[HTML][HTML] Consultation meeting on the development of therapeutic vaccines for post kala azar dermal leishmaniasis

H Ghalib, F Modabber - Kinetoplastid biology and disease, 2007 - Springer
H Ghalib, F Modabber
Kinetoplastid biology and disease, 2007Springer
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 …
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.
Conclusion and recommendations
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.
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