Cure of post Kala-azar dermal leishmaniasis with paromomycin/sodium stibogluconate combination: a proof of concept
Keywords:
Short course, Paromomycin/sodium stibogluconate combination, PKDLAbstract
Background: Post kala-azar dermal leishmaniasis (PKDL) is a recognized dermatologic complication of successfully treated visceral leishmaniasis (VL). PKDL lesions are suspected to be important reservoirs for VL transmission in Sudan. Prolonged treatment schedules, feeling of general well-being and the social stigmata of PKDL prevent most patients seeking treatment. The mainstay of treatment is cardiotoxic sodium stibogluconate (SSG) for 60-120 days. Recently, liposomal amphotericin B (Ambisome®) and immunochemotherapy gave promising results. Ambisome® is expensive and difficult to prepare under field conditions. Paromomycin/SSG combination has been shown to be safe, efficacious and can save time in VL treatment. This study aims to prove that Paromomycin/SSG combination can cure and reduce PKDL treatment duration.
Methods:We are reporting nine cases of patients with PKDL lesions of ≥6 months duration who were diagnosed by clinical signs, histopathological/immunohistochemical and PCR.
Results: Patients’ mean age was 11.7 ± 4.3 years. A third of the patients (3/9; 33.3%) who failed previous SSG treatment of 2-3 months duration responded completely to 40 days of paromomycin/SSG combination. The majority of patients (5/9; 55.6%) responded completely to 30 days of the combination. One patient (1/9; 11.1%) relapsed following 30 days paromomycin/SSG combination.
Conclusion:It was concluded that paromomycin/SSG combination for 30 days is time-saving, safe and efficacious for PKDL treatment.
References
Zijlstra EE, Khalil EA, Kager PA, El-Hassan AM. Post-Kala-azar dermal leishmaniasis in the Sudan: clinical presentation and differential diagnosis. Br J Dermatol. 2000;143:136-43.
Zijlstra EE, el-Hassan AM. Leishmaniasis in Sudan. Post Kala-azar dermal leishmaniasis. Trans R Soc Trop Med Hyg. 2001;95(Suppl 1):S59-76.
Musa AM, Khalil EA, Raheem MA, Zijlstra EE, Ibrahim ME, Elhassan IM, et al. The natural history of Sudanese post-Kala-azar dermal leishmaniasis: clinical, immunological and prognostic features. Ann Trop Med Parasitol. 2002;96:765-72.
Singh RP, Picado A, Alam S, Hasker E, Singh SP, Ostyn B, et al. Post-Kala-azar dermal leishmaniasis (PKDL) in visceral leishmaniasis-endemic communities in Bihar, India. Trop Med Int Health. 2012;17(11):1345-8.
el Hassan AM, Hashim FA, Abdullah M, Zijlstra EE, Ghalib HW. Distinguishing post-Kala-azar dermal leishmaniasis from leprosy: experience in the Sudan. Lepr Rev. 1993;64:53-9.
Zijlstra EE, Ali MS, el-Hassan AM, el-Toum IA, Satti M, Ghalib HW, et al. Kala-azar in displaced people from southern Sudan: epidemiological, clinical and therapeutic findings. Trans R Soc Trop Med Hyg. 1991;85:365-9.
El Hassan AM, Khalil, EA. Post-Kala-azar dermal leishmaniasis: does it play a role in the transmission of Leishmania donovani in the Sudan? Trop Med Int Health. 2001;6:743-4.
Khalil EA, Zijlstra EE, Kager PA, El Hassan AM. Epidemiology and clinical manifestations of Leishmania donovani infection in two villages in an endemic area in eastern Sudan. Trop Med Int Health. 2002;7:35-44.
el Hassan AM, Ghalib HW, Zijlstra EE, Eltoum IA, Satti M, Ali MS, et al. Post Kala-azar dermal leishmaniasis in the Sudan: clinical features, pathology and treatment. Trans R Soc Trop Med Hyg. 1992;86:245-8.
Gasim S, Elhassan AM, Khalil EA, Ismail A, Kadaru AM, Kharazmi A, et al. High levels of plasma IL-10 and expression of IL-10 by keratinocytes during visceral leishmaniasis predict subsequent development of post-Kala-azar dermal leishmaniasis. Clin Exp Immunol. 1998;111:64-9.
Ghalib HW, Piuvezam MR, Skeiky YA, Siddig M, Hashim FA, el-Hassan AM, et al. Interleukin 10 production correlates with pathology in human Leishmania donovani infections. J Clin Invest. 1993;92:324-9.
Ismail A, El Hassan AM, Kemp K, Gasim S, Kadaru AE, Moller T, et al. Immunopathology of post Kala-azar dermal leishmaniasis (PKDL): T-cell phenotypes and cytokine profile. J Pathol. 1999;189:615-22.
Gasim S, Elhassan AM, Kharazmi A, Khalil EA, Ismail A, Theander TG. The development of post-Kala-azar dermal leishmaniasis (PKDL) is associated with acquisition of Leishmania reactivity by peripheral blood mononuclear cells (PBMC). Clin Exp Immunol. 2000;119:523-9.
Zijlstra EE, Musa AM, Khalil EA, el-Hassan IM, el-Hassan AM. Post-Kala-azar dermal leishmaniasis. Lancet Infect Dis. 2003;3:87-98.
Ismail A, Khalil EA, Musa AM, El Hassan IM, Ibrahim ME, Theander TG, et al. The pathogenesis of post Kala-azar dermal leishmaniasis from the field to the molecule: does ultraviolet light (UVB) radiation play a role? Med Hypotheses. 2006;66:993-9.
Thakur CP, Kumar K. Efficacy of prolonged therapy with stibogluconate in post Kala-azar dermal leishmaniasis. Indian J Med Res. 1990;91:144-8.
Hashim FA, Khalil EA, Ismail A, el Hassan AM Apparently successful treatment of two cases of post Kala-azar dermal leishmaniasis with liposomal amphotericin B. Trans R Soc Trop Med Hyg. 1995;89:440.
Khalil E, Hashim FA, Ghalib HW, Zijlstra EE, El Hag IA, Satti MH, et al. Comparative study of liposomal amphotericin B (AmBisome) and sodium stibogluconate in the treatment of Kala-azar in the Sudan. East Afr Med J. 1998;75:37-45.
Roustan G, Jimenez JA, Gutierrez-Solar B, Gallego JL, Alvar J, Patron M. Post-Kala-azar dermal leishmaniasis with mucosal involvement in a kidney transplant recipient: treatment with liposomal amphotericin B. Br J Dermatol. 1998;138:526-8.
Musa AM, Khalil EA, Mahgoub FA, Hamad S, Elkadaru AM, El Hassan AM. Efficacy of liposomal amphotericin B (AmBisome) in the treatment of persistent post-Kala-azar dermal leishmaniasis (PKDL). Ann Trop Med Parasitol. 2005;99:563-9.
Thakur CP, Kumar K, Sinha PK, Mishra BN, Pandey AK. Treatment of post-Kala-azar dermal leishmaniasis with sodium stibogluconate. Br Med J (Clin Res Ed). 1987;295:886-7.
Thakur CP, Narain S, Kumar N, Hassan SM, Jha DK, Kumar A. Amphotericin B is superior to sodium antimony gluconate in the treatment of Indian post-Kala-azar dermal leishmaniasis. Ann Trop Med Parasitol. 1997;91:611-6.
Musa AM, Khalil EA, Mahgoub FA, Elgawi SH, Modabber F, Elkadaru AE, et al. Immunochemotherapy of persistent post-Kala-azar dermal leishmaniasis: a novel approach to treatment. Trans R Soc Trop Med Hyg. 2008;102:58-63.
Khalil EA, Nur NM, Zijlstra EE, El-Hassan AM, Davidson RN. Failure of a combination of two antifungal drugs, terbinafine plus itraconazole, in Sudanese post Kala-azar dermal leishmaniasis. Trans R Soc Trop Med Hyg. 1996;90:187-8.
Modak DBA, Bhattacharya R, Pramanik N, Barbhuia JN, Guha SK. Miltefosine in Post-Kala azar dermal leishmaniasis (PKDL). J Indian Acad Clin Med. 2010;11:199-203.
Musa AM, Younis B, Fadlalla A, Royce C, Balasegaram M, Wasunna M, et al. Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study. PLoS Negl Trop Dis. 2010;4:e855.
Musa A, Khalil E, Hailu A, Olobo J, Balasegaram M, Omollo R, et al. Sodium stibogluconate (SSG) & paromomycin combination compared to SSG for visceral leishmaniasis in East Africa: a randomised controlled trial. PLoS Negl Trop Dis. 2012;6:e1674.
Das VN, Siddiqui NA, Verma RB, Topno RK, Singh D, Das S, et al. Asymptomatic infection of visceral leishmaniasis in hyperendemic areas of Vaishali district, Bihar, India: a challenge to Kala-azar elimination programmes. Trans R Soc Trop Med Hyg. 2011;105:661-6.
Mondal D, Khan MG. Recent advances in post-Kala-azar dermal leishmaniasis. Curr Opin Infect Dis. 2011;24:418-22.
