Chloroquine hydrochloride

LONDON, UK I December 04, 2024 I GSK plc (LSE/NYSE: GSK) and Medicines for Malaria Venture (MMV) announced today that the World Health Organization (WHO) has awarded prequalification to tafenoquine , the first single-dose medicine for the prevention of relapse of Plasmodium vivax (P. vivax) malaria. Tafenoquine , co-administered with chloroquine, is now also included in WHO’s updated Guidelines for malaria, in South America, marking the first time the medicine has been recommended by WHO. This milestone is a significant step toward closing the treatment gap for P. vivax malaria. The WHO prequalification and updated guidelines include both adults and children aged 2 years and older, weighing at least 10 kg. A single-dose medicine provides an opportunity to overcome challenges with adherence to the existing longer, one-two week regimen of the standard of care, which can be a challenge for patients with relapsing malaria whose symptoms improve shortly after treatment initiation 1 . P. vivax is the dominant malaria parasite in most countries outside of sub-Saharan Africa, prevalent in most tropical and sub-tropical areas in the world, with children under five and migrant populations at particular risk. Among these vulnerable groups, infants and children carry a disproportionate burden, being highly vulnerable to severe disease, recurrence and anaemia 2 . The complex lifecycle of the P. vivax parasite includes a blood stage and an undetectable dormant liver stage, which can reactivate, causing repeated episodes of malaria following a single infectious bite of a mosquito carrying this parasite. Thomas Breuer, Chief Global Health Officer, GSK, said: “WHO prequalification of tafenoquine opens new possibilities to positively impact and protect more lives; lives of children and vulnerable populations who continue to bear the burden of this devastating disease. Inclusion of tafenoquine in the updated Guidelines for malaria is an equally important step forward in efforts to eliminate this preventable and treatable disease. Making treatments simpler for people to take is an ambition of ours across much of our Global Health pipeline and portfolio. Alongside our partners, we remain committed to enabling affordable and equitable access to this new single-dose treatment option for those in need in malaria-endemic countries.” Martin Fitchet, Chief Executive Officer, MMV, said: “Today marks a historic milestone in the fight against malaria. The WHO’s prequalification of tafenoquine and its inclusion in the updated Guidelines for malaria is a groundbreaking advancement on the road to elimination, which will transform lives by providing a well-tolerated, effective, and single-dose cure to prevent malaria relapses in some of the world’s most vulnerable communities. This achievement is a testament to the power of innovation and collaboration in global health, to bring us closer to our vision of a malaria-free world.” Tafenoquine , an 8-aminoquinoline antimalarial drug targeting the liver-stage of P. vivax malaria, is recommended as an alternative to primaquine (3.5 mg/kg total dose) for preventing malaria relapses in children over the age of two in South America. A single dose of tafenoquine administered to P. vivax patients who receive chloroquine treatment provides what is known as radical cure: the treatment of both the blood- and liver-stages of the disease. Tafenoquine , like all 8-aminoquinolines, has the potential to cause haemolytic anaemia in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency, therefore G6PD testing must be performed before prescribing. This is possible with the ‘STANDARD’ G6PD test, developed in collaboration between SD Biosensor and PATH, which provides a measure of a patient’s G6PD enzyme activity levels in two minutes based on a drop of blood from a finger-prick. WHO prequalification of medicines is crucial as it ensures that the medicine meets standards of quality, safety and efficacy, and is suitable for the target population. The prequalification programme has played a vital role in improving the access to life-saving medications used by millions in low- and middle-income countries. The WHO Guidelines for malaria are regularly reviewed and updated by the world’s leading malaria experts under WHO’s convening. This update includes a first recommendation for tafenoquine (150mg tablets and 50mg dispersible tablets) with chloroquine in South America. WHO prequalification and Guideline inclusion follows the launch of tafenoquine in Brazil and Thailand in June this year. Approvals for tafenoquine have been granted in Australia, Brazil, Colombia, Ethiopia, Guyana, Myanmar, Pakistan, Peru, the Philippines, Thailand, Vietnam and the United States, and the drug is undergoing marketing authorisation evaluation in a number of other countries where P. vivax is endemic. About tafenoquine Tafenoquine is an 8-aminoquinoline with activity against all stages of the P. vivax lifecycle, including hypnozoites. It was first synthesised by scientists at the Walter Reed Army Institute of Research in 1978. GSK’s legacy in the research and development of tafenoquine as a potential medicine for malaria commenced over 20 years ago.  In 2008, GSK entered into a collaboration with the not-for-profit drug research partnership, MMV, to develop tafenoquine as an anti-relapse medicine for patients infected with P. vivax . The tafenoquine clinical programme is part of GSK’s global health programme aimed at improving healthcare for vulnerable populations. About Standard G6PD test The STANDARD G6PD test was developed in collaboration between SD Biosensor and PATH. The handheld device provides a measure of a patient’s G6PD enzyme activity levels in two minutes based on a drop of blood from a finger-prick. The Test has been approved by the Australian TGA, and by the Global Fund Expert Review Panel on Diagnostics (ERPD) and is distributed to over 30 countries. Important safety information Tafenoquine can cause haemolytic anaemia in patients with G6PD deficiency. The most common side effects are difficulty sleeping, headache, dizziness, nausea and vomiting. Allergic hypersensitivity reactions can occur after taking the drug. Please refer to the Consumer Medicine Information (CMI) summary for important dosage, administration, and safety information available at this link: kozenis-cmi-au.pdf (gsk.com) About Plasmodium vivax malaria The Plasmodium parasite is a complex organism with a lifecycle spanning both humans and mosquitoes. After an infected mosquito bite, the P. vivax parasite infects the blood and causes an acute malaria episode. It also has the ability to lie dormant in the liver (in a form known as hypnozoite) from where it periodically reactivates to cause relapses of P. vivax malaria. Hence, a single P. vivax infection can give rise to multiple episodes of malaria, in the absence of a new mosquito bite. These relapses can occur weeks, months or even years after the initial infection. The dormant liver forms of the parasite cannot be readily treated with most anti-malarial treatments active against the blood-stage parasite. The current treatment (primaquine) for the dormant liver stage must be taken for 7 to 14 days to be effective, a regimen that is associated with poor compliance in unsupervised patients 3,4,5 . The use of a medicine that targets the dormant liver forms of the parasite, co-administered with a medicine to treat the blood stage, is known as radical cure. P. vivax malaria has a significant public health and economic impact, primarily in South-Asia, South-East Asia, Latin America and the horn of Africa. The disease is estimated to cause around 8.5 million clinical infections every year. The clinical features of P. vivax malaria include fever, chills, vomiting, malaise, headache and muscle pain, and in some cases, can lead to severe malaria and be fatal. About GSK GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com. About Medicines for Malaria Venture MMV is a Swiss-based not-for-profit organization working to deliver a portfolio of accessible medicines with the power to treat, prevent and eliminate malaria. Born in 1999, out of a need for greater health equity, we close critical gaps in research, development and access – working “end-to-end” to expand the use of existing antimalarials and innovate new compounds to protect public health. This starts with women and children. It’s working. As of 2023, MMV-supported products have effectively treated an estimated 680 million people and saved around 15.4 million lives. We cannot stop now. With a quarter of a billion malaria cases and more than 600,000 deaths reported in 2022, progress towards disease elimination has stalled. MMV is part of an ecosystem of partners determined to change this. Bringing public and private sector partners together, we pioneer new solutions that align with local and global health priorities and promote the equitable development of effective and affordable products that work to help end malaria and advance health for all. For more information, visit http://www.mmv.org . References SOURCE: GlaxoSmithKline

11.16 知识分子 The Intellectual 2024年8月23日，肯尼迪在亚利桑那州的一场选举前的集会上支持特朗普，为特朗普背书。图源：维基百科 2024年11月14日，特朗普宣布提名小肯尼迪为新的卫生与公众服务部（HHS）部长。小肯尼迪是著名的反疫苗人士，发表过大量反智反科学言论。他被提名HHS部长，不仅代表了相对特朗普1.0，特朗普2.0在美国医疗、健康政策上的重大转向，也是对科学界、医学界的重大威胁。说这是美国健康领域的至暗一刻并不为过。 撰文 | 周叶斌  ●                  　●                   　● 01 反疫苗阴谋论者被提名NHS部长 小肯尼迪，全名Robert F. Kennedy Jr，美国媒体有时候就叫他RFK Jr，美国前司法部长罗伯特·肯尼迪之子。小肯尼迪出生于1954年，9岁时叔叔肯尼迪总统遇刺身亡，14岁时，父亲，当时的纽约州参议员罗伯特·肯尼迪遇刺身亡。由于经历了多起家庭悲剧，小肯尼迪很小就通过滥用药物寻求解脱，16岁因携带大麻被捕，先后被两所寄宿学校开除。后来小肯尼迪延续叔叔与父亲的脚步，进入哈佛读法律，但在那个时候也是吸毒，被同学称为毒贩。 1982年，年仅28岁的肯尼迪就任曼哈顿的助理检察长，但仅一年，因为没有通过律师资格考试，不得不辞职。1983年，小肯尼迪还因携带海洛因被捕，并被判了两年的缓刑与社区服务。 这次判刑却改变了小肯尼迪的一生。一方面缓刑要求他接受戒毒治疗，据他说，这让他结束了长达14年的海洛因滥用。另外，更重要的是，他到自然资源保护协会（Natural Resources Defense Council）做志愿者，让他接触到了环保，可以说找到了人生追求。后来他到致力于改善纽约著名河流哈德逊河的环保组织Riverkeeper做志愿者，成为该组织的律师。他的一系列诉讼，对哈德逊河的环境改善乃至树立美国对水域环境治理的标准，都有着重要作用。 为此，小肯尼迪曾经是08年奥巴马政府的环保署署长候选人之一。非常遗憾的是，2010年以后，小肯尼迪逐渐由环保战士蜕变成了反疫苗运动代言人。2015年，他加入了反疫苗组织Children's Health Defense。这个组织前身叫World Mercury Project，因为部分疫苗里使用的少量硫柳汞防腐剂，宣称疫苗对儿童有害。实际上科学研究都证明了微量的硫柳汞不会对健康产生威胁。 小肯尼迪后来成了Children's Health Defense的主席。新冠疫情期间，小肯尼迪带着Children's Health Defense飞速发展，成了主要的反疫苗声音，大量散布疫苗导致自闭症，氯喹、伊维菌素可以治疗新冠等不实信息。 可以看到，小肯尼迪不仅没有医学背景，而且长期散播不实信息、阴谋论，这样的人被提名HHS部长，可以说是美国非常荒唐的一幕。 02 重大转变 2024年总统大选中，小肯尼迪一开始是对拜登发起初选挑战，失败后决定以独立候选人身份参选，但在24年8月他宣布退选并表态支持特朗普，条件就是在未来政府的健康决策里要扮演重要角色。而不同于基本在重复8年前口号的经济、移民等方向，在健康领域，特朗普从竞选时期到胜选后，在多个场合明确表示支持他这次选举的小肯尼迪将扮演重要角色。要让小肯尼迪在健康领域go wild（为所欲为）。 小肯尼不仅与当下拜登政府的健康官员们相去甚远，与特朗普1.0时的几位主要健康领域官员也有着完全不同的背景。 特朗普首次当选时，HHS部长为Alex Azar，法律背景，在小布什政府时期进入HHS，在小布什连任后成为HHS副部长。07年辞去HHS职务后任职制药巨头礼来十年。 当时的两任FDA局长，分别为Scott Gottlieb（2017-2019）与Stephen Hahn（2019-2021），Gottlieb辞任后，时任NCI主任Norman Sharpless曾短暂代理FDA局长。Gottlieb在成为FDA局长前，做过临床医生，在FDA与CMS（联邦医疗保险与联邦医疗辅助计划服务中心）任职过，后进入医疗投资。Stephen Hahn则是著名的放射科医生，成为FDA局长前为MD Anderson的首席医学官。CDC主任Redfield，研究HIV病毒出身。 从上述特朗普首次执政时与医药行业相关的政务官背景来看，当时极为反传统的特朗普，选择的健康领域官员却极为传统。考虑到新冠疫情中，特朗普与当时传统医学科学出身的FDA局长Stephen Hahn、NIAID主任Fauci产生严重矛盾，特朗普在2.0版政府里靠近小肯尼迪的医学观点并不令人意外。 相对这些传统科学背景或者至少不反科学的官员，小肯尼迪被提名HHS部长代表了特朗普2.0政府在健康尤其是公卫方面与1.0时比，发生了重大转向。这种转向可能给美国公众带来最直接的健康威胁。 毕竟四年多前，正是这些传统的健康官员坚持科学原则，才让FDA、CDC等机构维持了按科学证据做推荐，没有让尘嚣甚上的反疫苗阴谋论、氯喹伊维菌素能治疗新冠等伪科学造成更大危害。 03 小肯尼迪就任NHS部长带来多重威胁 HHS，美国的卫生与公众服务部，是所有美国政府部门里预算总最大的部门之一，2025财年HHS的可自由支配开支预算高达1300亿美元，仅次于国防部。 HHS有那么高的预算，很重要的原因是它下面有多个与民众健康密切相关的机构，像FDA，CDC都是HHS下旗下。HHS部长无疑是健康领域的要职，而小肯尼迪担任这个职位，也会带来多重威胁。 首先，美国监管药品与食品的部门，FDA，是归HHS管辖。而FDA的职责包括批准、审核药品，监管市场上的保健品、食品安全，每一项都与民众健康息息相关。HHS部长的位置让小肯尼迪有机会干预FDA的工作。而小肯尼迪还明确表达这种干涉倾向，他曾在采访中表示要消除FDA的整个营养部门。 目前FDA审批新药上市的经费大多来自药企申请药品上市的注册费，独立于政府预算。这种注册费制度保证了FDA有足够的人手，可以及时完成复杂的药品监管审理。可小肯尼迪却表示要取消注册费制度，若得以实行，可能严重拖延新药上市的速度，威胁患者利益。 其次，CDC隶属于HHS。作为最重要的公卫部门，CDC的ACIP（免疫规划委员会）负责疫苗的推荐。而只要是ACIP推荐的疫苗，美国的医保基本都会覆盖。而CDC也是目前最需要担心的，因为ACIP的委员由HHS部长任命。反疫苗的小肯尼迪一旦掌管HHS，完全可以通过任命与他想法类似的人进入ACIP，严重威胁美国的免疫规划。 小肯尼迪最近还表示要从饮用水中清除氟。在饮用水中加入少量氟，大幅降低了蛀牙率，被认为是美国历史上最突出的公卫成果之一。小肯尼迪却错误地宣称添加氟导致癌症，威胁孩童智力水平。实际上，美国饮用水普遍添加的氟剂量极低，完全在包括WHO在内各健康机构认定的安全范围内。从反对添加氟，也能看出小肯尼迪可能会推行反公共健康科学共识的政策，危害民众健康。 再次，全球最重要的生命科学研究机构，美国国立卫生研究院NIH，也在HHS旗下。小肯尼迪已经宣称要开掉600名NIH员工。很多最新的药物、治疗方法，表面上看是某某药企做出来的，但追本溯源，大多有NIH的基础研究的影子，甚至在后期研发里也离不开NIH的协助。像是新冠疫情期间起到关键保护作用的两个mRNA疫苗中，Moderna的新冠疫苗整个研发过程都获得了NIH的大力支持。过去，NIH的工作基本不受到美国政坛变化的干预。小肯尼迪若是打破该传统，对全球健康领域都是严重隐患。 04 小肯尼迪广泛的反科学反智思想 真正让小肯尼迪担任HHS部长这一要职异常危险的，是他长期的反科学反智倾向，参考他10月25日在社交网络上发的贴子： 该帖子中，小肯尼宣称FDA对公共健康的压迫即将结束，包括那些对致幻剂、多肽、干细胞、生牛奶、高压治疗、螯合物、伊维菌素、氯喹等这一系列有益健康的东西的打压。 伊维菌素、氯喹是重复新冠疫情期间这两个药物有治疗新冠作用的不实信息。他说的多肽、干细胞也不是指正经的获批药物，而是类似打干细胞、胶原蛋白有抗衰老功效等虚假宣传。 可以看出小肯尼对药物的看法并不基于科学，受很多类似顺势疗法等伪科学的影响。颇为讽刺的是，2017年，特朗普1.0时期的FDA局长Scott Gottlieb提出加强针对顺势治疗药物的监管，FDA也发出多封警告函，要求一些不安全的顺势疗法下市。如今很可能出现完全相反的局面。大量打着天然、自然的假药不必担心监管部门的审视。这在小肯尼迪等人看来可能是让美国再次健康，但其实是让美国生病。 食品领域，虽然RFK提倡健康饮食这些不违反科学的原则，但在具体方案、办法上，他往往会陷入反智圈套。像他提到的生牛奶就很能反映一个思维模式，所谓天然就是好。 生牛奶是指未经巴氏消毒的牛奶，一些人认为生牛奶有特殊的营养。但这并不符合事实。实际上，牛奶很容易被细菌污染，未经巴氏消毒的生牛奶蕴藏着巨大的安全隐患。根据CDC统计，1998到2018年间，美国发生了202起生牛奶导致的疾病暴发，而这还只是上报的数据，存在低估，因为大部分相关食物中毒根本不会报告到CDC。 此外，小肯尼迪还说过无线网络导致癌症，艾滋病不是HIV感染引发等各种反科学言论。显然，小肯尼迪的健康观点，以及他和特朗普鼓吹的让美国再次健康（make America healthy again），建立在大量的不实信息之上，一旦变成政府决策，危害无穷。 在所有反科学反智言论中，小肯尼迪最持之以恒，也最令人担心的无疑是反疫苗。这方面，他甚至可以说是双手沾满了鲜血。 2019年，人口仅20万的太平洋岛国萨摩亚暴发麻疹，造成5700例疾病，83人死亡。当时萨摩亚6-11个月的婴儿里20%感染了麻疹，每150名婴儿就有1人死于麻疹。 这次麻疹暴发最主要的原因便是当地麻疹疫苗接种率从2017年的74%突然下降到了2018年的34%。 为什么接种率会如此下滑？这要追溯到此前当地护士一次操作失误，将麻醉剂误用于稀释疫苗，导致两名孩童不幸身亡。而小肯尼迪为首的反疫苗人士抓住机会，大肆传播疫苗有严重危害，可以致死的虚假信息。 这就是小肯尼迪在健康领域go wild（为所欲为）的历史成绩。此前特朗普过渡团队的成员都承认小肯尼迪主管健康领域后，可能将疫苗下架。据称，小肯尼迪说要检验疫苗的数据，只要给他数据，就能证明这些疫苗不安全，制药公司将不得不下架疫苗。 可他鼓吹的疫苗导致自闭症早已被科学界证伪。而小肯尼迪此前领导的反疫苗组织Children’s Health Defenses散布过大量虚假信息，还起诉反驳这些不实信息的媒体机构。 执掌HHS，拿到疫苗安全性“数据”后，真能指望他会诚实宣布科学界早就知道的事实：上市的疫苗安全性有保障？根据世界卫生组织估计，全球儿童疫苗接种每年避免的死亡在400万以上，而小肯尼迪在2023年还宣称没有一个疫苗是安全的。他领导HHS，将是的公共健康的巨大威胁。 05 小肯尼迪恐怕只是开始 小肯尼迪还在帮特朗普筛选健康相关职位的官员候选人简历。物以类聚，人以群分，当小肯尼迪被提名HHS部长时，下一任的FDA局长、CDC主任、NIH主任又会是什么样的人？ 必须承认，小肯尼迪说的一些原则表面上没有问题，比如中止药品监管机构与制药行业的旋转门，减少对健康有负面作用的深加工食品。这些说法击中了我们对当下健康政策、行业管理的担忧，很有诱惑力。 但是解决或改善我们面临的健康挑战需要建立在科学之上，追随小肯尼迪这样的反智反科学思维，只会是缘木求鱼。 以药品监管与制药业的旋转门为例。确实有太多FDA高管跳槽企业或与企业交流过度的案例，严重威胁民众对FDA独立性的信任。但是我们也必须看到制药业的复杂性意味着无论是监管部门还是产业界，都需要有综合背景的人才。 以特朗普的首位FDA局Gottlieb为例。在他就任前，美国公众的一个普遍担忧是Gottlieb作为风投人与产业界有着极为密切的联系，是否会过度为医药企业站台。可上任后，Gottlieb过去广泛的政府、产业界经验带来了高度合作的管理方式，获得各方认可。他开创了因成瘾风险大而下架阿片药物的先例，推迟新的烟草类产品上市审核并开启对尼古丁含量监管，这些一方面有着政府健康部门出身不畏惧对产业界动手的态度，另一方面也带有产业界敢于使用新办法、定新规矩的特征。 我们需要更好的机制来维系FDA等部门的独立性，但我们不需要小肯尼迪那种偏颇、倒退的管理思维。 小肯尼迪被提名HHS部长，我们不得不担忧当健康部门的最高级别官员反科学，宣扬阴谋论，普通民众又能从那里获得可靠的健康建议、医学指导？ 这又怎么可能是让美国健康呢？这其实是美国科学界、医学界黑暗的一刻。  参考文献：（上下滑动可浏览）  1.https://www.vox.com/health/385541/rfk-jr-trump-hhs-vaccines-fluoride 2.https://www.reuters.com/world/us/rfk-jr-is-reviewing-resumes-top-trump-health-jobs-sources-say-2024-11-09/ 3.https://endpts.com/biotech-industry-worries-over-potential-for-rfk-jr-ally-as-fda-pick/ 4.https://www-nidcr-nih-gov.libproxy1.nus.edu.sg/health-info/fluoride/the-story-of-fluoridation 5.https://www-nih-gov.libproxy1.nus.edu.sg/news-events/news-releases/statement-nih-barda-fda-emergency-use-authorization-moderna-covid-19-vaccine 亲爱的读者们，不星标《知识分子》公众号，会错过每日科学新知！星标《知识分子》，紧跟前沿科学，一起探索科学的奥秘吧！   请戳上图卡片添加星标 关注《知识分子》视频号 get更多有趣、有料的科普内容 END