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Background Artemisinin-resistant falciparum malaria has emerged in Southeast Asia, posing a major threat to malaria control. It is characterised by delayed asexual-stage parasite clearance, which is the reference comparator for the molecular marker 'Kelch 13' and in vitro sensitivity tests. However, current cut-off values denoting slow clearance based on the proportion of individuals remaining parasitaemic on the third day of treatment ('day-3'), or on peripheral blood parasite half-life, are not well supported. We here explore the parasite clearance distributions in an area of artemisinin resistance with the aim refining the in vivo phenotypic definitions. Methods and Findings Data from 1,518 patients on the Thai-Myanmar and Thai-Cambodian borders with parasite half-life assessments after artesunate treatment were analysed. Half-lives followed a bimodal distribution. A statistical approach was developed to infer the characteristics of the component distributions and their relative contribution to the composite mixture. A model representing two parasite subpopulations with geometric mean (IQR) parasite half-lives of 3.0 (2.4-3.9) hours and 6.50 (5.7-7.4) hours was consistent with the data. For individual patients, the parasite half-life provided a predicted likelihood of an artemisinin-resistant infection which depends on the population prevalence of resistance in that area. Consequently, a half-life where the probability is 0.5 varied between 3.5 and 5.5 hours. Using this model, the current 'day-3' cut-off value of 10% predicts the potential presence of artemisinin-resistant infections in most but not all scenarios. These findings are relevant to the low-transmission setting of Southeast Asia. Generalisation to a high transmission setting as in regions of Sub-Saharan Africa will need additional evaluation. Conclusions Characterisation of overlapping distributions of parasite half-lives provides quantitative insight into the relationship between parasite clearance and artemisinin resistance, as well as the predictive value of the 10% cut-off in 'day-3' parasitaemia. The findings are important for the interpretation of in vitro sensitivity tests and molecular markers for artemisinin resistance and for contextualising the 'day 3' threshold to account for initial parasitaemia and sample size., Introduction Artemisinin combination therapies (ACTs) are currently the cornerstone of antimalarial treatment of uncomplicated falciparum malaria throughout the tropical world. There are no new antimalarial drugs of equivalent efficacy available [...]

Background Experimental treatments for Ebola virus disease (EVD) might reduce EVD mortality. There is uncertainty about the ability of different clinical trial designs to identify effective treatments, and about the feasibility of implementing individually randomised controlled trials during an Ebola epidemic. Methods and Findings A treatment evaluation programme for use in EVD was devised using a multi-stage approach (MSA) with two or three stages, including both non-randomised and randomised elements. The probabilities of rightly or wrongly recommending the experimental treatment, the required sample size, and the consequences for epidemic outcomes over 100 d under two epidemic scenarios were compared for the MSA, a sequential randomised controlled trial (SRCT) with up to 20 interim analyses, and, as a reference case, a conventional randomised controlled trial (RCT) without interim analyses. Assuming 50% 14-d survival in the population treated with the current standard of supportive care, all designs had similar probabilities of identifying effective treatments correctly, while the MSA was less likely to recommend treatments that were ineffective. The MSA led to a smaller number of cases receiving ineffective treatments and faster roll-out of highly effective treatments. For less effective treatments, the MSA had a high probability of including an RCT component, leading to a somewhat longer time to roll-out or rejection. Assuming 100 new EVD cases per day, the MSA led to between 6% and 15% greater reductions in epidemic mortality over the first 100 d for highly effective treatments compared to the SRCT. Both the MSA and SRCT led to substantially fewer deaths than a conventional RCT if the tested interventions were either highly effective or harmful. In the proposed MSA, the major threat to the validity of the results of the non-randomised components is that referral patterns, standard of care, or the virus itself may change during the study period in ways that affect mortality. Adverse events are also harder to quantify without a concurrent control group. Conclusions The MSA discards ineffective treatments quickly, while reliably providing evidence concerning effective treatments. The MSA is appropriate for the clinical evaluation of EVD treatments., Introduction The largest ever outbreak of Ebola virus disease (EVD) is ongoing in west Africa, killing up to 70% of those infected [1,2]. Whilst there is no available vaccine and [...]

Background In the absence of proper guidelines and algorithms, available rapid diagnostic tests (RDTs) for common acute undifferentiated febrile illnesses are often used inappropriately. Methods Using prevalence data of 5 common febrile illnesses from India and Cambodia, and performance characteristics (sensitivity and specificity) of relevant pathogen-specific RDTs, we used a mathematical model to predict the probability of correct identification of each disease when diagnostic testing occurs either simultaneously or sequentially in various algorithms. We developed a web-based application of the model so as to visualize and compare output diagnostic algorithms when different disease prevalence and test performance characteristics are introduced. Results Diagnostic algorithms with appropriate sequential testing predicted correct identification of etiology in 74% and 89% of patients in India and Cambodia, respectively, compared with 46% and 49% with simultaneous testing. The optimally performing sequential diagnostic algorithms differed in India and Cambodia due to varying disease prevalence. Conclusions Simultaneous testing is not appropriate for the diagnosis of acute undifferentiated febrile illnesses with presently available tests, which should deter the unsupervised use of multiplex diagnostic tests. The implementation of adaptive algorithms can predict better diagnosis and add value to the available RDTs. The web application of the model can serve as a tool to identify the optimal diagnostic algorithm in different epidemiological settings, while taking into account the local epidemiological variables and accuracy of available tests. [ABSTRACT FROM AUTHOR]

Research Findings: The increase in young Latino Dual Language Learners (DLLs) attending early care and education (ECE) programs has led to a focus on assessing classroom quality for DLLs, to evaluate the quality and impact of their early educational experiences. Experts have advocated for the use of multiple classroom observation tools (i.e., DLL-specific and general quality) to comprehensively understand ECE contexts for young DLLs. This study used two classroom quality tools to examine 37 Head Start classrooms serving Spanish and English-speaking DLLs, from both a DLL-specific and general teacher-child interaction quality perspective. Children (N = 411) were assessed in the fall and spring on language, cognitive, and academic domains. Classroom observations were conducted in the winter to measure DLL-specific quality and general teacher-child interaction quality, respectively. Results revealed low to moderate correlations between the two observation measures. Additionally, findings from both tools demonstrated a range of associations with children's outcomes, with the Supports for Home Language domain (measured by the DLL-specific tool) demonstrating the most consistent relationships with child outcomes across domains. Practice or Policy: Findings are discussed in the context of current ECE research to support young DLLs and provide additional evidence to describe the impact of early educational experiences on young Latino DLLs. [ABSTRACT FROM AUTHOR]

BACKGROUND: In many parts of the world, livestock production is undergoing a process of rapid intensification. The health implications of this development are uncertain. Intensification creates cheaper products, allowing more people to access animal-based foods. However, some practices associated with intensification may contribute to zoonotic disease emergence and spread: for example, the sustained use of antibiotics, concentration of animals in confined units, and long distances and frequent movement of livestock. OBJECTIVES: Here we present the diverse range of ecological, biological, and socioeconomic factors likely to enhance or reduce zoonotic risk, and identify ways in which a comprehensive risk analysis may be conducted by using an interdisciplinary approach. We also offer a conceptual framework to guide systematic research on this problem. DISCUSSION: We recommend that interdisciplinary work on zoonotic risk should take into account the complexity of risk environments, rather than limiting studies to simple linear causal relations between risk drivers and disease emergence and/or spread. In addition, interdisciplinary integration is needed at different levels of analysis, from the study of risk environments to the identification of policy options for risk management. CONCLUSION: Given rapid changes in livestock production systems and their potential health implications at the local and global level, the problem we analyze here is of great importance for environmental health and development. Although we offer a systematic interdisciplinary approach to understand and address these implications, we recognize that further research is needed to clarify methodological and practical questions arising from the integration of the natural and social sciences. KEY WORDS: emerging diseases, integrated ecology and human health, livestock production, risk characterization, risk management, zoonoses. Environ Health Perspect 121:873-877 (2013). http://dx.doi. org/10.1289/ehp.1206001 [Online 10 May 2013], Introduction Recent studies indicate that more than three-fourths of communicable human diseases are zoonotic in origin (Woolhouse and Gowtage-Sequeria 2005), including diseases associated with significant mortality and morbidity such as [...]