Epidemiology of Leishmaniasis in the Time of Drug Resistance (the Miltefosine Era)

Dujardin, Jean‐Claude

doi:10.1007/978-3-319-74186-4_4

Cited by 6 publications

(4 citation statements)

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“…Leishmania cause a broad spectrum of clinical presentations, the most severe being visceral leishmaniasis (VL) which annually affects up to 90,000 new individuals [1] and has a 10% mortality rate [2]. Ongoing control programs, like the one running in the Indian subcontinent (ISC) [3] could be challenged by several factors, including drug resistance [4,5] and emergence of new parasite variants [6,7]. More than ever, close surveillance is required to avoid new epidemics, including molecular tracking of the etiological agent.…”

Section: Introductionmentioning

confidence: 99%

Genomes of Leishmania parasites directly sequenced from patients with visceral leishmaniasis in the Indian subcontinent

et al. 2019

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Whole genome sequencing (WGS) is increasingly used for molecular diagnosis and epidemiology of infectious diseases. Current Leishmania genomic studies rely on DNA extracted from cultured parasites, which might introduce sampling and biological biases into the subsequent analyses. Up to now, direct analysis of Leishmania genome in clinical samples is hampered by high levels of human DNA and large variation in parasite load in clinical samples. Here, we present a method, based on target enrichment of Leishmania donovani DNA with Agilent SureSelect technology, that allows the analysis of Leishmania genomes directly in clinical samples. We validated our protocol with a set of artificially mixed samples, followed by the analysis of 63 clinical samples (bone marrow or spleen aspirates) from visceral leishmaniasis patients in Nepal. We were able to identify genotypes using a set of diagnostic SNPs in almost all of these samples (97%) and access comprehensive genome-wide information in most (83%). This allowed us to perform phylogenomic analysis, assess chromosome copy number and identify large copy number variants (CNVs). Pairwise comparisons between the parasite genomes in clinical samples and derived in vitro cultured promastigotes showed a lower aneuploidy in amastigotes as well as genomic differences, suggesting polyclonal infections in patients. Altogether our results underline the need for sequencing parasite genomes directly in the host samples

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Section: Introductionmentioning

confidence: 99%

Genomes of Leishmania parasites directly sequenced from patients with visceral leishmaniasis in the Indian subcontinent

et al. 2019

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“…It was synthesized according to the general procedure described above from 11bromoundecan-1-ol (6). Colourless oil [50]; yield: 3.1 g, 97%; 1 H-NMR (300 MHz, CDCl 3 ) δ 3.47 (t, J = 6.72 Hz, 2H), 3.14 (t, J = 6.72 Hz, 2H), 1.50-1.41 (m, 4H), 1.17 (s, 14H); 13…”

Section: -Azidoundecan-1-ol (9)mentioning

confidence: 99%

“…Unfortunately, the standard treatment of Leishmaniasis depends on poorly tolerated drugs with high toxicity. In addition, a major problem encountered in clinical practice is the increased chemoresistance of the parasite [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Antiparasitic Evaluation of Click Phospholipids

et al. 2021

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A library of seventeen novel ether phospholipid analogues, containing 5-membered heterocyclic rings (1,2,3-triazolyl, isoxazolyl, 1,3,4-oxadiazolyl and 1,2,4-oxadiazolyl) in the lipid portion were designed and synthesized aiming to identify optimised miltefosine analogues. The compounds were evaluated for their in vitro antiparasitic activity against Leishmania infantum and Leishmania donovani intracellular amastigotes, against Trypanosoma brucei brucei and against different developmental stages of Trypanosoma cruzi. The nature of the substituents of the heterocyclic ring (tail) and the oligomethylene spacer between the head group and the heterocyclic ring was found to affect the activity and toxicity of these compounds leading to a significantly improved understanding of their structure–activity relationships. The early ADMET profile of the new derivatives did not reveal major liabilities for the potent compounds. The 1,2,3-triazole derivative 27 substituted by a decyl tail, an undecyl spacer and a choline head group exhibited broad spectrum antiparasitic activity. It possessed low micromolar activity against the intracellular amastigotes of two L. infantum strains and T. cruzi Y strain epimastigotes, intracellular amastigotes and trypomastigotes, while its cytotoxicity concentration (CC50) against THP-1 macrophages ranged between 50 and 100 μM. Altogether, our work paves the way for the development of improved ether phospholipid derivatives to control neglected tropical diseases.

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“…In some regions, mainly where resistance has developed, miltefosine, paramycin, and liposomal amphotericin B are gradually replacing the antimonials ( 9 , 10 ). Nowadays, due to some factors such as side effects, drug resistance, excessive and economic costs of medical services, lack of easy access to these medications in some areas, researchers are looking for effective alternative drugs to reduce the side effects of CL treatment ( 11 , 12 , 13 ). One way to do so is the use of safe plant extracts in the treatment of the disease.…”

Section: Introductionmentioning

confidence: 99%

Anti Leishmanial Effect of Plantago psyllium (ovate) and White Vinegar on Leishmania major Lesion in BALB/c Mice

Moshfe¹,

Karami²,

Bahmani³

et al. 2022

JAD

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Background: Leishmania major is the etiologic agent of zoonotic cutaneous leishmaniasis in Iran, and glucantime injection is currently used for its treatment. This study aimed to evaluate the anti-leishmanial effect of topical Plantago psyllium and white vinegar in L. major infected BALB/c mice. Methods: Thirty infected mice were divided into five groups as follows: Group‌ 1: treated with the combination of ovata powder and white vinegar, Group 2: treated with glucantime, Group 3: treated with white vinegar, Group 4: treated with the combination of ovata powder and water, and Group 5: without any treatment. All the groups were treated for 18 days. Lesion size was measured, and final smears were prepared for microscopic examination. Results: The findings indicated that the difference in the mean areas of the ulcers in all the groups before and after treatment was not significant, except for the second (glucantime) and third (vinegar) groups. Also, the results showed that in the first, second, third, and fourth group, 6 (60%), 4 (80%), 3 (60%), and 2 (40%) mice were healed, respectively. However, ulcers remained in all the five mice of the control group. Conclusion: The combination of ovata powder and white vinegar has been traditionally used to treat leishmanial lesions in Iran. It seems the most anti-leishmanial effect is related to vinegar and supported by Plantago. The route of treatment with this combination is very simple and painless in comparison with injection. Thus, further studies on this issue could help to design more effective and easy-to-use drugs.

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Epidemiology of Leishmaniasis in the Time of Drug Resistance (the Miltefosine Era)

Cited by 6 publications

References 100 publications

Genomes of Leishmania parasites directly sequenced from patients with visceral leishmaniasis in the Indian subcontinent

Genomes of Leishmania parasites directly sequenced from patients with visceral leishmaniasis in the Indian subcontinent

Design, Synthesis and Antiparasitic Evaluation of Click Phospholipids

Anti Leishmanial Effect of Plantago psyllium (ovate) and White Vinegar on Leishmania major Lesion in BALB/c Mice

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