Clinical and Parasitological Features of Patients with American Cutaneous Leishmaniasis that Did Not Respond to Treatment with Meglumine Antimoniate

Abstract

BackgroundAmerican cutaneous leishmaniasis (ACL) is a complicated disease producing about 67.000 new cases per year. The severity of the disease depends on the parasite species; however in the vast majority of cases species confirmation is not feasible. WHO suggestion for ACL produced by Leishmania braziliensis, as first line treatment, are pentavalent antimonial derivatives (Glucantime or Sodium Stibogluconate) under systemic administration. According to different authors, pentavalent antimonial derivatives as treatment for ACL show a healing rate of about 75% and reasons for treatment failure are not well known.MethodsIn order to characterise the clinical and parasitological features of patients with ACL that did not respond to Glucantime, a cross-sectional observational study was carried out in a cohort of 43 patients recruited in three of the Colombian Army National reference centers for complicated ACL. Clinical and paraclinical examination, and epidemiological and geographic information were recorded for each patient. Parasitological, histopathological and PCR infection confirmation were performed. Glucantime IC50 and in vitro infectivity for the isolated parasites were estimated.ResultsPredominant infecting Leishmania species corresponds to L. braziliensis (95.4%) and 35% of the parasites isolated showed a significant decrease in in vitro Glucanatime susceptibility associated with previous administration of the medicament. Lesion size and in vitro infectivity of the parasite are negatively correlated with decline in Glucantime susceptibility (Spearman: r = (-)0,548 and r = (-)0,726; respectively).ConclusionA negative correlation between lesion size and parasite resistance is documented. L. braziliensis was found as the main parasite species associated to lesion of patients that underwent treatment failure or relapse. The indication of a second round of treatment in therapeutic failure of ACL, produced by L. braziliensis, with pentavalent antimonial derivatives is discussable.

Toward an objective diagnostic for detection of Leishmania RNA virus (LRV) in clinical samples from cutaneous leishmaniasis patients

“…The present study corresponds to a descriptive study with an experimental component using clinical samples (n=42) that had been collected previously. 21 samples collected from patients previously diagnosed as NRCL, of which 7 correspond to frozen biopsies and 14 to parasite isolates (34). 15 samples from patients with diagnosis of ML, of which 9 to frozen biopsies and 6 correspond to parasite isolates.…”

Natural Compounds and Extracts from Mexican Medicinal Plants with Anti-Leishmanial Activity: An Update

“…On the other hand, 24% of the new synthetic drugs have as a base molecule or are derived from, active molecules obtained from medicinal plants [8][9][10][11][12][13][14][15][16][17]. Another report states that between the years 2000-2005, 23 new natural-origin drugs were introduced into the market, all of which exhibited structural and biological diversity.…”

“…These compounds showed an IC 50 = 7.7-66.5 μM, respectively. In this study, some semisynthetic derivatives of these natural compounds were tested; the acetylated and methoxylated derivative [2′,4′-diacetoxi-3′-(3-methyl but-2-enyl)-chalcone (13) and 2′,4′-dimethoxy-3′-(3-methyl but-2-enyl)-chalcone (14)] were the most active, exhibiting an IC 50 = 3.10-11.70 μM against L. mexicana promastigotes, these semisynthetic derivates were more active than natural compounds [53].…”

“…Currently, treatment of leishmaniasis employs first-line drugs such as sodium stibogluconate (commercially known as Pentostam) and meglumine antimoniate (commercially known as Glucantime), and other options (second-line drugs) are pentamidine isothionate (commercially known as Pentamidine), amphotericin B, (Fungizone or Ambisome), miltefosine, and paramomycin sulfate (Aminosidine), although this latter option is not widely utilized in Mexico and is not effective when administered orally [11]. Even when administered in combination, the effectiveness of the drugs is less than optimal [12,13].…”

Leishmaniasis recidivans by Leishmania tropica in Central Rift Valley Region in Kenya

“…Control of CL is geared towards chemotherapy where the mainstay drugs are pentavalent antimonials (Rai et al, 2013;de Vries et al, 2015). Sodium stibogluconate (SSG) has been used worldwide for the treatment of CL for many decades (Frézard et al, 2014), however, parasite resistance against the drug and other antimonials has recently been reported in different parts of the world (Croft et al, 2006;Sundar et al, 2000;Perez-Franco et al, 2016;Lira et al, 1999).…”