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We conducted a matched case-control (MCC), test-negative case-control (TNCC) and case-cohort study in 2016 in Lusaka, Zambia, following a mass vaccination campaign. Confirmed cholera cases served as cases in all three study designs. In the TNCC, control-subjects were cases with negative cholera culture and polymerase chain reaction results. Matched controls by age and sex were selected among neighbours of the confirmed cases in the MCC study. For the case-cohort study, we recruited a cohort of randomly selected individuals living in areas considered at-risk of cholera. We recruited 211 suspected cases (66 confirmed cholera cases and 145 non-cholera diarrhoea cases), 1055 matched controls and a cohort of 921. Adjusted vaccine effectiveness of one dose of oral cholera vaccine (OCV) was 88.9% (95% confidence interval (CI) 42.7–97.8) in the MCC study, 80.2% (95% CI: 16.9–95.3) in the TNCC design and 89.4% (95% CI: 64.6–96.9) in the case-cohort study. Three study designs confirmed the short-term effectiveness of single dose OCV. Major healthcare-seeking behaviour bias did not appear to affect our estimates. Most of the protection among vaccinated individuals could be attributed to the direct effect of the vaccine.

BACKGROUND: In war-torn Yemen, reports of confirmed cholera started in late September, 2016. The disease continues to plague Yemen today in what has become the largest documented cholera epidemic of modern times. We aimed to describe the key epidemiological features of this epidemic, including the drivers of cholera transmission during the outbreak.METHODS: The Yemen Health Authorities set up a national cholera surveillance system to collect information on suspected cholera cases presenting at health facilities. Individual variables included symptom onset date, age, severity of dehydration, and rapid diagnostic test result. Suspected cholera cases were confirmed by culture, and a subset of samples had additional phenotypic and genotypic analysis. We first conducted descriptive analyses at national and governorate levels. We divided the epidemic into three time periods: the first wave (Sept 28, 2016, to April 23, 2017), the increasing phase of the second wave (April 24, 2017, to July 2, 2017), and the decreasing phase of the second wave (July 3, 2017, to March 12, 2018). We reconstructed the changes in cholera transmission over time by estimating the instantaneous reproduction number, Rt. Finally, we estimated the association between rainfall and the daily cholera incidence during the increasing phase of the second epidemic wave by fitting a spatiotemporal regression model.FINDINGS: From Sept 28, 2016, to March 12, 2018, 1 103 683 suspected cholera cases (attack rate 3·69%) and 2385 deaths (case fatality risk 0·22%) were reported countrywide. The epidemic consisted of two distinct waves with a surge in transmission in May, 2017, corresponding to a median Rt of more than 2 in 13 of 23 governorates. Microbiological analyses suggested that the same Vibrio cholerae O1 Ogawa strain circulated in both waves. We found a positive, non-linear, association between weekly rainfall and suspected cholera incidence in the following 10 days; the relative risk of cholera after a weekly rainfall of 25 mm was 1·42 (95% CI 1·31–1·55) compared with a week without rain.INTERPRETATION: Our analysis suggests that the small first cholera epidemic wave seeded cholera across Yemen during the dry season. When the rains returned in April, 2017, they triggered widespread cholera transmission that led to the large second wave. These results suggest that cholera could resurge during the ongoing 2018 rainy season if transmission remains active. Therefore, health authorities and partners should immediately enhance current control efforts to mitigate the risk of a new cholera epidemic wave in Yemen.FUNDING: Health Authorities of Yemen, WHO, and Médecins Sans Frontières.

International audience; objective To assess the performance of the SD Bioline Cholera Ag O1/O139 rapid diagnostic test (RDT) compared to a reference standard combining culture and PCR for the diagnosis of cholera cases during an outbreak.methods RDT and bacterial culture were performed on site using fresh stools collected from cholera suspected cases, and from stools enriched in alkaline peptone water. Dried stool samples on filter paper were tested for V. cholerae by PCR in Lusaka (as part of a laboratory technology transfer project) and at a reference laboratory in Paris, France. A sample was considered positive for cholera by the reference standard if any of the culture or PCR tests was positive for V. cholerae O1 or O139. results Among the 170 samples tested with SD Bioline and compared to the reference standard, the RDT showed a sensitivity of 90.9% (95% CI: 81.3–96.6) and specificity of 95.2% (95% CI: 89.1–98.4). After enrichment, the sensitivity was 95.5% (95% CI: 87.3–99.1) and specificity 100% (95% CI: 96.5–100). conclusion The observed sensitivity and specificity were within recommendations set by the Global Task Force for Cholera Control on the use of cholera RDT (sensitivity = 90%; specificity = 85%). Although the sample size was small, our findings suggest that the SD Bioline RDT could be used in the field to rapidly alert public health officials to the likely presence of cholera cases when an outbreak is suspected.

Producción Científica, Killed oral cholera vaccines (OCVs) are part of the standard response package to a cholera outbreak, although the two-dose regimen of vaccines that has been prequalified by the World Health Organization (WHO) poses challenges to timely and efficient reactive vaccination campaigns.1 Recent data suggest that the first dose alone provides short-term protection, similar to that of two doses, which may largely dictate the effect of OCVs during epidemics

The 2014–2015 Ebola crisis in West Africa has highlighted the practical limits of upholding human rights and common ethical principles when applying emergency public-health measures. The role of medical teams in the implementation of quarantine and isolation has been equivocal, particularly when such measures are opposed by communities who are coerced by the temporary suspension of civil liberties. In their encounters with Ebola victims, outreach teams face moral dilemmas, where the boundaries are unclear between coercion, persuasion and appeals for self-sacrifice. For those teams, we propose a set of practical recommendations aimed at respecting the autonomy of epidemic victims and easing tensions within communities. We recognize that some of these recommendations are progressively achievable, depending on the specific stage or setting of an outbreak. Yet with the increasing availability of experimental treatments and research interventions, weighing patients' autonomy against the common good will become an even more pressing ethical obligation.

To describe the implementation and feasibility of an innovative mass vaccination strategy - based on single-dose oral cholera vaccine - to curb a cholera epidemic in a large urban setting.In April 2016, in the early stages of a cholera outbreak in Lusaka, Zambia, the health ministry collaborated with Médecins Sans Frontières and the World Health Organization in organizing a mass vaccination campaign, based on single-dose oral cholera vaccine. Over a period of 17 days, partners mobilized 1700 health ministry staff and community volunteers for community sensitization, social mobilization and vaccination activities in 10 townships. On each day, doses of vaccine were delivered to vaccination sites and administrative coverage was estimated.Overall, vaccination teams administered 424 100 doses of vaccine to an estimated target population of 578 043, resulting in an estimated administrative coverage of 73.4%. After the campaign, few cholera cases were reported and there was no evidence of the disease spreading within the vaccinated areas. The total cost of the campaign - 2.31 United States dollars (US$) per dose - included the relatively low cost of local delivery - US$ 0.41 per dose.We found that an early and large-scale targeted reactive campaign using a single-dose oral vaccine, organized in response to a cholera epidemic within a large city, to be feasible and appeared effective. While cholera vaccines remain in short supply, the maximization of the number of vaccines in response to a cholera epidemic, by the use of just one dose per member of an at-risk community, should be considered.Rendre compte de la mise en œuvre et de la faisabilité d'une stratégie de vaccination de masse innovante – fondée sur un vaccin anticholérique oral à dose unique – pour enrayer une épidémie de choléra dans une vaste zone urbaine.En avril 2016, aux premiers stades d'une flambée de choléra à Lusaka, en Zambie, le ministère de la Santé a collaboré avec Médecins Sans Frontières et l'Organisation mondiale de la Santé pour organiser une campagne de vaccination de masse fondée sur un vaccin anticholérique oral à dose unique. Pendant 17 jours, ces partenaires ont fait appel à 1700 membres du personnel du ministère de la Santé et bénévoles communautaires pour mener des activités de sensibilisation des communautés, de mobilisation sociale et de vaccination dans 10 municipalités. Chaque jour, des doses de vaccins ont été livrées sur les sites de vaccination et une estimation de la couverture administrative a été effectuée.En tout, les équipes de vaccination ont administré 424 100 doses de vaccins à une population cible estimée à 578 043 individus, ce qui se traduit par une couverture administrative estimée à 73,4%. Après la campagne, seuls de rares cas de choléra ont été signalés et aucun signe de propagation de la maladie dans les zones de vaccination n'a été noté. Le coût total de la campagne – 2,31 dollars des États-Unis ($US) par dose – incluait le coût relativement bas de la livraison locale – 0,41 $US par dose.L'organisation d'une campagne de vaccination réactive précoce, ciblée et à grande échelle – fondée sur un vaccin oral à dose unique – pour répondre à une épidémie de choléra dans une grande ville s'est avérée faisable et efficace. Alors que les vaccins anticholériques demeurent rares, il convient d'envisager la maximisation du nombre de vaccins pour faire face à une épidémie de choléra à travers l'utilisation d'une seule dose par membre d'une communauté vulnérable.describir la aplicación y la viabilidad de una estrategia innovadora de vacunación masiva, basada en una vacuna oral contra el cólera de una sola dosis, para frenar una epidemia de cólera en un entorno urbano grande.en abril de 2016, en las primeras etapas de un brote de cólera en Lusaka, Zambia, el Ministerio de Salud colaboró con Médecins Sans Frontières y la Organización Mundial de la Salud en la organización de una campaña masiva de vacunación basada en una vacuna oral contra el cólera de una sola dosis. Durante un período de 17 días, los socios movilizaron a 1700 voluntarios de personal sanitario y voluntarios de la comunidad para sensibilizar a la comunidad y para actividades de vacunación y movilización social en 10 municipios. Cada día, las dosis de la vacuna se entregaron en los lugares de vacunación y se estimó la cobertura administrativa.en general, los equipos de vacunación administraron 424.100 dosis de la vacuna a una población objetivo de unos 578.043 habitantes, lo que resultó en una cobertura administrativa estimada del 73,4%. Después de la campaña, se registraron pocos casos de cólera y no hubo pruebas de propagación de la enfermedad dentro de las zonas vacunadas. El costo total de la campaña (2,31 dólares estadounidenses (USD) por dosis) incluyó el coste relativamente bajo de la entrega local (0,41 $ por dosis).se descubrió que una campaña reactiva temprana dirigida y en gran escala con una vacuna oral de dosis única, organizada en respuesta a una epidemia de cólera dentro de una gran ciudad, era factible y aparentemente efectiva. Si bien las vacunas contra el cólera siguen siendo escasas, se debe considerar la maximización del número de vacunados en respuesta a una epidemia de cólera, mediante el uso de una sola dosis por miembro de una comunidad en riesgo.وصف لإجراءات تنفيذ استراتيجية مبتكرة للتطعيم الجماعي وإمكانية تطبيقها – إذ تقوم الاستراتيجية على تقديم جرعة واحدة من لقاح الكوليرا يتم تلقيها عبر الفم – وذلك للحد من انتشار وباء الكوليرا في منطقة حضرية واسعة النطاق.شهد عام 2016، مع المراحل الأولى لظهور مرض الكوليرا في مدينة "لوساكا" في زامبيا، تعاونًا بين وزارة الصحة بالبلاد من جهة ومنظمة أطباء بلا حدود (Médecins Sans Frontières) ومنظمة الصحة العالمية من جهة أخرى بشأن تنظيم حملة تطعيم جماعي تقوم على تقديم جرعة واحدة عبر الفم من لقاح الكوليرا. وخلال فترة تبلغ 17 يومًا، عملت الأطراف المتعاونة على حشد 1700 فرد من العاملين بوزارة الصحة والمتطوعين في الخدمات المجتمعية من أجل تحقيق التوعية المجتمعية والتعبئة الاجتماعية وتنفيذ أنشطة التطعيم في 10 أقاليم. وتم توفير جرعات التطعيم في كل يوم في مواقع التطعيم وجرى تقييم للتغطية المتعلقة بالجرعات المقدمة.قدمت فرق التطعيم بوجه عام 424100 جرعة من اللقاح لمجموعة مستهدفة من السكان بلغ عددها 578043 فردًا حسب التقديرات، مما أثمر عن وجود تغطية للجرعات المقدمة تم تقديرها بنسبة ‏73.4%. وبعد الحملة، قل العدد الذي يتم الإبلاغ به من حالات الإصابة بالكوليرا، ولم يوجد أي دليل على انتشار المرض في المناطق التي تم فيها التطعيم. وكانت التكلفة الإجمالية للحملة – التي بلغت 2.31 دولارًا أمريكيًا للجرعة الواحدة، شاملةً التكلفة المنخفضة نسبيًا لتوفير الجرعة محليًا – قد بلغت 0.41 دولارًا أمريكيًا للجرعة الواحدة.تبين لنا أن تنفيذ حملة موجهة واسعة النطاق في مرحلة مبكرة للتصدي للمرض باستخدام جرعة واحدة من لقاح فموي – وهي الحملة التي تم تنظيمها لمواجهة وباء الكوليرا على نطاق مدينة كبرى – أمر يمكن تحقيقه وبدت له نتائج مجدية. وبالرغم من استمرار المعاناة من النقص في الموارد المتاحة للقاح الكوليرا، يجب النظر في تحقيق أقصى استفادة ممكنة من عدد اللقاحات المتاحة للتصدي لوباء الكوليرا، وذلك عن طريق استخدام جرعة واحدة فقط لكل فرد من أفراد المجتمع المهدد بالإصابة بالمرض.旨在说明基于单剂量口服霍乱疫苗的创新型大规模接种策略的实施和可行性，以遏制大型城市环境中的霍乱疫情。.2016 年 4 月，在赞比亚卢萨卡霍乱爆发的早期阶段，卫生部门与无国界医生组织和世界卫生组织合作组织了基于单剂量口服霍乱疫苗的大规模疫苗接种活动。在 17 天的时间里，合作方共动员了 1700 名卫生部工作人员和社区志愿者在 10 个乡镇开展社区宣传、社会动员和疫苗接种活动。每天将疫苗剂量送到疫苗接种处并估计接种覆盖率。.总体而言，疫苗接种小组对估计的目标人群 578043 人进行了 424100 剂疫苗接种，估计接种覆盖率为 73.4％。此项活动后，报告的霍乱案例很少，没有证据表明疫苗接种区域内有传染病。活动的总费用——每剂量 2.31 美元，包括相对较低的本地交付成本（每剂量 0.41 美元）。.我们发现，使用单剂量口服疫苗的早期大规模针对性反应性活动是为了应对大城市内的霍乱疫情而组织起来的，可行且有效。尽管霍乱疫苗仍然供不应求，但每一名处于危险社区中的成员只需一个剂量，应对霍乱疫情所需的最大接种疫苗数量应该考虑在内。.Описать реализацию и осуществимость инновационной стратегии массовой вакцинации, основанной на применении однодозовой пероральной противохолерной вакцины, для борьбы с эпидемией холеры в условиях крупных городов.В апреле 2016 года на ранних стадиях вспышки холеры в Лусаке, Замбия, Министерство здравоохранения сотрудничало с организацией «Врачи без границ» и Всемирной организацией здравоохранения при проведении кампании массовой вакцинации, основанной на применении однодозовой пероральной противохолерной вакцины. В течение 17 дней партнеры мобилизовали 1700 сотрудников Министерства здравоохранения и общинных добровольцев для повышения информированности населения, социальной мобилизации и вакцинации в 10 поселках. Ежедневно на участки вакцинации доставлялись дозы вакцины и оценивался административный охват вакцинацией.В целом группами вакцинации были введены 424 100 доз вакцины в предполагаемой целевой популяции в количестве 578 043 человек, в результате чего административный охват оценивался как 73,4%. После кампании сообщалось о редких случаях заболевания холерой и не было признаков распространения болезни в вакцинированных районах. Общие расходы на кампанию составили 2,31 доллара США (US$) на 1 дозу, включая относительно низкую стоимость местной доставки — 0,41 доллара США на 1 дозу.Мы обнаружили, что ранняя и крупномасштабная целевая реактивная кампания с применением однодозовой пероральной вакцины, организованная в ответ на эпидемию холеры в крупном городе, осуществима и эффективна. Поскольку по-прежнему имеется дефицит противохолерных вакцин, следует рассмотреть вопрос об увеличении числа доступных вакцин в ответ на эпидемию холеры за счет использования только одной дозы на одного члена сообщества, находящегося в зоне риска.

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, In the context the recent Ebola outbreak, Xavier Anglaret and colleagues test an experimental treatment, favipiravir, for Ebola virus disease in a multicenter non-randomized trial., Editors' Summary Background In 2014 and 2015, an Ebola virus outbreak larger than any known before occurred in West Africa. Ebola virus disease (EVD) is highly contagious, and many infected people die. Central to the emergency response to the recent outbreak were local Ebola treatment centers where patients were diagnosed, were isolated, and received supportive care. With thousands of patients dying and many health workers contracting the disease, fear was ubiquitous and distrust abundant. While conducting research in this environment was extremely challenging, the urgent need for treatments and the opportunity to conduct studies that could bring such treatments closer to reality was also recognized. In September 2014, WHO released a short list of existing drugs that were candidates for clinical trials among patients infected in the outbreak. Favipiravir, an antiviral drug developed in Japan for patients with severe influenza, was on the list. Why Was This Study Done? Because of the urgent need to find drugs that could reduce deaths caused by Ebola, the researchers decided to conduct a clinical trial using favipiravir in patients with EVD in Guinea. In view of the circumstances, they decided against a randomized controlled trial and instead designed a study where all participants would receive the same treatment. In randomized controlled trials only some participants receive the treatment in addition to standard care, while others serve as a control group and receive standard care only, or standard care plus a placebo. Such studies allow stronger conclusions to be drawn about whether a treatment is safe and whether it works or not. The researchers had two main reasons for this decision. First, patients from the same family or village often sought EVD treatment at the same time, and the researchers felt that it was ethically unacceptable to randomize such groups, with only some of them receiving the experimental drug. Second, the strict isolation procedures imposed to interrupt virus transmission had intensified fear in affected communities and fueled rumors of illicit drug experimentation and organ theft at the treatment centers. In this context, the researchers worried that a randomized study might increase distrust among the community and the reluctance of patients to seek care. Rather than seeking definitive answers about the safety and efficacy of favipiravir in patients with EVD, the objectives of the study as it was designed were to test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak and to learn lessons from the experience. In addition, the researchers planned to collect data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with EVD in the hope that their preliminary findings could improve the design of subsequent trials and the chance to provide conclusive answers. What Did the Researchers Do and Find? After 13 weeks of preparation, the trial took place from December 2014 to April 2015 at four separate Ebola treatment centers, three in rural areas and one in an urban setting. In addition to standard care (which included rehydration, antimalarial and antibacterial therapies, and medication to reduce fever, pain, and nausea), all participants were given favipiravir by mouth for ten days, at doses substantially higher than those recommended for patients with influenza. Outcomes measured were mortality, viral load changes over time (based on blood samples), and adverse events. EVD was confirmed with an assay that used patient blood and provided an estimate of the viral load, that is, of how much virus the blood contained. Because viral load was known to influence the course of EVD, the researchers analyzed the participants in two groups, namely, those with a viral load estimate above a certain threshold and those with viral load estimate below the threshold. They also used existing data from Guinean patients diagnosed with Ebola earlier in the outbreak who had received only standard care and calculated an expected mortality rate for patients above and below the viral load threshold. The researchers were able to enroll 126 participants in the trial. Of these, 111 were included in the final analysis. Of 99 adult and adolescent participants 13 years and older, 55 were in the lower viral load group and 44 in the higher viral load group. Mortality was 20% in the former and 91% in the latter. Neither mortality rate was significantly different from that of earlier patients who had received only standard care. The researchers also found that favipiravir was well tolerated. None of the patients stopped the course of treatment, vomiting following drug intake was rare, and no severe adverse events were attributed to the drug. The researchers did not see a difference in mortality between patients who reported onset of symptoms less than three days before the start of treatment and those whose symptoms had started more than three days the start of treatment. What Do these Findings Mean? The report shows that it is possible to conduct an emergency trial during an outbreak in a low-resource setting. In fact, at the time of its acceptance, this paper reported on an Ebola treatment trial larger than any other yet published. The experience described should be useful for similar undertakings in the future. The following conditions contributed to the success of the trial: close collaboration between researchers, local health officials, and affected communities on one hand, and flexibility in design, conduct, and analysis based on close monitoring and interim assessments on the other. Besides using interim results to influence the conduct and analysis of their own trial, the researchers also shared these results with the scientific community in real time, and this feedback influenced other research during the outbreak. The trial could not answer definitively whether favipiravir treatment was safe or reduced mortality in patients with EVD. The results suggest that the drug is unlikely to be beneficial for patients with very high viral loads, at least when given by itself. They also suggest that favipiravir is safe in patients with lower viral loads, and that in such patients additional efficacy studies are warranted. Intermediate analysis of various measurements in trial participants showed that the estimate of viral load from the field EVD diagnosis test is a good proxy for the actual viral load (determined after the samples were shipped to and analyzed in a reference laboratory in France) and suitable as a surrogate marker. The results also confirm that viral load is a strong predictor of mortality. Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001967. The World Health Organization has pages on Ebola virus disease, trials of Ebola treatments and vaccines, and the current update of the list of suitable drugs for testing or use in patients infected with Ebola (originally compiled in September 2014) US Centers for Disease Control and Prevention has information on the Ebola outbreak in West Africa The European Centre for Disease Prevention and Control also has information on the Ebola outbreak in West Africa

Outbreaks of filovirus (Ebola and Marburg) hemorrhagic fevers in Africa are typically the theater of rescue activities involving international experts and agencies tasked with reinforcing national authorities in clinical manage-ment, biological diagnosis, sanitation, public health surveillance and coordination. These outbreaks can be seen as a paradigm for ethical issues posed by epidemic emergencies, through the convergence of such themes as: isolation and quarantine, privacy and confidentiality and the interpretation of ethical norms across different eth-nocultural settings. With an emphasis on the boundaries between public health investigations and research, this article reviews specific challenges, past practices and current normative documents relevant to the application of ethical standards in the course of outbreaks of filovirus hemorrhagic fevers. Aside from commonly identified issues of informed consent and institutional review processes, we argue for more clarity over the specification of which communities are expected to share benefits, and we advocate for the use of collective definitions of duty to care and standard of care. We propose new elaborations around existing normative instruments, and we suggest some pathways toward more comprehensive approaches to the ethics of research in outbreak situations.

In an observational cohort study including 89 Ebola patients, predictive factors of death were analyzed. The crude mortality rate was 43.8%. Myalgia (adjusted odds ratio [OR], 4.04; P = .02), hemorrrhage (adjusted OR, 3.5; P = .02), and difficulty breathing (adjusted OR, 5.75; P = .01) were independently associated with death.

We report here the NMR structure of dendrotoxin I, a powerful potassium channel blocker from the venom of the African Elapidae snake Dendroaspis polylepis polylepis (black mamba), calculated from an experimentally–derived set of 719 geometric restraints. The backbone of the toxin superimposes on bovine pancreatic trypsin inhibitor (BPTI) with a root–mean–square deviation of

International audience; Theoretical studies of the sequence-dependent conformation of B-DNA have been carried out using Jumna, a helicoidal co-ordinate minimization algorithm. The results obtained for a series of six oligomers with repetitive sequences show that, with the exception of the homopolymers (dA)n.(dT)n and (dG)n.(dC)n, all sequences can adopt a variety of conformations characterized by considerable changes in helicoidal parameters and also in sugar puckers which adopt C(2')-endo (falling into 2 classes) or, in the case of pyrimidine nucleotides, O(1')-endo forms. These studies lead to an improved understanding of the role of base sequence on DNA conformation and point to a number of interesting correlations between the various structural parameters describing the double helix.Theoretical studies of the sequence-dependent conformation of B-DNA have been carried out using Jumna, a helicoidal co-ordinate minimization algorithm. The results obtained for a series of six oligomers with repetitive sequences show that, with the exception of the homopolymers (dA)n.(dT)n and (dG)n.(dC)n, all sequences can adopt a variety of conformations characterized by considerable changes in helicoidal parameters and also in sugar puckers which adopt C(2')-endo (falling into 2 classes) or, in the case of pyrimidine nucleotides, O(1')-endo forms. These studies lead to an improved understanding of the role of base sequence on DNA conformation and point to a number of interesting correlations between the various structural parameters describing the double helix.

Systematic theoretical modeling of symmetric DNA oligomers, carried out earlier for the B conformation, is now extended to A-DNA. In contrast to the previous results, it is found that A-DNA shows no multiplicity of low-energy substate conformations. The possibilities of the Jumna algorithm are subsequently applied to studying deformations of the oligomers. Controlled winding and stretching deformations are used to study how the two allomorphs and different base sequences absorb such external stress. The results help explain the internal mechanics of the DNA double helix and the extent to which fine structure influences this behavior. The results point to some differences between the A and B double helices, but also to many similarities. Sequence effects on flexibility are relatively limited compared to their impact on optimal energy conformations. It is also shown that the conformational substates detected for B-DNA oligomers are preserved under deformation, but have little influence on its energetics.Systematic theoretical modeling of symmetric DNA oligomers, carried out earlier for the B conformation, is now extended to A-DNA. In contrast to the previous results, it is found that A-DNA shows no multiplicity of low-energy substate conformations. The possibilities of the Jumna algorithm are subsequently applied to studying deformations of the oligomers. Controlled winding and stretching deformations are used to study how the two allomorphs and different base sequences absorb such external stress. The results help explain the internal mechanics of the DNA double helix and the extent to which fine structure influences this behavior. The results point to some differences between the A and B double helices, but also to many similarities. Sequence effects on flexibility are relatively limited compared to their impact on optimal energy conformations. It is also shown that the conformational substates detected for B-DNA oligomers are preserved under deformation, but have little influence on its energetics.

Calicheamicin gamma 1I is a recently discovered diyne-ene-containing antitumor antibiotic that cleaves DNA in a double-stranded fashion, a rarity among drugs, at specific sequences. It is proposed that the cutting specificity is due to a combination of the complementarity of the diyne-ene portion of the aglycone with DNA secondary structures and stabilization by association of the thiobenzoate-carbohydrate tail with the minor groove.