Biomarkers for susceptibility to infection and disease severity in human malaria

Malaria remains a major infectious disease that affects millions of people. Once infected with Plasmodium parasites, a host can develop a broad range of clinical presentations, which result from complex interactions between factors derived from the host, the parasite and the environment. Intense research has focused on the identification of reliable predictors for exposure, susceptibility to infection and the development of severe complications during malaria. Although most promising markers are based on the current understanding of malaria immunopathogenesis, some are also focused more broadly on mechanisms of tissue damage and inflammation. Taken together, these markers can help optimise therapeutic strategies and reduce disease burden. Here, we review the recent advances in the identification of malarial biomarkers, focusing on those related to parasite exposure and disease susceptibility. We also discuss priorities for research in biomarkers for severe malaria.

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.

Cytokines and visceral leishmaniasis: a comparison of plasma cytokine profiles between the clinical forms of visceral leishmaniasis

It is not well established whether cytokine production differs in response to different clinical forms of visceral leishmaniasis (VL). In this work, we performed a cross-sectional study to investigate the plasma levels of cytokines [interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-10 and IL-12] involved in the pathogenesis of VL in 80 subjects from VL endemic areas, including subjects with active VL, subjects with asymptomatic infection, subjects with cured VL and uninfected controls. The patients were recruited by sampling from a referral hospital and by random selection from a population-based cohort study. The results showed significant differences in the plasma concentration of all cytokines between the groups (p < 0.05). Patients with the active disease had higher plasma levels of IL-10, IL-4, INF-γ and TNF-α relative to the other groups and they produced more IL-12 than asymptomatic and cured subjects. Only the IL-2 concentration was higher in the asymptomatic and cured subjects relative to the patients with active disease (p < 0.05). Our results suggest that these cytokines can be used as markers in epidemiological studies conducted in endemic areas to distinguish between different clinical forms of VL. However, their usefulness should be confirmed in investigations conducted in other endemic areas.

Polycystic echinococcosis in the state of Acre, Brazil: contribution to patient diagnosis, treatment and prognosis

The lack of knowledge regarding polycystic hydatid disease results in delayed or even incorrect diagnosis. The lack of systematic information regarding treatment also makes it difficult to assess the results and prognosis in patients with peritoneal and hepatic lesions caused by Echinococcus vogeli. Here we describe the clinical features of patients, propose a radiological classification protocol and describe a therapeutic option for the treatment of hydatid disease that previously had only been used for cases of cystic echinococcosis (Echinococcus granulosus). A prospective cohort study was initiated in 1999 and by 2009 the study included 60 patients. These patients were classified according to the PNM classification (parasite lesion, neighbouring organ invasion and metastases) and placed in one of three therapeutic modalities: (i) chemotherapy with albendazole at a dose of 10 mg/kg/day, (ii) surgical removal of cysts or (iii) percutaneous puncture of the cysts via puncture, aspiration, injection and re-aspiration (PAIR). The results were stratified according to therapeutic outcome: "cure", "clinical improvement", "no improvement", "death" or "no information". The PNM classification was useful in indicating the appropriate therapy in cases of polycystic hydatid disease. In conclusion, surgical therapy produced the best clinical results of all the therapies studied based on "cure" and "clinical improvement" outcomes. The use of PAIR for treatment requires additional study.

Severity of tegumentary leishmaniasis is not exclusively associated with Leishmania RNA virus 1 infection in Brazil

Leishmania RNA virus (LRV) has been shown to be a symbiotic component of Leishmania parasites in South America. Nested retro-transcription polymerase chain reaction was employed to investigate LRV1 presence in leishmaniasis lesions from Brazil. In endemic areas of Rio de Janeiro (RJ), no LRV1 infection was observed even with mucosal involvement. LRV1 was only detected in Leishmania (V.) guyanensis cutaneous lesions from the northern region, which were obtained from patients presenting with disease reactivation after clinical cure of their primary lesions. Our results indicated that the severity of leishmaniasis in some areas of RJ, where Leishmania (V.) brazi-liensis is the primary etiological agent, was not associated with Leishmania LRV1 infection.

Molecular identification of Sporothrix species involved in the first familial outbreak of sporotrichosis in the state of Espírito Santo, southeastern Brazil

Sporotrichosis is a widespread subcutaneous mycosis caused by the dimorphic fungi now known as the Sporothrix schenckii complex. This complex is comprised of at least six species, including Sporothrix albicans, Sporothrix brasiliensis, Sporothrix globosa, Sporothrix luriei, Sporothrix mexicana and S. schenckii. Cases of sporotrichosis have significantly increased in Brazil over the past decade, especially in the state of Rio de Janeiro (RJ), where an epidemic among cat owners has been observed. The zoonotic transmission from cats to humans suggests a common source of infection and indicates that animals can act as vectors. We performed a molecular characterisation of samples collected during the first outbreak of familial sporotrichosis caused by S. brasiliensis in the state of Espírito Santo, Brazil. These results represent the first description of such an outbreak outside the endemic area of zoonotic sporotrichosis in RJ.

Immunoregulation in human malaria: the challenge of understanding asymptomatic infection

Asymptomatic Plasmodium infection carriers represent a major threat to malaria control worldwide as they are silent natural reservoirs and do not seek medical care. There are no standard criteria for asymptomaticPlasmodium infection; therefore, its diagnosis relies on the presence of the parasite during a specific period of symptomless infection. The antiparasitic immune response can result in reducedPlasmodium sp. load with control of disease manifestations, which leads to asymptomatic infection. Both the innate and adaptive immune responses seem to play major roles in asymptomatic Plasmodiuminfection; T regulatory cell activity (through the production of interleukin-10 and transforming growth factor-β) and B-cells (with a broad antibody response) both play prominent roles. Furthermore, molecules involved in the haem detoxification pathway (such as haptoglobin and haeme oxygenase-1) and iron metabolism (ferritin and activated c-Jun N-terminal kinase) have emerged in recent years as potential biomarkers and thus are helping to unravel the immune response underlying asymptomatic Plasmodium infection. The acquisition of large data sets and the use of robust statistical tools, including network analysis, associated with well-designed malaria studies will likely help elucidate the immune mechanisms responsible for asymptomatic infection.

The microbiological signature of human cutaneous leishmaniasis lesions exhibits restricted bacterial diversity compared to healthy skin

Localised cutaneous leishmaniasis (LCL) is the most common form of cutaneous leishmaniasis characterised by single or multiple painless chronic ulcers, which commonly presents with secondary bacterial infection. Previous culture-based studies have found staphylococci, streptococci, and opportunistic pathogenic bacteria in LCL lesions, but there have been no comparisons to normal skin. In addition, this approach has strong bias for determining bacterial composition. The present study tested the hypothesis that bacterial communities in LCL lesions differ from those found on healthy skin (HS). Using a high throughput amplicon sequencing approach, which allows for better populational evaluation due to greater depth coverage and the Quantitative Insights Into Microbial Ecology pipeline, we compared the microbiological signature of LCL lesions with that of contralateral HS from the same individuals.Streptococcus, Staphylococcus,Fusobacterium and other strict or facultative anaerobic bacteria composed the LCL microbiome. Aerobic and facultative anaerobic bacteria found in HS, including environmental bacteria, were significantly decreased in LCL lesions (p < 0.01). This paper presents the first comprehensive microbiome identification from LCL lesions with next generation sequence methodology and shows a marked reduction of bacterial diversity in the lesions.

Fatores que contribuem para a maturidade em gerenciamento de projetos: o caso de um governo estadual

No presente estudo, o objetivo é identificar os fatores que contribuem para o incremento da maturidade em gerenciamento de projetos em organizações públicas. Argumenta-se que a gestão de projetos é de suma importância para melhorar o desempenho organizacional e alinhar as atividades organizacionais aos objetivos estratégicos, além de estimular o desenvolvimento de inovações, o desenvolvimento de novos bens e serviços e a melhoria da eficiência organizacional. Metodologicamente, adotou-se uma postura quantitativa de natureza descritiva e realizou-se um survey com 161 gestores em nível de coordenação e subcoordenação, possibilitando um erro amostral inferior a 6% para 95% de confiança. Conclusivamente, no estudo identificaram-se oito fatores que, na visão dos gestores, contribuem para a maturidade na gestão dos projetos públicos, com destaque para a percepção de que a visibilidade proporcionada aos gestores é um dos fatores determinantes para o incremento da maturidade.

Questionário de dor McGill: proposta de adaptação para a língua portuguesa

Dor é uma experiência multidimensional e subjetiva. O desenvolvimento de instrumentos que possibilitem a avaliação da dor nos seus diversos aspectos, é fundamental para a compreensão do quadro álgico, implementação da terapêutica e apreciação de sua eficácia. O questionário McGill é considerado um dos melhores instrumentos para a avaliação das dimensões sensitiva-discriminativa, afetiva-motivacional e cognitiva-avaliativa da dor. Apresentar proposta de sua adaptação para a língua portuguesa é o objetivo deste estudo.

Liga de Dor: uma experiência de ensino extracurricular

Os objetivos deste estudo foram descrever um programa extracurricular de educação em dor, organizado na forma de Liga, e identificar a opinião dos alunos sobre esse modelo de ensino. O Estatuto e o Regimento Interno da Liga de Dor foram as fontes e dados para a descrição da sua organização e funcionamento. Todos os alunos que frequentaram a Liga de Dor nos anos de 1995 e 1996 foram solicitados a responder um questionário sobre suas experiências na Liga. A Liga de Dor foi organizada sob o patrocínio do Centro Acadêmico Osvaldo Cruz, da Faculdade de Medicina da USP, e Centro Acadêmico XXXI de Outubro, da Escola de Enfermagem da USP, em 1995. É composta por alunos dessas duas faculdades e profissionais enfermeiros e médicos, de várias especialidades. Todas as atividades são voluntárias, desenvolvidas em período extracurricular e os estudantes dirigem a Liga. Os objetivos da Liga são: melhorar a qualidade do ensino sobre dor nas escolas médica e de enfermagem, desenvolver pesquisas relativas à epidemiologia, clínica e controle da dor e promover modelo de assistência multidisciplinar e multiprofissional. A maioria dos alunos expressou ter alcançado seus objetivos, total ou parcialmente; ter aumentado seu conhecimento sobre as síndromes álgicas e sobre o manejo do doente com dor; sentir-se gratificado com sua atividade; que o tema dor deveria ser incluído no currículo de modo mais específico e que recomendaria a outros colegas a participação na Liga de Dor. As opiniões dos estudantes mostraram que a Liga de Dor pode ser um modelo útil para a introdução do ensino da dor nos cursos de graduação e enfermagem e de medicina.

Dor crônica e depressão: estudo em 92 doentes

O estudo objetivou analisar a existência de relações entre dor e depressão em noventa e dois doentes com doença oncológica avançada. Os doentes foram divididos em 2 grupos, com ou sem dor na semana anterior à entrevista. Havia dor em 62,0% dos avaliados, a duração média do quadro álgico foi 10 meses e a maioria referiu dor moderada. Os indivíduos do grupo com dor apresentaram escores de depressão significativamente mais altos que os do grupo sem dor (p<0,05). Doentes com mais altos escores de depressão experienciaram dor de maior intensidade (p<00,5). Sintomas depressivos associaram-se e agravaram a experiência dolorosa.

Fatores relacionados ao autocuidado de pessoas com diabetes mellitus atendidas em Serviço de Urgência no México

Estudo transversal com os objetivos de determinar a capacidade de autocuidado de pessoas com diabetes mellitus tipo 2 e relacionar tal capacidade com variáveis sociodemográficas e clínicas. Participaram 251 pessoas que ingressaram no Serviço de Urgência do Hospital Regional Mérida, em Yucatán, México, em 2006. Os dados foram obtidos mediante entrevista domiciliar dirigida, utilizando-se formulário, questionário e a Escala de Capacidade Autocuidado. Para a análise, utilizou-se a estatística descritiva e correlacional. Os resultados mostraram que 83 (33,5%) dos sujeitos apresentaram boa capacidade de autocuidado e 168 (66,5%), capacidade regular. Obteve-se correlação diretamente proporcional entre capacidade de autocuidado e anos de estudo (r=0,124; p<0,05), mas negativa para religião (rs=-0,435; p<0,05) e tempo de evolução da doença (r=-0,667; p<0,05). Para a promoção do autocuidado em pessoas com diabetes faz-se necessário considerar essas variáveis, bem como desenvolver novos estudos que enfoquem outras variáveis envolvidas no comportamento adotado em benefício da saúde.

Uso de álcool e espiritualidade entre estudantes de enfermagem

O objetivo deste estudo transversal foi investigar o uso de álcool e níveis de espiritualidade entre estudantes de Enfermagem. Aplicou-se o Teste de Identificação do Uso do Álcool e a Escala de Espiritualidade. Participaram 191 (80,2%) estudantes do curso de Enfermagem de uma cidade do interior de Minas Gerais, sendo 75,4% do sexo feminino, idade média 25 anos, 149 (78%) de religião católica. Quanto ao uso de álcool por sexo, 117 (75%) mulheres faziam uso de bebida alcoólica e 33 (56,9%) bebiam em nível problemático (p?0,05), contra 25 homens (43,1%). Foi encontrada uma pontuação baixa dos níveis de espiritualidade na amostra: em média, mulheres apresentaram escore menor em comparação aos homens (12,7 vs 13,5). Na comparação entre níveis de espiritualidade e beber problemático, observou-se que estudantes com uso de baixo risco apresentaram menores níveis de espiritualidade. Concluiu-se que a espiritualidade pode não funcionar como fator protetor para uso do álcool, sugerindo que esse comportamento pode estar sob o controle de outras variáveis.