The experimental chemotherapy of leishmaniasis, VI. The development of rodent models for cutaneous infection with L. major and L. mexicana amazonensis

Abstract

Two models have been established of leishmanial infections in random-bred TFW albino mice, one with Leishmania major LV39 and the other with L. mexicana amazonensis LV38. These parasites produce consistent lesions when injected subcutaneously a short distance anterior to the base of the tail. Consistent infections could not be produced in the mice with other lines of the L. mexicana group of skin-dwelling protozoa, nor with a line of L. braziliensis guyanensis (LV475). The development of procedures for the maintenance of these parasites, the routine infection of mice and drug testing are described. L. major inocula consist of 1--5 X 10(6) promastigotes derived from NNN culture. L. m. amazonensis inocula contain approximately 10(7) amastigotes obtained from lesions in hamsters. The effects of drugs on the rodent lesions are assessed by two methods. Method A provides a simple lesion score from 0 to 3 made when lesions in control animals begin to reach maximum development (about six weeks after infection). Method B summates earlier 'mean lesion scores' to provide a graphic analysis of doses giving 50 and 90% lesion suppression at the end of seven weeks after the start of treatment which is for five consecutive days (SD 50 and SD90). The activities of several compounds used for the treatment of human leishmanial infections (organic antimonials, diamidines, amphotericin B and primaquine) are compared in mice infected with L. major LV39, L. m. amazonensis LV78 and 'L. infantum LV9' (the latter as reported earlier). It is concluded that the rodent models provide a good parallel with the response to these compounds in man. The visceral organism is significantly more responsive to Pentostam and Glucantime than are L. major or L. m. amazonensis. Primaquine is active only against 'L. infantum LV9'. All three parasites in mice respond to Berenil, but not to pentamidine which is used in the treatment of kala-azar. Amphotericin B is effective against cutaneous and visceral infections, but precautions must be taken to ensure its absorption by experimental animals.