Testing Experimental Compounds against American Cutaneous and Mucocutaneous Leishmaniasis

摘要

Over a two year period eight WRAIR compounds have been tested against two subspecies of L. mexicana, three species of Leishmania braziliensis, and L. donovani. Five of these were 8-amonoquinolines, two were imidazoles, and the last was primaquine phosphate. Systemic Pentostam was tested in combination with Pentostam cream and with BCG in each of these models, as were anti-trypanosome compounds alpha D,L-difluoromethylornithine (DFMO) + Bleomycin. In the visceral model, all aminoquinolines were as active as Pentostam, as shown by Pentostam Indices of 1.4 to 11.8. Spleens from these mice were all culture positive, however, and no cures were observed. The imidazole ketoconazole and its acid hydrolystate are active against Trypanosoma and Leishmania species in vitro. Three types of combination chemotherapy were tested against viscereal, cutaneous, and/or mucocutaneous infections in BALB/c mice. These included systemic and tropical application of Pentostam against L. braziliensis Pentostam and bacille Calmette-Guerin (BCG) against L. mexicana amazonensis, and DFMO in combination with Bleomycin against L. donovani infections. Of the combinations tested, only 1% DFMO in the drinking water in combination with 3 mkd Bleomycin was competitive with Pentostam. This is the first time in more than 30 years a specific, nontoxic treatment against leishmaniasis is competitive with antimonials.