title: Immunochemotherapy of persistent post-kala-azar dermal leishmaniasis: a novel approach to treatment.
abstract: Post-kala-azar dermal leishmaniasis (PKDL) is a recognized dermatosis that follows successful treatment of visceral leishmaniasis in the Sudan. This randomized and double-blind study aimed to assess safety, immunogenicity and curative potentials of a novel immunochemotherapy regimen in patients with persistent PKDL. Following informed consent, 30 patients were randomized to receive alum-precipitated autoclaved Leishmania major (Alum/ALM) vaccine+Bacille Calmette-Guérin (BCG) and sodium stibogluconate (SSG) or vaccine diluent and SSG. The SSG+Alum/ALM+BCG proved safe with minimal local adverse events. In the SSG+vaccine group, 87% of the patients were cured by day 60 compared with 53% in the SSG alone group (SSG+vaccine efficacy=71%, 95% CI for risk ratio 0.7-1.16). On day 90 of follow-up there were two relapses in the SSG alone arm and none in the SSG+vaccine arm. Pre-treatment cytokines showed high IFN-gamma or high IFN-gamma/IL-10 levels and leishmanin skin test (LST) non-reactivity, while healing/clinical improvement were associated with LST reactivity and low IFN-gamma levels in both study groups (P=0.004). In conclusion, SSG+Alum/ALM+BCG is safe and immunogenic with significant healing potentials in persistent PKDL lesions. Immunochemotherapy probably augmented IFN-gamma production, which induced healing. Leishmanin skin reactivity is a good surrogate marker of cure in persistent PKDL lesions.
authors.affiliation: Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
authors.forename: Ahmed Mudawi
authors.initials: AM
authors.lastname: Musa
authors.forename: Eltahir Awad Gasim
authors.initials: EA
authors.lastname: Khalil
authors.forename: Fawzi Abd Elrahim
authors.initials: FA
authors.lastname: Mahgoub
authors.forename: Sara Hamad Hassab
authors.initials: SH
authors.lastname: Elgawi
authors.forename: Farroukh
authors.initials: F
authors.lastname: Modabber
authors.forename: Abd Elgadir Mohamed Yousif
authors.initials: AE
authors.lastname: Elkadaru
authors.forename: Mona Hussein
authors.initials: MH
authors.lastname: Aboud
authors.forename: Sassan
authors.initials: S
authors.lastname: Noazin
authors.forename: Hashim Warsama
authors.initials: HW
authors.lastname: Ghalib
authors.forename: Ahmed Mohamed
authors.initials: AM
authors.lastname: El-Hassan
mesh_terms: D000293:Adolescent; D000328:Adult; D000967:Antimony Sodium Gluconate / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000276:immunology*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D054332:Leishmaniasis Vaccines / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D013223:Statistics as Topic; D013397:Sudan; D016896:Treatment Outcome; D017778:Vaccines, Combined
chemical_list: D000981:Antiprotozoal Agents; D001500:BCG Vaccine; D054332:Leishmaniasis Vaccines; D017778:Vaccines, Combined; C416262:autoclaved Leishmania major vaccine; D016753:Interleukin-10; D007371:Interferon-gamma; D000967:Antimony Sodium Gluconate