Asuman AKAR, Necdet KUYUCU

Visseral Leishmaniasis (Kala Azar) tedavisinde allopurinol ve ketakonazol kullanımı

Amaç: Kala-azar klasik olarak beş değerlikli antimon bileşikleri (Stibogluconate sodyum = pentostam, methylglucamine antimoniate = Glucantim) ile tedavi edilir. Beş değerlikli antimon bileşiklerine dirençli vakalarda pentamidine (Lomidine), lipozomal amfoterisin B, interferon-γ, granülosit-makrofaj koloni stimule edici faktör, aminosidin, miltefosine gibi ilaçların diğer ilaçlarla birlikte veya tek başlarına tedavide başarılı olduğu bildirilmektedir. Alternatif bir tedavi rejimi de daha az toksik olan allopurinol ve ketakonazol gibi ilaçların kullanımıdır. Bu çalışmada allopurinol ve ketakonazolün birlikte kullanımı ile tedavi etkinliği araştırılmıştır. Yöntem: Mersin Üniversitesi Tıp Fakültesinde viseral leishmania tanısı ile izlenen 6 çocuk hastada bir yıl içinde oral ketakonazol ve allopürinol tedavisi değerlendirildi. Vakaların tamamına 1 ay süreyle Allopürinol (20mg/kg/gün/2 dozda) ve ketakonazol (5mg/kg/gün/2 dozda) verildi. Bulgular: Bir aylık tedavi sonrasında dört vakada tam remisyon görülürken iki vakada remisyon sağlanamadı. Remisyon sağlanamayan vakaların biri başka bir merkezde tanı almış olup Glucantim tedavisi verilmişti. Ateş, halsizlik ve solukluk yakınması ile bize başvurduğunda kemik iliğinde leishmania amostigotlarının görülmesi üzerine relaps olarak değerlendirildi. Allopurinol ve ketakonazol tedavisi başlandı. Tedavi ile remisyonda kabul edilen hasta tedavi bitiminden kırkbeş gün sonra tekrar aynı bulgularla bize başvurdu. İkinci relaps olarak değerlendirilerek Amfoterisin B (3mg/kg/gün) tedavisi verildi. Remisyon sağlanamayan diğer vakada tedavi başlangıcından sonraki otuzaltıncı günde reaktivasyon gelişti. Amfoterisin tedavisi verilerek remisyon sağlandı. Sonuç: Kala-azar tedavisinde beş değerli antimon bileşikleri ve Amfoterisin B kullanılabilir. Bununla birlikte oral olarak kullanılan allopürinol ve ketakonazol güvenli ve ucuz bir tedavi yöntemi olarak ülkemizde diğer bir tedavi seçeneği olabileceği kanısındayız.

Anahtar Kelimeler:

Leishmania tedavisi, allopürinol, ketakonasol

Treatment of Viscelar Leishmaniasis the Use of allopurinol and ketoconazole

Aim: Leishmania is traditionally treated with pentavalent antimony compounds (Stibogluconate sodium = pentostam, methylglucamine antimonate = Glucanim). Drugs such as pentamidine (Lomidine), liposomal amphotericin B, interferon-γ, granulocyte-macrophage colony-stimulating factor, aminosidine, miltefosine are known to be successful in treatment with or without other drugs in resistant cases to pentavalent antimony compounds. An alternative treatment regimen is the use of drugs such as allopurinol and ketoconazole, which are less toxic. In this study, the efficacy of allopurinol and ketaconazole in combination therapy was investigated. Method: Oral ketoconazole and allopurinol treatment was evaluated in 6 children with visceral leishmania in Mersin University Faculty of Medicine. All the cases were given Allopurinol (20mg / kg / day / 2 doses) and ketoconazole (5mg / kg / day / 2 doses) for 1 month. Result: After one month of treatment, complete remission was observed in four cases, but no remission was achieved in two cases. One of the cases that could not be remitted was diagnosed in another center and was given Glucantim treatment. When fever, fatigue and pallor complained to us, it was evaluated as a relapse on the appearance of leishmania amostigotes in bone marrow. Allopurinol and ketoconazole therapy started. The patient was admitted to treatment with remission and applied to us with the same findings again forty-five days after the end of the treatment. Amphotericin B (3 mg / kg / day) was given as the second relapse. In the other case reactivation occurred in thirty-sixth day after initiation of treatment. Conclusion: Five valuable antimony compounds and Amphotericin B can be used in the treatment of leishmenia. Nevertheless, allopurinol and ketoconazole, which are used orally, are safe and inexpensive treatment methods and we think that it may be another treatment option in our country.

Keywords:

Leishmania treatment, alloprurinol, ketakonasol,

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1. Wilson ME. Leishmaniasis. Curr Opin Infect Dis 1993; 6: 331-341.2. Wittner M. Leishmaniasis. In: Feigin RD, Cherry JD. Textbook of pediatric infectious disease. Philedelphia: W.B. Saunders Company 1998: 2452-2458.3. Guerin PJ, Olliaro P, Sundar S et al. Visceral leishmaniasis: current status of control, diagnosis and treatment and a proposed research and development agenda. Lancet İnfect Dis 2002; 2: 494-501.4. Aronson NE, Wortmann GW, Johnson SC et al. Safety and efficacy of intravenous sodium stibogluconate in the treatment of leishmaniasis: recent U.S. military experience. 5. Hepburn NC, Nolan J, Herd RM, Neilson JM, Sutherland GR. Cardiac effects of sodium stibogluconate: myocardial, electrophysiological and biochemical studies. Q J Med 1994; 87: 465-472.6. Catania S, Aiassa C, Izathzoglou S, et al. Visceral leishmaniasis treated with liposomal amphotericin B. Pediatr Infect Dis J 1999; 18: 73-74.7. Sundar S, Thakur CP, Ehgel J et al. Oral miltefosine for İndian visceral leishmaniasis. N. Eng J Med 2002; 347: 1739-1746. 8. Herwald BL, Berman JD. Recommandations for treating leishmaniasis with sodium stibogluconate(Pentostam) and rewiev of the pertinent clinical studies. Am J Trop Med Hyg 1992; 46: 296-306.9. Kuyucu N, Kara C, Bakirtaç A, Teziç T. Successful treatment of visceral leishmaniasis with allopürinol plus ketoconazole in an infant who developed pancreatitis caused by meglumine antimoniate. Pediatr Infect Dis J 2001; 20:456-458.10. Lee MB, Gilbert HM. Current approaches to leishmaniasis. Infect Med 1999;16:37-45.11. Berman JD: Human leishmaniasis: clinical, diagnosis and chemothrepuetic developments in the last 10 years. Clin Infect Dis 1997; 24: 684-703.12. Seaman J, Boer C, Wilkinson R, et al. Liposomal amphotericin B (Ambisome) in the treatment of complicated kala-azar under field conditions. Clin Infect Dis 1995; 21:188-193.13. Kager PA, Rees PH, Wellde BT, Hockmeyer WT, Lyerly WH. Allopürinol in the treatment of visceral leishmaniasis. Trans R Soc Trop Med Hyg 1981; 75: 556-559.14. Ragusa R, Di Cataldo A, Sanperi P, Schiliro G. Treatment of visceral leismaniasis with meglumine and allopürinol. Am J Dis Child 1993; 147: 611-612.15. Wali JP, Aggarwal P, Gupta U, Saluja S, Singh S. Ketocanozole in treatment of visceral leismaniasis. Lancet 1990; 336: 810-811.16. Wali JP, Aggarwal P, Gupta U, Saluja S, Singh S. Ketocanozole in the treatment antimony-and pentamidine resistant kala-azar. J Infect Dis 1992; 166: 215-216.17. Sundar S, Kumar K, Singh VP. Ketocanozole in visceral leismaniasis. Lancet 1990; 336: 1582-1583. 18. Halim MA, Alfurayh O, Kalin ME, Dammas S, Al-Eisa A, Damanhouri G. Successful treatment of visceral leishmaniasis with allopürinol plus ketocanozol in renal transplant recipient after the occurence of pancreatitis due to stibogluconate. Clin Infect Dis 1993; 16: 397-399.19. Torrus D, Massa B, Boix V, Portilla J, Perez-Mateo M. Meglumine antimonate-induced pancreatitis. Am J Gastroenterol 1996; 91: 820-821.20. Huesa M, Bover J, Seron D, et al. The renal transplant patient with visceral leishmaniasis who could not tolerate meglumine antimonate: cure with ketocanozole and allopürinol. Nephrol Dial Transplant. 1999;14(12):2941-2943.