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International audience; Due to travel restrictions, a dramatic decrease of rabies post-exposure demand was observed in 2020 in the Ile-de-France region. The recovery of international travels may lead to a rebound in rabies exposures. This risk need to be anticipated and prevention messages delivered to people travelling to rabies-enzootic countries.

It is difficult to deliver adequate training for people working in rabies control in low and middle-income countries. Popular e-learning systems for low-income settings are not well suited to developing and testing practical skills, including laboratory methods.We customized training in rabies control methods for African professionals and students from different disciplines. Trainees participated in preparatory online sessions, evaluations and exercises before and after a 12-day workshop. Trainees and mentors continued to interact through an online forum up to one year after the workshop.In Africa, 15,000 deaths from rabies occur each year due to a lack of awareness, inaccessibility of post-exposure prophylaxis, inadequate or absent canine rabies-control programmes and lack of governmental financial support.Thirty two trainees - working in health departments, hospitals, veterinary stations and research institutes - were selected to participate; 28 completed the course and passed the final evaluation. Pilot rabies investigation programmes were developed, and two manuscripts submitted for publication. An online forum facilitated further progress for a year after the workshop.A combination of customized online and onsite training is suitable for teaching disease-control personnel in low-income countries. Participation in this course enabled trainees to advocate for the development of national disease-control strategies. Mentoring is needed to develop a strong network of experts in similar settings.Il est difficile de dispenser une formation appropriée aux personnes intervenant dans la lutte contre la rage dans les pays à revenu faible et intermédiaire. Les systèmes populaires d'apprentissage en ligne conçus pour les pays à faible revenu ne sont pas adaptés au développement et au test des compétences pratiques, notamment en ce qui concerne les méthodes analytiques.Nous avons adapté la formation sur les méthodes de lutte contre la rage à l'intention de professionnels et d'étudiants africains issus de différentes disciplines. Les bénéficiaires de la formation ont participé à des séances de préparation en ligne, à des évaluations et à des exercices, avant et après un atelier de 12 jours. Puis, les bénéficiaires de la formation et les tuteurs ont continué à interagir jusqu'à un an après l'atelier via un forum accessible en ligne.En Afrique, 15.000 décès dus à la rage surviennent chaque année. Cette situation vient d'un manque de sensibilisation, de l'inaccessibilité des traitements de prophylaxie post-exposition, de programmes de lutte contre la rage canine inappropriés voire inexistants et d'un manque de soutien financier gouvernemental.Trente-deux bénéficiaires de la formation (qui travaillent dans des services de santé, des hôpitaux, des centres vétérinaires ou des instituts de recherche) ont été sélectionnés pour la formation ; vingt-huit l'ont achevée et ont passé avec succès l'évaluation finale. Des programmes pilotes d'enquête sur la rage ont été élaborés et deux manuscrits ont été soumis pour publication. Un forum en ligne a facilité la poursuite des progrès pendant l'année qui a suivi l'atelier.L'association de modules proposés en ligne et sur place est adaptée à la formation du personnel de lutte contre la maladie dans les pays à faible revenu. La participation à cette formation a permis à ses bénéficiaires de plaider pour l'élaboration de stratégies nationales de lutte contre la maladie. Un tutorat est nécessaire pour constituer un solide réseau d'experts dans des contextes similaires.Es difícil proporcionar una formación adecuada a aquellos que trabajan en el control de la rabia en países de ingresos bajos y medios. Los populares sistemas de aprendizaje en línea en comunidades de ingresos bajos no son adecuados para desarrollar y poner a prueba las habilidades prácticas, incluidos los métodos de laboratorio.Se personalizó la formación en los métodos de control de la rabia para los profesionales y estudiantes africanos de diferentes disciplinas. Los alumnos participaron en sesiones preparatorias, evaluaciones y ejercicios en línea antes y después de un taller de 12 días. Los alumnos y los profesores siguieron interactuando a través de un foro en línea hasta un año después del taller.En África, hay 15.000 muertes de rabia cada año debidas a la falta de concienciación, la inaccesibilidad de la profilaxis postexposición, los programas inadecuados o ausentes de control de la rabia canina y la falta de apoyo financiero del gobierno.Treinta y dos alumnos que trabajan en departamentos de salud, hospitales, clínicas veterinarias e institutos de investigación fueron seleccionados para participar. 28 de ellos completaron el curso y aprobaron la evaluación final. Se desarrollaron programas piloto de investigación de la rabia y se presentaron 2 manuscritos para su publicación. Gracias al foro en línea, se pudo seguir progresando hasta un año después del taller.La combinación de la formación en línea y presencial es adecuada para enseñar al personal de control de enfermedades en países de ingresos bajos. La participación en este curso permitió a los alumnos promocionar el desarrollo de estrategias nacionales de control de enfermedades. La tutoría es necesaria para desarrollar una sólida red de expertos en marcos similares.يصعب تقديم التدريب الكافي للعاملين في مكافحة داء الكَلَب في البلدان منخفضة ومتوسطة الدخل. ولا تُعد نظم التعليم الإلكتروني الشعبية للمواقع منخفضة الدخل مناسبة تمامًا لتطوير واختبار المهارات العملية، بما في ذلك الأساليب المختبرية.لقد قمنا بتخصيص تدريبات في أساليب مكافحة داء الكَلَب للمختصين الأفارقة والطلبة من مختلف الاختصاصات. وشارك المتدربون في الجلسات والتقييمات والتمارين التحضيرية المباشرة على شبكة الإنترنت، قبل وبعد إجراء حلقة عمل لمدةفي أفريقيا، تحدثتم اختيار اثنان وثلاثين متدربًا – يعملون في الأقسام والإدارات الصحية، والمستشفيات، والمحطات البيطرية، ومعاهد الأبحاث – للمشاركة؛ وقد قاممن المناسب الجمع بين التدريبات المباشرة على الإنترنت والتدريبات الميدانية في الموقع لتعليم العاملين المختصين بمكافحة الأمراض في البلدان منخفضة الدخل. كان للمشاركة في هذه الدورة التدريبية أثر في تمكين المتدربين من الدعوة إلى إعداد استراتيجيات وطنية لمكافحة الأمراض. وهناك حاجة إلى التوجيه لإعداد شبكة قوية من الخبراء في بيئات مشابهة.在中低收入国家中难以为从事狂犬病控制的人员提供合适的培训。低收入环境中普及的电子学习系统不太适于开发并测试实践技能，包括化验方法。.我们针对不同学科的非洲专业人员和学生开展了关于狂犬病控制方法的定制化培训。受训人员在为期 12 天的研讨会前后参与了预备在线课程、评估和练习。受训人员和导师在研讨会结束后继续通过在线论坛进行了长达一年的互动交流。.在非洲，每年有 15 000 人死于狂犬病，这是因为缺乏意识、无法在接触后采取预防措施、狂犬病控制计划的制定不充分或没有制定，以及政府财政支持不足。.选出 32 名就职于卫生部门、医院、兽医站和研究所的受训人员参与培训，其中有 28 名完成了课程并通过了最终评估。制定出试行的狂犬病调查计划，并提交了 2 份原稿用于出版。研讨会结束后，在线论坛进一步推动了为期一年的进展。.定制化的在线和现场培训相结合，适合用于教导低收入国家的疾病控制人员。参与此项课程有助于让受训人员拥护国家疾病控制策略的发展。在相似的环境中，需要在指导下开发强大的专家网络。.В странах с низким и средним уровнем доходов населения трудно обеспечить адекватное обучение специалистов по контролю распространения бешенства. Популярные системы электронного обучения для стран с низким уровнем дохода плохо подходят для развития и проверки практических навыков, включая знания лабораторных методов контроля.Обучение методам контроля распространения бешенства было адаптировано для африканских специалистов и студентов различных дисциплин. Обучаемые проходили 12-дневный практический курс. Перед курсом и после него проводились подготовительные занятия, тестирование и практические занятия в режиме онлайн. Обучаемые и кураторы продолжали взаимодействие через онлайн-форум на протяжении одного года после окончания курса.В Африке от бешенства ежегодно умирает 15 000 человек. Причиной тому является слабая информированность населения, недоступность постконтактной профилактики, неэффективность или отсутствие программ контроля распространения бешенства среди собак и отсутствие финансовой поддержки от государства.Для участия в курсе были отобраны 32 сотрудника из департаментов здравоохранения, больниц, ветеринарных станций и исследовательских институтов; 28 человек окончили курс и прошли окончательное тестирование. Были разработаны пилотные программы по исследованию бешенства, и две рукописи были сданы в печать. Онлайн-форум способствовал дальнейшему обучению участников на протяжении одного года после окончания курса.Для обучения специалистов по контролю распространения заболеваний в странах с низким уровнем дохода населения подходит сочетание индивидуализированного обучения онлайн и на местах. Участие в данном курсе позволило обучаемым выступить в поддержку разработки национальных стратегий по контролю распространения заболеваний. Для создания сети высококвалифицированных специалистов в подобных условиях необходимо организовать эффективный процесс наставничества.

International audience; INTRODUCTION:Benefit-risk of different anti-rabies post-exposure prophylaxis (PEP) strategies after scratches or bites from dogs with unknown rabies status is unknown in very low rabies risk settings.DESIGN AND SETTING:A cost-effectiveness analysis in metropolitan France using a decision-tree model and input data from 2001 to 2011.POPULATION:A cohort of 2807 patients, based on the mean annual number of patients exposed to category CII (minor scratches) or CIII (transdermal bite) dog attacks in metropolitan France between 2001 and 2011.INTERVENTIONS:Five PEP strategies: (A) no PEP for CII and CIII; (B) vaccine only for CIII; (C) vaccine for CII and CIII; (D) vaccine+ rabies immunoglobulin (RIG) only for CIII; and (E) vaccine for CII and vaccine+ RIG for CIII.MAIN OUTCOMES MEASURES:The number of deaths related to rabies and to traffic accidents on the way to anti-rabies centers (ARC), effectiveness in terms of years of life gained by reducing rabies cases and avoiding traffic accidents, costs, and incremental cost-effectiveness ratios (ICER) associated with each strategy.RESULTS:Strategy E led to the fewest rabies cases (3.6 × 10(-8)) and the highest costs (€ 1,606,000) but also to 1.7 × 10(-3) lethal traffic accidents. Strategy A was associated with the most rabies cases (4.8 × 10(-6)), but the risk of traffic accidents and costs were null; therefore, strategy A was the most effective and the least costly. The sensitivity analysis showed that, when the probability that a given dog is rabid a given day (PA) was > 1.4 × 10(-6), strategy D was more effective than strategy A; strategy B became cost-effective (i.e. ICER vs strategy A < 3 × French Gross Domestic Product per capita) when PA was > 1 .4 × 10(-4).CONCLUSIONS:In the metropolitan France's very low rabies prevalence context, PEP with rabies vaccine, administered alone or with RIG, is associated with significant and unnecessary costs and unfavourable benefit-risk ratios regardless to exposure category.

International audience; Rabies is responsible for 50,000 deaths per year worldwide. Mainland France has been officially freed from rabies in non-flying animals since 2001.; We wanted to provide an update on the French situation, using published data, and describe possible options since official guidelines are lacking.; Post-exposure prophylaxis (PEP) (early and careful cleaning and dressing of the wound, vaccination, and in case of high-risk exposure, injection of specific anti-rabies immunoglobulins) is known to be efficient except in rare cases. It is recommended after grade II contact (+specific immunoglobulins in immunodepressed patients), or grade III contact (vaccination+immunoglobulins).; Mainland France being rabies-free, 3 options may be considered in case of bite by a dog or a cat that cannot be monitored in France: (a) consider the risk of rabies as null, so no PEP should be administrated, whatever the severity of bites; (b) consider there is a weak but lethal risk, so the international recommendations should be applied, using immunoglobulins in some cases; (c) consider that the risk is extremely low but cannot be excluded, and that the patient should be vaccinated to be protected, but without adding immunoglobulins (whether in case of grade II or III bites).; There are no national guidelines for rabies in France, and so the physician managing the patient is the one who will decide to treat or not.

Background The nonhuman primate (NHP)-related injuries in rabies-enzootic countries is a public health problem of increasing importance. The aims of this work are to collect data concerning rabies transmission from NHPs to humans; to collate medical practices regarding rabies postexposure prophylaxis (PEP) in different countries, and to provide an evidence base to support the decision to apply rabies PEP in this context. Methodology To retrieve information, we conducted a literature search from 1960 to January 2013. All reports of rabies in NHPs and rabies transmission to humans by infected NHPs were included. Also included were studies of travelers seeking care for rabies PEP in various settings. Data collected by the French National Reference Centre for Rabies concerning NHPs submitted for rabies diagnosis in France and human rabies exposure to NHPs in travelers returning to France were analyzed for the periods 1999–2012 and 1994–2011, respectively. Principal findings A total of 159 reports of rabies in NHPs have been retrieved from various sources in South America, Africa, and Asia, including 13 cases in animals imported to Europe and the US. 134 were laboratory confirmed cases. 25 cases of human rabies following NHP-related injuries were reported, including 20 from Brazil. Among more than 2000 international travelers from various settings, the proportion of injuries related to NHP exposures was about 31%. NHPs rank second, following dogs in most studies and first in studies conducted in travelers returning from Southeast Asia. In France, 15.6% of 1606 travelers seeking PEP for exposure to any animal were injured by monkeys. Conclusions/significance Although less frequently reported in published literature than human rabies, confirmed rabies cases in NHPs occur. The occurrence of documented transmission of rabies from NHPs to human suggests that rabies PEP is indicated in patients injured by NHPs in rabies-enzootic countries., Author Summary No international consensus or even a consensus among existing national recommendations about rabies postexposure prophylaxis (PEP) following a nonhuman primate (NHP)-related injury currently exists. Epidemiologic studies and reports collated in this review indicate that the number of rabies case reported in NHPs are rare compared with humans. This finding might be because of a lower contact rate of NHPs with rabid reservoir but also very likely because of underreporting. Nevertheless, documented cases and subsequent transmission to humans have been reported from various sources in South America, Africa, and Asia. Further, international travelers often report NHP-related injuries and NHPs can be close to humans. Little is currently known of the pathobiology of rabies virus shedding in primates, which implies that rabies PEP and administration of rabies immunoglobulin should be considered in patients with a possible exposure.

International audience; Rabies virus, a neurotropic lyssavirus responsible for unavoidable fatal encephalitis, is transmitted by saliva of infected animals through bite, scratch or licking of broken skin or a mucous membrane. Infection can be prevented by timely prevention (wash for several minutes, antisepsis and vaccination completed by antirabies immunoglobulins [Ig] according to the severity of exposure). The 55,000 human deaths estimated annually worldwide result mainly from uncontrolled canine rabies in enzootic countries (particularly in Africa and in Asia), attributable to a lack of resources or interest for this disease. Bat rabies, henceforth first cause of human's rabies in many countries in America, affects a very small number of individuals but seems more difficult to control. Shortened vaccine protocols, rationalized use of Ig and development of products of substitution should enhance access of exposed patients to prevention. Finally, research on the biological cycle, the pathogeny and on escape of virus-induced mechanisms from the immune system should continue to pave the way for presently unknown treatments of clinical rabies.

Presented in part as an oral communication at the 10th Journées Nationales d’Infectiologie, Marseille, France, June 10-12, 2009.; International audience; On May 27, 2008, a patient died from rabies at the Cayenne Hospital in French Guiana. Postexposure prophylaxis vaccination was implemented for all health care workers exposed to this patient. Examining the management of such a rare risk reveals important factors in the education of personnel who may have contact with a patient with rabies, to permit appropriate risk assessment and reduce unnecessary postexposure prophylaxis, taking into account the risks and costs of adverse events.

We report on a case of imported human rabies in Portugal, in July 2011 in a woman who presented initially complaining of back pain, without relating exposure to animal bites. She had travelled from Portugal to Bissau, Guinea-Bissau, in April where she had been bitten by a dog on 1 May. She was diagnosed with rabies on 26 July and died two weeks later in spite of being treated following the Milwaukee protocol.

Background Until 2008, human rabies had never been reported in French Guiana. On 28 May 2008, the French National Reference Center for Rabies (Institut Pasteur, Paris) confirmed the rabies diagnosis, based on hemi-nested polymerase chain reaction on skin biopsy and saliva specimens from a Guianan, who had never travelled overseas and died in Cayenne after presenting clinically typical meningoencephalitis. Methodology/Principal Findings Molecular typing of the virus identified a Lyssavirus (Rabies virus species), closely related to those circulating in hematophagous bats (mainly Desmodus rotundus) in Latin America. A multidisciplinary Crisis Unit was activated. Its objectives were to implement an epidemiological investigation and a veterinary survey, to provide control measures and establish a communications program. The origin of the contamination was not formally established, but was probably linked to a bat bite based on the virus type isolated. After confirming exposure of 90 persons, they were vaccinated against rabies: 42 from the case's entourage and 48 healthcare workers. To handle that emergence and the local population's increased demand to be vaccinated, a specific communications program was established using several media: television, newspaper, radio. Conclusion/Significance This episode, occurring in the context of a Department far from continental France, strongly affected the local population, healthcare workers and authorities, and the management team faced intense pressure. This observation confirms that the risk of contracting rabies in French Guiana is real, with consequences for population educational program, control measures, medical diagnosis and post-exposure prophylaxis., Author Summary Until 2008, rabies had never been described within the French Guianan human population. Emergence of the first case in May 2008 in this French Overseas Department represented a public health event that markedly affected the local population, healthcare workers and public health authorities. The antirabies clinic of French Guiana, located at Institut Pasteur de la Guyane, had to reorganize its functioning to handle the dramatically increased demand for vaccination. A rigorous epidemiological investigation and a veterinary study were conducted to identify the contamination source, probably linked to a bat bite, and the exposed population. Communication was a key factor to controlling this episode and changing the local perception of this formerly neglected disease. Because similar clinical cases had previously been described, without having been diagnosed, medical practices must be adapted and the rabies virus should be sought more systematically in similarly presenting cases. Sharing this experience could be useful for other countries that might someday have to manage such an emergence.

Background Imported cases threaten rabies reemergence in rabies-free areas. During 2000–2005, five dog and one human rabies cases were imported into France, a rabies-free country since 2001. The Summer 2004 event led to unprecedented media warnings by the French Public Health Director. We investigated medical practice evolution following the official elimination of rabies in 2001; impact of subsequent episodic rabies importations and national newspaper coverage on demand for and delivery of antirabies prophylaxis; regular transmission of epidemiological developments within the French Antirabies Medical Center (ARMC) network; and ARMC discussions on indications of rabies post-exposure prophylaxis (RPEP). Methodology/Principal Findings Annual data collected by the National Reference Center for Rabies NRCR (1989–2006) and the exhaustive database (2000–2005) of 56 ARMC were analyzed. Weekly numbers of patients consulting at ARMC and their RPEP- and antirabies-immunoglobulin (ARIG) prescription rates were determined. Autoregressive integrated moving-average modeling and regression with autocorrelated errors were applied to examine how 2000–2005 episodic rabies events and their related national newspaper coverage affected demand for and delivery of RPEP. A slight, continuous decline of rabies-dedicated public health facility attendance was observed from 2000 to 2004. Then, during the Summer 2004 event, patient consultations and RPEP and ARIG prescriptions increased by 84%, 19.7% and 43.4%, respectively. Moreover, elevated medical resource use persisted in 2005, despite communication efforts, without any secondary human or animal case. Conclusions Our findings demonstrated appropriate responsiveness to reemerging rabies cases and effective newspaper reporting, as no secondary case occurred. However, the ensuing demand on medical resources had immediate and long-lasting effects on rabies-related public health resources and expenses. Henceforth, when facing such an event, decision-makers must anticipate the broad impact of their media communications to counter the emerging risk on maintaining an optimal public health organization and implement a post-crisis communication strategy., Author Summary Rabies has been eliminated from a large part of the European Union and, thus, any newly imported cases threaten its reemergence. The 2000–2005 data derived from the exhaustive surveillance system implemented in France was analyzed to evaluate the impact on demand for and delivery of antirabies prophylaxis following introduction of five rabies-infected dogs and one infected human into this rabies-free area. Using these events, we were able to illustrate the difficulties encountered in reducing the demand for and prescription of post-exposure rabies prophylaxis in this context of episodic importation. Moreover, we highlighted the need for public health decision-makers to anticipate the broad spectrum of consequences of their media communications and to prepare appropriate responses (in terms of health resources) to maintain an optimally effective public health organization after importation of an exotic infectious agent or its emergence. These responses are particularly relevant in the context of limited availability of rabies post-exposure prophylaxis, especially antirabies immunoglobulin.

As the demand for rabies post-exposure prophylaxis (PEP) treatments has increased exponentially in recent years, the limited supply of human and equine rabies immunoglobulin (HRIG and ERIG) has failed to provide the required passive immune component in PEP in countries where canine rabies is endemic. Replacement of HRIG and ERIG with a potentially cheaper and efficacious alternative biological for treatment of rabies in humans, therefore, remains a high priority. In this study, we set out to assess a mouse monoclonal antibody (MoMAb) cocktail with the ultimate goal to develop a product at the lowest possible cost that can be used in developing countries as a replacement for RIG in PEP. Five MoMAbs, E559.9.14, 1112-1, 62-71-3, M727-5-1, and M777-16-3, were selected from available panels based on stringent criteria, such as biological activity, neutralizing potency, binding specificity, spectrum of neutralization of lyssaviruses, and history of each hybridoma. Four of these MoMAbs recognize epitopes in antigenic site II and one recognizes an epitope in antigenic site III on the rabies virus (RABV) glycoprotein, as determined by nucleotide sequence analysis of the glycoprotein gene of unique MoMAb neutralization-escape mutants. The MoMAbs were produced under Good Laboratory Practice (GLP) conditions. Unique combinations (cocktails) were prepared, using different concentrations of the MoMAbs that were capable of targeting non-overlapping epitopes of antigenic sites II and III. Blind in vitro efficacy studies showed the MoMab cocktails neutralized a broad spectrum of lyssaviruses except for lyssaviruses belonging to phylogroups II and III. In vivo, MoMAb cocktails resulted in protection as a component of PEP that was comparable to HRIG. In conclusion, all three novel combinations of MoMAbs were shown to have equal efficacy to HRIG and therefore could be considered a potentially less expensive alternative biological agent for use in PEP and prevention of rabies in humans., Author Summary Human mortality from endemic canine rabies is estimated to be 55,000 deaths per year in Africa and Asia, yet rabies remains a neglected disease throughout most of these countries. More than 99% of human rabies cases are caused by infections resulting from a dog-bite injury. In the vast majority of human exposures to rabies, patients require post-exposure prophylaxis (PEP), which includes both passive (rabies immunoglobulin, RIG) and active immunization (rabies vaccine). The number of victims requiring PEP has increased exponentially in recent years, and human and equine RIG (HRIG and ERIG) were not sufficiently available in countries where canine rabies is endemic. Rabies virus-neutralizing monoclonal antibodies (MAbs) of mouse (Mo) origin have been identified as promising alternatives to HRIG and ERIG. We have developed and assessed both in vitro and in vivo unique mouse monoclonal antibody (MoMAb) cocktails, which are highly efficacious. Three novel combinations were shown to have an equal or superior efficacy to HRIG and therefore could be considered a potentially less expensive alternative for passive prophylactic use to prevent the development of rabies in humans, particularly where needed most in developing countries.