Quantitative in vitro drug potency and drug susceptibility evaluation of Leishmania ssp. from patients unresponsive to pentavalent antimony therapy.

Quantitative in vitro drug sensitivity of 32 Leishmania isolates (16 from patients failing pentavalent antimony [SbV] therapy) was determined using a radiorespirometric microtechnique (RAM). Of 30 isolates with histories, 22 (73%) RAM tests agreed with patient history; the remaining 8 (27%) did not. There was no difference in RAM drug sensitivity: clinical correlation between 15 isolates tested blindly and 15 with known clinical history (4 did not agree with clinical history in both). Test sensitivity appeared to be limited only by the sensitivity of the Leishmania to SbV and could be detected at 2 micrograms/ml Sb (about 10% of serum drug level). An isolate from a patient with untreated self-healing cutaneous disease was drug resistant. Using RAM, parasite drug sensitivity can be quantified apart from patient physiologic and immunologic variables intrinsic to clinical data. Potency differed a maximum of 100% (weight% Sb:weight% Sb) among drug lots and also between Glucantime and Pentostam. Potency changes between drug lots were not explainable based on Sb content or test-to-test variability. This microtest offers a rapid method for evaluating the drug sensitivity of patient isolates and for determining of the activity of pentavalent antimonials and other candidate anti-leishmanials prior to the initiation of therapy.

Treatment of malaria--1990.

Malaria has become an increasingly common health problem in the 1970s and 1980s, both in areas where infection is endemic and in travellers returning to non-endemic areas. The severity of infection varies widely, depending on the plasmodial species involved, and there is an extensive chemotherapeutic armamentarium currently available to combat malarial infection. Drug chemistry, pharmacokinetics, mechanism of drug action and resistance, and toxicities are outlined for the cinchona alkaloids (quinine and quinidine), chloroquine, amodiaquine, pyrimethamine, the sulphonamides, pyrimethamine/sulfadoxine, mefloquine, pyrimethamine/sulfadoxine/mefloquine, the sesquiterpene lactones, primaquine, and other drugs. A knowledge of the distribution of drug resistance is vital for the provision of effective antimalarial therapy, and current information in this area is outlined. Chloroquine remains the mainstay of treatment for the erythrocytic stages of Plasmodium vivax, P. ovale, P. malariae, and chloroquine-sensitive P. falciparum malaria. The dormant hepatic stages of P. vivax and P. ovale also require further treatment with primaquine. Quinine, alone or in combination with other drugs, is the primary agent used to treat chloroquine-resistant falciparum malaria. Falciparum infection can rapidly become fatal, therefore its complications of multiple organ failure, heavy parasitaemias, cerebral malaria, and hypoglycaemia must be recognised and managed promptly. Because these protozoal parasitic infections are now encountered throughout the world and can become life-threatening, a wide variety of practitioners must become more familiar with their correct treatment.