Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S...

19
1 Equine Protozoal Myeloencephalitis ) '!"#) ! - &" - &!#" & "# '!"#) ! Content "" "" &"$" "&! $" !&, !$ !## &!!# !$" .&"$ #!##" ( ( !' #!## !"&#"+

Transcript of Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S...

Page 1: Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S neurona: Surface Antigens 1- 6 • snSAG-1 test insensitive • snSAG-1,5,6 replaces this

1

Equine Protozoal Myeloencephalitis

Content

   

  

   

Page 2: Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S neurona: Surface Antigens 1- 6 • snSAG-1 test insensitive • snSAG-1,5,6 replaces this

2

Clinical Signs: Summary

  

   

   

What Clinical Signs EPM?

   

Page 3: Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S neurona: Surface Antigens 1- 6 • snSAG-1 test insensitive • snSAG-1,5,6 replaces this

3

   

  

Asymmetry of Pelvic Limb Signs EPM

1.  L head tilt –VIII L or R 2.  L facial paresis – VII L 3.  Dull – RAS 1 focus? – L rostral medulla?

Multifocal Signs EPM

4.  R masseter - Vm R

1 focus – R pons

≥2 foci EPM

Page 4: Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S neurona: Surface Antigens 1- 6 • snSAG-1 test insensitive • snSAG-1,5,6 replaces this

4

Asymmetric Muscle atrophy EPM

Clinical Signs as Diagnosis

  

   

Page 5: Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S neurona: Surface Antigens 1- 6 • snSAG-1 test insensitive • snSAG-1,5,6 replaces this

5

Immunodiagnostics

    

  

Sarcocystis neurona – endemic EPM

Page 6: Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S neurona: Surface Antigens 1- 6 • snSAG-1 test insensitive • snSAG-1,5,6 replaces this

6

Neospora hughesi – sporadic EPM

   

  

S neurona: Surface Antigens 1-6

Page 7: Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S neurona: Surface Antigens 1- 6 • snSAG-1 test insensitive • snSAG-1,5,6 replaces this

7

S neurona: Surface Antigens 1- 6

•  snSAG-1 test insensitive •  snSAG-1,5,6 replaces this test

Distribution: seropositive rates

0%

39% 53%

62%

56%47%

45%

27%

63%43% 22%

Brazil 35%Argentina 35%

Western Canada 0%

45%

28%

0-10% 10-20% 20-30% 30-40% 40-50% 50-60% 60-70%

Page 8: Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S neurona: Surface Antigens 1- 6 • snSAG-1 test insensitive • snSAG-1,5,6 replaces this

8

Distribution: EPM

0.06%

0.07%

0.12% 0.43%

NAHMS ‘98

EPM: Prevalence Rates by Activity

0.0 0.2 0.4 0.6 0.8 1.0

Total

Ranch

Pleasure

Breeding

Racing

Showing

Prevalence of EPM (%)

NAHMS ‘98

Page 9: Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S neurona: Surface Antigens 1- 6 • snSAG-1 test insensitive • snSAG-1,5,6 replaces this

9

  ≈

     

  

Infection vs. Disease

0

2

4

6

8

10

12

0 2 4 6 8 10

IgG

Con

cent

ratio

n

VACCINE

Why a Serum:CSF Ratio?

weeks

CSF IgGs

Serum IgG

Page 10: Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S neurona: Surface Antigens 1- 6 • snSAG-1 test insensitive • snSAG-1,5,6 replaces this

10

0

2

4

6

8

10

12

0 2 4 6 8 10

IgG

Con

cent

ratio

n

S. neurona sporocysts weeks

CSF S. neurona IgGs

Serum S. neurona IgG

Serum IgG is Filtered into CSF

CSF IgGs

Serum IgG

False Positive!!

0

2

4

6

8

10

12

0 2 4 6 8 10

IgG

Con

cent

ratio

n

weeks

WB-positive concentration

+ ++ +++ False

Positive!!

S. neurona sporocysts

CSF S. neurona IgGs

Serum S. neurona IgG

Serum IgG is Filtered into CSF

Page 11: Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S neurona: Surface Antigens 1- 6 • snSAG-1 test insensitive • snSAG-1,5,6 replaces this

11

0

2

4

6

8

10

12

0 2 4 6 8 10

IgG

Con

cent

ratio

n

at a Constant Serum/CSF Ratio

9.5

9.5 ÷1.9 = 5.0

1.9

9.5

1.9

weeks

CSF S. neurona IgG Serum S. neurona IgG

S. neurona sporocysts

0

2

4

6

8

10

12

0 2 4 6 8 10

IgG

Con

cent

ratio

n 9.5

9.5 ÷1.9 = 5.0

1.9 1.1

3.0

9.5 ÷3.0 = 3.2

S. neurona sporocysts S. neurona invades CNS!!

CSF S. neurona IgGs

Serum S. neurona IgG

weeks

Intrathecal IgG Lowers the Ratio

CSF S. neurona IgGc

EPM

Page 12: Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S neurona: Surface Antigens 1- 6 • snSAG-1 test insensitive • snSAG-1,5,6 replaces this

12

0

2

4

6

8

10

12

0 2 4 6 8 10

IgG

Con

cent

ratio

n 9.5

9.5 ÷3.0 = 3.2

Blood IgG is Filtered into CSF

EPM

CSF S. neurona IgGs

Serum S. neurona IgG

CSF S. neurona IgGc

SnSAG2,4/3 serum:CSF ratio test

  

   

   

Page 13: Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S neurona: Surface Antigens 1- 6 • snSAG-1 test insensitive • snSAG-1,5,6 replaces this

13

Summary of Immunodiagnostics

  

Treatment

      

Page 14: Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S neurona: Surface Antigens 1- 6 • snSAG-1 test insensitive • snSAG-1,5,6 replaces this

14

Ponazuril

1970 1980 1990 2000

Sulfa/pyrimethamine

Nitazoxanide

2010

Diclazuril

Thirty-seven years of treatment

Ponazuril

1970 1980 1990 2000

Sulfa/pyrimethamine

Nitazoxanide

2010

Diclazuril

Thirty-seven years of treatment

Page 15: Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S neurona: Surface Antigens 1- 6 • snSAG-1 test insensitive • snSAG-1,5,6 replaces this

15

Conventional Antiprotozoal Treatment

   

  

  

  

Unofficial/Off-Label/Illegal

   

   

   

Page 16: Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S neurona: Surface Antigens 1- 6 • snSAG-1 test insensitive • snSAG-1,5,6 replaces this

16

This should also be on the list

    

Characteristics of EPM Drugs

Item PYR Ponazuril Diclazuril Decoq

In vitro activity + ++ ++++ ++++

Bioavailability ++ + + ?

Crosses BBB +++ ++ + ?

Enters cells ? ? ? ?

Cidal + - - +

Toxicity ++ - - -

Page 17: Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S neurona: Surface Antigens 1- 6 • snSAG-1 test insensitive • snSAG-1,5,6 replaces this

17

Immunostimulants

  

  

  

  

Treatment Outcomes (Recovery)

0

20

40

60

80

100

1 2 3 4

Rec

over

y (%

)

Time to first treatment

Grade 1 Grade 2 Grade 3 Grade 4

1 day 1 week 1 month 1 year

Page 18: Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S neurona: Surface Antigens 1- 6 • snSAG-1 test insensitive • snSAG-1,5,6 replaces this

18

Treatment Outcomes

What can we do better?

  Diagnose early  Use the full course  Combine with immunostimulant  Change drugs if unresponsive  If possible, treat to serum/CSF ratio 100  Treat around stressful periods 0

20

40

60

80

100

0

100

200

300

400

500

600

30-Jul 18-Sep 7-Nov 27-Dec

Ser

um

/C

SF

Rat

io

Com

bin

ed S

AG

2,4

/3

tit

er

serum

CSF

Ratio

  Post-treatment intermittent therapy after relapse

Page 19: Equine Protozoal Myeloencephalitis - CVMAmembers.cvma.net/images/cvmaimages/MacKayEPM.pdf7 S neurona: Surface Antigens 1- 6 • snSAG-1 test insensitive • snSAG-1,5,6 replaces this

19

   

  

  

Prevention