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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060 EISSN: 1678-8060
Vol. 93, Num. 4, 1998, pp. 515
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Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 93 (4), July/August 1998,
pp. 515
RESEARCH NOTE
Failure of Albendazole as an Alternative Treatment of Cutaneous
Leishmaniasis in the Hamster Model
B Travi^+, Y Osorio
Centro Internacional de Entrenamiento e Investigaciones Medicas (CIDEIM),
AA 5390, Cali, Colombia
^+Corresponding author. Fax: +57-2-667.2989
Received 18 December 1997; Accepted 1 April 1998
Code Number:OC98100
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Key words: albendazole - cutaneous leishmaniasis - Colombia
RESEARCH NOTE
Search for better anti-leishmanial drugs is still imperative, since the
current treatment with antimonials is toxic, expensive, and requires
prolonged intramuscular administration (EM Netto et al. 1990
Transactions 84: 367). All these features are serious obstacles to
compliance in endemically exposed populations.
Evaluation of antiparasitic drugs that are already marketed and used for
other infectious diseases should be regarded as a viable, and expeditious
alternative to the costly development of new compounds. Albendazole has
been shown to inhibit the growth of various protozoal parasites in
vitro, and was successfully used for treating immunocompromised
individuals infected with microsporidial infections (R Weber et al. 1994
Clin Microbiol Rev 7: 426). Since these organisms are
intracellular parasites it was speculated that an aggressive treatment
schedule similar to that used in AIDS patients, could also be active
against Leishmania, another intracellular protozoan parasite. To
explore this possibility we used the golden hamster (Mesocricetus
auratus), which has been shown to be an adequate model for studying
anti-Leishmania therapy (WL Hanson et al. 1991 J Parasitol
77: 780, BL Travi et al. 1993 Transactions 87: 567).
A subline of MHA inbred hamsters (n=14) was inoculated s.c. in the hindfoot
with 1x10^4 promastigotes of L. (V.) panamensis (MHOM/COL/84/1099).
Thirty days postinfection seven hamsters were treated orally with
albendazole (Zentel, SmithKline Beecham) (40mg/kg/twice a day) during six
weeks, while the remaining seven animals were used as untreated controls.
The clinical evolution of the lesion was monitored by measuring the
infected and contralateral uninfected foot at weekly intervals until the
end of treatment. Parasite burden at the lesion site was roughly estimated
by microscopy (1,000 X) in Giemsa-stained impression smears. Dissemination
to reticuloendothelial tissues was determined by culturing in Senekjie's
medium samples from lymph nodes draining the lesion, distant lymph nodes,
spleen and liver.
Although the inflammatory signs of the lesions of treated hamsters were
less conspicuous, the parasite burden was similar to that of untreated
animals (mean 4.8 vs 6.1 amastigotes/100 cells, respectively).
Although cutaneous metastasis was significantly less frequent in the
treated group (2.4 vs 17%; P=0.025), no difference in internal
amastigote dissemination was found.
This experiment showed that albendazole, even at large doses, had a
negligible anti-leishmanial effect in hamsters infected with L.
panamensis, as compared with antimonials (Travi et al. 1993 loc.
cit). The low intestinal absortion of the drug could explain in part
the treatment failure, although it was postulated that the high and
prolonged administration of albendazole should have compensated for this
pharmacokinetic drawback. The reason as to why cutaneous metastases in
treated animals were significantly reduced is not clear; this phenomenon
might have been related to the amelioration of the inflammatory response.
It is worth noting that inflammation has already been associated with the
expression of metastasis in the hamster model (BL Travi et al. 1996 J
Parasitol 82: 454). Also, in an unpublished experiment, we have
observed a significant reduction of cutaneous metastases (33.3 vs
7.1%, P< 0.005) in hamsters infected with L. panamensis and
subsequently treated with the anti-inflammatory drug indomethacine
(Upjohn). Despite the negative results with albendazole, preclinical trials
should continue to be carried out whenever additional, less toxic
benzimidazoles with higher intestinal absortion, and proven antiprotozoal
activity become available.
This work was supported by the U.S. National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Tropical Medicine
Research Center Grant P50-AI30603-04 and COLCIENCIAS 2229-04-004-92.
Copyright 1998 Fundacao Oswaldo Cruz - Fiocruz
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