Reviews Of Anti‐infective Agents: Liposomal Amphotericin B for the Treatment of Visceral Leishmaniasis

Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Clinical Infectious Diseases (Impact Factor: 8.89). 11/2006; 43(7):917-24. DOI: 10.1086/507530
Source: PubMed

ABSTRACT During the past decade, liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL). The World Health Organization convened a workshop to review current knowledge and to develop guidelines for liposomal amphotericin B use for VL. In Europe, liposomal amphotericin B is widely used to treat VL. In Africa and Asia, the VL disease burden is high and drug access is poor; liposomal amphotericin B is available only through preferential pricing for nonprofit groups in East Africa. Clinical trials and experience demonstrate high efficacy and low toxicity for liposomal amphotericin B (total dose, 20 mg/kg) in immunocompetent patients with VL. Combination trials in areas with antileishmanial drug resistance, and treatment and secondary prophylaxis trials in VL-human immunodeficiency virus-coinfected patients, are important to safeguard the current armamentarium and to optimize regimens. The public health community should work to broaden access to preferential liposomal amphotericin B pricing by public sector VL treatment programs.

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Available from: Luigi Gradoni, Sep 28, 2015
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    • "Amphotericin B, a second-line drug, is a highly hydrophobic antifungal product with an effective antileishmanial activity; however, its clinical use is also limited by its high toxicity (Annaloro et al., 2009; Ribeiro et al., 2014). To improve the therapeutic index of AmpB in an attempt to reduce its cytotoxicity, lipid-based formulations have been developed, such as Ambisome ® , AmphocilH ® , and Abelcet ® (Bern et al., 2006). The World Health Organization has recommended the use of liposomal AmpB (L-AmpB) based on its high efficacy and safety (WHO, 2010). "
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    ABSTRACT: The present study aimed to investigate the in vitro antileishmanial activity of strychnobiflavone flavonoid against Leishmania infantum, as well as its mechanism of action, and evaluate the ex vivo biodistribution profile of the flavonoid in naive BALB/c mice. The antileishmanial activity (IC50 value) of strychnobiflavone against stationary promastigote and amastigote-like stages of the parasites was of 5.4 and 18.9 μM, respectively; with a 50% cytotoxic concentration (CC50) value of 125.0 μM on murine macrophages, resulting in selectivity index (SI) of 23.2 and 6.6, respectively. Amphotericin B, used as a positive control, presented SI values of 7.6 and 3.3 for promastigote and amastigote-like stages of L. infantum, respectively. The strychnobiflavone was also effective in reducing in significant levels the percentage of infected macrophages, as well as the number of amastigotes per macrophage, after the treatment of infected macrophages using the flavonoid. By using different fluorescent probes, we investigated the bioenergetics metabolism of L. infantum promastigotes and demonstrated that the flavonoid caused the depolarization of the mitochondrial membrane potential, without affecting the production of reactive oxygen species. In addition, using SYTOX(®) green as a fluorescent probe, the strychnobiflavone demonstrated no interference in plasma membrane permeability. For the ex vivo biodistribution assays, the flavonoid was labeled with technetium-(99m) and studied in a mouse model by intraperitoneal route. After a single dose administration, the scintigraphic images demonstrated a highest uptake by the liver and spleen of the animals within 60 min, resulting in low concentrations after 24 h. The present study therefore demonstrated, for the first time, the antileishmanial activity of the strychnobiflavone against L. infantum, and suggests that the mitochondria of the parasites may be the possible target organelle. The preferential distribution of this compound into the liver and spleen of the animals could warrant its employ in the treatment of visceral leishmaniasis.
    Parasitology Research 09/2015; DOI:10.1007/s00436-015-4708-4 · 2.10 Impact Factor
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    • "At the present time, the best approach for diagnosis remains the combination of methods [4]. Amphotericin was the drug of choice for the majority of patients, and the liposomal formulation was preferred [27] [28]. "
    Clinical Microbiology and Infection 01/2015; 21(1):89-95. · 5.77 Impact Factor
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    • "Lipid formulations of the polyene antibiotic AmB are now the mainstay for the treatment of Leishmania in the epidemic region of Bihar in India where nearly 65% of the cases are refractory to the first line antimonial drugs (Bern et al., 2006; Chappuis et al., 2007). Although some sporadic unusual cases have been reported recently (Srivastava et al., 2011; Purkait et al., 2012), clinical resistance has not yet threatened the efficacy of AmB, even when used through many courses as for treating HIV co-infected patients (Lachaud et al., 2009). "
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    ABSTRACT: Amphotericin B (AmB) in its liposomal form is now considered as either first- or second-line treatment against Leishmania infections in different part of the world. Few cases of AmB resistance have been reported and resistance mechanisms toward AmB are still poorly understood. This paper reports a large-scale comparative proteomic study in the context of AmB resistance. Quantitative proteomics using stable isotope labeling of amino acids in cell culture (SILAC) was used to better characterize cytoplasmic and membrane-enriched (ME) proteomes of the in vitro generated Leishmania infantum AmB resistant mutant AmB1000.1. In total, 97 individual proteins were found as differentially expressed between the mutant and its parental sensitive strain (WT). More than half of these proteins were either metabolic enzymes or involved in transcription or translation processes. Key energetic pathways such as glycolysis and TCA cycle were up-regulated in the mutant. Interestingly, many proteins involved in reactive oxygen species (ROS) scavenging and heat-shock proteins were also up-regulated in the resistant mutant. This work provides a basis for further investigations to understand the roles of proteins differentially expressed in relation with AmB resistance.
    International Journal for Parasitology: Drugs and Drug Resistance 08/2014; 4(2):126–132. DOI:10.1016/j.ijpddr.2014.05.002 · 3.29 Impact Factor
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