BACKGROUND

Trypanosomiasis is a parasitic disease caused by species of flagellate protozoa belonging to the genus
Trypanosoma which inhabit the blood plasma and various body tissues and fluids. These parasites are
found in many animals but seem to be pathogenic only for mammals, including man.
Animal trypanosomiasis occurs in most of the tropical regions, but only in equatorial Africa does it
constitute a major obstacle to the development of animal production. The considerable economic and
social repercussions make control of this disease a priority operation for the development of a large part
of the African continent.
There are various measures for control of trypanosomiasis and include (a) chemotherapy, (b)
chemoprophylaxis, (c) breeding of trypanosome-tolerant animals and (d) vector control.
For the context of my study, I shall centre on CHEMOTHERAPY and CHEMOPROPHYLAXIS.
Since 1938, the date of the discovery of the trypanocidal properties of the phenanthridines, the
chemotherapy of animal trypanosomiasis has made great progress and there are several highly active
drugs now available which are easy to use. The use of trypanocides has consequently become widespread,
and the number of trypanocidal treatments carried out every year in Africa can be estimated at over 6
million, the great majority of them for combating bovine trypanosomiasis.
The trypanocides currently employed are: homidium salts (Ethidium-Novidium); quinapyramine sulfate
(Antrycide); diminazene aceturate (Berenil); isometamidium (Samorin-Trypamidium) and suramin
sodium.
(adapted from www.fao.org/docrep/010/ah809e/AH809E02.htm)
But each of these drugs have there shortcomings and I will explain one by one as follows;
i.

Homidium salts (ethidium-novidium)

They are 2 salts; Homidium chloride and Homidium bromide.

Dose: Homidium chloride given by deep intramuscular injection as a 2.5% w/v aqueous solution at a rate
of 1mg/kg body weight. Homidium bromide given in cattle by subcutaneous injection of 1% solution at a
rate of 0.1 mg to 0.3 mg/kg body weight will usually control T. congolense. Higher doses are
recommended for T. vivax and if 1.0mg/kg or more is used by intramuscular injection, produces less
reaction.
Toxicity: treatment with 10mg/kg may be followed by death or transient liver damage. As a rule up to
5mg/kg bw is tolerated by cattle. There is a local reaction with edematous swellings and thickening of the
subcutaneous tissues which may leave small scars. It is also a carcinogenic drug.
Drug resistance: resistance to Homidium bromide can occur and such resistant strains cannot be treated
with dimidium bromide.
Use: effective against T. congolense in cattle and T. vivax. The drug has been shown to be effective
against strains of trypanosomes resistant to dimidium bromide and antrycide (quinapyramine). Up to 6

weeks prophylaxis against T. congolense and T. vivax has been shown under field conditions. (adapted
from veterinary protozoology by U. F. Richardson et al3rd edition 1963)
ii.

Quinapyramine (antrycide):

It is a complex chemical compound containing a quinolone and a pyrimidine group. Examples are:
quinapyramine sulfate which is very soluble in water forming a stable solution. Quinapyramine chloride
which is almost insoluble in water, only dissolves in warm water and is stable to heat.
Uses: so far antrycide/quinapyramine has proved effective against certain trypanosomes. It is not known
to have any action against other protozoa. Particularly activity has been shown against T. congolense, T.
evansi, T. equinum and T. equiperdum. T. brucei and T. simiae are also susceptible. T. vivax is relatively
resistant. After subcutaneous injection, quinapyramine sulfate is rapidly absorbed and rapidly excreted.
Quinapyramine chloride remains at the site of injection and is absorbed very slowly. The slow rate of
absorption accounts for its prophylactic action.
Toxicity: as a rule the drug is safe in its use. 5mg/kg qinapyramine sulfate is the maximum tolerated dose
in African cattle. Horses are much more susceptible to toxicity than are cattle. Broadly speaking, young
animals are much more susceptible to toxic effects than are mature animals. Treated stock should be
handled carefully and kept cool. Hard swellings may develop at the site of inoculation. In addition there
may be acute or chronic systemic disturbance. Acute symptoms include twitching of nostrils and lips,
followed by salivation, muscular tremors, distressed breathing and collapse. Chronic toxicity may be
associated with dysentery sufficiently severe to cause death. (adapted from veterinary protozoology by
U.F. Richardson et al3rd edition 1963 Pg 245, 246)
iii.

Diminazene aceturate:

Can be used for treatment of trypanosomiasis in cattle, sheep, camels, goats, cats, dogs, horses, cattle,
sheep, swine. It is for subcutaneous or intramuscular administration. It is contraindicated for animals
hypersensitive to diminazene or phenazone and animals with impaired renal or hepatic function. Has
relatively poor effect against the brucei group; better against T. congolense (Davy 1957). A poor action
against T. simiae (Bauer 1955). Used against T. brucei in horse but there may be local reaction. Leach
(1961) found 3.5mg/kg ineffective against some strains of T. evansi in camels. High blood concentrations
are of relatively short duration i.e the drug is primarily curative rather than prophylactic; particularly
useful against strains of trypanosomes resistant to other drugs. (adapted from Veterinary protozoology by
U.F.Richardson et al 3rd edition 1963).
Toxicity/Side effects include; in some instances 7mg/kg has been given safely but Leach found this toxic
for adult camels (Leach 1961). Also causes hypersensitivity reactions, salivation, sweating, tremors can
occur. Multiple therapeutic doses can produce severe nervous signs and prominent hemorrhagic lesions of
cerebellum, midbrain and thalamus in dogs. After multiple therapeutic changes degenerative fatty changes
can occur in liver, kidneys, myocardium and muscles multiple therapeutic doses can produce prominent
hemorrhagic and malacic lesions of the cerebellum and the thalamus in cattle. (Adapted from
www.kari.org/.../E-Mifugo%20Animal%20Trypano)
iv.
v.

Isometamidium chloride:
Suramin sodium:

This is white or cream white soft microcrystalline powder, readily soluble in cold water. The anhydrous
form can be sterilized by heat. It is very hygroscopic and should be kept in closed containers. Use: it is

used as a 10% solution in sterile water or saline. It is effective against both T. gambiense and T.
rhodesiense in man. In domestic animals T. evansi and T. brucei and other members of their groups are
sensitive. T. equinum and T. equiperdum are somewhat less sensitive. (It is fairly easy to cure horses in the
early stages of the disease but the dose is dangerously high). T. vivax and T. congolense are resistant. It is
however often used in combination with other drugs.
Dose:
(a) By intravenous injection for curative treatment; horse and donkey give 0.35 to 0.5gm/50kg, cattle
nd buffalo give 0.6gm/50kg, camels 3.0 to 5.0gm/camel depending on size, dogs and pigs
0.007gm/kg.
(b) For prophylaxis - by subcutaneous injection; horses 1g every three months, 4g every two
months. The prophylactic use of suramin is particularly useful in horses. The drug is retained for
long periods in the plasma and tissue protein. It can be detected in the plasma for as long as 5
months after injection.
Toxicity: Toxicity is particularly evident in horses. Symptoms which may follow use of the drug at
minimum levels at which it is therapeutically active, may include albuminaria, urticaria, swellings under
the skin of legs, belly, throat, etc., eczematous eruptions of the mouth and anus and laminitis. There is no
margin between the toxic and therapeutic dose and safe effective therapy depends on the experience of
the veterinary surgeon. Calcium lactate intravenously is reported to help avoid toxicity. All mammals
other than horse appear to be much more tolerant.
Drug resistance: resistance has been reported with T. evansi in the camel, but it is not usually a serious
hazard. (adapted from veterinary protozoology by U. F. Richardson et al3rd edition 1963)

Problem statement.
To find out a better drug with greater efficacy for the treatment of trypanosomiasis.
Also to find out which trypanosomes are highly resistant to diminazene aceturate.
Justification of my study.
I am going to use about 100 laboratory mice as sample animals for culturing the trypanosomes. I am
going to inoculate them with blood samples containing live trypanosoma parasites, then I follow them
from day 1 up to when parasitemia builds up.
After I will start treating them with diminazene aceturate and keep testing to see how the parasiteamia
builds up.
Expectations: with this, I will be able to see efficacy of diminazene aceturate on the trypanosomes. I will
be able to know which trypanosomes are resistant to diminazene aceturate.
Research questions
Why trypanosomiasis is still a major problem to farmers domestic animals in Africa?

How does diminazene aceturate exert its therapeutic effect on trypanosomes?

Which trypanosomes best respond to diminazene aceturate and those that are resistant?