BALB/c Mice Infected with Antimony Treatment Refractory Isolate of Leishmania braziliensis Present Severe Lesions due to IL-4 Production

Leishmaniasis is a neglected disease that affects more than 12 million people worldwide. In Brazil, the cutaneous disease is more prevalent with about 28,000 new cases reported each year, and L. braziliensis is the main causative agent. The interesting data about the infection with this parasite is the wide variety of clinical manifestations that ranges from single ulcerated lesions to mucocutaneous and disseminated disease. However, experimental models to study the infection with this parasite are difficult to develop due to high resistance of most mouse strains to the infection, and the mechanisms underlying the distinct manifestations remain poorly understood. Here, the authors use a mouse experimental model of infection with different L. braziliensis isolates, known to induce diseases with distinct severity in the human hosts, to elucidate immune mechanisms that may be involved in the different manifestations. They showed that distinct parasite isolates may modulate host response, and increased IL-4 production and Arg I expression was related to more severe disease, resulting in longer length of disease with larger lesions and reduced parasite clearance. These findings may be useful in the identification of immunological targets to control L. braziliensis infection and potential clinical markers of disease progression

TLR1/2 Activation during Heterologous Prime-Boost Vaccination (DNA-MVA) Enhances CD8+ T Cell Responses Providing Protection against Leishmania (Viannia)

Leishmania (Viannia) are the predominant agents of leishmaniasis in Latin America. Given the fact that leishmaniasis is a zoonosis, eradication is unlikely; a vaccine could provide effective prevention of disease. However, these parasites present a challenge and we do not fully understand what elements of the host immune defense prevent disease. We examined the ability of vaccination to protect against L. (Viannia) infection using the highly immunogenic heterologous prime-boost (DNA-modified vaccinia virus) modality and a single Leishmania antigen (TRYP). Although this mode of vaccination can induce protection against other leishmaniases (cutaneous, visceral), no protection was observed against L. (V.) panamensis. However, we found that if the vaccination was modified and the innate immune response was activated through Toll-like receptor1/2(TLR1/2) during the DNA priming, vaccinated mice were protected. Protection was dependent on CD8 T cells. Vaccinated mice had higher CD8 T cell responses and decreased levels of cytokines known to promote infection. Given the long-term persistence of CD8 T cell memory, these findings are encouraging for vaccine development. Further, these results suggest that modulation of TLR1/2 signaling could improve the efficacy of DNA-based vaccines, especially where CD8 T cell activation is critical, thereby contributing to effective and affordable anti parasitic vaccines

The storm of NGS in NSCLC diagnostic-therapeutic pathway: How to sun the real clinical practice

The increasing number of approved drugs along with next generation sequencing (NGS) technologies look out as potential revolution of biomolecular characterization of non-small-cell lung cancer (NSCLC). Nevertheless, several aspects impact on success rate of NGS in clinical practice: a multidisciplinary approach and thorough knowledge of strengths and limits of each technologic diagnostic tool are required. Crucial preliminary step is the selection of the best available sample before testing, aware of clinical condition and setting of disease. Genomic data should be than integrated in the clinical context and matched with available therapeutic options; Molecular Tumor Boards (MTB) are worldwide emerging interdisciplinary groups implemented to transfer the impact of precision medicine in clinical practice. In order to guarantee equity in treatment, these considerations should find their application widely and rapidly. Aim of this review is offering an overview of emerging biomarkers, relative upcoming targeted drugs, and new diagnostic chances with an authors’ perspective about a real-life diagnostic-therapeutic algorithm useful for daily clinical practice

Leishmaniose tegumentar americana: histórico, epidemiologia e perspectivas de controle American cutaneous leishmaniasis: history, epidemiology and prospects for control

A Leishmaniose Tegumentar Americana (LTA) é uma doença causada por protozoários do gênero Leishmania, transmitida ao homem pela picada de mosquitos flebotomíneos (Ordem Diptera; Família Psychodidae; Sub-Família Phlebotominae). No Brasil existem atualmente 6 espécies de Leishmania responsáveis pela doença humana, e mais de 200 espécies de flebotomíneos implicados em sua transmissão. Trata-se de uma doença que acompanha o homem desde tempos remotos e que tem apresentado, nos últimos 20 anos, um aumento do número de casos e ampliação de sua ocorrência geográfica, sendo encontrada atualmente em todos os Estados brasileiros, sob diferentes perfis epidemiológicos. Estima-se que, entre 1985 e 2003, ocorreram 523.975 casos autóctones, a sua maior parte nas regiões Nordeste e Norte do Brasil. Neste estudo, são discutidos aspectos relacionados ao tratamento e ao controle dessa doença, assim como também as dificuldades para a implementação dessas medidas. São apontadas alternativas que passam pela estruturação dos serviços de saúde, com respeito ao diagnóstico, no desenvolvimento de drogas de aplicação tópica ou por via oral, no desenvolvimento de vacinas, no controle diferenciado de vetores e no aprofundamento de estudos relacionados à biologia celular do parasita.<br>American Cutaneous Leishmaniasis (ACL) is an infectious disease transmitted by the bite of phlebotomines mosquitos (Order Diptera: Family Psychodidae: Sub-Family Phlebotominae) and caused by protozoa from the genus Leishmania (ROSS 1903). In Brazil, there are six different species of Leishmania and more than 200 different species of phlebotomines. It's a disease that has been afflicting human beings for many centuries, and in Brazil, in the past two decades, there has been an important increase in the number of cases and also in its geographical distribution. Presently, ACL cases are registered in all Brazilian states under three different epidemiological profiles (sylvatic, sylvatic-modified and periurban). Between 1985 and 2003, 523,975 cases were registered, mainly in the northeast and north of the country, although the north has the highest incidence rate. In this study, aspects related to difficulties in treatment and transmission control, and new strategies to approach the disease are discussed. Alternatives such as the development of new drugs (topical and oral routes), the implementation of diagnostic methods in public health services, differentiated transmission control based on the 3 different epidemiological profiles and basic research on the molecular biology of the parasite are pointed out

Italian Survey on adjuvant treatment of non-small cell lung cancer

Background: A recent pooled analysis of randomized trials indicated significant improvement in overall survival from cisplatin-based adjuvant chemotherapy for non-small cell lung cancer (NSCLC), depending on disease stage (only in stages II and III) and PS (≤1). Post-operative radiotherapy (RT) is optional for pN2 tumours. Patients and methods: To evaluate opinions and daily clinical practice of Italian Oncologists about adjuvant treatment of NSCLC, a 46-item questionnaire was delivered via e-mail. Results: Seventy-eight physicians from 68 Centers (out of 98 contacted) returned their questionnaire. Seventy-four, 86, 94, and 78% of them give the indication for adjuvant chemotherapy for stage IIA, IIB, IIIA, and IIIB disease, respectively and 14% in stage IB disease. Stage, PS, and age are taken into consideration evaluating adjuvant approach by 97, 95 and 73%, respectively. Cisplatin-vinorelbine (64%) and cisplatin-gemcitabine (33%), for 4 cycles (81%), are the preferred regimens, while 32% use different regimens. Ninety-two percent indicate RT in pN2 disease and/or positive resection margins. Real Number of patients Needed to Treat (NNT) is probably not completely known/understood and/or used by physicians. Conclusions: A substantial adherence between clinical daily practice in Italy and scientific progresses is described in this paper, even with some discordances regarding the most appropriate adjuvant chemotherapy regime