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Comparing	
  results	
  and	
  predic2ons	
  of	
  different	
  
surveillance	
  approaches	
  for	
  Lyme	
  borreliosis	
  
Canine	
  seroprevalence	
  in	
  New	
  Brunswick	
  as	
  a	
  case	
  study	
  
	
  	
  
Dr. Vett Lloyd
Mt. Allison University
Faculty/Presenter	
  Disclosure	
  
•  Faculty:	
  	
  Ve3	
  Lloyd	
  
•  Rela2onships	
  with	
  commercial	
  interests:	
  
–  Grants/Research	
  Support:	
  NSERC	
  
–  Speakers	
  Bureau/Honoraria:	
  Academic	
  only	
  
–  Consul2ng	
  Fees:	
  None	
  
–  Other:	
  Employee	
  of	
  Mt.	
  Allison	
  University	
  
	
  
Disclosure	
  of	
  Commercial	
  Support	
  
•  This	
  program	
  has	
  received	
  financial	
  support	
  from	
  NSERC	
  in	
  the	
  form	
  of	
  
Discovery	
  Grant,	
  MITACS	
  grant.	
  
•  Poten2al	
  for	
  conflict(s)	
  of	
  interest:	
  
•  	
  None	
  
	
  
MiHgaHng	
  PotenHal	
  Bias	
  
•  NSERC	
  does	
  not	
  dictate	
  or	
  prescribe	
  research	
  results.	
  	
  
	
  
Content:	
  
	
  
1. Different	
  surveillance	
  approaches	
  and	
  the	
  
role	
  of	
  canine	
  seroprevalence	
  studies	
  
2. Canine	
  seroprevalence	
  in	
  New	
  Brunswick	
  
.	
  	
  
Surveillance	
  of	
  Hcks	
  in	
  New	
  Brunswick,	
  2012-­‐1015.	
  Julie	
  Lewis,	
  Ve3	
  Lloyd.	
  
Unpublished.	
  	
  
Lyme	
  disease	
  risk	
  in	
  Dogs	
  in	
  New	
  Brunswick	
  
Natalie	
  K.	
  Bjurman1,	
  Gina	
  Bradet2,	
  Ve3	
  K.	
  Lloyd1,3	
  CVJ,	
  in	
  press	
  
Surveillance	
  for	
  2cks	
  and	
  2ck-­‐vectored	
  diseases	
  	
  
November	
  3rd	
  2014	
  
AcHve	
  Hck	
  surveillance	
  
Canine	
  seroprevalence	
  	
  
Passive	
  Hck	
  surveillance	
  
Human	
  case	
  reports	
  
Labour	
  intensive	
  
and	
  expensive	
  
Low	
  sensiHvity	
  
Under-­‐reporHng	
  
Used	
  extensively	
  in	
  US,	
  
Europe	
  and	
  Asia	
  
Limited	
  use	
  in	
  Canada	
  
PaHcularly	
  useful	
  in	
  areas	
  of	
  
emerging	
  risk	
  
h3p://www.express.co.uk/news/nature/
439432/Mystery-­‐of-­‐killer-­‐canine-­‐
disease-­‐spreading-­‐from-­‐the-­‐New-­‐Forest	
  
Why	
  this	
  works:	
  
h3p://www.dog-­‐care-­‐
knowledge.com/dog-­‐Hck-­‐
removal.html	
  
h3p://www.wellcomeimageawards.org/2014/
Hck-­‐sucking-­‐blood-­‐from-­‐human-­‐leg	
  
Humans	
  and	
  dogs	
  get	
  Lyme	
  
disease	
  in	
  the	
  same	
  way	
  
Advantages	
  –informaHon	
  on	
  canine	
  Lyme	
  is	
  rouHnely	
  collected	
  by	
  veterinary	
  clinics	
  
using	
  standardized	
  and	
  validated	
  methodologies.	
  It	
  is	
  freely	
  available	
  on	
  line	
  which	
  
is	
  valuable	
  for	
  public	
  awareness	
  and	
  educaHon.	
  	
  
Pet	
  Disease	
  Report	
  -­‐	
  IDEXX	
  
h3p://www.petdiseasereport.com/content/
prevmap.aspx?currentprev=LS	
  
New	
  Brunswick	
  as	
  a	
  case	
  study	
  on	
  the	
  use	
  of	
  
canine	
  seroprevalence	
  as	
  a	
  predictor	
  of	
  
human	
  Lyme	
  disease	
  risk	
  
Why	
  New	
  Brunswick?	
  
Leiske,	
  D	
  and	
  V.	
  Lloyd	
  –	
  in	
  review	
  
Surveillance	
  of	
  Hcks	
  in	
  New	
  Brunswick,	
  2012-­‐1015.	
  Julie	
  Lewis,	
  
Ve3	
  Lloyd.	
  Unpublished.	
  	
  
Why	
  
•  Live	
  with	
  humans	
  
•  Robust	
  immune	
  response	
  
•  When	
  ill,	
  similar	
  clinical	
  
manifestaHons	
  of	
  disease	
  
(symptoms)	
  ie	
  arthriHs,	
  
lameness,	
  and	
  neurological	
  
disease	
  	
  
•  InfecHon	
  detected	
  with	
  
commercial	
  kits	
  
Methods	
  
nutrasilver.com	
  
How	
  
•  Recruitment	
  of	
  veterinary	
  clinics	
  
•  100	
  canine	
  blood	
  samples	
  for	
  each	
  of	
  
the	
  7	
  NB	
  health	
  districts	
  
•  Tested	
  699	
  samples	
  using	
  IDEXX	
  
Snap4Dx+C6	
  ELISA	
  and	
  immunoblot	
  
•  Risk	
  factor	
  correlaHon	
  
Borrelia	
  infec2on	
  (Lyme	
  disease	
  risk)	
  in	
  Dogs	
  in	
  New	
  Brunswick	
  
Natalie	
  K.	
  Bjurman1,	
  Gina	
  Bradet2,	
  Ve3	
  K.	
  Lloyd1,3	
  
Results	
  
Rapid	
  recent	
  increase	
  in	
  
canine	
  seroposi2vity	
  (6	
  fold	
  
in	
  6	
  years)	
  
	
  
Western	
  blohng	
  results	
  were	
  
generally	
  consistent	
  with	
  C6	
  
ELISAs	
  but	
  both	
  tests	
  had	
  
false	
  posiHves	
  and	
  possibly	
  
false	
  negaHves	
  
	
  
There	
  is	
  no	
  accepted	
  
algorithm	
  for	
  interpretaHon	
  
of	
  western	
  blots	
  and	
  
posiHve/negaHve	
  calls	
  varied	
  
by	
  algorithm	
  
So	
  what	
  does	
  this	
  mean	
  for	
  humans?	
  
1:6	
  raHo	
  of	
  human:dog	
  infecHons	
  
6,475	
  humans	
  with	
  Lyme	
  
New	
  Brunswick	
  Public	
  Health	
  
	
  
	
  5	
  
Re-­‐assessment	
  approach	
  
ProporHon	
  of	
  
infected	
  Hcks	
  (I)	
  
Number	
  of	
  infected	
  
humans	
  
X	
   X	
   =	
  
x	
  
x	
  
x	
  
x	
  x	
   x	
  
x	
   x	
  
ProporHon	
  
engorging	
  on	
  
humans(F)	
  
Number	
  of	
  Hck	
  bites	
  (T)	
  
X	
   X	
   =	
  
x	
  
x	
  
x	
  
x	
  x	
   x	
  
x	
   x	
  
ProporHon	
  of	
  
infected	
  Hcks	
  (I)	
  
ProporHon	
  
engorging	
  on	
  
dogs	
  (F)	
  
Number	
  of	
  Hck	
  bites	
  (T)	
   Number	
  of	
  infected	
  
dogs	
  
Propor2on	
  of	
  infected	
  2cks	
  -­‐	
  I	
  
I	
  =	
  0.123	
  (NML	
  low	
  value	
  .068,	
  high	
  value	
  .159)	
  	
  
Ogden	
  et	
  al.	
  2006 	
  Dibernardo	
  et	
  al	
  2014	
  Lewis	
  and	
  Lloyd	
  (in	
  prep)	
  
	
  
1990-­‐2003 	
  2012 	
   	
  	
  	
  	
  	
  	
  2014	
  
	
  
151 	
   	
  364 	
   	
  	
  	
  	
  	
  	
  536	
  
	
  
15.9% 	
   	
  6.8% 	
   	
  	
  	
  	
  	
  	
  12.3%	
   	
  	
  	
  
year	
  
Number	
  
tested	
  
%	
  
infecHon	
  
Propor2on	
  of	
  fed	
  2cks	
  -­‐	
  F	
  
F	
  =	
  0.614	
  /0.08	
  (humans)	
  or	
  0.974/.60	
  (dogs)	
  
0	
  
1	
  
2	
  
3	
  
4	
  
5	
  
6	
  
7	
  
8	
  
9	
  
10	
  
0	
   2	
   4	
   6	
   8	
   10	
  
BL/SL	
  ra2o	
  
BW/SW	
  ra2o	
  
NB	
  2014	
  Hcks	
  
Literature	
  
Tick	
  size	
  vs	
  2me	
  feeding	
  
72hrs	
  
0-­‐24h	
   19	
  
1-­‐2	
  days	
   1	
  
2-­‐3	
  days	
   3	
  
3+	
  days	
   2	
  
0-­‐24h	
   25	
  
1-­‐2	
  days	
   18	
  
2-­‐3	
  days	
   97	
  
3+	
  days	
   208	
  
humans	
   dogs	
  
x	
  
x	
  
x	
  
x	
  x	
   x	
  
x	
   x	
  
Number	
  of	
  2ck	
  bites	
  -­‐	
  T	
  
2014	
  -­‐	
  111,677	
  dogs	
  in	
  NB	
  -­‐	
  	
  
	
  
6,700	
  (6%)	
  Borrelia	
  seroposiHve	
  	
  
Ipsos-­‐Forward	
  on	
  behalf	
  of	
  the	
  Canadian	
  
Animal	
  Health	
  InsHtute	
  (
h3p://www.cahi-­‐icsa.ca/companion-­‐
animal-­‐health/	
  	
  
and	
  StaHsHcs	
  Canada	
  	
  
To	
  produce	
  6,700	
  Borrelia	
  seroposiHve	
  dogs	
  with	
  
a	
  Hck	
  infecHon	
  rate	
  of	
  12.3%	
  and	
  with	
  60%	
  fed	
  3+	
  
days	
  gives	
  an	
  esHmated	
  90,786	
  2ck	
  bites	
  	
  
Adjustments:	
  	
  
Average	
  1.33	
  Hcks/dogs	
  (so	
  more	
  Hck	
  bites)	
  
Not	
  all	
  Hcks	
  found	
  by	
  dog	
  owners	
  (so	
  more	
  Hck	
  bites)	
  
Tick	
  infecHon	
  rate	
  can	
  reflect	
  infecHon	
  acquired	
  from	
  host	
  so	
  
infecHon	
  rate	
  could	
  really	
  be	
  11.56%	
  –	
  so	
  more	
  Hck	
  bites	
  
Part	
  1.	
  Dogs	
  
Part	
  2.	
  Extrapola2ng	
  dog	
  to	
  human	
  2ck	
  bites:	
  	
  
Number	
  of	
  2ck	
  bites	
  -­‐	
  T	
  
To	
  what	
  extent	
  does	
  a	
  Hck	
  prefer	
  a	
  dog	
  
to	
  a	
  human?	
  	
  
This	
  can	
  be	
  esHmated	
  from	
  return	
  rates	
  
from	
  passive	
  surveillance	
  programmes	
  or	
  
from	
  the	
  literature.	
  	
  
h3p://www.feathersandfleece.com/
gpage13.htmlfgfr	
  
	
   	
   	
  NB	
  Hcks	
  from	
  humans 	
  NB	
  Hcks	
  from	
  dogs	
  
Dibernardo	
  et	
  al	
  (2014)	
   	
  123 	
   	
   	
  187	
  
	
  
Lewis	
  and	
  Lloyd	
  (in	
  prep) 	
  25	
   	
   	
   	
  429	
  	
  
	
   	
   	
  148 	
   	
   	
  616	
  
19.4%	
  of	
  Hcks	
  on	
  humans	
  vs	
  dogs	
  
Lindenmeyer	
  et	
  al	
  1991	
  :human:dog	
  Hck	
  raHo	
  of	
  1:6	
  (14.3%)	
  	
  
This	
  gives	
  us	
  an	
  esHmate	
  of	
  19.4%	
  x	
  90786	
  dog	
  Hck	
  bites	
  17,612	
  human	
  2ck	
  bites	
  (T).	
  	
  
	
  
So	
  what	
  does	
  this	
  mean	
  for	
  humans?	
  
Lindenmeyer	
  et	
  al	
  1991	
  
6,475	
  humans	
  with	
  Lyme	
  
5	
  
New	
  Brunswick	
  Public	
  Health	
  
LB	
  =	
  I	
  x	
  F	
  x	
  T(h)	
  
MulHplied	
  by	
  the	
  infecHon	
  rate	
  (I)	
  of	
  
12.3%	
  and	
  probability	
  of	
  a	
  Hck	
  on	
  a	
  
human	
  having	
  fed	
  3+	
  days	
  (F),	
  8%	
  
173	
  predicted	
  
human	
  infecHons	
  
in	
  NB	
  in	
  2014.	
  	
  
(ConservaHve	
  
esHmate)	
  
Discrepancies:	
  
	
  
	
  
TesHng	
  at	
  the	
  Hme	
  of	
  Hck	
  bite	
  
	
  
Lyme	
  diagnosis	
  not	
  considered	
  
	
  
Under-­‐reporHng	
  
	
  
Single	
  Her	
  vs	
  two	
  Hered	
  tesHng	
  
	
  
SensiHvity	
  of	
  tesHng	
  
	
  
Perdurance	
  of	
  canine	
  seroposiHvity	
  
	
  
IDEXX	
  tech	
  notes	
  
Conclusions	
  
Canine	
  seroposi2vity	
  surveillance	
  
is	
  a	
  powerful	
  complement	
  to	
  2ck	
  
surveillance	
  approaches	
  
	
  
•  Inexpensive	
  (as	
  it	
  is	
  already	
  
being	
  done)	
  
•  Standardized	
  methodologies	
  
•  NaHonal	
  infrastructure	
  in	
  place	
  
•  Directly	
  relevant	
  to	
  humans	
  
•  InsensiHve	
  to	
  problems	
  with	
  
Hck	
  endemnicity	
  

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English: Dr. Vett Lloyd

  • 1. Comparing  results  and  predic2ons  of  different   surveillance  approaches  for  Lyme  borreliosis   Canine  seroprevalence  in  New  Brunswick  as  a  case  study       Dr. Vett Lloyd Mt. Allison University
  • 2. Faculty/Presenter  Disclosure   •  Faculty:    Ve3  Lloyd   •  Rela2onships  with  commercial  interests:   –  Grants/Research  Support:  NSERC   –  Speakers  Bureau/Honoraria:  Academic  only   –  Consul2ng  Fees:  None   –  Other:  Employee  of  Mt.  Allison  University    
  • 3. Disclosure  of  Commercial  Support   •  This  program  has  received  financial  support  from  NSERC  in  the  form  of   Discovery  Grant,  MITACS  grant.   •  Poten2al  for  conflict(s)  of  interest:   •   None    
  • 4. MiHgaHng  PotenHal  Bias   •  NSERC  does  not  dictate  or  prescribe  research  results.      
  • 5. Content:     1. Different  surveillance  approaches  and  the   role  of  canine  seroprevalence  studies   2. Canine  seroprevalence  in  New  Brunswick   .     Surveillance  of  Hcks  in  New  Brunswick,  2012-­‐1015.  Julie  Lewis,  Ve3  Lloyd.   Unpublished.     Lyme  disease  risk  in  Dogs  in  New  Brunswick   Natalie  K.  Bjurman1,  Gina  Bradet2,  Ve3  K.  Lloyd1,3  CVJ,  in  press  
  • 6. Surveillance  for  2cks  and  2ck-­‐vectored  diseases     November  3rd  2014   AcHve  Hck  surveillance   Canine  seroprevalence     Passive  Hck  surveillance   Human  case  reports   Labour  intensive   and  expensive   Low  sensiHvity   Under-­‐reporHng   Used  extensively  in  US,   Europe  and  Asia   Limited  use  in  Canada   PaHcularly  useful  in  areas  of   emerging  risk  
  • 7. h3p://www.express.co.uk/news/nature/ 439432/Mystery-­‐of-­‐killer-­‐canine-­‐ disease-­‐spreading-­‐from-­‐the-­‐New-­‐Forest   Why  this  works:   h3p://www.dog-­‐care-­‐ knowledge.com/dog-­‐Hck-­‐ removal.html   h3p://www.wellcomeimageawards.org/2014/ Hck-­‐sucking-­‐blood-­‐from-­‐human-­‐leg   Humans  and  dogs  get  Lyme   disease  in  the  same  way  
  • 8. Advantages  –informaHon  on  canine  Lyme  is  rouHnely  collected  by  veterinary  clinics   using  standardized  and  validated  methodologies.  It  is  freely  available  on  line  which   is  valuable  for  public  awareness  and  educaHon.     Pet  Disease  Report  -­‐  IDEXX   h3p://www.petdiseasereport.com/content/ prevmap.aspx?currentprev=LS  
  • 9. New  Brunswick  as  a  case  study  on  the  use  of   canine  seroprevalence  as  a  predictor  of   human  Lyme  disease  risk  
  • 10. Why  New  Brunswick?   Leiske,  D  and  V.  Lloyd  –  in  review   Surveillance  of  Hcks  in  New  Brunswick,  2012-­‐1015.  Julie  Lewis,   Ve3  Lloyd.  Unpublished.    
  • 11. Why   •  Live  with  humans   •  Robust  immune  response   •  When  ill,  similar  clinical   manifestaHons  of  disease   (symptoms)  ie  arthriHs,   lameness,  and  neurological   disease     •  InfecHon  detected  with   commercial  kits   Methods   nutrasilver.com   How   •  Recruitment  of  veterinary  clinics   •  100  canine  blood  samples  for  each  of   the  7  NB  health  districts   •  Tested  699  samples  using  IDEXX   Snap4Dx+C6  ELISA  and  immunoblot   •  Risk  factor  correlaHon   Borrelia  infec2on  (Lyme  disease  risk)  in  Dogs  in  New  Brunswick   Natalie  K.  Bjurman1,  Gina  Bradet2,  Ve3  K.  Lloyd1,3  
  • 12. Results   Rapid  recent  increase  in   canine  seroposi2vity  (6  fold   in  6  years)     Western  blohng  results  were   generally  consistent  with  C6   ELISAs  but  both  tests  had   false  posiHves  and  possibly   false  negaHves     There  is  no  accepted   algorithm  for  interpretaHon   of  western  blots  and   posiHve/negaHve  calls  varied   by  algorithm  
  • 13.
  • 14. So  what  does  this  mean  for  humans?   1:6  raHo  of  human:dog  infecHons   6,475  humans  with  Lyme   New  Brunswick  Public  Health      5  
  • 15. Re-­‐assessment  approach   ProporHon  of   infected  Hcks  (I)   Number  of  infected   humans   X   X   =   x   x   x   x  x   x   x   x   ProporHon   engorging  on   humans(F)   Number  of  Hck  bites  (T)  
  • 16. X   X   =   x   x   x   x  x   x   x   x   ProporHon  of   infected  Hcks  (I)   ProporHon   engorging  on   dogs  (F)   Number  of  Hck  bites  (T)   Number  of  infected   dogs  
  • 17. Propor2on  of  infected  2cks  -­‐  I   I  =  0.123  (NML  low  value  .068,  high  value  .159)     Ogden  et  al.  2006  Dibernardo  et  al  2014  Lewis  and  Lloyd  (in  prep)     1990-­‐2003  2012              2014     151    364              536     15.9%    6.8%              12.3%         year   Number   tested   %   infecHon  
  • 18. Propor2on  of  fed  2cks  -­‐  F   F  =  0.614  /0.08  (humans)  or  0.974/.60  (dogs)   0   1   2   3   4   5   6   7   8   9   10   0   2   4   6   8   10   BL/SL  ra2o   BW/SW  ra2o   NB  2014  Hcks   Literature   Tick  size  vs  2me  feeding   72hrs   0-­‐24h   19   1-­‐2  days   1   2-­‐3  days   3   3+  days   2   0-­‐24h   25   1-­‐2  days   18   2-­‐3  days   97   3+  days   208   humans   dogs  
  • 19. x   x   x   x  x   x   x   x   Number  of  2ck  bites  -­‐  T   2014  -­‐  111,677  dogs  in  NB  -­‐       6,700  (6%)  Borrelia  seroposiHve     Ipsos-­‐Forward  on  behalf  of  the  Canadian   Animal  Health  InsHtute  ( h3p://www.cahi-­‐icsa.ca/companion-­‐ animal-­‐health/     and  StaHsHcs  Canada     To  produce  6,700  Borrelia  seroposiHve  dogs  with   a  Hck  infecHon  rate  of  12.3%  and  with  60%  fed  3+   days  gives  an  esHmated  90,786  2ck  bites     Adjustments:     Average  1.33  Hcks/dogs  (so  more  Hck  bites)   Not  all  Hcks  found  by  dog  owners  (so  more  Hck  bites)   Tick  infecHon  rate  can  reflect  infecHon  acquired  from  host  so   infecHon  rate  could  really  be  11.56%  –  so  more  Hck  bites   Part  1.  Dogs  
  • 20. Part  2.  Extrapola2ng  dog  to  human  2ck  bites:     Number  of  2ck  bites  -­‐  T   To  what  extent  does  a  Hck  prefer  a  dog   to  a  human?     This  can  be  esHmated  from  return  rates   from  passive  surveillance  programmes  or   from  the  literature.     h3p://www.feathersandfleece.com/ gpage13.htmlfgfr        NB  Hcks  from  humans  NB  Hcks  from  dogs   Dibernardo  et  al  (2014)    123      187     Lewis  and  Lloyd  (in  prep)  25        429          148      616   19.4%  of  Hcks  on  humans  vs  dogs   Lindenmeyer  et  al  1991  :human:dog  Hck  raHo  of  1:6  (14.3%)     This  gives  us  an  esHmate  of  19.4%  x  90786  dog  Hck  bites  17,612  human  2ck  bites  (T).      
  • 21. So  what  does  this  mean  for  humans?   Lindenmeyer  et  al  1991   6,475  humans  with  Lyme   5   New  Brunswick  Public  Health   LB  =  I  x  F  x  T(h)   MulHplied  by  the  infecHon  rate  (I)  of   12.3%  and  probability  of  a  Hck  on  a   human  having  fed  3+  days  (F),  8%   173  predicted   human  infecHons   in  NB  in  2014.     (ConservaHve   esHmate)  
  • 22. Discrepancies:       TesHng  at  the  Hme  of  Hck  bite     Lyme  diagnosis  not  considered     Under-­‐reporHng     Single  Her  vs  two  Hered  tesHng     SensiHvity  of  tesHng     Perdurance  of  canine  seroposiHvity     IDEXX  tech  notes  
  • 23. Conclusions   Canine  seroposi2vity  surveillance   is  a  powerful  complement  to  2ck   surveillance  approaches     •  Inexpensive  (as  it  is  already   being  done)   •  Standardized  methodologies   •  NaHonal  infrastructure  in  place   •  Directly  relevant  to  humans   •  InsensiHve  to  problems  with   Hck  endemnicity