Disposable electrochemical platform based on solid-binding peptides and carbon nanomaterials: an alternative device for leishmaniasis detection.

Neglected tropical diseases are those caused by infectious agents or parasites and are considered endemic in low-income populations. These diseases also have unacceptable indicators and low investment in research, drug production, and control. Tropical diseases such as leishmaniasis are some of the main causes of morbidity and mortality around the globe. Electrochemical immunosensors are promising tools for diagnostics against these diseases. One such benefit is the possibility of assisting diagnosis in isolated regions, where laboratory infrastructure is lacking. In this work, different peptides were investigated to detect antibodies against Leishmania in human and canine serum samples. The peptides evaluated (395-KKG and 395-G) have the same recognition site but differ on their solid-binding domains, which ensure affinity to spontaneously bind to either graphene oxide (GO) or graphene quantum dots (GQD). Cyclic voltammetry and differential pulse voltammetry were employed to investigate the electrochemical behavior of each assembly step and the role of each solid-binding domain coupled to its anchoring material. The graphene affinity peptide (395-G) showed better reproducibility and selectivity when coupled to GQD. Under the optimized set of experimental conditions, negative and positive human serum samples responses were distinguished based on a cut-off value of 82.5% at a 95% confidence level. The immunosensor showed selective behavior to antibodies against Mycobacterium leprae and Mycobacterium tuberculosis, which are similar antibodies and potentially sources of false positive tests. Therefore, the use of the graphene affinity peptide as a recognition site achieved outstanding performance for the detection of Leishmania antibodies.

Unwelcome prevalence of leishmaniasis with several other infectious diseases.

Co-infection among leishmaniasis and other infectious diseases is common among natural populations especially in the endemic areas of the disease. It depends on the environmental factors, vector availability, host-parasite interactions and above all geographical boundaries. Leishmaniasis being an immunosuppressive disease empowers the invading opportunistic infections to invade and successfully colonize. A variety of infections coexist with leishmaniasis like HIV, leprosy, tuberculosis, schistosomiasis etc. With the different pathology and immune status, co-infection in most cases leads to disease severity and increased mortality.Inevitably, co-infection increases the complexity and poses a threat in the cure and control programmes. This is the first review which highlights the existing co-infections of leishmaniasis with other infectious diseases. The review also focuses on the immunology of co-infections together, diagnosis and the treatment options available for treating such cases. With the changing environment and the overlapping endemic areas of leishmaniasis with other diseases, it becomes difficult to treat a disease without accurate diagnosis. Thus, the review insists on the need for more research on development of newer and differential diagnostic methods for co-infected individuals with theoverlapping symptoms.

Rapid diagnosis of Leishmania infection with a portable loopmediated isothermal amplification device.

L. donovani is an intracellular protozoan parasite, that causes visceral leishmaniasis (VL), and consequently, post-kala azar dermal leishmaniasis (PKDL). Diagnosis and treatment of leishmaniasis is crucial for decreasing its transmission. Various diagnostic techniques like microscopy, enzyme-linked immunosorbent assays (ELISA) and PCR-based methods are used to detect leishmaniasis infection. More recently, loop-mediated isothermal amplification (LAMP) assay has emerged as an ideal diagnostic measure for leishmaniasis, primarily due to its accuracy, speed and simplicity. However, point-of-care diagnosis is still not been tested with the LAMP assay. We have developed a portable LAMP device for the monitoring of Leishmania infection. The LAMP assay performed using our device can detect and amplify as little as 100 femtograms of L. donovani DNA. In a preliminary study, we have shown that the device can also amplify L. donovani DNA present in VL and PKDL patient samples with high sensitivity (100%), specificity (98%) and accuracy (99%), and can be used both for diagnostic and prognostic analysis. To our knowledge, this is the first report to describe the development and application of a portable LAMP device which has the potential to evolve as a point-of-care diagnostic and prognostic tool for Leishmania infections in future.

Potential of recombinant LiHyQ, a novel Leishmania infantum protein, for the diagnosis of canine visceral leishmaniasis and as a diagnostic and prognostic marker for human leishmaniasis and human immunodeficiency virus co-infection: A preliminary study.

Laboratory diagnosis of leishmaniasis shows variable efficacy in detecting infected mammalian hosts and there is a need to identify suitable antigens to improve the accuracy of diagnostic tests. In the present study, a L. infantum hypothetical protein called LiHyQ was evaluated for the diagnosis of tegumentary (TL) and visceral (VL) leishmaniasis using canine and human samples. A collection of dog sera (n=155) were tested and contained samples from asymptomatic (n=20) and symptomatic (n=25) VL animals, from healthy dogs living in endemic (n=25) or non-endemic (n=25) areas of disease, from Leish-Tec® vaccinated dogs (n=20) or from dogs infected with Ehrlichia canis (n=15), Babesia canis (n=10) and Trypanosoma cruzi (n=15). Sensitivity (Se), Specificity (Sp), Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of 100% were observed for rLiHyQ with these samples, whereas the Se, Sp, PPV and NPV values with L. infantum Soluble Leishmania Antigen (SLA) preparation were 60.0%, 99.0%, 96.0% and 86.0%, respectively. A collection of human sera (n=305) were tested and contained samples from TL (n=50) and VL (n=40) patients, from VL/HIV co-infected patients (n=35), from patients infected with HIV alone (n=30), Chagas Disease (n=30), malaria (n=10), tuberculosis (n=10), paracoccidioidomycosis (n=15), leprosy (n=30) or aspergillosis (n=15); and from healthy subjects (n=40). Se, Sp, PPV and NPV values of 100% were observed for rLiHyQ with these samples, whereas the Se, Sp, PPV and NPV values with SLA were 58.0%, 76.0%, 50.0% and 82.0%, respectively. The antibody reactivity against the protein was compared with commercial kits, and the kappa index varied from 0.95 to 1.00 for rLiHyQ, and of 0.55 to 0.82 for the kits. In addition, the serological follow-up of treated patients showed a significant reduction in rLiHyQ-specific IgG antibody levels. All canine and human samples were tested at the same time using the same reagents, in order to reduce experimental variation and interference in data interpretation. In conclusion, our preliminary data suggest a diagnostic and prognostic role for rLiHyQ against leishmaniasis.

Zoonotic parasites infecting free-living armadillos from Brazil.

Armadillos are specialist diggers and their burrows are used to find food, seek shelter and protect their pups. These burrows can also be shared with dozens of vertebrate and invertebrate species and; consequently, their parasites including the zoonotics. The aim of this study was to diagnose the presence of zoonotic parasites in four wild-caught armadillo species from two different Brazilian ecosystems, the Cerrado (Brazilian savanna) and the Pantanal (wetland). The investigated parasites and their correspondent diseases were: Toxoplasma gondii (toxoplasmosis), Trypanosoma cruzi (Chagas disease), Leishmania spp., (leishmaniasis), Paracoccidioides brasiliensis (Paracoccidioidomicosis) and Mycobacterium leprae (Hansen's disease). Forty-three free-living armadillos from Pantanal and seven road-killed armadillos from the Cerrado were sampled. Trypanosoma cruzi DTU TcIII were isolated from 2 out of 43 (4.65%) armadillos, including one of them also infected with Trypanosoma rangeli. Antibodies anti-T. gondii were detected in 13 out of 43 (30.2%) armadillos. All seven armadillos from Cerrado tested positive for P. brasiliensis DNA, in the lungs, spleen, liver fragments. Also, by molecular analysis, all 43 individuals were negative for M. leprae and Leishmania spp. Armadillos were infected by T. cruzi, T. rangeli, P. brasiliensis and presented seric antibodies to T. gondii, highlighting the importance of those armadillos could have in the epidemiology of zoonotic parasites.

Validation of a cross-NTD toolkit for assessment of NTD-related morbidity and disability. A cross-cultural qualitative validation of study instruments in Colombia.

BACKGROUND: Many neglected tropical diseases (NTDs) are not fatal, but they are disabling, disfiguring and stigmatizing. More accurate data on these aspects would benefit planning, monitoring and evaluation of interventions, as well as provision of appropriate services for the often life-long consequences. In 2015, a cross-NTD toolkit was developed, consisting of a variety of existing questionnaires to measure morbidity, disability and health-related quality of life. The toolkit covers the domains of the International Classification of Functioning, Disability and Health (ICF) framework. These tools have been developed in a source country, however, it was intended for the cross-NTD toolkit to be applicable across NTDs in many countries with different cultures and languages in order to generate universally comparative data. Therefore; the present study aimed to validate several tools of the toolkit among people affected by leprosy or leishmaniasis in the cultural settings of Cartagena and Cúcuta, Colombia. METHODOLOGY: This study aimed to validate the following tools among 55 participants between 18-85 years old, affected by leprosy and leishmaniasis: (I) Clinical Profile, (II) Self-Reporting Questionnaire (SRQ), (III) WHO Quality of Life assessment-abbreviated version (WHOQOL-BREF), and (IV) WHO Quality of Life assessment-Disability (WHOQOL-DIS). The tools were administered during face-to-face interviews and were followed by open questions about the respondents' thoughts on format of the tool and the understanding, relevance and acceptability of the items. The tools were validated using a qualitative method approach based on the framework for cultural equivalence, measured by the cultural, item, semantic and operational equivalences. RESULTS: The Clinical Profile was seen as acceptable and relevant, only the semantic equivalence was not as satisfying and needs a few adaptations. The SRQ was very well understood and shows to reach the equivalences for the population of Colombia without any additional changes. Several items of the WHOQOL-BREF and the WHOQOL-DIS were not well understood and changes are recommended due to semantic difficulties. Operational equivalence of both questionnaires was not as desired in relation to the used response scales. The participants shared that the tools are relevant and important for their particular situation. CONCLUSIONS/SIGNIFICANCE: The SRQ is found to be a valid tool for Colombia and can be included in the cross-NTD toolkit. The Clinical Profile, WHOQOL-BREF & WHOQOL-DIS need changes and retesting among Colombian people affected by an NTD. The toolkit as a whole is seen as useful to show the effects leprosy and leishmaniasis have on the participants. This cultural validation will contribute to a universally applicable cross-NTD toolkit.

As doenças negligenciadas e suas representações sociais: um estudo com profissionais de saúde / Neglected diseases and their social representations: a study with health professionals

As doenças negligenciadas são caracterizadas por um grupo de enfermidades infecciosas que atingem principalmente a população de baixa renda nos países em desenvolvimento, com poucos investimentos em pesquisa e tecnologia para avançar no controle, na prevenção e tratamento medicamentoso. São assim denominadas também pelo fato de não despertarem o interesse econômico e financeiro das grandes indústrias farmacêuticas proporcionando a continuidade do ciclo da pobreza e diminuição da qualidade de vida das pessoas. O objetivo geral foi analisar as representações sociais acerca das doenças negligenciadas para os profissionais de saúde com ênfase nas dimensões conceitual e prática destas representações. Trata-se de uma pesquisa de natureza qualitativa, com sustentação na Teoria das Representações Sociais, em suas abordagens processual e estrutural, realizada com 90 profissionais de saúde que atuam em instituições de atenção primária e secundária à saúde, no município de Jequié/BA. A pesquisa aconteceu em três fases distintas, a saber: na primeira fase aplicou-se a técnica de evocações livres, com uso do termo indutor: doenças negligenciadas, sendo analisadas pela técnica do quadrante de quatro casas, com auxílio do EVOC, versão 2005; na segunda etapa, retornou-se ao campo de pesquisa, para aplicar ao um total de 27 participantes do mesmo grupo anterior, os instrumentos de testes de centralidade: a constituição de pares pareados e os esquemas cognitivos de base. Foram analisados pela análise de similitude e pelos índices de valência, respectivamente. Na terceira fase aplicou-se o instrumento da entrevista em profundidade, para 27 profissionais de saúde, sendo analisados com auxílio do IRAMUTEQ através da análise lexical mecanizada. Na análise estrutural, identificou-se o núcleo central, com os elementos descaso e ignorância, que organizaram as representações sociais dos profissionais de saúde em um contínuo que foi da dimensão individual à político-social, perpassando pelas dimensões socioindividual e imagética. Com relação ao conteúdo, no âmbito da abordagem processual, encontrou-se um corpus geral constituído por 27 entrevistas, separados em 1.076 segmentos de textos (ST) com aproveitamento de 1.043 STs (96,93 %). Emergiram 38.421 ocorrências (palavras, formas ou vocábulos), sendo 2.349 palavras distintas e 978 com uma única ocorrência. O conteúdo analisado foi categorizado em 07 classes distintas que evidenciaram as dimensões teórica e prática das representações sociais. As representações sociais dos profissionais de saúde sobre as doenças negligenciadas possuem uma atitude normativa, apesar de conviverem cotidianamente em seu ambiente de trabalho com estas enfermidades. Isto implicou na construção de julgamentos com elementos negativos, por parte dos profissionais de saúde, sobre as condutas e práticas dos sujeitos que compõem a tríade (indivíduo, equipe de saúde e gestores) no enfrentamento das doenças negligenciadas. Conclui-se que, as representações sociais dos profissionais de saúde acerca das doenças negligenciadas gerenciam e influenciam suas práticas de cuidado, modificando a realidade que os cerca e protagonizando novos saberes e conhecimentos indispensáveis para o controle, a prevenção e o tratamento destas entidades mórbidas.

Neglected diseases are characterized by a group of infectious diseases that mainly affect low-income people in developing countries, with little investment in research and technology to enhance their control, prevention and drug treatment. Their denomination is due to the fact that they do not arouse the economic and financial interest of the big pharmaceutical industries, maintaining the continuity of the poverty cycle and diminishing the quality of life of the people. Our general objective was to analyze the social representations about neglected diseases in health professionals, with emphasis on the conceptual and practical dimensions of these representations. It is a research of a qualitative nature, supported by the Theory of Social Representations, in its procedural and structural approaches, carried out with 90 health professionals who work in primary and secondary health care institutions, in the municipality of Jequié, Bahia, Brazil. The research was carried out in three distinct phases: in the first stage we used the technique of free evocations, with the inductor term: neglected diseases, being analyzed by the four quadrants technique, with the help of EVOC, 2005 version; in the second stage, we returned to the field of research, to apply to a total of 27 participants of the same previous group the instruments of the centrality tests: the constitution of matched pairs and the basic cognitive schemes. They were analyzed by the similitude analysis and by the valence indices, respectively. In the third phase, we applied the instrument of the in-depth interview to 27 health professionals, being analyzed with the help of IRAMUTEQ through the mechanized lexical analysis. In the structural analysis, the central nucleus was identified, with the elements neglect and ignorance, which organized the social representations of health professionals in a continuum that went from the individual to the social-political dimension, spanning the social-individual and imagery dimensions. Regarding the content, in the scope of the procedural approach, a general corpus was composed of 27 interviews, separated into 1,076 text segments (TS) from which 1,043 TS (96.93%) were used. 38,421 occurrences (words, forms or terms) emerged, being 2,349 distinct words and 978 with a single occurrence. The analyzed content was categorized into 07 distinct classes that showed the theoretical and practical dimensions of social representations. The social representations of the health professionals on neglected diseases show that they have a normative attitude, although they interact daily with these diseases in their work environment. This implied the construction of judgments with negative elements, by the health professionals, about the behaviors and practices of the subjects that make up the triad (individual, health team and managers) in coping with neglected diseases. It is concluded that the social representations of the health professionals on neglected diseases manage and influence their care practices, modifying the reality that surrounds them and playing a leading role in new and indispensable knowledge for the control, prevention and treatment of these morbid entities.

Las enfermedades descuidadas son caracterizadas por un grupo de enfermedades infecciosas que afectan principalmente a la populación de baja renta en los países en desarrollo, con pocas inversiones en investigación y tecnología para avanzar en el control, en la prevención y tratamiento medicamentoso. Son así denominadas también por el hecho de no despertar el interés económico y financiero de las grandes industrias farmacéuticas proporcionando la continuidad del ciclo de pobreza y la disminución de la calidad de vida de las personas. El objetivo general fue analizar las representaciones sociales acerca de las enfermedades descuidadas para los profesionales de la salud con énfasis en las dimensiones conceptual y práctica de estas representaciones. Se trata de una investigación de naturaleza cualitativa, sustentada en la Teoría de las Representaciones Sociales, en sus abordajes procesual y estructural, realizada con 90 profesionales de la salud que actúan en instituciones de atención primaria y secundaria a la salud, en el municipio de Jequié, Bahia, Brasil. La investigación aconteció en tres fases distintas, a saber: en la primera fase se aplicó la técnica de evocaciones libres, con uso del término inductor: enfermedades descuidadas, siendo analizadas por la técnica del cuadrante de cuatro casas, con auxilio del EVOC, versión 2005; en la segunda etapa, se retornó al campo de investigación, para aplicar a un total de 27 participantes del mismo grupo anterior los instrumentos de pruebas de centralidad: la constitución de pares pareados y los esquemas cognitivos de base. Fueron analizados por el análisis de similitud y por los índices de valencia, respectivamente. En la tercera fase, se aplicó el instrumento de la entrevista en profundidad, para 27 profesionales de la salud, siendo analizado con auxilio del IRAMUTEQ a través del análisis lexical mecanizado. En el análisis estructural, se identificó el núcleo central, con los elementos descaso e ignorancia, que organizaron las representaciones sociales de los profesionales de la salud en un continuo que fue de la dimensión individual a la político-social, pasando por las dimensiones socio individual e imagética. Con relación al contenido, en el ámbito del abordaje procesual, se encontró un corpus general constituido por 27 entrevistas, separadas en 1.076 segmentos de textos (ST) con aprovechamiento de 1.043 STs (96,93 %). Emergieron 38.421 ocurrencias (palabras, formas o vocablos), siendo 2.349 palabras distintas y 978 con una única ocurrencia. El contenido analizado fue categorizado en 07 clases distintas que evidenciaron las dimensiones teórica y práctica de las representaciones sociales. Las representaciones sociales de los profesionales de la salud sobre las enfermedades descuidadas tienen una actitud normativa, a pesar de convivir cotidianamente en su ambiente de trabajo con estas enfermedades. Esto implicó la construcción de juicios con elementos negativos, por parte de los profesionales de la salud, sobre las conductas y prácticas de los sujetos que componen la tríade (individuo, equipo de salud y gestores) en el enfrentamiento de las enfermedades descuidadas. Se concluye que las representaciones sociales de los profesionales de la salud acerca de las enfermedades descuidadas gerencian e influencian sus prácticas de cuidado, modificando la realidad que los rodea y protagonizando nuevos saberes y conocimientos indispensables para el control, la prevención y el tratamiento de esas entidades mórbidas.

Correlates of GLA family adjuvants' activities.

Lipopolysaccharide (LPS) is a well-defined agonist of Toll-like receptor (TLR) 4 that activates innate immune responses and influences the development of the adaptive response during infection with Gram-negative bacteria. Many years ago, Dr. Edgar Ribi separated the adjuvant activity of LPS from its toxic effects, an effort that led to the development of monophosphoryl lipid A (MPL). MPL, derived from Salmonella minnesota R595, has progressed through clinical development and is now used in various product-enabling formulations to support the generation of antigen-specific responses in several commercial and preclinical vaccines. We have generated several synthetic lipid A molecules, foremost glucopyranosyl lipid adjuvant (GLA) and second-generation lipid adjuvant (SLA), and have advanced these to clinical trial for various indications. In this review we summarize the potential and current positioning of TLR4-based adjuvant formulations in approved and emerging vaccines.

Nanopharmaceuticals as a solution to neglected diseases: Is it possible?

The study of neglected diseases has not received much attention, especially from public and private institutions over the last years, in terms of strong support for developing treatment for these diseases. Support in the form of substantial amounts of private and public investment is greatly needed in this area. Due to the lack of novel drugs for these diseases, nanobiotechnology has appeared as an important new breakthrough for the treatment of neglected diseases. Recently, very few reviews focusing on filiarasis, leishmaniasis, leprosy, malaria, onchocerciasis, schistosomiasis, trypanosomiasis, and tuberculosis, and dengue virus have been published. New developments in nanocarriers have made promising advances in the treatment of several kinds of diseases with less toxicity, high efficacy and improved bioavailability of drugs with extended release and fewer applications. This review deals with the current status of nanobiotechnology in the treatment of neglected diseases and highlights how it provides key tools for exploring new perspectives in the treatment of a wide range of diseases.

[Description of duplicate records held on the Notifiable Diseases Information System, Brazil, 2008-2009]. / Descrição dos registros repetidos no Sistema de Informação de Agravos de Notificação, Brasil, 2008-2009.

OBJECTIVE: to describe the proportion of duplicate records held on the Brazilian Notifiable Diseases Information System, 2008-2009. METHODS: identification of duplicate records of dengue, leprosy, visceral leishmaniasis and cutaneous leishmaniasis, meningitis and tuberculosis was conducted using Reclink III(r); the proportion of duplicate records was calculated by geographical region, state and municipal population size categories. RESULTS: visceral leishmaniasis (VL) and meningitis had higher proportions of duplicate notification (5.3% and 3.6%, respectively) whilst leprosy had the lowest (0.7%); the states with highest repetitions were Rio Grande do Norte (VL 6.8% and leprosy 5.1%), Rio de Janeiro (tuberculosis 2.5% and meningitis 4.9%) and Goiás (dengue 2.0% and meningitis 7.2%). CONCLUSION: the Northeast region had the highest proportion of duplicate records for four of the six diseases analyzed; with the exception of dengue, percentage repetition was lower in municipalities with larger population size.

Towards a toolkit for cross-neglected tropical disease morbidity and disability assessment.

BACKGROUND: Neglected tropical diseases (NTDs) are a group of often chronic and disabling infectious conditions, closely related to poverty and inequities. While it is estimated that millions of people are affected, accurate and internationally comparable data about NTD-related morbidity and disability are lacking. Therefore we aimed to develop and pilot a toolkit to assess and monitor morbidity and disability across NTDs. METHODS: A cross-sectional, non-random survey design with a mixed methods approach was used. We conducted a literature review on existing tools to assess and monitor disability, followed by a Delphi study with NTD experts to compile a prototype toolkit. A first-phase validation study was conducted in Northeast Brazil among people with Chagas disease, leishmaniasis, leprosy and schistosomiasis. RESULTS: Instruments included were the clinical profile, WHODAS, P-scale, SRQ, WHOQOL-BREF and WHOQOL-DIS. Most questions in the various instruments were readily understood with the exception of the WHOQOL-BREF, where additional explanations and examples were often needed. The respondents were very appreciative of the instruments and found it valuable to have the opportunity to talk about these aspects of their condition. CONCLUSIONS: Our findings support the acceptability and relevance of five of the six instruments tested and the concept of a cross-NTD toolkit.

The diagnostic challenge of mapping elephantiasis in the Tigray region of northern Ethiopia.

BACKGROUND: In Ethiopia, lymphatic filariasis and podoconiosis are the two neglected tropical diseases planned to be mapped together within the recently launched Ethiopian neglected tropical diseases master plan (2013-2015). However, other disorders cause tropical lymphedema, and this report aims to identify clinical epidemiological aspects of limb swelling in northern Ethiopia and to provide an algorithm orienting the clinical diagnosis. METHODS: Medical records of patients with lower limb elephantiasis attending the Italian Dermatological Centre of Mekele, Tigray capital city, over a 4-year period (2005-2009) were retrospectively analyzed. Nine variables were collected from the charts comprising demographic data, job, origin, literacy, clinical, histopathologic, microscopic, and cultural findings. RESULTS: Over a total of 511 patients, lymphedema resulted from trauma (40.7%), chronic venous insufficiency (12.5%), deep mycoses (10.8%), lymphatic filariasis (9.2%), elephantiasis nostras verrucosa (7.0%), tropical ulcer (6.3%), leprosy (4.9%), recurrent infections (3.1%), podoconiosis (1.8%), tuberculosis (1.0%), malignancy (1.3%), Kaposi's sarcoma (1.0%), leishmaniasis (0.2%), and neurofibromatosis (0.2%). CONCLUSIONS: Advanced-stage elephantiasis, chronic osteomyelitis, and podoconiosis not previously reported in Tigray were observed. Further epidemiological investigation and training programs addressed to healthcare providers at the peripheral level are needed to detect elephantiasis early, prevent disabilities, and improve patients' quality of life.

A lupane-triterpene isolated from Combretum leprosum Mart. fruit extracts that interferes with the intracellular development of Leishmania (L.) amazonensis in vitro.

BACKGROUND: 3beta,6beta,16beta-trihydroxylup-20(29)-ene is a lupane triterpene isolated from Combretum leprosum fruit. The lupane group has been extensively used in studies on anticancer effects; however, its possible activity against protozoa parasites is yet poorly known. The high toxicity of the compounds currently used in leishmaniasis chemotherapy stimulates the investigation of new molecules and drug targets for antileishmanial therapy. METHODS: The activity of 3beta,6beta,16beta-trihydroxylup-20(29)-ene was evaluated against Leishmania (L.) amazonensis by determining the cytotoxicity of the compound on murine peritoneal macrophages, as well as its effects on parasite survival inside host cells. To evaluate the effect of this compound on intracellular amastigotes, cultures of infected macrophages were treated for 24, 48 and 96 h and the percentage of infected macrophages and the number of intracellular parasites was scored using light microscopy. RESULTS: Lupane showed significant activity against the intracellular amastigotes of L. (L.) amazonensis. The treatment with 109 µM for 96 h reduced in 80 % the survival index of parasites in BALB/c peritoneal macrophages. At this concentration, the triterpene caused no cytotoxic effects against mouse peritoneal macrophages. Ultrastructural analyses of L. (L.) amazonensis intracellular amastigotes showed that lupane induced some morphological changes in parasites, such as cytosolic vacuolization, lipid body formation and mitochondrial swelling. Bioinformatic analyses through molecular docking suggest that this lupane has high-affinity binding with DNA topoisomerase. CONCLUSION: Taken together, our results have showed that the lupane triterpene from C. leprosum interferes with L. (L.) amazonensis amastigote replication and survival inside vertebrate host cells and bioinformatics analyses strongly indicate that this molecule may be a potential inhibitor of topoisomerase IB. Moreover, this study opens major prospects for the development of novel chemotherapeutic agents with leishmanicidal activity.

The application of biomedical engineering techniques to the diagnosis and management of tropical diseases: a review.

This paper reviews a number of biomedical engineering approaches to help aid in the detection and treatment of tropical diseases such as dengue, malaria, cholera, schistosomiasis, lymphatic filariasis, ebola, leprosy, leishmaniasis, and American trypanosomiasis (Chagas). Many different forms of non-invasive approaches such as ultrasound, echocardiography and electrocardiography, bioelectrical impedance, optical detection, simplified and rapid serological tests such as lab-on-chip and micro-/nano-fluidic platforms and medical support systems such as artificial intelligence clinical support systems are discussed. The paper also reviewed the novel clinical diagnosis and management systems using artificial intelligence and bioelectrical impedance techniques for dengue clinical applications.

The molecular genetics of inflammatory, autoimmune, and infectious diseases of the sinonasal tract: a review.

CONTEXT: The sinonasal tract is frequently affected by a variety of nonneoplastic inflammatory disease processes that are often multifactorial in their etiology but commonly have a molecular genetic component. OBJECTIVE: To review the molecular genetics of a variety of nonneoplastic inflammatory diseases of the sinonasal tract. DATA SOURCES: Inflammatory lesions of the sinonasal tract can be divided into 3 main categories: (1) chronic rhinosinusitis, (2) infectious diseases, and (3) autoimmune diseases/vasculitides. The molecular diagnosis and pathways of a variety of these inflammatory lesions are currently being elucidated and will shed light on disease pathogenesis and treatment. CONCLUSIONS: The sinonasal tract is frequently affected by inflammatory lesions that arise through complex interactions of environmental, infectious, and genetic factors. Because these lesions are all inflammatory in nature, the molecular pathology surrounding them is most commonly due to upregulation and down-regulation of genes that affect inflammatory responses and immune regulation.