A simple approach improving the performance of urine reagent strips for rapid diagnosis of urinary schistosomiasis in Nigerian schoolchildren

In Nigeria, schistosomiasis, caused predominantly by the species Schistosoma haematobium, is highly endemic in resource-poor communities. We performed a school-based survey in two rural communities in Osun State (Southwestern Nigeria) and assessed macrohaematuria, microhaematuria and proteinuria as indirect indicators for the presence of disease. Urine samples were inspected macroscopically for haematuria and screened for microhaematuria and proteinuria using urine reagent strips. The microscopic examination of schistosome eggs was used as the gold standard for diagnosis. In total, 447 schoolchildren were included in this study and had a 51% prevalence of urinary schistosomiasis. The sensitivity of microhaematuria (68%) and proteinuria (53%) for infection with S. haematobium was relatively low. In patients with a heavy infection (>500 eggs/10 mL), the sensitivity of microhaematuria was high (95%). When the presence of macrohaematuria and the concomitant presence of microhaematuria and proteinuria were combined, it revealed a sensitivity of 63%, a specificity of 93% and a positive predictive value of 91%. Macrohaematuria also showed high specificity (96%) and a positive predictive value of 92%, while sensitivity was < 50%. These data show that combining urine reagent strip tests (presence of proteinuria and microhaematuria) and information on macrohaematuria increased the accuracy of the rapid diagnosis of urinary schistosomiasis in an endemic rural West African setting. This simple approach can be used to increase the quality of monitoring of schistosomiasis in schoolchildren.

A new approach for potential drug target discovery through in silico metabolic pathway analysis using Trypanosoma cruzi genome information

The current drug options for the treatment of chronic Chagas disease have not been sufficient and high hopes have been placed on the use of genomic data from the human parasite Trypanosoma cruzi to identify new drug targets and develop appropriate treatments for both acute and chronic Chagas disease. However, the lack of a complete assembly of the genomic sequence and the presence of many predicted proteins with unknown or unsure functions has hampered our complete view of the parasite's metabolic pathways. Moreover, pinpointing new drug targets has proven to be more complex than anticipated and has revealed large holes in our understanding of metabolic pathways and their integrated regulation, not only for this parasite, but for many other similar pathogens. Using an in silicocomparative study on pathway annotation and searching for analogous and specific enzymes, we have been able to predict a considerable number of additional enzymatic functions in T. cruzi. Here we focus on the energetic pathways, such as glycolysis, the pentose phosphate shunt, the Krebs cycle and lipid metabolism. We point out many enzymes that are analogous to those of the human host, which could be potential new therapeutic targets.

Clinical-epidemiologic profile of the schistosomal myeloradiculopathy in Pernambuco, Brazil

This was a retrospective descriptive study on a series of cases of schistosomal myeloradiculopathy (SMR) and the aim was to investigate the incidence of this disease and its clinical and epidemiological characteristics in cases diagnosed at three healthcare units in Pernambuco, Brazil between 1994-2006. The data were collected by reviewing the medical records from both the neurological and paediatric outpatient clinics and wards of the Hospital Clinics, Hospital of the Restoration and Pernambuco Mother and Child Institute. To gather the data, a spinal cord schistosomiasis evaluation protocol was used. The diagnoses were based on positive epidemiological evidence of schistosomiasis, clinical findings and laboratory tests (stool parasitological examination or rectal biopsies, magnetic resonance imaging findings and cerebrospinal fluid investigations). A total of 139 cases aged between 2-83 years were found. The most important determinants of SMR were male sex (66.2%), contact with fresh water (91%), origin in endemic regions (39.5%), lower-limb muscle weakness (100%), sensory level at the lower thoracic medulla (40.3%), myeloradicular form (76%) and presence of eggs in the stool parasitological examination (48%). This sample indicates the need for intervention policies guided by diagnostic standardization, thereby avoiding disease under-notification.

A geoprocessing approach for studying and controlling schistosomiasis in the state of Minas Gerais, Brazil

Geographical information systems (GIS) are tools that have been recently tested for improving our understanding of the spatial distribution of disease. The objective of this paper was to further develop the GIS technology to model and control schistosomiasis using environmental, social, biological and remote-sensing variables. A final regression model (R² = 0.39) was established, after a variable selection phase, with a set of spatial variables including the presence or absence of Biomphalaria glabrata, winter enhanced vegetation index, summer minimum temperature and percentage of houses with water coming from a spring or well. A regional model was also developed by splitting the state of Minas Gerais (MG) into four regions and establishing a linear regression model for each of the four regions: 1 (R² = 0.97), 2 (R² = 0.60), 3 (R² = 0.63) and 4 (R² = 0.76). Based on these models, a schistosomiasis risk map was built for MG. In this paper, geostatistics was also used to make inferences about the presence of Biomphalaria spp. The result was a map of species and risk areas. The obtained risk map permits the association of uncertainties, which can be used to qualify the inferences and it can be thought of as an auxiliary tool for public health strategies.

Schistosomiasis risk mapping in the state of Minas Gerais, Brazil, using a decision tree approach, remote sensing data and sociological indicators

Schistosomiasis mansoni is not just a physical disease, but is related to social and behavioural factors as well. Snails of the Biomphalaria genus are an intermediate host for Schistosoma mansoni and infect humans through water. The objective of this study is to classify the risk of schistosomiasis in the state of Minas Gerais (MG). We focus on socioeconomic and demographic features, basic sanitation features, the presence of accumulated water bodies, dense vegetation in the summer and winter seasons and related terrain characteristics. We draw on the decision tree approach to infection risk modelling and mapping. The model robustness was properly verified. The main variables that were selected by the procedure included the terrain's water accumulation capacity, temperature extremes and the Human Development Index. In addition, the model was used to generate two maps, one that included risk classification for the entire of MG and another that included classification errors. The resulting map was 62.9% accurate.

Predictors of local malaria outbreaks: an approach to the development of an early warning system in Colombia

Risk factor surveillance is a complementary tool of morbidity and mortality surveillance that improves the likelihood that public health interventions are implemented in a timely fashion. The aim of this study was to identify population predictors of malaria outbreaks in endemic municipalities of Colombia with the goal of developing an early warning system for malaria outbreaks. We conducted a multiple-group, exploratory, ecological study at the municipal level. Each of the 290 municipalities with endemic malaria that we studied was classified according to the presence or absence of outbreaks. The measurement of variables was based on historic registries and logistic regression was performed to analyse the data. Altitude above sea level [odds ratio (OR) 3.65, 95% confidence interval (CI) 1.34-9.98], variability in rainfall (OR 1.85, 95% CI 1.40-2.44) and the proportion of inhabitants over 45 years of age (OR 0.17, 95% CI 0.08-0.38) were factors associated with malaria outbreaks in Colombian municipalities. The results suggest that environmental and demographic factors could have a significant ability to predict malaria outbreaks on the municipal level in Colombia. To advance the development of an early warning system, it will be necessary to adjust and standardise the collection of required data and to evaluate the accuracy of the forecast models.

Delimitation of kala-azar risk areas in the district of Vaishali in Bihar (India) using a geo-environmental approach

Remote sensing and geographical information technologies were used to discriminate areas of high and low risk for contracting kala-azar or visceral leishmaniasis. Satellite data were digitally processed to generate maps of land cover and spectral indices, such as the normalised difference vegetation index and wetness index. To map estimated vector abundance and indoor climate data, local polynomial interpolations were used based on the weightage values. Attribute layers were prepared based on illiteracy and the unemployed proportion of the population and associated with village boundaries. Pearson's correlation coefficient was used to estimate the relationship between environmental variables and disease incidence across the study area. The cell values for each input raster in the analysis were assigned values from the evaluation scale. Simple weighting/ratings based on the degree of favourable conditions for kala-azar transmission were used for all the variables, leading to geo-environmental risk model. Variables such as, land use/land cover, vegetation conditions, surface dampness, the indoor climate, illiteracy rates and the size of the unemployed population were considered for inclusion in the geo-environmental kala-azar risk model. The risk model was stratified into areas of "risk"and "non-risk"for the disease, based on calculation of risk indices. The described approach constitutes a promising tool for microlevel kala-azar surveillance and aids in directing control efforts.

A combined approach of VNTR and MLST analysis: improving molecular typing of Argentinean isolates of Leptospira interrogans

Leptospirosis is an emerging infectious disease that has been identified as both a human and animal health problem worldwide. Regular outbreaks associated with specific risk factors have been reported in Argentina. However, there are no available data concerning the genetic population level for this pathogen. Therefore, the aim of this work was to describe the genetic diversity of Leptospira interrogans through the application of two molecular typing strategies: variable number of tandem repeats (VNTR) and multilocus sequence typing (MLST). For this purpose, seven reference strains and 18 non-epidemiologically related isolates from diverse hosts and Argentinean regions were analysed. Among them, nine genotypes and seven sequence types (STs), including three unreported STs, were described using VNTR and MLST, respectively. eBURST analysis demonstrated that ST37 was the most frequent and founder genotype of a clonal complex (CCs) containing STN1 and STN3, suggesting the importance of studying the serovars belonging to this CC in Argentina. The data from maximum parsimony analysis, which combined both techniques, achieved intra-serovar discrimination, surmounted microscopic agglutination test discrepancies and increased the discriminatory power of each technique applied separately. This study is the first to combine both strategies for L. interrogans typing to generate a more comprehensive molecular genotyping of isolates from Argentina in a global context.

Outbreak of carbapenem-resistant Klebsiella pneumoniae: two-year epidemiologic follow-up in a tertiary hospital

This study describes a carbapenem-resistant Klebsiella pneumoniae (CRKP) outbreak that occurred from October 2008-December 2010. Polymerase chain reaction assays were performed to detect the blaKPC gene and molecular typing was performed using pulsed-field gel electrophoresis (PFGE). There were 33 CRKP infections; PFGE revealed five genotypes: genotype A in five (15%), B in 18 (55%), C in eight (24%) and two unique profiles. Genotype B was disseminated in all hospital units and belonged to the same clone identified in 11 different hospitals in the state of São Paulo. Sixteen (48%) patients died. Seven isolates (21%) were resistant to polymyxin B and 45% were resistant to tigecycline and amikacin.

Identification and characterisation of microRNAs in young adults of Angiostrongylus cantonensis via a deep-sequencing approach

Angiostrongylus cantonensis is an important causative agent of eosinophilic meningitis and eosinophilic meningoencephalitis in humans. MicroRNAs (miRNAs) are small non-coding RNAs that participate in a wide range of biological processes. This study employed a deep-sequencing approach to study miRNAs from young adults of A. cantonensis. Based on 16,880,456 high-quality reads, 252 conserved mature miRNAs including 10 antisense miRNAs that belonging to 90 families, together with 10 antisense miRNAs were identified and characterised. Among these sequences, 53 miRNAs from 25 families displayed 50 or more reads. The conserved miRNA families were divided into four groups according to their phylogenetic distribution and a total of nine families without any members showing homology to other nematodes or adult worms were identified. Stem-loop real-time polymerase chain reaction analysis of aca-miR-1-1 and aca-miR-71-1 demonstrated that their level of expression increased dramatically from infective larvae to young adults and then decreased in adult worms, with the male worms exhibiting significantly higher levels of expression than female worms. These findings provide information related to the regulation of gene expression during the growth, development and pathogenesis of young adults of A. cantonensis.

A directed approach for the identification of transcripts harbouring the spliced leader sequence and the effect of trans-splicing knockdown in Schistosoma mansoni

Schistosomiasis is a major neglected tropical disease caused by trematodes from the genus Schistosoma. Because schistosomes exhibit a complex life cycle and numerous mechanisms for regulating gene expression, it is believed that spliced leader (SL) trans-splicing could play an important role in the biology of these parasites. The purpose of this study was to investigate the function of trans-splicing in Schistosoma mansoni through analysis of genes that may be regulated by this mechanism and via silencing SL-containing transcripts through RNA interference. Here, we report our analysis of SL transcript-enriched cDNA libraries from different S. mansoni life stages. Our results show that the trans-splicing mechanism is apparently not associated with specific genes, subcellular localisations or life stages. In cross-species comparisons, even though the sets of genes that are subject to SL trans-splicing regulation appear to differ between organisms, several commonly shared orthologues were observed. Knockdown of trans-spliced transcripts in sporocysts resulted in a systemic reduction of the expression levels of all tested trans-spliced transcripts; however, the only phenotypic effect observed was diminished larval size. Further studies involving the findings from this work will provide new insights into the role of trans-splicing in the biology of S. mansoni and other organisms. All Expressed Sequence Tags generated in this study were submitted to dbEST as five different libraries. The accessions for each library and for the individual sequences are as follows: (i) adult worms of mixed sexes (LIBEST_027999: JZ139310 - JZ139779), (ii) female adult worms (LIBEST_028000: JZ139780 - JZ140379), (iii) male adult worms (LIBEST_028001: JZ140380 - JZ141002), (iv) eggs (LIBEST_028002: JZ141003 - JZ141497) and (v) schistosomula (LIBEST_028003: JZ141498 - JZ141974).

Mansonella ozzardi in the municipality of Tefé, Amazonas, Brazil, 60 years after the first report: an epidemiologic study

The prevalence of mansonelliasis was studied in the municipality of Tefé, state of Amazonas, Brazil. The prevalence (thick blood smear method) was 13.6% (147/1,078), higher in the Solimões River region (16.3%) than in the Tefé River region (6.3%). In the sampled communities in the Solimões River region, a higher density of cases was observed, as indicated by a kernel analysis (odds ratio 0.34; 95% confidence interval: 0.20-0.57). Males had a higher prevalence (χ2 = 31.292, p < 0.001) than women. Mansonella ozzardi prevalence was higher in retirees and farmers (28.9% and 27%, respectively). Prevalence also significantly increased with age (χ2 = -128.17, p < 0.001), with the highest numbers occurring in persons older than 67 years.

Yellow fever impact on brown howler monkeys (Alouatta guariba clamitans) in Argentina: a metamodelling approach based on population viability analysis and epidemiological dynamics

In South America, yellow fever (YF) is an established infectious disease that has been identified outside of its traditional endemic areas, affecting human and nonhuman primate (NHP) populations. In the epidemics that occurred in Argentina between 2007-2009, several outbreaks affecting humans and howler monkeys (Alouatta spp) were reported, highlighting the importance of this disease in the context of conservation medicine and public health policies. Considering the lack of information about YF dynamics in New World NHP, our main goal was to apply modelling tools to better understand YF transmission dynamics among endangered brown howler monkey (Alouatta guariba clamitans) populations in northeastern Argentina. Two complementary modelling tools were used to evaluate brown howler population dynamics in the presence of the disease: Vortex, a stochastic demographic simulation model, and Outbreak, a stochastic disease epidemiology simulation. The baseline model of YF disease epidemiology predicted a very high probability of population decline over the next 100 years. We believe the modelling approach discussed here is a reasonable description of the disease and its effects on the howler monkey population and can be useful to support evidence-based decision-making to guide actions at a regional level.

A three-pronged approach to social business: a Brazilian multi-case analysis

Social businesses present a new paradigm to capitalism, in which private companies, non-profit organizations and civil society create a new type of business with the main objective of solving social problems with financial sustainability and efficiency through market mechanisms. As any new phenomenon, different authors conceptualize social businesses with distinct views. This article aims to present and characterize three different perspectives of social business definitions: the European, the American and that of the emerging countries. Each one of these views was illustrated by a different Brazilian case. We conclude with the idea that all the cases have similar characteristics, but also relevant differences that are more than merely geographical. The perspectives analyzed in this paper provide an analytical framework for understanding the field of social businesses. Moreover, the cases demonstrate that in the Brazilian context the field of social business is under construction and that as such it draws on different conceptual influences to deal with a complex and challenging reality.

The generation and re-generation of social capital and enterprises in multi-stakeholders social cooperative enterprises: a system dynamic approach

Theories on social capital and on social entrepreneurship have mainly highlighted the attitude of social capital to generate enterprises and to foster good relations between third sector organizations and the public sector. This paper considers the social capital in a specific third sector enterprise; here, multi-stakeholder social cooperatives are seen, at the same time, as social capital results, creators and incubators. In the particular enterprises that identify themselves as community social enterprises, social capital, both as organizational and relational capital, is fundamental: SCEs arise from but also produce and disseminate social capital. This paper aims to improve the building of relational social capital and the refining of helpful relations drawn from other arenas, where they were created and from where they are sometimes transferred to other realities, where their role is carried on further (often working in non-profit, horizontally and vertically arranged groups, where they share resources and relations). To represent this perspective, we use a qualitative system dynamic approach in which social capital is measured using proxies. Cooperation of volunteers, customers, community leaders and third sector local organizations is fundamental to establish trust relations between public local authorities and cooperatives. These relations help the latter to maintain long-term contracts with local authorities as providers of social services and enable them to add innovation to their services, by developing experiences and management models and maintaining an interchange with civil servants regarding these matters. The long-term relations and the organizational relations linking SCEs and public organizations help to create and to renovate social capital. Thus, multi-stakeholder cooperatives originated via social capital developed in third sector organizations produce new social capital within the cooperatives themselves and between different cooperatives (entrepreneurial components of the third sector) and the public sector. In their entrepreneurial life, cooperatives have to contrast the "working drift," as a result of which only workers remain as members of the cooperative, while other stakeholders leave the organization. Those who are not workers in the cooperative are (stake)holders with "weak ties," who are nevertheless fundamental in making a worker's cooperative an authentic social multi-stakeholders cooperative. To maintain multi-stakeholder governance and the relations with third sector and civil society, social cooperatives have to reinforce participation and dialogue with civil society through ongoing efforts to include people that provide social proposals. We try to represent these processes in a system dynamic model applied to local cooperatives, measuring the social capital created by the social cooperative through proxies, such as number of volunteers and strong cooperation with public institutions. Using a reverse-engineering approach, we can individuate the determinants of the creation of social capital and thereby give support to governance that creates social capital.