title: Consultation meeting on the development of therapeutic vaccines for post kala azar dermal leishmaniasis.
abstract: BACKGROUND
  Post kala azar dermal leishmaniasis (PKDL) is a disease that appears after treatment of visceral leishmaniasis (VL). The highest incidence of PKDL in the world is in Sudan. Many patients heal spontaneously within 6 months but those who don't are difficult to treat, often requiring months of daily injections. These patients harbour parasite in their skin and are believed to be a source of infection and possibly epidemics. Present treatment modalities of PKDL are inadequate and impractical due to cost, duration of treatment required and side effects. New approach for treatment of PKDL is required. A joint meeting of the UNICEF/UNDP/World Bank/WHO Special Programme for research and training in Tropical Disease (TDR) and the Infectious Disease Research Institute (IDRI) Seattle, USA was held to review the progress of therapeutic vaccines and plan the development of treatment modalities for PKDL.
  
  
  METHODS
  The history of leishmaniasis vaccine development for prophylaxis and therapy was reviewed. Other than previous infection - simulated by inoculation of live Leishmania as a vaccine (leishmanization), none of the preparations of killed parasite with or without adjuvants have shown significant prophylactic efficacy. Killed L. major absorbed with alum and mixed with BCG remains to be tested as a prophylactic vaccine.
  
  
  RESULTS
  Killed parasite preparations i.e. L. mexicana mixed with BCG and L. amazonensis (combined with low dose of antimonial), have shown efficacy in immunotherapy and immuno-chemotherapy, respectively. In addition combined full antimonial plus alum-absorbed autoclaved L. major vaccine has been shown to significantly improve therapy of refractory PKDL patients. These are all crude preparations of parasites and are difficult to define and standardize. However, there is now a new, second generation vaccine, Leish-111f + MPL-SE, composed of a recombinant protein comprising three leishmanial antigens and a defined adjuvant in clinical development.
  
  
  CONCLUSIONS
  Immuno-chemotherapy has the potential of becoming a practical and affordable treatment modality for PKDL and other forms of leishmaniasis. The encouraging results with alum-autoclaved L. major + antimonial should be pursued. However, before further trials, availability of the vaccine and its production under Good Manufacturing Product, hence quality control must be assured. Following satisfactory safety profile of Leish-111f+MPL-SE, clinical trials using this vaccine initially with antimonials should be initiated. Similarly immunotherapy of VL should be considered with the view to controlling development of PKDL. Some immunological studies are required prior to initiation of immunotherapy in VL patients.
authors: Centre for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran. modabberf@yahoo.com.
authors: Hashim
authors: H
authors: Ghalib
authors: Farrokh
authors: F
authors: Modabber
references: Mem Inst Oswaldo Cruz. 2004 Feb;99(1):57-62
references: 15057348
references: Clin Infect Dis. 2006 Mar 1;42(5):608-13
references: 16447104
references: Mol Biochem Parasitol. 1997 Nov;89(2):179-93
references: 9364964
references: Ann Trop Med Parasitol. 2002 Dec;96(8):765-72
references: 12625930
references: Trans R Soc Trop Med Hyg. 2003 May-Jun;97(3):365-8
references: 15228261
references: Infect Immun. 2002 Jun;70(6):2828-36
references: 12010969
references: J Clin Invest. 1993 Jul;92(1):324-9
references: 8326000
references: Clin Dermatol. 1996 Sep-Oct;14(5):503-12
references: 8889328
references: Eur J Immunol. 1997 Oct;27(10):2634-42
references: 9368620
references: Clin Exp Immunol. 2005 May;140(2):349-53
references: 15807861
references: Trends Parasitol. 2005 May;21(5):244-9
references: 15837614
references: Lancet. 1998 May 23;351(9115):1540-3
references: 10326536
references: Infect Immun. 2001 Jun;69(6):4103-8
references: 11349082
references: Trans R Soc Trop Med Hyg. 2003 Jul-Aug;97(4):469-72
references: 15259484
references: Lancet. 2000 Nov 4;356(9241):1565-9
references: 11075771
references: Braz J Infect Dis. 2001 Aug;5(4):223-32
references: 11712967
references: Infect Immun. 1998 Jul;66(7):3279-89
references: 9632596
references: Vaccine. 2005 May 25;23(28):3642-8
references: 15882524
references: Clin Microbiol Rev. 2006 Jan;19(1):111-26
references: 16418526
references: Vaccine. 1999 Feb 5;17(5):466-72
references: 10073725
references: Ann Trop Med Parasitol. 2005 Sep;99(6):563-9
references: 16156969
references: J Immunol. 1998 Dec 1;161(11):6171-9
references: 9834103
references: Trop Med Int Health. 2001 Sep;6(9):743-4
references: 11555443
references: J Infect Dis. 2006 Oct 15;194(8):1151-9
references: 16991091
references: Trans R Soc Trop Med Hyg. 2005 Aug;99(8):593-8
references: 15893351
references: Am J Trop Med Hyg. 1994 Dec;51(6):826-36
references: 7810819
references: J Immunol. 1999 Oct 15;163(8):4481-8
references: 10510390
references: Infect Immun. 2002 Aug;70(8):4215-25
references: 12117930
references: Int J Dermatol. 2002 Feb;41(2):73-8
references: 11982640
references: Lancet Infect Dis. 2003 Feb;3(2):87-98
references: 12560194
references: J Exp Med. 1995 Apr 1;181(4):1527-37
references: 7699334
references: J Immunol. 1996 Dec 1;157(11):5034-41
references: 8943412
references: Vaccine. 2001 May 14;19(25-26):3485-92
references: 11348715
references: Trends Microbiol. 2002;10(10 Suppl):S32-7
references: 12377566