The potential economic value of a cutaneous leishmaniasis vaccine in seven endemic countries in the Americas. Vaccine

Department of Biomedical Informatics, School of Medicine, University of Pittsburgh, 3520 Forbes Avenue, First Floor, Pittsburgh, PA 15213, USA
Vaccine (Impact Factor: 3.62). 11/2012; 31(3). DOI: 10.1016/j.vaccine.2012.11.032
Source: PubMed


Cutaneous leishmaniasis (CL) and its associated complications, including mucocutaneous leishmaniasis (MCL) and diffuse CL (DCL) have emerged as important neglected tropical diseases in Latin America, especially in areas associated with human migration, conflict, and recent deforestation. Because of the limitations of current chemotherapeutic approaches to CL, MCL, and DCL, several prototype vaccines are in different states of product and clinical development. We constructed and utilized a Markov decision analytic computer model to evaluate the potential economic value of a preventative CL vaccine in seven countries in Latin America: Bolivia, Brazil, Colombia, Ecuador, Mexico, Peru, and Venezuela. The results indicated that even a vaccine with a relative short duration of protection and modest efficacy could be recommended for use in targeted locations, as it could prevent a substantial number of cases at low-cost and potentially even result in cost savings. If the population in the seven countries were vaccinated using a vaccine that provides at least 10 years of protection, an estimated 41,000-144,784 CL cases could be averted, each at a cost less than the cost of current recommended treatments. Further, even a vaccine providing as little as five years duration of protection with as little as 50% efficacy remains cost-effective compared with chemotherapy; additional scenarios resembling epidemic settings such as the one that occurred in Chaparral, Colombia in 2004 demonstrates important economic benefits.

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    • "Estimates of potential economic value of a prophylactic vaccine indicated that even a vaccine with a relatively short duration of protection and modest efficacy could prevent a substantial number of cases at low-cost. Further, a vaccine providing ~5 years duration of protection with as little as 50% efficacy remains cost–effective compared with chemotherapy (4). Development of a prophylactic vaccine against Leishmania has gone through a long trajectory that includes phases of systematic selection of antigens, adjuvants, natural immune parameters to identify correlates of protection [reviewed in Ref. (5)]. "
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    ABSTRACT: Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, sub-unit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in L. donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen1-/- in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated in normal individuals.
    Frontiers in Immunology 05/2014; 5:241. DOI:10.3389/fimmu.2014.00241
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    ABSTRACT: Leishmaniasis is a protozoan parasitic disease endemic to the tropical and subtropical regions of the world, with three major clinical forms, self-healing cutaneous leishmaniasis, mucocutaneous leishmaniasis, and fatal visceral leishmaniasis (VL). Drug treatment is expensive, and often results in the development of resistance due to lack of compliance and prolonged use. No vaccine is available against leishmaniasis. Immunization with fi rst- and second-generation Leishmania vaccines has shown some effi cacy in animal models but little or none in humans. However, individuals who recover from a natural infection are protected from reinfection and develop lifelong protection, suggesting infection may be a prerequisite for creating immunological memory. Genetically altered live attenuated parasites with controlled infectivity could achieve such immunological memory and yield protection without overt disease. In this chapter, we discuss development and characteristics of genetically altered live attenuated Leishmania donovani parasites and their possible use as vaccine candidates against VL. In addition, we discuss the challenges with regard to safety and immunogenicity of the live attenuated parasites.
    Edited by Abhay Satoskar, Ravi Durvasula, 01/2014; Springer.
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