Establishment of a cohort of HC of CL patients in <i>L. braziliensis</i> endemic area.

<p>Establishment of a cohort of HC of CL patients in <i>L. braziliensis</i> endemic area.</p

Demographic and epidemiologic features of patients with cutaneous leishmaniasis and household contacts with and without evidence of immune response to leishmania antigen.

<p>Values with identical superscripts are significantly different. Statistical tests and p-values are below.</p><p>P-values for pair-wise Bonferroni post-hoc tests:</p>a<p> = 0.002,</p>b<p> = 0.004,</p>c<p> = 0.005,</p>d<p> = 0.003,</p>e<p> = 0.009,</p>f<p><0.001.</p>*<p>one-way ANOVA test.</p>**<p>Pearson's chi-square test.</p>***<p>before 4:00 pm.</p

Correlation between IFN-γ and CXCL10 production to soluble <i>Leishmania</i> antigen.

<p>The data was obtained from 54 household contacts (HC) with evidence of immune response and 51 household contacts without evidence of immune response which were selected among individuals living in the same households as HC with evidence of immune response. Values of IFN-γ (pg/ml) and CXCL10 (pg/ml) from 105 HC were plotted in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001947#pntd-0001947-g003" target="_blank">Figure 3</a> and these data were analyzed by the Spearman correlation test. P<0.0001, r = 0,74.</p

Production of CXCL9 and CXCL10 in cultures with or without stimulation with soluble <i>Leishmania</i> antigen.

<p>Aliquots of 1 ml of heparinized peripheral blood were cultured in the absence (medium) or stimulated with SLA for 72 hours. Chemokines production was determined by ELISA and results are expressed as pg/ml. Figure A shows the data obtained for CXCL9 and Figure B CXCL10. Values statistically different are indicated as: *** p<0.0001; *p<0.05; Wilcoxon test; GraphPad Prism 4. Medium; SLA.</p

Spontaneous and SLA induced IFN-γ and chemokines production by cells of household contacts of cutaneous leishmaniasis patients with and without evidence of immune response to leishmania antigen.

<p>Values with identical super-scripts are significantly different. Statistical tests and p-values are below:</p><p>P-values for Kruskal Wallis Dunn's post test:</p>a<p><0.05,</p>b<p><0.001,</p>c<p><0.001,</p>d<p><0.001,</p>e<p><0.001,</p>f<p><0.001,</p>g<p><0.001,</p>h<p><0.001,</p>i<p> = <0.001,</p>j<p> = 0.01,</p>k<p><0.001,</p>l<p><0.001,</p>m<p><0.001,</p>n<p><0.001.</p>*<p>one-way ANOVA test;</p>**<p>Kruskal Wallis test;</p>***<p><a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001947#s3" target="_blank">Results</a> expressed as Median value (inter-quartile range).</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 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

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

Atypical (ACL) and localized cutaneous leishmaniasis (CL) cases distribute similarly in Corte de Pedra, Brazil.

<p>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.</p