Arboviruses

Arbovirus general info

  • extrinsic incubation period (EIP) - time taken from virus ingestion to subsequent transmissability 
  • arbovirus - arthropod-borne virus - virus transmitted by arthropods (mosquitos, ticks, biting flies) 
  • Cycle of infection:
  • insect bites infected vertebrate host with sufficiently high viraemia to infect vector 
  • virus replicates within insect
  • replication usually causes no harm to the insect vector and the virus disseminates thorugh its tissues and eventually reaches a location that can enable its onward transmission
  • once titre of virus in salivary glands has reached sufficient level can be passed onto new vertebrate host when insect feeds again 
  • alternative route of vector infection is from transovarial transfer to subsequent generations
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Properties of arthropod vectors

  • must be present in the environment where virus is circulating
  • must feed upon host species that carries the virus
  • must be susceptible to infection by bite-sized dose of virus 
  • must be able to replicate the virus in its salivary glands to levels that can be transmitted to new host
  • particular arboviruses are often associated with a restricted range of insect vector hosts
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Arbovirus life cycles

  • simplest cycle involves a primary vertebrate host species and a primary vector species -virus is transmitted in a continuous cycle between these hosts
  • more promiscuous vectors may cross-feed on and infect other host species causing disease these secondary hosts may produce sufficient viraemia to contribute to cycle or may be dead-end hosts 
  • e.g. West Nile fever virus (WNFV) circulates in sylvatic cycle between passerine birds and Culex mosquitos 
    • Culex pipiens will cross-feed on humans and horses and cause disease 
    • both humans and horses are dead end hosts for WNFV 
  • e.g. Bluetongue virus (BTV) replicates in sheep and cows and is transmitted by Culicoides midges 
    • sheep get clinical bluetongue - cattle are usually inapparently infected
    • infected cattle act as amplifier hosts - important maintenance reservoir 
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Seasonality

  • arbovirus transmission is dependent on the vector and consequently is sucject to vector population size and behaviour 
  • when vector numbers are low, trasmission rates fall
  • vector population size is seasonal, being determined by rainfall  and temperature 
  • temperature is also a critical parameter for virus replication 
  • lower the temp the lower the rate of replication - longer EIP 
  • at temperatures below 12C virus replication may cease altogether - eg in BTV
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Overwintering

  • in temperate climates winter poses restriction on arbovirus distribution
  • vector numbers/activity may be absent for parts of year - vector free period 
  • either side of the vector free period vector numbers/activity may be substantial but temperature conditions may reduce virus replication below threshold for transmission - transmission free period 
  • if duration of these periods exceeds time that virus can maintain itself in infected vertebrate host the virus will be eliminated before transmission cycle can restart 
  • in order for an arbovirus to persist in a temperate region it must have a mechanism for overwintering:
    • transovarial transmission to subsequent generations of vector 
    • vector hibernation - migration to warmer areas eg barns
    • longer duration/persistent infection of reservoir host 
    • transplacental transmission 
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Control of arboviruses (general principles)

  • control can be achieved by several approaches:
    • identifying and isolating/eliminating infected hosts 
    • movement restrictions - except possibly in transmission free periods 
    • vaccination - to reduce susceptible host population size below level required for sustained transmission 
    • housing animals during peak activity periods
    • insecticidal dripping
    • reduce vector nubers by destroying habitats and using insceticides 
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Impact of Climate Change

  • global warming - will shorten overwintering periods, extend vector-active seasons, increase vector activity at night, increase vector numbers
  • virus replication will increase - shortening EIP
  • rapid growth of vector results in 'leaky guts' circumventing mesenteron escape barrier - allows previously non-vector species to become competent vectors and potentially increasing geographical and ecological range of virus
  • climate instability may change rainfall patters 
  • more severe weather may blow vectors large distances enabling colonisation of new areas 
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Bluetongue Virus

  • transmitted by Culicoides midges 
    • C. imicola - classically 
    • C. obsoletus 
    • C. pulicaris
    • C. dewulfi 
  • infects all known ruminant species 
  • principally a disease of sheep - usually causes inapparent infection in cattle and goats
  • meat and dairy products pose no transmission hazard 
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Geographic distribution of Bluetongue

  • widely distributed over Africa, Asia, and the Americas 
  • present in Australia in cattle, has not yet caused disease in sheep 
  • periodically occured in Europe but did not usually persist 
  • increasingly common outbreaks in Italy, Yugoslavia, Turkey, Bulgaria, Greece and Corsica - outbreak in N. Europe in 2006 - UK 2007 - now eradicated 
  • expansion of C. imicola territory enabled BTV to establish itself in S and E Europe 
  • blown across from N Africa and overland via Turkey, Yugoslavia and Bulgaria 
  • disease spread beyond C. imicola's range as C. pulicaris and obsoletus are competent vectors and have more northerly range - baton effect 
  • route to N Europe unknown 
  • blown from N Europe to UK - aerial plankton
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Control of Bluetongue

  • largely eliminated from Europe by widespread and effective vaccination policy 
  • policy applied to BTV8 outbreak in UK - v. successful
    • protection zone covered whole of UK
    • strongly encouraged but voluntary vaccination programme (33p-39p per ml dose - 1 for sheep 2 for cows)
    • UK part of larger 'restricted zone' - much of continental Europe too - movement permitted within zone 
    • UK later declared lower risk zone - restrict importation from other zones - keep vaccinating 
    • vectors - removal of habitat and use of insecticides 
    • last confirmed case - November 2008
    • UK declared BTV free since July 2011 - vaccination no longer permitted 
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Overwintering of BTV

  • no evidence of transovarial transmission 
  • infectious virus is detectable in blood for 5 weeks in sheep and 8 weeks in cattle - too short for effective over-wintering 
  • persistent infections of cattle are probably important for over-wintering 
  • possibly latent infection in gamma-delta T cells that harbour the virus over winter and are recruited to bite sites and re-express virus at the start of the next season 
  • virus detectable in blood by PCR for up to 14 weeks in sheep and 20 weeks in cattle 
  • transplacental feature is rare for wild strains but known for vaccine strains 
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West Nile Fever Virus

  • circulates in passerine birds
  • transmitted by Culex pipiens mosquitoes 
  • cross-feeding transmission to horses and humans 
  • can cause severe neurological infection - esp in horses 
  • rapidly lethal to corvids - act as heralds of the arrival of WNFV to a new location 
  • viraemia in birds is usually short-lived 
  • virus overwinters by:
    • transovarial transmission 
    • vector hibernation 
    • long-lived vectors eg ticks 
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Geography/Control WNFV

  • pre-1999 WNFV was absent from USA
  • introduction through unknown means led to extremely rapid spread across entire continental USA 
  • large number of competent vectors 
  • virus adapted and expanded its range of vectors 
  • control - now endemic in USA
  • controlled in horses in USA 
    • vaccination 
    • exposure avoidance 
    • insect repellents 
  • WNFV infects birds in UK - no evidence of disease in horses or humans in UK
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