Antimony susceptibility of Leishmania isolates collected over a 30-year period in Algeria

Abstract

BackgroundIn Algeria, the treatment of visceral and cutaneous leishmanioses (VL and CL) has been and continues to be based on antimony-containing drugs. It is suspected that high drug selective pressure might favor the emergence of chemoresistant parasites. Although treatment failure is frequently reported during antimonial therapy of both CL and VL, antimonial resistance has never been thoroughly investigated in Algeria. Determining the level of antimonial susceptibility, amongst Leishmania transmitted in Algeria, is of great importance for the development of public health policies.Methodology/Principal findingsWithin the framework of the knowledge about the epidemiology of VL and CL amassed during the last 30 years, we sampled Leishmania isolates to determine their susceptibility to antimony. We analyzed a total of 106 isolates including 88 isolates collected between 1976 and 2013 in Algeria from humans, dogs, rodents, and phlebotomines and 18 collected from dogs in France. All the Algerian isolates were collected in 14 localities where leishmaniasis is endemic. The 50% inhibitory concentrations (IC50) of potassium antimony tartrate (the trivalent form of antimony, Sb(III)) and sodium stibogluconate (the pentavalent form of antimony, Sb(V)) were determined in promastigotes and intramacrophage amastigotes, respectively. The epidemiological cutoff (ECOFF) that allowed us to differentiate between Leishmania species causing cutaneous or visceral leishmaniases that were susceptible (S+) or insusceptible (S-) to the trivalent form of antimony was determined. The computed IC50 cutoff values were 23.83 μg/mL and 15.91 μg/mL for VL and CL, respectively. We report a trend of increasing antimony susceptibility in VL isolates during the 30-year period. In contrast, an increase in the frequency of S- phenotypes in isolates causing CL was observed during the same period. In our study, the emergence of S- phenotypes correlates with the inclusion of L. killicki (syn: L. tropica) isolates that cause cutaneous leishmaniasis and that have emerged in Algeria during the last decade.Conclusion/SignificanceOur results provide insight into the spatiotemporal dynamics of Leishmania antimony susceptibility in Algeria. We highlight the need for the future implementation of an effective methodology to determine the antimony susceptibility status of Leishmania isolates to detect the emergence of and prevent the dissemination of drug-resistant strains.

In Vitro Benznidazole and Nifurtimox Susceptibility Profile of Trypanosoma cruzi Strains Belonging to Discrete Typing Units TcI, TcII, and TcV

“…This is obtained by computing the epidemiological cut-off value (CO wt ) of natural T. cruzi populations [24]. This methodological approach has already been used to delineate wild-type (susceptible) Leishmania parasites from those with lower susceptibility (not wild-type forms) [25,26]. As a first step we compute the susceptibility threshold (CO wt ) of T. cruzi epimastigotes, trypomastigotes, and amastigotes against BZN and NFX from a panel of previously characterized strains [22], and investigate the frequency of the sensitive (wild type) phenotype within 3 DTUs, namely TcI, TcII, and TcV.…”

Antioxidant and Leishmanicidal Evaluation of Pulicaria Inuloides Root Extracts: A Bioguided Fractionation

“…In particular, Algeria is endemic for cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) [2]. CL, also called "Biskra boil" in the local language, is a serious public health problem because the country has the second largest focus in the Pathogens 2019, 8,201 2 of 11 world after Afghanistan. It is reported to be endemic in 328 third sub-national administrative levels with 10 million populations at risk, rising 13106 numbers of cases reported in 2017 [3].…”

“…The treatment of the population is provided free of charge in the public sector, with the following antileishmanial medicines included in the national List of Essential Medicines: amphotericin B deoxycholate, liposomal amphotericin B and meglumine antimoniate [6,7]. In spite of the high prevalence, current chemotherapy for leishmaniasis is compromised by high cost, toxicity associated with long-term treatments, route of administration, drug resistance, and different strain sensitivity to the available drugs [8]. These drawbacks lead to an urgent need to develop new treatments with acceptable efficacy and safety profile.…”

Leishmanicidal and Cytotoxic Activity of Algerian Medicinal Plants on Leishmania major and Leishmania infantum

“…Three species are prevalent in Algeria; Leishmania infantum in the north of the country is responsible for cutaneous and visceral leishmaniasis, Leishmania killicki CL occurs in single foci of Ghardaia in the central south of Algeria, and Leishmania major CL accounts for most cutaneous form cases. Leishmania major predominates in extremely different foci and ecosystems and infects humans, rodents, and sandflies [5][6][7].…”

“…3 costs and growing resistance [8,9,10]. Currently, there is a need for the development of safer and more effective drugs against leishmaniasis, especially in Algeria, where Glucantime ® is the primary treatment [7].…”