scholarly journals Praziquantel for Schistosomiasis: Single-Drug Metabolism Revisited, Mode of Action, and Resistance

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Nuno Vale ◽  
Maria João Gouveia ◽  
Gabriel Rinaldi ◽  
Paul J. Brindley ◽  
Fátima Gärtner ◽  
...  

ABSTRACT Schistosomiasis, a major neglected tropical disease, affects more than 250 million people worldwide. Treatment of schistosomiasis has relied on the anthelmintic drug praziquantel (PZQ) for more than a generation. PZQ is the drug of choice for the treatment of schistosomiasis; it is effective against all major forms of schistosomiasis, although it is less active against juvenile than mature parasites. A pyrazino-isoquinoline derivative, PZQ is not considered to be toxic and generally causes few or transient, mild side effects. Increasingly, mass drug administration targeting populations in sub-Saharan Africa where schistosomiasis is endemic has led to the appearance of reduced efficacy of PZQ, which portends the selection of drug-resistant forms of these pathogens. The synthesis of improved derivatives of PZQ is attracting attention, e.g., in the (i) synthesis of drug analogues, (ii) rational design of pharmacophores, and (iii) discovery of new compounds from large-scale screening programs. This article reviews reports from the 1970s to the present on the metabolism and mechanism of action of PZQ and its derivatives against schistosomes.

Open Praxis ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 405 ◽  
Author(s):  
Judith Pete ◽  
Fred Mulder ◽  
Jose Dutra Oliveira Neto ◽  
Kathleen Ludewig Omollo

This paper is the second in a series of three with a common goal to present a fair OER picture for Sub-Saharan Africa, represented by large-scale studies in three countries: Kenya, Ghana, and South Africa. This paper examines a deliberate selection of four Ghanaian universities with randomly sampled students and lecturers. Distinct questionnaires for students and the lecturers have been used, which generated a response from in total 818 students and 38 lecturers. The major outcomes based on the empirical data are: (i) there is a significant digital differentiation among lecturers and students at technical versus comprehensive universities in terms of their proficiency and internet accessibility; and (ii) the awareness and appreciation of the OER concept and open licensing is low but from the actual variety and types of processing by respondents of educational resources (not necessarily open) there is a preparedness for openness for the future.


2018 ◽  
Vol 1 (1) ◽  
pp. 32-36
Author(s):  
Eleazar Ndabarora ◽  
Dariya Mukamusoni ◽  
Clarte Ndikumasabo ◽  
Védaste Ngirinshuti

Cervical cancer is one of the leading causes of morbidity and mortality globally and in Sub-Saharan Africa in particular. There is evidence that early detection and early management of cases are the best strategies to prevent and control this health threat, since treatment of the later stages of the diseases are very expensive. The objectives of the review were: (1) to identify and review studies on the prevalence of cervical cancer and determinants of early detection in Sub-Saharan Africa, and (2) to recommend further studies and interventions based on the findings of this review. Extensive literature search was conducted using the MeSH terms. Articles on cervical cancer and/or determinants of early detection which fulfilled inclusion criteria were reviewed independently by three reviewers. The prevalence of cervical cancer in Sub-Saharan Africa is increasing. Although there are evidences that cervical cancer screening programs are practical and feasible even in resource-limited settings in Sub-Saharan Africa, there is a very low uptake of cervical cancer screening and there are key factors that need to be addressed in order to make these programs established and effective.


2021 ◽  
Vol 13 (3) ◽  
pp. 1158
Author(s):  
Cecilia M. Onyango ◽  
Justine M. Nyaga ◽  
Johanna Wetterlind ◽  
Mats Söderström ◽  
Kristin Piikki

Opportunities exist for adoption of precision agriculture technologies in all parts of the world. The form of precision agriculture may vary from region to region depending on technologies available, knowledge levels and mindsets. The current review examined research articles in the English language on precision agriculture practices for increased productivity among smallholder farmers in Sub-Saharan Africa. A total of 7715 articles were retrieved and after screening 128 were reviewed. The results indicate that a number of precision agriculture technologies have been tested under SSA conditions and show promising results. The most promising precision agriculture technologies identified were the use of soil and plant sensors for nutrient and water management, as well as use of satellite imagery, GIS and crop-soil simulation models for site-specific management. These technologies have been shown to be crucial in attainment of appropriate management strategies in terms of efficiency and effectiveness of resource use in SSA. These technologies are important in supporting sustainable agricultural development. Most of these technologies are, however, at the experimental stage, with only South Africa having applied them mainly in large-scale commercial farms. It is concluded that increased precision in input and management practices among SSA smallholder farmers can significantly improve productivity even without extra use of inputs.


2021 ◽  
Vol 22 (15) ◽  
pp. 7773
Author(s):  
Neann Mathai ◽  
Conrad Stork ◽  
Johannes Kirchmair

Experimental screening of large sets of compounds against macromolecular targets is a key strategy to identify novel bioactivities. However, large-scale screening requires substantial experimental resources and is time-consuming and challenging. Therefore, small to medium-sized compound libraries with a high chance of producing genuine hits on an arbitrary protein of interest would be of great value to fields related to early drug discovery, in particular biochemical and cell research. Here, we present a computational approach that incorporates drug-likeness, predicted bioactivities, biological space coverage, and target novelty, to generate optimized compound libraries with maximized chances of producing genuine hits for a wide range of proteins. The computational approach evaluates drug-likeness with a set of established rules, predicts bioactivities with a validated, similarity-based approach, and optimizes the composition of small sets of compounds towards maximum target coverage and novelty. We found that, in comparison to the random selection of compounds for a library, our approach generates substantially improved compound sets. Quantified as the “fitness” of compound libraries, the calculated improvements ranged from +60% (for a library of 15,000 compounds) to +184% (for a library of 1000 compounds). The best of the optimized compound libraries prepared in this work are available for download as a dataset bundle (“BonMOLière”).


Land ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 295
Author(s):  
Yuan Gao ◽  
Anyu Zhang ◽  
Yaojie Yue ◽  
Jing’ai Wang ◽  
Peng Su

Suitable land is an important prerequisite for crop cultivation and, given the prospect of climate change, it is essential to assess such suitability to minimize crop production risks and to ensure food security. Although a variety of methods to assess the suitability are available, a comprehensive, objective, and large-scale screening of environmental variables that influence the results—and therefore their accuracy—of these methods has rarely been explored. An approach to the selection of such variables is proposed and the criteria established for large-scale assessment of land, based on big data, for its suitability to maize (Zea mays L.) cultivation as a case study. The predicted suitability matched the past distribution of maize with an overall accuracy of 79% and a Kappa coefficient of 0.72. The land suitability for maize is likely to decrease markedly at low latitudes and even at mid latitudes. The total area suitable for maize globally and in most major maize-producing countries will decrease, the decrease being particularly steep in those regions optimally suited for maize at present. Compared with earlier research, the method proposed in the present paper is simple yet objective, comprehensive, and reliable for large-scale assessment. The findings of the study highlight the necessity of adopting relevant strategies to cope with the adverse impacts of climate change.


2016 ◽  
Vol 40 (6) ◽  
pp. 500-525 ◽  
Author(s):  
Ben Kelcey ◽  
Zuchao Shen ◽  
Jessaca Spybrook

Objective: Over the past two decades, the lack of reliable empirical evidence concerning the effectiveness of educational interventions has motivated a new wave of research in education in sub-Saharan Africa (and across most of the world) that focuses on impact evaluation through rigorous research designs such as experiments. Often these experiments draw on the random assignment of entire clusters, such as schools, to accommodate the multilevel structure of schooling and the theory of action underlying many school-based interventions. Planning effective and efficient school randomized studies, however, requires plausible values of the intraclass correlation coefficient (ICC) and the variance explained by covariates during the design stage. The purpose of this study was to improve the planning of two-level school-randomized studies in sub-Saharan Africa by providing empirical estimates of the ICC and the variance explained by covariates for education outcomes in 15 countries. Method: Our investigation drew on large-scale representative samples of sixth-grade students in 15 countries in sub-Saharan Africa and includes over 60,000 students across 2,500 schools. We examined two core education outcomes: standardized achievement in reading and mathematics. We estimated a series of two-level hierarchical linear models with students nested within schools to inform the design of two-level school-randomized trials. Results: The analyses suggested that outcomes were substantially clustered within schools but that the magnitude of the clustering varied considerably across countries. Similarly, the results indicated that covariance adjustment generally reduced clustering but that the prognostic value of such adjustment varied across countries.


2017 ◽  
Vol 55 (3) ◽  
pp. 395-422 ◽  
Author(s):  
Matt Kandel

ABSTRACTRising competition and conflict over land in rural sub-Saharan Africa continues to attract the attention of researchers. Recent work has especially focused on land governance, post-conflict restructuring of tenure relations, and large-scale land acquisitions. A less researched topic as of late, though one deserving of greater consideration, pertains to how social differentiation on the local-level shapes relations to land, and how these processes are rooted in specific historical developments. Drawing on fieldwork conducted in Teso sub-region of eastern Uganda, this paper analyses three specific land conflicts and situates them within a broad historical trajectory. I show how each dispute illuminates changes in class relations in Teso since the early 1990s. I argue that this current period of socioeconomic transformation, which includes the formation of a more clearly defined sub-regional middle class and elite, constitutes the most prominent period of social differentiation in Teso since the early 20th century.


AMBIO ◽  
2022 ◽  
Author(s):  
Dilini Abeygunawardane ◽  
Angela Kronenburg García ◽  
Zhanli Sun ◽  
Daniel Müller ◽  
Almeida Sitoe ◽  
...  

AbstractActor-level data on large-scale commercial agriculture in Sub-Saharan Africa are scarce. The peculiar choice of transnational investing in African land has, therefore, been subject to conjecture. Addressing this gap, we reconstructed the underlying logics of investment location choices in a Bayesian network, using firm- and actor-level interview and spatial data from 37 transnational agriculture and forestry investments across 121 sites in Mozambique, Zambia, Tanzania, and Ethiopia. We distinguish four investment locations across gradients of resource frontiers and agglomeration economies to derive the preferred locations of different investors with varied skillsets and market reach (i.e., track record). In contrast to newcomers, investors with extensive track records are more likely to expand the land use frontier, but they are also likely to survive the high transaction costs of the pre-commercial frontier. We highlight key comparative advantages of Southern and Eastern African frontiers and map the most probable categories of investment locations.


2021 ◽  
Author(s):  
Javier Perez-Saez ◽  
Justin Lessler ◽  
Elizabeth C. Lee ◽  
Francisco J. Luquero ◽  
Espoir B. Malembaka ◽  
...  

Background Cholera remains a major threat in Sub-Saharan Africa (SSA) where some of the highest case fatality risks are reported. Knowing in what months and where cholera tends to occur across the continent can aid in improving efforts to eliminate cholera as a public health concern; though largely due to lack of unified large-scale datasets, no continent-wide estimates exist. In this study we aim to estimate cholera seasonality across SSA. Methods We leverage the Global Task Force on Cholera Control (GTFCC) global cholera database with statistical models to synthesize data across spatial and temporal scale in order to infer the seasonality of excess suspected cholera occurrence in SSA. We developed a Bayesian statistical model to infer the monthly risk of excess cholera at the first and/or second administrative levels. Seasonality patterns were then grouped into spatial clusters. Finally, we studied the association between seasonality estimates and hydro-climatic variables. Findings The majority of studied countries (24/34) have seasonal patterns in excess cholera, corresponding to approximately 85% of the SSA population. Most countries (19/24) also had sub-national differences in seasonality patterns, with strong differences in seasonality strength between regions. Seasonality patterns clustered into two macro-regions (West Africa and the Sahel vs. Eastern and Southern Africa), which were composed of sub-regional clusters with varying degrees of seasonality. Exploratory association analysis found most consistent and positive correlations between cholera seasonality and precipitation, and to a lesser extent with temperature and flooding. Interpretation Widespread cholera seasonality in SSA offers opportunities for intervention planning. Further studies are needed to study the association between cholera and climate. Funding The NASA Applied Sciences Program and the Bill and Melinda Gates Foundation.


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