title: Safety and immunogenicity of a candidate vaccine for visceral leishmaniasis (Alum-precipitated autoclaved Leishmania major + BCG) in children: an extended phase II study.
abstract: BACKGROUND
  Untreated visceral leishmaniasis (VL) is an inevitably fatal childhood disease. First-generation candidate vaccines for VL [autoclaved Leishmania major (ALM) + BCG] have been found to be safe and immunogenic but not superior to BCG alone. Modulation of ALM by adsorption to Alum significantly increases the immunogenicity. The Alum-adsorbed ALM vaccine was found to be safe and strongly immunogenic in healthy adult volunteers in a non-VL-endemic area. This study aimed at establishing the safety and immunogenicity of Alum-precipitated autoclaved L. major + BCG vaccine in children under field conditions.
  
  
  METHODS
  A total of 544 healthy, leishmanin non-reactive children (<15 y) were randomly allocated to receive either a single intradermal injection of Alum/ALM + BCG or vaccine diluent (placebo). Volunteers were closely followed for 2 years at 6-month intervals for vaccine safety and immunogenicity.
  
  
  RESULTS
  The vaccine was well tolerated with minimal side-effects. Leishmanin skin test conversion (>or=5 mm) was seen in 56%, 50%, 25% and 31% at 6, 12, 18 and 24 months post-vaccination, respectively; conversion in the placebo group was 4%, 12%, 3% and 13% at the same follow-up visits. There was no significant increase in anti-leishmanial antibodies in either study arm at any of the follow-up visits. During the study, four patients in the placebo arm developed parasitologically confirmed VL.
  
  
  CONCLUSIONS
  Alum/ALM + BCG vaccine is safe and immunogenic in children under field conditions. Multiple injections might be needed to obtain results similar to those obtained in healthy volunteers.
authors.affiliation: Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan. eltahirk@iend.org
authors.forename: Eltahir Awad Gasim
authors.initials: EA
authors.lastname: Khalil
authors.forename: Ahmed Mudawi
authors.initials: AM
authors.lastname: Musa
authors.forename: Farroukh
authors.initials: F
authors.lastname: Modabber
authors.forename: Ahmed Mohamed
authors.initials: AM
authors.lastname: El-Hassan
mesh_terms: D000293:Adolescent; D000534:Alum Compounds; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000097:blood; D001500:BCG Vaccine / Q000009:adverse effects / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018320:Leishmania major / Q000276:immunology*; D054332:Leishmaniasis Vaccines; D007898:Leishmaniasis, Visceral / Q000517:prevention & control*; D008297:Male; D016052:Protozoan Vaccines / Q000009:adverse effects / Q000276:immunology*; D012882:Skin Tests; D017778:Vaccines, Combined / Q000009:adverse effects / Q000276:immunology
chemical_list: D000534:Alum Compounds; D000913:Antibodies, Protozoan; D001500:BCG Vaccine; D054332:Leishmaniasis Vaccines; D016052:Protozoan Vaccines; D017778:Vaccines, Combined; C416262:autoclaved Leishmania major vaccine; C041524:aluminum sulfate