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Chemotherapy of Leishmaniasis.
Final rept. May 81-Jul 82,
LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE (ENGLAND) DEPT OF MEDICAL PROTOZOOLOGY
Pagination or Media Count:
Standard Leishmania strains used in this laboratory have been characterised by their isoenzymes. The relationship of antimonial treatment of L. donovani-infected BALBc mice and host immunity has been established. Treatment very early or very late in the infection is optimal ie before parasite numbers have greatly increased, or after the establishment of cell-mediated immunity. Rifampicin and isoniazid exhibit a marked potentiation against L. mexicana amazonensis in mice. No potentiation is seen in mice infected with L. donovani. L. major, L.m. amazonensis and L. donovani in macrophage cultures are used to evaluate candidate antileishmanial drugs, using sodium stibogluconate Pentostam as standard. Of a selection of anti-mycobacteria drugs tested so far, clofazimine has shown marked activity, mostly against L. major but also against the other species. Oxytetracycline also shows some activity against L. major in this system. The new 8-aminoquinoline WR 6026 has proved very active, with a Pentostam index of 10 against L. donovani, 7 against L.m.amazonensis and 29 against L. major. In mode of action studies we are developing an amastigote system to measure respiration. Developmental difficulties relate mainly to the preparation of sufficient numbers of amastigotes of the same three species of Leishmania. An ultrastructural study on the effect of WR 6026 on L.m. amazonensis in mice has shown that the drug induces membrane changes in the outer membrane of the amastigotes within the flagellar pocket and some evidence of early changes in the mitochondria and kinetoplast are present.
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