Thermotherapy. An alternative for the treatment of American cutaneous leishmaniasis.

Trials

Iván D Vélez¹  Margarita Vargas²  Martha Robayo²  Liliana López¹ 

[1] Program for the Study and Control of Tropical Disease, University of Antioquia, Carrera 53 #61-30, Medellín, Colombia;Dirección de Sanidad, DISAN, Colombia Army, Bogotá, Colombia

关键词: treatment;    Meglumine antimoniate;    American cutaneous leishmaniasis;    Thermotherapy;   

Others  :  1095590
DOI  :  10.1186/1745-6215-13-58

 received in 2011-09-26, accepted in 2012-05-17,  发布年份 2012

【 摘 要 】

Background

Pentavalent antimonials (Sb⁵) and miltefosine are the first-line drugs for treating cutaneous leishmaniasis in Colombia; however, toxicity and treatment duration negatively impact compliance and cost, justifying an active search for better therapeutic options. We compared the efficacy and safety of thermotherapy and Meglumine antimoniate for the treatment of cutaneous leishmaniasis in Colombia.

Method

An open randomized Phase III clinical trial was performed in five military health centres. located in northwestern, central and southern Colombia. Volunteers with parasitological positive diagnosis (Giemsa-stained smears) of cutaneous leishmaniasis were included. A single thermotherapy session involving the application of 50°C at the center and active edge of each lesion. Meglumine antimoniate was administered intramuscularly at a dose of 20 mg Sb⁵/kg weight/day for 20 days.

Results

Both groups were comparable. The efficacy of thermotherapy was 64% (86/134 patients) by protocol and 58% (86/149) by intention-to-treat. For the Meglumine antimoniate group, efficacy by protocol was 85% (103/121 patients) and 72% (103/143) by intention-to-treat, The efficacy between the treatments was statistically significant (p 0.01 and <0.001) for analysis by intention to treat and by protocol, respectively. There was no difference between the therapeutic response with either treatment regardless of the Leishmania species responsible for infection. The side effects of Meglumine antimoniate included myalgia, arthralgia, headache and fever. Regarding thermotherapy, the only side effect was pain at the lesion area four days after the initiation of treatment.

Conclusion

Although the efficacy rate of Meglumine antimoniate was greater than that of thermotherapy for the treatment of cutaneous leishmaniasis, the side effects were also greater. Those factors, added to the increased costs, the treatment adherence problems and the progressive lack of therapeutic response, make us consider thermotherapy as a first line treatment for cutaneous leishmaniasis. Registered ClinicalTrials.gov NCT00471705

【 授权许可】

   
2012 López et al; BioMed Central Ltd.

【 参考文献 】

• [1]Bailey MS, Lockwood DN, 2: Cutaneous leishmaniasis. Clin Dermatol 2007, 25:203-211. Mar-Apr
• [2]Bejarano EE, Sierra D, Perez-Doria A, Velez ID: First finding of Lutzomyia tihuiliensis (Diptera: Psychodidae) in the Valle de Aburra, Colombia. Biomedica 2006, 26(Suppl 1):228-231.
• [3]WHO (World Health Organization).Control of the leishmaniases. 2010.
• [4]Gonzalez U, Pinart M, Rengifo-Pardo M, Macaya A, Alvar J, Tweed JA: Interventions for American cutaneous and mucocutaneous leishmaniasis. Cochrane Database Syst Rev 2009, 2:CD004834.
• [5]Arevalo I, Tulliano G, Quispe A, Spaeth G, Matlashewski G, Llanos-Cuentas A, et al.: Role of imiquimod and parenteral meglumine antimoniate in the initial treatment of cutaneous leishmaniasis. Clin Infect Dis 2007, 44(12):1549-1554.
• [6]Berman JD: Treatment of New World cutaneous and mucosal leishmaniases. Clin Dermatol 1996, 14(5):519-522. Sep-Oct
• [7]Kedzierski L, Sakthianandeswaren A, Curtis JM, Andrews PC, Junk PC, Kedzierska K: Leishmaniasis: current treatment and prospects for new drugs and vaccines. Curr Med Chem 2009, 16(5):599-614.
• [8]Murray HW, Berman JD, Davies CR, Saravia NG: Advances in leishmaniasis. Lancet 2005, 366(9496):1561-1577. Oct 29-Nov 4
• [9]Ouellette M, Drummelsmith J, Papadopoulou B: Leishmaniasis: drugs in the clinic, resistance and new developments. Drug Resist Updat 2004, 7(4–5):257-266. Aug-Oct
• [10]Palumbo E: Current treatment for cutaneous leishmaniasis: a review. Am J Ther 2009, 16(2):178-182. Mar-Apr
• [11]Sampaio RN, de Paula CD, Sampaio JH, Furtado Rde S, Leal PP, Rosa TT, et al.: The evaluation of the tolerance and nephrotoxicity of pentavalent antimony administered in a dose of 40 mg Sb V/kg/day, 12/12 hr, for 30 days in the mucocutaneous form of leishmaniasis. Rev Soc Bras Med Trop 1997, 30(6):457-463. Nov-Dec
• [12]Seaton RA, Morrison J, Man I, Watson J, Nathwani D: Out-patient parenteral antimicrobial therapy–a viable option for the management of cutaneous leishmaniasis. QJM 1999, 92(11):659-667.
• [13]Soto J, Soto P: Current situation and future of antileishmanial therapy in Colombia. Biomedica 2006, 26(Suppl 1):194-206.
• [14]Hadighi R, Mohebali M, Boucher P, Hajjaran H, Khamesipour A, Ouellette M: Unresponsiveness to Glucantime treatment in Iranian cutaneous leishmaniasis due to drug-resistant Leishmania tropica parasites. PLoS Med 2006, 3(5):e162.
• [15]Hadighi 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(5):1319-1322.
• [16]Osorio LE, Palacios R, Chica ME, Ochoa MT: Treatment of cutaneous leishmaniasis in Colombia with dapsone. Lancet 1998, 351(9101):498-499.
• [17]Momeni AZ, Aminjavaheri M, Omidghaemi MR: Treatment of cutaneous leishmaniasis with ketoconazole cream. J Dermatolog Treat 2003, 14(1):26-29.
• [18]Singh S, Singh R, Sundar S: Failure of ketoconazole treatment in cutaneous leishmaniasis. Int J Dermatol 1995 Feb, 34(2):120-121.
• [19]Hendrickx EP, Agudelo SP, Munoz DL, Puerta JA, Velez Bernal ID: Lack of efficacy of mefloquine in the treatment of New World cutaneous leishmaniasis in Colombia. Am J Trop Med Hyg 1998 Dec, 59(6):889-892.
• [20]Velez I, Agudelo S, Hendrickx E, Puerta J, Grogl M, Modabber F, et al.: Inefficacy of allopurinol as monotherapy for Colombian cutaneous leishmaniasis. A randomized, controlled trial. Ann Intern Med 2010, 126(3):232-236.
• [21]Soto J, Berman J: Treatment of New World cutaneous leishmaniasis with miltefosine. Trans R Soc Trop Med Hyg 2006 Dec, 100(Suppl 1):S34-S40.
• [22]Soto J, Toledo JT: Oral miltefosine to treat new world cutaneous leishmaniasis. Lancet Infect Dis 2007 Jan, 7(1):7.
• [23]Velez I, Lopez L, Sanchez X, Mestra L, Rojas C, Rodriguez E: Efficacy of miltefosine for the treatment of American cutaneous leishmaniasis. Am J Trop Med Hyg 2010, 83(2):351-6.
• [24]Mohebali M, Fotouhi A, Hooshmand B, Zarei Z, Akhoundi B, Rahnema A, et al.: Comparison of miltefosine and meglumine antimoniate for the treatment of zoonotic cutaneous leishmaniasis (ZCL) by a randomized clinical trial in Iran. Acta Trop 2007 Jul, 103(1):33-40.
• [25]Esmaeili J, Mohebali M, Edrissian GH, Rezayat SM, Ghazi-Khansari M, et al.: Evaluation of miltefosine against Leishmania major (MRHO/IR/75/ER): in vitro and in vivo studies. Acta Med Iran 2008, 46(3):191-196.
• [26]Bari AU, Rahman SB: A Therapeutic update on Cutaneous leishmaniasis. J Coll Physicians Surg Pak 2003 Aug, 13(8):471-476.
• [27]Willard RJ, Jeffcoat AM, Benson PM, Walsh DS: Cutaneous leishmaniasis in soldiers from Fort Campbell, Kentucky returning from Operation Iraqi Freedom highlights diagnostic and therapeutic options. J Am Acad Dermatol 2005 Jun, 52(6):977-987.
• [28]Levine N: Cutaneous leishmaniasis treated with controlled localized heating. Arch Dermatol 1992 Jun, 128(6):759-761.
• [29]Navin TR, Arana BA, Arana FE, de Merida AM, Castillo AL, Pozuelos JL: Placebo-controlled clinical trial of meglumine antimonate (glucantime) vs. localized controlled heat in the treatment of cutaneous leishmaniasis in Guatemala. Am J Trop Med Hyg 1990 Jan, 42(1):43-50.
• [30]Velasco-Castrejon O, Walton BC, Rivas-Sanchez B, Garcia MF, Lazaro GJ, Hobart O, et al.: Treatment of cutaneous leishmaniasis with localized current field (radio frequency) in Tabasco, Mexico. Am J Trop Med Hyg 1997 Sep, 57(3):309-312.
• [31]Moreira Rda C, Rebelo JM, Gama ME, Costa JM: Knowledge level about of American tegumentary leishmaniasis (ATL) and use of alternative therapies in an endemic area in the Amazon Region in the State of Maranhao, Brazil. Cad Saude Publica 2002, 18(1):187-195. Jan-Feb
• [32]Velez ID, Hendrickx E, Robledo SM, del Pilar Agudelo S: Gender and cutaneous leishmaniasis in Colombia. Cad Saude Publica 2001, 17(1):171-180. Jan-Feb
• [33]Weigel MM, Armijos RX: The traditional and conventional medical treatment of cutaneous leishmaniasis in rural Ecuador. Rev Panam Salud Publica 2001, 10(6):395-404.
• [34]Adams E: Thermosurgery in dermatology. Boston,. MA: Thecnology Assessment Program, Office of Patient Care Services 2008.
• [35]Ramirez JR, Agudelo S, Muskus C, Alzate JF, Berberich C, Barker D, et al.: Diagnosis of cutaneous leishmaniasis in Colombia: the sampling site within lesions influences the sensitivity of parasitologic diagnosis. J Clin Microbiol 2000, 38(10):3768-3773.
• [36]Robinson RJ, Agudelo S, Muskus C, Alzate JF, Berberich C, Barker DC, et al.: The method used to sample ulcers influences the diagnosis of cutaneous leishmaniasis. Trans R Soc Trop Med Hyg 2002, 96(Suppl 1):S169-S171.
• [37]Montalvo Alvarez AM, Nodarse JF, Goodridge IM, Fidalgo LM, Marin M, Van Der Auwera G, et al.: Differentiation of Leishmania (Viannia) panamensis and Leishmania (V.) guyanensis using BccI for hsp70 PCR-RFLP. Trans R Soc Trop Med Hyg 2010, 104(5):364-7.
• [38]Montalvo AM, Monzote L, Fraga J, Montano I, Muskus C, Marin M, et al.: PCR-RFLP and RAPD for typing neotropical Leishmania. Biomedica 2008, 28(4):597-606.
• [39]Trotti A, Colevas AD, Setser A, Rusch V, Jaques D, Budach V, et al.: CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 2003 Jul, 13(3):176-181.
• [40]Guía de atención de la leishmaniasis. Ministerio de la Proteccion Social, Bogotá; 2007.
• [41]Soto JTJ, Vega J, Berman J: Short report: efficacy of pentavalent antimony for treatment of colombian cutaneous leishmaniasis. Am J Trop Med Hyg 2005, 72(4):421-422. Apr
• [42]Palacios R, Osorio LE, Grajalew LF, Ochoa MT: Treatment failure in children in a randomized clinical trial with 10 and 20 days of meglumine antimonate for cutaneous leishmaniasis due to Leishmania viannia species. Am J Trop Med Hyg 2001, 64(3–4):187-193.
• [43]Vélez IDA, del Pilar Agudelo S, Hendrickx E, Puerta JA, Grogl M, Modabber F, et al.: Inefficacy of allopurinol as monotherapy for colombian cutaneus leishmaniasis. Ann Intern Med 1997, 126:232-236.
• [44]Reithinger RMM, Wahid M, Bismullah M, Quinnell RJ, Davies CR, et al.: Efficacy of thermotherapy to treat cutaneous leishmaniasis caused by Leishmania tropica in Kabul, Afghanistan: a randomized, controlled trial. Clin Infect Dis 2005, 40(8):1148-1155. Apr 15
• [45]Aronson NE, Wortmann GW, Byrne WR, Howard RS, Bernstein WB, Marovich MA, et al.: A randomized controlled trial of local heat therapy versus intravenous sodium stibogluconate for the treatment of cutaneous Leishmania major infection. PLoS Negl Trop Dis 2010, 4(3):628.
• [46]Tuon FF, Amato VS, Graf ME, Siqueira AM, Nicodemo AC, Amato Neto V: Treatment of New World cutaneous leishmaniasis–a systematic review with a meta-analysis. Int J Dermatol 2008 Feb, 47(2):109-124.
• [47]Vega JC, Sanchez BF, Montero LM, Montana R, Mahecha Mdel P, Duenes B, et al.: The efficacy of thermotherapy to treat cutaneous leishmaniasis in Colombia: a comparative observational study in an operational setting. Trans R Soc Trop Med Hyg 2009 Jul, 103(7):703-706.