MSD Finca Productiva Salud Del Hato

1. THE COVEXIN 10 STORY

2. WHAT ARE CLOSTRIDIALS
• Anaerobic organisms
• Spore forming bacteria
• Normal flora for sheep and cattle
• Opportunistic pathogens
• Toxigenic
• Deadly (disease almost always results
in death)

3. WHY COVEXIN 10?
• Clostridials distributed World-Wide

4. WHY COVEXIN 10?
• Clostridials distributed World-Wide
• No specific time frame for infection

5. WHY COVEXIN 10?
• Clostridials distributed World-Wide
• No specific time frame for infection
• Spores can lie dormant for decades

6. WHY COVEXIN 10?
• Clostridials distributed World-Wide
• No specific time frame for infection
• Spores can lie dormant for decades
• High levels of animal travel

7. WHY COVEXIN 10?
• Clostridials distributed World-Wide
• No specific time frame for infection
• Spores can lie dormant for decades
• High levels of animal travel
• Disease often a result of management
practise.

8. WHY COVEXIN 10?
• Clostridials distributed World-Wide
• No specific time frame for infection
• Spores can lie dormant for decades
• High levels of animal travel
• Disease often a result of management
practise.
• Infected with Clostridials from birth

9. WHY COVEXIN 10?
• Clostridials distributed World-Wide
• No specific time frame for infection
• Spores can lie dormant for decades
• High levels of animal travel
• Disease often a result of management
practise.
• Infected with Clostridials from birth
• Vaccination = Insurance

10. Edad de susceptilidad del ganado
al CLOSTRIDIO COMUN
Clostridium Approximate Age of Susceptibility*
0 – 14 days 2 – 13 weeks 3 – 12 months 1 – 3 years >3 years
C. perfringens type A + + + - -
C. perfringens type B + + + - -
C. perfringens type C + + + - -
C. perfringens type D + + + + -
C. septicum + + + + -
C. chauvoei - - + + -
C. novyi B - - + + +
C. sordellii - - + + -
C. haemolyticum - - - + +
C. tetani + + + + +

11. AGE OF SUSCEPTABILITY OF
SHEEP TO COMMON
CLOSTRIDIA
Clostridium Approximate Age of Susceptibility
0–14 2–4 4-12 3–6 6-12 1-3year >3
days weeks weeks months months s years
C. perfringens type A ++ + +
C. perfringens type B ++ + +
C. perfringens type C ++ + + + +
C. perfringens type D ++ + ++ + +
C. septicum ++ + + ++ ++
C. chauvoei + + ++ ++ ++ ++ ++
C. novyi B + ++ ++
C. sordellii ++ + ++ + ++
C. haemolyticum ++ ++
C. tetani ++ ++ ++ ++ ++ ++ ++

12. HISTORY

13. HISTORY
•1961 – The Electroferm process
•Early 1980’s – First experiments by Wellcome
on Covexin 10
•Late 1980’s – Wellcome looks to get out of
Animal Health

14. HISTORY
• 1961 – The Electroferm process
• Early 1980’s – First experiments by
Wellcome on Covexin 10
• Late 1980’s – Wellcome looks to get out of
Animal Health
• Merger with ICI Tasman of New Zealand
• Enter Pitman-Moore
• Building of $40 million dollar production
facility 1992

15. HISTORY
• Name change to Mallinckrodt
• Research centralized in Mundelein
• 1997 – Schering Plough buys Mallinckrodt
veterinary
• 1998 – Work on Covexin 10 resurrected
• Newer demands on vaccines

16. WHAT ARE THE “NEWER
DEMANDS?”
• Lower dose
• Higher potency vs reactivity
• Earlier age of vaccination (more flexibility)
• Maternal interference
• Global focus
• BSE, foot and mouth issues
• Coverage of disease where diagnostics
hasn’t caught up

17. Diagnosis of Disease
Photo: M. Gilmore/Alistair Johnston

18. Necropsy
Gonzalez, Pineda, Astiz, Cervino.
"Atlas de las enfermedades del ternero" SP.SA. 2003

20. Necropsy
Gonzalez, Pineda, Astiz, Cervino.
"Atlas de las enfermedades del ternero" SP.SA. 2003

21. Necropsy
Gonzalez, Pineda, Astiz, Cervino.
"Atlas de las enfermedades del ternero" SP.SA. 2003

22. Necropsy
Gonzalez, Pineda, Astiz, Cervino.
"Atlas de las enfermedades del ternero" SP.SA. 2003

23. KEY ELEMENTS TO
DIAGNOSING CLOSTRIDIAL
DISEASE
• Necropsy pathology
• Husbandry changes
• Culture of both affected and non-effected
• Necropsy within 2 hours of death
• Samples shipped properly for diagnosis
• Take genetic analysis with grain of salt
• Be wary of toxin specific diagnosis
• Mixed infections very common

24. CLOSTRIDIAL DISEASES
MUSCLE ORIENTED (Blackleg)
– C. chauvoei
– C. septicum
– C. sordellii
– C. novyi
– C. perfringens type A

25. CLOSTRIDIAL DISEASES
• INTESTINAL DISEASE (Pulpy Kidney)
– C. perfringens type A
– C. perfringens type B
– C. perfringens type C
– C. perfringens type D
– C. sordellii
– C. septicum

26. CLOSTRIDIAL DISEASES
• LIVER DISEASE (Infectious necrotic
hepatitis)
– C. novyi
– C haemolyticum
– C. sordellii
– C. septicum

27. CLOSTRIDIAL DISEASES
• NEUROLOGICAL DISEASE
– C. tetani
– C. perfringens type D

28. WHAT’S IN CURRENT EU
VACCINES?
• C. chauvoei

29. C. chauvoei
• Animals, water, soil?
• Blackleg, malignant
edema, black quarter
• Death 1-2 days
• High fever, lameness,
gas gangrene,
swelling
• Wounding, bruising
• 3 months - 3 years

30. C. chauvoei
• Animals, water, soil?
• Blackleg, malignant
edema, black quarter
• Death 1-2 days
• High fever, lameness,
gas gangrene,
swelling
• Wounding, bruising
• 3 months - 3 years

31. WHAT’S IN CURRENT EU
VACCINES?
• C. chauvoei
• C. septicum

32. C. septicum
• Soil or intestinal tract
• Malignant edema,
enteric disease
• Death 1-4 days
• Gas gangrene,
swelling, edema,
lameness, fever.
• Wounding
• Any age, primarily < 3

33. C. septicum
• Soil or intestinal tract
• Malignant edema,
enteric disease
• Death 1-4 days
• Gas gangrene,
swelling, edema,
lameness, fever.
• Wounding
• Any age, primarily < 3

34. WHAT’S IN CURRENT EU
VACCINES?
• C. chauvoei
• C. septicum
• C. novyi type B

35. THE DISTRIBUTION OF THE MAJOR LETHAL
TOXINS AMONG THE TYPES OF C. novyi
Toxin
Type Alpha Beta
A ++ -
B ++ +
C - +
D - +++

36. C. novyi type B
• In the soil and
ingested as cattle
graze
• Infectious necrotic
hepatitis
• Death extremely rapid
• Liver flukes
• Mostly older cattle

37. C. novyi type B
• In the soil and
ingested as cattle
graze
• Infectious necrotic
hepatitis
• Death extremely rapid
• Liver flukes
• Mostly older cattle

38. WHAT’S IN CURRENT EU
VACCINES?
• C. chauvoei
• C. septicum
• C. novyi type B
• C. perfringens type C
• C. perfringens type D

39. WHAT’S IN CURRENT EU
VACCINES?
• C. chauvoei
• C. septicum
• C. novyi type B
• C. perfringens type C
• C. perfringens type D
• C. tetani

40. C. tetani
• Entry through wounds
or skin openings
• Hyperesthesia,
tetany, convulsions
• Death 24 hours - 2
wks
• Ear Tagging,
dehorning, castration
and injections.
• All ages, all species

41. C. tetani
• Entry through wounds
or skin openings
• Hyperesthesia,
tetany, convulsions
• Death 24 hours - 2
wks
• Ear Tagging,
dehorning, castration
and injections.
• All ages, all species

42. WHAT ARE WE GAINING IN
COVEXIN 10
• C. perfringens type A
• C. sordellii
• C. haemolyticum

43. TOTAL COVERAGE FOR ALL
CLOSTRIDIAL ORGANISMS
• C. chauvoei
• C. septicum
• C. novyi type B
• C. perfringens type B
• C. perfringens type C
• C. perfringens type D
• C. tetani
• C. sordellii
• C. perfringens type A
• C. haemolyticum

44. CLOSTRIDIUM PERFRINGENS
THE DISTRIBUTION OF THE MAJOR LETHAL TOXINS
AMONG THE TYPES OF C. perfringens
Toxin
Type Alpha Beta Epsilon Iota
A + - - -
B + + + -
C + + - -
D + - + -
E + - - +

45. CLOSTRIDIUM PERFRINGENS
Alpha toxin gene
Plasmid that codes
for beta toxin
C. perfringens type A
Plasmid that codes
for Epsilon toxin

46. CLOSTRIDIUM PERFRINGENS
Alpha toxin gene
C. perfringens type C
Plasmid that codes
for Epsilon toxin
Plasmid that codes
for beta toxin

47. CLOSTRIDIUM PERFRINGENS
Alpha toxin gene
Plasmid that codes
for beta toxin
C. perfringens type D
Plasmid that codes
for Epsilon toxin

48. CLOSTRIDIUM PERFRINGENS
Alpha toxin gene
C. perfringens type B
Plasmid that codes
for Epsilon toxin
Plasmid that codes
for beta toxin

49. CLOSTRIDIUM PERFRINGENS
C. perfringens type A C. perfringens type B
C. perfringens type C C. perfringens type D

50. C. perfringens type A

51. C. perfringens type A
• Enterotoxemia, gas
gangrene, sudden death
• Death up to 24 hours
• Sudden changes in diet
• Often mistaken for C.
perfringens type D
• May be linked to C.
sordellii
• Disease associated with
the alpha toxin

52. C. perfringens type A
• Enterotoxemia, gas
gangrene, sudden death
• Death up to 24 hours
• Sudden changes in diet
• Often mistaken for C.
perfringens type D
• May be linked to C.
sordellii
• Disease associated with
the alpha toxin

53. C. perfringens type B/C
• Hemorrhagic enteritis
• Death 48 hours or less
• Hemorrhagic diarrhoea
• Trypsin inhibitors,
dietary stress, weaning
• Cause of lamb
dysentery and Struck
• Disease associated
with the beta toxin

54. Type B vs. Type C perfringens
• Produces both beta and • Produces only the beta toxin
epsilon toxins • Cause of Struck in sheep
• True enterotoxemia • Rarest of the
• Cause of lamb dysentery enterotoxemias in sheep/
• Neurological signs prior to Common in cattle
death • Diarrhoea not usually a
• Blood stained diarrhoea symptom

55. Type B/C vs. Type D perfringens
• Disease primarily caused by • Disease caused by the
Beta toxin epsilon toxin
• Cause of Lamb dysentery • True enterotoxemia
and Struck in sheep
• Neurological signs
• Occasional neurological
signs prior to death • Enteritis not normally
involved
• True enteritis
• Disease enhanced by
• Disease inhibited by trypsin
trypsin
• Disease of younger animals
• Disease of older animals

56. Type B/C vs. Type D
perfringens
• Disease primarily caused by • Disease caused by the
Beta toxin epsilon toxin
• Cause of Lamb dysentery • True enterotoxemia
and Struck in sheep
• Neurological signs
• Occasional neurological
signs prior to death • Enteritis not normally
involved
• True enteritis
• Disease enhanced by
• Disease inhibited by trypsin
trypsin
• Disease of younger animals
• Disease of older animals

57. C. sordellii
• Soil
• Sudden death (enteric),
malignant edema
• Death 1-2 days
• Swelling, depression,
gas gangrene, dyspnea
• Dietary change,
wounding, parasites
• Greater than 3 months

58. C. sordellii
• Soil
• Sudden death (enteric),
malignant edema
• Death 1-2 days
• Swelling, depression, gas
gangrene, dyspnea
• Dietary change, wounding,
parasites
• Greater than 3 months

59. C. sordellii
• Soil
• Sudden death (enteric),
malignant edema
• Death 1-2 days
• Swelling, depression, gas
gangrene, dyspnea
• Dietary change, wounding,
parasites
• Greater than 3 months

60. THE DISTRIBUTION OF THE MAJOR LETHAL
TOXINS AMONG THE TYPES OF C. novyi
Toxin
Type Alpha Beta
A ++ -
B ++ +
C - +
D - +++

61. C. haemolyticum
• Soil, animals
• Bacillary
hemoglobulinuria
• Death 1-2 days
• Dark red urine, bloody
feces, liver damage
• Liver insult, flukes,
plant toxins,
chemicals
• Greater than 1 year

62. C. haemolyticum
• Soil, animals
• Bacillary
hemoglobulinuria
• Death 1-2 days
• Dark red urine, bloody
feces, liver damage
• Liver insult, flukes,
plant toxins,
chemicals
• Greater than 1 year