Post-exposure prophylaxis following high-risk contact with Ebola virus, using immunotherapies with monoclonal antibodies, in the eastern Democratic Republic of the Congo: an emergency use program.

INTRODUCTION: With the development of therapeutics and vaccine against Ebola virus disease (EVD), the question of post-exposure prophylaxis for high-risk contact has emerged. Immunotherapies (monoclonal antibodies [mAbs]) recently validated for treating infected patients appear to be a good candidate for protecting contacts. DESIGN: During the tenth EVD outbreak in the Democratic Republic of the Congo, we have administrated mAbs (Mab114 or REGN-EB3) to high and intermediate-risk contacts of EVD patients. RESULTS: Overall, 23 non-vaccinated contacts received mAbs after a median delay between contact and post-exposure prophylaxis of 1 day (interquartile range 1-2). All contacts were free of symptoms, and all had negative reverse transcriptase-polymerase chain reaction 14 days after the contact. CONCLUSION: Immunotherapies appear to be promising candidates to protect EVD contacts. Interaction with vaccine needs to be analyzed and a larger study on efficacy conducted.

Are we ready to track climate-driven shifts in marine species across international boundaries? - A global survey of scientific bottom trawl data.

Marine biota are redistributing at a rapid pace in response to climate change and shifting seascapes. While changes in fish populations and community structure threaten the sustainability of fisheries, our capacity to adapt by tracking and projecting marine species remains a challenge due to data discontinuities in biological observations, lack of data availability, and mismatch between data and real species distributions. To assess the extent of this challenge, we review the global status and accessibility of ongoing scientific bottom trawl surveys. In total, we gathered metadata for 283,925 samples from 95 surveys conducted regularly from 2001 to 2019. We identified that 59% of the metadata collected are not publicly available, highlighting that the availability of data is the most important challenge to assess species redistributions under global climate change. Given that the primary purpose of surveys is to provide independent data to inform stock assessment of commercially important populations, we further highlight that single surveys do not cover the full range of the main commercial demersal fish species. An average of 18 surveys is needed to cover at least 50% of species ranges, demonstrating the importance of combining multiple surveys to evaluate species range shifts. We assess the potential for combining surveys to track transboundary species redistributions and show that differences in sampling schemes and inconsistency in sampling can be overcome with spatio-temporal modeling to follow species density redistributions. In light of our global assessment, we establish a framework for improving the management and conservation of transboundary and migrating marine demersal species. We provide directions to improve data availability and encourage countries to share survey data, to assess species vulnerabilities, and to support management adaptation in a time of climate-driven ocean changes.

Investigation of a cross-border case of Lassa fever in West Africa.

BACKGROUND: Infectious disease prevention and control strategies require a coordinated, transnational approach. To establish core capacities of the International Health Regulations (IHR), the World Health Organization (WHO) developed the Integrated Diseases Surveillance and Response (IDSR) strategy. Epidemic-prone Lassa fever, caused by Lassa virus, is an endemic disease in the West African countries of Ghana, Guinea, Mali, Benin, Liberia, Sierra Leone, Togo and Nigeria. It's one of the major public health threats in these countries. Here it is reported an epidemiological investigation of a cross-border case of Lassa fever, which demonstrated the importance of strengthened capacities of IHR and IDSR. CASE PRESENTATION: On January 9th, 2018 a 35-year-old Guinean woman with fever, neck pain, body pain, and vomiting went to a hospital in Ganta, Liberia. Over the course of her illness, the case visited various health care facilities in both Liberia and Guinea. A sample collected on January 10th was tested positive for Lassa virus by RT-PCR in a Liberian laboratory. The Guinean Ministry of Health (MoH) was officially informed by WHO Country Office for Guinea and for Liberia. CONCLUSION: This case report revealed how an epidemic-prone disease such as Lassa fever can rapidly spread across land borders and how such threat can be quickly controlled with communication and collaboration within the IHR framework.

Surface modification with highly-homogeneous porous silica layer for enzyme immobilization in capillary enzyme microreactors.

Immobilized enzyme micro-reactors (IMERs) are of vital importance in developing miniaturized bioanalytical systems and have promising applications in various biomanufacturing. An inherent limitation in designing IMERs is the one-dimensional cylindrical geometry of micro-channels that offers limited exposed surface area for molecular reorganization and enzyme immobilization. In this study, we report a robust capillary-IMER based on a three dimensional porous layer open tubular (3D-PLOT) column which is prepared by an easy-to-control surface modification strategy via single-step in situ biphasic reaction. The 3D-PLOT column with highly uniform porous geometry and narrow distribution of porosity can greatly enhance the surface-area-to-volume ratio of the micro-channels, showing the beneficial effects for enzyme immobilization to enhance reaction efficiency and shorten analysis time. Taking trypsin as a model enzyme, enzymatic activities of immobilized enzyme are analyzed. We compare enzyme assays using the proposed 3D-PLOT-IMER with those using normal capillary-IEMR without surface modification as well as free trypsin. The 3D-PLOT-IMER exhibits excellent stability and inter/intra-day reproducibility, and these characteristics imply the reliability of the proposed IMERs for accurate enzyme assay. The feasibility of the proposed method for potential application in biological analysis is demonstrated by coupling the 3D-PLOT-IMER with a nano-LC-MS/MS system for online digestion of standard proteins, cell extraction and living Hela cells. Our study show that the surface modification with the proposed 3D-porous layer is a simple and efficient approach for enzyme immobilization, and could be widely suitable for different kinds of IMERs.

Impact of infection prevention and control training on health facilities during the Ebola virus disease outbreak in Guinea.

BACKGROUND: In 2014-2016, West Africa faced the most deadly Ebola Virus Disease (EVD) outbreak in history. A key strategy to overcome this outbreak was continual staff training in Infection Prevention and Control (IPC), with a focus on Ebola. This research aimed to evaluate the impact of IPC training and the quality of IPC performance in health care facilities of one municipality of Conakry, Guinea. METHODS: This study was conducted in February 2016. All health facilities within Ratoma municipality, Conakry, Guinea, were evaluated based on IPC performance standards developed by the Guinean Ministry of Health. The IPC performance of healthcare facilities was categorised into high or low IPC scores based on the median IPC score of the sample. The Mantel-Haenzsel method and logistic regression were used for statistical analysis. RESULTS: Twenty-five percent of health centres had one IPC-trained worker, 53% had at least two IPC-trained workers, and 22% of health centres had no IPC-trained workers. An IPC score above median was positively associated with the number of trained staff; health centres with two or more IPC-trained workers were eight times as likely to have an IPC score above median, while those with one IPC-trained worker were four times as likely, compared to centres with no trained workers. Health centres that implemented IPC cascade training to untrained medical staff were five times as likely to have an IPC score above median. CONCLUSIONS: This research highlights the importance of training healthcare staff in IPC and organising regular cascade trainings. IPC strategies implemented during the outbreak should continue to be reinforced for the better health of patients and medical staff, and be considered a key factor in any outbreak response.

Correction: Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea.

[This corrects the article DOI: 10.1371/journal.pmed.1001967.].

Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea.

BACKGROUND: Ebola virus disease (EVD) is a highly lethal condition for which no specific treatment has proven efficacy. In September 2014, while the Ebola outbreak was at its peak, the World Health Organization released a short list of drugs suitable for EVD research. Favipiravir, an antiviral developed for the treatment of severe influenza, was one of these. In late 2014, the conditions for starting a randomized Ebola trial were not fulfilled for two reasons. One was the perception that, given the high number of patients presenting simultaneously and the very high mortality rate of the disease, it was ethically unacceptable to allocate patients from within the same family or village to receive or not receive an experimental drug, using a randomization process impossible to understand by very sick patients. The other was that, in the context of rumors and distrust of Ebola treatment centers, using a randomized design at the outset might lead even more patients to refuse to seek care. Therefore, we chose to conduct a multicenter non-randomized trial, in which all patients would receive favipiravir along with standardized care. The objectives of the trial were to test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak, and to collect data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with EVD. The trial was not aimed at directly informing future guidelines on Ebola treatment but at quickly gathering standardized preliminary data to optimize the design of future studies. METHODS AND FINDINGS: Inclusion criteria were positive Ebola virus reverse transcription PCR (RT-PCR) test, age ≥ 1 y, weight ≥ 10 kg, ability to take oral drugs, and informed consent. All participants received oral favipiravir (day 0: 6,000 mg; day 1 to day 9: 2,400 mg/d). Semi-quantitative Ebola virus RT-PCR (results expressed in "cycle threshold" [Ct]) and biochemistry tests were performed at day 0, day 2, day 4, end of symptoms, day 14, and day 30. Frozen samples were shipped to a reference biosafety level 4 laboratory for RNA viral load measurement using a quantitative reference technique (genome copies/milliliter). Outcomes were mortality, viral load evolution, and adverse events. The analysis was stratified by age and Ct value. A "target value" of mortality was defined a priori for each stratum, to guide the interpretation of interim and final analysis. Between 17 December 2014 and 8 April 2015, 126 patients were included, of whom 111 were analyzed (adults and adolescents, ≥13 y, n = 99; young children, ≤6 y, n = 12). Here we present the results obtained in the 99 adults and adolescents. Of these, 55 had a baseline Ct value ≥ 20 (Group A Ct ≥ 20), and 44 had a baseline Ct value < 20 (Group A Ct < 20). Ct values and RNA viral loads were well correlated, with Ct = 20 corresponding to RNA viral load = 7.7 log10 genome copies/ml. Mortality was 20% (95% CI 11.6%-32.4%) in Group A Ct ≥ 20 and 91% (95% CI 78.8%-91.1%) in Group A Ct < 20. Both mortality 95% CIs included the predefined target value (30% and 85%, respectively). Baseline serum creatinine was ≥110 µmol/l in 48% of patients in Group A Ct ≥ 20 (≥300 µmol/l in 14%) and in 90% of patients in Group A Ct < 20 (≥300 µmol/l in 44%). In Group A Ct ≥ 20, 17% of patients with baseline creatinine ≥110 µmol/l died, versus 97% in Group A Ct < 20. In patients who survived, the mean decrease in viral load was 0.33 log10 copies/ml per day of follow-up. RNA viral load values and mortality were not significantly different between adults starting favipiravir within <72 h of symptoms compared to others. Favipiravir was well tolerated. CONCLUSIONS: In the context of an outbreak at its peak, with crowded care centers, randomizing patients to receive either standard care or standard care plus an experimental drug was not felt to be appropriate. We did a non-randomized trial. This trial reaches nuanced conclusions. On the one hand, we do not conclude on the efficacy of the drug, and our conclusions on tolerance, although encouraging, are not as firm as they could have been if we had used randomization. On the other hand, we learned about how to quickly set up and run an Ebola trial, in close relationship with the community and non-governmental organizations; we integrated research into care so that it improved care; and we generated knowledge on EVD that is useful to further research. Our data illustrate the frequency of renal dysfunction and the powerful prognostic value of low Ct values. They suggest that drug trials in EVD should systematically stratify analyses by baseline Ct value, as a surrogate of viral load. They also suggest that favipiravir monotherapy merits further study in patients with medium to high viremia, but not in those with very high viremia. TRIAL REGISTRATION: ClinicalTrials.gov NCT02329054.

Determination of the inhibitory effect of green tea extract on glucose-6-phosphate dehydrogenase based on multilayer capillary enzyme microreactor.

Natural herbal medicines are an important source of enzyme inhibitors for the discovery of new drugs. A number of natural extracts such as green tea have been used in prevention and treatment of diseases due to their low-cost, low toxicity and good performance. The present study reports an online assay of the activity and inhibition of the green tea extract of the Glucose 6-phosphate dehydrogenase (G6PDH) enzyme using multilayer capillary electrophoresis based immobilized enzyme microreactors (CE-IMERs). The multilayer CE-IMERs were produced with layer-by-layer electrostatic assembly, which can easily enhance the enzyme loading capacity of the microreactor. The activity of the G6PDH enzyme was determined and the enzyme inhibition by the inhibitors from green tea extract was investigated using online assay of the multilayer CE-IMERs. The Michaelis constant (Km ) of the enzyme, the IC50 and Ki values of the inhibitors were achieved and found to agree with those obtained using offline assays. The results show a competitive inhibition of green tea extract on the G6PDH enzyme. The present study provides an efficient and easy-to-operate approach for determining G6PDH enzyme reaction and the inhibition of green tea extract, which may be beneficial in research and the development of natural herbal medicines. Copyright © 2016 John Wiley & Sons, Ltd.

How women are treated during facility-based childbirth: development and validation of measurement tools in four countries - phase 1 formative research study protocol.

BACKGROUND: Every woman has the right to dignified, respectful care during childbirth. Recent evidence has demonstrated that globally many women experience mistreatment during labour and childbirth in health facilities, which can pose a significant barrier to women attending facilities for delivery and can contribute to poor birth experiences and adverse outcomes for women and newborns. However there is no clear consensus on how mistreatment of women during childbirth in facilities is defined and measured. We propose using a two-phased, mixed-methods study design in four countries to address these research gaps. This protocol describes the Phase 1 qualitative research activities. METHODS/DESIGN: We will employ qualitative research methodologies among women, healthcare providers and administrators in the facility catchment areas of two health facilities in each country: Ghana, Guinea, Myanmar and Nigeria. In-depth interviews (IDIs) and focus group discussions (FGDs) will be conducted among women of reproductive age (15-49 years) to explore their perceptions and experiences of facility-based childbirth care, focused on how they were treated by healthcare workers and perceived factors affecting how they were treated. IDIs will also be conducted with healthcare providers of different cadres (e.g.: nurses, midwives, medical officers, specialist obstetricians) and facility administrators working in the selected facilities to explore healthcare providers' perceptions and experiences of facility-based childbirth care and how staff are treated, colleagues and supervisors. Audio recordings will be transcribed and translated to English. Textual data will be analysed using a thematic framework approach and will consist of two levels of analysis: (1) conduct of local analysis workshops with the research assistants in each country; and (2) line-by-line coding to develop a thematic framework and coding scheme. DISCUSSION: This study serves several roles. It will provide an in-depth understanding of how women are treated during childbirth in four countries and perceived factors associated with this mistreatment. It will also provide data on where and how an intervention could be developed to reduce mistreatment and promote respectful care. The findings from this study will contribute to the development of tools to measure the prevalence of mistreatment of women during facility-based childbirth.

Sequential capillary electrophoresis analysis using optically gated sample injection and UV/vis detection.

We present sequential CE analysis of amino acids and L-asparaginase-catalyzed enzyme reaction, by combing the on-line derivatization, optically gated (OG) injection and commercial-available UV-Vis detection. Various experimental conditions for sequential OG-UV/vis CE analysis were investigated and optimized by analyzing a standard mixture of amino acids. High reproducibility of the sequential CE analysis was demonstrated with RSD values (n = 20) of 2.23, 2.57, and 0.70% for peak heights, peak areas, and migration times, respectively, and the LOD of 5.0 µM (for asparagine) and 2.0 µM (for aspartic acid) were obtained. With the application of the OG-UV/vis CE analysis, sequential online CE enzyme assay of L-asparaginase-catalyzed enzyme reaction was carried out by automatically and continuously monitoring the substrate consumption and the product formation every 12 s from the beginning to the end of the reaction. The Michaelis constants for the reaction were obtained and were found to be in good agreement with the results of traditional off-line enzyme assays. The study demonstrated the feasibility and reliability of integrating the OG injection with UV/vis detection for sequential online CE analysis, which could be of potential value for online monitoring various chemical reaction and bioprocesses.

Application of capillary enzyme micro-reactor in enzyme activity and inhibitors studies of glucose-6-phosphate dehydrogenase.

In this study, we present an on-line measurement of enzyme activity and inhibition of Glucose-6-phosphate dehydrogenase (G6PDH) enzyme using capillary electrophoresis based immobilized enzyme micro-reactor (CE-based IMER). The IMER was prepared using a two-step protocol based on electrostatic assembly. The micro-reactor exhibited good stability and reproducibility for on-line assay of G6PDH enzyme. Both the activity as well as the inhibition of the G6PDH enzyme by six inhibitors, including three metals (Cu(2+), Pb(2+), Cd(2+)), vancomycin, urea and KMnO4, were investigated using on-line assay of the CE-based IMERs. The enzyme activity and inhibition kinetic constants were measured using the IMERs which were found to be consistent with those using traditional off-line enzyme assays. The kinetic mechanism of each inhibitor was also determined. The present study demonstrates the feasibility of using CE-based IMERs for rapid and efficient on-line assay of G6PDH, an important enzyme in the pentosephosphate pathway of human metabolism.

Management of diabetes in Guinean traditional medicine: an ethnobotanical investigation in the coastal lowlands.

ETHNOPHARMACOLOGICAL RELEVANCE: This survey was carried out in the coastal lowlands of Guinea-Conakry in order to make an inventory of plants used by traditional healers, herbalists and diabetic patients for the management of diabetes mellitus. MATERIALS AND METHODS: Frequent ethnomedical and ethnobotanical investigations were conducted from June 2008 to December 2009 in Conakry, Kindia, Forécariah, Dubréka, Boke, Fria and Boffa. It is a cross-sectional survey and data collection is based on the interactive method. During this period a total of 112 people aged from 39 to 76 years old were interviewed. RESULTS: During this investigation 146 plant species belonging to 55 families were collected. The most cited plants were Anacardium occidentale L. and Ficus spp., while the Fabaceae family was the most represented, followed by the Euphorbiaceae and Rubiaceae. The most frequently plant parts used by the traditional healers and the herbalists were the stem-bark and decoctions the most common preparation mode. CONCLUSIONS: It is clear that a variety of plants is used in the management and treatment of diabetes. Due to the increasing prevalence of type 2 diabetes, there is an urgent need for scientific investigations to rationalise the use of these traditional remedies, which could represent accessible alternative medicines for the Guinean populations.