43
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Drug Resistance in Visceral Leishmaniasis

      review-article
      *
      Journal of Biomedicine and Biotechnology
      Hindawi Publishing Corporation

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Visceral leishmaniasis remains a public health problem worldwide. This illness was included by the World Health Organization in the list of neglected tropical diseases targeted for elimination by 2015. The widespread emergence of resistance to pentavalent antimonials in India where half cases occur globally and the unavailability of a vaccine in clinical use constitute major obstacles in achieving this goal. The last decade new antileishmanials became available, including the oral agent miltefosine. However, in poor endemic countries their wide use was curtailed because of the high costs, and also due to concerns of toxicity and emergence of resistance. Various mechanisms of antileishmanial resistance were identified recently in field isolates. Their elucidation will boost the design of new drugs and the molecular surveillance of resistance. Combination regimens should be evaluated in large trials. Overall, the development of antileishmanials has been generally slow; new drugs are needed. In order to control visceral leishmaniasis worldwide, treatment advances should become affordable in the poorest countries, where they are needed most.

          Related collections

          Most cited references59

          • Record: found
          • Abstract: found
          • Article: not found

          The relationship between leishmaniasis and AIDS: the second 10 years.

          To date, most Leishmania and human immunodeficiency virus (HIV) coinfection cases reported to WHO come from Southern Europe. Up to the year 2001, nearly 2,000 cases of coinfection were identified, of which 90% were from Spain, Italy, France, and Portugal. However, these figures are misleading because they do not account for the large proportion of cases in many African and Asian countries that are missed due to a lack of diagnostic facilities and poor reporting systems. Most cases of coinfection in the Americas are reported in Brazil, where the incidence of leishmaniasis has spread in recent years due to overlap with major areas of HIV transmission. In some areas of Africa, the number of coinfection cases has increased dramatically due to social phenomena such as mass migration and wars. In northwest Ethiopia, up to 30% of all visceral leishmaniasis patients are also infected with HIV. In Asia, coinfections are increasingly being reported in India, which also has the highest global burden of leishmaniasis and a high rate of resistance to antimonial drugs. Based on the previous experience of 20 years of coinfection in Europe, this review focuses on the management of Leishmania-HIV-coinfected patients in low-income countries where leishmaniasis is endemic.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Interleukin-10 and the pathogenesis of human visceral leishmaniasis.

            The mechanisms underlying the failure to control the growth and systemic spread of Leishmania parasites in human visceral leishmaniasis (VL) are not well understood. Although the absence of antigen-specific Th1 responses in the peripheral blood mononuclear cells from VL patients is thought to be causally related to disease progression, the finding that these patients also express elevated interferon-gamma mRNA in lesional tissue, as well as elevated serum levels of proinflammatory cytokines, suggests that their immunological defect cannot be explained simply by immune tolerance or Th2 polarization. As a possible homeostatic mechanism to control persistent infection-induced inflammation, elevated levels of the regulatory cytokine interleukin (IL)-10 have been reported repeatedly in clinical studies of VL. Here, we review the studies with relevance to immune responses in human VL and highlight the central role that IL-10 might have in the pathogenesis of VL and as a target for immune-based therapy.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Phase 4 trial of miltefosine for the treatment of Indian visceral leishmaniasis.

              Visceral leishmaniasis (VL) is a major public health problem in Bihar, accounting for 90% of all cases in India. Development of high levels of resistance to various existing drugs necessitated the search for alternative orally administered drugs. Hospital-based studies have shown that oral miltefosine is a highly effective treatment for VL both in adults and in children. An open, single-arm trial was designed to investigate the feasibility of treatment of VL patients with miltefosine in field conditions in 13 centers in Bihar. The phase 4 study was conducted among 1132 adult and pediatric VL patients. Compliance was good, with 1084 (95.5%) patients completing the full 28-day treatment course. Nine hundred and seventy-one (85.8%) patients returned for the final cure assessment at 6 months after treatment. The final cure rate was 82% by intention to treat analysis and 95% by per protocol analysis (similar to the 94% cure rate in hospitalized patients). Treatment-related adverse events of common toxicity criteria grade 3 occurred in ~3% of patients, including gastrointestinal toxicity and rise in aspertate amino transferase, alanine amino transferase, or serum creatinine levels, similar to previous clinical experience. This study supports the use of miltefosine in an outpatient setting in an area where VL is endemic.
                Bookmark

                Author and article information

                Journal
                J Biomed Biotechnol
                JBB
                Journal of Biomedicine and Biotechnology
                Hindawi Publishing Corporation
                1110-7243
                1110-7251
                2010
                1 November 2009
                : 2010
                : 617521
                Affiliations
                Department for Interventions in Health-Care Facilities, Hellenic Center for Disease Control and Prevention, 15123 Athens, Greece
                Author notes

                Academic Editor: Abhay R. Satoskar

                Article
                10.1155/2010/617521
                2771279
                19888437
                d455059d-8d03-4550-9070-6a4ae819a0fc
                Copyright © 2010 Helena C. Maltezou.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 June 2009
                : 10 August 2009
                : 30 August 2009
                Categories
                Review Article

                Molecular medicine
                Molecular medicine

                Comments

                Comment on this article