Risk factors for transmission of Ebola or Marburg virus disease: a systematic review and meta-analysis

Background The Ebola virus disease outbreak that started in Western Africa in 2013 was unprecedented because it spread within densely populated urban environments and affected many thousands of people. As a result, previous advice and guidelines need to be critically reviewed, especially with regard to transmission risks in different contexts. Methods Scientific and grey literature were searched for articles about any African filovirus. Articles were screened for information about transmission (prevalence or odds ratios especially). Data were extracted from eligible articles and summarised narratively with partial meta-analysis. Study quality was also evaluated. Results 31 reports were selected from 6552 found in the initial search. Eight papers gave numerical odds for contracting filovirus illness, 23 further articles provided supporting anecdotal observations about how transmission probably occurred for individuals. Many forms of contact (conversation, sharing a meal, sharing a bed, direct or indirect touching) were unlikely to result in disease transmission during incubation or early illness. Amongst household contacts who reported directly touching a case, the attack rate was 32% (95% CI 26-38%). Risk of disease transmission between household members without direct contact was low (1%; 95% CI 0-5%). Caring for a case in the community, especially until death, and participation in traditional funeral rites were strongly associated with acquiring disease, probably due to a high degree of direct physical contact with case or cadaver. Conclusions Transmission of filovirus is unlikely except through close contact, especially during the most severe stages of acute illness. More data are needed about the context, intimacy and timing of contact required to raise the odds of disease transmission. Risk factors specific to urban settings may need to be determined

Progress of using risk assessment to manage small drinking-water supplies in Rwanda: a preliminary study

The World Health Organization promotes risk assessment and risk management through Water Safety Plans (WSPs) as the most effective way to manage drinking-water supplies. Despite proven advantages of this approach in other regions, WSPs are still not widely used across small drinking-water supplies in Sub Saharan Africa. The aim of this research is to identify good practices and related gaps which may assist with formal uptake of WSPs for small drinking-water supplies in Rwanda. Through semi-structured interviews with the key stakeholders involved in small drinking-water supply management across Rwanda, the aim is achieved through the investigation of the following: (i) current drinking-water management challenges; (ii) stakeholder collaboration and data management activities including reporting of information; and (iii) the regulatory and policy environment. The use and awareness of WSPs in Rwanda was confirmed as low. However certain drinking-water management activities which align with the WSP methodology are being carried out. These include catchment management and stakeholder collaboration. Although legislation and policy are in place in Rwanda, communication and training of methods to implement WSPs are required to sustainably embed WSPs into practice. Several elements, including community engagement, systematic review of risks and data management, require greater focus to align with the WSP methodology. Respondents highlighted key drinking-water management challenges, including reactive budgeting and lack of sector prioritization, which could benefit from formal WSP implementation

The potential for citizen science to improve the reach of sanitary inspections

To achieve Sustainable Development Goals (SDGs) 6, universal and equitable access to safe and affordable drinking-water quality and sanitation for all, and 10, to reduce inequality within and among countries, additional and urgent work is required. Efforts to achieve these Goals in the context of small drinking-water supplies, which are the furthest behind in regards to progress, are of particular need. Reasons for this disparity in progress include the remoteness of access to small drinking-water supplies and the lack of technical and financial capacity for monitoring supplies. The World Health Organization promote the use of Sanitary inspection (SI) as an on-site assessment of risk. Despite the potential to increase the body of knowledge and information on supplies in a region, there has been limited research into the role of citizen science and SIs. To meet SDG targets, we need to improve the reach of SIs. This study uses a mixed methods approach of quantitative on-site SI data collection and remote SI data collection via photographic images, together with qualitative data collection, collected by non-expert students, who are citizens of Malawi, as well as a panel of experts in the field of SI. Results indicate that, although further research into the topic is required prior to widescale implementation, the potential exists for citizens to conduct SI, with remote expert verification of the results using photographic images of supplies. Further documentation or guidance is required to support citizens in this process. The results highlight a critical gap in the availability of appropriate documentation for unprotected spring sources which is urgently required. The use of citizen science for SI data collection is in its infancy. However, this study indicates that there is potential to explore the use of citizen science in this area, which will contribute to achieving SDGs 6 and 10

Recommendations for dealing with waste contaminated with Ebola virus: a Hazard Analysis of Critical Control Points approach

Objective To assess, within communities experiencing Ebola virus outbreaks, the risks associated with the disposal of human waste and to generate recommendations for mitigating such risks. Methods A team with expertise in the Hazard Analysis of Critical Control Points framework identified waste products from the care of individuals with Ebola virus disease and constructed, tested and confirmed flow diagrams showing the creation of such products. After listing potential hazards associated with each step in each flow diagram, the team conducted a hazard analysis, determined critical control points and made recommendations to mitigate the transmission risks at each control point. Findings The collection, transportation, cleaning and shared use of blood-soiled fomites and the shared use of latrines contaminated with blood or bloodied faeces appeared to be associated with particularly high levels of risk of Ebola virus transmission. More moderate levels of risk were associated with the collection and transportation of material contaminated with bodily fluids other than blood, shared use of latrines soiled with such fluids, the cleaning and shared use of fomites soiled with such fluids, and the contamination of the environment during the collection and transportation of blood-contaminated waste. Conclusion The risk of the waste-related transmission of Ebola virus could be reduced by the use of full personal protective equipment, appropriate hand hygiene and an appropriate disinfectant after careful cleaning. Use of the Hazard Analysis of Critical Control Points framework could facilitate rapid responses to outbreaks of emerging infectious disease

Success Factors for Water Safety Plan Implementation in Small Drinking Water Supplies in Low- and Middle-Income Countries

Water Safety Plan (WSP) implementation has the potential to greatly improve, commonly very challenging and resource limited, small drinking water supplies. Although slower than in urban or high-income settings, the uptake of WSPs in low- and middle-income countries (LMICs) is accelerating. Understanding the factors which will make a WSP successful will further improve efficient uptake and assist with its long-term sustainability. Based on an extensive literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISM-A) methodology, 48 publications, including case studies and guidance documentation, formed the basis of this review. These were analysed using inductive and deductive coding methods to (i) identify the success factors applicable to WSP implementation in small drinking water supplies in LMICs and (ii) to investigate which factors are more or less critical depending on the geography and level of development of the implementing country. Key challenges identified during the review process were also noted. A comparison of these success factors was made with those identified from high-income and urban settings. The three most important success factors identified are the development of technical capacity, community engagement, and monitoring and verification. Factors specific to small drinking water supplies in LMICs include support from non-government organisations, integration into existing water sanitation and hygiene (WASH) programs, simplicity, and community engagement. Certain factors, such as adaptability, the use of guidance documentation, international collaboration, the role of pilot studies, knowledge sharing, and stakeholder involvement are applicable to all WSP settings. Due to the specific challenges faced by small drinking water systems and the limited number of original research publications on this topic, this study highlights the need for further data collection and research focused on success factors in these settings. It is anticipated that the consideration of the success factors identified in this study will assist implementers in improving the uptake and long-term sustainability of WSPs in small drinking water supplies in low- and middle-income settings

Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review

Background: The 2013-15 Ebola outbreak was unprecedented due to sustainedtransmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Methods: Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. [1] Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. Results: 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Conclusions: Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the major risk for disease transmission because of the known high viral loads in blood

Reduced response to IKr blockade and altered hERG1a/1b stoichiometryin human heart failure

Heart failure (HF) claims 250,000 lives per year in the US, and nearly half of these deaths are sudden and presumably due to ventricular tachyarrhythmias. QT interval and action potential (AP) prolongation are hallmark proarrhythmic changes in the failing myocardium, which potentially result from alterations in repolarizing potassium currents. Thus,we aimed to examinewhether decreased expression of the rapid delayed rectifier potassiumcurrent, IKr, contributes to repolarization abnormalities in human HF. Tomap functional IKr expression across the left ventricle (LV), we optically imaged coronary-perfused LV free wall from donor and end-stage failing human hearts. The LV wedge preparation was used to examine transmural AP durations at 80% repolarization (APD80), and treatment with the IKr-blocking drug, E-4031, was utilized to interrogate functional expression. We assessed the percent change in APD80 post-IKr blockade relative to baseline APD80 (ΔAPD80) and found that ΔAPD80s are reduced in failing versus donor hearts in each transmural region, with 0.35-, 0.43-, and 0.41-fold reductions in endo-, mid-, and epicardium, respectively (p = 0.008, 0.037, and 0.022). We then assessed hERG1 isoform gene and protein expression levels using qPCR and Western blot. While we did not observe differences in hERG1a or hERG1b gene expression between donor and failing hearts, we found a shift in the hERG1a:hERG1b isoform stoichiometry at the protein level. Computer simulations were then conducted to assess IKr block under E-4031 influence in failing and nonfailing conditions. Our results confirmed the experimental observations and E-4031-induced relative APD80 prolongationwas greater in normal conditions than in failing conditions, provided that the cellularmodel of HF included a significant downregulation of IKr. In humanHF, the response to IKr blockade is reduced, suggesting decreased functional IKr expression. This attenuated functional response is associated with altered hERG1a:hERG1b protein stoichiometry in the failing human LV, and failing cardiomyoctye simulations support the experimental findings. Thus, of IKr protein and functional expression may be important determinants of repolarization remodeling in the failing human LV.We thank the Translational Cardiovascular Biobank & Repository (TCBR) at Washington University for provision of donor/patient records. The TCBR is supported by the NIH/CTSA (UL1 TR000448), Children's Discovery Institute, and Richard J. Wilkinson Trust. We also thank the laboratory of Dr. Sakiyama-Elbert for the use of the StepOnePlus equipment We appreciate the critical feedback on the manuscript by Dr. Jeanne Nerbonne. This work has been supported by the National Heart, Lung & Blood Institute (NHLBI, R01 HL114395). K. Holzem has been supported by the American Heart Association (12PRE12050315) and the NHLBI (F30 HL114310).Holzem, KM.; Gómez García, JF.; Glukhov, AV.; Madden, EJ.; Koppel, AC.; Ewald, GA.; Trénor Gomis, BA.... (2016). Reduced response to IKr blockade and altered hERG1a/1b stoichiometryin human heart failure. Journal of Molecular and Cellular Cardiology. 96:82-92. https://doi.org/10.1016/j.yjmcc.2015.06.008S82929

Correction: Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype–phenotype correlation

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Vocal learning-associated convergent evolution in mammalian proteins and regulatory elements.

Vocal production learning (vocal learning) is a convergently evolved trait in vertebrates. To identify brain genomic elements associated with mammalian vocal learning, we integrated genomic, anatomical, and neurophysiological data from the Egyptian fruit bat (Rousettus aegyptiacus) with analyses of the genomes of 215 placental mammals. First, we identified a set of proteins evolving more slowly in vocal learners. Then, we discovered a vocal motor cortical region in the Egyptian fruit bat, an emergent vocal learner, and leveraged that knowledge to identify active cis-regulatory elements in the motor cortex of vocal learners. Machine learning methods applied to motor cortex open chromatin revealed 50 enhancers robustly associated with vocal learning whose activity tended to be lower in vocal learners. Our research implicates convergent losses of motor cortex regulatory elements in mammalian vocal learning evolution