ECFECFECFECF

Dr Reza BENTALEBCEVA T h i l & M k ti M I t t i l Af i Z

Dr Reza BENTALEB

CEVA Technical & Marketing Manager- Intertropical Africa Zone

reza.bentaleb@ceva.com

ticks

14-19 billions of dollars (Young et all 1998)

important diseases vector14 19 billions of dollars (Young et all., 1998)

80% of the cattles

Dr Reza BENTALEB

Classification of ticks Embrencht : ARHTROPODES

Classe :ARACHNIDES

Sous classe : ACARIENS

ordre

tickS = IXODIDA

Sous ordre

Nuttallielloides (1 espece)

IXODIDA ARGASINA

Nuttallielloidés

Nuttallielloides (1 espece)

Argasidés

Argasoides (167 especes)

Fam :

SuperFamNuttallielloidés

Ixodoides (643 especes) ArgasCarios

Argasinae

AlectorobiusAlveonasus

Ornithodorinae

S- Fam :

Ixodinae Eschatocephalinae

Ixodidés

HaemaphysalisAmblyomma

Ambyommidés

CariosOgadenus

AlveonasusAntricolaNothoaspisOrnthodorosOtobiusParantricola

Genre

Ixodes CeratixodesLepidixodesEschatocephalusScaphixodes

AmblyommaAponommaDermacentorAnocentorCosmiommaHyalomma

Subparmatus

Dr Reza BENTALEB

Pholeoixodesy

AnomalohimalayaRhipicephalusRhipicentorBoophilusMargaropus

biologyCycle with differents durationCycle with differents duration

H I H II H III

Larve Nymphe femelle

larve nympheMale ou f ll W

femelle é

Larveengorgé

Nympheengorgé

femelle engorgé

larve nymphe femelle W engorgé

Monoxen Dixen Trixen obs2 to 8 weeks L

H1H1

H1

H13 to 10 days

N H2 Frenquently birds, reptiles…

Ad H2 H3 Mainly big mamalian

Dr Reza BENTALEB

Ad H2 H3 Mainly big mamalian

Can be more than 1 year

Ad 5000 To 30000 eggs

The periods of vectors activity on the hosts determine infections &

re-infections periods.

Dr Reza BENTALEB

Climate

T°: dynamic factor T° limit per species

•Min : pause winter

•Max : activity

Humidity : static factor •Microclimat levelHumidity : static factor Microclimat level

•Size of the tick

•vegetation

Dr Reza BENTALEB

Climate

D J F M A M J Jt A S O N D J Fsub-equatorial/tropics

D J F M A M J Jt A S O N D J F

D J F M A M J Jt A S O N D J FIntermediate area

equatorial

D J F M A M J Jt A S O N D J Fequatorial

Dr Reza BENTALEB

Climate

humidity & la temperature control the activity of the ticks

Eurasie septentrionaleN D J F M A M J Jt A S O N D J F

Eurasie moyenneN D J F M A M J Jt A S O N D J F

Mediteranean zone

N D J F M A M J Jt A S O N D J F

Depend of species

N D J F M A M J Jt A S O N D J F1

Depend of species

Dr Reza BENTALEB

2

Ticks pic activity

D J F M A M J Jt A S O N D J Fsub-equatorial/tropics

Intermediate areaD J F M A M J Jt A S O N D J F

Intermediate area

D J F M A M J Jt A S O N D J Fequatorial

Dr Reza BENTALEB

No saisonality, simultaneous generation

Ticks control

Vegetation

climate Control host

species / area

Dr Reza BENTALEB

Control system

Strategic Tactic Traitement occasionnel :

Momentané sur les animaux parasités

Traitement différencié :

Nécessite une bonne connaissance

• Écologie

• Saison et dynamique des vecteurs

• Épidémiologie des maladies

Seulement les animaux qui présentent habituellement les plus hauts niveaux d’infestations

Traitement intensif et régulier :

transmises

Permet de réduire de manière raisonnée la population de tick ciblée

•Toute l’année

•Saisonnier

•Sur les zones à forte pression de maladie

Il vaut mieux avoir un plan de compagne annuel pour réduire la population de ticks, mieux que d’attendre

Dr Reza BENTALEB

l’apparition des foyers de maladies.

Control using acaricides

species

Nearly all transmit diseases ECF is transmited by 3 species of ticks

(4 to 5 days on the animal only) Treatment every 2 to 3 weeks

Short interval or remanent product

The shortest interval between treatment are recomanded

Dr Reza BENTALEB

Cattle immunity

+

stable endemic situation

passive protection hight

ed ti

cks

Cases with endemic type

loss of passive protectionof

infe

cte

yp p

Critical endemique No passive protectionNom

ber o

situation No passive protection

-

Dr Reza BENTALEB

Eradication

Safe area in the meadle of infected one

« trap situation »« trap situation »

i iblimposible

&&

To avoid

Dr Reza BENTALEB

Tick born diseasesPARASITE NOM GENERIQUE VECTEUR BOVINS PETIS RTS

BABESIFORMES BABESIIDES Babesia babesia ticks B.divergens, B.bovis B.ovis

Babesia piroplasma B.bigemina, B.major B.motasi

Babesia Achromaticus

THELERIIDES Theileria Th.mutans, th.annulata, Th.orientalis, Th.parva, Th.velifera

Th.ovis, Th.lestoquardi, Th.sergenti, Th.separata

DACTYLOSOMIDES Anthemosoma Phlebotom

ADELEIFORMES HEPATOZOON ticks

EIMERIIFORMES PLASMODIUM Culicides

FLAGELLES TRYPANOSOMA Glossines

Taons, puces, ticks

T. vivax, T.congolense, T.brucei, T.br.rhodesienceT.theileri

T. vivax, T.congolense, T.brucei, T.br.rhodesienceT.theodori, , p ,

Taons , Stomoxes, T.evansiT.melophagiumT.evansi

LEISHMANIA Phlébotome

RICKETTSIALES ANAPLASMATACEES Anaplasma ticks, taonsStomoxes

A.marginalesA.central

A.ovisA.mesaeterum

Eperythrozoon Anoplour ticks

Ep.wenyoniEp.teganodes, Eptuomii

Ep.ovis

Haemobartonella Anoplour Hb.bovis, Hb.sturmani

BARTONELLACES Bartonella Grahamella Phlébotome

C S C SRICKETTSIACES Rickettsia ticks Anoplour

R.conoriR.prowazekii

Coxiella ticksContage direct

Cx.burnetti Cx.burnetti

EHRLICHIACEES Cowdria ticks C.ruminatum C.ruminatum

Dr Reza BENTALEB

Ehrlichia E.pahgocytophilaE.bovis

E.pahgocytophilaE. ovis

CHLMIDYALES CHLAMYDIACES Chlamydia ticksContage direct

Chlamydia sp Chlamydia sp

SPIROCHAETALES Borrelia ticks, Anoplour B.theileri, B.burgdoferi B.theileri, B.burgdoferi

EPIDEMIOLOGY

immunity

animaltype

Age

Biting Frequence (number)Transmission

Age

Exemple :

Most of the Theileria areruminants

infection infection of the ticks

ruminants parasites

Dr Reza BENTALEB

Maladie germs Vector Pathogeny Symptoms

Babesiose Babesia divergensBabesia bovis

I Ricinus, I persulcatusB microplus B annulatus

Perte d’élasticité des hématies

Choc par stase sanguine

Aiguë (4-5 jours) T°

Main diseases Photos : from Infectious diseases of live stock Edited by J.AW Coetzer G.R.Thomson R.C.Tustin

Babesia bovis B. microplus, B. annulatushyper coagulabilitéHémolyse + (secondaire)

gThromboseHemorragiesSignes nerveux

TSignes générauxSur-aiguë :T° très élevéeMort brutale sans autre sympsub aiguë : signes généraux

Babesiosepiroplasmose

Piroplasma bigeminaPiroplasma major

Boophilus (4 espèces) Hémolyse +++ Ictère importantHemoglobinurieNephritesplenomégalie

Aiguë (2-12jours) / sub aiguë (2-3sem)T°AnémieIctère francAmaigrissementDé h d t tiDéshydratationAnorexieMort (cas graves)

Theileriose East cost fever

Th.mutans, th.annulata, Th.orientalis, Th.parva, Th.velifera

Rhipicephalus sppHyalomma spp

Perturbation su système lymphocytaire

Adénite généraliséeImmunodepressionFoyers

Adénite généralisée+++Amaigrissement rapideAnorexie+++y p y

(hématies occasionnelle)

Foyers hémorragiques

Anorexie+++Abattement +++Anémie Pétéchies (muqueuses)Signes diegestifsNodules sous cutanéesMort en 4 5joursMort en 4-5jours

Anaplasmose RICKETTSIES genre anaplasma

Boophilus+++Stomoxes, taons

Phagocytose des hématies infectés Hémolyse faible

Anémie fébrile lente rarement suraiguëAcidose on compensé

En général subaiguë ou chroniqueT° élevée (durable)AmaigrissementMaladies intercurrentesPas d’ictère (parfois en phase de

Dr Reza BENTALEB

convalescence)

CowdrioseHeart water

Cowdria ruminatium Amblyomma (5 éspèces)A. variegatumA. hebraeumA. Gemma…

Nécrose du cortex cérébelleuxŒdème des gaines axonesLésions vasculaires

Gastro-enteritePéricardite exsudativeTroubles nerveux (parfois)

EAST COST FEVER - CORRIDOR DISEASE

THEILERIOSESInfectious parasitic disease

Virulent

Inoculable non contagiousInoculable, non contagious

Domestic & wild ruminantDomestic & wild ruminant

Sporozoites = Theileria (rts Cn)Sporozoites = Theileria (rts, Cn)

Dr Reza BENTALEB

vector = ticks

Arnold THEILER

Arnold Theiler(1867-1936),

vétérinaire suisse qui fit une brillante carrière en Afrique du Sudvétérinaire suisse qui fit une brillante carrière en Afrique du Sud. Il fut le premier directeur de l'Onderstepoort Veterinary Institute, s'intéressa à

la piroplasmose du cheval dont il démontra la transmission par une tick, il découvrit l'agent de l'East African Coast Fever, Theileria parva (élu en 1920).

Dr Reza BENTALEB

Pathogenic species in cattle

Sporozoites = Theileria

Th Mutans Th Barnetti Th

Theileria parva Theileria annulata

Rhipicephalus appendiculatus H l d d t i

Th. Mutans, Th. Barnetti, Th. Velifera, Th. Sergentis,

Rhipicephalus appendiculatus

Austral side of africa (altitude above 1250m)

Rh. zambeziensis

Hyalomma d. detrium

Mediteranean areas

Hyalomma a. anatolicum

Asia central & occidentalsouth Tanzania, zambia, zimbabwe, botswanna,

namibie

Rh. duttoni

Asia central & occidental

Égypt , north of soudan, Pakistan, India, Sri-lanka,

China

AngolaÉrythree, Djibouti, Somalia*

Rh. duttoni

Angola

Dr Reza BENTALEB

*reduced population of H. anatolicum but no confirmation of presence of Th annulata

Contamination

H I H II H III

Larve Nymph femelle

larve nymphMale ou femalle

Wfemelle

C b i f t t b t

++++Can be infectant but

as the quantity of blood is very low the rate of infection is

reduced

Dr Reza BENTALEB

Multiplication lymphocyte lymphoblaste

trophozoitessporozoites trophoblastessporozoites trophozoitessporozoites trophoblastes

…

schizont…4 days after feed

Dr Reza BENTALEB

feed

…..

S hi t

macroschizont

Schizont

50 à 120Merozoites

initial Schizont final Schizont

Toxins releases by schizonts

Red Blood cellsnon infected

Dr Reza BENTALEB

cells Lymphocytes

PATHOGENY et SYMPTOMS

Affect maily the lymphocyte systm

Theileria parva Theileria annulata

Lymphocyte T et B Lymphocyte B

& macrophages

hyperplastic lymph node

Destruction of non infected lymphocytes

2 to 3 weeks (incubation

period)

Drop of lymphocytes

Schizonts : 7X109

Dr Reza BENTALEBFever T° 41 – 42°c (106°F)

hyperplastic lymph node

The first clinical sign of ECF is usually a swelling of the draining lymph node, usually the parotid, for the ear is the preferred feeding y p , y p , p gsite of the vector; this is followed by a generalised lymphadenopathy in which superficial lymph nodes such as the parotid, prescapular, and prefemoral lymph nodes, can easily be

Dr Reza BENTALEB

seen and palpated

Other clinical signs

Fever • Fever ensues and continues throughout the course of infection; this rise in temperature is rapid and may

Adenopathy

; p p yreach 106°F (42°C)

• There is marked petechial and ecchymotic haemorrhage on most mucous membranes of the conjunctiva and the buccal cavity

Weight loss

Deh dratation

conjunctiva and the buccal cavity

• Anorexia develops, and loss of condition follows

• Other clinical signs may include lacrimation, corneal opacity nasal discharge terminal dyspnoea and

exhaustion-

Dehydratation opacity, nasal discharge, terminal dyspnoea, and diarrhoea

• Before death the animal is usually recumbent, the temperature falls, and there is a severe dyspnoea

anorexia p y p

due to pulmonary oedema that is frequently seen as a frothy nasal discharge

• Mortality in fully susceptible cattle can be nearly 100% Death

Dr Reza BENTALEB

100% Death

Anemia

abortion

l iagalaxia

Petechial haemorrhages

li ti t bli l i

digestive & respiratory Signs

nervous : salivation, trembling, paralysis

Dr Reza BENTALEB

PRONOSTIC

Pathogenic ECF Benign ECF (occasionnelle)

Immunodepression affects the resistance

to ticks

(occasionnelle)

Longuer incubation

Low virulenceto ticks

The highest average abondance of ticks ison the non sick

cattles

peracute : Mortal

acute : with reservations (mortal if no treatment)acute : with reservations (mortal if no treatment)

Local species : + resistant

Dr Reza BENTALEB

After-effect (digestive, kidney, lung…)

DIAGNOSTIC / EPIDEMIOLOGY

Clinic

General hyperplastic

Necrops

General hyperplastic

parasitologic

Presence of schyzonts

Serologic

Indirect Fluorescence & lymph node

Feverlymph node

Petechial haemorrhages

Necrotic lesions

in the lymphoblasts

Présence de merozoites in the RBC

(complement)

others metghods

(ie babesiosis)

Necrotic lesions

Digestives and lung lesions

Dr Reza BENTALEB

Differential diagnostisisECF Babesiosis Piroplasmosis Anaplasmosis Cowdriosis/heart

water

Fever ++++plateau

++plateau

++plateau

+inconstant

+/-

Icterus (haemolyse) -Final phase

++ +++Frenquently strong

- -

Anemia ++ ++ +++ ++++Anemia ++rapid

++ +++ ++++ -

haemoglobin - + ++ - -

Coagulation time - ++ ++ - -

General signs ++++ +++ +++ ++ +General signsIntense & rapid

General hyperplastic lymph node

++++ - - - -

digestives & respiratory Signs

+++ - - - ++digestivep y S g digestive

photosensitive - - ++ - -

Abortion et agalaxia +Précoce

+ + + -

N i + + +/ +Nervous signs + +Tooth grating,

agressivity

+/- + -

Pronostic : fatal ++ + +/- - -

lesions General hyperplastic l mph node

Hyperplastic spleen & li er

Hyperplastic spleen & li er icter s

thinness, hyperplastic kidne

Cerebral, necrosis, h dropericardi m

Dr Reza BENTALEB

lymph node

Petechial haemorrhages

Necrotic lesions

Digestives and lung lesions

spleen & liver, icterus,

intravascular coagulation

liver, icterus, intravascular coagulation

kidney hydropericardium, hydrothorax,

pulmonary oedema,

ECF CONTROL

INTEGRATED STRATEGY

R d th ti k h ll b Reduce the ticks challenge by applying VECTOCID

Introduce immunization control merthods

Treat sick animals with BUTALINE

Dr Reza BENTALEB

Vaccination Immunisation :

par des schizontes non atténués

par des schizontes atténués

Méthode de choix

Innocuité variable

Efficacité souvent démontrée par des schizontes atténués

par infection virulente contrôlé

par schizontes irradiés

Efficacité souvent démontrée

Chimio-immunisation

C bi i hi i +b t d ti k par sporozoites non atténués

par sporozoites irradiés

par antigènes des mérozoites

Combinaison chimio+broyat de ticks infectée

Chimio-immunisation

par antigènes moléculaires Combinaison chimio+broyat de ticks infectée

Recherches :

Vaccins recombinants

Dr Reza BENTALEB

TICKS CONTROL

Dipping Spray

Dr Reza BENTALEBPour-On Foot bath

CHEMOTHERAPY

OXYTETRACYCLIN 1975-1980

Control but no cure ImidocarbeCyclohexylotylnaphtoquinon

Parvaquone

Buparvaquone

HalofuginoneHalofuginone

Primaquine

Antifolates

Dr Reza BENTALEB

BUTALINEBUTALINE®®BUTALINEBUTALINE®®

Dr Reza BENTALEB

BUTALINEBUTALINE®®

Treatment & prophylaxis of East Cost Fever (ECF) /

Theileriosis

Administration : intra-muscular route 1ml of BUTALINE® per 20kg

Adapted presentations40 ml & 20ml

Dr Reza BENTALEB

p gbodyweight.

BUTALINEBUTALINE®®

Dr Reza BENTALEB

BUTALINEBUTALINE®®

COMPOUND OF CHOICE

BUTALINE®

is an injectable solution, the active ingredient is a d ti h d hth i ithsecond-generation hydroxynaphthoquinone with

features that make it a compound of choice for the therapy and prophylaxis of all forms of theileriosis

in cattle, sheep and goats.

Dr Reza BENTALEB

INDICATIONS

Dr Reza BENTALEB

BUTALINEBUTALINE®®

C21H26O3

Mode of action

Inhibition of cytochroms b & c of the parasite y prespiratory chain

active against both stages :

Dr Reza BENTALEB

Schizontes et Merozoites

BUTALINEBUTALINE®®

The most active SchizonticidThe most active Schizonticid

20 times more active than parvaquone

H lf lif t i l ( th 20 h ) thHalf-life twice as long (more than 20 hours) than parvaquone

The curative effect is 90% better against Th ParvaThe curative effect is 90% better against Th. Parva

It is active against both piroplasm and schizont stagesIt is active against both piroplasm and schizont stagesof theileria and may be used in the incubation stage ofthe disease or when the clinical signs are apparent.

Dr Reza BENTALEB

Blood concentration

5

6

7

mic

ro g

/m

ParvaquoneHalf life :

Parvaquone = 11h

2

3

4

-con

cent

ratio

n m

Buparvaquone = 26h

0

1

2

0 0,5 0,7 0,8 1 1,5 2,5 3 4,2 6 8 10 12 14 16 18 20 22 24 26 28 30

plas

ma-

heures/hours

0,08

0,1

0,12

on m

icro

g/m

l Buparvaquone

0,02

0,04

0,06

asm

a-co

ncen

trat

io

Dr Reza BENTALEB

0

0 0,5 1 3 6 10 14 18 22 26 30

heures/hours

pla

Duration of the blood concentration after intramuscular injection in cattles

(Kinabo & al 1988)

Efficacy

120 T, annulata macroschizontes

80

100

ortio

n of

cel

ls

izon

ts

T, parva macroschizontesT, annulata TrophozoitesT, parva sporozoites

40

60

duct

ion

in p

ropo

with

mac

rosc

h

0

20

1 2 4 24 48 96 168 336(h)

% o

f re

1 2 4 24 48 96 168 336

buparvaquone effect (%)T, annulata macroschizontes, T, parva macroschizontes, T, annulata Trophozoites, T, parva sporozoites

Dr Reza BENTALEB

(Wilkie & al 1998)

QUALITY

Optimal quality guaranteed atOptimal quality guaranteed at all stagesBUTALINE® is prod ced b CEVA in o r GMPBUTALINE® is produced by CEVA in our GMP European Union approved

manufacturing site, guaranteeing excellent quality at all stagesall stages.

Dr Reza BENTALEB

DOSAGE AND ADMINISTRATION

1ml of BUTALINE® per 20kg bodyweight.

A single treatment is usually sufficient

Re-treatment 48-72 hours following the initial injection mayb be given if necessary, particularly in severe cases.

Injection

I t l t l- Intramucular route only

- Avoid the neck for draught animals

- Respect the fundamental rules of safep

and clean injection

Dr Reza BENTALEB

PRECAUTIONS

BUTALINE® must not be given by intravenous or subcutaneous routes. In case it is necessary to inject a large volume, it is recommended to divide the total dose and inject in two separate sites.

WITHDRAWAL PERIOD

• Meat and offal: 42 days.

• Milk: 48 hours (for human consumption).

SIDE EFFECTS : When used as directed, no side effects are observed.

STORAGE CONDITIONS : Store below 25°C, Protected from light in its original packaging.

Dr Reza BENTALEB

Dr Reza BENTALEB