Safety and Efficacy of miltefosine alone and in combination with sodium stibogluconate and liposomal amphotericin B for the treatment of primary visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial

Omollo, Raymond; Nast, Alexander; Edwards, Tansy; Khalil, E. A. G.; Younis, Brima M.; Abuzaid, Abuzaid A.; Wasunna, Monique; Njoroge, Njenga; Kinoti, Dedan; Kirigi, George; Dorlo, Thomas P. C.; Ellis, Sally; Balasegaram, Manica; Musa, Ahmed

doi:10.1186/1745-6215-12-166

Cited by 45 publications

(43 citation statements)

References 16 publications

(19 reference statements)

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“…Several successful reports on adjunct therapy of antimony with other drugs for treatment of leishmaniasis have been published (22)(23)(24)(25)(26). The antileishmanial efficacy of miltefosine, the only available oral drug, was also found to be enhanced when given in combination with paromomycin or an immunomodulator, picroliv (17,18,27).…”

Section: Discussionmentioning

confidence: 97%

Nanotized Curcumin and Miltefosine, a Potential Combination for Treatment of Experimental Visceral Leishmaniasis

Tiwari

Pahuja

Kumar

et al. 2017

Antimicrob Agents Chemother

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Leishmaniasis chemotherapy remains very challenging due to high cost of the drug and its associated toxicity and drug resistance, which develops over a period of time. Combination therapies (CT) are now in use to treat many diseases, such as cancer and malaria, since it is more effective and affordable than monotherapy. CT are believed to represent a new explorable strategy for leishmaniasis, a neglected tropical disease caused by the obligate intracellular parasite Leishmania. In the present study, we investigated the effect of a combination of a traditional Indian medicine (ayurveda), a natural product curcumin and miltefosine, the only oral drug for visceral leishmaniasis (VL) using a Leishmania donovani-hamster model. We developed an oral nanoparticle-based formulation of curcumin. Nanoformulation of curcumin alone exhibited significant leishmanicidal activity both in vitro and in vivo. In combination with miltefosine, it exhibited a synergistic effect on both promastigotes and amastigotes under in vitro conditions. The combination of these two agents also demonstrated increased in vivo leishmanicidal activity accompanied by increased production of toxic reactive oxygen/nitrogen metabolites and enhanced phagocytic activity. The combination also exhibited increased lymphocyte proliferation. The present study thus establishes the possible use of nanocurcumin as an adjunct to antileishmanial chemotherapy.

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Section: Discussionmentioning

confidence: 97%

Nanotized Curcumin and Miltefosine, a Potential Combination for Treatment of Experimental Visceral Leishmaniasis

Tiwari

Pahuja

Kumar

et al. 2017

Antimicrob Agents Chemother

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“…SSG, ampB, and miltefosine have all been evaluated as combinatorial therapies for VL in the clinic (Musa et al, 2012; Omollo et al, 2011). Sundar et al have shown that combinations of sub-optimal anti-leishmanial compounds have the potential to be a more efficacious treatment with fewer side effects, however, combinatorial therapies using compounds that clear infections through non-host-mediated mechanisms are still at risk for cultivating resistant strains (Sundar et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Host-mediated Leishmania donovani treatment using AR-12 encapsulated in acetalated dextran microparticles

Collier

Peine

Gautam

et al. 2016

International Journal of Pharmaceutics

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Leishmaniasis is a disease caused by parasites of Leishmania sp., which effects nearly 12 million people worldwide and is associated with treatment complications due to widespread parasite resistance toward pathogen-directed therapeutics. The current treatments for visceral leishmaniasis (VL), the systemic form of the disease, involve pathogen-mediated drugs and have long treatment regimens, increasing the risk of forming resistant strains. One way to limit emergence of resistant pathogens is through the use of host-mediated therapeutics. The host-mediated therapeutic AR-12, which is FDA IND-approved for cancer treatment, has shown activity against a broad spectrum of intracellular pathogens; however, due to hydrophobicity and toxicity, it is difficult to reach therapeutic doses. We have formulated AR-12 into microparticles (AR-12/MPs) using the novel biodegradable polymer acetalated dextran (Ace-DEX) and used this formulation for the systemic treatment of VL. Treatment with AR-12/MPs significantly reduced liver, spleen, and bone marrow parasite loads in infected mice, while combinatorial therapies with amphotericin B had an even more significant effect. Overall, AR-12/MPs offer a unique, host-mediated therapy that could significantly reduce the emergence of drug resistance in the treatment of VL.

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“…Encouraged by this new treatment approach, an exploratory study with miltefosine alone and combinations of single dose of L-AmB (10 mg/kg) with SSG (20 mg/kg) for 10 days and L-AmB (10 mg/kg) with miltefosine for 10 days is being done in East Africa. 179 …”

Section: Review Of Antileishmanial Agentsmentioning

confidence: 99%

An update on pharmacotherapy for leishmaniasis

Sundar

Chakravarty

2014

Expert Opinion on Pharmacotherapy

253

191

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Introduction Leishmaniasis broadly manifests as visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL). The treatment of leishmaniasis is challenging and the armamentarium of drugs is small, duration of treatment is long, and most drugs are toxic. Areas covered A literature search on treatment of leishmaniasis was done on PubMed. Single dose of liposomal amphotericin B (L-AmB) and multidrug therapy (L-AmB + miltefosine, L-AmB + paromomycin (PM), or miltefosine + PM) are the treatment of choice for VL in the Indian subcontinent. A 17-day combination therapy of pentavalent antimonials (Sbv) and paromomycin remains the treatment of choice for East African VL. L-AmB is the recommended regimen for VL in the Mediterranean region and South America. Treatment of CL should be decided by the severity of clinical lesions, etiological species and its potential to develop into mucosal leishmaniasis. Expert opinion There is an urgent need to implement a single dose L-AmB or combination therapy in the Indian subcontinent. Combination therapy with newer drugs needs to be tested in Africa. Due to the toxicity of systemic therapy, a trend towards local treatment for New World CL (NWCL) is preferred in patients without risk of mucosal disease.

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Safety and Efficacy of miltefosine alone and in combination with sodium stibogluconate and liposomal amphotericin B for the treatment of primary visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial

Cited by 45 publications

References 16 publications

Nanotized Curcumin and Miltefosine, a Potential Combination for Treatment of Experimental Visceral Leishmaniasis

Nanotized Curcumin and Miltefosine, a Potential Combination for Treatment of Experimental Visceral Leishmaniasis

Host-mediated Leishmania donovani treatment using AR-12 encapsulated in acetalated dextran microparticles

An update on pharmacotherapy for leishmaniasis

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