dr g.h. gerdes & ref. laboratory staff onderstepoort · 2016-10-17 · 28 mill. sheep sub...
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DR G.H. GERDES & REF.
LABORATORY STAFF
ONDERSTEPOORT
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SOUTH AFRICA
Total Ruminants
12 mill. cattle
5 mill. goats
28 mill. sheep
Sub tropical
N. East
Temperate
S West
><
30th driest country
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THE VIRUS -background
Entire southern Africa endemic (Sahara)
- present since antiquity
- introduction merino sheep late 18th C
- 1943 C.imicola vector
- 1948 plurality of serotypes
pre 1960 - 12 serotypes
1960 - 1970 - 4 serotypes
post 1970 - 8 serotypes
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(cont.)
- two large merino introductions
late 1600 and late 1700
- BT recognized in early 1800
- 1876 outbreak serious febrile disease
- SNTs developed typing (first 12 then 16 serotypes)
- Theiler 1900 Cape Province BTV 4 oldest
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BTV SEROTYPES1983 - 2003
Sheep Isolates - 258
0
10
20
30
40
50
60
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
BT Serotypes
Isolates
*
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05
101520253035404550
Cases
1 2 3 4 5 6 8 11 24
Serotypes
HIGH EPIDEMIC POTENTIAL
1983 - 2003
LOW EPIDEMIC POTENTIAL
05
101520253035404550
7 15 18
Serotypes
Cases
EVERY SEASON LOWER LEVELS
05
101520253035404550
9 10 12 13 16 19
Serotypes
Cases
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0
5
10
15
20
25
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
BT Serotypes
Isolates
Onderstepoort
CULICOIDES SURVEY1978 - 1985
: not the highest or lowesthottest wettest
but > no. of collections> no. of isolates> no. of serotypes
*
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“Up to the present (1932) it has been accepted
that bluetongue is a disease specifically and
exclusively confined to sheep”
(Bekker et al 1934)
BLUETONGUE IN CATTLE
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BLUETONGUE TRIAL
SYMPTOMS FIELD CATTLE EXPERIMENTAL CATTLE EXPERIMENTAL SHEEP
Eye discharge + + +
Nose discharge + + +
Salivation ++ slight Frothing
Swollen tongue + - +
Stomatitis ++ + ++
Torticollis - - + (late)
Skin lesions + - +
Stiffness + - -
S/c oedema - - +
Coronitis + - ++
(Bekker et al 1934)
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DISEASE IN CATTLE1996
0123456789
10
1 2 3 4 5 6 7 8
Serotypes
Cases
Ovine Bovine
BTV 12, 15, 22 cattle strains
Closely related to EHD
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BLUETONGUE IN GAME
0
50
100
150
200
250
300
350
400
450
500
1997 1998 1999 2000
Number
Total Positive
Dec. < role as maintenance/amplifying host(23 official protected areas)
A - Export dataB - Survey data
A: In 4 yrs exported - 1,511 game 30% BT Pos.
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0102030405060708090
100% Positive
1 2 3 4 5 6 7 8 9 10 11 12Game
BT
(Barnard 1997)
1. Blk w/beest2. Bl w/beest3. Red h/beest4. Bl/buck5. S/buck6. Impala7. G/buck8. Buffalo9. Kudu10. Eland11. B/buck12. Giraffe
B: Single survey 1997
- 4 vegetation types
- rainfall 280mm . 900mm
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VACCINE - background
1° - Theiler Sheep blood vaccine BTV 4
- used at # 11, 33, 54
alternative host system
egg
- progressive serial # in eggs (temp)
2° - pre 1959 used polyvalent egg attenuated
(BTV 3, 4, 11, 12)
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- Absence of clinical Sx ? Attenuation
- Index of infection = solid homologous immunity
after challenge
- attenuation - decrease severity fever
- absence mouth and foot lesions
- shortened febrile reaction
ATTENUATION
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(cont.)
BTV 9 & 10 most pronounced clinical Sx
prolonged viraemia
Higher egg # foot lesions disappeared
Low virus yield in some egg strains
go to TC
Pathogenicity of original virus reduced by serial #
Febrile reaction ± 1 day
Egg/TC better than Egg only
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(cont.)
No concept Master Seed Virus
Some egg # >100
3° 14 strains (TC adapted Egg attenuated) in 1 dose
failed to stimulate polyvalent immunity
- loss antigenicity
- role interferon
- competition between 2 Ag s
- rapid : slower growing strains
Viraemia essential for high a/b titers
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EVOLUTION OF A NEW VACCINE
Effective & Practical control measure
Goals :
Inactivated - complete inactivation- minimal loss antigenicity
Attenuated - adaptation to new hostor
prolonged # in TC- genetically stable agent- avirulent
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(cont.)
Move away - highly attenuated egg#
- use of 14 strains in 1
Selection of strains
1 – 14 were not selected used (old and widespread)
(3) 17, 20, 21 exotic
(6) 15, 16, 18, 22, 23, 24 low pathogenicity for sheep
low presence in Culicoidesall recent isolates
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(cont.)
1976 floods – outbreak of two new viruses BTV 18 & 19
19 very pathogenic
Directly related to 7 (weak immunogen)
19 became the 15° strain of the 3 x pentavalent product
A – B- C divide based on degree attenuation
degree relatedness
BTV 4 A (amnestic response)
10 11 B
13 C
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BTV VP2
11
1712
2219
424
237
2091215
1881410
2163135
16
3
16
13
14
621
23
8
18
1
2
5
9
7
19
10
4 2024
11
1715
12
22
0.2
Serological relationshipPhylogenetic relationship
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VACCINE STRAINS
HAD HAVE1 53 E 4TC 50 E 3P 4BHK2 80 E 50 E 3P 4BHK3 60 E 45 E 2 BHK 3P 5BHK4 80 E 60 E 3P 9BHK5 63 E 50 E 2BHK 3P 6BHK6 80 E 60E 3P 7BHK7 80 E 60 E 3P 4BHK8 80 E 50 E 3BHK 10P 7BHK9 80 E 70 E - - - -10 80 E E 8211 45 E 35 E 3P 5BHK12 60 E 55 E 3P 4BHK13 80 E 45 E 2BHK 3P 4BHK14 80 E 60 E 3P 4BHK19 29 E 3P 3BHK
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BTV VACCINE STRAINS
Not all South African – exotics in vaccine
3 - Cyprus
10 - Portugal
16 - Pakistan
East : West
Italians have BTV 9 – E
Vaccine is BTV 9 – W
Effective (a/body)
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(cont.)
Primary vacc. – Bottle A a/bodies to 3
- Bottles A, B, C protection against 9
Annual vacc. X 3 – full protection to 15
- chose the lowest available egg passage
- plaque purify on TC
Modified live - plaque selection avirulent/virulent ratio
(no genetic marker – choose large number)
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(cont.)
chose 10 P 3 P 1 P
sheep sheep sheep vaccine candidate
Extensively tested - SA conditions
- SA merinos
In use 40 yrs 12 – 14 million doses
8 million doses
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CAUTION
- Live attenuated risks
* not first ½ pregnancy
* temporary infertility
- Objections
* reversion to virulence
* re assortment
* vector spread (viraemia)
* no DIVA test – trade difficulties
Teratogenicity - potent cause of early foetal death
- lesser extent foetal malformations
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RE ASSORTMENT
EU PROJECT – VP2 sequences 130 strains
1982 – 2003
- 8 vaccine strains
BTV 2, 3, 5, 6, + 14
1982 death
- PAGE gel 7 vaccine segments +
- animal trial pending
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MISCELLANEOUS
1. Game - springbok with mouth lesions/muscle necrosis
- sable antelope with torticollis
2. Alpacca - two separate submissions with pneumonia
3. Goats - often with coronitis
- Angoras with hyperaemia base horns
- drop in milk production & torticollis (Saanen)
Abortion?
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FOOT NOTE A
Vaccination History:-
1. Unvaccinated 24 cases13 serotypes
2. Vaccinated 16 cases6 serotypes
- multiple serotypes- majority were BTV 4, 3 and 12- only BTV 16 and 24 not in the vaccine
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FOOT NOTE B
Serotype 16
- not South Africa- not in the vaccine- Eastern strain- included in an Israeli product- recent strain- not tested in the field here
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