Chemotherapy of visceral leishmaniasis (Leishmania donovani) in the squirrel monkey (Saimiri sciureus)

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Abstract
The relationship of the numbers of amastigotes in the liver to the duration of infection with two lines of a Khartoum strain of Leishmania donovani [designated the parent (P) line and the meglumine antimoniate (Glucantime®) resistant (MAR) line] and the effect of meglumine antimoniate on these two lines of Leishmania were studied in the squirrel monkey. All experimental monkeys were inoculated via the saphenous vein with 32·5 × 106 amastigotes (per kg body weight), obtained from heavily-infected hamster spleens. Subsequently in Experiment I, liver biopsy samples were taken chronologically from all monkeys. Imprints of liver were made on glass slides and stained with Giemsa's staining solution, and parasite density per gram of liver tissue was determined. The parasites reached a maximum density of 6·2 × 106 amastigotes per gram between two to four weeks and 9·4 × 107 amastigotes per gram between four to six weeks in the monkeys receiving the P line and the MAR line, respectively. Parasite numbers then decreased, and all the livers and spleens of all monkeys became microscopically negative for Leishmania eight to 13 weeks post-infection. Comparison of the multiplication of the two lines of Leishmania indicated that the MAR line persisted longer in the livers than did the P line. A slight decrease in body weight was observed at eight weeks post-infection. Packed cell volume and haemoglobin were low at four to eight weeks post-infection, but were within the normal range. In Experiment II, a liver biopsy sample was taken from each monkey on day 8 after inoculation and parasite density determined as in Experiment I. Glucantime was administered via the intramuscular route at 104 mg Sb kg−1 day−1 for ten days beginning on day 15 post-infection. Numbers of amastigotes per gram of liver and spleen were determined from imprints at necropsy two days after termination of treatment. Glucantime was active against the P line but was inactive against the MAR line. These results are similar to those obtained in hamsters with this dosage level of Glucantime against both parasite lines (Waits et al., personal communication). The squirrel monkey was found to be susceptible to L. donovani and should be a useful model for certain types of chemotherapeutic and immunological studies. In addition, this model can be used to compare virulence of different lines or isolates of the same or different species of Leishmania.

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