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Clinical and parasitological factors in parasite persistence after treatment and clinical cure of cutaneous leishmaniasis.

ABSTRACT:

Background

The determinants of parasite persistence or elimination after treatment and clinical resolution of cutaneous leishmaniasis (CL) are unknown. We investigated clinical and parasitological parameters associated with the presence and viability of Leishmania after treatment and resolution of CL caused by L. Viannia.

Methods

Seventy patients who were treated with meglumine antimoniate (n = 38) or miltefosine (n = 32) and cured, were included in this study. Leishmania persistence and viability were determined by detection of kDNA and 7SLRNA transcripts, respectively, before, at the end of treatment (EoT), and 13 weeks after initiation of treatment in lesions and swabs of nasal and tonsillar mucosa.

Results

Sixty percent of patients (42/70) had evidence of Leishmania persistence at EoT and 30% (9/30) 13 weeks after treatment initiation. A previous episode of CL was found to be a protective factor for detectable Leishmania persistence (OR: 0.16, 95%CI: 0.03-0.92). kDNA genotyping could not discern differences between parasite populations that persisted and those isolated at diagnosis.

Conclusions

Leishmania persist in skin and mucosal tissues in a high proportion of patients who achieved therapeutic cure of CL. This finding prompts assessment of the contribution of persistent infection in transmission and endemicity of CL, and in disease reactivation and protective immunity.

SUBMITTER: Martinez-Valencia AJ

PROVIDER: S-EPMC5526576 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Publications

Clinical and parasitological factors in parasite persistence after treatment and clinical cure of cutaneous leishmaniasis.

Martínez-Valencia Alvaro J AJ Daza-Rivera Carlos Frisherald CF Rosales-Chilama Mariana M Cossio Alexandra A Casadiego Rincón Elkin J EJ Desai Mayur M MM Saravia Nancy Gore NG Gómez María Adelaida MA

PLoS neglected tropical diseases 20170713 7

<h4>Background</h4>The determinants of parasite persistence or elimination after treatment and clinical resolution of cutaneous leishmaniasis (CL) are unknown. We investigated clinical and parasitological parameters associated with the presence and viability of Leishmania after treatment and resolution of CL caused by L. Viannia.<h4>Methods</h4>Seventy patients who were treated with meglumine antimoniate (n = 38) or miltefosine (n = 32) and cured, were included in this study. Leishmania persiste ...[more]

PMID: 28704369

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Project description: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.

Project description:BackgroundThe contribution of individuals with subclinical infection to the transmission and endemicity of cutaneous leishmaniasis (CL) is unknown. Immunological evidence of exposure to Leishmania in residents of endemic areas has been the basis for defining the human population with asymptomatic infection. However, parasitological confirmation of subclinical infection is lacking.MethodsWe investigated the presence and viability of Leishmania in blood and non-invasive mucosal tissue samples from individuals with immunological evidence of subclinical infection in endemic areas for CL caused by Leishmania (Viannia) in Colombia. Detection of Leishmania kDNA was conducted by PCR-Southern Blot, and parasite viability was confirmed by amplification of parasite 7SLRNA gene transcripts. A molecular tool for genetic diversity analysis of parasite populations causing persistent subclinical infection based on PCR amplification and sequence analysis of an 82bp region between kDNA conserved blocks 1 and 2 was developed.Principal findingsPersistent Leishmania infection was demonstrated in 40% (46 of 114) of leishmanin skin test (LST) positive individuals without active disease; parasite viability was established in 59% of these (27 of 46; 24% of total). Parasite burden quantified from circulating blood monocytes, nasal, conjunctival or tonsil mucosal swab samples was comparable, and ranged between 0.2 to 22 parasites per reaction. kDNA sequences were obtained from samples from 2 individuals with asymptomatic infection and from 26 with history of CL, allowing genetic distance analysis that revealed diversity among sequences and clustering within the L. (Viannia) subgenus.ConclusionsOur results provide parasitological confirmation of persistent infection among residents of endemic areas of L. (Viannia) transmission who have experienced asymptomatic infection or recovered from CL, revealing a reservoir of infection that potentially contributes to the endemicity and transmission of disease. kDNA genotyping establishes proof-of-principle of the feasibility of genetic diversity analysis in previously inaccessible and unexplored parasite populations in subclinically infected individuals.

Project description:BackgroundTo date, there is no specific literature available on the determinants for therapeutic failure (TF) with meglumine antimoniate (MA) in Northwestern-Argentina. This study aimed to identify epidemiological, clinical, and treatment-related factors that could be involved in TF.Methodology/principal findingsWe performed a case-control study. Cases were represented by patients who showed TF after administration of the first course of MA treatment, whereas, controls were determined as patients who evolved towards healing after the first MA cycle received. Crude Odds Ratios and their corresponding 90% confidence intervals (CI) were calculated, and risk factors were then tested by multivariate analysis using logistic binary regression. Three hundred and eighty-four patients with a presumptive diagnosis of ACL were recruited, and 153 with a positive diagnosis were selected. We included in the study 71 patients, who underwent specific treatment with MA, presented complete data on response to treatment, and had a minimum post-treatment follow-up of 6 months in cutaneous leishmaniasis, and 12 months in mucosal leishmaniasis. Of these, 34 (47.9%) presented TF. In the initial analysis, TF was significantly associated with the geographical area of disease acquisition (p = 0.036), the presence of mucosal lesions (p = 0.042), the presence of concomitant skin and mucosal lesions (p = 0.002), and lesion age ≥ 6 months (p = 0.018). Risk factors influencing TF in the final multivariate model included the geographical area where the disease was acquired (adjusted Odd Ratio 8.062; 95% CI 1.914-33.959; p = 0.004), and lesion age ≥ 6 months (adjusted Odd Ratio 10.037; 95% CI 1.383-72.843; p = 0.023).Conclusions/significanceThe results of the present study suggest the existence of some risk factors linked to TF in Northwestern-Argentina, which deserve further investigation. Herein we recorded a high percentage of TF and we described clinical and epidemiological characteristics associated with TF that could be taken into account improving the clinical management of patients.

Dataset Information

Clinical and parasitological factors in parasite persistence after treatment and clinical cure of cutaneous leishmaniasis.

Background

Methods

Results

Conclusions

Publications

Clinical and parasitological factors in parasite persistence after treatment and clinical cure of cutaneous leishmaniasis.

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