’ NOTES ON THE TRYPANOCIDAL ACTIVITY OF ...
’
NOTES ON THE TRYPANOCIDAL ACTIVITY OF
ISOMETAMIDIUM ADMINISTERED INTRAVENOUSLY
S.M.TOURE
Institute d’Elevage et de Médicine Vétérinaire des Pays tropicaux
Laboratoire national de 1’Elevage et de Recherches Vétérinaires,
Dakar-Hann, Sénégal
Isometamidium is used more and more previously infected. The drug was given in a
frequently for prophylaxis and treatment of solution of 1 part per 100 at a level of 0.5 mg-
animal trypanosomiasis. This drug is an
1 mg/kg. Parasite analyses were done daily.
excellent trypanocide but it does cause
The seventeen cattle were treated in several
necrosis at the injection site when adminis-
ways :
tered intramuscularly. This is a serious
(a) 14 got Isometamidium intravenously at
drawback to the use of the drug as it means
0.5 mg/kg and were then inoculated
that part of the carcass Will be rejected by
with T. vivax at various intervals.
the slaughterhouse. Similar observations have
(b) Steers were inoculated with T. brucei
been made by many veterinarians who use
instead of T. vivax.
the drug intramuscularly several months
Analyses of the parasitism in the cattle
prior to slaughter. However, Isometamidium were done daily.
(5
cari be administered intravenously. Finelle
and Yvore (1962) and Finelle and Lacotte
RESULTS
injected Isometamidium chloride hydrochlo-
‘#
rate intravenously in a solution of 1 part per
(1) Observations on the goats
100 at a dosage of OS-3 mg/kg. The curative
Two of the goats infected with T. vivax
properties are good and the animals stand were inoculated with 1 mg/kg of Isometami-
the drug relatively well up to 2 mg/kg.
dium 9 and 17 days after the trypanosome
However, we had no precise indication of the injection respectively. At this dosage, death
preventive properties of the drug adminis-
occurred swiftly-in 4 hours in each case. The
tered intravenously. This paper reports the high degree of parasitism at the time of the
reactions of goats and cattle infected with treatment could not cause these sudden
trypanosomes before and after they received deaths. A new goat which received the same
Isometamidium intravenously.
dosage of the drug also died quickly, although
it was not infected. According to our obser-
MATERIALS AND METHODS
vations, the dosage of 1 mg/kg administered
intravenously seems to be excessive for goats,
This experiment was conducted at the even though this dosage is well tolerated
Veterinary Laboratory in Dakar.
when given intramuscularly.
%
Five of the six goats used in the experi-
Three other goats received Isometamidium
ment were infected with a strain of Trypano-
at 0.5 mg/kg on the 9th, 15th and 17th days
soma vivax. They showed a high degree of respectively after the T. vivax injection, when
c
parasitism between the 9th and the 17th day the level of parasitism was high. The animals
post injection and Isometadium was then tolerated the drug well and the trypanosomes
administered. The remaining goat was given disappeared within 48 hours. These three
Isometamidium, although it had not been goats were thcn re-inoculated with T. Cvax
2
subcutaneously on the 16th, 18th and 20th They were then examined daily for 2 months
days respectively, after the Isometamidium and showed no signs of trypanosomes.
treatment. Their tests were negative. They
were then re-inoculated with trypanosomes
on the 31st, 32nd and 35th days respectively
DISCUSSION AND CONCLUSTON
and the tests were again negative. One of the
In these trials, it did not seem necessary to
*
goats was re-inoculated with trypanosomes on have a control group. It was shown that
the 62nd day and again the test proved unprotected cattle infected with T. vivax and
negative. The re-inoculation of the two T. brucei strains become diseased after an
remaining goats could not be done because average of one week and the disease becomes
the T. vivax strain was lost.
severe if these animals are not treated. This
(2) Observations on the cattle
is proved by the fact that there was patent
infection of the experimental animals prior to
This part of the experiment dealt with 17
treatment or when the drug had worn off.
Zebu cattle which received Isometamidium
The minimal immunity period cannot be
intravenously at a dosage of 0.5 mg/kg of the
deduced exactly from the preceding experi-
1 part per 100 solution. Al1 the animals ment. The important facts are the following:
tolerated the drug well.
1. Isometamidium, in a solution of 1 part
(a) A group of 14 of the animals weighing per 100, when administered intravenously at a
164-268 kilos was given a dose of about dosage of 0.5 mg/kg, is well tolerated by both
15 x 10’ T. vivax individually, on the 6th day goats and cattle.
after treatment with the drug. Their tests
2. The curative effect is extraordinary in
were negative on the following days. On the regard to T. vivax complete disappearance of
3
17th day, these animals were inoculated trypanosomes within 24-48 hours, with no
again with 25 x 10” trypanosomes. Conse-
recurrence.
cutive analyses were negative. On the 48th
3. The preventive powers of the drug -c
day, the animais were inoculated with 3 x 10” persist when it is administered intravenously.
trypanosomes. Analyses made during the Within the time limits of the experiment, the
following month were negative. Because the 3 steers which got T. brucei remained immune
T. vivax strain was lest, we were unable to do for 34 and 49 days; the 14 cattle and 1 goat
any inoculations following that of the 98th
which got T. vivax remained immune for
day, which was 6 >: 10” T. vivax per animal.
48 and 62 days respectively. However, it is
Of the 14 animais inoculated, 9 were positive probable that the immunity lasts longer, but
on the 10th day, 2 on the 19th day and the
not more than 98 days.
remaining 3 were examined for 66 days and
Na’lsa (1969), experimenting w i t h t h e
showed no trypanosomes. As soon as para- drug to try to protect 60 cattle during their
sitism was discovered in the positive animais,
migration through areas where the risk of
they were treated with Isometamidium intra- trypanosomiasis was high, obtained good
venously at 0.5 mg/kg. Their analyses proved results using dose of 0.25 mg/kg and 0.5 mg/
negative 24-48 hours after treatment and
kg, administered intramuscularly. Jones-
there was no recurrence of the parasitism.
Davies did the same in 1967. From these two
(b) After Isometamidium was administered experiments, immunity seems to vary accord-
to three other steers weighing 100-126 kilos, ing to dosage; at 0.50 mg/kg, 28 days (Na’lsa,
they were inoculated with an indefinite
196X) or 59 days (Jones-Davies, 1967) would
amount of T. brucei. This was done 34 days
be the minimum and 84 days (Jones-Davies,
after treatment for 2 of the steers, and 49
1967) would be the maximum. The ability of a
days after treatment for the remaining steer.
trypanocide to immunize seems to be tied to
3
its ability to be fixed in the tissues (A. E.
RESUME
Taylor, 1960; Benazet, 1962), and Isometa-
L’Isométamidium provoque des réactions
,P
midium seems capable of doing this when
inflammatoires quand il est administré par
administered intravenously. Thus, this drug
could be used on a large scale in animals voie intramusculaire. Toutefois ce produit
peut être injecté par voie intraveineuse. Six
\\
which are destined to be slaughtered, without chèvres et dix-sept bovins ont reçu 0,5 mg/kg
the tissue damage resulting from the intra-
(1 mg/kg chez 3 chèvres) d’lsométamidium à
muscular use of the drug which causes part
1 p. 100 par voie intraveineuse. La dose de
of the carcass to be rejected.
1 mg/kg a été mortelle pour la chèvre. A
0,5 mg/kg, le médicament est bien supporté
SUMMARY
par tous les animaux. Cette dose entraîne, en
Tsometamidium causes inflammations when 24 à 48 heures la disparition des trypano-
administered intramuscularly. However, this
somes chez les animaux infectés par Trq’pa-
drug cari be used intravenously. Six goats and
nosomu ~GIx. L’effect préventif, évalué par
17 cattle were treated with Isometamidium in réinoculation de trypanosomes, est conservé
a solution of 1 part per 100, at a dosage of
dans le traitement intraveineux. Les durées
0.5 mg/kg. The dosage of 1 mg/kg proved de protections observées ont été de 34 jours
fatal in goats. At a dosage of 0.5 mg/kg the et 49 jours chez 3 bovins ayant reçu T. brrrcei,
drug was well tolerated by a11 the animals. 48 jours et 62 jours respectivement chez 14
This dosage brings about the complete dis-
bovins et une chèvre ayant reçu T. Ixh)ax. La
appearance of trypanosomes in animais
protection conférée n’atteint pas 98 jours.
infected with T. vivax within 24-48 hours. The
?-
preventive properties of the drug, which were REFERENCES
evaluated by repeated trypanosome injections,
IEenazet F. (1962). Rev. Elev. Med. Veter. Pavs troo..
‘ I
are retained when it is administered intra-
15,
11. ’
‘i
Finelle, P., and Yvore, P. (1962).
venously. Three cattle which received
I.S.C.T.R., (62,) 14.
T.
Finelle, P. and Lacotte, R. (1963). Rev. Elev. Med.
brucei remained immune for 34 and 49 days,
Veter. Pays trop., 16, 405.
14 cattle and 1 goat infected with
Jones-Davies, W. J. (1967). Bull.
T. ~irax
epizoot. Dis. Afi.,
15, 323.
remained immune 48 and 62 days respectively. Na’lsa, B. K. (1969). Bull. epizoot. Diu. Afr., 17, 45.
Taylor, A. E. R.
Immunity does not last longer than 98 days.
(1960). Brit. J. Pharmacol. Chemot.,
15, 235.
(Received for publiaition 4 April 1972)
NOTES ON THE TRYPANOCIDAL ACTIVITY OF
ISOMETAMIDIUM ADMINISTERED INTRAVENOUSLY
S.M.TOURE
Institute d’Elevage et de Médicine Vétérinaire des Pays tropicaux
Laboratoire national de 1’Elevage et de Recherches Vétérinaires,
Dakar-Hann, Sénégal
Isometamidium is used more and more previously infected. The drug was given in a
frequently for prophylaxis and treatment of solution of 1 part per 100 at a level of 0.5 mg-
animal trypanosomiasis. This drug is an
1 mg/kg. Parasite analyses were done daily.
excellent trypanocide but it does cause
The seventeen cattle were treated in several
necrosis at the injection site when adminis-
ways :
tered intramuscularly. This is a serious
(a) 14 got Isometamidium intravenously at
drawback to the use of the drug as it means
0.5 mg/kg and were then inoculated
that part of the carcass Will be rejected by
with T. vivax at various intervals.
the slaughterhouse. Similar observations have
(b) Steers were inoculated with T. brucei
been made by many veterinarians who use
instead of T. vivax.
the drug intramuscularly several months
Analyses of the parasitism in the cattle
prior to slaughter. However, Isometamidium were done daily.
(5
cari be administered intravenously. Finelle
and Yvore (1962) and Finelle and Lacotte
RESULTS
injected Isometamidium chloride hydrochlo-
‘#
rate intravenously in a solution of 1 part per
(1) Observations on the goats
100 at a dosage of OS-3 mg/kg. The curative
Two of the goats infected with T. vivax
properties are good and the animals stand were inoculated with 1 mg/kg of Isometami-
the drug relatively well up to 2 mg/kg.
dium 9 and 17 days after the trypanosome
However, we had no precise indication of the injection respectively. At this dosage, death
preventive properties of the drug adminis-
occurred swiftly-in 4 hours in each case. The
tered intravenously. This paper reports the high degree of parasitism at the time of the
reactions of goats and cattle infected with treatment could not cause these sudden
trypanosomes before and after they received deaths. A new goat which received the same
Isometamidium intravenously.
dosage of the drug also died quickly, although
it was not infected. According to our obser-
MATERIALS AND METHODS
vations, the dosage of 1 mg/kg administered
intravenously seems to be excessive for goats,
This experiment was conducted at the even though this dosage is well tolerated
Veterinary Laboratory in Dakar.
when given intramuscularly.
%
Five of the six goats used in the experi-
Three other goats received Isometamidium
ment were infected with a strain of Trypano-
at 0.5 mg/kg on the 9th, 15th and 17th days
soma vivax. They showed a high degree of respectively after the T. vivax injection, when
c
parasitism between the 9th and the 17th day the level of parasitism was high. The animals
post injection and Isometadium was then tolerated the drug well and the trypanosomes
administered. The remaining goat was given disappeared within 48 hours. These three
Isometamidium, although it had not been goats were thcn re-inoculated with T. Cvax
2
subcutaneously on the 16th, 18th and 20th They were then examined daily for 2 months
days respectively, after the Isometamidium and showed no signs of trypanosomes.
treatment. Their tests were negative. They
were then re-inoculated with trypanosomes
on the 31st, 32nd and 35th days respectively
DISCUSSION AND CONCLUSTON
and the tests were again negative. One of the
In these trials, it did not seem necessary to
*
goats was re-inoculated with trypanosomes on have a control group. It was shown that
the 62nd day and again the test proved unprotected cattle infected with T. vivax and
negative. The re-inoculation of the two T. brucei strains become diseased after an
remaining goats could not be done because average of one week and the disease becomes
the T. vivax strain was lost.
severe if these animals are not treated. This
(2) Observations on the cattle
is proved by the fact that there was patent
infection of the experimental animals prior to
This part of the experiment dealt with 17
treatment or when the drug had worn off.
Zebu cattle which received Isometamidium
The minimal immunity period cannot be
intravenously at a dosage of 0.5 mg/kg of the
deduced exactly from the preceding experi-
1 part per 100 solution. Al1 the animals ment. The important facts are the following:
tolerated the drug well.
1. Isometamidium, in a solution of 1 part
(a) A group of 14 of the animals weighing per 100, when administered intravenously at a
164-268 kilos was given a dose of about dosage of 0.5 mg/kg, is well tolerated by both
15 x 10’ T. vivax individually, on the 6th day goats and cattle.
after treatment with the drug. Their tests
2. The curative effect is extraordinary in
were negative on the following days. On the regard to T. vivax complete disappearance of
3
17th day, these animals were inoculated trypanosomes within 24-48 hours, with no
again with 25 x 10” trypanosomes. Conse-
recurrence.
cutive analyses were negative. On the 48th
3. The preventive powers of the drug -c
day, the animais were inoculated with 3 x 10” persist when it is administered intravenously.
trypanosomes. Analyses made during the Within the time limits of the experiment, the
following month were negative. Because the 3 steers which got T. brucei remained immune
T. vivax strain was lest, we were unable to do for 34 and 49 days; the 14 cattle and 1 goat
any inoculations following that of the 98th
which got T. vivax remained immune for
day, which was 6 >: 10” T. vivax per animal.
48 and 62 days respectively. However, it is
Of the 14 animais inoculated, 9 were positive probable that the immunity lasts longer, but
on the 10th day, 2 on the 19th day and the
not more than 98 days.
remaining 3 were examined for 66 days and
Na’lsa (1969), experimenting w i t h t h e
showed no trypanosomes. As soon as para- drug to try to protect 60 cattle during their
sitism was discovered in the positive animais,
migration through areas where the risk of
they were treated with Isometamidium intra- trypanosomiasis was high, obtained good
venously at 0.5 mg/kg. Their analyses proved results using dose of 0.25 mg/kg and 0.5 mg/
negative 24-48 hours after treatment and
kg, administered intramuscularly. Jones-
there was no recurrence of the parasitism.
Davies did the same in 1967. From these two
(b) After Isometamidium was administered experiments, immunity seems to vary accord-
to three other steers weighing 100-126 kilos, ing to dosage; at 0.50 mg/kg, 28 days (Na’lsa,
they were inoculated with an indefinite
196X) or 59 days (Jones-Davies, 1967) would
amount of T. brucei. This was done 34 days
be the minimum and 84 days (Jones-Davies,
after treatment for 2 of the steers, and 49
1967) would be the maximum. The ability of a
days after treatment for the remaining steer.
trypanocide to immunize seems to be tied to
3
its ability to be fixed in the tissues (A. E.
RESUME
Taylor, 1960; Benazet, 1962), and Isometa-
L’Isométamidium provoque des réactions
,P
midium seems capable of doing this when
inflammatoires quand il est administré par
administered intravenously. Thus, this drug
could be used on a large scale in animals voie intramusculaire. Toutefois ce produit
peut être injecté par voie intraveineuse. Six
\\
which are destined to be slaughtered, without chèvres et dix-sept bovins ont reçu 0,5 mg/kg
the tissue damage resulting from the intra-
(1 mg/kg chez 3 chèvres) d’lsométamidium à
muscular use of the drug which causes part
1 p. 100 par voie intraveineuse. La dose de
of the carcass to be rejected.
1 mg/kg a été mortelle pour la chèvre. A
0,5 mg/kg, le médicament est bien supporté
SUMMARY
par tous les animaux. Cette dose entraîne, en
Tsometamidium causes inflammations when 24 à 48 heures la disparition des trypano-
administered intramuscularly. However, this
somes chez les animaux infectés par Trq’pa-
drug cari be used intravenously. Six goats and
nosomu ~GIx. L’effect préventif, évalué par
17 cattle were treated with Isometamidium in réinoculation de trypanosomes, est conservé
a solution of 1 part per 100, at a dosage of
dans le traitement intraveineux. Les durées
0.5 mg/kg. The dosage of 1 mg/kg proved de protections observées ont été de 34 jours
fatal in goats. At a dosage of 0.5 mg/kg the et 49 jours chez 3 bovins ayant reçu T. brrrcei,
drug was well tolerated by a11 the animals. 48 jours et 62 jours respectivement chez 14
This dosage brings about the complete dis-
bovins et une chèvre ayant reçu T. Ixh)ax. La
appearance of trypanosomes in animais
protection conférée n’atteint pas 98 jours.
infected with T. vivax within 24-48 hours. The
?-
preventive properties of the drug, which were REFERENCES
evaluated by repeated trypanosome injections,
IEenazet F. (1962). Rev. Elev. Med. Veter. Pavs troo..
‘ I
are retained when it is administered intra-
15,
11. ’
‘i
Finelle, P., and Yvore, P. (1962).
venously. Three cattle which received
I.S.C.T.R., (62,) 14.
T.
Finelle, P. and Lacotte, R. (1963). Rev. Elev. Med.
brucei remained immune for 34 and 49 days,
Veter. Pays trop., 16, 405.
14 cattle and 1 goat infected with
Jones-Davies, W. J. (1967). Bull.
T. ~irax
epizoot. Dis. Afi.,
15, 323.
remained immune 48 and 62 days respectively. Na’lsa, B. K. (1969). Bull. epizoot. Diu. Afr., 17, 45.
Taylor, A. E. R.
Immunity does not last longer than 98 days.
(1960). Brit. J. Pharmacol. Chemot.,
15, 235.
(Received for publiaition 4 April 1972)