JCDSA  Vol.6 No.3 , June 2016
Treatment of Acute Cutaneous Leishmaniasis by Oral Zinc Sulfate and Oral Ketocanazole Singly and in Combination
Abstract: Background: Cutaneous Leishmaniasis (CL) is an endemic disease in many countries and caused by different species of Leishmania parasite. It results in a deformed scar after a relatively long period. Many therapies have been tried in treatment of this disease. Objective: To compare the effect of oral zinc sulfate and oral ketoconazole singly and in combination in the treatment of acute cutaneous leishmaniasis. Patients and Methods: This single, blinded, therapeutic, controlled study was conducted in the Department of Dermatology, Baghdad Teaching Hospital, Baghdad, Iraq, during the period, January 2015 to July 2015. Seventy-five patients with acute CL were enrolled in this study. The total numbers of lesions were 327, and the duration of lesions ranged from 4 to 12 (6.9 ± 0.7) weeks. The diagnosis was confirmed by smear and histopathology. Patients were divided into three groups: 24 patients in Group A were treated with oral zinc sulfate capsules 10 mg/kg/day for 6 weeks; 24 patients in Group B were treated with ketoconazole tablets 200 mg twice daily for 6 weeks and 27 patients in Group C were treated orally with a combination of zinc sulfate and ketoconazole for 6 weeks. All patients were seen regularly every 2 weeks for 6 weeks of treatment period, then monthly for the next three months as follow up period. Healing of the lesions was assessed by using Sharquie’s modified Leishmania score to assess the objective response to the topical or systemic therapy. ResultsAfter six weeks, 75 patients have completed the treatment, 24patients received zinc sulfate capsule, 24 patients received oral ketoconazole and 27 patients received a combination of both treatments. The cure rate was (60%) in the group receiving oral zinc sulfate capsuleand (50%) in the one receiving oral ketoconazole tablet (P = 0.146) and (96%) in the combination group (P ? 0.04). Conclusion: The combination therapy using oral zinc sulfate and oral ketoconazole gave a high cure rate. The combination therapy is a new mode of therapy as both drugs act in a synergistic way.
Cite this paper: Sharquie, K. , Noaimi, A. , Al-Salam, W. (2016) Treatment of Acute Cutaneous Leishmaniasis by Oral Zinc Sulfate and Oral Ketocanazole Singly and in Combination. Journal of Cosmetics, Dermatological Sciences and Applications, 6, 105-115. doi: 10.4236/jcdsa.2016.63014.

[1]   Desjeux, P. (2004) Leishmaniasis: Current Situation and New Perspectives. Comparative Immunology Microbiology and Infectious Diseases, 27, 305-318.

[2]   Dowlati, Y. (1996) Treatment of Cutaneous Leishmaniasis (Old World). Clinics in Dermatology, 14, 513-517.

[3]   Khatami, A., Firooz, A., Gorouhi, F. and Dowlati, Y. (2007) Treatment of Acute Old World Cutaneous Leishmaniasis: A Systematic Review of the Randomized Controlled Trials. Journal of the American Academy of Dermatology, 57, 335.e1-335.e29.

[4]   Lawn, S.D., Yardley, V., Vega-Lopez, F., Watson, J. and Lockwood, D.N. (2003) New World Cutaneous Leishmaniasis in Returned Travelers: Treatment Failures Using Intravenous Sodium Stibogluconate. Transactions of the Royal Society of Tropical Medicine and Hygiene, 97, 443-445.

[5]   Sharquie, K.E., Najim, R.A. and Farjou, I.B. (1998) Zinc Sulphate in the Treatment of Cutaneous Leishmaniasis: An in Vitro and Animal Study. Memórias do Instituto Oswaldo Cruz, 93, 831-837.

[6]   Sharquie, K.E., Najim, R.A., Farjou, I.B. and Al-Timimi, D.J. (2001) Oral Zinc Sulphate in the Treatment of Acute Cutaneous Leishmaniasis. Clinical and Experimental Dermatology, 26, 21-26.

[7]   Sharquie, K.E. and Najim, R.A. (2004) Disseminated Cutaneous Leishmaniasis. Saudi Medical Journal, 25, 951-954.

[8]   Firooz, A., Khatami, A., Khamesipour, A., Nassiri-Kashani, M., Behnia, F., Nilforoushzadeh, M., et al. (2005) Intralesional Injection of 2% Zinc Sulfate Solution in the Treatment of Acute Old World Cutaneous Leishmaniasis: A Randomized, Double-Blind, Controlled Clinical Trial. Journal of Drugs in Dermatology, 4, 73-79.

[9]   Hell, R.C., Brogden, R.N., Carmen, A., Morley, P.A., Speight, T.M. and Avery, G.S. (1982) Ketocanazole: A Review of Its Therapeutic Efficacy in Superficial and Systemic Fungal Infections. Drug, 23, 1-23.

[10]   Cupp-Vickery, J.R, Garciaa, C., Hofacrea, A. and McGee-Estrada, K. (2001) Ketoconazole-Induced Conformational Changes in the Active Site of Cytochrome P450eryF1. Journal of Molecular Biology, 311, 101-110.

[11]   Sharquie, K.E. and Al-Talib, K. (1988) Intralesional Therapy of Cutaneous Leishmaniasis with Sodium Stibogluconate Antimony. British Journal of Dermatology, 119, 53-57.

[12]   Sharquie, K.E., Hussian, A.K. and Turki, K.M. (1994) Intralesional Therapy of Cutaneous Leishmaniasis with Hypertonic Sodium Chloride Solution. Pan-Arab Ass dermatologists, 5, 85-91.

[13]   Sharquie, K.E. and Al-Azzawi, K.E. (1996) Intralesional Therapy of Cutaneous Leishmaniasis with 2% Zinc Sulfate Solution. J Pan Arab League Dermatologist, 7, 41-46.

[14]   Al-Sudany, N.K. and Ali, Y.J. (2015) Intralesional 8.33% Rifamycin Infiltration; New Treatment for Cutaneous Leishmaniasis. Journal of Dermatology & Dermatologic Surgery, 20, 39-45.

[15]   Bryceson, A.D.M. (1987) Therapy in Man. In: Peters, W. and Killick-Kendrick, R., Eds., The Leishmaniasis in Biology and Medicine.

[16]   Sharquie, K.E., Noaimi, A.A. and Al-Ghazzi, G. (2015) Treatment of Cutaneous Leishmaniasis by Topical 25% Podophyllin Solution. Journal of Dermatology & Dermatologic Surgery, 15, 108-113.

[17]   Zarcarian, S.A. (1985) Complication, Indication and Contraindication in Cryosurgery. In: Zarcarian, S.A., Ed., Cryosurgery for Skin Cancer and Cutaneous Disorders, Mosby, St. Louis, 283-298.

[18]   Vegas-lopez and Hay, R.T. (2004) Parasitic Worm and Protozoa. In: Burn, B. and Coxn, G.C., Eds., Rook’s Textbook of Dermatology, Vol. 32, 7th Edition, Black Well Publishing, Oxford, 1-48.

[19]   World Health Organization (1984) The Leishmaniasis: Report of a WHO Express Committee. WHO Technical Report Series No. 701, World Health Organization, Geneva.

[20]   World Health Organization (1992) Allopurinol. In: A New Perspective in the Treatment of Cutaneous Leishmaniasis. WHO Drug Information, 6, 45-46.

[21]   James, W.D., Berger, T.G. and Elson, D.M., Eds. (2006) Parasitic Infestation, Sting, and Bites. Andrews’ Diseases of the Skin: Clinical Dermatology, Vol. 20, 10th Edition, WB Saunders Company, Toronto, 421-457.

[22]   Joshi, R.K. and Nambair, P.M.K. (1989) Dermal Leishmaniasis and Rifampicin. International Journal of Dermatology, 28, 612-614.

[23]   Berman, J.D., Goad, L.J., Beach, D.H. and Holz, J.J. (1986) Effect of Ketoconazole on the Sterol Biosynthesis by Leishmania mexicana mexicana amastigotes in Murine Macrophage Tumor Cells. Molecular and Biochemical Parasitology, 20, 85-92.

[24]   Turki, K.M. and Abboud, M.M. (1983) Effect Inhibitors of Folic Acid Biosynthesis on Promastigotes L. donovani. Iraqi Journal of Science, 24, 131-134.

[25]   Buller, P.G. (1978) Levamisole Therapy of Chronic L. tropica. The American Journal of Tropical Medicine and Hygiene, 81, 221-224.

[26]   Dogra, J. (1991) A Double Blind Study on the Efficacy of Oral Dapson in Cutaneous Leishmaniasis. Transactions of the Royal Society of Tropical Medicine and Hygiene, 85, 212-213.

[27]   Bryceson, A. (1979) Review of Tropical Dermatology. Cutaneous Leishmaniasis. British Journal of Dermatology, 94, 223-226.

[28]   Sarhan, G.M. (1985) Epidemiological and Clinical Studies on Cutaneous Leishmaniasis. Postgraduate Thesis, College of Medicine, University of Baghdad, Baghdad.

[29]   Sharquie, K.E., Khorsheed, A.A. and Al-Nuaimy, A.A. (2007) Topical Zinc Sulphate Solution for Treatment of Viral Warts. Saudi Medical Journal, 28, 1418-1421.

[30]   Mathur, K., Bumb, R.A., Mangal, H.N. and Sharma, M.L. (1984) Oral Zinc as an Adjunct to Dapsone in Lepromatous Leprosy. International Journal of Leprosy and Other Mycobacterial Diseases, 52, 331-338.

[31]   Cunliffe, W.J. (1979) Unacceptable Side-Effects of Oral Zinc Sulphate in the Treatment of Acne Vulgaris. British Journal of Dermatology, 101, 363.

[32]   Ikeda, M., Arata, J. and Isaka, I. (1982) Erosive Pustular Dermatosis of the Scalp Successfully Treated with Oral Zinc Sulphate. British Journal of Dermatology, 106, 742-743.

[33]   Piérard-Franchimont, C., Goffin, V., Decroix, J. and Piérard, G.E. (2002) A Multicenter Randomized Trial of Ketoconazole 2% and Zinc Pyrithione 1% Shampoos in Severe Dandruff and Seborrheic Dermatitis. Skin Pharmacology and Applied Skin Physiology, 15, 434-441.

[34]   Prasad, A.S. (2009) Zinc: Role in Immunity, Oxidative Stress and Chronic Inflammation. Current Opinion in Clinical Nutrition & Metabolic Care, 12, 646-652.

[35]   Puentes, F., Guzmán, F., Marín, V., Alonso, C., Patarroyo, M.E. and Moreno, A. (1999) Leishmania: Fine Mapping of the Leishmanolysin Molecule’s Conserved Core Domains Involved in Binding and Internalization. Experimental Parasitology, 93, 7-22.

[36]   Bernstein, B.E., Hoffman, R.C. and Klevit, R.E. (1994) Sequence-Specific DNA Recognition by Cys2, His2 Zinc Fingers. Annals of the New York Academy of Sciences, 726, 92-104.

[37]   Rhodes, D. and Klug, A. (1993) Zinc Fingers. Scientific American, 268, 56-65.

[38]   Eil, C. (1992) Ketoconazole Binds to the Human Androgen Receptor. Hormone and Metabolic Research, 24, 367-370.

[39]   Bossche, H.V., Lauwers, W., Willemsens, G., Marichal, P., Cornelissen, F. and Cools, W. (1984) Molecular Basis for the Antimycotic and Antibacterial Activity of N-Substituted Imidazoles and Triazoles: The Inhibition of Isoprenoid Biosynthesis. Pesticide Science, 15, 188-198.

[40]   Cutsem, J.V., Gerven, F.V., Cauwenbergh, G., Odds, F., Paul, A.J. and Janssen, P.A. (1991) The Anti-Inflammatory Effects of Ketoconazole: A Comparative Study with Hydrocortisone Acetate in a Model Using Living and Killed Staphylococcus aureus on the Skin of Guinea Pigs. Journal of the American Academy of Dermatology, 25, 257-261.

[41]   Alsaleh, Q.A., Dvorak, R. and Nanda, A. (1995) Ketoconazole in the Treatment of Cutaneous Leishmaniasis in Kuwait. International Journal of Dermatology, 34, 495-497.

[42]   Berman, J.D., Waddell, D. and Hanson, B.D. (1985) Biochemical Mechanisms of the Antileishmanial Activity of Sodium Stibogluconate. Antimicrobial Agents and Chemotherapy, 27, 916-920.

[43]   Berman, J.D. (1988) Inhibition of Leishmanial Protein Kinase by Anti-Leishmanial Drugs. The American Journal of Tropical Medicine and Hygiene, 38, 298-303.

[44]   Neal, R.A. (1987) Experimental Chemotherapy. In: Peters, W. and Killick-kendrik, R., Eds., The Leishmaniasis in Biology and Medicine, Academic Press, London.

[45]   Bryceson, A.D., Chulay, J.D., Mugambi, M., Were, J.B., Gachihi, G., Chunge, C.N., Muigai, R., Bhatt, S.M., Ho, M., Spencer, H.C., et al. (1985) Visceral Leishmaniasis Unresponsive to Antimonial Drugs. II. Response to High Dosage Sodium Stibogluconate or Prolonged Treatment with Pentamidine. Transactions of the Royal Society of Tropical Medicine and Hygiene, 79, 705-714.

[46]   Wang, Y.H., Li, K.J., Mao, L., Hu, X., Zhao, W.J., Hu, A., Lian, H.Z. and Zheng, W.J. (2013) Effects of Exogenous Zinc on Cell Cycle, Apoptosis and Viability of MDAMB231, HepG2 and 293 T Cells. Biological Trace Element Research, 154, 418-426.

[47]   Sharquie, K.E., Noaimi, A.A. and Shararah, Z.A. (2015) Topical Therapy of Acute Cutaneous Leishmaniasis Using Zinc Sulphate (25%) Solution versus Podophyllin Solution (25%). A Thesis Submitted to the Scientific Council of the Iraqi Board for Medical Specializations in Dermatology and Venereology.