Suppression of posttreatment recurrence of experimental visceral Leishmaniasis in T-cell-deficient mice by oral miltefosine

Abstract

T-cell-deficient nude mice infected with Leishmania donovani were treated with miltefosine and then given either no treatment or intermittent miltefosine. Intracellular visceral infection recurred in untreated mice but was suppressed by once- or twice-weekly oral administration of miltefosine. Miltefosine may be useful as oral maintenance therapy for T-cell-deficient patients with visceral leishmaniasis.

FIG. 1

Initial effect of miltefosine treatment in nude BALB/c mice and prevention of subsequent relapse. Two weeks after infection, nude mice were initially treated with drug for 5 days. Two days later (end of week 3), treated mice either were given no further drug or received single doses every second week, once weekly, or twice weekly for the next 9 weeks. Results are from two experiments and are means ± SEMs for seven to eight mice per group.

FIG. 2

Photomicrographs of livers of nude mice 12 weeks after L. donovani infection. (a) Mice treated with miltefosine during week 2 to 3 only (no maintenance therapy) show recurrent infection, with multiple heavily parasitized foci (arrows). Magnification, ×500. (b) In contrast, mice treated during week 2 to 3 and twice weekly thereafter show markedly reduced liver parasite burdens at week 12, with only one infected focus in a lower-power field (arrow). Magnification, ×315.