THE  EFFECT  OF  ECOLOGICAL  AND  ENVIRONMENTAL  FACTORS  ON  WEST  NILE  VIRUS  PREVALENCE  IN  HUMANS  

 Matthew  Schell  

 BIOS  3010  Ecology,  fall  2012  

Department  of  Biological  Sciences,  Western  Michigan  University  Kalamazoo,  MI  49008,  USA  

   Abstract     This  study  set  out  to   investigate  the  ecological   factors  which   influence  the  prevalence  of  West  Nile   Virus   in   humans.     Several   different   ecological   variables   were   examined   including:     temperature,  precipitation,  urbanization,  hydrogeography,  association  with  birds,  and  vector  species  feeding  patterns.    The  extent  to  which  these  variables  affect  the  abundance  of  the  vector  mosquito  species  population  and  thus,   infection   rates   in   humans   is   varied.     An   increase   in   temperature   had   the   strongest   and   most  consistent   effect   on   increasing   abundance   of   mosquitoes   and   infection   rates   in   humans.     Increased  urbanization   and   decreased   hydrogeography   also   increased   human   infection   rates.     Results   for  precipitation   were   inconclusive,   as   were   correlations   with   vector   species   association   with   birds   and  feeding  patterns.    These  variables  all  contribute  significantly  to  modeling  both  mosquito  populations  and  infection  rates  in  humans,  and  continued  studies  examining  the  interplay  of  these  variables  will  result  in  models  with  increasing  accuracy.    Key  words:    West  Nile  Virus,  mosquito,  vector-­‐borne  disease,  climate,  ecology,  corvid  birds,  temperature,  precipitation,  urbanization,  hydrogeography    Introduction  

  West  Nile  Virus  (WNV)  is  a  vector  born  disease  that  was  first  found  in  the  United  States  in  1999,  having  originated   from  Uganda.    West  Nile  Virus   is  now  a   large  public  health  concern  near   the  end  of  every  summer  because  of  the  prevalence  of  effective  mosquito  vectors  at  this  time  of  year.    Generally,  WNV  causes  asymptomatic  illness  in  humans,  with  some  people  developing  flu-­‐like  symptoms  that  last  for   a   few   days.     In   rare   cases  WNV   can   progress   to   encephalitis,  which   can   lead   to   permanent   brain  damage  or  death  (Goldblum  et  al.  1956).      

The   virus   was   first   successfully   isolated   in   Uganda   in   1937   from   a   woman   in   the   West   Nile  district   in   Northern   Uganda   (Smithburn   et   al.   1940).     The   initial   tests   which   were   done   on   the   virus  revealed  that  WNV  was  similar  in  nature  to  other  vector  borne  diseases  capable  of  causing  encephalitis  such  as  St.  Louis  encephalitis,  louping  ill,  and  Japanese  B  encephalitis  (Smithburn  et  al.  1940).    

 After   this   first   isolation,   the  virus   remained  common  and  at  endemic   levels   throughout  Africa  with  occasional  forays  into  the  Middle  East  and  Africa  (Tsai  et  al.  1998).    Periodic  epidemics  occurred  in  Israel  and  Africa  throughout  this  time  period;  however,  Europe  remained  relatively  free  of  the  virus  until  

1996  when  the  first  epidemic  of  WNV  struck  Southeastern  Romania  (Tsai  et  al.  1998).    The  first  major  outbreak  in  Europe  was  closely  followed  by  the  transfer  of  the  virus  to  North  America  in  1999.    The  virus  was   first   isolated   in   New   York   in   the   late   summer   of   that   year   (Lanciotti   et   al.   1999).     Using   DNA  evidence,  it  was  determined  that  the  strain  of  WNV  present  in  New  York  was  most  closely  related  to  a  strain  of  WNV  isolated  from  Israel  in  1998  (Lanciotti  et  al.  1998)  (Figure  1).          

This  allows  a  clearer  picture  of  how  the  introduction  of  WNV  to  North  America  occurred.    Three  explanations  seem  plausible.    First,  an  individual  may  have  contracted  WNV  while  in  Israel  and  returned  to   the  United   States.     After   returning   to   the  United   States   that   individual  may  have  been  bitten  by   a  mosquito   while   still   infected.     The   now   infected   mosquito   may   have   then   fed   on   other   hosts,   thus  transmitting   and   amplifying   the   virus.     Second,   some   sort   of   infected   animal   host   may   have   been  inadvertently  transported  to  New  York  via  airplane  or  ship.    Third,  one  or  more  infected  mosquitoes  may  vectors  have  been  transported  and  upon  arrival  in  the  United  States,  these  mosquitoes  could  have  then  infected  a  number  of  hosts,  amplifying  and  transmitting  the  virus.      

After  arriving  in  the  United  States,  WVN  quickly  spread  throughout  the  continental  US,  moving  westward  with  each  successive  year  and  was  present   in  all  areas  of   the  United  States  by  2008  (Young  and   Jensen   2012).     It   has   been   proposed   that   the   spreading   mechanism   for   WNV   was   along   bird  migratory  routes,  since  normal  mosquito  dispersal  patterns  were  not  extensive  enough  to  account   for  the  rapid  spread  of  the  virus  (Young  and  Jensen  2012).    The  distribution  of  WNV  cases  throughout  the  US,  however,  is  not  uniform,  but  aggregated  in  certain  areas.    Generally,  there  appears  to  be  more  cases  of  WNV  in  and  near  urban  centers.    This  is  true  when  looking  at  absolute  numbers  of  human  WNV  cases,  but  also  when  looking  at  proportions.    In  addition  to  the  aggregation  of  cases  near  urban  areas,  a  much  higher   than   expected   proportion   of   human   cases   is   found   in   the   upper  mid-­‐west   and   the  Mississippi  River  Valley  (Young  and  Jensen  2012)  (Figure  2  and  Figure  3).  

As  with  any  emerging  disease,  WNV  is  a  cause  for  concern  because  of  the  unknown  effects  it  will  have  on  human  and  animal  populations  throughout  North  America.    While  data  exists  on  the  prevalence  and   intensity   of   infections   in   other   parts   of   the   world,   ecological   and   environmental   factors   in   the  United  States  are  different  and  may  lead  to  a  higher  incidence  of  infection.    In  addition,  WNV  has  shown  the   ability   to   form  new   strains,   as   evidenced   by   the   extensive   phylogenic   tree   stretching   back   to   the  initial  isolation  (Lanciotti  et  al.  1999).    It  is  possible  that  a  new  strain  may  become  more  pathogenically  virulent  than  previous  strains,   thus   leading  to  a  higher   incidence  of  deaths  or  serious  health  problems  among   humans.     Also,   the   possibility   of   a   new   public   health   issue   has   the   potential   to   add   a   great  amount  of  cost  to  the  health  care  system  in  America.    All  of  these  valid  concerns  about  WNV  have  led  to  extensive  research  in  an  effort  to  learn  about  and  control  the  spread  of  the  disease.    

Considering  the  potential  effects  of  extensive  WNV  infection  among  humans,  understanding  the  way   in   which   WNV   is   spread   is   of   the   utmost   importance   to   medical   personnel.     Ideally,   the   basic  reproductive  rate   (Rp)  of  WNV  would  be   lower   than  1,   leading  to  a  decrease   in   the  number  of  human  cases   experienced   by   the   population   each   year.     Since   the   reproductive   rate   is   a   product   of   disease  latency,  density  of  susceptibles,  and  transmission  rate,  where  Rp=LSβ,  there  are  two  ways  in  which  it  is  possible  to  lower  the  Rp  of  WNV  (Begon  et  al.    2006).    First,  the  transmission  rate  (β)  of  the  disease  could  be  lowered.    In  the  context  of  WNV  this  would  mean  reducing  the  probability  that  an  infected  mosquito  comes  in  contact  with  a  susceptible  human,  or  reducing  the  affinity  of   infected  mosquitoes  for  human  hosts.    To  reduce  β  the  number  of  infected  mosquitoes  would  have  to  be  reduced,  meaning  that  control  measures   for  mosquito   populations   in  WNV-­‐prone   areas  would   need   to   be   instituted.     Decreasing   Rp  may   also   be   accomplished   by   reducing   the   number   of   susceptible   human  hosts,   S,   in   the   population.    The   discovery   and   use   of   a   vaccine   for   WNV   would   be   a   possible   way   to   reduce   the   number   of  

susceptible   individuals.     In   addition   to   reducing   the   number   of   susceptible   individuals,   a   vaccine  may  result   in   decreased   length   of   infectious   periods,   L,   in   individuals   who   experience   secondary  breakthrough  of   the  disease   (Andre  et  al.  2008).    Those   individuals  who  receive  a  vaccination,  yet  still  contract   the   disease   generally   have   more   mild   cases   for   a   shorter   duration   (Andre   et   al.   2008).    However,  in  order  for  a  vaccination  program  to  be  effective,  a  critical  proportion  of  the  population  (pc)  would   need   to   be   vaccinated   in   order   to   establish   herd   immunity.     The   proportion   of   a   population  required   to   reach   herd   immunity   is   related   to   Rp   by   the   equation   pc=1-­‐(1/Rp)   (Begon   et   al.   2006).    Normally   the  proportion  of   the  population   required   to   reach  herd   immunity   is  quite  high,   requiring  a  great   deal   of   money   and   effort   to   be   successful.     While   the   development   and   widespread   use   of   a  vaccine  would  most  likely  be  successful,  at  this  point  in  time  the  number  and  severity  of  WNV  cases  do  not  create  the  demand  for  such  efforts.    Therefore,  affecting  β  is  a  much  more  probable  solution  to  the  problem  of  human  WNV  infection  when  considering  costs  and  benefits.     In  order  to   institute  the  most  effective  control  measures,  modeling  mosquito  populations  in  a  region  is  important.    The  most  effective  control  measures  will  be  established  in  areas  of  high  vector  mosquito  abundance,  or  areas  of  high  WNV  infection  rates;  therefore,  the  ability  to  predict  these  at-­‐risk  areas  using  models  is  a  useful  tool.  

West   Nile   Virus   is   a   vector   born   disease,   transmitted   by   certain  mosquito   species   as   vectors;  thus,  controlling  mosquito  distribution  and  abundance  will  lead  to  a  decrease  in  the  number  of  human  WNV  infections.    Many  species  of  mosquitos  are  present   in  the  United  States;  however,  a   few  species  have  been  identified  as  having  the  greatest  impact  on  human  WNV  cases.    These  species  include:    Culex  pipiens,  Culex  quinquefasciatus,  and  Culex  restuans  (Molaei  et  al.  2006;  Hamer  et  al.  2008;  Farajollahi  et  al.  2011).    The  distribution  and  abundance  of  these  mosquitos,  as  with  most  other  organisms,  is  a  result  of  a  combination  of  environmental  and  ecological  factors.    Many  of  these  factors  are  useful  for  modeling  mosquito   populations   and   human   WNV   infection   rates.     Factors   that   influence   mosquito   vector  abundance   include   temperature,   precipitation,   urbanization,   hydrogeography,   and   host   species  abundance.    It  is  important  to  note  that  many  of  the  mosquito  species  that  play  host  for  WNV  feed  on  diets  of  birds  and  mammals,  with  most  showing  a  preference  for  birds.    Therefore,  the  distribution  and  abundance  of  non-­‐human  hosts,  such  as  birds,  may  play  a  role   in  vector  mosquito  species  distribution  and  abundance.    Also,   these  environmental   and  ecological   variables  do  not  operate   in   a   vacuum,  but  many  times  interact  and  influence  each  other.    Therefore,  while  it  is  useful  to  examine  each  variable  in  an  isolated  way,  looking  at  the  big  picture  is  equally  important.  

If   there   was   no   relationship   among   human  WNV   cases,   mosquito   abundance,   and   ecological  factors,   then   it   would   be   expected   that   the   incidence   of   human   infections   would   randomly   occur  throughout   any   given   area   independent  of  mosquito   abundance   and  ecological   variables.     A   series   of  null  hypotheses  can  be  developed  to  examine  these  ecological  factors.    First,  temperature  will  have  no  effect  on  mosquito  vector  density  and  WNV  transmission.    Precipitation  will  have  no  effect  on  mosquito  vector  density  and  WNV  transmission.    Urbanization  will  have  no  effect  on  mosquito  density  and  WNV  transmission.    Hydrogeography  will  have  no  effect  on  mosquito  vector  density  and  WNV  transmission.    Finally,  mosquito   feeding   patterns   and   density   of   avian   hosts  will   have   no   effect   on  mosquito   vector  density   and   WNV   transmission.     Alternatively,   if   human   WNV   infections   are   affected   by   mosquito  abundance   and   the   ecological   factors   named   in   the   null   hypotheses,   then   aggregation   of   human  infections  will  be  evident.     In  order  to  determine  the  validity  of  the  hypotheses  several   lines  of  inquiry  must  be   investigated.     It  must  be  determined  what  variables  affect   the  distribution  and  abundance  of  vector  mosquito   species   (temperature,   precipitation,  urbanization,  hydrogeography,  mosquito   feeding  patterns,  and  density  of  avian  hosts).    Therefore,  each  variable  that  affects  the  mosquito  species  must  be   investigated   and   related   to   a   change   in   mosquito   abundance.     Positive   and   negative   effects   on  mosquito  population  will  allow  for  a  greater  understanding  of  mosquito  population  dynamics.    Feeding  

and  behavioral  patterns  of   the  vector   is   important   to  understand   in  order   to  determine   the  extent   to  which   infected  mosquitoes  are  coming   into  contact  with  humans.    A  mosquito  population  with  a  high  prevalence  of  infection,  but  low  preference  for  human  hosts  may  not  be  as  dangerous  as  a  population  with  a  moderate  rate  of  infection,  and  high  preference  for  human  hosts.  

Methods  

  The   idea   for   this   review   came   from   the   extensive  media   coverage   given   to  WNV   at   the   time  when  I  was  choosing  my  topic.    My  research  into  WNV  included  searches  on  three  different  databases  at  Western  Michigan  University’s  library:    Web  of  Science,  BIOSIS  Previews,  and  Pubmed.    The  objective  for  my  initial  research  into  this  topic  was  to  build  background  knowledge,  to  understand  the  major  areas  on  inquiry   in  WNV  research,  and  what  ecological  concepts  were  being   investigated.     I   spent  1.5  hours  on  this  part  of  the  research,  using  different  key  word  searches  in  all  3  databases  and  gathering  a  wide  array  of  sources.      

  My   first   keyword   search   used   three   terms:     “west   nile”,   “mosquito”,   and   “climate”,   which  returned   results   of   108   on  Web   of   Science,   37   on   BIOSIS   Previews,   and   94   on   Pubmed.     The   second  keyword  search  used:    “west  nile”,  “temperature”,  and  “geography”,  and  returned  8  results  on  Web  of  Science,  0  on  BIOSIS  Previews,  and  24  on  Pubmed.    The  final  keyword  search  of  “west  nile”,  “mosquito”,  and  “geography”  gave  results  of  23  on  Web  of  Science,  6  on  BIOSIS  Previews,  and  24  on  Pubmed.    From  these   initial  searches   I   found  10  articles  that   I  determined  to  be  useful   in  my  paper   including:    8   from  Web  of  Science,  1  from  BIOSIS  Previews,  and  1  from  Pubmed.  

  After   the   initial   search,   using   general   keywords   related   to   the   topic   of   WNV,   I   continued   to  return   to   the  databases   for   two   reasons.     First,   I  would   search   for  more  articles  when  a  new  path  on  inquiry   was   discovered.     Second,   if   I   was   unable   to   draw   conclusions   about   a   specific   variable,   or   I  required  more   information  on  the  topic,   I  would  do  more  research.    For  example,  as   I  was  reading  an  article   found   in   the   initial   searches,   I   came   across   a   discussion   of   the   correlation   of   corvid   birds   and  WNV.    Therefore,  I  returned  to  the  databases  and  used  the  search  terms  “west  nile”  and  “corvid  birds”  in   order   to   obtain   articles   looking   at   the   relationship   between   these   two   topics.    More   commonly,   I  searched  for  articles  cited  within  the  article  I  was  reading.    This  seemed  to  be  the  most  efficient  way  to  find  relevant  articles.     I  noticed  that  while  searching  with  key  words  many  unrelated  articles  would  be  found,  which  would  require  time  to  sort  through  and  identify  relevant  ones.  

In  addition  to  the  data  collected,  I  noticed  some  differences  in  the  types  of  articles  I  would  find  when  comparing  databases.    Web  of  Science  was  by  far  the  most  useful  database  for  my  purpose.    This  was  where   I   found   the  vast  majority  of  my  articles,   and   it  was   the   first  database   I  would  go   to  when  looking  for  a  specific  article  cited  in  previously  found  literature.    I  noticed  that  BIOSIS  Previews  seemed  to  return  a  fewer  number  of  articles  using  the  same  keywords  than  Web  of  Science,  and  many  articles  would  be   (were?)   the   same.    While  Pubmed   contained  a   great  deal   of   articles   related   to   the  medical  implications  and  descriptions  of  WNV,  few  were  related  to  ecological  issues  affecting  the  spread  of  the  infection.    Therefore,  I  rarely  found  myself  returning  to  this  database  after  the  initial  search.  

 

 

 

Results  

Temperature  

  Increased  temperature  has  been   linked  with  an   increased  risk  of  human  WNV  cases   in  several  studies,  due  to  the  increase  in  abundance  of  vector  mosquito  species  (Pecoraro  et  al.  2007;  Roth  et  al.  2009;  Deichmeister  and  Telang  2010;  Morin  and  Comrie  2010;  Reisen  et  al.  2010).    The  vector  species  of  WNV  generally   appear   to   be   able   to   reproduce   and   survive   for   longer   periods   of   time  under  warmer  conditions.    One  article  discusses  an  increase  in  temperature  in  the  context  of  the  overwintering  ability  of  vector  species  (Reisen  et  al.  2010).    In  areas  such  as  California  and  Florida,  winter  temperatures  have  the  potential   to  be  mild   enough   to   allow   for   survival   of   some  mosquitoes   from   the  previous   year.     If  these  mosquitoes  are  infected  with  WNV,  it   is  possible  that  an  increase  in  WNV  cases  will  be  seen  the  next  year  due  to  the  increased  prevalence  of  mosquito  vectors.      

  Also,  it  has  been  identified  that  range  expansion  of  vector  mosquitoes,  and  consequently  human  WNV  infections,  have  geographically  expanded  to  areas  with  increased  temperatures  (Roth  et  al.  2009).    The   expansion   of   WNV   into   British   Columbia   is   an   example   of   the   relationship   between   WNV   and  increased  temperature.    A  large  portion  of  Canada  has  been  infected  with  WNV  since  2002,  with  British  Columbia  being  the  only  southern  province  absent  of  the  infection  until  2009.    The  exact  cause  of  this  7  year  gap  between  infection  of  the  majority  of  Canada  and  the  infection  of  British  Columbia  is  unknown;  however,  in  2009  temperatures  were  above  the  10-­‐year  average.    Additionally,  the  area  where  the  first  human  WNV  cases  were  found  was  in  the  hottest  part  of  British  Columbia  (Roth  et  al.  2009).  

Precipitation  

  Precipitation   is   another   variable   that   is   widely   discussed   as   having   an   effect   on   human  WNV  infections;   however,   a   direct   causal   relationship   is   unable   to   be   drawn.   (Pecoraro   et   al.   2007;  Deichmeister   and   Telang   2010;  Morin   and   Comrie   2010;  Walsh   2012)).     Studies   that   have   found   low  levels  of  precipitation  to  be  linked  to  an  increase  in  WNV  infections  in  humans  have  generally  done  so  in  urban   areas   (Deichmeister   and   Telang   2010).     Urban   areas   generally   have   an   extensive   storm   drain  system  to  handle  runoff.    During  periods  of  high  rain  this  storm  drain  system  consists  mostly  of  moving  water,   which   is   an   unsuitable   habitat   for   mosquitoes.     However,   during   periods   of   low   rainfall,   or  drought,  water  within  the  system  becomes  stagnant,  and  mosquitoes  are  able  to  reproduce  much  more  effectively.    The  large  amount  of  suitable  breeding  grounds  for  vector  species  in  urban  areas  leads  to  an  increase  in  abundance,  and  thus,  an  increase  in  WNV  human  infections.  

  Other   studies   have   found   precipitation   not   to   be   correlated   to   WNV   infection   in   humans  (Pecoraro  et  al.  2007).    Although  this  study  examined  some  urban  and  suburban  areas,  it  also  included  areas  outside  of  the  urban  environment.    It  is  possible  then,  that  precipitation  plays  a  large  role  in  urban  areas  and  is  less  important  in  more  rural  settings.  

  Also,  the  amount  of  water  naturally  present  in  an  environment  may  determine  the  effect  rainfall  has  on  mosquito  abundance.    Since  mosquitoes  need  water  to  reproduce,  in  severe  drought  conditions  where   no   standing  water   is   present,  mosquito   abundance  will   be   reduced   (Morin   and   Comrie   2010).    However,  in  periods  of  drought  where  reproductive  areas  still  exist  for  mosquitoes  (such  as  storm  drain  systems   in   urban   areas),   abundance  may   increase   due   to   reproductive   habitats   being   undisturbed   by  rainfall.    Therefore,  it  may  be  the  case  that  suitable  habitats  for  reproduction  (surface  water)  are  more  important  than  the  absolute  amount  of  rainfall  received  by  a  region  (Walsh  2012).    

Urbanization  

  Urbanization  has  been   linked  to   increased  abundance  of  mosquito  vector  species   (Pecoraro  et  al.   2007;   Peterson   et   al.   2008;   Deichmeister   and   Telang   2010;).     In   one   study,   which   looked   at   the  abundance  and  variety  of  species  in  rural,  suburban,  and  urban  sites,  the  urban  sites  had  a  significantly  larger   number   of   common  WNV   vector   species  Cx.   pipiens   (Pecoraro   et   al.   2007).     In   addition   to   the  higher   abundance   of   this   vector   species   in   urban   sites,   the   variety   of   species  was  much   lower  when  compared  to  rural  sites.    Rural  sites  tended  to  have  a  much  greater  diversity  of  mosquito  species  when  compared  to  an  urban  environment,  and  many  of  the  rural  species  are  not  known  WNV  carriers,  possibly  reducing   the   risk   of   infection   outside   of   urban   areas.     Therefore,   the   higher   risk   of  WNV   infection   in  urban  areas   can  be  partially   attributed   to   the   lower   species  diversity  and  higher  abundance  of   vector  species.  

  While  it  is  known  that  urban  sites  are  correlated  with  increased  WNV  prevalence,  there  may  be  several   causes   for   this   increase.     One   such   cause  may   be   the   interplay   between   precipitation,   storm  drain   systems,   and   the  mosquito’s   reproductive   behaviors   (Deichmeister   and   Telang   2010).     Another  cause  may  be   the   reduction   in  vegetation  present   in  cities.     It  has  been   found   that  a   reduction   in   the  amount  of  vegetation  in  an  area  is  correlated  with  increased  WNV  transmission  (Peterson  et  al.  2008).    This  has  obvious  implications  for  urban  areas  where  vegetation  is  nearly  absent.    The  large  reduction  in  vegetation  resultant  from  urbanization  may  be  a  factor  driving  the   increase   in  WNV  infection   in  cities.    However,  this  correlation  may  also  help  to  explain  another   infection  pattern  seen  in  rural  areas  of  the  upper  Midwest.     In   the   upper  Great   Plains   region,   there   is   a   proportionally   higher   incidence   of  WNV  infection  after  normalization  by  population  (Young  and  Jensen  2012).    This  area  of  the  United  States  is  mostly  used  for  agriculture  and  is  naturally  grassland.    Compared  to  the  forested  areas  of  much  of  the  rest  of   the  United  States,   the   relatively   low  vegetation   in   this   area  may  help   to  explain   the   increased  incidence  of  infections.  

Hydrogeography  

  Hydrogeography  is  the  study  of  the  orientation  and  amount  of  water  across  a  landscape.    It  has  been  found  that  an  increase  in  hydrogeographic  area  (that  is,  an  increase  in  the  density  of  surface  water  present)   will   result   in   a   decrease   of   WNV   cases   in   humans   (Walsh   2012).     While   this   may   seem  counterintuitive   at   first,   due   to  mosquitoes’   requirement   for   surface  water   to   reproduce,   the   feeding  behavior  of  mosquitoes  lends  an  explanation.    The  vector  species  responsible  for  transmission  of  WNV  to  humans   feed  on  both  birds  and  mammals  at   various   rates,   and  most   species  prefer  birds  as  hosts.    Since  birds  require  a  large  amount  of  water,  an  increase  in  hydrogeographic  area  results  in  an  increase  of   bird   population   density.     With   more   birds   available   for   feeding   the   vector   mosquito   species,   the  mosquitoes   will   feed   on   birds   at   a   higher   rate   than   they   feed   on   mammals,   thus   reducing   the  transmission  to  humans.  

Mosquito  Feeding  Patterns  and  Birds  

  The   vector   species   mosquito’s   diet   varies   from   region   to   region,   and   with   the   abundance   of  hosts.    Generally,  vector  species  feed  mainly  on  birds  and  mammals,  with  a  preference  for  birds  (Ward  et   al.   2008;   Farajollahi   et   al.   2011;  Molaei   et   al.   2011)   (Figure   4).     The   way   by   which  many   humans  become   infected  with  WNV   is  when   they  are  bitten  by  a  mosquito   that  has  previously   fed  on  a  WNV  infected  bird.    Therefore,  identifying  the  prevalence  of  WNV  in  bird  species,  and  the  feeding  patterns  of  species  of  vector  mosquitoes  may  allow  for  prediction  and  modeling  of  WNV  human  infections.      

Crows  have  been  reported  to  be  a  good  indicator  species  for  WNV  prevalence  in  a  region,  since  crows  are  especially  sensitive  to  WNV  and  carry  a  high  viral  load  (Eidson  et  al.  2005;  Bouden  et  al.  2008).    Reporting  and  analyzing  data  of  dead  crows  and  infection  rates  of  crows  in  an  area  may  be  a  good  way  to  predict  the  imminent  introduction  of  WNV  into  a  region  (Eidson  et  al.  2005).    The  interplay  of  crows  and  mosquito   populations   also   affects   the   prevalence   of  WNV   and  modeling   can   be   used   to   predict  epidemics  (Bouden  et  al.  2008).    While  these  studies  suggest  a  simple  relationship  between  crows  and  WNV  infection  in  humans,  the  true  interaction  between  vector  mosquitoes  and  their  hosts  is  much  more  complex.  

Two  species  of  mosquitoes  appear  to  be  prevalent  in  urban  areas  throughout  the  world  and  act  as  vectors  for  WNV,  Culex  pipiens  and  Cx.  quinquefasciatus  (Farajollahi  et  al.  2011).    In  addition  to  these  two  species,  Cx   restuans  and  Cx  salinarius  have  also  been   identified  as  vectors   in   certain  areas  of   the  United  States  (Molaei  et  al.  2006;  Hamer  et  al.  2008).    All  of  these  species  have  a  clear  preference  for  bird   hosts   compared   to  mammals;   however,   crows   constitute   a   very   small   portion   of   the  mosquito’s  diet.    By  sampling  mosquitoes  and  analyzing  their  last  blood  meal,  it  was  found  that  American  robins  and  sparrows  were  much  more  common  hosts  than  crows  (Kilpatrick  et  al.  2006,  Molaei  et  al.  2006).    Given  this  knowledge  of  feeding  patterns  of  mosquitoes,   it  seems  logical  to  measure  the  prevalence  of  WNV  and  death  of  these  more  common  hosts  instead  of  crows.    

One  study   investigated  the  reason  for  an   increase   in  WNV  prevalence  during  the   late  summer  months  (Kilpatrick  et  al.  2006).    Near  the  end  of  summer,  mosquito’s  preferred  bird  species  hosts  start  to  migrate  away  from  the  area.    In  the  northeastern  portion  of  the  United  States,  the  preferred  host  for  Cx.   pipiens   is   the   American   robin,   which   starts   to   migrate   during   the   later   summer   months.     This  decreased  availability  of   its  preferred  host  causes  Cx.  pipiens   to  search  for  new  hosts   in  order  to  feed.    Therefore,   the  mosquito   feeds  more  on  human  hosts  during   this   time.    Unsurprisingly,   this   change   in  feeding  pattern  leads  to  a  greater  infection  rate  in  humans  (Kilpatrick  et  al.  2006).  

Modeling  

  The   use   of   modeling   to   predict   the   number   of   human   cases   of  WNV   can   take   one   of   a   few  different   forms   including:     directly   modeling   human   cases   of   WNV,   modeling   the   distribution   and  abundance  of  mosquito  vector  species,  or  modeling   the  non-­‐human  host  populations  such  as  birds  or  horses.    The  most  desirable  way  to  model  WNV  is  to  predict  directly  the  number  of  human  cases.    If  an  accurate  model   can   be   created   to   predict   the   number   of   human   cases   of  WNV   then   it   simplifies   the  process  and  reduces  the  leaps  in  logic  required  to  go  from  either  mosquito  or  non-­‐human  host  data  to  human   infection.     Several   attempts   have   been  made   to   create   an   accurate  model   to   predict   human  cases  with  some  success  (Peterson  et  al.  2008;  Liu  et  al.  2009).    These  studies  integrate  climate  variables  (temperature,   precipitation,   etc),   mosquito   abundance,   and   WNV-­‐positive   bird   abundance   into   their  models   in  an  effort  to  model  the  patterns  of  human  infection  as  closely  as  possible.    One  study,  while  finding  some  significant  results,  was  limited  by  a  small  number  of  infections  and  a  lack  of  consistency  in  mosquito  trapping  efforts  over  the  study  period  (Liu  et  al.  2009).    Another  study  also  found  limitations  in  their  effort  to  model  human  infections  in  the  form  of  an  inability  to  know  exactly  where  an  infection  had  occurred,   compared   to   where   that   infected   person   lived.     Also   in   this   model,   differences   in   the  distribution   of   people  were   not   taken   into   account,   so   large   concentrations   of   people   (such   as   large  urban   centers)   skewed   the  data   (Peterson  et   al.   2008).     Together   these   two   studies   demonstrate   the  difficulty  in  creating  an  effective  model  for  human  WNV  infections.  

  Other  studies  have  sought  to  model  and  describe  mosquito  or  non-­‐human  host  abundance  and  infections  (Bouden  et  al.  2008;  Ward  et  al.  2009;  Morin  and  Comrie  2010;).    One  study  sought  to  model  the   interactions  between  mosquitoes  and  birds,  using  crows  as  the  primary  mosquito  host  (Bouden  et  al.   2008).    While   this   study  met  with   some   success,   its   concentration   on   a   small   number   of   variables  leaves   it   vulnerable   to   unexpected   changes.     Another   study   investigated   the   interdependence   of  temperature  and  precipitation  and  its  effect  on  a  specific  mosquito  species  (Morin  and  Comrie  2010).    A  final  study  looked  at  the  effect  of  a  large  number  of  variables  on  infections  of  horses  with  WNV  (Ward  et  al.  2009).      

  Taken   together   one   can   see   there   is   a   large   and   highly   variable   effort   under   way   to   model  different  aspects  of  the  WNV  infection  cycle.    The  ultimate  goal  appears  to  be  modeling  human  risk  and  infections;   however,   this   effort   is   hampered   by   a   large   number   of   variables.     In   response,   efforts   to  model   these   variables   have   given   rise   to   some   success,   yet   leave   room   for   interpretive   error   as   the  results  of  these  models  must  be  further  applied  if  human  risk  and  infection  is  to  be  determined.  

Discussion  

  It  is  clear  that  WNV  will  remain  prevalent  in  North  America  for  the  foreseeable  future.    The  quick  spread  of  the  virus  throughout  the  continent,  along  with  the  retention  of  the  virus  from  year  to  year  in  previously   infected   areas,   shows   this   characteristic.     Additionally,   the   public   health   concerns   brought  about  by  this  virus  ensures  it  will  remain  a  high  priority.      

  The  current  research  has  identified  certain  mosquito  species  which  are  vital  to  the  transmission  of   the   disease   and   non-­‐human   hosts   which   serve   as   a   reservoir   for   the   virus.     Therefore,   study   and  control   of   the   transmission   agents   and   reservoirs   are   imperative   to   controlling  human   cases  of  WNV.    Thus  far,  increased  temperature  has  nearly  uniformly  been  identified  as  a  risk  factor  for  increased  WNV  cases  in  humans.    This  has  to  do  with  an  increase  in  mosquito  breeding  and  feeding  frequency  in  periods  of   hot   weather.     Precipitation   seems   to   affect   mosquito   distribution   and   abundance;   however,  controversy  remains  regarding  what  extent   this  variable  plays   in  WNV   infections   in  humans.     It   seems  likely   that   precipitation   alters   infection   rates   in   humans   by   affecting   reproductive   habitats   of  mosquitoes.     Therefore   regional   hydrogeography,   climate,   and   other   landscape   variables   (cities,  mountains,   etc.)   play   a   role   in   determining   the   significance   of   precipitation   on   vector   species  populations,   and   thus,  human  WNV   infections.    Urbanization  appears   to   result   in   an   increased   risk  of  human   infection.     This   stems   from   the   interplay   between   rainfall,   storm   drains,   and   reproductive  habitats  for  vector  species.    Cities  also  tend  to  support  a  smaller  variety  of  mosquito  species,  so  vector  species  play  a  more  prominent  role.    Many  of  the  vector  species  feed  on  birds  as  their  primary  source  of  food;  however,  the  crow  has  been  singled  out  as  an  indicator  species.    While  vector  species  do  feed  on  the  crow,  it  is  a  very  small  portion  of  the  mosquito’s  diet,  and  therefore,  other  birds  may  provide  a  more  accurate  description  of  the  disease  dynamics  of  WNV  within  a  community.      

  For   many   studies,   modeling   and   prediction   is   the   goal   of   testing   and   manipulating   variables  affecting  mosquito  population.    Humans   care  about  WNV,  as  with  any  disease,  because  of   the  health  implications  on  humans.    The  ability  to  accurately  model  and  predict   infection  rates   in  space  and  time  will   lead   to   more   effective   treatment,   and   perhaps   more   importantly,   better   control   of   the   disease  through  manipulation  of  the  mosquito  population.  

  In   the   future,  climate  change  will   continue   to  affect  many  of   the  variables   that  determine   the  distribution   and   abundance   of   vector   mosquito   species.     Temperature   is   increasing,   and   variation   in  

precipitation  amount   is  becoming  more  common.    This  has   implications  for  mosquitoes   in  the  form  of  overwintering   ability   and   range   expansion   (Hongoh   et   al.   2012;   Roth   et   al.   2010;   Reisen   et   al.   2010).    With   increasing   temperatures   vector   species   such   as  Culex   pipiens  may  be   able   to   survive   in   habitats  farther  north  into  Canada,  thus  exposing  a  larger  number  of  people  to  WNV  (Hongoh  et  al.  2012;  Roth  et  al.  2010).    In  addition,  increasing  temperatures  in  more  mild  climates  will  allow  a  greater  proportion  of  the  mosquitoes   to   successfully   over  winter,   possibly   increasing   the   abundance   of  mosquitoes   for   the  next  year  (Reisen  et  al.  2010).    Moreover,  the  increased  temperatures  throughout  the  current  habitats  of   vector   species   during   breeding   season   may   increase   their   abundance   and   biting   frequency  significantly.    

  In   conclusion,   WNV   is   a   serious   vector   borne   illness   that   is   only   in   the   beginning   stages   of  transmission   in   the  Western   Hemisphere.    While   some   variables   have   shown   a   consistent   predictive  pattern,   others   variables   and   their   link   with   WNV   remain   unclear   and   further   study   is   warranted.    Furthermore,  the  interaction  between  variables  must  be  investigated,  and  effective  models  need  to  be  produced  in  order  to  most  effectively  control  transmission  to  humans.      

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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Figure  1:    This  figure  shows  the  genetic  relationships  between  different  strains  of  WNV  based  on  a  the  nucleotide  sequence  of  a  specific  protein.    It  has  been  determined  that  the  first  WNV  infection  in  humans  in  New  York  was  most  closely  related  to  a  strain  isolated  in  Israel  during  the  previous  year  (Lanciotti  et  al.  1999).    

 

 

Figure  2:    Shown  here  is  the  absolute  number  of  WNV  cases  throughout  the  country  from  introduction  in  1999  to  2008.    Each  dot  is  equal  to  5  cases.    Notice  the  clustering  of  cases  near  urban  centers,  the  Mississippi  River  Valley,  and  throughout  the  upper  Mid-­‐West  (Young  and  Jensen  2012).  

 

 

 

 

 

 

 

 

Figure  3:    This  proportional  map  of  human  WNV  infections  between  1999-­‐2008  demonstrates  the  significance  of  the  clustering  of  cases  near  urban  centers  and  the  upper  mid-­‐west  region.    It  appears  that  while  urbanization  plays  some  role  in  increasing  human  WNV  infections,  other  variables  are  at  work  in  some  regions  of  the  country  (Young  and  Jensen  2012).  

 

 

 

 

 

 

Figure  4:    The  proportions  of  hosts  in  4  vector  species  diets.    The  left  vertical  axis  shows  proportion  for  bird  and  mammal  feedings,  while  the  right  vertical  axis  shows  proportions  for  human  feedings.    All  4  vector  species  show  a  significant  preference  for  birds  when  compared  to  mammals,  with  humans  making  up  a  small  percentage  of  mammal  feedings  (Farajollahi  et  al  2011).