Diphtheria

国家疾病预防控制局发布的数据显示，2024年2月共报告百日咳17105例，比2023年12月多了7979例，是去年同期的近32倍，其中更是有13例病例不幸死亡。根据统计数据，今年的前两个月百日咳的发病数已经与去年全年的发病数接近，死亡数加起来超过了2018-2023年的总和。近年百日咳发病率也呈明显上升趋势百日咳是由百日咳鲍特杆菌引起的急性呼吸道传染性疾病，自1974年全球开展百白破混合疫苗接种以来，百日咳发病率明显下降，然而，在过去的10年中，欧洲和美国等疫苗覆盖率较高的发达国家，百日咳的发病率逐渐增加，称为“百日咳再现”， 2006 年至2010年我国百日咳年均报告发病率已降至0.2/10万，但2019年报告发病率却上升至2.15/10万，近年百日咳发病率也呈明显上升趋势。中国疾控中心主任沈洪兵也在最近召开的2024年疫苗与免疫大会上深入剖析了当前百日咳疫情的严峻形势。据其介绍，自2014年以来中国百日咳发病率呈明显上升趋势。截至2023年的最新报告显示，病例已高达38000多例。“这一数据引发了百日咳防控工作的高度关注和认识。”不仅在我国，其他国家的百日咳疫情也在恶化。自2023年以来，西班牙的百日咳病例不断增加，2023年下半年更是出现了第一例死亡病例。《理性报》报道，根据卡洛斯三世卫生研究所最新流行病学报告数据显示，自2024年1月1日以来累计确诊百日咳病例为5242例，而2023年同期仅为50例。今年以来，累计病例数比2023年的总数（2211例）高出85%。除了西班牙，菲律宾、英国、塞尔维亚、克罗地亚、丹麦、以色列、拉脱维亚和捷克共和国均出现了百日咳疫情恶化的情况。几天前，捷克报告了近年来最严重的百日咳疫情，在短短两个月内就出现了1666例病例。为何百日咳在全球有再现趋势？有学者认为，百日咳在全球有再现趋势，再现的可能因素包括：①医务人员对百日咳的知晓度和关注度的提高；②监测敏感度的提升；③PCR等实验室检测技术的应用；④部分地区疫苗接种率下降；⑤疫苗保护效果不佳；⑥疫苗接种后保护作用持续时间较短；⑦抗生素耐药等。近日，一位感染防控专家接受记者采访时则表示：“百日咳‘再现’说了已有十年，但目前来看仍处于低水平流行。今年病例较去年有显著上升，主要是因为新冠期间其他大部分呼吸道感染都呈现大幅下降的趋势，所以和去年同期没有可比性。”上述专家表示，值得警惕的是，小儿百日咳发病率增加，可能的因素是由于成人免疫力下降后更容易感染百日咳，但成人以轻症或无症状为主，传给小孩后，可能导致更为严重的症状。关于白百破疫苗接种中国疾控中心主任沈洪兵16日在“2024疫苗与免疫大会”上表示，我国百日咳发病率从2014年起呈明显上升趋势。他还称，接种疫苗可以降低重症和死亡风险。但无论是疫苗接种还是自然感染，均不能获得终身保护。目前针对百日咳接种的疫苗为“百白破”疫苗，即百日咳、白喉、破伤风联合疫苗。根据《国家免疫规划疫苗儿童免疫程序及说明（2021年版）》 ，百白破疫苗一共5剂，接种时间分别为：3月龄、4月龄、5月龄、18月龄各接种1剂百白破疫苗，6周岁接种1剂白破疫苗。但此方案不能有效保护免疫力低下的新生儿。针对这个问题，国外已建议实施更积极的预防策略，给妊娠27～36周的孕妇接种疫苗，给能够接触婴儿的人员均接种疫苗(蚕茧保护战略)，以及新生儿在出生时就开始接种DTaP疫苗(百白破三联疫苗)，前3次接种在出生后3个月内完成。数据显示，孕妇疫苗策略实施后小婴儿因百日咳住院的人数大幅下降。我国亦有预防接种专家共识推荐妊娠期孕母27~36周接种百白破疫苗，然而有研究显示，孕期接种百日咳疫苗可能在一定程度上影响婴儿出生后接种百日咳疫苗的主动免疫应答。因此，妊娠期孕母是否加强接种百日咳疫苗，仍需我国流行病学及预防接种等学科专家结合我国国情共同探讨。撰文 | 梅斯医学编辑 | Swagpp● 柳叶刀最新：全球生育率持续下降，逼近临界值！25年后，近50%国家的自然增长率为负，中国人口将持续减少● 怪不得他总是get不到你！Neuron最新：两性基因的神经环路不同，导致共情行为存在性别差异● 热议！专科生应聘影像技师，主任无奈拒绝：你很优秀，但我们只招本科！医生：初中生都能胜任，赶快取消这个专业吧，本科生恨它恨得牙痒痒版权说明：梅斯医学（MedSci）是国内领先的医学科研与学术服务平台，致力于医疗质量的改进，为临床实践提供智慧、精准的决策支持，让医生与患者受益。欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。点击下方「阅读原文」 立刻下载梅斯医学APP！

Sanofi’s outsourced marketing move mirrors similar strategies employed by Swiss drugmaker Novartis and British pharma powerhouse GSK. For various reasons, pharma firms often favor distribution pacts rather than relying on local subsidiaries to market their drugs. Now, French major Sanofi has enlisted three local companies to help enhance the profile of its medicines across South and East Asia. Sanofi has inked deals with India’s Cipla and Dr. Reddy's Laboratories, as well as South Korea’s SK Bioscience, to help sell its central nervous system (CNS) drugs and vaccines in those countries. Concerning Cipla, the Indian manufacturer is set to market six Sanofi central nervous system (CNS) medicines, including the leading epilepsy med Frisium. Sanofi will continue to own, import and manufacture its full spectrum of CNS products, both in-country and internationally, according to a release. "Cipla’s wide presence will enable us to expand the reach of this portfolio to healthcare professionals and patients across all India," Sanofi India managing director Rodolfo Hrosz said in a statement. Also in India, Sanofi struck a vaccine distribution accord with Dr. Reddy's, which will help hawk adult and pediatric shots. In South Korea, SK Bioscience will sell five Sanofi vaccines, including three for childhood diphtheria, tetanus and pertussis (DTap), plus a similar vaccine for adults and a meningococcal shot dubbed Menactra. The SK Bioscience deal spans the rest of 2024, with the potential to be expanded in the future.  Sanofi’s outsourced marketing move mirrors similar strategies employed by Swiss drugmaker Novartis and British pharma powerhouse GSK. Back in October, GSK announced a deal with Chongqing Zhifei Biological Products to help promote its shingles vaccine Shingrix in China. At the time, GSK hinted the pact could be a precursor to a similar arrangement between the companies for its new respiratory syncytial virus (RSV) shot Arexvy. Meanwhile, back in February 2022, Novartis forged an exclusive sales and distribution pact with Dr. Reddy’s Laboratories centered on certain established meds, including the pain-relief drug Voveran and Methergine, which is used to treat severe bleeding from the uterus after childbirth. As part of the distribution sales move, Novartis announced that it would cut 400 jobs in India. At the time, the Swiss company employed more than 10,000 full-time staffers in the populous South Asian country.

Theradaptive founder and CEO Luis Alvarez discusses how his team’s groundbreaking novel protein engineering platform promises to unlock the vast potential of therapeutic proteins in regenerative medicine, trauma and oncology. By Luis Alvarez, Theradaptive The more than 100,000 different proteins in the body play an instrumental role in the systems and processes that sustain life. These proteins transmit cellular signals, trigger tissue behaviors, direct immune responses, catalyze chemical reactions and are integral to tissue, organ and bone structure. It is this vast variety of functions that gives them such favorable potential as therapeutics. Harnessing the power of proteins is not a new concept. The first Nobel Prize in Physiology or Medicine was awarded in recognition of the discovery and use of a therapeutic protein, an antibody-based treatment for diphtheria. More than 100 years later, the therapeutic applications of proteins are vast and span almost every branch of modern medicine. But we have yet to harness much of the vast potential of therapeutic proteins to repair and regenerate tissue, partly because we lack the ability to reliably target the activity of a protein to a specific location in the body with anatomical precision for an extended period of time. Currently, the naturally occurring proteins used to regenerate bone disperse away from the site where they are needed, leading to off-target effects such as bone growth and inflammation elsewhere in the body. This is the problem Theradaptive is on a mission to solve. Our unique protein engineering platform enables us to modify bioactive proteins to create variants that bind to implants or devices and can be applied to the surface of an implant like a coat of paint. This enables the precision delivery and control of that protein through placement of the implant, optimizing efficacy where it is needed and removing the risk of off-target effects and toxicity. Benefits beyond binding Proteins initiate cell signaling that drives tissue repair and regeneration, but there needs to be an elevated presence of that protein for a sustained period generally ranging from days to months. There have been technologies that use encapsulation techniques or timed-release mechanisms to maintain sufficient protein levels at the site of repair, but a downside to these is that the majority of therapeutic protein is sequestered and not available to the damaged tissues at any given time, limiting efficacy. Our approach overcomes this by coating the device or implant with a stable layer of the therapeutic protein, which ensures that the entire therapeutic dose is available all of the time to interact with cells and initiate the required repair-signaling pathways. By making the entire surface of the device or implant bioactive, we maximize the surface area that can interact with cells, maximizing the efficacy of the protein. Navigating protein complexity Proteins are large, complex molecules with an enormous number of variations possible through amino acid substitutions. An even larger universe of variants emerges when you consider changes in solution conditions at protein–material interfaces that can trigger significant changes in side group properties. This latter effect can result in striking deviations from predicted affinity based on amino acid identity alone. This makes identifying suitable variants that retain therapeutic activity — while demonstrating strong binding and solution stability — like looking for a particular grain of sand on a beach. We have developed novel computational methods that streamline this process and allow us to mine large sequence libraries to identify variants of existing therapeutic proteins that have promising binding potential. We then take those promising variants and repeatedly modify and refine them using our own bioinformatics resource to focus that refinement toward the additional characteristics we want — stronger binding or enhanced stability, for example — without impacting therapeutic activity. It’s a computationally informed, accelerated evolution that results in a protein variant that is primed for highly desirable combined efficacy, stability and substrate binding. This refinement is possible for many proteins of therapeutic interest because the region of the molecule that is therapeutically active constitutes a very small part of the overall molecule. Compared to the complexity involved in producing an optimized material-binding variant of a therapeutic protein, the application of that protein to the chosen carrier — such as an implant or another device — is relatively simple: the carrier can be simply dipped in a liquid formulation of the protein for a few minutes. When properly optimized, the protein variant behaves like a paint that coats the surface of the implant or device, creating a stable surface layer of bioactive protein. Stabilizing proteins as a surface layer in this way also has other advantages, as it renders them far more robust and stable than free proteins in solution. In an unexpected application of this phenomenon, we have developed methods that permit us to terminally sterilize implants and devices coated with bioactive proteins without impacting the clinical efficacy of the bound protein. This results in manufacturing workflows that do not require aseptic techniques, vastly simplifying the process and reducing costs. The resulting product also shows excellent thermal stability, allowing terminally sterilized products to be stored at room temperature. Reducing development risk and accelerating the regulatory path Accurately predicting potential therapeutic activity of a novel protein can be challenging and can result in costly false starts. Our first products have focused on proteins with proven therapeutic activity in animal or human studies, thus reducing or eliminating efficacy risk. For example, bone morphogenetic protein 2 (BMP2) drives bone formation and has been used in various orthopedic indications for over 20 years. But without a way to deliver it with anatomical precision and prevent it from dispersing to other areas of the body, its use has been associated with significant off-target effects including heterotopic bone formation and severe edema. To address this, we used our protein engineering platform to create a material-binding, or “sticky,” variant of BMP2 that we call AMP2. AMP2 retains the naturally occurring osteoinductive properties of BMP2, but delivers bone growth in a targeted anatomically precise manner. Our lead product, OsteoAdapt SP, is a resorbable spinal fusion implant with a bioactive surface coating of AMP2. This enables the precision placement of this powerful bone formation protein in the exact location where it is needed to maximize therapeutic effect while eliminating off-target effects associated with BMP2. OsteoAdapt SP has been granted three FDA Breakthrough Device Designations due to its clinical potential and the promise of improvement over current therapeutics. These designations permit the acceleration of regulatory review and clinical development to deliver this much-needed innovation in spinal fusion to patients. Fertile ground to drive our transformation With our first clinical trial for OsteoAdapt SP beginning in late March, it is a pivotal moment for Theradaptive. We are now a clinical-stage company, and embarked on this transformation from the strongest of foundations. When Theradaptive was formed, we chose to locate in Frederick, Maryland to be part of the world-leading life sciences ecosystem that Maryland has to offer. The wealth of support from local and state agencies such as the Maryland Stem Cell Research Fund (MSCRF) and technology incubators such as the Frederick Innovative Technology Center (FITCI)were instrumental to our early progress. We are now at an entirely different stage as a company, but the resources, infrastructure and talent we can tap into given our location will continue to put us in the best position to accelerate growth and allow us to expand our world-class team for the journey ahead. In 2024, we look forward to collecting our first clinical data, as well as continuing to develop our pipeline of targeted protein therapeutics for indications beyond orthopedics and spine. In 2023, we launched a program in tumor targeted immuno-oncology, thus extending our platform in a promising new direction. Ultimately, we seek to harness the hidden power of proteins to not only exert their expected therapeutic effect, but to also allow us control their fate once placed inside the body. Theradaptive founder and CEO Luis Alvarez is a West Point graduate who served in the U.S. Army for 20 years and earned his a Ph.D. in biological engineering at MIT after seeing fellow service members with tissue damage undergo delayed amputations. Alvarez was also the founding deputy director of the Department of Defense’s Regenerative Medicine Program Office as well as the lead for DOD’s $720M nerve agent pharmaceutical countermeasures program. How to submit a contribution to MDO The opinions expressed in this blog post are the author’s only and do not necessarily reflect those of Medical Design & Outsourcing or its employees.