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Equine Protozoal Myeloencephalitis
Content
2
Clinical Signs: Summary
What Clinical Signs EPM?
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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
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Asymmetric Muscle atrophy EPM
Clinical Signs as Diagnosis
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Immunodiagnostics
Sarcocystis neurona – endemic EPM
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Neospora hughesi – sporadic EPM
S neurona: Surface Antigens 1-6
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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%
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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
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
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
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
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
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Summary of Immunodiagnostics
Treatment
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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
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Conventional Antiprotozoal Treatment
Unofficial/Off-Label/Illegal
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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 ++ - - -
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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
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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
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Prevention