Efficacy of experimental trypanocidal compounds against a multiple drug-resistant Trypanosoma brucei brucei stock in mice.

Several experimental trypanocidal compounds, 6-amidino-2-(4-amidinophenyl)indole dilactate (DAPI), DL-alpha-difluoromethylornithine (DFMO), 2-(dimethylamino)-4'-[(1-methyl-2-nitroimidazole-5-yl) methoxy] aceto-anilide (Ro 15-0216), sinefungin, and triacetylbenzene-tris(guanylhydrazone)trimethanesulfonate hydrate (TBG-MS) were tested to evaluate their ability to cure mouse infections with a multiple drug-resistant Trypanosoma brucei brucei stock (CP 547). This stock proved to be drug-resistant against diminazene aceturate, homidium chloride, isometamidium, quinapyramine sulfate, Mel B, and pentamidine isethionate but fully sensitive to suramin. Compared with the sensitive stock CP 462, the drug-resistant stock CP 547 was completely resistant to 16-fold the curative dose of sinefungin and partially resistant to 4-fold the curative dose of DAPI and to 13-fold the curative dose of TBG-MS, a dose that killed 25% of the animals due to its toxicity. Ro 15-0216 cured all mice when 18 times the usual curative dose level was given. DFMO was equally effective against both stocks.

Trypanocidal activity of a 5-substituted 2-nitroimidazole compound (Ro 15-0216) in mice.

The trypanocidal activity of a 5-substituted 2-nitroimidazole compound (Ro 15-0216, 2-(dimethylamino)-4'-[(1-methyl-2-nitroimidazole-5-yl) methoxy] acetanilid) was tested in stocks of T.b. brucei, T.b. evansi, T. vivax, and T. congolense. The trypanosome stocks showed different sensitivities, the Trypanozoon group was most sensitive followed by T. vivax and T. congolense. Administration of the compound in the drinking water was superior to single intraperitoneal injections. A T.b. brucei stock with reduced sensitivity to Mel B and insensitive to diminazene aceturate was cured by a dose 13 times greater than that necessary for the drug-sensitive T.b. brucei stock, administered in the drinking water. Quinapyramine- and quinapyramine/suramin-resistant stocks of T.b. evansi were eliminated with doses of 63 and 160 mg/kg i.p., respectively; to eliminate the drug-sensitive T.b. brucei stock, 250 mg/kg i.p. were required. The combination of Ro 15-0216 with suramin showed a synergistic effect in suramin-sensitive and in suramin-resistant stocks of T.b. evansi, although high doses of suramin were applied in the latter. Synergism of Ro 15-0216 with diminazene aceturate was demonstrated in T. congolense-infected mice.

The treatment of Trypanosoma (Nannomonas) simiae in pigs with diminazene aceturate in combination with a 5-substituted 2-nitroimidazole compound (Ro 15-0216).

Swine Trypanosoma (N.) simiae infections were treated with diminazene aceturate and a 5-substituted 2-nitroimidazole compound (Ro 15-0216). This combination of the two trypanocidal compounds has been successful. Ten mg/kg of diminazene aceturate and 50 mg/kg of Ro 15-0216 or 20 mg/kg of diminazene aceturate and 25 mg/kg of Ro 15-0216 were equally effective, while either drug alone was ineffective. Multiple administration of compound Ro 15-0216 (4 x 20 mg/kg; 3 x 50 mg/kg) at 2 hourly intervals did not cure the animals.

The sensitivity to trypanocidal drugs of Trypanosoma vivax isolated in Kenya and Somalia.

The drug sensitivity of seven Trypanosoma vivax-isolates from Kenya and Somalia was examined. With the exception of diminazene aceturate all commercially available trypanocidal drugs failed to effect a cure. The results suggest the existence of multiple drug resistance of T. vivax-strains, geographically widely distributed along the East African Coast. The isolates were resistant to the recommended dose rates of isometamidium, homidium and quinapyramine. Isometamidium showed no prophylactic properties when tested against one of the isolates. All were sensitive to diminazene aceturate.

Evaluation of sinefungin for the treatment of Trypanosoma (Nannomonas) congolense infections in goats.

Caprine Trypanosoma (N.) congolense infections were treated with sinefungin, an antifungal antibiotic nucleoside. Single doses from 10 to 20 mg/kg bodyweight given intramuscularly were not curative for goats; single doses of 25 and 50 mg/kg were toxic, and caused death. Five and 7.5 mg/kg administered twice daily over a three-day period, resulted in a cure in 2 animals, while 2 others relapsed. All animals relapsed when given a single daily dose of 5 or 7.5 mg/kg for 4 consecutive days. When such doses were given twice a day, they caused death in 50% of the goats and the remainder were cured. Raised serum urea levels indicated the severe nephrotoxic side-effects of sinefungin even at subcurative levels. Histopathological examinations revealed an acute tubulonephrosis.

An enzyme-linked immunosorbent assay for the detection of antibodies to Trypanosoma (T.) brucei evansi in camels (Camelus dromedarius) using peroxidase-conjugated protein A.

Serum samples from dromedary camels naturally and experimentally infected with Trypanosoma (T.) brucei evansi were examined by means of the ELISA, using either an anti-camel or a protein A conjugate. The protein A horseradish peroxidase conjugate was found to bind to camel IgG and thus to be a suitable alternative to the anti-camel conjugate. Results obtained from both tests showed that the respective values correlate significantly.

Wildlife rabies in Zambia.

Wildlife species made up 26 (2.0%) of 1,304 positive rabies cases received between 1969 and 1976. The jackal (Canis adustus) was the predominate wildlife species involved (69%) and played a role in the epidemiology of bovine rabies in remote farm areas. Rabies appears to be absent from the intact wildlife communities in Zambia, especially the National Parks; this is considered in the light of the epidemiology of the disease in wildlife.