Background: Malaria parasites have developed resistance to most of the known antimalarial drugs in clinical practice, with reports of artemisinin resistance emerging in South East Asia (SEA). We sort to find the status of artemisinin resistance and efficacy of different modalities of the current artemisinin-based combination therapies (ACTs). Methods: We carried out a systematic search in 11 electronic databases to identify in vivo studies published between 2001 and 2017 that reported artemisinin resistance. This was then followed by A network meta-analysis to compare the efficacy of different ACTs. Quality assessment was performed using the Cochrane Risk of Bias (ROB) tool for randomized controlled trials and National Institute of Health (NIH) tool for cross-sectional studies. The study protocol was registered in PROSPERO under number CRD42018087574. Results: With 8400 studies initially identified, 82 were eligible for qualitative and quantitative analysis. Artemisinin resistance was only reported in South East Asia. K13 mutation C580Y was the most abundant mutation associated with resistance having an abundance of 63.1% among all K13 mutations reported. Although the overall network meta-analysis had shown good performance of dihydroartemisinin piperaquine in the early years, a subgroup analysis of the recent years revealed a poor performance of the drug in relation to

Generation of three dimensional structures of macromolecules using in silico structural modeling technologies such as homology and de novo modeling has improved dramatically and increased the speed by which tertiary structures of organisms can be generated. This is especially the case if a homologous crystal structure is already available. High-resolution structures can be rapidly created using only their sequence information as input, a process that has the potential to increase the speed of scientific discovery. In this study, homology modeling and structure prediction tools such as RNA123 and SWISS–MODEL were used to generate the 40S ribosomal subunit from Plasmodium falciparum. This structure was modeled using the published crystal structure from Tetrahymena thermophila, a homologous eukaryote. In the absence of the Plasmodium falciparum 40S ribosomal crystal structure, the model accurately depicts a global topology, secondary and tertiary connections, and gives an overall root mean square deviation (RMSD) value of 3.9 Å relative to the template׳s crystal structure. Deviations are somewhat larger in areas with no homology between the templates. These results demonstrate that this approach has the power to identify motifs of interest in RNA and identify potential drug targets for macromolecules whose crystal structures are unknown. The results also show the utility of RNA homology modeling software for structure determination and lay the groundwork for applying this approach to larger and more complex eukaryotic ribosomes and other RNA-protein complexes. Structures generated from this study can be used in in silico screening experiments and lead to the determination of structures for targets/hit complexes.

Introduction Approximately 1000 children die each year due to preventable water and sanitation-related diarrheal diseases. Six in 10 people lacked access to safely managed sanitation facilities in 2015. Numerous community- and school-based approaches have been implemented to eradicate open defecation practices, promote latrine ownership, improve situation sanitation, and reduce waterborne disease. Objective Given that current evidence for sanitation interventions seem promising, the aim of this study was to systematically summarize existing research on the effectiveness of community- and school-based randomized controlled sanitation intervention in improving (1) free open defecation (safe feces disposal), (2) latrine usage, (3) latrine coverage or access, and (4) improved latrine coverage or access. Methods Eight electronic databases were searched: PubMed, Scopus, WHO Global Health Library (GHL), Virtual Health Library (VHL), POPLINE, Web of Science, Cochrane, and Google Scholar up to 26 April 2019. Original randomized clinical trials addressing community-based or school-based intervention that reported feces disposal and latrine coverage were deemed eligible. More than two researchers independently contributed to screening of papers, data extraction, and bias assessment. We conducted a meta-analysis by random-effects model. The risk of bias was assessed by the Cochrane risk of bias tool. Results Eighteen papers that matched all criteria and 16 studies were included in the final meta-analysis. Compared to the control, the sanitation intervention significantly increased safe feces disposal (OR 2.19, 95% CI 1.51–3.19, p < 0.05, I2 = 97.28), latrine usage (OR 3.72, 95% CI 1.71–8.11, p < 0.05, I2 = 91.52), latrine coverage or access (OR 3.95, 95% CI 2.08–7.50, p < 0.05, I2 = 99.07), and improved latrine coverage or access (OR 3.68, 95% CI 1.52–8.91, p < 0.05, I2 = 99.11). A combination of education and latrine construction was more effective compared to educational intervention alone. Conclusion Our study showed strong evidence for both community- and school-based sanitation interventions as effective for the safe disposal of human excreta. The finding suggests major implications for health policy and design of future intervention in developing countries.

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.