Nanoparticulate drug delivery systems for the treatment of neglected tropical protozoan diseases

Neglected Tropical Diseases (NTDs) comprise of a group of seventeen infectious conditions endemic in many developing countries. Among these diseases are three of protozoan origin, namely leishmaniasis, Chagas disease, and African trypanosomiasis, caused by the parasites Leishmania spp., Trypanosoma cruzi, and Trypanosoma brucei respectively. These diseases have their own unique challenges which are associated with the development of effective prevention and treatment methods. Collectively, these parasitic diseases cause more deaths worldwide than all other NTDs combined. Moreover, many current therapies for these diseases are limited in their efficacy, possessing harmful or potentially fatal side effects at therapeutic doses. It is therefore imperative that new treatment strategies for these parasitic diseases are developed. Nanoparticulate drug delivery systems have emerged as a promising area of research in the therapy and prevention of NTDs. These delivery systems provide novel mechanisms for targeted drug delivery within the host, maximizing therapeutic effects while minimizing systemic side effects. Currently approved drugs may also be repackaged using these delivery systems, allowing for their potential use in NTDs of protozoan origin. Current research on these novel delivery systems has provided insight into possible indications, with evidence demonstrating their improved ability to specifically target pathogens, penetrate barriers within the host, and reduce toxicity with lower dose regimens. In this review, we will examine current research on these delivery systems, focusing on applications in the treatment of leishmaniasis, Chagas disease, and African trypanosomiasis. Nanoparticulate systems present a unique therapeutic alternative through the repositioning of existing medications and directed drug delivery.(AU)

Sentidos das Doenças Negligenciadas na agenda da Saúde Global: o lugar de populações e territórios / Meanings of Neglected Diseases in the Global Health agenda: the place of populations and territories

Resumo A agenda da saúde global tem apresentado avanços significativos no campo das doenças negligenciadas. Num movimento dinâmico, assume prioridades, estratégias e sentidos diversos ao longo das duas últimas décadas. Entretanto, permanecem desafios importantes em termos geopolítico, econômico, epistemológico e do desenvolvimento social. A designação e localização das doenças negligenciadas em determinados territórios e populações guarda relação, historicamente, com algumas dinâmicas como as de natureza colonial e capitalista. Informam linhas de continuidades na racionalidade de políticas e ações, operadas na assimetria entre povos, instituições e nações. Ainda que tendo incluído positivamente o debate sobre negligência de doenças, argumenta-se a favor de uma agenda da saúde global que assuma e evoque, com mais vigor teórico e metodológico, a dimensão da negligência de corpos e populações, aprofundando o debate com as matrizes biomédica e político-econômica. Significa reforçar o entendimento crítico sobre a histórica vulnerabilização de sujeitos na produção de conhecimento, bem como dar protagonismo e levar em consideração seus modos de andar a vida em diálogo com prioridades e práticas de saúde situadas.

Abstract The global health agenda has made significant strides in neglected diseases. In a dynamic movement, throughout the past two decades, it has assumed different priorities, strategies and meanings. Nevertheless, important challenges persist in terms of geopolitical, economic, epistemological and social development. The designation and location of neglected diseases in certain territorial spaces and populations is historically related to some dynamics such as those of a colonial and capitalistic nature. They reveal continuities in the rationality of policies and actions, pervading asymmetries between peoples, institutions and nations. Although it has positively included the debate on neglected diseases, it can be argued the global agenda of public health has yet to assume and evoke the dimension of neglected bodies and populations with more theoretical and methodological vigor, by intensifying the dialogue between biomedical and political-economic fields. It means reinforcing the critical understanding of the historical vulnerabilities of individuals in the production of knowledge, as well as giving prominence and taking into account their ways of leading their lives in conjunmction with local public health priorities and practices.

Avaliação da atividade anti-Leishmania e anti-Trypanosoma do extrato etanólico das folhas de Annona squamosa L / Evaluation of the anti-leishmania and anti-trypanosoma activity of ethanolic extract from the leaves of Annona squamosa L

As doenças parasitárias, também chamadas de “doenças negligenciadas”, continuam sendo uma grande dificuldade para o desenvolvimento social e econômico dos países mais pobres. Podemos citar como exemplo dessas doenças, a leishmaniose e a doença de Chagas. A leishmaniose é causada por parasitas do gênero Leishmania e afeta cerca de 12 milhões de pessoas. A doença de Chagas, causada pelo protozoário Trypanosoma cruzi, causa aproximadamente 50.000 mortes por ano. Os fármacos disponíveis para o tratamento dessas doenças são altamente tóxicos, sendo este um dos motivos que leva à busca por drogas eficazes e seguras para seus tratamentos. As folhas da Annona squamosa, espécie da família Annonaceae, já foram descritas na literatura por suas atividades hepatoprotetora, antiparasitária, pesticida e antimicrobiana. Nesse estudo avaliamos a atividade anti-leishmania e tripanocida do extrato etanólico das folhas de Annona squamosa L. (EEAS) em formas promastigota do parasita Leishmania braziliensis e Leishmania infantum e epimastigota de Trypanosoma cruzi, além de avaliar a atividade citotóxica em fibroblasto. Os resultados demonstram que o extrato apresentou uma melhor atividade contra Leishmania infantum e Leishmania brasiliensis quando comparados com Trypanosoma cruzi; e que apresentou uma maior toxicidade nas concentrações de 500 e 1000 μg/ml, com mortalidade dos fibroblastos de aproximadamente 85% e 100%, respectivamente. Esse estudo aponta para uma perspectiva terapêutica alternativa que se mostrou eficaz frente aos parasitas aqui estudados, exceto a forma epimastigota de Trypanosoma cruzi. Com relação aos testes de citotoxicidade fazem-se necessários novos testes, uma vez que apresentou um alto nível de toxicidade, viabilizando assim futuros ensaios in vivo.

The parasitic diseases, also calls by “neglected diseases”, continue being a major difficulty for the social and economic development of the poorest countries. We can cite as an example of these diseases, the leishmaniasis and the Chagas disease. Leishmaniasis is caused by parasites of the genus Leishmania and affects about 12 million people. The Chagas disease, caused by the protozoan Trypanosoma cruzi, causes approximately 50,000 deaths per year. The drugs available for the treatment of these diseases are highly toxic, being this one of the reasons that leads to the search for effective and safe drugs for their treatments. The leaves of the Annona squamosa, species of the family Annonaceae, have already been described in the literature by their hepatoprotective activities, antiparasitic, pesticide and antimicrobial. In this study we assessed the activity tripanocidal and antileishmania of ethanolic extract from the leaves of Annona squamosa L. (EEAS) in promastigota forms of the parasite Leishmania braziliensis and Leishmania infantum and epimastigota of Trypanosoma cruzi, in addition to evaluating the cytotoxic activity in fibroblasts. The results demonstrate that the extract presented a better activity against Leishmania infantum and Leishmania brasiliensis when compared with Trypanosoma cruzi; and which presented a greater toxicity at concentrations of 500 and 1000 μg/ml, with mortality of fibroblasts of approximately 85% and 100%, respectively. This study points to an alternative therapeutic perspective that showed effective against the parasites here studied, except the epimastigota form of Trypanosoma cruzi. With relation to cytotoxicity tests are required new tests, once presented a high level of toxicity, thus enabling future in vivo assays.

Ebola virus – from neglected threat to global emergency state / Vírus ébola – de ameaça negligenciada ao estado de emergência global

SUMMARY Objective: This review aims to update knowledge about Ebola virus disease (EVD) and recent advances in its diagnosis, treatment and prevention. Method: A literature review was performed using the following databases: ISI Web of Knowledge, PubMed, IRIS, Scopus and the websites of the CDC and the WHO. Additionally, we have included articles and reports referenced in the basic literature search, and news that were considered relevant. Results: The Ebola virus, endemic in some parts of Africa, is responsible for a severe form of hemorrhagic fever in humans; bats are probably its natural reservoir. It is an extremely virulent virus and easily transmitted by bodily fluids. EVD's complex pathophysiology, characterized by immunosuppression as well as stimulation of an intense inflammatory response, results in a syndrome similar to septic shock. The diagnosis is difficult due to the initial symptoms that mimic other diseases. Despite the high mortality rates that can amount to 90%, a prophylaxis (chemical or vaccine) or effective treatment does not exist. Two vaccines and experimental therapies are being developed for the prevention and treatment of EVD. Conclusion: Although the virus is known for about 40 years, the lack of knowledge obtained and the disinterest of government authorities in the countries involved justify the state of emergency currently exists regarding this infectious agent. Only the coordination of multiple entities and the effective commitment of the international community will facilitate the control and effective prevention of EVD.

RESUMO Objetivo: esta revisão tem como objetivo atualizar os conhecimentos sobre a doença do vírus ébola (DVE) e sobre os recentes avanços nos métodos de diagnóstico, tratamento e prevenção. Método: foi realizada uma revisão de literatura, utilizando as seguintes bases de dados: ISI Web of Knowledge, PubMed, IRIS, Scopus e os sites do Centers for Disease Control and Prevention (CDC) e da Organização Mundial da Saúde (OMS). Adicionalmente, foram incluídos artigos e relatórios referenciados na pesquisa bibliográfica de base e notícias consideradas relevantes. Resultados: o vírus ébola, endêmico de algumas regiões da África, é responsável por uma forma grave de febre hemorrágica no homem, e os morcegos são provavelmente o seu reservatório natural. É um vírus extremamente virulento e de fácil transmissão pelos fluidos corporais. A complexa fisiopatologia da doença, caracterizada pela imunossupressão e pelo estímulo a uma intensa resposta inflamatória, resulta em uma síndrome semelhante ao choque séptico. O seu diagnóstico é difícil, por causa da sintomatologia inicial, que mimetiza outras doenças. Apesar das altas taxas de mortalidade, que podem alcançar os 90%, não existe profilaxia (química ou vacinal) ou tratamento eficaz. Encontram-se em desenvolvimento duas vacinas e terapias experimentais para a prevenção e o tratamento da DVE. Conclusão: apesar de ser um vírus conhecido há cerca de 40 anos, o escasso conhecimento obtido e o desinteresse das entidades governamentais de países envolvidos justificam o estado de emergência que se vive atualmente em relação a esse agente infeccioso. A coordenação por múltiplas entidades e o empenho efetivo da comunidade internacional facilitarão o seu controle e a prevenção eficaz.

Chromoblastomycssis: a neglected tropical disease / Cromoblastomicose: doença tropical negligenciada

SUMMARYChromoblastomycosis (CMB) is a chronic fungal infection of the skin and the subcutaneous tissue caused by a transcutaneous traumatic inoculation of a specific group of dematiaceous fungi occurring mainly in tropical and subtropical zones worldwide. If not diagnosed at early stages, patients with CBM require long term therapy with systemic antifungals, sometimes associated with physical methods. Unlike other neglected endemic mycoses, comparative clinical trials have not been performed for this disease. Nowadays, therapy is based on a few open trials and on expert opinion. Itraconazole either as monotherapy or associated with other drugs, or with physical methods, is widely used. Recently, photodynamic therapy has been successfully employed in combination with antifungals in patients presenting with CBM. In the present revision the most used therapeutic options against CBM are reviewed as well as the several factors that may have impact on the patient's outcome.

RESUMOCromoblastomicose (CMB) é uma infecção fúngica crônica da pele e tecido subcutâneo causada pela inoculação transcutânea traumática de um grupo específico de fungos dermatiáceos que ocorrem principalmente em zonas tropicais e subtropicais do mundo. Quando não são diagnosticados nas fases iniciais, pacientes com CBM necessitam de tratamentos prolongados com antifúngicos sistêmicos, por vezes associados a métodos físicos. Diferentemente de outras micoses endêmicas negligenciadas, não foram realizados ensaios clínicos comparativos para esta doença. Atualmente a terapia é baseada em alguns poucos ensaios abertos e em opiniões de especialistas. Itraconazol é amplamente utilizado como monoterapia ou em associação com outras drogas, ou com métodos físicos. Recentemente, a terapia fotodinâmica foi empregada com sucesso combinada a antifúngicos em pacientes com CBM. Neste manuscrito as opções terapêuticas mais utilizadas contra CBM foram revistas, assim como os diversos fatores que podem influenciar a evolução dos pacientes.

Is locally advanced breast cancer a neglected disease.

Background and Aims: Breast cancer is the second most common malignancy in India, and majority of patients present as a locally advanced breast carcinoma (LABC). Evaluating the prevalence of LABC and assessing the causes of local advancement and delayed presentation is the aim of the present study. Settings and Design: This was a rural hospital-based prospective cross-sectional study. Statistical Analysis: Descriptive statistics. Materials and Methods: Seventy-one cytologically/histopathologically confirmed cases of breast carcinoma were enrolled in the study. Breast sarcomas and lymphoma were excluded and, of them, prevalence of LABC and causes of delay and local advancement, i.e. patient factors, system factors and biological factors, were evaluated. Results: LABC accounted for 50.7% of these patients. On assessing the cause of advancement of LABC, patient factor (69.8%) was the major cause for delayed presentation, followed by system delay (23.6%). Patient factors were lack of awareness of breast cancer (75%) and financial constraints (52.8%). The system factor was nonreferral by general practitioners to specialty centers or trying to treat these patients with other allied modalities of treatment. Conclusions: LABC in the Indian scenario is an outcome of neglect due to patient and system factors. These factors offer an excellent opportunity to plan a community-oriented preventive strategy for the general population and practitioners to decrease the incidence of LABC.