Overcoming the Challenge; In Vivo Efficacy of Miltefosine for Chronic Cutaneous Leishmaniasis
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ORIGINAL PAPER
Overcoming the Challenge; In Vivo Efficacy of Miltefosine for Chronic Cutaneous Leishmaniasis Varol Tunalı1,2 · Mehmet Harman3 · İbrahim Çavuş4 · Cumhur Gündüz5 · Ahmet Özbilgin4 · Nevin Turgay2 Received: 22 July 2020 / Accepted: 15 September 2020 © Witold Stefański Institute of Parasitology, Polish Academy of Sciences 2020
Abstract Background Cutaneous Leishmaniasis (CL) is the most common form of leishmaniasis. CL can be divided into two major groups: acute CL (ACL) and chronic CL (CCL). The aim of this study is to compare the efficacy of miltefosin and pentavalent antimony compounds in vivo with the CCL patient samples. Materials Three study groups were formed, each consisting of five male Mus musculus (Balb/C) mice. In this model, promastigotes from the culture of a CCL patient were utilized. 100 μL L. tropica promastigote suspension with a density of 108 promastigotes/ml were injected into the hint-right footpad of each experimental animal intradermally. Footpads of the mice were measured every two weeks until 24th week. From the 13th week, miltefosin 50 mg/kg/day was administered orally using gavage for 21 days, Meglumin antimoniate (MA) was administered by intramuscular (IM) injection daily for 21 days at 50 mg/kg/day and saline was administered IM for 21 days for the miltefosine, MA and control group, respectively. Results The footpad measurements of the miltefosine group were lower than the control group statistically. Between the MA group and the miltefosine group and MA group and the control group, there was no statistically significant difference. Giemsa stained slides revealed amastigotes in one, two and all of the slides for the miltefosine, MA and control group, respectively. Molecular tests were performed with the Rotor-Gene device and L. tropica consistent peaks were obtained in one of the miltefosine group, four in the MA group and all mice in the control group. Conclusions Demonstration of both clinical and laboratory improvement in four of the five experimental animals provides strong evidence that miltefosine is an effective drug in the treatment of CCL. In the literature, no clinical or laboratory studies using miltefosine have been performed with CCL patients only. Keywords Cutaneous leishmaniasis · Drug resistance · Animal model · Turkey
Introduction
* Varol Tunalı [email protected] 1
Department of Emergency Medicine, Faculty of Medicine, Muğla Sıtkı Koçman University, Muğla, Turkey
2
Department of Parasitology, Ege University, Faculty of Medicine, İzmir, Turkey
3
Department of Dermatology, Dicle University, Faculty of Medicine, Diyarbakır, Turkey
4
Department of Parasitology, Celal Bayar University, Faculty of Medicine, Manisa, Turkey
5
Department of Medical Biology, Ege University, Faculty of Medicine, İzmir, Turkey
According to the World Health Organisation’s (WHO) list of neglected diseases, Leishmaniasis is the second parasitic disease that causes the highest number of deaths in the World after malaria. Cutaneous Leishmaniasis (CL) is th
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