93 - 97 de-la-rosa.pmd
24(2): 93–97 (2007)
Study of the reproductive capacity of Trichinella spiralis
recovered from experimentally infected mice under-dosed
with albendazole or mebendazole
de-la-Rosa, J.L.1, Álvarez, N.1 and Gómez-Priego, A.1,21 Laboratory of Tissular Helminthes, Institute of Epidemiological Diagnostic and Reference. Ministry of Health.
Mexico City, 11340. Mexico.
2 Department of Microbiology and Parasitology, School of Medicine, National Autonomous University ofMexico. Mexico City, 04510. MéxicoE-mail: [email protected]
24 April 2007; received in revised form 3 May 2007; accepted 8 May 2007
The reproductive capacity of Trichinella spiralis
recovered from experimentally
infected mice under-dosed with albendazole (ALB) or mebendazole (MEB) was studied.
Different groups of male C57/BL mice were infected with 10 ± 0.5 muscular larvae (ML) per
gram of body weight and treated with a single dose by oral (20 mg/kg) of ALB,
praziquantel (PZQ) given at 5th day post infection (DPI), during the intestinal phase of
infection. In other group of mice, treatment with the same drugs and dosage was for seven
days, starting at day 45 PI through the stage of encapsulating larvae (parenteral phase of
infection). A reduction of 72.9 to 89.9% in the parasitic load was observed in ALB or MEB
treated groups but not in mice untreated or administered with PZQ. The recovered larvae were
used to infect naïve mice and, after 45 DPI, a similar Reproductive Capacity Index (RCI) was
observed between the different groups (P=0.323, one-way ANOVA), either from mice infected
recovered from the intestinal treatments (RCI-ALB = 51.6 ± 12.1 and RCI-MEB =
49.2 ± 14.) or from the parenteral ones (RCI-ALB = 52.2 ± 14.0 and RCI-MEB = 51.9 ± 11.8).
The RCI of non-treated ML was 59.5 ± 7.7 and 57.9 ± 15.9 for PZQ. This information is
significant for practical strategies when under-dosage is dispensed.
To prevent and control parasitic diseases,
levels, and a number of factors contribute
one of the most popular is the dispensation
in treatment failure, as seen in the single
morbidity control (van Wyk et al
Geerts & Gryseels, 2000). The factors are:
dose, generic products of the drugs are of
derivatives are 100 – 200 mg twice a day
for three days or 400 – 500 mg in a single
inappropriately repacked or reformulated,
expired and of poor-quality.
As a result of
dosage must be daily administered for two
or three weeks (de-Silva et al
anthelmintics were administered orally.
derivatives, and remain infective to naïve
mice (Pozio et al
., 2000; Marinculic et al
control in the experiments, another control
2001; Casulli et al
., 2006). However, the
PZQ, since it is known that PZQ is highly
effective in eradicating cestodes but not
of T. spiralis
recovered from experi-
maintained in culture media for 18 hours.
albendazole (ALB) or mebendazole (MEB).
pepsin-HCl artificial digestion of minced
from control mice. For statistical analysis
experiments; details for the experimental
trials are described in Table 1. All used
Table 1. Experimental trials for the treatment with albendazole (ALB), mebendazole (MEB), andpraziquantel (PZQ) of mice infected with Trichinella spiralis
DPI: days post infection, AW: adult worm, ML: muscular larvae, WTR: water.
ALB, MEB and PZQ were commercially acquired from Laboratorios Hormona, Laboratorios A. F. and Merckrespectively, all from Mexico City.
— * None
infection (Fernandez & Wakelin, 1989). In
intestinal nematodes) or water,
analyzed with the factorial ANOVA test and
Student’s t test; WRI for PZQ = 0.437 ±
0.122 and WRI for WTR = 0.402 ± 0.127).
larvae (experiments 4 and 5) with the one
To determine if the reproductive capacity
applied (experiments 4 and 5, Table 1).
summarized in Table 2. As expected, there
was a reduction in the parasite densities at
all stages of infection, i. e., at day 5 PI
were not statistically significant, according
(intestinal, experiments 1 and 2) or at 45
ALB or MEB eliminated the 70 – 80% of AW
relation to the effect of the drug and the
small proportion of surviving parasites was
Table 2. Results of the albendazole (ALB), mebendazole (MEB), and praziquantel (PZQ) treatmenton Trichinella spiralis
a WTR: waterb Factorial ANOVA test, p = 0.733* ND: Not done
Figure 1. Reproductive capacity of Trichinella spiralis
muscle larvae recovered after anthelmintictreatment. Larvae recovered from mice experimentally infected and treated with a specificanthelmintic were used to infect naïve mice. Albendazole (ALB), mebendazole (MEB), praziquantel(PZQ) or water (WTR) were given to donors animals at day 5 (open bars) or 45 (close bars) post-infection and larvae were recovered, respectively, at days 45 and 60 post infection. Thereproductive capacity index was calculated as the number of ML recovered over the number ofML given as infection.
are able to
surviving treatment with
or flubendazole, remained infective
these parasites are able to complete their
to naïve mice (Pozio et al
., 2000; Cheng et
life cycle with intact fecundity. In this
., 2001; Marinculic et al
., 2001; Casulli et
., 2006) but the reproductive capacity of
Marinculic et al
. (2001) and Casulli et al
(2006). In relation to this, Campbell &
mice sacrificed at 45 days PI, had ML.
Therefore, the results of this study indicate
thiabendazole were not infective to other
the drug when it is treated under-dosage.
Although, it is not easily understood how
could be hypothised that the differences in
chloride solutions in vitro
. Our results are
in contrast with those previously published
alternative hypothesis could be that under-
Cheng, M.S., Joo, K.H., Quan, F.S., Kwon,
in mice. Parasite
since resistance to antiparasitic drugs has
Dawson-Saunders, B. & Trapp, R.G. (1994).
been widely suggested (Geerts & Gryseels,
. 2ª. Edición
2000; Torres-Acosta et al
., 2003). Although
several other hypotheses can be suggested,
de-Silva, N., Guyatt, H. & Bundy D. (1997).
there is a need for additional studies to
their clinical pharmacology. Drugs 53
supporting parasite evasion and the effect
Fernandez, F.B. & Wakelin, D. (1989).
Infectivity of Trichinella
be a useful strategy to control morbidity,
responsiveness. Parasitology 99:
parasites, as shown in this study, are able
Geerts, S. & Gryseels, B. (2000). Drug
to preserve their reproductive capacity.
situation and lessons from livestock.
wild-types could result in an anthelmintic
Clinical Microbiology Reviews 13
resistant worm population over a period of
Geerts, S. & Gryseels, B. (2001). Anthel-
. The authors wish
International Health 6:
suggestions; I. Valle and M. Piñón for care
Marinculic, A., Fajdiga, M. & Durakovic, E.
of the experimental animals maintained at
against Trichinella spiralis
Pozio, E., Sacchi, D., Tamburrini, A. &
Alberici, F. (2000). Failure ofmebendazole in treatment of humanswith Trichinella spiralis
the stage of encapsulating larvae.Clinical Infectious Diseases 32:
Campbell, W.C. & Cuckler, A.C. (1964).
Aguilar-Caballero, A.J. & Rodríguez-
trichinosis in mice. The Journal of
Casulli, A., Morales, M.A., Gallinella, B.,
Veterinary Parasitology 114:
van Wyk, J.A., Malan, F.S., van Rensburg,
L.J., Oberem, P.T., & Allan, M.J. (1997).
larvae of Trichinella spiralis
mintics: is it adequate? Veterinary
microbial Chemotheraphy 58:
B o l e t í n O f i c i a l P r o v i n c i a d e O u r e n s e n . º 1 8 5 · X o v e s , 1 8 a g o s t o 2 0 1 1 dentro del plazo de diez días, contados desde el siguiente a la Estatuto dos traballadores, texto refundido aprobado polo publicación del presente edicto en el Boletín Oficial de la Real decreto lexislativo 1/1995, do 24 de marzo, Real decre-to 713/2010 sobre rexistro e dep
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