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Treatment of visceral leishmaniasis in Brazil still relies on meglumine antimoniate, with less than ideal efficacy and safety, making new therapeutic tools an urgent need. The oral drug miltefosine was assayed in a phase II clinical trial in Brazil with cure rates lower than previously demonstrated in India. The present study investigated the susceptibility to miltefosine in 73 Brazilian strains of from different geographic regions, using intracellular amastigote and promastigote assays. The EC for miltefosine of 13 of these strains evaluated in intracellular amastigotes varied between 1.41 and 4.57 μM. The EC of the 73 strains determined in promastigotes varied between 5.89 and 23.7 μM. No correlation between in vitro miltefosine susceptibility and the presence of the miltefosine sensitive locus was detected among the tested strains. The relatively low heterogeneity in miltefosine susceptibility observed for the 73 strains tested in this study suggests the absence of decreased susceptibility to miltefosine in Brazilian and does not exclude future clinical evaluation of miltefosine for VL treatment in Brazil.
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http://dx.doi.org/10.3390/microorganisms9061228 | DOI Listing |
PLoS Pathog
March 2025
Laboratório de Pesquisa em Leishmanioses, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
Background: The present study investigates implications of a sub-chromosomal deletion in Leishmania infantum strains, the causative agent of American Visceral Leishmaniasis (AVL). Primarily found in New World strains, the deletion leads to the absence of the ecto-3'-nucleotidase/nuclease enzyme, impacting parasite virulence, pathogenicity, and drug susceptibility. The factors favoring prevalence and the widespread geographic distribution of these deleted mutant parasites (DEL) in the NW (NW) are discussed under the generated data.
View Article and Find Full Text PDFMycoses
March 2025
Pharmaceutical Sciences Research Centre, Haemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran.
Introduction: Dermatophytosis, a cutaneous fungal infection worldwide, is generally localised to the skin's superficial layers and keratinised structures. Although most agents are susceptible to current antifungal drugs available in clinical settings, frequent relapses and failures, especially in cases due to Trichophyton indotineae, have been frequently reported. Therefore, alternative targets and therapeutic approaches are highly required.
View Article and Find Full Text PDFMicroorganisms
January 2025
Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, UMAE Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico.
Pentavalent antimonials are the first line for leishmaniasis treatment, although they induce many adverse side effects and treatment failure and parasite resistance have been detected. Cutaneous leishmaniasis is the main clinical manifestation of the disease in Oaxaca State, Mexico; however, its presence is under-registered, and information about the species that circulate and cause the disease in the region is limited. In this study, the presence of was analyzed in 24 skin smears and 2 biopsies from lesions suspicious for leishmaniasis in inhabitants of the Tehuantepec Isthmus and Papaloapan Basin regions, Oaxaca State.
View Article and Find Full Text PDFInt J Parasitol Drugs Drug Resist
April 2025
São Paulo State University (Unesp), School of Pharmaceutical Sciences, Araraquara, São Paulo, Brazil. Electronic address:
Leishmaniasis is a neglected disease that remains with a limited number of drugs available for chemotherapy and has an increased drug resistance that affects treatment outcomes. Metal-based drugs such as cyclopalladated complex [Pd(dmba)(μ-N)] (CP2), a Leishmania topoisomerase IB inhibitor involved in calcium dysregulation and mitochondrial dysfunction of the parasite, had been an alternative to outline the appearance of chemoresistance. To identify new molecular targets and point out possible resistance mechanisms, a CP2-resistant Leishmania amazonensis (LaR) was selected by stepwise exposure to increasing drug pressure until a line capable of growth in 13.
View Article and Find Full Text PDFParasitol Int
June 2025
Manisa Celal Bayar University, Medical Faculty, Department of Parasitology, Manisa, Turkey.
This study aims to identify the most sensitive colorimetric test for assessing intracellular drug susceptibility of Leishmania tropica to conventional antileishmanial drugs. To this end, the efficacy of four colorimetric methods-MTT, XTT, MTS, and WST-8-was compared using reference L. tropica promastigotes.
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