Topical treatment with hexadecylphosphocholine (Miltex (R)) efficiently reduces parasite burden in experimental cutaneous leishmaniasis

Ether-lipids and alkylphosphocholines have been found to have anti-leishman ial activity. Oral treatment with hexadecylphosphocholine (HePC) efficientl y reduces parasite burden in murine visceral leishmaniasis. Drugs for the t reatment of cutaneous leishmaniasis are most commonly administered parenter ally, whereas efficient drugs for topical treatment are not in current use. Here we investigate the efficacy of topical treatment with HePC in mice in fected with Leishmania mexicana or L. major, causative agents of cutaneous leishmaniasis in the New and Old World, respectively. BALB/c, CBA/J and C57 BL/6 inbred mice do not control infection with L. mexicana because they do not mount an efficient Th1-type antiparasitic lymphocyte response. In contr ast, C57BL/6 mice are resistant to an infection with L. major, developing o nly transient lesions that heal spontaneously owing to an efficient Th1 res ponse. BALB/c, CBA/J and C57BL/6 mice were infected subcutaneously with L. Mexicana amastigotes, causing nodular lesions after 5 months. Topical treat ment with HePC (Miltex((R))) was highly effective in reducing parasite burd en and healed established lesions. The treatment did not induce a Th1 respo nse in L. mexicana-infected susceptible mice and most of the mice relapsed. In resistant C57BL/6 mice infected subcutaneously with 2 x 10(6) L. major promastigotes at the tail base, nodular lesions developed after 2 weeks. To pical treatment with Miltex reduced the parasite load and the mice healed t heir lesions much faster than the untreated infected controls. The clinical application of Miltex for treatment of cutaneous leishmaniasis may be high ly efficient because humans, similarly to resistant mice, in general do not relapse after healing. Clinical trials should be straightforward consideri ng that Miltex is an approved drug for the treatment of breast cancer metas tases.