Analysis of macrophage subtypes and annexin A1 expression in lesions of patients with cutaneous leishmaniasis

Abstract INTRODUCTION: Cutaneous leishmaniasis is caused by protozoa of the genus Leishmania and transmission occurs through the bite of sandflies. It is an infectious disease, which affects skin and mucosa. The aim was to quantify the macrophages M1 and M2 and the annexin A1 expression in the skin lesions of patients with cutaneous leishmaniasis. METHODS: Skin biopsies from patients (n = 50) were analyzed and classified according to the lesion type as: exudative cellular reaction, exudative granulomatous reaction, exudative necrotic reaction, exudative necrotic-granulomatous reaction. Using the immunofluorescence technique, macrophages were identified by CD163 marker, differentiated by anti-MHCII and anti-CD206 antibodies, and annexin A1 expression was determined by arbitrary unit (a.u.) densitometry. RESULTS: In M1 macrophages, a greater expression of this protein was observed in the exudative cellular reaction type lesions (136.3 ± 2.6 a.u., assuming mean and standard derivation) when compared to the expression in the lesions of exudative granulomatous reaction, exudative necrotic reaction and exudative necrotic-granulomatous reaction patients (108.0 ± 2.3, 121.6 ± 3.2 and 124.7 ± 2.4 a.u., respectively). Regarding M2 macrophages, it was observed that patients with exudative cellular reaction lesion also had a higher expression of this protein (128.8 ± 2.6 a.u.), when compared to the expression in the lesions of exudative granulomatous reaction, exudative necrotic reaction and exudative necrotic-granulomatous reaction patients (105.6 ± 2, 113.9 ± 2.8, 114.3 ± 2.1 a.u., respectively). CONCLUSIONS: These data suggest that annexin A1 is assisting macrophages in the phagocytosis process of patients with exudative cellular reaction lesion type.

Expression of annexin A1 in Leishmania-infected skin and its correlation with histopathological features

ABSTRACTINTRODUCTION:The aim of this study was quantify annexin A1 expression in macrophages and cluster of differentiation 4 (CD4) + and cluster of differentiation 8 (CD8)+ T cells from the skin of patients with cutaneous leishmaniasis (n=55) and correlate with histopathological aspects.METHODS:Infecting species were identified by polymerase chain reaction-restriction fragment length polymorphism, and expression of annexin A1 was analyzed by immunofluorescence.RESULTS:All patients (n = 55) were infected with Leishmania braziliensis . Annexin A1 was expressed more abundantly in CD163 + macrophages in infected skin (p < 0.0001) than in uninfected skin. In addition, macrophages in necrotic exudative reaction lesions expressed annexin A1 at higher levels than those observed in granulomatous (p < 0.01) and cellular lesions p < 0.05). This difference might be due to the need to clear both parasites and necrotic tissue from necrotic lesions. CD4 + cells in cellular lesions expressed annexin A1 more abundantly than did those in necrotic (p < 0.05) and granulomatous lesions (p < 0.01). Expression in CD8 + T cells followed the same trend. These differences might be due to the pervasiveness of lymphohistiocytic and plasmacytic infiltrate in cellular lesions.CONCLUSIONS:Annexin A1 is differentially expressed in CD163 + macrophages and T cells depending on the histopathological features of Leishmania -infected skin, which might affect cell activation.

Varicella zoster virus reactivation during or immediately following treatment of tegumentary leishmaniasis with antimony compounds

Antimony compounds are the cornerstone treatments for tegumentary leishmaniasis. The reactivation of herpes virus is a side effect described in few reports. We conducted an observational study to describe the incidence of herpes zoster reactivation during treatment with antimony compounds. The global incidence of herpes zoster is approximately 2.5 cases per 1,000 persons per month (or 30 cases per 1,000 persons per year). The estimated incidence of herpes zoster in patients undergoing antimony therapy is higher than previously reported.

Development and validation of PCR-based assays for diagnosis of American cutaneous leishmaniasis and identificatio nof the parasite species

In this study, PCR assays targeting different Leishmania heat-shock protein 70 gene (hsp70) regions, producing fragments ranging in size from 230-390 bp were developed and evaluated to determine their potential as a tool for the specific molecular diagnosis of cutaneous leishmaniasis (CL). A total of 70 Leishmania strains were analysed, including seven reference strains (RS) and 63 previously typed strains. Analysis of the RS indicated a specific region of 234 bp in the hsp70 gene as a valid target that was highly sensitive for detection of Leishmania species DNA with capacity of distinguishing all analyzed species, after polymerase chain reaction-restriction fragment length polymorfism (PCR-RFLP). This PCR assay was compared with other PCR targets used for the molecular diagnosis of leishmaniasis: hsp70 (1400-bp region), internal transcribed spacer (ITS)1 and glucose-6-phosphate dehydrogenase (G6pd). A good agreement among the methods was observed concerning the Leishmania species identification. Moreover, to evaluate the potential for molecular diagnosis, we compared the PCR targets hsp70-234 bp, ITS1, G6pd and mkDNA using a panel of 99 DNA samples from tissue fragments collected from patients with confirmed CL. Both PCR-hsp70-234 bp and PCR-ITS1 detected Leishmania DNA in more than 70% of the samples. However, using hsp70-234 bp PCR-RFLP, identification of all of the Leishmania species associated with CL in Brazil can be achieved employing a simpler and cheaper electrophoresis protocol.

Fatores associados ao insucesso do tratamento da leishmaniose cutânea com antimoniato de meglumina / Factors associated with treatmet failure of cutaneous leishmaniasis with meglumine antimoniate

Foram investigados os fatores associados ao insucesso do tratamento da leishmaniose cutânea com antimoniato de meglumina num servico de referência para leishmanioses, em Mato Grosso. Uma coorte histórica de 151 pacientes com diagnóstico de leishmaniose cutânea foi construída com informacões dos prontuários. A incidência de insucesso após o primeiro ciclo de antimonial foi 47 por cento (IC95 por cento=39,2 por cento-55 por cento). Dose de antimonial inferior a 10mg/kg/dia (RR=1,8; IC95:1,1-3,0), tratamento prévio para leishmaniose (RR=1,7; IC95:1,3-2,4), três ou mais lesões (RR=1,9; IC95:1,4-2,5), tratamento irregular (RR=1,9; IC95:1,3-2,6) e peso maior que 68kg (RR=1,7; IC95:1,1-2,5) foram associados ao insucesso terapêutico. Após ajuste, permaneceram associados ao insucesso os seguintes fatores: 3 ou mais lesões cutâneas (OR=4,6; IC95 por cento=1,2-17,4), tratamento anterior para leishmaniose tegumentar americana (OR=4,5; IC95 por cento=1,1-7,5), peso maior que 68kg (OR=4,3; IC95 por cento=1,5-11,9) e irregularidade no tratamento (OR=12,5; IC95 por cento=2,1-75,4), embora o peso possivelmente tenha sido associado ao insucesso devido à limitacão da dose máxima. Estes achados auxiliam na identificacão de pacientes com maior risco de insucesso no tratamento da leishmaniose cutânea com antimonial.

Entomoftoromicose (zigomicose) causada por Conidiobolus coronatus em Mato Grosso (Brasil): relato de caso / Entomophthoramycosis (zygomycosis) caused by Conidiobolus coronatus in Mato Grosso (Brazil): case report

Zigomicoses são micoses subcutâneas causadas por fungos do solo, que geralmente manifestam-se como uma infiltração granulomatosa crônica da submucosa nasal, estendendo-se para o tecido subcutâneo e pele da face. Descreve-se aqui o primeiro caso de zigomicose nasofacial causada pelo Conidiobolus coronatus, ocorrendo em Mato Grosso, Brasil.

Leishmaniose tegumentar no Estado do Mato Grosso (Brasil): estudo clínico, laboratorial e terapêutico / Tegumentary leishmaniasis in the State of Mato Grosso(Brazil): clinical, laboratoty and therapeutic studies

A expressão clínica da leishmaniose tegumentar americana (LTA) é variável e depende de alguns fatores, como a espécie de Leishmania envolvida, e da relação do parasito com seu hospedeiro. Avaliar clínica e laboratorialmente os pacientes com LTA atendidos no Ambulatório de Referência para Leishmanioses do Hospital Universitário Júlio Müler (ARL-HUJM) da Universidade Federal do Mato Grosso, Brasil, e identificar no nível de complexo as espécies de Leishmania causadoras da doença. Foram estudados pacientes de LTA atendidos por demanda espontânea, entre mai/97 a fev/98, no ARL-HUJM. Para a inclusão no presente estudo foram considerados critérios clínicos, laboratoriais e terapêuticos. Sessenta e sete pacientes foram incluídos no estudo. Predominaram adultos jovens, trabalhadores rurais, com lesão cutânea ulcerada e única, acometendo preerencialmente as extremidades. A resolução das lesões ocorreu de forma precoce após a terapêutica antinomial pentavalente, exceto nas formas mucosas. Dos parasitos isolados 96,4 por cento percenciam ao complexo Leishmania braziliensis. Embora este estudo não permita concluir pela magnitude do problema da LTA no Estado de Mato Grosso, ele sugere que a LTA consitui um problema de saúde pública, havendo necessidade de caracterização do ciclo epidemiológico, incluindo a identificação da espécie, a fim de serem adotadas medidas de controle

Paracoccidioidomicose ocular: relato de um caso de doença multifocal com envolvimento da pálpebra e, presumivelmente, da córnea, vítreo e retina / Ocular paracoccidioidomycosis with palpebral involvement, and with probable corneal, vitreous and retinal damages: a case report

E descrito um caso de paracoccidioidomicose multifocal com comprometimento da pálpebra, córnea, vítreo e retina que, apesar da boa resposta à terapêutica antimicótica, evoluiu com sinéquia palpebral e perda total da visäo do olho direito. Os autores alertam para a necessidade de investigaçäo sistemática do olho em portadores da doença multifocal que apresentem qualquer sintoma ocular.