Histopathological findings in canine leishmaniasis ulcers.

(A) Dog 1 Ulcer with intense inflammation 4X. (B) Dog 1 Tissue granulation 20X. (C) Dog 5 Intense inflammation, plasma cells 40X. (D) Dog 26 Granuloma 20X. (E) Dog 1 Necrosis 20X. (F) Dog 2 Fibrosis (4X). (G) Dog 1 Amastigotes inside macrophage (arrow) 10X. (H) Dog 1 Amastigotes inside macrophage (arrow) 100X. (I) Dog 2 Fibrosis in blue (same of F) stained by Masson`s Trichrome 4X.</p

Cutaneous and mucosal lesions caused by <i>Leishmania (Viannia) braziliensis</i>.

The ulcerated lesions suggestive of ATL were located in the scrotal sac (A and B), muzzle (C and D) and ears (E and F), being, for the most part, single lesions, ulcerated or ulcero-crusted and of chronic evolution.</p

Clinical and demographic features of 61 dogs with ulcerated skin or mucosal lesions in the village of Corte de Pedra.

Clinical and demographic features of 61 dogs with ulcerated skin or mucosal lesions in the village of Corte de Pedra.</p

Frequency distribution of seven alleles in <i>L</i>. <i>braziliensis</i> locus CHR28/425451 among ATL patients and domestic dogs from Corte de Pedra, Bahia, Northeast Brazil.

Frequency distribution of seven alleles in L. braziliensis locus CHR28/425451 among ATL patients and domestic dogs from Corte de Pedra, Bahia, Northeast Brazil.</p

Histopathological findings in dogs with ulcerated lesions.

Histopathological findings in dogs with ulcerated lesions.</p

Clinical variables compared between 51 atypical (ACL) and 51 localized cutaneous leishmaniasis (CL) temporally matched patients from Corte de Pedra, Brazil.

<p>Clinical variables compared between 51 atypical (ACL) and 51 localized cutaneous leishmaniasis (CL) temporally matched patients from Corte de Pedra, Brazil.</p

Comparison of SNP haplotypes frequencies in locus CHR28/425451 between <i>L</i>. <i>(V</i>.<i>) braziliensis</i> isolated from 16 atypical (ACL) and 38 localized cutaneous leishmaniasis (CL) temporally matched patients from Corte de Pedra, Brazil.

<p>Comparison of SNP haplotypes frequencies in locus CHR28/425451 between <i>L</i>. <i>(V</i>.<i>) braziliensis</i> isolated from 16 atypical (ACL) and 38 localized cutaneous leishmaniasis (CL) temporally matched patients from Corte de Pedra, Brazil.</p

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

<div><p>Background</p><p>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.</p><p>Methodology/Principal Findings</p><p>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 <i>L</i>. <i>(V</i>.<i>) braziliensis</i> 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.</p><p>Conclusions/Significance</p><p>ACL found in Northeast Brazil is caused by distinct genotypes of <i>L</i>. <i>(V</i>.<i>) braziliensis</i> 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.</p></div

Comparison of SNP allele frequencies in locus CHR28/425451^* between <i>L. (V.) braziliensis</i> isolated from 16 atypical (ACL) and 38 localized cutaneous leishmaniasis (CL) temporally matched patients from Corte de Pedra, Brazil.

<p>SNPs in this table correspond to individual SNPs in haplotypes delineated in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0005100#pntd.0005100.t002" target="_blank">Table 2</a>.</p

Cytokine levels in supernatants of peripheral blood monuclear cells from atypical (ACL) and localized cutaneous leishmaniasis (CL) patients stimulated with <i>L</i>. <i>(V</i>.<i>) braziliensis</i> soluble antigen (SLA) in vitro.

<p>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.</p