<HTML><FONT FACE=arial,helvetica><HTML><FONT SIZE=2 PTSIZE=10 FAMILY="SANSSERIF" FACE="Arial" LANG="1">Ive sent a letter to a english veterinary rewiew ( The veterinary record) about the risks of the use of meglumine antimoniate in canine leishmaniasis )<BR>
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(I know that it is probably too late, but i had mentioned these facts in previous papers) <BR>
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Lamothe J Use of meglumine antimoniate in canine leishmaniasis.Vet Rec. 2004 Mar 20;154(12):378</FONT><FONT COLOR="#000000" BACK="#ffffff" style="BACKGROUND-COLOR: #ffffff" SIZE=3 PTSIZE=12 FAMILY="SANSSERIF" FACE="Arial" LANG="1"> <BR>
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Regards <BR>
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<BR>
SIR<BR>
<BR>
<BR>
Dogs are reservoirs of visceral leishmaniasis, a zoonosis caused bythe parasite Leishmania infantum. The annual incidence is estimated at<BR>
500,000 cases throughout more than 88 countries (Desjeux 1996).<BR>
Leishmaniasis is found in Latin America, the Mediterranean Basin and Asia.<BR>
The two important groups of humans infected are children under the age of<BR>
three years old and HIV infected adults.<BR>
The disease is transmitted from dogs to humans by sandflies. The treatment<BR>
for canine leishmaniasis is a combination of meglumine antimoniate and<BR>
allopurinol; after clinical cure maintenance treatment with allopurinol<BR>
alone is given for the rest of the dogšs life. Widespread use of antimonials<BR>
can result in the selection of resistant strains; strains isolated from<BR>
treated dogs are from eight to 41 times more resistant than those isolated<BR>
from the same dog before treatment (Gramiccia 1992). and there is potential for<BR>
resistant strains to spread as a result of transmission between dogs.<BR>
It is also possible that resistant strains harboured by dogs might be<BR>
transmitted to humans by sandflies.Failures of antimonials in the treatment of human disease (adults or children) have been reported for many years. In a study performed in the<BR>
south of France (Faraut-Gambarelli and others 1997), the susceptibility of<BR>
strains isolated from 11 non-immunocompromised children and 19 young adults<BR>
infected by HIV was measured before and after the treatment. Out of 20<BR>
patients tested before treatment, six patients had the susceptibility<BR>
modified, (the strain was more resistant to meglumine antimoniate) and four<BR>
of them relapsed. A study regarding the susceptibility of 43 human and<BR>
canine strains to meglumine antimoniate in Spain indicated similar results<BR>
to those obtained in the south of France (Carrio and others 2001).<BR>
Obviously, it is difficult to prove that those resistant strains come from<BR>
the canine reservoir, but it is also difficult to find another explanation<BR>
considering that dogs are the unique reservoir of visceral leishmaniasis.<BR>
In my view allopurinol alone should be the first line of treatment for dogs.<BR>
Almost all published studies report satisfactory results and the treatment<BR>
leads to 50 per cent of clinical cure after four months treatment and 80 per<BR>
cent after nine months. Long term studies have shown a 78 per cent chance of<BR>
survival for more than four years (Slappendal and others 1999).<BR>
I would question the justification for meglumine antimoniate use in dogs<BR>
when other drugs may have the same efficacy, even though the clinical cure<BR>
is obtained less quickly.<BR>
In France where this resistance problem has been found, and perhaps in other<BR>
countries where it is likely to be found, the risk of causing resistance in<BR>
human strains outweighs the convenience in using the drug in dogs.<BR>
<BR>
<BR>
<BR>
<BR>
References<BR>
Carrio, J., Riera, C., Gallego, M. &Portus, M. (2001) In vitro activity of<BR>
pentavalent antimony derivatives on promastigotes and intracellular<BR>
amastigotes of Leishmania infantum strains from humans and dogs in Spain.<BR>
Acta Tropica 79, 179-183Desjeux, P. (1996) Leishmaniasis. Public health aspects and control.Clinical Dermatology 14, 417-423<BR>
Faraut-Gambarelli, F., Piarroux, R., Deniau, M., Giusiano, B., Marty, P.,<BR>
Michel, G., Faugere, B. &Dumon, H. (1997) In vitro and in vivo resistance<BR>
of Leishmania infantum to meglumine antimoniate: a study of 37 strains<BR>
collected from patients with visceral leishmaniasis. Antimicrobial Agents<BR>
and Chemotherapy 41, 827-830<BR>
Slappendal, R. J. &Teske, E. (1999) A review of canine leishmaniasis<BR>
presenting outside endemic areas. In Canine Leishmaniasis: an Update.<BR>
Proceedings of a Canine Leishmaniasis Forum. Ed R. Killick-Kendrick.<BR>
Barcelona, Intervet. pp 54-59<BR>
Gramiccia, M., Gradoni, L., Orsini, S. (1992) Decreased sensitivity to meglumine antimoniate (Glucantime Ž) of Leishmania infantum isolated from dogs after several courses of drug treatment. Annals of Tropical Medicine and Parasitology. 86, 613-20 <BR>
<BR>
<BR>
<BR>
<BR>
Dr Jacques Lamothe<BR>
<BR>
Clinique veterinaire <BR>
<BR>
1 rond point de la roya <BR>
F 06510 CARROS <BR>
(0)4 93 29 06 95<BR>
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