curative and prophylactic trypanocides

Introduction:

Trypanosomosis is a disease caused by trypanosoma species. These include: Trypanosoma brucei brucei , T. congolense, T. vivax, T. simiae, T. dimorphon, T. suis, T. lewis, T. evansi, T. equinum, T. equiperdum, for animals while T. gambiense, and T. rhodesiense infest man. trypanosomasis is the presence of trypanosoma in the blood.

Clinical signs: The disease is acute (in Pig), emaciation, anaemia, weakness, collapse, death, intermittent fever, lymphadenopathy, decrease milk yield in dairy animals, CNS signs, Oedema, Cardiac lesion, diarrhea, kerattitis, lacrimination, loss of appetite, abortion, premature birth, perinatal losses, testicular damage, enlarged lymph nodes, visceral and mucosal hemorrhage in gastrointestinal tract, inflammation, degeneration, and necrosis.

Diagnosis: The tentative diagnosis is based on history, post Mortem, and Clinical signs. The definitive diagnosis can done

1) directly through :

a) Direct microscopic diagnosis: Wet blood film, fresh preparation of lymph (T. vivax), Thick blood film, Thin blood smears, Thin lymph smear.

b) Concentrated method: Buffy coat examination ( Woo method), dark ground/phase contrast Buffy coat techniques, Lysis and centrifugation,

c) Use of experimental animals.

2) Indirectly:

a) Serology test

b) Molecular test.

Curative and prophylactic trypanocides, pharmacologically, are under Chemotherapy and Chemoprophylaxis. Chemotherapy can, simply, be defined as the treatment of disease(s) by the use of chemical agents (drugs) which are of curative purposes. On the other hand, Chemoprophylaxis (chemoprevention) can be defined as the prevention of disease(s) by the use of chemical agents (drugs).

Therefore, a drug can be defined, in veterinary medicine, as any mixture or substance that is administered to animals destined for use in the diagnosis, treatment, investigations, or prevention of disease or for modification of physiological functions (omoja). This can be synthetic or natural agents.

Trypanosoma is a protozoa consequently, its treatment involves the use of an anti-protozoa drug , in this case, an anti-trypanosomal drug for specificity.

The chemotherapeutical administration of drugs can be for:

a) Curative

b) Preventive

c) Immunomodulation


Immunomodulation is not usually effective in the trypanosomosis because of antigenic variation.

Therefore antitrypanospomal agents can be divided into trypanocidal agents (curative) and trypanoprophylactic (preventive) agents. Consequently, drugs used for curative purposes in the treatment of trypanosomasis are called trypanocidal drugs while those drugs used in the prevention of the same disease are called trypanoprophylactic drugs.

Trypanocidal and Trypanoprophylactic drugs

a) The difference between trypanocidal and trypanoprophylactic drugs

In as much as there is no essential difference between the two categories of drugs. However, a trpanoprophylactic drug is also a trypanocidal drug but a trypanocidal is not necessarily a trypanoprophylactic drug. The main property of trypanoprophylactic drugs is that they persist longer than trypanocidal drugs. That is such drugs has residual effect because prevention depends on how long a drug persists in the system of the animal.

b) When to use trypanocidal or trypanoprophylactic

Trypanocidal drugs are used in areas with low incidence of the disease while trypanoprophylactic drugs are used in areas with high incidence of the disease. This is because of the risk associated with keeping animals in such high-risk areas, especially non-trypanotolerant animals.

Some Trypanoprophylactic drugs:

1) Antrycide: It was introduced in 1960. It is a pro-salt ( Quinapyramine chloride and Sulphate). It used prophylactically at 7.4mg/kg. At 4-5mg/kg of 5-10% solution against T. brucei in Horses for curative purpose. It is less used in Cattle. The adverse effect of the drug includes: Local tissue reaction, swelling, necrosis, and sloughing.

2) Suramin (Naganol): used prophylactically and curatively at 10mg/kg in cattle and horses. It must be given intravenously. It has low margin of safety and it potentiates of other drugs.

3) Antrycide-Suramin complex: it is the only other drug effective against T. simiae in Pigs. It is used prophylactically at 40mg/kg ( Radostits)

4) Isometamidium chloride ( Trypamidium, Samorin): It has low margin of safety . It is the major drug used against Bovine Trypanosomosis. It is given deep intramuscular injection at 0.25-05kg/kg for curative and 0.5-1mg/kg for prophylaxis. It is highly tissue bound and can remain for several months. Consequently, it can offer protection for 3-6months and 3 injection in a year can be given. It causes local necrosis at the site of injection. However, when used with dextran, the local and systemic toxicity is reduced. It is used at 12.5-35mg/kg for prophylaxis in Pigs (Radostits).

5) Pyrithridium bromide (prothridium): The drug is less used. However, it is prophylaxis at 2mg/kg.

6) Ethidium (Homidium bromide) and Novidium ( Homidium chloride): there are phenanthridines derivatives. Homidium bromide has been withdrawn because of

a) Delay toxicity,

b) Photosensitization,

c) Development of resistant strains

1 mg/kg of 2% solution. Prophylaxis can last for 5 months. Four or five treatments per year can be given.

Some Trypanocidal drugs: As noted above, trypanoprophylactic drugs can be used for curative purposes at same or varied doses. Consequently, there is no need mentioning all the drugs again. However, other trypanocidal drugs include:

1) Diminazene aceturate (Berenil, Trypadium): it is effective T. vivax, T. congolense, less effective against T. brucei. In Camel, for T. evansi, it is toxic and ineffective. It is not tolerated in horses. 3.5-7mg/kg, subcutaneously or intramuscularly in dogs and in cattle the muscle of the mid-neck. The drug has a short duration of stability so phenyldimethyl pyrazone (an antipyretic) acts as a stabilizer in the drug formulation. Consequently, the drug contains 1.05g Diminazene aceturate, and 1.31g Antipyrine to give 2.36g which is dissolved, according to manufacturer’s instruction, in sterile water, 12.5ml, to give 15ml solution of 7% Diminazene, and 8.75% antipyrine (phenazone also reduces pain).

The effectiveness of the drug depends on the species of the animal, stage of the infection, and the dosage. Relapse usually occur due to:

a) Parasite resistance

b) Sub-therapeutic administration

c) Lodgment of the parasite in the brain (cryptic site) in chronic infection

d) Large molecular size, which prevent entry of the drug into the central nervous system

However, the combination of 10ug/kg Lithiumchloride and 7mg/kg diminazene aceturate and administered intramuscularly helps to improve the entry/concentration of diminazene in the brain.


2) Melarsoprol and Aspherinamine : these are organic arsenical compounds used in clinical handling of CNS involvement of the disease. It is used mainly in human trypanosomosis.



3) Quinapyramine sulfate( Antrycide): it is used curatively at 5mg/kg against T. brucei in Horses and less used in cattle.

4) Homidium bromide (Ethidium) and Homidium chloride (Novidium): used curatively at 1mg/kg of 2% solution given intramuscular.

Conclusion: In Veterinary trypanosomosis chemotherapy, seven main drugs are currently in use more frequently either for curative or prophylactic or both. There are Diminazene aceturate, Homidium, Suramin, Isometamidium, Pyrithidium, Bromide, and Quinapyramine.

References:

http://www.fao.org/docrep/006/x0413e/x0413e05.htm

Y. O. Aliu: veterinary pharmacology first edition (2007)

O.M. Radostits et al: Veterinary Medicine: A text book for disease of Cattle, Sheep, Pigs, Goats, and Horses

OMOJA V. U.: 2011/2012 Lecture note on General Veterinary pharmacology

Anaga A. O.: 2012/2013 Lecture note on Chemotherapy

TABLE 1
Some Commercial trypanocides*

Generic name

Trade names**

Solution for use

Dosage rate***

Route

Remarks

Suramin

Naganol

10%

10 mg/kg
(1 ml/1O kg)

IV

Mainly used against T. evansi in camels

Diminazene aceturate

Berenil, Ganaseg, Trypazen, Veriben

7%

3.5–7 mg/kg
(1–2 ml/20 kg)

IM

Mainly used in cattle and small ruminants

Homidium bromide

Ethidium bromide

2.5%

1 mg/kg
(1 ml/25 kg)

IM

Mainly used in cattle and small ruminants. Should be dissolved in hot water. Potentially carcinogenic

Homidium chloride

Ethidium C, Novidium

2.5%

1 mg/kg
(1 ml/25 kg)

IM

See above, but soluble in cold water

Quinapyramine methyl sulphate

Antrycide, Trypacide, Noroquin, Quintrycide

10%

5 mg/kg
(1 ml/20 kg)

SC

Now mainly used against T. evansi and T. brucei in camels and horses

Mel cy

Cymelarsan

0.5%

0.25–0.5 mg/kg
(1–2 ml/20 kg)

IM or SC

Registered only for use against T. evansi in camels

Isometamidium chloride

Samorin, Trypamidium

1%

2%

0.25–0.5 mg/kg
(1.25–2.5 ml/50 kg)
1 .0 mg/kg
(2.5 ml/50 kg)

IM

Used mainly in cattle, as a curative at lower rates, as a prophylactic at higher rates. Also contains homidium, and is therefore to be considered as potentially carcinogenic as well

* Not all of these trypanocides may be available in every country and there is also no guarantee that production of all of them will be continued. The situation is rather fluctuating, mainly because of economical reasons.

** The list of trade names is not complete, and names listed do not imply a qualitative judgement

*** Dosage rate of solutions for use are given in brackets.

(adapted from http://www.fao.org/docrep/006/x0413e/x0413e05.htm)

Corneal opacity

Cornea Opacity

Cornea opacity is one of the clinical sings of canine trypanosomosis
Cornea opacity is one of the clinical sings of canine trypanosomosis

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