Activities of Hexadecylphosphocholine (Miltefosine), AmBisome, and Sodium Stibogluconate (Pentostam) against
            <i>Leishmania donovani</i>
            in Immunodeficient
            <i>scid</i>
            Mice

Escobar, Patricia; Yardley, Vanessa; Croft, Simon L.

doi:10.1128/aac.45.6.1872-1875.2001

Cited by 88 publications

(67 citation statements)

References 32 publications

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“…This same inflammatory mechanism also supports the efficacy of conventional antileishmanial chemotherapy-T cells and endogenous IL-12 and IFN-␥ are required for expression of the visceral leishmanicidal action of pentavalent antimony (Sb) in experimental infection (12,40,41). As judged by results with additional cytokine gene-disrupted mice, TNF and IL-4 also optimize the host response to Sb (2,42).…”

mentioning

confidence: 64%

Antagonizing Deactivating Cytokines To Enhance Host Defense and Chemotherapy in Experimental Visceral Leishmaniasis

Murray¹,

Flanders

Donaldson³

et al. 2005

Infect Immun

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In experimental visceral leishmaniasis, inhibition of interleukin 10 (IL-10) signaling enhances Th1-cellassociated responses, promoting gamma interferon (IFN-␥) secretion, granuloma assembly, macrophage activation with substantial liver parasite killing, and synergy with pentavalent antimony (Sb) chemotherapy. To determine if inhibiting other suppressive cytokines has similar therapeutic potential, Leishmania donovaniinfected BALB/c mice were injected with anti-IL-4 monoclonal antibody or receptor fusion antagonists of IL-13 or transforming growth factor ␤ (TGF-␤). Targeting IL-13 or TGF-␤ enabled inhibition of L. donovani replication but little parasite killing; anti-IL-4 had no effect. None of the three antagonists promoted IFN-␥ production, granuloma maturation, or Sb efficacy. Excess IL-13 and TGF-␤ exacerbated liver infection; however, effects were transient. Among IL-10, IL-4, IL-13, and TGF-␤, cytokines capable of disabling Th1-cell mechanisms (including those which support chemotherapy), IL-10 appears to be the appropriate target for therapeutic inhibition in visceral L. donovani infection.

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mentioning

confidence: 64%

Antagonizing Deactivating Cytokines To Enhance Host Defense and Chemotherapy in Experimental Visceral Leishmaniasis

Murray¹,

Flanders

Donaldson³

et al. 2005

Infect Immun

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“…The basis for this lack of activity of pentavalent antimonials has been explored in immunodeficient mouse models for which the effects are probably due to deficiencies of both Th1-cell-mediated and macrophage responses (109). Experimental models have shown that the antileishmanial activity of pentamidine is also T-cell dependent whereas those of amphotericin B and miltefosine are T-cell independent (61,108). Irrespective of the findings of the experimental models, it is now known that intact immunity holds the key to the curative ability of antileishmanial drugs, including amphotericin B.…”

Section: Host Factors Host Immune Statusmentioning

confidence: 99%

Drug Resistance in Leishmaniasis

2006

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SUMMARY Leishmaniasis is a complex disease, with visceral and cutaneous manifestations, and is caused by over 15 different species of the protozoan parasite genus Leishmania. There are significant differences in the sensitivity of these species both to the standard drugs, for example, pentavalent antimonials and miltefosine, and those on clinical trial, for example, paromomycin. Over 60% of patients with visceral leishmaniasis in Bihar State, India, do not respond to treatment with pentavalent antimonials. This is now considered to be due to acquired resistance. Although this class of drugs has been used for over 60 years for leishmaniasis treatment, it is only in the past 2 years that the mechanisms of action and resistance have been identified, related to drug metabolism, thiol metabolism, and drug efflux. With the introduction of new therapies, including miltefosine in 2002 and paromomycin in 2005-2006, it is essential that there be a strategy to prevent the emergence of resistance to new drugs; combination therapy, monitoring of therapy, and improved diagnostics could play an essential role in this strategy.

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“…In India, where resistance to antimonial agents is very high, miltefosine has been used since 1998 for the treatment of Visceral Leishmaniasis (VL) produced by L. donovani 7,24 . This has motivated its evaluation for the treatment of other leishmaniasis 25 .…”

Section: Introductionmentioning

confidence: 99%

Thermoterapy effective and safer than miltefosine in the treatment of cutaneous leishmaniasis in Colombia

López

Cruz

Godoy

et al. 2013

Rev. Inst. Med. trop. S. Paulo

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SUMMARYIn Colombia, pentavalent antimonials and miltefosine are the drugs of choice for the treatment of cutaneous leishmaniasis; however, their toxicity, treatment duration, (treatment adherence problems), cost, and decreased parasite sensitivity make the search for alternative treatments of American cutaneous leishmaniasis necessary. Based on the results found in a controlled, open, randomized, phase III clinical trial, the efficacy and safety of miltefosine was compared to that of thermotherapy for the treatment of cutaneous leishmaniasis in Colombia. Adult patients from the Colombian army participated in the study; they received either 50 mg of miltefosine three times per day for 28 days by the oral route (n = 145) or a thermotherapy (Thermomed ® ) application of 50 ºC for 30 seconds over the lesion and surrounding area (n = 149). Both groups were comparable with respect to their sociodemographic, clinical, and parasitological characteristics. The efficacy of miltefosine by protocol and by intention to treat was 70% (85/122 patients) and 69% (85/145 patients), respectively. The adverse effects were primarily gastrointestinal for miltefosine and pain at the lesion site after treatment for thermotherapy. No statistically significant difference was found in the efficacy analysis (intention to treat and protocol) between the two treatments. ClinicalTrials.gov: NCT00471705.

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Activities of Hexadecylphosphocholine (Miltefosine), AmBisome, and Sodium Stibogluconate (Pentostam) against Leishmania donovani in Immunodeficient scid Mice

Cited by 88 publications

References 32 publications

Antagonizing Deactivating Cytokines To Enhance Host Defense and Chemotherapy in Experimental Visceral Leishmaniasis

Antagonizing Deactivating Cytokines To Enhance Host Defense and Chemotherapy in Experimental Visceral Leishmaniasis

Drug Resistance in Leishmaniasis

Thermoterapy effective and safer than miltefosine in the treatment of cutaneous leishmaniasis in Colombia

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