Leishmaniasis: treatment, drug resistance and emerging therapies

Sundar, Shyam; Chakravarty, Jaya; Meena, Lalit Prashant

doi:10.1080/21678707.2019.1552853

Cited by 51 publications

(38 citation statements)

References 85 publications

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“…The therapeutic options for visceral and cutaneous leishmaniasis are focused on two major drugs, the pentavalent antimonials and amphotericin B [ 5 ]. In addition, other alternative drugs or formulations have been employed in the treatment of leishmaniasis, as is the case of the highly active drug Ambisome ® , a liposomal drug containing amphotericin B, which has been used to minimize all side-effects caused by amphotericin B; however, the high costs related to the treatment is a major drawback in low income countries, such as East Africa and Brazil [ 6 ]. More recently, the antineoplastic miltefosine, the only available oral antileishmanial drug, has been used in some countries, but over a decade of use, its effectiveness has decreased significantly [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…[ 10 , 11 ]. Association between drugs has been considered a consensus among specialists for several reasons [ 6 ]. Combination of drugs from different chemical classes may increase the effectiveness of therapy, reduce the dose and time of treatment that has a direct effect in the toxicity, and consequently patient tolerance and compliance increases during the treatment [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Association between drugs has been considered a consensus among specialists for several reasons [ 6 ]. Combination of drugs from different chemical classes may increase the effectiveness of therapy, reduce the dose and time of treatment that has a direct effect in the toxicity, and consequently patient tolerance and compliance increases during the treatment [ 6 ]. Combined therapy can delay the onset of resistance and increase the shelf life of different drugs, as has been observed in the treatment of some infectious diseases, such as malaria, tuberculosis, and HIV [ 10 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Ursolic Acid Potentializes Conventional Therapy in Experimental Leishmaniasis

et al. 2020

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Ursolic acid (UA) is a triterpene with a broad array of pharmacological activities. In leishmaniasis, UA killed different species of parasites, and it was active in the experimental model of cutaneous and visceral leishmaniasis. Thus, the objective of this work was to study the therapeutic efficacy of the conventional drugs amphotericin B (AmB) or glucantime (Glu) combined with UA in experimental visceral and cutaneous leishmaniasis, respectively. L. (L.) infantum-infected hamsters were treated with AmB alone or combined with UA. L. (L.) amazonensis-infected BALB/c mice were treated with Glu alone or combined with UA. Animals were treated for 15 consecutive days by intraperitoneal or intralesional routes. Following one week after the last dose, the tissue parasitism and cellular immune responses were analyzed. Hamsters treated with 0.2 and 1.0 mg/kg of AmB plus 1.0 mg/kg of UA showed low hepatic and splenic parasitisms; however, AmB given as monotherapy did not reduce the number of viable parasites in the spleen of treated animals. In cutaneous leishmaniasis, Glu given as monotherapy was inactive at 2.0 mg/kg, showed mild activity at 10.0 mg/kg, and at 50.0 mg/kg was highly active at eliminating parasites in the skin. When animals were treated with Glu plus UA, higher leishmanicidal activity was observed in comparison to all groups treated with monotherapy schemes, and such activity was related to lesion improvement and upregulation of IFN-γ production. Altogether, data suggest that the association of drugs for the treatment of leishmaniasis can increase the efficiency of the treatment and decrease the toxicity associated to the conventional drugs.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ursolic Acid Potentializes Conventional Therapy in Experimental Leishmaniasis

et al. 2020

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“…Multiple factors are involved in the correct chemotherapy choice, which may vary according to regional or national guidelines (Graebin et al 2009 ; Sundar et al 2019 ). In addition to important adverse effects, drug resistance has already been reported for currently employed drugs (Sundar et al 2019 ; Tiwari et al 2018 ). Current strategies to overcome the lack of treatment options are based on drug repurposing, multidrug therapy, and development of novel compounds.…”

Section: Introductionmentioning

confidence: 99%

Revisiting nature: a review of iridoids as a potential antileishmanial class

2021

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Leishmaniasis still stands as one of the most prevalent neglected tropical diseases in the least developed and emerging countries. The recommended therapeutic arsenal to treat leishmaniasis is characterized by several shortcomings, and resistance has already been reported. Hence, this dramatic background highlights the pressing need to develop novel, affordable, and safe antileishmanial drugs. Multiple classes of natural compounds have been reported to possess antileishmanial activity. Among these classes, iridoids stand out as a special type of monoterpenoids with diverse biological properties—including their antileishmanial potential. This review aims to discuss the available literature between 1991 and 2020 related to the antileishmanial activity of the iridoid class. Throughout the past decades, various investigations attributed antileishmanial action to assorted iridoid types, including inhibitory potential towards validated drug targets and immunomodulatory activity. The latter deserves special attention due to the ability of some iridoids to improve the host’s immune response against parasites. It opens the possibility of iridoids become adjuncts in leishmaniasis treatments by improving the efficacy of currently employed drugs. Furthermore, the present study intends to provide a convenient visual representation of which iridoids and Leishmania spp. species have been most investigated as a guide for further researches.

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“…Amphotericin B is considered an effective drug for VL in the Indian subcontinent [ 16 – 18 ]. However, increased cases of resistance to Amphotericin B in VL patients [ 19 ] and the rate of relapse in PKDL patients (after treatment) have increased substantially [ 20 , 21 ]. At the same time, combination therapy proved to be more effective in treating VL than monotherapy [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Differentially modulated proteins associated with Leishmaniasis—a systematic review of in-vivo and in-vitro studies

2020

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High-throughput proteomic technologies are widely used for understanding the disease mechanism, drug-resistant mechanism, and to identify drug targets and markers for diagnostics. Studies with proteomics applications, relating to Leishmaniasis, are being constantly reported in the literature. However, from such studies, a readily accessible knowledge of differentially modulated proteins associated with Leishmaniasis is lacking. Hence, we performed a systematic review concerning differentially modulated proteins (DMP) in Leishmania as well as host infected with Leishmania from the published articles between the years 2000 and 2019. This review is classified into five different sections, namely, DMP in the host after Leishmania infection, DMP between different strains of Leishmania , DMP in drug-resistant Leishmania , DMP in Leishmania under stress, and DMP in different life stages of Leishmania. A lot of consensuses could be observed among the DMP in drug-resistant and stressed Leishmania . In addition to the review, a database was constructed with the data collected in this study (protein accession ID, protein name, gene name, host organism, experimental conditions, fold change, and regulatory data). A total of 2635 records are available in the database. We believe this review and the database will help the researcher in understanding the disease better and provide information for the targeted proteomics study related to Leishmaniasis. Database availability: http://ldepdb.biomedinformri.com/ . Electronic supplementary material The online version of this article (10.1007/s11033-020-05936-z) contains supplementary material, which is available to authorized users.

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Leishmaniasis: treatment, drug resistance and emerging therapies

Cited by 51 publications

References 85 publications

Ursolic Acid Potentializes Conventional Therapy in Experimental Leishmaniasis

Ursolic Acid Potentializes Conventional Therapy in Experimental Leishmaniasis

Revisiting nature: a review of iridoids as a potential antileishmanial class

Differentially modulated proteins associated with Leishmaniasis—a systematic review of in-vivo and in-vitro studies

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