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L. (viannia) braziliensis infection causes American Tegumentary Leishmaniasis (ATL), with prolonged time to healing lesions. The potent inflammatory response developed by the host is important to control the parasite burden and infection however an unbalanced immunity may cooperate to the tissue damage observed. The range of mechanisms underlying the pathological responses associated with ATL still needs to be better understood. That includes epigenetic regulation by non-coding MicroRNAs (miRNAs), non-coding sequences around 22 nucleotides that act as post-transcriptional regulators of RNAs encoding proteins. The miRNAs have been associated with diverse parasitic diseases, including leishmaniasis. Here we evaluated miRNAs that targeted genes expressed in cutaneous leishmaniasis lesions (CL) by comparing its expression in both CL and normal skin obtained from the same individual. In addition, we evaluated if the miRNAs expression would be correlated with clinical parameters such as therapeutic failure, healing time as well as lesion size. The miR-361-3p and miR-140-3p were significantly more expressed in CL lesions compared to normal skin samples (p = 0.0001 and p < 0.0001, respectively). In addition, the miR-361-3p was correlated with both, therapeutic failure and healing time of disease (r = 0.6, p = 0.003 and r = 0.5, p = 0.007, respectively). In addition, complementary analysis shown that miR-361-3p is able to identify with good sensitivity (81.2%) and specificity (100%) patients who tend to fail initial treatment with pentavalent antimonial (Sbv). Finally, the survival analysis considering “cure” as the endpoint showed that the higher the expression of miR-361-3p, the longer the healing time of CL. Overall, our data suggest the potential of miR-361-3p as a prognostic biomarker in CL caused by L. braziliensis.

This paper records the plants used in the treatment of cutaneous leishmaniasis due to Leishmania (Viannia) braziliensis (L(V)b) among the rural population of a cocoa- producing coastal area of Bahia state, Brazil. An enquiry conducted among a hundred patients identified 49 plant species used to treat skin ulceration caused by this Leishmania species. The principal plants used are caju-branco (Anacardium occidentale - Anacardiaceae), used by 65% of the population, folha-fogo (Clidemia hirta - Melastomataceae) 39%, alfavaca-grossa (Plectranthus amboinicus - Lamiaceae) 33%, mastruz (Chenopodium ambrosioides - Chenopodiaceae) 31%, erva-de-santa-maria (Solatium americanum - Solanaceae) (25%) and transagem (Plantago major - Plantaginaceae.) 2%.

Os autores relatam que durante 14 anos de trabalho clínico em campo, realizado nas comunidades de Três Braços e Corte de Pedra, Bahia, acompanharam 1.416 pacientes portadores de Leishmaniose Tegumentar Americana, cuja espécie envolvida na transmissão, é predominantemente a Leishmania Viannia brasilienses. A terapêutica utilizada rotineiramente nos casos é o antimoniato-N-metilglucamina (Glucantime). Contudo, 16 pacientes do sexo masculino recusaram-se a utilizar a medicação e 6 do sexo feminino encontravam-se em período gestacional, portanto não utilizaram o medicamento. Estes pacientes foram acompanhados por um período entre 4 a 12 anos, a partir do diagnóstico. Observou-se que em 9 pacientes (40,9%) desta casuística, o tempo de cicatrizaçâo após o aparecimento da lesão, pode ser calculado em 6 meses de evolução. Quando se eleva a observação para 12 meses, temos que 19 pacientes (86,3%) cicatrizaram suas lesões neste período. Em 3 casos (13,6%) as lesões permaneceram ativas por mais de 12 meses. Conclui-se que os determinantes da cicatrizaçâo natural das lesões produzidas por Leishmania Viannia Braziliensis permanecem desconhecidos, dificultando para nós entendermos e compararmos aos efeitos das drogas utilizadas no tratamento da leishmaniose tegumentar.

De acordo com o cadastro de 1416 pacientes portadores de leishmaniose tegumentar americana (L. T.A) referentes ao período de janeiro de 1976 a maio de 1987, os autores realizaram um levantamento da procedência dos casos dessa parasitose atendidos nas áreas endêmicas de Três Braços e Corte de Pedra no estado da Bahia. Os pacientes procediam de 24 dos 89 municípios que compõem a região cacaueira da Bahia, destacando-se os municípios de Valença, Wenceslau Guimarães e Teolândia como os de maior prevalência, somando juntos 923 casos (65,1%), com 520 destes residindo em umas poucas localidades contínuas entre si, formando uma área endêmica, com transmissão ocorrendo provavelmente no peri, intradomicílio e nas lavouras de cacau e cravo localizadas nas encostas da floresta atlântica. Nota-se que a partir de 1983, houve um aumento do número de casos em toda a região, havendo evidências da leishmaniose tegumentar americana comportasse como uma doença ocupacional em toda a região estudada.An analysis of 1416 records of patients with American tegumentary leishmaniasis recorded from 1976 to 1987 in the endemic areas of Três Braços and Corte de Pedra as regards details of the origin of the patient was performed. The patients came from 24 of the 89 municipalities which constitute the cocoa growing zone of Bahia. The municipalities of Valença, Wenceslau Guimarães and Teolândia had the highestprevalence accounting for 923 cases (65,1 %). Five hundred twenty of these cases lived in ten localities which form an endemic area with transmission probably occurring in the peri and intradomiciliary area, as well as the plantations of cocoa and cloves. We note that from 1983 there has been an increase in the number of cases throughout the region. There is evidence that tegumentary leishmaniasis in an ocupational disease in the region under study.

BackgroundLeishmaniases are neglected tropical diseases that inflict great burden to poor areas of the globe. Intense research has aimed to identify parasite genetic signatures predictive of infection outcomes. Consistency of diagnostic tools based on these markers would greatly benefit from accurate understanding of Leishmania spp. population genetics. We explored two chromosomal loci to characterize a population of L. braziliensis causing human disease in Northeast Brazil.Methodology/principal findingsTwo temporally distinct samples of L. braziliensis were obtained from patients attending the leishmaniasis clinic at the village of Corte de Pedra: (2008-2011) primary sample, N = 120; (1999-2001) validation sample, N = 35. Parasites were genotyped by Sanger's sequencing of two 600 base pairs loci starting at nucleotide positions 3,074 and 425,451 of chromosomes 24 and 28, respectively. Genotypes based on haplotypes of biallelic positions in each locus were tested for several population genetic parameters as well as for geographic clustering within the region. Ample geographic overlap of genotypes at the two loci was observed as indicated by non-significant Cusick and Edward's comparisons. No linkage disequilibrium was detected among combinations of haplotypes for both parasite samples. Homozygous and heterozygous genotypes displayed Hardy-Weinberg equilibrium (HWE) at both loci in the two samples when straight observed and expected counts were compared by Chi-square (p>0.5). However, Bayesian statistics using one million Monte-Carlo randomizations disclosed a less robust HWE for chromosome 24 genotypes, particularly in the primary sample (p = 0.04). Fixation indices (Fst) were consistently lower than 0.05 among individuals of the two samples at both tested loci, and no intra-populational structuralization could be detected using STRUCTURE software.Conclusions/significanceThese findings suggest that L. braziliensis can maintain stable populations in foci of human leishmaniasis and are capable of robust genetic recombination possibly due to events of sexual reproduction during the parasite's lifecycle.

Os autores relatam o caso de uma criança portadora de Leishmaniose Tegumentar Americana causada por Leishmania braziliensis braziliensis que foi infectada durante a amamentação, desenvolvendo lesão infiltrativa e nodular nos lábios, com posterior disseminação para os seios da face, fossas nasais e pavilhão auricular e cuja evolução clinica pós-terapêutica caracterizou-se por períodos sucessivos de regressão e de reativação da lesão. Enfatizam a gravidade do caso, e as dificuldades terapêuticas com a utilização dos antimoniais pentavalentes, antimoniato-N-metil glucamina (Glucantime) e o stibogluconato de sódio(Pentostam).The authors report a case of a child infected with Leishmania viannia braziliensis during breast feeding, who developed an infiltrated, granulomatous lesion of the lips, followed by dissemination to the face, nasal fossae and external ears. Post therapeutic clinical evolution was characterized by periods of regression and lesion reactivation. The seriousness of the case, and the therapeutic difficulties with the utilization of pentavalent antimonials, meglumine antimoniate (glucantime) and sodium stibogluconate (Pentostam) are discussed.

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

Cutaneous leishmaniasis due to L. braziliensis (CL) is characterized by a positive delayed type hypersensitivity test (DTH) leishmania skin test (LST) and high IFN-γ production to soluble leishmania antigen (SLA). The LST is used for diagnosis of CL and for identification of individuals exposed to leishmania infection but without disease. The main aim of the present study was to identify markers of exposure to L. braziliensis infection. METHODOLGY/PRINCIPAL FINDINGS: This cohort study enrolled 308 household contacts (HC) of 76 CL index cases. HC had no active or past history of leishmaniasis. For the present cross-sectional study cytokines and chemokines were determined in supernatants of whole blood culture stimulated with SLA. Of the 308 HC, 36 (11.7%) had a positive LST but in these IFN-γ was only detected in 22 (61.1%). Moreover of the 40 HC with evidence of IFN-γ production only 22 (55%) had a positive LST. A total of 54 (17.5%) of 308 HC had specific immune response to SLA. Only a moderate agreement (Kappa = 0.52; 95% CI: 0.36-0.66) was found between LST and IFN-γ production. Moreover while enhancement of CXCL10 in cultures stimulated with SLA was observed in HC with DTH+ and IFN-γ+ and in patients with IFN-γ(+) and DTH(-), no enhancement of this chemokine was observed in supernatants of cells of HC with DTH(+) and IFN-γ(-).This study shows that in addition of LST, the evaluation of antigen specific IFN-γ production should be performed to determine evidence of exposure to leishmania infection. Moreover it suggests that in some HC production of IFN-γ and CXCL10 are performed by cells not involved with DTH reaction.