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Preclinical toxicologic study of 2,3-dihydro-1H-imidazo[1,2-b] pyrazole (IMPY) in mice, dogs, and monkeys.

Single-treatment schedules in mice and dogs and multiple-treatment schedules in dogs and monkeys were used to evaluate the toxicity of 2,3-dihydro-1H-imidazo[1,2-b]pyrazole. The LD50 of the iv single dose in male and female mice collectively was 993 mg/kg (2980 mg/m2). The major target organs in mice, dogs, and monkeys were the bone marrow, lymphoid tissue, and gastrointestinal tract. Clinical signs at lethal and high toxic doses were weight loss, diarrhea, hematochezia, emesis, anorexia, mydriasis, dyspnea, lethargy, and stupor. The immediate toxic effect on blood cells was a depression of rbcs with suppression of lymphoid elements occurring later. In dogs, the most toxic schedule was single bolus injections. Attenuation of toxic responses occurred if rest periods were introduced between single or repeated daily dose schedules. The monkeys were more sensitive than the dogs to the high toxic dose on a milligram per meter squared basis, with similar sensitivity to the low toxic dose in the repeated daily injections.

Animals↗

PubMedDate not supplied

[Chloroquine resistance and malaria control in Ivory Coast].

We present here data from the Ivory Coast on the susceptibility of Plasmodium falciparum to chloroquine, obtained since the first chloroquine-resistant strains were discovered in 1987. Susceptibility was assessed using the WHO 7-day field test. Almost all the tests were carried out in the capital, Adidjan, and in the southern forest zone. The frequency of chloroquine resistance was below 30% in most cases, the actual frequency differing between regions. The frequency of R3 chloroquine-resistant P. falciparum was very low. Such resistant parasites were found only on an oil-palm plantation and in the south west of the country, probably due to the free medical care available at both locations. In general, access to health care is limited. Fevers attributed to malaria are generally treated at home using plants or incomplete courses of chloroquine. Our data suggest that R3 chloroquine-resistant P. falciparum strains are selected by repeated high doses of chloroquine, rather than by low doses. Thus, symptomatic treatment of uncomplicated malaria and treatment at home with the "correct" medication may be more effective than systematic medication, for limiting the level of chloroquine resistance in the parasite. Pyrethroid-resistant Anopheles gambiae s.l. is present in West Africa and this may reduce the short-term effectiveness of impregnated mosquito nets. In the absence of R3 chloroquine-resistant P. falciparum, self-medication at home may be a practical and realistic way to treat malaria. However, more knowledge about the effectiveness of anti-malaria drugs, their use in various social, cultural and economic environments and the geographical distribution of insecticide-resistant vectors is required before effective strategies can be designed. However, it would certainly be of value to consistently check the quality of anti-malaria drugs and to try to improve the effectiveness of self-medication at home.

Adolescent↗