Evaluation of Correlation between the in Vitro Susceptibility of Field Isolates of Leishmania major and Clinical Outcomes of Meglumine Antimoniate Therapy in Fars Province, Iran
,
Abstract
Background: This study was designed to detect whether there is a correlation between in vitro susceptibility of field isolates of Leishmania major and the clinical outcomes of meglumine antimoniate (Glucantime®) therapy, the mainstay of cutaneous leishmaniasis treatment in Iran.
Methods: Forty-three patients infected with L. major were enrolled in this study from October 2009 to March 2010 and categorized as responsive or unresponsive to Glucantime® treatment after receiving the appropriate therapy. Then, intracellular amastigote approach was conducted on these field strains to investigate in vitro drug susceptibility as well.
Results: At clinical level, out of 43 patients, 15 were clinically non-responsive and 28 were responsive to antimony therapy. All those 28 clinically sensitive strains were susceptible to antimony in the in vitro assay, whereas merely 11 isolates from 15 non-healing isolates were resistant in vitro. Finally, a good correlation (78.9%) with high sensitivity, specificity (100/73) between clinical outcomes and the in vitro susceptibility test was achieved.
Conclusion: The intracellular amastigote model could be an appropriate assay for evaluation of the in vivo drug sensitivity of field isolates. However, more comprehensive studies with larger sets of isolates are needed to confirm these preliminary data.
Aït-Oudhia K, Gazanion E, Sereno D, Oury B, Dedet J, Pratlong F, Lachaud L (2012) In vitro susceptibility to anti- monials and amphotericin B of Leish- mania infantum strains isolated from dogs in a region lacking drug selection pressure. Vet Parasitol. 187(3): 386–393.
Akhoundi M, Hajjaran H, Baghaei A, Mo- hebali M (2013) Geographical distri- bution of leishmania species of human cutaneous leishmaniasis in fars Prov- ince, southern iran. Iran J Parasitol. 8 (1): 85–91.
Alvar J, Velez ID, Bern C, Herrero M, Desjeux P, Cano J, Jannin J, den Boer M, Team WLC (2012) Leishmaniasis worldwide and global estimates of its incidence. PloS One. 7(5): e35671.
Campino S, Kwiatkowski D, Dessein A (2006) Mendelian and complex genetics of sus- ceptibility and resistance to parasitic in- fections. Semin Immunol. 18(6): 411–422.
Chakravarty J, Sundar S (2010) Drug re- sistance in leishmaniasis. J Glob Infect Dis. 2(2): 167–176.
Coelho AC, Trinconi CT, Costa CH, Uliana SR (2014) In Vitro and In Vivo Mil- tefosine Susceptibility of a Leishmania amazonensis Isolate from a Patient with Diffuse Cutaneous Leishmaniasis. Plos Neglect Trop D. 8(7): e2999.
Croft SL (2001) Monitoring drug resistance in leishmaniasis. Trop Med Int Health.6(11): 899–905.
Croft SL, Sundar S, Fairlamb AH (2006) Drug resistance in leishmaniasis. Clin Microbiol Rev. 19(1): 111–126.
da Luz RI, Vermeersch M, Dujardin JC, Cos P, Maes L (2009) In vitro sensitivity testing of Leishmania clinical field iso- lates: preconditioning of promastigotes enhances infectivity for macrophage host cells. Antimicrob Agents Ch. 53 (12): 5197–5203.
Faraut-Gambarelli F, Piarroux R, Deniau M, Giusiano B, Marty P, Michel G, Faugère B, Dumon H (1997) In vitro and in vivo resistance of Leishmania infantum to meglumine antimoniate: a study of 37 strains collected from pa- tients with visceral leishmaniasis. Anti- microb Agents Ch. 41(4): 827–830.
Fumarola L, Spinelli R, Brandonisio O (2004) In vitro assays for evaluation of drug activity against Leishmania spp. Res Microbiol. 155(4): 224–230.
Hadighi R, Mohebali M, Boucher P, Haj- jaran H, Khamesipour A, Ouellette M (2006) Unresponsiveness to Glucantime treatment in Iranian cutaneous leishma- niasis due to drug-resistant Leishmania tropica parasites. PLoS Med. 3(5): e162.
Jacobson RL (2011) Leishmaniasis in an era of conflict in the Middle East. Vector- Borne Zoonotic. 11(3): 247–258.
Jeddi F, Piarroux R, Mary C (2011) Anti- mony resistance in Leishmania, focusing on experimental research. J Tropic Med.2011(1): 15–30.
Lira R, Sundar S, Makharia A, Kenney R, Gam A, Saraiva E, Sacks D (1999) Evidence that the high incidence of treatment failures in Indian kala-azar is due to the emergence of antimony-re- sistant strains of Leishmania donovani. J Infect Dis. 180(2): 564–567.
Maia C, Nunes M, Marques M, Henriques S,Rolao N, Campino L (2013) In vitro drug susceptibility of Leishmania infantum isolated from humans and dogs. Exp Parasitol. 135(1): 36–41.
Mohammadzadeh M, Behnaz F, Golshan Z (2013) Efficacy of glucantime for treat- ment of cutaneous leishmaniasis in Cent- ral Iran. J Iinfect Public Health. 6(2):120–124.
Murray HW, Delph-Etienne S (2000) Roles of endogenous gamma interferon and macrophage microbicidal mechanisms in host response to chemotherapy in ex- perimental visceral leishmaniasis. Infect Immun. 68(1): 288–293.
Ouellette M, Drummelsmith J, Papadopoulou B (2004) Leishmaniasis: drugs in the clinic, resistance and new developments. Drug Resist Update. 7(4): 257–266.
Polonio T, Efferth T (2008) Leishmaniasis: drug resistance and natural products (review). Int J Mol Med. 22(3): 277–286. Pourmohammadi B, Motazedian M, Handjani F, Hatam G, Habibi S, Sarkari B (2011) Glucantime efficacy in the treatment of zoonotic cutaneous leishmaniasis. Southeast Asian J Trop Med Public Health. 42(3): 502–508.
Razmjou S, Hejazy H, Motazedian MH, Baghaei M, Emamy M, Kalantary M (2009) A new focus of zoonotic cuta- neous leishmaniasis in Shiraz, Iran. T Roy Soc Trop Med. 103(7): 727–730.
Rijal S, Yardley V, Chappuis F, Decuypere S, Khanal B, Singh R, Boelaert M, De Doncker S, Croft S, Dujardin JC (2007) Antimonial treatment of visceral leish- maniasis: are current in vitro suscepti- bility assays adequate for prognosis of in vivo therapy outcome?. Microbs In- fect. 9(4): 529–535.
Rojas R, Valderrama L, Valderrama M, Va- rona MX, Ouellette M, Saravia NG
(2006) Resistance to antimony and treatment failure in human Leishmania (Viannia) infection. J Infect Dis. 193 (10): 1375–1383.
Sereno D, Cordeiro da Silva A, Mathieu- Daude F, Ouaissi A (2007) Advances and perspectives in Leishmania cell based drug-screening procedures. Para- sitol Int. 56(1): 3–7.
Sundar S, Goyal N (2007) Molecular mecha- nisms of antimony resistance in Leish- mania. J Med Microbio. 56(2): 143–153. Sundar S, Singh A, Singh OP (2014) Stra- tegies to overcome Antileishmanial Drugs unresponsiveness. J Trop Med.2014(1): 7.
Vanaerschot M, Decuypere S, Berg M, Roy S, Dujardin JC (2013) Drug-resistant microorganisms with a higher fitness- can medicines boost pathogens?. Crit Rev Microbiol. 39(4): 384–394.
Vanaerschot M, Maes I, Ouakad M, Adaui V, Maes L, De Doncker S, Rijal S, Chappuis F, Dujardin JC, Decuypere S (2010) Linking in vitro and in vivo survival of clinical Leishmania donovani strains. PLoS One. 5(8): e12211.
Vermeersch M, da Luz RI, Toté K, Tim- mermans JP, Cos P, Maes L (2009) In vitro susceptibilities of Leishmania do- novani promastigote and amastigote stages to antileishmanial reference drugs: practical relevance of stage-specific dif- ferences. Antimicrob Agents Ch. 53(9):3855–3859.
Yardley V, Ortuño N, Llanos-Cuentas A, Chappuis F, De Doncker S, Ramirez L, Croft S, Arevalo J, Adui V, Ber- mudez H (2006) American tegumentary leishmaniasis: is antimonial treatment outcome related to parasite drug sus- ceptibility?. J Ifect Dis. 194(8): 1168–1175.
| Files | ||
| Issue | Vol 11 No 1 (2017) | |
| Section | Original Article | |
| Keywords | ||
| In vitro susceptibility Antimonial resistance Leishmania major Iran | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
