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FMD in African Buffalo (Syncerus
caffer): Differences in host responses
between SAT 1,2 and 3 in
experimentally infected and contact
infected individuals
Brianna	Beechler,	Eva	Perez,	Bryan	Charleston,	Caroline	Glidden,	Nick	
Juleff,	LinMari	de	Klerk-Lorist,	Francois	Maree,	Katherine	ScoB,	Louis	
van	Schalkwyk,	Fuquan	Zhang,	Anna	Jolles
FMDV in African Buffalo 
•  SAT	1,2,3	are	endemic	in	buffalo	in	
KNP,	South	Africa	
•  Typically	“sub-clinically	infected”	
unlike	caCle	
•  But	what	does	sub-clinically	mean	in	
wildlife?	
•  Does	it	differ	by	SAT	type	or	by	
infecHon	style?
Study Design – Experimental set-up
•  12	FMDV	naïve	young	buffalo	
obtained	from	HIP	were	needle	
infected	with	SAT	1,2,3	(4	with	
each	serotype)		
•  Virus	prepared	by	OVI	-	F.	Maree	
•  kept	in	separate	bomas	
•  On	day	2	-	12	FMDV	naïve	young	
buffalo	(4	per	group)	were	
introduced	
•  Monitored	for	FMDV	and	clinical	
signs	on	day	4,	6,	8,	11,	14,	30
Measured parameters 
•  Viremia	(by	PCR)	–	by	Pirbright	InsHtute	
•  Body	temperature	(via	intraruminal	temperature	loggers	that	report	
every	15	minutes)	
•  Presence/Absence	of	mucosal	lesions	
•  Acute	Phase	Proteins:	Haptoglobin	&	Serum	Amyloid	A	
•  In	caCle	are	elevated	a`er	FMDV	infecHon,	peak	correlates	with	the	
development	of	mucosal	lesions	(Stenfeldt	2011)	
•  Inflammatory	Cytokines:	TNF	alpha	&	IFN	gamma
Results of infecMon 
•  Contact	buffalo	rapidly	infected	with	FMDV	from	needle	infected	
•  Carrier	informaHon	&	transmission	–	Eva	Perez	
•  Measuring	transmission	rate		–	Anna	Jolles	&	Jan	Medlock
Host Response – Development of Oral
Mucosal Lesions
Needle	Infected	 Contact	Infected	
SAT	1	 2/4	 1/4	
SAT	2	 1/4	 0/4	
SAT	3	 0/4	 1/4	
Very	small	lesions	developed	infrequently
Host Response – Acute Phase Proteins
•  Haptoglobin	and	Serum	Amyloid	A	–elevated	in	caCle	post	infecHon	
•  Buffalo?	
D
ay
0
D
ay
2
D
ay
4
D
ay
6
D
ay
8
D
ay
11
D
ay
14
D
ay
30
0
200000
400000
600000
800000
Day
Haptoglobin(ng/ml)
D
ay
2
D
ay
4
D
ay
6
D
ay
8
D
ay
11
D
ay
14
D
ay
30
0
200000
400000
600000
800000
Day
Haptoglobin(ng/ml)
Needle	Infected	 Contact	Infected
Host Response – Acute Phase Proteins
•  Haptoglobin	and	Serum	Amyloid	A	–elevated	in	caCle	post	infecHon	
(Stenfeldt	2011)	
•  Buffalo?	 D
ay
0
D
ay
2
D
ay
4
D
ay
6
D
ay
8
D
ay
11
D
ay
14
D
ay
30
0
5000
10000
15000
20000
Day
SAAng/ml
D
ay
2
D
ay
4
D
ay
6
D
ay
8
D
ay
11
D
ay
14
D
ay
30
0
5000
10000
15000
20000
Day
SAAng/ml
Needle	Infected	 Contact	Infected
Does the magnitude of the response differ
between SAT types and infecMon route
S
AT
1
NI
S
AT
1
CI
S
AT
2
NI
S
AT
2
CI
S
AT
3
NI
S
AT
3
CI
0
200000
400000
600000
800000
Animal Group
Haptoglobinng/ml
S
AT
1
NI
S
AT
1
CI
S
AT
2
NI
S
AT
2
CI
S
AT
3
NI
S
AT
3
CI
5000
10000
15000
20000
Animal Group
SAAng/ml
Host Response - Fever
•  Preliminary	Data	
•  All	SAT	1	needle	infected	buffalo	mounted	a	fever	response	detectable	
~24-36	hours	a`er	infecHon	
•  Analysis	of	peak	and	duraHon	sHll	in	progress	
•  Some	of	the	SAT	2	and	3	needle	infected	buffalo	mounted	a	fever	response	
but	it	was	more	variable	in	Hming	
•  Analysis	of	peak	and	duraHon	sHll	in	progress	
•  	Data	for	contact	infected	individuals	not	analyzed	yet
Summary so far
•  Buffalo	rarely	develop	oral	vesicles		
•  Buffalo	do	mount	fever	responses	
•  They	do	mount	an	inflammatory	response	
•  SAT	3	contact	infected	buffalo	had	a	reduced	haptoglobin	response	(peak)	to	
FMDV	infecHon	compared	to	SAT	3	needle	infected.
Host Response – Inflammatory Cytokines
•  Are	TNFalpha	and	IFNgamma	elevated	post-infecHon	
Needle	Infected	 Contact	Infected
Host Response – Inflammatory Cytokines
•  Are	TNFalpha	and	IFNgamma	elevated	post-infecHon	
Needle	Infected	 Contact	Infected	
D
ay
0
D
ay
2
D
ay
4
D
ay
6
D
ay
8
D
ay
11
D
ay
14
D
ay
30
0
5
10
15
Day
IFNyng/ml
D
ay
2
D
ay
4
D
ay
6
D
ay
8
D
ay
11
D
ay
14
D
ay
30
0
5
10
15
Day
IFNyng/ml
Does the magnitude of the response differ
between SAT types and infecMon route
Take Home Points
•  Buffalo	rarely	develop	oral	vesicles		
•  Buffalo	do	mount	fevers	
•  They	do	mount	an	inflammatory	response	
•  SAT	3	contact	infected	buffalo	had	a	reduced	haptoglobin	response	(peak)	to	
FMDV	infecHon	compared	to	SAT	3	needle	infected.	
•  Buffalo	have	elevated	TNFa	and	IFNy	when	needle	infected		
•  But	no	TNFa	infecHon	when	contact	infected
Remaining QuesMons
•  Why	do	buffalo	seldom	show	oral	vesicles	or	severe	clinical	signs	but	
do	mount	very	high	inflammatory	immune	responses?	
•  What	does	this	mean	for	transmission?	
	
•  Are	the	differences	between	needle	infected	and	contact	infected	(no	
TNFa	response,	reduced	haptoglobin	response	in	SAT	3)	relevant	to	
progression	and	transmission?
Thank you! - Acknowledgements
Jan Medlock
Brian Dugovich
Caroline Glidden
Hannah Tavalire
Julie Rushmore
Lin-Mari de Klerk-Lorist
Louis van Schalkwyk
Simon Gubbins
Eva Perez
Fuquan Zhang
Bryan Charleston
Peter Buss
Markus Hofmeyr
Marius Kruger
Henri Combrink
Kath Forssman
Darryn Knobel
Courtney Coon
Francois Maree
Katherine Scott
Lorens Maake
Dan Haydon
Funding:
Erin Gorsich
Danielle Sisson
Claire Couch
Michele	Miller

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OS16 - 6.G10.b FMD in African Buffalo (Syncerus Caffer): Differences in Host Responses Between SAT1, 2 and 3 in Experimental and Natural Infection - B. Beechler

  • 1. FMD in African Buffalo (Syncerus caffer): Differences in host responses between SAT 1,2 and 3 in experimentally infected and contact infected individuals Brianna Beechler, Eva Perez, Bryan Charleston, Caroline Glidden, Nick Juleff, LinMari de Klerk-Lorist, Francois Maree, Katherine ScoB, Louis van Schalkwyk, Fuquan Zhang, Anna Jolles
  • 2. FMDV in African Buffalo •  SAT 1,2,3 are endemic in buffalo in KNP, South Africa •  Typically “sub-clinically infected” unlike caCle •  But what does sub-clinically mean in wildlife? •  Does it differ by SAT type or by infecHon style?
  • 3. Study Design – Experimental set-up •  12 FMDV naïve young buffalo obtained from HIP were needle infected with SAT 1,2,3 (4 with each serotype) •  Virus prepared by OVI - F. Maree •  kept in separate bomas •  On day 2 - 12 FMDV naïve young buffalo (4 per group) were introduced •  Monitored for FMDV and clinical signs on day 4, 6, 8, 11, 14, 30
  • 4. Measured parameters •  Viremia (by PCR) – by Pirbright InsHtute •  Body temperature (via intraruminal temperature loggers that report every 15 minutes) •  Presence/Absence of mucosal lesions •  Acute Phase Proteins: Haptoglobin & Serum Amyloid A •  In caCle are elevated a`er FMDV infecHon, peak correlates with the development of mucosal lesions (Stenfeldt 2011) •  Inflammatory Cytokines: TNF alpha & IFN gamma
  • 5. Results of infecMon •  Contact buffalo rapidly infected with FMDV from needle infected •  Carrier informaHon & transmission – Eva Perez •  Measuring transmission rate – Anna Jolles & Jan Medlock
  • 6. Host Response – Development of Oral Mucosal Lesions Needle Infected Contact Infected SAT 1 2/4 1/4 SAT 2 1/4 0/4 SAT 3 0/4 1/4 Very small lesions developed infrequently
  • 7. Host Response – Acute Phase Proteins •  Haptoglobin and Serum Amyloid A –elevated in caCle post infecHon •  Buffalo? D ay 0 D ay 2 D ay 4 D ay 6 D ay 8 D ay 11 D ay 14 D ay 30 0 200000 400000 600000 800000 Day Haptoglobin(ng/ml) D ay 2 D ay 4 D ay 6 D ay 8 D ay 11 D ay 14 D ay 30 0 200000 400000 600000 800000 Day Haptoglobin(ng/ml) Needle Infected Contact Infected
  • 8. Host Response – Acute Phase Proteins •  Haptoglobin and Serum Amyloid A –elevated in caCle post infecHon (Stenfeldt 2011) •  Buffalo? D ay 0 D ay 2 D ay 4 D ay 6 D ay 8 D ay 11 D ay 14 D ay 30 0 5000 10000 15000 20000 Day SAAng/ml D ay 2 D ay 4 D ay 6 D ay 8 D ay 11 D ay 14 D ay 30 0 5000 10000 15000 20000 Day SAAng/ml Needle Infected Contact Infected
  • 9. Does the magnitude of the response differ between SAT types and infecMon route S AT 1 NI S AT 1 CI S AT 2 NI S AT 2 CI S AT 3 NI S AT 3 CI 0 200000 400000 600000 800000 Animal Group Haptoglobinng/ml S AT 1 NI S AT 1 CI S AT 2 NI S AT 2 CI S AT 3 NI S AT 3 CI 5000 10000 15000 20000 Animal Group SAAng/ml
  • 10. Host Response - Fever •  Preliminary Data •  All SAT 1 needle infected buffalo mounted a fever response detectable ~24-36 hours a`er infecHon •  Analysis of peak and duraHon sHll in progress •  Some of the SAT 2 and 3 needle infected buffalo mounted a fever response but it was more variable in Hming •  Analysis of peak and duraHon sHll in progress •  Data for contact infected individuals not analyzed yet
  • 11. Summary so far •  Buffalo rarely develop oral vesicles •  Buffalo do mount fever responses •  They do mount an inflammatory response •  SAT 3 contact infected buffalo had a reduced haptoglobin response (peak) to FMDV infecHon compared to SAT 3 needle infected.
  • 12. Host Response – Inflammatory Cytokines •  Are TNFalpha and IFNgamma elevated post-infecHon Needle Infected Contact Infected
  • 13. Host Response – Inflammatory Cytokines •  Are TNFalpha and IFNgamma elevated post-infecHon Needle Infected Contact Infected D ay 0 D ay 2 D ay 4 D ay 6 D ay 8 D ay 11 D ay 14 D ay 30 0 5 10 15 Day IFNyng/ml D ay 2 D ay 4 D ay 6 D ay 8 D ay 11 D ay 14 D ay 30 0 5 10 15 Day IFNyng/ml
  • 14. Does the magnitude of the response differ between SAT types and infecMon route
  • 15. Take Home Points •  Buffalo rarely develop oral vesicles •  Buffalo do mount fevers •  They do mount an inflammatory response •  SAT 3 contact infected buffalo had a reduced haptoglobin response (peak) to FMDV infecHon compared to SAT 3 needle infected. •  Buffalo have elevated TNFa and IFNy when needle infected •  But no TNFa infecHon when contact infected
  • 16. Remaining QuesMons •  Why do buffalo seldom show oral vesicles or severe clinical signs but do mount very high inflammatory immune responses? •  What does this mean for transmission? •  Are the differences between needle infected and contact infected (no TNFa response, reduced haptoglobin response in SAT 3) relevant to progression and transmission?
  • 17. Thank you! - Acknowledgements Jan Medlock Brian Dugovich Caroline Glidden Hannah Tavalire Julie Rushmore Lin-Mari de Klerk-Lorist Louis van Schalkwyk Simon Gubbins Eva Perez Fuquan Zhang Bryan Charleston Peter Buss Markus Hofmeyr Marius Kruger Henri Combrink Kath Forssman Darryn Knobel Courtney Coon Francois Maree Katherine Scott Lorens Maake Dan Haydon Funding: Erin Gorsich Danielle Sisson Claire Couch Michele Miller