Short communication: The miR-155a-5p is correlated with increased ROS and impaired apoptosis in macrophages infected by Leishmania braziliensis.

Cutaneous leishmaniasis (CL) caused by Leishmania braziliensis, is a disease characterized by well-limited ulcerated lesions with raised borders in exposed parts of the body. miRNAs are recognized for their role in the complex and plastic interaction between host and pathogens, either as part of the host's strategy to neutralize infection or as a molecular mechanism employed by the pathogen to modulate host inflammatory pathways to remain undetected. The mir155 targets a broad range of inflammatory mediators, following toll-like receptors (TLRs) signaling. In this work, we evaluated the effects of the expression of miR155a-5p in human macrophages infected with L. braziliensis. Our results show that miR155a-5p is inversely correlated with early apoptosis and conversely, seems to influence an increment in the oxidative burst in these cells. Altogether, we spotted a functional role of the miR155a-5p in CL pathogenesis, raising the hypothesis that an increased miR-155 expression by TLR ligands influences cellular mechanisms settled to promote both killing and control of parasite density after infection.

Consolidation of a Molecular Signature of Healing in Cutaneous Leishmaniasis Is Achieved during the First 10 Days of Treatment.

The immune response is central to the pathogenesis of cutaneous leishmaniasis (CL). However, most of our current understanding of the immune response in human CL derives from the analysis of systemic responses, which only partially reflect what occurs in the skin. In this study, we characterized the transcriptional dynamics of skin lesions during the course of treatment of CL patients and identified gene signatures and pathways associated with healing and nonhealing responses. We performed a comparative transcriptome profiling of serial skin lesion biopsies obtained before, in the middle, and at the end of treatment of CL patients (eight who were cured and eight with treatment failure). Lesion transcriptomes from patients who healed revealed recovery of the stratum corneum, suppression of the T cell-mediated inflammatory response, and damping of neutrophil activation, as early as 10 d after initiation of treatment. These transcriptional programs of healing were consolidated before lesion re-epithelization. In stark contrast, downregulation of genes involved in keratinization was observed throughout treatment in patients who did not heal, indicating that in addition to uncontrolled inflammation, treatment failure of CL is mediated by impaired mechanisms of wound healing. This work provides insights into the factors that contribute to the effective resolution of skin lesions caused by Leishmania (Viannia) species, sheds light on the consolidation of transcriptional programs of healing and nonhealing responses before the clinically apparent resolution of skin lesions, and identifies inflammatory and wound healing targets for host-directed therapies for CL.

Estudo da competência vetorial de Lutzomyia intermedia (Lutz & Neiva, 1912) para Leishmania (Viannia) braziliensis, Vianna, 1911 / Study of the vectorial competence of Lutzomyia intermedia (Lutz & Neiva, 1912) for Leishmania (Viannia) braziliensis, Vianna, 1911

This paper investigated the vectorial competence of Lutzomyia intermedia (Diptera: Psychodidae) in Vale do Ribeira (SP) to strains of Leishmania (Viannia) braziliensis (Kinetoplastida: Trypanosomatidae), by means of a search for natural infection; exposure of wild and colonized females (F1) to the lesions of experimentally infected hamsters and transmission tests by bite. The natural infection and the transmission tests were negative. In the exposures of Lu. intermedia to infected lesions we found rates of 74% (123+/166 dissected) and 70% (115+/164 dissected) for the wild and colonized females respectively. The development of the parasites was compatible with the development model of Peripilaria. The susceptibility of the tested strains associated with the epidemiological indicators contribute to the vectorial role suspicion of Lutzomyia intermedia in the studied region.

Estudou-se a competência vetorial de Lutzomyia intermedia (Diptera: Psychodidae) do Vale do Ribeira (SP) para estirpes de Leishmania (Viannia) braziliensis (Kinetoplastida: Trypanosomatidae), mediante pesquisa de infectividade natural; exposições de fêmeas silvestres e colonizadas (F1) às lesões de hamsters experimentalmente infectados e testes de transmissão via picada. A infectividade natural e os testes de transmissão revelaram-se negativos e, nas exposições, foram obtidas positividades de 74% (123+/166 dissecados) e 70% (115+/164 dissecados) para fêmeas silvestres e colonizadas respectivamente, e o desenvolvimento das formas evolutivas compatíveis com o modelo Peripilaria. A suscetibilidade às estirpes testadas associada aos indicadores epidemiológicos concorrem para a suspeita do papel vetorial de Lutzomyia intermedia na região estudada.

Variation between geographical populations of Lutzomyia (Nyssomyia) whitmani (Antunes & Coutinho, 1939) sensu lato (Diptera: Psychodidae: Phlebotominae) in Brazil

Phylogenetic analysis of morphometric and biological characteres indicated that there are two distinct forms of Lutzomyia whitmani in Brazil: one is present both north and south of the river Amazonas in the state of Pará while the other occurs in northeast Brazil, in the state of Ceará, and further south, including the type locality in state of Bahia. The Amazonian form is reportedly neither strongly anthropophilic nor synanthropic, and it is the vector of Leishmania shawi; whereas the southern form is often collected peridomestically, while biting man, and has been found infected with Le. (V.) braziliensis. The ratio of the length of the genital filaments to that the genital pump was found to be consistently smaller in males of the Amazonian populations. A middle repetitive DNA element was isolated by differentially screening a genomic library made using Amazonian material, and the sequence was diagnostic for this form of Lu. whitmani (being absent or occurring in low copy number in the southern form). The total evidence suggests there are at least two, geographically-isolated forms of Lu. whitmani, which may represent different cryptic species.

Development of Colombian isolates of Leishmania (Viannia) panamensis, Le. (V.) guyanensis and Le. (V.) braziliensis in the sandfly Lutzomyia intermedia (Lutz & Neiva, 1912) under experimental conditions

The development of Colombian Leishmania species of the subgenus Viannia in Lutzomyia intermedia was similar to that observed with Brazilian Le. (V.) braziliensis: colonization of the pylorus by paramastigotes; promastigotes in the midgut and massive infection of stomodeal valve. Difference was observed in the number of paramastigotes colonizing the pylorus, which was smaller in Colombian Leishmania species than Brazilian Le. braziliensis

Perfil epidemiológico da leishmaniose tegumentar no Brasil / Epidermological profile of cutaneous and mucocutaneous leishmaniasis in Brazil

A discussäo sobre o perfil epidemiológico da leishmaniose tegumentar no Brasil levou em conta as notificaçöes de casos humanos, raio de dispersäo dos agentes etiológicos e sinantropia de populaçöes silvestres. Foi analisado o resultado de 105.988 casos nos últimos dez anos e a persistência de focos ativos em matas remanescentes. O crescimento anual da incidência na regiäo Norte a tornou mais problemática no Brasil. Destacou-se também o crescente intercâmbio de populaçöes que sobreviveram em matas residuais com as do ambiente domiciliar. Nesta situaçäo, L. intermedia e L. braziliensis mostraram variado grau de adaptaçäo ao último ambiente. O processo sinantrópico em desenvolvimento para ambas espécies e seus reflexos nas mudanças de padräo epidemiológico da doença sugerem clara evoluçäo da leishmaniose tegumentar. Portanto, permanecerá tendência para aumento ds infecçöes humanas em ambiente extraflorestal no Brasil. O risco de contraí-la é igual para todos os indivíduos independente da idade e sexo

DNA probes for distinguishing Psychodopygus wellcomei from Psychodopygus complexus (Diptera: Psychodidae)

Genomic DNA fragments from males of Psychodopygus wellcomei were isolated and shown to be useful as sensitive diagnostic probles for positively separting individuals of this species from those of Ps. complexus. These two members of the Ps. squamiventris series are found sympatrically in foci of cutaneous leishmaniasis in the hill forests of southern Pará State. Of the two species, only Ps. welcomei is thought to be an important vector of Leishmania braziliensis sensu stricto, buth this is based on circumstantial evidence because of the difficulties of identifying female sandflies wothin the series. The diagnostic probes were isolated from a library of Ps. wellcomei built by ligationg short fragments of Sau 3A-resistricted, genomic DNA into the plasmid vector PUC 18. Differential screening of 1316 library clones with total genomic DNA of Ps. Wellcomei and Ps. complexus identified 5 recombinants, with cross-hybridizing inserts of repetitive DNA, that showed strong specificity for Ps. wellcomei. As little as 0.4% of the DNA extracted from an individual sandfly (=ca. 0.5 namograms) was specifically detected. The diagnostic probes were used to identify as Ps. wellcomei a wild-caught female sandfly found infected with L. braziliensis s.s., providing only the second positive association between these two species

Experimental infection with Leishmania (Viannia) braziliensis, and Leishmania (Leishmania) amazonensis in the marmoset, Callithrix penicillata (Primates: Callithricidae)

Foureen marmosets (Callithrix penicillata) were inoculated intradermally with promastigotes and/or amastigotes of Leishmania (Viannia) brazilensis (L. (V) b.) strains MHOM/BR/83/LTB-300MHOM/BR/85/LTB-12 MHOM/BR/81/LTB-179 and MHOM/BR/82/LTB-250. The evolution of subsequent lesions was studied for 15 to 75 weeks post-inoculation (PI). All but of the L. (V) b. injected marmosets developed a cutaneous lesion at the point of inoculation after 3 to 9 weeks, characterized by the appearance of subcutaneous nodules containing parasites. parasites were isolated by culture (Difco Blood Agar) from all 11 positive animals. The maximum size of the lesions was variable and ranged between 37 mm² to 107 mm². Ulceration of primary nodules became evident after 3 to 12 weeks in all infected marmosets, but was faster and larger in 5 of the 11 animals. The active lesions persisted in 9 out of 11 Callithrix until the en of the observation period, which varied from 15-75 weeks. In 3 animals spontaneous healing of their lesions (13 to 25 weeks, PI) was observed buth with cryptic parasitism. In another 2 infected animals there was regression followed by reactivation of the cutaneous lesions. The appearance of smaller satellite lesions adjacent to primary ones, as well as metastatic lesions to the ear lobes, were documented in 2 animals. Promastigotes of L. (Leishmania) amazonensis (L.(L)a.) MHOM/BR/77/LTB-16 were inoculated in 1 marmoset. This animal remained chronically infected for 6 months and the lesions developed in a similar manner to L.(V)b. infected marmosets. No significant differences in clinical and parasitological behaviour were observed between promastigote or amastigote derived infections of the 2 species. Both produced chronic, long lasting lesions which eventually healed. The same was true for parameters of size and ulceration. Skin tests converted to parasite in 11 of 15 inected masmosets and in 1-0 of 12 parasites positive animnals. Moderate levels of circulating antibodies we also observed by IFAT/IgG assays. In spite of the failure to rep[roduce the mucosal form of the disease, an important aspect of the Callithrix model in experimental cutaneous leishmaniasis lies in the reproduction of 2 clinical events that are common in humans, namely, the chronic ulceration and spontaneous healing of the lesions

Aspectos ecologicos da leishmaniose tegumentar americana: 8. avaliacao da atividade enzootica de Leishmania (Viannia) braziliensis, em ambiente florestal e peridomiciliar, regiao do vale do Ribeira, Estado de Sao Paulo, Brasil / Ecological aspects of American tegumentary leishmaniasis: 8. Evaluation of the enzootic activity of Leishmania (Vianna) braziliensis, in forest and peridomiciliary environments of the Ribeira Valey region, Sao Paulo State, Brazil

A evidencia da transmissao extraflorestal da leishmaniose cutaneo-mucosa na regiao do Vale do Ribeira ensejou o presente estudo epidemiologico prospectivo, visando avaliar a atividade enzootica de L. (V.) braziliensis. A pesquisa paratisologica da infeccao natural em pequenos mamiferos e populacao canina foi complementada com o teste de imunofluorescencia indireta (IFI) para caes e captura de flebotomineos em ambiente florestal e peridomiciliar. A positividade para o teste sorologico e exame parasitologico somente foi observada para caes residentes e com taxas de 5,6 e 2,4 por cento, respectivamente. Entre animais silvestres e sinantropicos capturados, destacam-se os pertencentes a Oryzomys (Oligoryzomys) e Rattus rattus, ambos assinalados em proporcoes equivalentes (29,3 por cento) em ambiente peridomiciliar. Foram capturados apenas 166 exemplares femininos de Lutzomyia intermedia, fato atribuido a borrifacao das habitacoes humanas e anexos com DDT. No contexto epidemiologico mais amplo, discute-se a fragilidade do ciclo extraflorestal da L. (V.) braziliensis; o papel do cao e de pequenos mamiferos, como fonte de infeccao domiciliar, alem de analisar o potencial deles na dispersao do parasita na area estudada

Xenodiagnostico con Lutzomyia youngi en casos venezolanos de leishmaniasis cutaned por Leishmania braziliensis / Xenodiagnosis with Lutzomyia youngi in Venezuelan cases of cutaneous leishmaniais due to Leishmania braziliensis

Xenodiagnósticos con Lutzomya yungi aplicados en los bordes de las úlceras de pacientes infectados con Leishmania braziliensis antes y después del tratamiento con 10 dosis de antimonial pentavalente y un aminoglicósido, evidencian la condición reservoria de leishmanias del enfermo, para flebótomos endofágicos y la utilidad de un tratamiento específico-temprano que no solamente conduce a la curación clínica, sino a la eliminación del riesgo de una eventual transmisión intradomiciliar por insectos que pican dentro del domicilio durante la noche

Sobre os reservatorios naturais da leishmaniose tegumentar Americana / On the natural reservoirs of integumentary leishmaniasis American

Apos passar em revista a literatura existente sobre o assunto, o autor relata resultados de suas investigações sobre a existencia de reservatorios naturais da Leishmania brasiliensis. Foram encontradas leishmanias em tres roedores silvestres das seguintes especies: Kannabateomys amblyonyx, Cuniculus paca e Dasyprocta azarae. A identificação dessas leishmanias com a produtora da moletsia no homem, nao foi possivel. A interpretação desses resultados juntamente com os dados conhecidos até agora, permite construir hipotese sobre a estrutura epidemiologica da leishmaniose tegumentar na natureza. Essa estrutura compreenderia doi tipos um selvatico com reservatorios silvestres e outro mais adaptado ao homem com reservatorio domesticos.