天使还是魔鬼：登瓦夏疫苗的另一面

The U.S. Food and Drug Administration just approved one of the most sought after vaccines in recent decades.

美国食品和药物管理局曾批准了近几十年来最受欢迎的疫苗之一。

It's the world's first vaccine to prevent dengue fever — a disease so painful that its nickname is "breakbone fever."

这是世界上第一种预防登革热的疫苗—登革热是一种非常痛苦的疾病，它的绰号是“断骨热”。

The vaccine, called Dengvaxia, is aimed at helping children in Puerto Rico and other U.S. territories where dengue is a problem.

这种名为登瓦夏的疫苗旨在帮助波多黎各和登革热成灾的美国其他地区的儿童。

But this vaccine has a dark — and deadly — history.

但这种疫苗有一段黑暗而致命的历史。

One that has led to criminal charges in the Philippines, sparked national panic and fueled a massive measles outbreak that has already killed more than 355 people.

这次事件在菲律宾引发了刑事指控，引发了全国恐慌，并引发了大规模的麻疹疫情，目前已有355人死亡。

That story begins on a stage in Manila in 2016.

这个故事从2016年的马尼拉开始。

A young girl, about age 9 or 10, sat on a chair surrounded by health officials.

一个大约9岁或10岁的小女孩坐在一把椅子上，周围都是卫生官员。

She wore a bright yellow T-shirt with the words "Dengue is dangerous" across it.

她穿着一件亮黄色的t恤，上面写着“登革热很危险”。

She squeezed her eyes and bit her lip as the health secretary of the Philippines, Dr. Janette Garin, gave her a shot in the arm.

当菲律宾卫生部长珍妮特·加林给她在胳膊上打针时，她紧紧地闭上眼睛，咬着嘴唇。

That shot launched a massive vaccine campaign to inoculate nearly 1 million schoolchildren with Dengvaxia.

那次注射是一场大规模的疫苗注射的开端，近100万学龄儿童接种了登瓦夏疫苗。

The goal was to save thousands of kids' lives and prevent an estimated 10,000 hospitalizations over a five-year period.

们的目标是在5年内挽救数千名儿童的生命，并防止估计1万名儿童住院治疗。

But in the end, estimates are that more than 100,000 Philippine children received a vaccine that health officials say increased their risk of a severe and sometimes deadly condition.

但据估计，最终有超过10万名菲律宾儿童接种了疫苗，卫生官员说，这种疫苗增加了他们患上严重疾病、有时甚至致命疾病的风险。

In addition, other children who received the vaccine may have been endangered because, their parents alleged, they were not in good health.

此外，其他接受疫苗的儿童也可能受到威胁，因为他们的父母声称，他们的健康状况不佳。

The French pharmaceutical company Sanofi Pasteur spent 20 years — and about $2 billion — to develop Dengvaxia.

法国制药公司赛诺菲巴斯德花了20年时间和大约20亿美元来开发登瓦夏。

The company tested it in several large trials with more than 30,000 kids globally and published the results in the prestigious New England Journal of Medicine.

该公司在全球范围内对3万多名儿童进行了几项大型试验，并将结果发表在著名的《新英格兰医学杂志》上。

But halfway around the world from the Philippines, in a Washington, D.C., suburb, one scientist was worried about the new vaccine.

但是对于半个地球之外的菲律宾来说，华盛顿特区的一位科学家对这种新疫苗感到担忧。

"When I read the New England Journal article, I almost fell out of my chair," says Dr. Scott Halstead, who has studied dengue for more than 50 years with the U.S. military.

“当我读到《新英格兰杂志》上的那篇文章时，我几乎要从椅子上摔下来，”斯科特·霍尔斯特德博士说，他在美国军方研究登革热已经超过50年。

When Halstead looked at the vaccine's safety data in the clinical trial, he knew right away there was a problem.

当霍尔斯特德在临床试验中看到疫苗的安全性数据时，他立刻就知道存在问题。

For some children, the vaccine didn't seem to work.

对一些儿童来说，疫苗似乎并不起作用。

In fact, Halstead says, it appeared to be harmful.

霍尔斯特德说，事实上，它似乎是有害的。

When those kids caught dengue after being vaccinated, the vaccine appeared to worsen the disease in some instances.

当这些孩子在接种疫苗后感染登革热时，疫苗在某些情况下似乎会使病情恶化。

Specifically, for children who had never been exposed to dengue, the vaccine seemed to increase the risk of a deadly complication called plasma leakage syndrome, in which blood vessels start to leak the yellow fluid of the blood.

具体来说，对于从未接触过登革热的儿童来说，疫苗似乎会增加一种致命并发症的风险，这种并发症被称为血浆渗漏综合征，即血管开始渗出血液中的黄色液体。

"Then everything gets worse, and maybe it's impossible to save your life," Halstead says.

“然后一切都变得更糟，甚至将没法挽救你的生命，”霍尔斯特德说。

"A child can go into shock."

“孩子可能会进入休克状态。”

"The trouble is that the disease occurs very rapidly, just in a matter of a few hours," he adds.

他补充说:“问题是这种疾病发生得非常快，只需要几个小时。”

"And there's nothing on the outside of the body to signify the person is leaking fluid on the inside."

“而且在身体的外部没有任何东西表明这个人体内有液体泄漏。”

The complication is rare, says Halstead.

霍尔斯特德说，这种并发症很少见。

Still, he was so worried about the safety concerns that he wrote at least six editorials for scientific journals.

尽管如此，他还是非常担心这种安全问题，为此他曾为科学期刊撰写了至少六篇评论文章。

He even made a video to warn the Philippine government about the problem.

他甚至制作了一段视频来警告菲律宾政府注意这个问题。

"I just think, 'No, you can't give a vaccine to a perfectly normal, healthy person and then put them at an increased risk for the rest of their lives for plasma leakage syndrome,' " Halstead says.

霍尔斯特德说:“我只是想，'不，你不能给一个完全正常、健康的人接种疫苗，然后让他们在余生中患上血浆渗漏综合症的风险增加。’”

"You can't do that."

“不能这样做 。”

The vaccine manufacturer disagreed with Halstead's interpretation of the study's results.

疫苗制造商则又不同意霍尔斯特德对研究结果的解释。

The company wrote a rebuttal, asserting that regulatory agencies had approved Dengvaxia "on the basis of the vaccine's proven protection and acceptable safety profile."

该公司写了一份反驳声明，声称监管机构“基于该疫苗已证实的保护作用和可接受的安全性”批准了登瓦夏。

The company also said it would perform additional studies to "further access the safety, efficacy and effectiveness" of the vaccine.

该公司还表示，将开展更多研究，以“进一步了解疫苗的安全性、有效性和效力”。

Despite these concerns, in July 2016, the World Health Organization went ahead and recommended the vaccine for all children ages 9 to 16.

尽管存在这些担忧，2016年7月，世界卫生组织还是决定为所有9至16岁的儿童推荐这种疫苗。

"Yes, we did. It was what we call a 'conditional recommendation' with the emphasis to minimize potential risks," says Dr. Joachim Hombach, who led WHO's review of the vaccine.

“是的,我们做到了。这就是我们所说的'有条件的建议’，其重点是将潜在风险降到最低，”领导世卫组织疫苗审查的乔其姆.赫姆巴赫博士说。

"We saw the problems. We also clearly pointed to the data gaps."

“我们看到了问题。我们也明确指出了数据上的差距。”

WHO recommended that Sanofi do more experiments to better understand the vaccine's safety issues.

世卫组织建议赛诺菲公司做更多的实验，以更好地了解疫苗的安全问题。

In its assessment, WHO pointed out that the vaccine "may be ineffective or may theoretically even increase the future risk of [being] hospitalized or severe dengue illness" in people who have never been exposed to dengue — which is about 10% to 20% of Philippine children.

世卫组织在其评估中指出，该疫苗“可能无效，或者在理论上甚至可能增加从未接触过登革热的人(约占菲律宾儿童的10%至20%)未来住院或罹患严重登革热的风险”。

WHO's recommendation came three months after the Philippines launched its mass vaccination campaign in April 2016.

世卫组织的建议是在菲律宾于2016年4月启动大规模疫苗接种运动三个月后提出的。

A year and half later, that campaign came to a screeching halt.

一年半后，这场疫苗注射运动被勒令停止。

In November 2017, Sanofi published an announcement on its website saying it had new information about Dengvaxia's safety.

2017年11月，赛诺菲安万特在其网站上发布声明称，该公司掌握了有关登瓦夏安全的新信息。

Halstead's fears were confirmed.

霍尔斯特德的担心得到了证实。

Sanofi had found evidence that the vaccine increases the risk of hospitalization and cytoplasmic leakage syndrome in children who had no prior exposure to dengue, regardless of age.

赛诺菲安万特已发现证据表明，疫苗增加了此前未接触登革热的儿童(不论年龄)住院和细胞质泄漏综合征的风险。

"For individuals who have not been previously infected by dengue virus, vaccination should not be recommended," the company wrote.

该公司写道:“对于以前没有感染登革热病毒的个人，不应该推荐接种疫苗。”

Panic hit the Philippines.

菲律宾则发生了恐慌。

In news reports, parents said that the vaccine contributed to the deaths of 10 children.

在新闻报道中，家长们说疫苗已经导致了10名儿童死亡。

Protests erupted.

抗议爆发了。

The Congress of the Philippines launched investigations into the vaccine's purchase and the immunization campaign.

菲律宾国会对疫苗的购买和免疫效果展开了调查。

And Philippine health officials started performing autopsies on children who died after receiving the vaccine.

菲律宾卫生官员开始对接种疫苗后死亡的儿童进行尸检。

"In total, the deaths of about 600 children who received Dengvaxia are under investigation by the Public Attorney's Office, " the South China Morning Post reported last month.

《南华早报》上月报道称:“总而言之，检察官办公室正在调查约600名接受登瓦夏治疗的儿童的死亡情况。

Investigators have not yet released their results.

调查人员尚未公布结果。

Here's the problem with Dengvaxia.

接下来我们来说说登瓦夏存在的问题。

Typically, a vaccine works by triggering the immune system to make antibodies against the virus.

通常情况下，疫苗的工作原理是触发免疫系统产生针对病毒的抗体。

These antibodies then fight off the virus during an infection.

然后，这些抗体在感染过程中击退病毒。

But dengue is a tricky virus.

但登革热是一种棘手的病毒。

Dengue antibodies don't always protect a person.

登革热抗体并不总是保护一个人。

In fact, these antibodies can make an infection worse.

事实上，这些抗体可能会使感染更加严重。

The dengue virus actually uses the antibodies to help it spread through the body.

登革热病毒实际上利用抗体来帮助它在体内传播。

So a second infection with dengue — when your blood already has antibodies in it — can actually be worse than the first; a person is at a higher risk of severe complications like plasma leakage syndrome.

因此，第二次登革热感染——当你的血液中已经有抗体时——实际上可能比第一次更严重;一个人有更高的风险出现严重并发症，如血浆渗漏综合征。

In its follow-up study, Sanofi found evidence that Dengvaxia acts like the first infection for a person who has not been previously infected.

在其后续研究中，赛诺菲发现了一些证据，表明登瓦夏对以前没有感染过登革热的人来说，就像第一次被病毒感染一样。

The body produces antibodies against the vaccine, which have a similar potential for harm.

人体会产生针对疫苗的抗体，而疫苗也有类似的潜在危害。

The increased risk seems small. The vaccine raises the risk of hospitalization after a dengue infection from about 1.1% to 1.6%, the follow-up study from Sanofi found. So out of 1 million kids in the Philippines, the vaccine would cause about 1,000 to be hospitalized over five years, Sanofi estimated.

增加的风险似乎很小。赛诺菲的后续研究发现，这种疫苗将登革热感染后住院的风险从1.1%左右提高到1.6%，赛诺菲公司估计，在菲律宾，每100万名儿童中，就有1000名儿童在未来五年内需要住院治疗。

(On the other hand, the vaccine would prevent about 12,000 hospitalizations for a new dengue infection in children who have had a prior dengue infection during this same time period.)

(另一方面，该疫苗将防止约1.2万名此前在同一时期感染登革热的儿童因新感染登革热而住院。）

But in the world of vaccines, that's not an acceptable risk.

但在疫苗的世界里，这种风险是不能被接受的。

A risk needs to be exceedingly small to be tolerated.

风险必须非常小才能被容忍。

For example, with the measles vaccine, the risk of encephalitis is about 1 in 1 million, or 1,000 times less than the risk from a measles infection, WHO says.

例如，世卫组织说，使用麻疹疫苗后，患上脑炎的风险约为百万分之一，比麻疹感染的风险低1000倍。

WHO eventually changed its recommendation.

世界卫生组织最后改变了自己的建议。

The agency now says the vaccine is safe only for children who have had a prior dengue infection.

该机构现在表示，这种疫苗只对以前感染过登革热的儿童安全。

By the time Sanofi acknowledged this problem with the vaccine, about 800,000 Philippine children had been vaccinated.

到赛诺菲公司承认疫苗存在这一问题时，大约有80万菲律宾儿童已经接种了疫苗。

The Sanofi study estimated that more than 100,000 of them had never been infected with dengue and should not have received the shot, according to WHO's revised recommendation.

根据世卫组织修订后的建议，赛诺菲的研究估计，其中超过10万人从未感染登革热，不应该接种疫苗。

Given the concerns by Halstead and the initial unknowns about the vaccine's safety, Philippine parents should have been warned about a potential risk, says Dr. Isabel Rodriguez at the University of California, San Francisco.

加州大学旧金山分校的伊莎贝尔·罗德里格斯博士说，考虑到霍尔斯特德的担忧，以及疫苗安全性的最初未知，菲律宾父母应该对潜在风险发出警告。

"What bothers me most about this story is risk communication," says Rodriguez, who studies dengue in South America.

“这个故事最让我困扰的是风险沟通，”罗德里格斯说，他在南美研究登革热。

"There was a lot of uncertainty from the beginning [about the vaccine's safety]. That needed to be communicated explicitly. You need to be honest about what evidence is out there."

“从一开始(疫苗的安全性)就有很多不确定性。这需要明确传达。你需要对现有的证据诚实。”

Dr. Su-Peing Ng, global medical head of Sanofi Pasteur, says the company followed all World Health Organization guidelines while developing the vaccine and communicated honestly throughout the process.

赛诺菲巴斯德全球医疗主管恩苏平博士说，该公司在开发疫苗时遵循了世界卫生组织的所有指导方针，并在整个过程中进行了诚实的沟通

"We've always been very transparent in sharing the results of our research," Ng says.

“我们一直非常透明地分享我们的研究结果，”恩博士说。

"And I just want to stress that we have full confidence in our vaccine as it's been approved by regulatory agencies in over 20 countries."

“我想强调的是，我们对我们的疫苗充满信心，因为它已经被20多个国家的监管机构批准。”

In hindsight, Ng says, Sanofi wouldn't do anything differently with the development of the vaccine: "No, we have been very, very close to the research community, working closely with them over the last 20 years in the effort to find a solution for public health needs."

事后看来，恩博士说，赛诺菲对疫苗的开发不会有任何不同:“不，我们一直非常非常接近研究团体，在过去20年里与他们密切合作，努力为公共卫生需求找到解决方案。”

In April, the Philippine government indicted 14 government officials over the deaths of 10 children who received the Dengvaxia vaccine.

今年4月，菲律宾政府起诉了14名政府官员，原因是10名儿童因接种登瓦夏疫苗而死亡。

The government said the officials acted with "undue haste" in procuring the vaccine and launching the mass immunization campaign.

政府说，官员们在采购疫苗和开展大规模免疫运动方面“操之过急”。

The Philippine Department of Justice said the campaign started before the clinical trials were finished.

菲律宾司法部表示，这项运动在临床试验结束前就开始了。

Six Sanofi officials were also indicted for not properly helping children who had serious reactions to the shot.

赛诺菲安万特的六名管理人员也被起诉，罪名是没有适当帮助对疫苗注射反应严重的儿童。

Sanofi disputes this and other allegations, adding in a written statement to us: "We strongly disagree with the DOJ's findings made against Sanofi's officials (current and past) and we will vigorously defend them.

赛诺菲对此和其他指控提出异议，并在一份书面声明中补充称:“我们强烈反对司法部对赛诺菲官员(无论是现在还是过去)的调查结果，我们将积极为其辩护。

There is no clinical evidence that any reported fatalities were causally related to vaccination.

目前没有临床证据表明任何报告的死亡与接种疫苗有因果关系。

Regardless of how these trials turn out, the debacle in the Philippines offers a key lesson for governments and manufacturers when it comes to approving and selling new vaccines: Slow down, says physician and bioethicist Keymanthri Moodley. Mistakes with vaccines can erode the public's trust and have long-term consequences for the health of an entire country.

医生兼生物伦理学家Keymanthri Moodley说，无论这些试验结果如何，菲律宾的溃败给政府和制造商在批准和销售新疫苗方面提供了一个关键的教训:放慢速度。疫苗方面的错误会侵蚀公众的信任，并对整个国家的健康产生长期影响。

问题

登瓦夏从接种运动启动到被停止经历了多长的时间呢？

留言回复正确答案，前十名朋友可以获得红包奖励哦，赶快来试试吧！

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