ABSTRACT
Objective:
Meglumine antimoniate (Glucantime®) and Sodium stibogluconate (Pentostam®) are used for the treatment of cutaneous leismaniasis in Turkey. There is a reported resistance to these drugs in recent years. The aim of the present study was to compare the in vitro sensitivities of resistant Leishmania isolates against Amphotericin B, Miltefosine, Meglumine Antimoniate, Paromomycin and Sodium Stibogluconate.
Methods:
Five Leishmania isolates of patients with cutaneous leishmaniasis, who showed no clinical recovery despite two consecutive meglumine antimoniate treatments, which were stored in the Parasite Bank in Manisa Celal Bayar University Medical Faculty were selected. They were genotyped with Real-Time PCR using specific primers and probes to ITS1 region. Drug resistance levels of each Leishmania isolate were analysed for Amphotericin B, Miltefosine, Meglumine Antimoniate, Paromomycin, and Sodium Stibogluconate at concentrations of 500, 250, 125, 50, 25 μg/mL with XTT method and hemocytometer.
Results:
It was observed that the resistant Leishmania tropica isolates showed no resistance to Amphotericin B, and were sensitive to Miltefosine, Sodium Stibogluconate, Paromomycin and Meglumin Antimonate, respectively. In addition, Leishmania tropica (MHOM/AZ/1974/SAF-K27) isolate of the control group could stay viable in none of the drug concentrations of five agents in the study.
Conclusion:
It was determined that none of the selected resistant L. tropica isolates showed resistance to Amphotericin B and that was also shown statistically (p<0.05). The results of this study are important in guiding clinicians and researchers who conduct studies on drugs and search for new drug molecules.
Keywords:
Cutaneous leishmaniasis, resistance, treatment, resistance tests, Turkey
References
1Gürel MS, Yeşilova Y, Ölgen MK, Özbel Y. Türkiye’de kutanöz leishmaniasisin durumu. Türkiye Parazitol Derg 2012;36:121-9.
2Özbel Y, Özensoy Töz S. Leishmaniasis. Özcel MA, Özbel Y, Ak M, editors. Özcel’in Tıbbi Parazit Hastalıkları Kitabı. Türkiye Parazitoloji Derneği Yayını, No: 22; 2007. p.197-244.
3WHO Technical Report Series-949. Report of a meeting of the WHO Expert Committee on the Control of Leishmaniases, Geneva, 22-26 March 2010.
4https://hsgm.saglik.gov.tr/tr/zoonotikvektorel-sarkcibani/istatistik
5Özbilgin, A, Çavuş İ, Yıldırım A, Kaya T, Ertabaklar H. Leishmania tropica Üzerinde In vitro ve In vivo İlaç Etkinliğinin Değerlendirilmesi: Pilot Çalışma. Türkiye Parazitoloji Dergisi 2018;42:11-19.
6Uzun S, Gürel MS, Harman M. Kutanöz Layşmanyazis Tanı ve Tedavi Rehberi. Türk Dermatoloji Derneği, Haziran 2017. Galenos Yayınevi, İstanbul, Türkiye. Available from: URL: http://cms.galenos.com.tr/SolvePark/Uploads/files/573ed560a9ec42ed8c04c39ec743e34e.pdf
7Yeşilova Y, Turan E, Sürücü H A, Aksoy M, Özbilgin A. (2014). Sistemik lipozomal amfoterisin B tedavisine cevap veren kutanöz leishmaniasis olgusu. Turkiye Parazitol Derg 2015;39:63-65.
8Ateş F, Or E, Körpınar M A, Gönül R, Bahçeci T. Leishmaniasisin tedavisinde antimon bileşiklerinin kullanımı. Yüzüncü Yıl Üniversitesi Veteriner Fakültesi Dergisi 2011;22:53-57.
9Mussi SV, Fernandes AP, Ferreira LA. Comparative study of the efficacy of formulations containing fluconazole or paromomycin for topical treatment of infections by Leishmania (Leishmania) major and Leishmania (Leishmania) amazonensis. Parasitol Res 2007;100:1221-6.
10Scott JA, Davidson RN, Moody AH, Grant HR, Felmingham D, Scott GM, et al. Aminosidine (paromomycin) in the treatment of leishmaniasis imported into the United Kingdom. Transactions of the Royal Society of Tropical Medicine and Hygiene 1992;86:617-9.
11El Tai NO, Osman OF, El Fari M, Presber W, Schönian G. Genetic heterogeneity of ribosomal internal transcribed spacer in clinical samples of Leishmania donovani spotted on filter paper as revealed by single-strand conformation polymorphisms and sequencing. Transactions of the Royal Society of Tropical Medicine and Hygiene 2000;94:575-9.
12Toz SO, Culha G, Zeyrek FY, Ertabaklar H, Alkan MZ, Vardarlı AT, et al. A real-time ITS1-PCR based method in the diagnosis and species identification of Leishmania parasite from human and dog clinical samples in Turkey. PLoS neglected tropical diseases 2013;7:e2205.
13Uzun S, Gürel MS, Durdu M, Akyol M, Fettahlıoğlu Karaman B, Aksoy M, et al. Clinical practice guidelines for the diagnosis and treatment of cutaneous leishmaniasis in Turkey. International journal of dermatology 2018;57:973-982.
14Arevalo I, Ward B, Miller R, Meng TC, Najar E, Alvarez E, et al. Successful treatment of drug-resistant cutaneous leishmaniasis in humans by use of imiquimod, an immunomodulator. Clinical infectious diseases 2001;33:1847-51.
15Berman JD, Goad LJ, Beach DH, Holz GG. Effects of ketakonazole on sterol biosynthesis by Leishmania mexicana mexicana amastigotes in murine macrophage tumor cells. Mol Biochem Parasito 1986;20:85-92.
16Berman J. Current treatment approaches to leishmaniasis. Curr Opin Infect Dis. 2003;16:397-401.
17Berman JD. Human leishmaniasis: Clinical, diagnosis and chemotherapeutic developments in the last 10 years. Clin Infect Dis 1997;24:684-703.
18Scott JA, Davidson RN, Moddy AH, Grant HR, Felmingham D, Scott GM, et al. Aminosidine (paramomycin) in the treatment of leishmaniasis imported into the United Kingdom. Trans R Soc Trop Med Hyg 1992;86:617-9.
19García Bustos MF, Barrio A, Prieto GG, de Raspi EM, Cimino RO, Cardozo RM, et al. In vivo antileishmanial efficacy of miltefosine against Leishmania (Leishmania) amazonensis. J Parasitol 2014;100:840-7.
20Mushtaq S, Dogra D, Dogra N. Clinical Response with intralesional Amphotericin B in the treatment of old world cutaneous leishmaniasis: a preliminary report. Dermatol Ther 2016;29:398-405.
21van der Snoek EM, Couwenberg SM, Stijnis C, Kortbeek LM, Schadd EM. Two cases of cutaneous leishmaniasis in Dutch military personnel treated with oral miltefosine. Journal of the Royal Army Medical Corps 2017;163:68-70.
22Hamzavi SS, Sanaei Dashti A, Kadivar MR, Pouladfar G, Pourabbas B. Successful treatment of disseminated cutaneous leishmaniasis with liposomal amphotericin B and miltefosine in an eight-year-old girl. The Pediatric infectious disease journal 2018;37:275-277.
23Harman M. Kutanöz Leishmaniasis. Turkish Journal of Dermatology/Turk Dermatoloji Dergisi 2015;9:168-76.
24 El-On J, Livshin R, Even-Paz Z, Hamburger D, Weinrauch L. Topical treatment of cutaneous leishmaniasis. J Invest Dermatol 1986;87:284-8.
25Chacko A, Joseph M, Feltis T, Morris S K. Successful Treatment of Cutaneous Leishmaniasis with Topical Paramomycin in a Child After Treatment Failure with Systemic Fluconazole. The American journal of tropical medicine and hygiene 2016;95:793-794.
26Hadighi R, Boucher P, Khamesipour A, Meamar AR, Roy G, Ouellette M, et al. Glucantime-resistant Leishmania tropica isolated from Iranian patients with cutaneous leishmaniasis are sensitive to alternative antileishmania drugs. Parasitol Res 2007;101:1319-22.