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Leishmania infantum isolates exhibit high infectivity and reduced susceptibility to amphotericin B.

ABSTRACT: Leishmaniasis is a neglected disease caused by a protozoan parasite of the Leishmania species in over 98 countries in five continents. Visceral leishmaniasis is one of the main forms of the disease and is mainly caused by Leishmania infantum, whose main vector is the dipteran Lutzomyia longipalpis. The presence of the vector in Uruguay was recorded for the first time in 2010 and an autochthonous outbreak of canine visceral leishmaniasis occurred in the northern locality of the country in 2015. We report the isolation in blood-free FBS-supplemented defined media of five isolates responsible for the referred outbreak, and characterize them in terms of their growth as promastigotes, infectivity and replication in human derived monocytes and drug resistance. Results indicate similar promastigote growth among the strains, enhanced infectivity and replication for the five strains isolated from the Uruguayan outbreak when compared with reference strains from South America, equivalent drug susceptibility for miltefosine and nifurtimox and a significant difference in IC₅₀ values for amphotericin B between the Uruguayan strains, 3-4 fold higher than the reference strain.

SUBMITTER: Faral-Tello P

PROVIDER: S-EPMC7651856 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Leishmania infantum is the main etiological agent of both visceral and cutaneous clinical forms of leishmaniasis in the Mediterranean area. Leishmania/HIV coinfection in this area is characterized by a chronic course and frequent recurrences of clinical episodes. The present study using Multilocus Microsatellite Typing (MLMT) analysis, a highly discriminative tool, aimed to genetically characterize L. infantum isolates taken from monitored Leishmania/HIV coinfected patients presenting successive clinical episodes.In this study, by the analysis of 20 microsatellite loci, we studied the MLMT profiles of 25?L. infantum isolates from 8 Leishmania/HIV coinfected patients who had experienced several clinical episodes. Two to seven isolates per patient were taken before and after treatment, during clinical and non-clinical episodes, with time intervals of 6 days to 29 months. Genetic diversity, clustering and phenetic analyses were performed.MLMT enabled us to study the genetic characteristics of the 25?L. infantum isolates, differentiating 18 genotypes, corresponding to a genotypic diversity of 0.72. Fifteen genotypes were unique in the total sample set and only 3 were repeated, 2 of which were detected in different patients. Both clustering and phylogenetic analyses provided insights into the genetic links between the isolates; in five patients isolates showed clear genetic links: either the genotype was exactly the same or only slightly different. In contrast, the isolates of the other three patients were dispersed in different clusters and some could be the result of mixing between populations.Our data indicated a great MLMT variability between isolates from coinfected patients and no predominant genotype was observed. Despite this, almost all clinical episodes could be interpreted as a relapse rather than a reinfection. The results showed that diverse factors like an intrapatient evolution over time or culture bias could influence the parasite population detected in the patient, making it difficult to differentiate between relapse and reinfection.

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Leishmania infantum isolates exhibit high infectivity and reduced susceptibility to amphotericin B.

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