Iranian Journal of Parasitology 2013. 8(3):396-401.

Evaluation of a Possible Synergistic Effect of Meglumine Antimoniate with Paromomycin, Miltefosine or Allopurinol on in Vitro Susceptibility of Leishmania tropica Resistant Isolate.
Tahereh Rezaei Riabi, Iraj Sharifi, Akram Miramin Mohammadi, Ali Khamesipour, Maryam Hakimi Parizi



Background: Pentavalent antimonials are still the first choice treatment for leishmaniasis, but with low efficacy and resistance is emerging. In the present study, the effect of meglumine antimoniate (MA, Glucantime) combined with paromomy-cin, miltefosine or allopurinol on in vitro susceptibility of Leishmania tropica resistant isolate was evaluated.

Method: The drugs were obtained from commercial sources and diluents of each drug in medium were prepared on the day of experiment. J774 A.1 murine macro-phage cell lines were attached to the cultured on slide and incubated at 37 0C with 5% CO2 for 24 h. Then the stationary phase promastigotes were added to the cells and after 4 hrs of incubation different concentrations of MA, paromomycin, miltefosine or allopurinol were added and incubated for an additional of 72 h. Then the slides were dried and fixed with methanol, stained by Giemsa and studied under a light microscope. Drug activity was evaluated by assessing the macrophage infec-tion rate and the number of amastigotes per infected macrophage was done by ex-amining 100 macrophages. The experiment was done in triplicates.

Result : Various concentrations of MA along with paromomycin, miltefosine or allopurinol significantly inhibited (P<0.01) the proliferation of L. tropica amastigote stage in the macrophage cell line as compared with MA alone or positive control.

Conclusion: Combination of Glucantime with paromomycin, miltefosine or allo-purinol showed a synergistic effect on the clinical isolate of L. tropica in vitro. Use of combination therapy is a new hope and a logical basis for therapy of the patients with cutaneous leishmaniasis. Further investigations are needed to evaluate the therapeutic effects of these drugs on the CL patients.


In vitro; Leishmania tropica; Resistance; Treatment

Full Text:



Sayed El• M, Anwar AE. Intralesional sodium stibogluconate alone or its combination with either intramuscular sodium stibogluconate or oral ketoconazole in the treatment of localized cutaneous leishmaniasis: a comparative study. J Europ Acad Dermatol Venereol. 2009; 24(3): 335-340.

Esfandiarpour I and Dabiri SH. Treatment of cutaneous leishmaniasis recidivans with a com-bination of allopurinol and meglumine anti-moniate: a clinical and histological study. Int J Dermatol. 2007; 46(8): 848-852.

Hadighi R, Boucher P, Khamesipour A, Mea-mar AR, Roy G, Ouellette M, Mohebali M. Glucantime-resistant Leishmania tropica isolated from Iranian patients with cutaneous leishmaniasis are sensitive to alternative antileishmania drugs. Parasitol Res. 2007; 101(5):1319-1322.

World Health Organization. Control of the Leishmaniases: Report of a Meeting of the WHO Expert Committee on the Control of Leishmaniases, Geneva, 22-26 March 2010: World Health Organization.

Noazin S, Modabber F, Khamesipour A, Smith PG, Moulton LH, Nasseri K, Sharifi I, Khalil EAG, Bernal IDV, Antunes CMF, Kieny MP, Tann M. First generation leishmaniasis vaccines: A review of field effi-cacy trials. Vaccine. 2008; 26( 52): 6759–6767.

Croft SL, Sundar S, Fairlamb AH. Drug resis-tance in leishmaniasis. Clin Microbiol Rev. 2006; 19(1): 111-126.

7. Hadighi R, Mohebali M, Boucher P, Hajjaran H, Khamesipour A, Ouellette M. Unre-sponsiveness to Glucantime treatment in Ira-nian cutaneous leishmaniasis due to drug-resis-tant Leishmania tropica parasites. PLoS Med. 2006; 3(5): 162.

Pour R, Sharifi I, Kazemi B, Zarean M. Identi-fication of non responsive isolates to Glucan-time in patients with cutaneous leishmaniasis in Bam. J Kerman Uni Med Sci. 2011; 18(2): 123-33.

Postigo JAR. Leishmaniasis in the world health organization eastern mediterranean region. Int J Antimicrob Agents. 2010; 36(1): 6.

Ouellette M, Drummelsmith J, Leprohon P, El Fadili K, Foucher A, Vergnes B, Lagara D. Drug resistance in Leishmania. Leishmania after the genome, 1st ed. Caister Academic Press, Norfolk, United Kingdom. 2008; 159-176.

Shokri A, Sharifi I, Khamesipour A, Nakhaee N, Fasihi Harandi M, Nosratabadi J, Hakimi Parizi M, Barati M. The effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of Leishmania tropica to meglu-mine antimoniate. Parasitol Res. 2012; 110(3):1113-7.

Jones PM, George AM. Multidrug resistance in parasites: ABC transporters, P-glycoproteins and molecular modeling. Int J Parasitol. 2005; 35(5): 555-566.


  • There are currently no refbacks.

Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.