
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Spread FMDV

  • most likely route into UK is illegal importation of meat and unprocessed swill feeding 
  • bio-terrorism possibility for the future 
  • long distance - airbone plumes, esp. in temperate climates, transport vehicles eg UK 2007 
  • local spread - within 3km of another case - ~80% of cases, multiple possible routes - mainly aerosol; cross boundary contacts, farm labour, vehicle and animal movements, vets and wildlife 
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Why is FMDV important?

  • mortality generally low - except in young animals 
  • economic impact is more significant than animal welfare 
  • decreased productivity - 50% reduction in milk yield, retarded growth
  • OIE listed pathogen
  • epidemics are very expensive 
  • UK 2001 
    • 6.5million animals slaughtered - 2.5 million on welfare grounds 
    • £3 billion to control plus £3 billion lost in tourist revenue - 0.2% GDP lost 
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FMDV control

  • majority of developed countries no longer used, or never used vaccination 
  • traditional approach 
  • prevention - strict quarantine laws and standstill policies
  • control by movement band and slaughter policies 
  • 3Km exclusion zones - 10Km surveillance zones 
  • rapid slaughter of animals of infected premises (IP) and dangerous contacts (DC)
  • adaptive approach 
  • computer prediction is used to identify secondary risk areas 
  • culling of contiguous premises - apparently unaffected 
  • firebreak culling 
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Vaccination FMDV?

  • Universal - not cost effective - emergeny vaccination? 

Pros

  • reduced excretion of virus
  • logistical benefits - animal movement 
  • conserve resources
  • more palatable to public 

Cons 

  • delay before protective - slaughter?
  • confounds serological surveillance 
  • conceals carriers 
  • prolongs reacquisition of disease free status  
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Persistently infected FMDV animals

  • difficult to detect as vaccine suppresses replication may reduce response to NSP proteins - false negative 
  • anecdotal evidence suggests transmission from persistently infected animals exists - no experimental evidence for transmission 
  • may be a trigger required to facilitate transmission from persistently infected animals 
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Coping with emerging virus infections

  • recognise the threat early 
  • trying to anticipate is unlikely to be cost effective 
  • global national monitoring for new disease outbreaks (GOARN) necessary to identify new patterns of disease 
  • respond effectively and rapidly 
  • vaccination and movement control policies are best tools for containment 
  • next gen sequencing is an extremely rapid way to identify and characterise a new virus - valuable tool 
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Avoiding Risk Factors

  • factors promoting cross-species transmission
    • encroachment into new habitats - inevitable 
    • changing distribution of vectors - reduce vector numbers? - impractical
    • mixed species farming/markets etc - can be achieved 
  • factors that promote epidemic transmission 
    • high population densities - intensive production, urban populations 
    • international travel and animal importation 
    • global warming 
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