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. 2016 Dec 1;10(12):e0005100.
doi: 10.1371/journal.pntd.0005100. eCollection 2016 Dec.

Atypical Manifestations of Cutaneous Leishmaniasis in a Region Endemic for Leishmania braziliensis: Clinical, Immunological and Parasitological Aspects

Affiliations

Atypical Manifestations of Cutaneous Leishmaniasis in a Region Endemic for Leishmania braziliensis: Clinical, Immunological and Parasitological Aspects

Luiz Henrique Guimarães et al. PLoS Negl Trop Dis. .

Abstract

Background: Atypical cutaneous leishmaniasis (ACL) has become progressively more frequent in Corte de Pedra, Northeast Brazil. Herein we characterize clinical presentation, antimony response, cytokine production and parasite strains prevailing in ACL.

Methodology/principal findings: Between 2005 and 2012, 51 ACL (cases) and 51 temporally matched cutaneous leishmaniasis (CL) subjects (controls) were enrolled and followed over time in Corte de Pedra. Clinical and therapeutic data were recorded for all subjects. Cytokine secretion by patients' peripheral blood mononuclear cells (PBMC) stimulated with soluble parasite antigen in vitro, and genotypes in a 600 base-pair locus in chromosome 28 (CHR28/425451) of the infecting L. (V.) braziliensis were compared between the two groups. ACL presented significantly more lesions in head and neck, and higher rate of antimony failure than CL. Cytosine-Adenine substitutions at CHR28/425451 positions 254 and 321 were highly associated with ACL (p<0.0001). In vitro stimulated ACL PBMCs produced lower levels of IFN-γ (p = 0.0002) and TNF (p <0.0001), and higher levels of IL-10 (p = 0.0006) and IL-17 (p = 0.0008) than CL PBMCs.

Conclusions/significance: ACL found in Northeast Brazil is caused by distinct genotypes of L. (V.) braziliensis and presents a cytokine profile that departs from that in classical CL patients. We think that differences in antigenic contents among parasites may be in part responsible for the variation in cytokine responses and possibly immunopathology between CL and ACL.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Examples of common presentations found among atypical cutaneous leishmaniasis (ACL) patients in Corte de Pedra region, Northeast Brazil.
(A) Crusted, (B) verrucous, (C) lupoid, (D) Zoster-like and (E) vegetative lesion. Pictures depict actual ACL study subjects. All patients whose photographs are shown gave their permission to publish the pictures after the photographing author (LHG) identified himself and explained the purpose of the photograph.
Fig 2
Fig 2. Atypical (ACL) and localized cutaneous leishmaniasis (CL) cases distribute similarly in Corte de Pedra, Brazil.
ACL (N = 51) and temporally matched CL (N = 51) cases diagnosed between 2005 and 2012 in Corte de Pedra were mapped, and the resulting sets of geographic events were statistically compared. Black dots and red triangles correspond to ACL and CL patients, respectively. Total number of dots and triangles plotted is smaller than the actual number of corresponding cases due to overlap of some patients' geographic coordinates. The two manifestations of leishmaniasis present similar distributions in Corte de Pedra, with Cuzick and Edward ́s comparison yielding non-significant (p = 0.26). For details refer to Methods section.
Fig 3
Fig 3. Cytokine levels in supernatants of peripheral blood monuclear cells from atypical (ACL) and localized cutaneous leishmaniasis (CL) patients stimulated with L. (V.) braziliensis soluble antigen (SLA) in vitro.
Levels of IFN-γ, TNF and IL-10 were determined by ELISA in culture supernatants of PBMCs stimulated in vitro with SLA for 72 h. Levels of IL-17 were determined after 96 h of stimulation. Data are expressed in pg/mL. Black and white columns depict average cytokine levels produced by ACL and CL patients, respectively. Bars denote standard error of the means. All comparisons rendered significant to p<0.001 by Mann Whitney test.

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