The laboratory to watch...

“The protection recommendedby those who know”.

“Kinga anayoathiminiwa na walio Jua”.

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T R Y P A N O C I D E

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Is caused by the presenceand the multiplication of aparasite in the host’s blood: the trypanosome. It has ap a t h o l o g i c a l e f f e c t i nhumans “sleeping sickness”,and also in catt le causingtrypanosomiasis or “nagana”.

The persistence of the disease isrelated to two major factors:

� The presence of “vectors”: tsetseflies

� The presence of a reservoir oftrypanosomes in sick or healthycarrier animals.

CEVA Animal Healtto the control of try

Field work

Partnership & support

Customerrelationships

Trypanosomiasis

Training and accom

Research anddevelopment

Institut

University

School

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Every year Trypanosomosis kills3 million cattle in Africa and costs 4,5billions dollars (FAO –2002).

PRODUCTIVITY LOSSES

• Drop in overall productivity• Decrease of milk production• Immunosuppression and development

of intercurrent diseases• Reduction of work capacity

(especially important in terms ofability to plough)

These “hidden” production losses needto be added to the direct cost ofmortality.

The hidden “cost”of trypanosomiasis

l Health committedl of trypanosomosis

A range perfectly adapted to thecontrol of trypanosomiasis

Always leading the way in developingmore innovative trypanocides

Tools and services designed to achievebetter disease control

1st trypanocidewith B12 vitamin

long acting

An injectable trypanocide, “ready to use”

nd accompaniment

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VERIDIUM® production

VERIDIUM® is produced at CEVA plant,which is GMP European Union approved,guaranteeing excellent quality at all stages.

Consistency of VERIDIUM® quality

As with all CEVA Santé Animale products,VERIDIUM® has a constant quality.

Isometamidium, (VERIDIUM®) is a long actingtrypanocide (aminophenanthridium), which canbe used both to cure and prevent

trypanosomiasis.

Its broad spectrum of activity ranges fromT.vivax, T.congolense to T.brucei and T.evansi,the major parasites implied in ruminantstrypanosomiasis.

Isometamidium : a specificmolecule for trypanosomiasiscontrol

Optimal qualityassured at all stages

D A breakdown of each lot of VERIDIUM® by isometamidium concentrationshows that they have all reached minimum standard

Minimumstandard CEVA

Lots

Per

cent

age

of a

ctiv

e is

omet

amid

ium

For more than 10 years, VERIDIUM has met GMP specificationsof the fules in force.

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DFigure 1 : comparison of VERIDIUM ®’s prophylacticactivity vs the product of reference product, oncattle (Nguruman, KETRI, Kenya - 2000) (2)

The guaranteed lasting protection

A trial carried out under fieldchallenge demonstrated

the excellent prophylacticactivity of VERIDIUM®compared to

the reference product whenfaced with local strains

infestations.

During a trial carried out undervery heavy field challenge, the

duration of VERIDIUM®’s protectionwas equivalent to the reference

procuct.

days after treatment

leve

l of p

rote

ctio

n (%

)

0

25

50

75

100

0 10 20 30 40 50 60

Reference procuct VERIDIUM Control

Hight Challenge

DFigure 2 : Comparison of VERIDIUM®’s prophylacticactivity vs the product of reference, on cattle underfield challenge (Mkwaja ranch, Tanzanie,ADRI - 1997 ) (3)

20 40 60 80 100

days after treatment

leve

l of p

rote

ctio

n (%

)

0

25

50

75

100

Reference procuct VERIDIUM Control

Hight Challenge

In several field trials VERIDIUM® has proven its prophylactic capacity tocontrol trypanosomiasis. The protection period against re-infestations can reach up to6 months, depending on the level of challenge.

D Comparison of the curative activity of VERIDIUM ® and the reference product vsTrypanosoma congolense in mice. (KETRI, Kenya - 1996) (1)

**ED80 : Minimum dose of isomethamedium wich temporarily clears parasitamia but does not cureinfection in at least 80 % of mice.

**CD80 : Minimum dose of isomethamedium wich cure infection in at least 80 % of mice.

ED80* CD80**

VERIDIUM® 0,003 à 0,01 mg/kg 0,03 à 0,1 mg/kg

Reference product 0,003 à 0,01 mg/kg 0,03 à 0,1 mg/kg

VERIDIUM®, proven efficacy against trypanosomiasis

The total curative efficacy

An evaluation of curative activity, demonstrated that VERIDIUM was able to clearall trypanosomes without any reappearance at 60 days following treatment.

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Integrated controlIntegrated control is themost effective approach,combining the control ofthe vector and thetrypanosomose thanks tostrategic use oftrypanocides.

SanativePair

Ectoparasiticide

D When an animal is sick between two cycles of tthat it has been contaminated by a trypanososensitive to isométamidium thus sensitive to case we treat with VERIBEN B12 LA.

Ectoparasiticide treatment should be repeated at least on a monthly basis

The interval between 2 administrations dependson the local field challenge (between 2 to 6 months)

Ask advice fveterinary s

CEVA a

If the animal is sick it must betreated with VERIBEN B12 LA

15 Days

VERIBEN® B12 LAVERIBEN® VERIDIUM®

Vect

or c

ontr

oltr

ypan

osom

es c

ontr

ol

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The SOS Uganda project* is an example of thesuccess of the integrated control approach.

Each year, 500.000 new human cases oftrypanosomiasis (sleeping sickness) are detectedin Africa, where living in the absence of care,death is inescapable. The World Health Organization(WHO) estimates that 55 million people lives in rural regionsare exposed to the tsetse fly. The large ruminants, andparticularly the cattle, represent the carrier oftrypanosomes even if they lodge the parasite withoutappearing to suffer from it.

The parasitic treatment of herds reduces the number ofcases of human mortality.

The SOS Uganda project* is an example, this strategy whichcombines the improvement of animal health and humanhealth. The infected cattle are treated and cured by injectingtrypanocides (VERIDIUM® or VERIBEN®) then protected fromnew infections by a monthly spray with our acaricide(Vectocid®). This project was conceived by the veterinaryscientists of the universities of Edinburgh in Scotland andMakerere in Uganda. The project is supported in the field bythe laboratory CEVA Santé Animale and a caritativeinstitution IKARE.

*Stamp Out Sleeping sickness

T. b

ruce

i s.l.

pre

vele

nce

(%)

0

5

10

15

20

3 month postintervention

Baseline

3 months after the beginning of the study a significant reduction(70%) of prevalence of T. brucei brucei and T. brucei rhodesience was

recorded in the concerned areas.

THE SANATIVE PAIR

VERIDIUM® and VERIBEN®whenused together form what isknown “the sanative pair”.Trypanosomes which may beresistant to one of the productsof the pair are usually sensitiveto the other.The entire herd should betreated with VERIBEN®at thestart of the trypanosomiasis riskperiod, then re-treated againwith VERIDIUM® (15 daysminimum later) to eliminate thepersistent trypanosomes(resistant to diminazene) whichare sensitive to isometamidium.

SOS, A sign of commitment

tween two cycles of treatment, it meansated by a trypanosome that is not verym thus sensitive to diminazene. In thisN B12 LA.

Ask advice from yourveterinary surgeon or

CEVA agent.

Ectop arasiticidetreatment

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1 - Sterile water.

2 - Make sure that all the product iswell dissolved before injection.

3 - Carefully clean the materialafter use.

Dosage respectCOMPOSITION• Sachet of 125 mg :

Isometamidium chloride hydrochloride .......................125 mg• Sachet of 1 g :

Isometamidium chloride hydrochloride ..............................1 g

PROPERTIESIsometamidium, an aminophenanthridium compound, has trypa-nocidal action used in curative and preventive treatment of animaltrypanosomiasis.Its spectrum of activity ranges from T. vivax, T. congolense toT. brucei and T. evansi. It could be administered to the followingtarget species: ruminants (cattle, buffalo, goat, sheep), equines(horses, donkeys), camels and dogs.As the mechanism of action of VERIDIUM® (isometamidium) andVERIBEN® (diminazene) acts on different targets, they could becombined in integrated programmes in order to control the deve-lopment of resistant strains and potentialize preventive action ofisometamidium. Duration of the preventive effect varies from 8 to16 weeks according to the fly challenge.

INDICATIONSCattle (incl. zebu), buffaloes, sheep, goats, camels, equines,dogs: Curative and preventive treatment of trypanosomiasis.

ADMINISTRATION AND DOSAGECattle, buffaloes, sheep, goats:Deep intramuscular route in the neck muscles.• Sterile or distilled water should be used to prepare the solutionwhich must be used extemporaneously or stored in the fridge for24 hours maximum.• The dosage should be adjusted according to the sensitivity oflocal strains of trypanosoma.• Potential usefull combination:Preventive treatment: the preventive effect of VERIDIUM® will beincreased if animals receive a curative treatment, at least 2weeks before, with a non-linked molecule, such as diminazene(VERIBEN®).Curative treatment: animals already treated for prevention whichdevelop clinical form of trypanosomiasis could be treated with anon-linked molecule such as diminazene (VERIBEN®) in order toavoid the development of resistant strains.Horses: treatment of horses trypanosomiasis: 0.5 mg/kg throughslow intravenous injection or deep intramuscular injection, followingusual aseptic recommendations.Camels: treatment of camels trypanosomiasis: 0.5 mg/kgthrough slow intravenous injection following usual aseptic recom-mendations.Dogs: treatment of dogs trypanosomiasis: (T. brucei et T. congo-lense): 1mg/kg by deep intramuscular injection.

PRECAUTIONSDo not inject subcutaneously.Do not inject more than 15 ml by site of injection: in case of highervolume, divide the total dose in 2 injections one far from the other.Do not inject VERIDIUM® with another trypanocide at the same time.

WITHDRAWAL PERIODMeat: 1 month.Remove muscles corresponding to the site of injection, unfit forhuman consumption.Milk: nil.

PRESENTATIONS• Box with 10 x 125 mg sachet.• Box with 10 x 1 g sachet.

FOR ANIMAL TREATMENT ONLY

VERIDIUM®

• Intramuscular route• Avoid the neck fordraught animals

• Respect the fundamentalrules of asepsis

Injection

Solutionpreparation

CEVA SANTE ANIMALE S.A. La Ballastière - B.P. 126 - 33501 Libourne Cedexcontact@ceva.com - wwww.ceva.com Tél. : 33 (0)5 57 55 40 40 - Fax : 33 (0)5 57 55 41 98

The dosage will be adapted in each area according to the epi-demiologic situation.

Weight 2 % SOLUTIONof the animal 0,5 mg/kg 1 mg/kg

50 kg 1,25 ml 2,5 ml

100 kg 2,50 ml 5 ml

150 kg 3,75 ml 7,5 ml

200 kg 5 ml 10 ml

250 kg 6,25 ml 12,5 ml

300 kg 7,5 ml 15 ml

350 kg 8,75 ml 17,5 ml

400 kg 10 ml 20 ml

Ref bibliographique :

1 KETRI-Kenya (1996) : Etude de l’activité curative de VERIDIUM® et du produitde référence. (Rapport d’étude)

2 Stevenson et al (2000) : Comparison of ismetamidium-based trypanocydaldrugs Samorin and veridium in cattle under field conditions at Nguruman,Kenya. Acta tropica (2000) 77 : 195-201

3 ADRI-Tanzanie (1997) : Evaluation terrain de l’efficacité de VERIDIUM® et duproduit de référence. (Rapport d’étude)

Protection seal

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disolve 1gm in 50ml of water

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