Immunochemotherapy of persistent post-kala-azar dermal leishmaniasis: a novel approach to treatment.
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.
Musa
Ahmed Mudawi
AM
Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Khalil
Eltahir Awad Gasim
EA
Mahgoub
Fawzi Abd Elrahim
FA
Elgawi
Sara Hamad Hassab
SH
Modabber
Farroukh
F
Elkadaru
Abd Elgadir Mohamed Yousif
AE
Aboud
Mona Hussein
MH
Noazin
Sassan
S
Ghalib
Hashim Warsama
HW
El-Hassan
Ahmed Mohamed
AM
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
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