2005 4-k o'connell clostridial disease msd finca productiva salud del hato

THE COVEXIN 10 STORYTHE COVEXIN 10 STORY

WHAT ARE CLOSTRIDIALSWHAT ARE CLOSTRIDIALS

• Anaerobic organismsAnaerobic organisms• Spore forming bacteriaSpore forming bacteria• Normal flora for sheep and cattleNormal flora for sheep and cattle• Opportunistic pathogensOpportunistic pathogens• ToxigenicToxigenic• Deadly (disease almost always results Deadly (disease almost always results

in death)in death)

WHY COVEXIN 10?WHY COVEXIN 10?

• Clostridials distributed World-WideClostridials distributed World-Wide

WHY COVEXIN 10?WHY COVEXIN 10?

• Clostridials distributed World-WideClostridials distributed World-Wide• No specific time frame for infectionNo specific time frame for infection

WHY COVEXIN 10?WHY COVEXIN 10?WHY COVEXIN 10?WHY COVEXIN 10?

• Clostridials distributed World-WideClostridials distributed World-Wide

• No specific time frame for infectionNo specific time frame for infection

• Spores can lie dormant for decadesSpores can lie dormant for decades

WHY COVEXIN 10?WHY COVEXIN 10?

• Clostridials distributed World-WideClostridials distributed World-Wide• No specific time frame for infectionNo specific time frame for infection• Spores can lie dormant for decadesSpores can lie dormant for decades• High levels of animal travelHigh levels of animal travel

WHY COVEXIN 10?WHY COVEXIN 10?

• Clostridials distributed World-WideClostridials distributed World-Wide• No specific time frame for infectionNo specific time frame for infection• Spores can lie dormant for decadesSpores can lie dormant for decades• High levels of animal travelHigh levels of animal travel• Disease often a result of management Disease often a result of management

practise.practise.

WHY COVEXIN 10?WHY COVEXIN 10?

• Clostridials distributed World-WideClostridials distributed World-Wide• No specific time frame for infectionNo specific time frame for infection• Spores can lie dormant for decadesSpores can lie dormant for decades• High levels of animal travelHigh levels of animal travel• Disease often a result of management Disease often a result of management

practise.practise.• Infected with Clostridials from birthInfected with Clostridials from birth

WHY COVEXIN 10?WHY COVEXIN 10?

• Clostridials distributed World-WideClostridials distributed World-Wide• No specific time frame for infectionNo specific time frame for infection• Spores can lie dormant for decadesSpores can lie dormant for decades• High levels of animal travelHigh levels of animal travel• Disease often a result of management Disease often a result of management

practise.practise.• Infected with Clostridials from birthInfected with Clostridials from birth• Vaccination = InsuranceVaccination = Insurance

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 + + + + +

AGE OF SUSCEPTABILITY OF SHEEP TO COMMON

CLOSTRIDIA

++++++++++++++C. tetani

++++C. haemolyticum

++++++++C. sordellii

+++++C. novyi B

++++++++++++C. chauvoei

++++++++C. septicum

+++++++C. perfringens type D

++++++C. perfringens type C

++++C. perfringens type B

++++C. perfringens type A

>3 years

1-3years

6-12 months

3–6 months

4-12 weeks

2–4 weeks

0–14days

Approximate Age of SusceptibilityClostridium

HISTORY

HISTORYHISTORY

•1961 – The Electroferm process1961 – The Electroferm process•Early 1980’s – First experiments by Wellcome Early 1980’s – First experiments by Wellcome on Covexin 10on Covexin 10•Late 1980’s – Wellcome looks to get out of Late 1980’s – Wellcome looks to get out of Animal HealthAnimal Health

HISTORYHISTORY

• 1961 – The Electroferm process1961 – The Electroferm process• Early 1980’s – First experiments by Early 1980’s – First experiments by

Wellcome on Covexin 10Wellcome on Covexin 10• Late 1980’s – Wellcome looks to get out of Late 1980’s – Wellcome looks to get out of

Animal HealthAnimal Health• Merger with ICI Tasman of New ZealandMerger with ICI Tasman of New Zealand• Enter Pitman-MooreEnter Pitman-Moore• Building of $40 million dollar production Building of $40 million dollar production

facility 1992facility 1992

HISTORYHISTORY

• Name change to MallinckrodtName change to Mallinckrodt• Research centralized in MundeleinResearch centralized in Mundelein• 1997 – Schering Plough buys Mallinckrodt 1997 – Schering Plough buys Mallinckrodt

veterinaryveterinary• 1998 – Work on Covexin 10 resurrected1998 – Work on Covexin 10 resurrected• Newer demands on vaccinesNewer demands on vaccines

WHAT ARE THE “NEWER WHAT ARE THE “NEWER DEMANDS?”DEMANDS?”

• Lower doseLower dose• Higher potency vs reactivityHigher potency vs reactivity• Earlier age of vaccination (more flexibility)Earlier age of vaccination (more flexibility)• Maternal interferenceMaternal interference• Global focusGlobal focus• BSE, foot and mouth issuesBSE, foot and mouth issues• Coverage of disease where diagnostics Coverage of disease where diagnostics

hasn’t caught uphasn’t caught up

Diagnosis of DiseaseDiagnosis of Disease

Photo: M. Gilmore/Alistair JohnstonPhoto: M. Gilmore/Alistair Johnston

NecropsyNecropsy

Gonzalez, Pineda, Astiz, Cervino. Gonzalez, Pineda, Astiz, Cervino.

"Atlas de las enfermedades del ternero" SP.SA. 2003"Atlas de las enfermedades del ternero" SP.SA. 2003

NecropsyNecropsy

Gonzalez, Pineda, Astiz, Cervino. Gonzalez, Pineda, Astiz, Cervino.

"Atlas de las enfermedades del ternero" SP.SA. 2003"Atlas de las enfermedades del ternero" SP.SA. 2003

NecropsyNecropsy

Gonzalez, Pineda, Astiz, Cervino. Gonzalez, Pineda, Astiz, Cervino.

"Atlas de las enfermedades del ternero" SP.SA. 2003"Atlas de las enfermedades del ternero" SP.SA. 2003

NecropsyNecropsy

Gonzalez, Pineda, Astiz, Cervino. Gonzalez, Pineda, Astiz, Cervino.

"Atlas de las enfermedades del ternero" SP.SA. 2003"Atlas de las enfermedades del ternero" SP.SA. 2003

KEY ELEMENTS TO KEY ELEMENTS TO DIAGNOSING CLOSTRIDIAL DIAGNOSING CLOSTRIDIAL

DISEASEDISEASE• 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

CLOSTRIDIAL DISEASESCLOSTRIDIAL DISEASES

MUSCLE ORIENTED (Blackleg)MUSCLE ORIENTED (Blackleg)– C. chauvoeiC. chauvoei– C. septicumC. septicum– C. sordelliiC. sordellii– C. novyiC. novyi– C. perfringens type AC. perfringens type A

CLOSTRIDIAL DISEASESCLOSTRIDIAL DISEASES

• INTESTINAL DISEASE (Pulpy Kidney)INTESTINAL DISEASE (Pulpy Kidney)– C. perfringensC. perfringens type A type A– C. perfringensC. perfringens type B type B– C. perfringensC. perfringens type C type C– C. perfringensC. perfringens type D type D– C. sordelliiC. sordellii– C. septicumC. septicum

CLOSTRIDIAL DISEASESCLOSTRIDIAL DISEASES

• LIVER DISEASE (Infectious necrotic LIVER DISEASE (Infectious necrotic hepatitis)hepatitis)– C. novyiC. novyi– C haemolyticumC haemolyticum– C. sordelliiC. sordellii– C. septicumC. septicum

CLOSTRIDIAL DISEASESCLOSTRIDIAL DISEASES

• NEUROLOGICAL DISEASENEUROLOGICAL DISEASE– C. tetaniC. tetani– C. perfringensC. perfringens type D type D

WHAT’S IN CURRENT EU WHAT’S IN CURRENT EU VACCINES?VACCINES?

• C. chauvoeiC. chauvoei

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

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

WHAT’S IN CURRENT EU WHAT’S IN CURRENT EU VACCINES?VACCINES?

• C. chauvoeiC. chauvoei• C. septicumC. septicum

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

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

WHAT’S IN CURRENT EU WHAT’S IN CURRENT EU VACCINES?VACCINES?

• C. chauvoeiC. chauvoei• C. septicumC. septicum• C. novyiC. novyi type B type B

THE DISTRIBUTION OF THE MAJOR LETHAL TOXINS AMONG THE TYPES OF C. novyi

+++-D

+-C

+++B

-++A

BetaAlphaType

Toxin

C. novyi type B

• In the soil and ingested as cattle graze

• Infectious necrotic hepatitis

• Death extremely rapid• Liver flukes• Mostly older cattle

C. novyi type B

• In the soil and ingested as cattle graze

• Infectious necrotic hepatitis

• Death extremely rapid• Liver flukes• Mostly older cattle

WHAT’S IN CURRENT EU WHAT’S IN CURRENT EU VACCINES?VACCINES?

• C. chauvoeiC. chauvoei• C. septicumC. septicum• C. novyiC. novyi type B type B• C. perfringens C. perfringens type Ctype C• C. perfringens C. perfringens type Dtype D

WHAT’S IN CURRENT EU WHAT’S IN CURRENT EU VACCINES?VACCINES?

• C. chauvoeiC. chauvoei• C. septicumC. septicum• C. novyi C. novyi type Btype B• C. perfringens C. perfringens type Ctype C• C. perfringens C. perfringens type Dtype D• C. tetaniC. tetani

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

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

WHAT ARE WE GAINING IN COVEXIN 10

• C. perfringens type A• C. sordellii• C. haemolyticum

TOTAL COVERAGE FOR ALL TOTAL COVERAGE FOR ALL CLOSTRIDIAL ORGANISMSCLOSTRIDIAL ORGANISMS

• C. chauvoeiC. chauvoei• C. septicumC. septicum• C. novyi C. novyi type Btype B• C. perfringens C. perfringens type Btype B• C. perfringens C. perfringens type Ctype C• C. perfringens C. perfringens type Dtype D• C. tetaniC. tetani• C. sordelliiC. sordellii• C. perfringens C. perfringens type Atype A• C. haemolyticumC. haemolyticum

CLOSTRIDIUM PERFRINGENSCLOSTRIDIUM PERFRINGENS

THE DISTRIBUTION OF THE MAJOR LETHAL TOXINS AMONG THE TYPES OF C. perfringens

+--+E

-+-+D

--++C

-+++B

---+A

IotaEpsilonBetaAlphaType

Toxin

CLOSTRIDIUM PERFRINGENSCLOSTRIDIUM PERFRINGENS

Plasmid that codes for Epsilon toxin

Plasmid that codes for beta toxin

C. perfringens type A

Alpha toxin gene

CLOSTRIDIUM PERFRINGENSCLOSTRIDIUM PERFRINGENS

Plasmid that codes for Epsilon toxin

Plasmid that codes for beta toxin

C. perfringens type C

Alpha toxin gene

CLOSTRIDIUM PERFRINGENSCLOSTRIDIUM PERFRINGENS

Plasmid that codes for Epsilon toxin

Plasmid that codes for beta toxin

C. perfringens type D

Alpha toxin gene

CLOSTRIDIUM PERFRINGENSCLOSTRIDIUM PERFRINGENS

Plasmid that codes for Epsilon toxin

Plasmid that codes for beta toxin

C. perfringens type B

Alpha toxin gene

CLOSTRIDIUM PERFRINGENSCLOSTRIDIUM PERFRINGENS

C. perfringens type B

C. perfringens type C C. perfringens type D

C. perfringens type A

C. perfringens C. perfringens type Atype A

C. perfringens C. perfringens type Atype A

• Enterotoxemia, gas Enterotoxemia, gas gangrene, sudden deathgangrene, sudden death

• Death up to 24 hoursDeath up to 24 hours• Sudden changes in dietSudden changes in diet• Often mistaken for Often mistaken for C. C.

perfringens perfringens type Dtype D• May be linked to May be linked to C. C.

sordelliisordellii• Disease associated with Disease associated with

the alpha toxinthe alpha toxin

C. perfringensC. perfringens type A type A

• Enterotoxemia, gas Enterotoxemia, gas gangrene, sudden deathgangrene, sudden death

• Death up to 24 hoursDeath up to 24 hours• Sudden changes in dietSudden changes in diet• Often mistaken for Often mistaken for C. C.

perfringens perfringens type Dtype D• May be linked to May be linked to C. C.

sordelliisordellii• Disease associated with Disease associated with

the alpha toxinthe alpha toxin

C. perfringens C. perfringens type Btype B/C/C

• Hemorrhagic enteritisHemorrhagic enteritis• Death 48 hours or lessDeath 48 hours or less• Hemorrhagic diarrhoea Hemorrhagic diarrhoea • Trypsin inhibitors, Trypsin inhibitors,

dietary stress, weaningdietary stress, weaning• Cause of lamb Cause of lamb

dysentery and Struckdysentery and Struck• Disease associated Disease associated

with the beta toxinwith the beta toxin

Type B vs. Type C Type B vs. Type C perfringensperfringens

• Produces both beta and Produces both beta and epsilon toxinsepsilon toxins

• True enterotoxemiaTrue enterotoxemia• Cause of lamb dysenteryCause of lamb dysentery• Neurological signs prior to Neurological signs prior to

deathdeath• Blood stained diarrhoeaBlood stained diarrhoea

• Produces only the beta toxinProduces only the beta toxin• Cause of Struck in sheepCause of Struck in sheep• Rarest of the Rarest of the

enterotoxemias in sheep/ enterotoxemias in sheep/ Common in cattleCommon in cattle

• Diarrhoea not usually a Diarrhoea not usually a symptomsymptom

Type B/C vs. Type D Type B/C vs. Type D perfringensperfringens

• Disease primarily caused by Disease primarily caused by Beta toxinBeta toxin

• Cause of Lamb dysentery Cause of Lamb dysentery and Struck in sheep and Struck in sheep

• Occasional neurological Occasional neurological signs prior to deathsigns prior to death

• True enteritisTrue enteritis• Disease inhibited by trypsinDisease inhibited by trypsin• Disease of younger animalsDisease of younger animals

• Disease caused by the Disease caused by the epsilon toxinepsilon toxin

• True enterotoxemiaTrue enterotoxemia• Neurological signsNeurological signs• Enteritis not normally Enteritis not normally

involvedinvolved• Disease enhanced by Disease enhanced by

trypsintrypsin

• Disease of older animalsDisease of older animals

Type B/C vs. Type D Type B/C vs. Type D perfringens perfringens

• Disease primarily caused by Disease primarily caused by Beta toxinBeta toxin

• Cause of Lamb dysentery Cause of Lamb dysentery and Struck in sheep and Struck in sheep

• Occasional neurological Occasional neurological signs prior to deathsigns prior to death

• True enteritisTrue enteritis• Disease inhibited by trypsinDisease inhibited by trypsin• Disease of younger animalsDisease of younger animals

• Disease caused by the Disease caused by the epsilon toxinepsilon toxin

• True enterotoxemiaTrue enterotoxemia• Neurological signsNeurological signs• Enteritis not normally Enteritis not normally

involvedinvolved• Disease enhanced by Disease enhanced by

trypsintrypsin

• Disease of older animalsDisease of older animals

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

C. sordelliiC. sordellii

• SoilSoil• Sudden death (enteric), Sudden death (enteric),

malignant edemamalignant edema• Death 1-2 daysDeath 1-2 days• Swelling, depression, gas Swelling, depression, gas

gangrene, dyspnea gangrene, dyspnea • Dietary change, wounding, Dietary change, wounding,

parasitesparasites• Greater than 3 monthsGreater than 3 months

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

THE DISTRIBUTION OF THE MAJOR LETHAL TOXINS AMONG THE TYPES OF C. novyi

+++-D

+-C

+++B

-++A

BetaAlphaType

Toxin

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

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