antimony-sodium-gluconate and Trypanosomiasis--African

The currently available anti-leishmanial antimonial drugs, together with other antimony compounds were individually tested, in combination with difluoromethylornithine (DFMO), against experimental murine trypanosomiasis with central nervous system involvement. Satisfactory cure rates could be achieved using a combination treatment of DFMO with most of these anti-leishmanial drugs, but in general, only when they were administered at least twice daily. Of the compounds tested, the most effective was antimony dimercaptosuccinate (Astiban).

Topics: Animals; Antimony; Antimony Sodium Gluconate; Drug Synergism; Drug Therapy, Combination; Eflornithine; Female; Meglumine; Meglumine Antimoniate; Mice; Organometallic Compounds; Succimer; Tartrates; Trypanocidal Agents; Trypanosoma brucei brucei; Trypanosomiasis, African

The efficacy of melarsoprol in the treatment of chronic T. b. brucei infections in mice can be increased approximately 5 times if DL-a-difluoromethylornithine (DFMO) is given in the drinking water at the same time. A more detailed study substantiated the concept that a reduction in both the size and the rate of replacement of the trypanothione pool are the key factors in the efficiency of melarsoprol chemotherapy. It was therefore best to give the melarsoprol towards the end of the DFMO regimen, and as a guanylhydrazone (TBG) also blocks trypanothione (polyamine) biosynthesis, if TBG/DFMO are given together the treatment period can be reduced to 8 days. The antimony compound, sodium stibogluconate (Pentostam), used in combination with DFMO can also cure these infections and demonstrates that arsenic could be substituted by antimony in the treatment of CNS infections.

Topics: Animals; Antimony Sodium Gluconate; Arsenicals; Drug Synergism; Drug Therapy, Combination; Eflornithine; Melarsoprol; Mice; Mitoguazone; Trypanosoma brucei brucei; Trypanosomiasis, African

Metronidazole has been claimed in several earlier reports to be active in human cases of leishmaniasis and trypanosomiasis. Its efficacy against the protozoa causing these diseases was tested in hamsters infected with Leishmania mexicana or L. donovani, and in mice infected with Trypanosoma brucei brucei. In separate experiments, hamsters were either inoculated intradermally into the nose with 5 million amastigotes of L. mexicana or intracardially with 10-30 million amastigotes of L. donovani, and mice were infected intraperitoneally with 30 million T. b. brucei. Metronidazole was administered in four oral doses on alternate days for a total of 375 mg/kg to hamsters and 500 mg/kg to mice. Sodium stibogluconate (Pentostam) served as a positive control. In hamsters the extent of infection was assessed by the appearance of flagellates in blood agar cultures of nose and spleen, by counting amastigotes in nose and liver impression smears, and by measuring the size of nose lesions. Ultrastructure of nose lesions before and after treatment with metronidazole or Pentostam was also evaluated. Infection in mice was assessed by the extent of parasitemia and/or survival to 30 days. In no case did metronidazole-treated animals differ from untreated controls. Metronidazole shows no activity against experimental infections of leishmaniasis or trypanosomiasis in these animal models.

Topics: Animals; Antimony Sodium Gluconate; Cricetinae; Leishmaniasis; Leishmaniasis, Visceral; Mesocricetus; Metronidazole; Mice; Microscopy, Electron; Nose; Pentamidine; Trypanosoma brucei brucei; Trypanosomiasis, African