Enhanced activation of blood neutrophils and monocytes in patients with Ethiopian localized cutaneous leishmaniasis in response to Leishmania aethiopica Neutrophil activation in Ethiopian cutaneous leishmaniasis

Acta Tropica ◽  
2021 ◽  
pp. 105967
Author(s):  
Menberework Chanyalew ◽  
Markos Abebe ◽  
Birtukan Endale ◽  
Selfu Girma ◽  
Geremew Tasew ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Neutrophil Activation ◽  
Leishmania Aethiopica ◽  
Blood Neutrophils

scholarly journals Cutaneous Leishmaniasis Due to Leishmania aethiopica

2018 ◽  
Vol 6 ◽  
pp. 69-81 ◽  
Author(s):  
Saskia van Henten ◽  
Wim Adriaensen ◽  
Helina Fikre ◽  
Hannah Akuffo ◽  
Ermias Diro ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Aethiopica

scholarly journals Profiles of Local and Systemic Inflammation in the Outcome of Treatment of Human Cutaneous Leishmaniasis Caused by Leishmania (Viannia)

2019 ◽  
Vol 88 (3) ◽  
Author(s):  
Adriana Navas ◽  
Olga Fernández ◽  
Carolina Gallego-Marín ◽  
María del Mar Castro ◽  
Mariana Rosales-Chilama ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Treatment Failure ◽  
Cutaneous Leishmaniasis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Neutrophil Activation ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Biopsy Specimens

ABSTRACT The immune mechanisms that contribute to the efficacy of treatment of cutaneous leishmaniasis (CL) are not fully understood. The aim of this study was to define immune correlates of the outcome of treatment of CL caused by Leishmania (Viannia) species during standard of care treatment with pentavalent antimonials. We conducted a comparative expression profiling of immune response genes in peripheral blood mononuclear cells (PBMCs) and lesion biopsy specimens obtained from CL patients before and at the end of treatment (EoT) with meglumine antimoniate. The ex vivo response of PBMCs to L. (V.) panamensis partially reflected that of lesion microenvironments. Significant downregulation of gene expression profiles consistent with local innate immune responses (monocyte and neutrophil activation and chemoattractant molecules) was observed at EoT in biopsy specimens of patients who cured (n = 8), compared to those from patients with treatment failure (n = 8). Among differentially expressed genes, pretreatment expression of CCL2 was significantly predictive of the therapeutic response (receiver operating characteristic [ROC] curve, area under the curve [AUC] = 0.82, P = 0.02). Polymorphisms in regulatory regions of the CCL2 promoter were analyzed in a pilot cohort of DNA samples from CL patients (cures, n = 20, and treatment failure, n = 20), showing putative association of polymorphisms rs13900(C/T) and rs2857656(G/C) with treatment outcome. Our data indicate that dampening gene expression profiles of monocyte and neutrophil activation characterize clinical cure after treatment of CL, supporting participation of parasite-sustained inflammation or deregulated innate immune responses in treatment failure.

scholarly journals Optimization of Methods for the Accurate Characterization of Whole Blood Neutrophils

2021 ◽  
Author(s):  
Ashley N. Connelly ◽  
Richard P.H. Huijbregts ◽  
Harish C. Pal ◽  
Valeriya Kuznetsova ◽  
Marcus D. Davis ◽  
...  
Keyword(s):  
Whole Blood ◽  
Neutrophil Activation ◽  
Immune Defense ◽  
Experimental Conditions ◽  
Adaptive Immune ◽  
Blood Neutrophils ◽  
One Step ◽  
And Function ◽  
Adaptive Immune Systems

Abstract Neutrophils are the most abundant circulating leukocyte population with critical roles in immune defense, regulation of innate and adaptive immune systems, and disease pathogenesis. Our progress in understanding precise mechanisms of neutrophil activation, recruitment, and function has been hampered by the lack of optimized and standardized methods for the characterization and phenotyping of this readily activated population. By comparing eight methods of neutrophil characterization, we demonstrate that the level of neutrophil activation and degranulation is associated with specific experimental conditions and the number and type of manipulation steps employed. Staining whole blood at 4ºC and removal of remaining unbound antibodies prior to one-step fixation and red blood cell lysis minimizes neutrophil activation, decreases phenotypic alterations during processing, and prevents nonspecific antibody binding. The effects of anticoagulants used for collection, processing delays, and time and temperature during sample analysis on neutrophil phenotype are addressed. The presented data provide a foundation for higher quality standards of neutrophil characterization improving consistency and reproducibility among studies.

scholarly journals Miltefosine for the treatment of cutaneous leishmaniasis—A pilot study from Ethiopia

2021 ◽  
Vol 15 (5) ◽  
pp. e0009460
Author(s):  
Saskia van Henten ◽  
Annisa Befekadu Tesfaye ◽  
Seid Getahun Abdela ◽  
Feleke Tilahun ◽  
Helina Fikre ◽  
...  
Keyword(s):  
Side Effects ◽  
Cutaneous Leishmaniasis ◽  
Systemic Treatment ◽  
Initial Response ◽  
Tablet Form ◽  
Leishmania Aethiopica ◽  
Mucosal Involvement ◽  
Observational Cohort ◽  
Good Improvement ◽  
Favorable Side Effect Profile

Background Cutaneous leishmaniasis (CL) in Ethiopia, caused by Leishmania aethiopica, is often severe and hard to treat compared to CL caused by other species elsewhere. Miltefosine is the only oral anti-leishmanial drug, with a favorable side-effect profile compared to routinely available sodium stibogluconate (SSG), but evidence about its use for L. aethiopica is lacking. Methodology and principal findings In an observational cohort study, treatment outcomes, safety and adherence among CL patients who required systemic treatment and received miltefosine for 28 days in Boru Meda Hospital and University of Gondar Hospital were studied. Patient cure was defined as 100% flattening for non-ulcerated lesions and 100% flattening and 100% re-epithelization for ulcerated lesions. Outcomes were documented for day 28, 90 and 180, both per site, and pooled, adjusting for site as a fixed effect with effect coding. Among 94 included patients (32 in Gondar, 62 in Boru Meda), median lesion duration was 12 months, median size six cm, and mucosal involvement (46.8%) and diffuse (30.9%) lesions were common. Adherence to miltefosine was good, and side-effects were tolerable. Initial outcomes at day 28 were promising, with 68.8% and 94.0% of patients having good improvement or cure in Gondar and Boru Meda respectively. In Boru Meda, outcomes were good with 72.7% and 72.9% cure at day 90 and day 180 respectively. In Gondar, results were less promising, with only 12.5% and 26.7% cure at day 90 and day 180, although confidence intervals were wide. In pooled estimates, 48.7% of patients reached cure at day 180, and 32.3% relapsed. Outcomes were better in Boru Meda Hospital, for smaller lesions and for mucosal lesions. Conclusions/Significance Based on miltefosine’s good initial response, tolerable side-effects, tablet-form, we propose to include miltefosine for future clinical trials using extended treatment schedules, combination therapy, or targeting specific subgroups. Trial registration ClinicalTrials.gov NCT04004754.

scholarly journals Treatment of Cutaneous Leishmaniasis Caused by Leishmania aethiopica: A Systematic Review

2016 ◽  
Vol 10 (3) ◽  
pp. e0004495 ◽  
Author(s):  
Johan van Griensven ◽  
Endalamaw Gadisa ◽  
Abraham Aseffa ◽  
Asrat Hailu ◽  
Abate Mulugeta Beshah ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Aethiopica

scholarly journals Leishmaniasis recidivans in Ethiopia: cutaneous and mucocutaneous features

2017 ◽  
Vol 11 (01) ◽  
pp. 106-110 ◽  
Author(s):  
Federica Dassoni ◽  
Frehiwot Daba ◽  
Bernard Naafs ◽  
Aldo Morrone
Keyword(s):  
Cutaneous Leishmaniasis ◽  
New World ◽  
Leishmania Braziliensis ◽  
Leishmania Tropica ◽  
Clinical Form ◽  
Leishmania Aethiopica ◽  
Mucosal Involvement ◽  
Leishmania Panamensis ◽  
First Time ◽  
Leishmania Guyanensis

Cutaneous leishmaniasis (CL) is endemic in Ethiopia. An unusual clinical form of this disease is leishmaniasis recidivans (LR), a prolonged, relapsing form of cutaneous leishmaniasis resembling tuberculosis of the skin that may persist for many years with a chronic and relapsing course. This rare variant has been shown to be caused by Leishmania tropica species in the Old World and by Leishmania braziliensis, Leishmania amazonensis, Leishmania panamensis, and Leishmania guyanensis in the New World, as reported in various studies. To our knowledge, there are no reports from Ethiopia, and mucocutaneous involvement of LR has not been described to date. This was a retrospective analysis of the patients seen at the Italian Dermatological Center in Mekelle on the Tigrean highlands over a three-year period (2008–2011). Seven patients with typical clinical features of LR were seen. Two of them presented with signs of mucosal involvement. To date, Leishmania aethiopica is shown to be the only species causing CL that is endemic in the Ethiopian highlands. Therefore, it had to be assumed that the lesions in these patients were caused by this species. The aims of this communication are to report, for the first time, the presence of LR, most likely due to Leishmania aethiopica, in Ethiopia, and to report mucosal involvement in this rare clinical form of CL.

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