LECTURE 6 Visions of the Future of Mucocutaneous Leishmaniasis Jackson M. L. Costa Gon alo Moniz Research Center - F

3. Objectives To understand Mucocutaneous Leishmaniasis in Brazil To learn about the importance of different clinical forms of the disease To discuss different factors that contribute to the persistence of the disease in Brazil To consider different options for controlling the disease

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34. Development of mucosal lesions in Brazil The lifetime risk of mucosal lesion is likely under 10% during the first 5-10 years after the primary lesions start (experience in Tr�s Bra�os, Bahia, Brazil); No evidence in the literature in support of a non-zero protective efficacy for any Sb+5 regime.

35. Extension of Mucosal Lesions Nose Nasopharynx Palate Epiglottis Larynx Vocal cords Trachea Conjuntiva

59. Strains of Leishmania reduced by deletion of specific genes. Expression of specific peptides for reduced agents, like the BCG. Vaccines of DNA. Powers of dendritics cells; Imunomodulation of the host against sandfly bites

61. What do we want ? A vaccine for human and / or animal; Act against MCL and / or Visceral Leishmaniasis; For protection against MCL, the vaccination of populations or segments with exhibition is a sensible alternative; In VL, considering that a dog is an important reservoir and s responsible for the maintenance of the cycle, its vaccination is relevant.

65. Pentavalents Antimonials (Sb+5) (Favorable results in the treatment of the MCL in Brazil) Pentamidines (Several side effects observed - Few trials realized); Sulphate of Aminosidine (Few trials realized); Amphotericin B � Phase II in Brazil (Desoxicolate: Results in Montes Claros for VL: 78/80 (97.5 %) with 14 doses of 1mg/kg/dia); Lipidics Formulations (Good results with colloidal dispersion 20/20 (100%); Anphotericin B + Sb+5 in Montes Claros for VL (Good results); Miltefosine (Trials in progress for MCL and VL)

66. 1 - The Sb+5 presents good results and must be maintained like 1st line drugs; 2 - Must be challenged by studies of Phase III with Anphotericin B Desoxicolate and / or Lipidic Formulations; 3 - Aminosidine sulphate and Miltefosine must be valued at Phase II (Miltefosine is already).  Leishmaniasis Therapies

67. Trials (Phase II) for Pentamidines, Aminosidine and Miltefosine. Trials (Phase III) for Anphotericin B (desoxicolate and lipidics formulations) x Sb+5. Trials for co-infection of Leishmaniasis & HIV. Studies on factors for prognosis: identification of targets for prevention or early intervention.

70. In spite of: Increase in the global amount of research for health � from US$ 30 bi in 1986 to US$ 106 bi in 2004 (Monitoring Financial Flows for Health Research, Global Forum for Health Research, 2004) Increased levels of protection of intellectual property did not result in an increase of R&D of necessary medicines for global health (UK Commission on Intellectual Property Rights, 2002)