Am. J. Trop. Med. Hyg., 82(1), 2010, pp. 1-3
doi:10.4269/ajtmh.2010.09-0490;
Copyright © 2010 by The American Society of Tropical Medicine and Hygiene
Resolution of Cutaneous Old World and New World Leishmaniasis after Oral Miltefosine Treatment
Dennis Tappe*,
Andreas Müller, AND
August Stich
Institute of Hygiene and Microbiology, University of Würzburg, Würzburg, Germany; Department of Tropical Medicine, Medical Mission Hospital, Würzburg, Germany
An Afghan migrant who had returned from a visit to the Middle East 2 years before was seen with a non-healing painless lesion on the forearm (Figure 1A). A skin biopsy showed intracellular Leishmania parasites in the subcutis (Figure 1B and C), and the polymerase chain reaction (PCR) was positive for Leishmania tropica. At the same time, a German traveler who had returned from a vacation to Central America 1 month before was seen with progressively ulcerating painless lesions on the ankle, thigh, and forearm (Figure 2A). Scarification of the lesions' margins showed sparse Leishmania amastigotes (Figure 2B and C) and the PCR from biopsies was positive for L. braziliensis. A 28-day treatment with oral miltefosine (2 mg and 2.5 mg/kg, respectively) was initiated in both individuals and the patients were seen at intervals of several weeks (Figures 3 and 4). All lesions healed, but both patients developed nausea and elevated liver function tests during pharmacotherapy. The highest values of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were 66 U/L and 44 U/L in the female migrant and 73 U/L and 33 U/L in the male traveler, respectively. Bilirubin levels were normal in both patients, but the male patient developed 
GT levels of 113 U/L. All values returned to normal 2 and 3 weeks after the end of treatment, respectively. Neither patient's lesions showed clinical relapse when examined 4 months after the end of therapy. Miltefosine (hexadecylphosphocholine) has been shown to be effective in cutaneous and visceral leishmaniasis.1 At least some strains of L. braziliensis, a species that can cause both cutaneous and mucocutaneous disease in the New World, have demonstrated a decreased sensitivity to the drug in vitro, however.2
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Figure 1. Cutaneous Old World leishmaniasis caused by Leishmania tropica in an Afghan woman. A, Initial presentation of the dry, plaque-like lesion with central nodule on the forearm. B, Intracellular parasites in vacuoles of a giant cell (arrowheads). Haematoxylin and eosin stain, magnification x1,000. C, Leishmania in macrophages (arrowheads). Haematoxylin and eosin stain, magnification x1,000. This figure appears in color at www.ajtmh.org.
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Figure 2. Cutaneous New World leishmaniasis caused by Leishmania braziliensis in a German traveler after a vacation in Costa Rica and Belize. A, Initial presentation of the wet ulcerated lesion on the ankle (upper row), thigh (middle row), and forearm (lower row). Lesions were superinfected with Panton Valentine leukocidin-negative Staphylococcus aureus, Escherichia coli, and viridans streptococci. B, Extracellular Leishmania amastigote in tissue scarification. Giemsa stain, magnification x1,000. C, Intracellular parasite in a monocyte (arrowhead). Giemsa stain, magnification x1,000. This figure appears in color at www.ajtmh.org.
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Figure 3. Follow-up presentation of Old World cutaneous leishmaniasis. A, Increasing local inflammation 14 days after start of miltefosine treatment. The lesion looks more nodular than before treatment. B, Decreasing inflammation 21 days after start of pharmacotherapy. C, Resolution of lesion 4 weeks after the end of treatment. Repeated Leishmania serology remained negative throughout the observation period in this patient. This figure appears in color at www.ajtmh.org.
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Figure 4. Follow-up presentation of New World cutaneous leishmaniasis. A, Inflammatory accentuation of the lesions' ring walls 2 weeks after start of miltefosine treatment. B, Wounds are nearly fully covered by scar tissue 3 weeks after cessation of miltefosine therapy. C, Resolution of lesions 7 weeks after the end of treatment. Upper row, lesion on the ankle; middle row, lesion on the thigh; lower row, lesion on the forearm. Leishmania immunoblot was positive in this patient at initial presentation. This figure appears in color at www.ajtmh.org.
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Received August 24, 2009.
Accepted for publication September 28, 2009.
Authors' addresses: Dennis Tappe, Institute of Hygiene and Microbiology, University of Würzburg, Würzburg, Germany and Department of Tropical Medicine, Medical Mission Hospital, Würzburg, Germany, E-mail: dtappe{at}hygiene.uni-wuerzburg.de. Andreas Müller and August Stich, Department of Tropical Medicine, Medical Mission Hospital, Würzburg, Germany, E-mails: andreasmueller{at}missioklinik.de and stich{at}missioklinik.de. 
*Address correspondence to Dennis Tappe, Institute of Hygiene and Microbiology, University of Würzburg, Josef-Schneider-Str.2, 97080 Würzburg, Germany. E-mail: dtappe{at}hygiene.uni-wuerzburg.de
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- Sánchez-Cañete MP, Carvalho L, Pérez-Victoria FJ, Gamarro F, Castanys S, 2009. Low plasma membrane expression of the miltefosine transport complex renders Leishmania braziliensis refractory to the drug. Antimicrob Agents Chemother 53: 1305–1313.[Abstract/Free Full Text]
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