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Studies of Giardia lamblia

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Technical Report

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Uniformed Services University Of The Health Sciences Bethesda United States

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Three different aspects of the biology of the parasite Giardia lamblia were addressed. They were the ability of different strains of G. lamblia to elicit differential delayed type hypersensitivity responses in mice, the development of a hybridoma cell line which produced antibodies to a 47.7 kd antigen of whole trophozoites, and the development and characterization of G. lamblia resistant to a 9 micromolar concentration of albendazole for 24 hours. Albendazole has been suggested asan alternative therapy to the currently used chemotherapeutic agent, metronidazole, since G. lamblia is increasingly resistant to metronidazole . It was found thatresistance was reversible over time, such that a strain resistant to an exposure to 9 micromolar albendazole for 24 hours could show a resistance reduced to a maximum of 7 micromolar albendazole for 24 hours after as little as two weeks without re-exposure to the 9 micromolar dose of albendazole. When culture supernate containing drug was incubated with resistant trophozoites, it retained its ability to kill susceptible trophozoites. The resistant trophozoites retained their ability to encyst. There was no resistance to metronidazole conferred by albendazole resistance. Ultrastructural examination of resistant trophozoites after a 24 hour exposure to 9 micromolar albendazole showed that resistant trophozoites were able to maintain a structurally sound striated disk, while susceptible trophozoites showed degradation of the striated disk. Uptake of 14C-labeled albendazole showed that the resistant trophozoites took up more of the radiolabeled drug within the first 38 hours of exposure. Albendazole resistance in the laboratory model is probably due to a change in the target of action of the drug, requiring a greater amount of drug to act against this target to effect killing of the trophozoite.

Subject Categories:

  • Medicine and Medical Research
  • Pharmacology
  • Biology

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