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The gutsy — possibly crazy — scientists who risked death testing vaccines on themselves | The Washington Post.

[March 7, 2020 at 12:30 p.m. GMT]

Jonas Salk, developer of the polio vaccine, holds a rack of test tubes in his lab in Pittsburgh in 1954. (AP) Jonas Salk, developer of the polio vaccine, holds a rack of test tubes in his lab in Pittsburgh in 1954. (AP)

Michael S. Rosenwald writes:

In 1875, high up in the Andes mountains, hundreds of Peruvian railroad workers began coming down with a strange fever, which was followed by severe joint pain and then death.

As the body count soared, alarm set in across the country. Desperate to explain the origins of this strange new malady, a Peruvian medical society announced a contest.

A 26-year-old medical student named Daniel Carrión entered.

Scientists in Peru had a hunch the fever was connected to verruga peruana, also known as Peruvian warts. But they struggled to prove a link. To Carrión, whose father was a well-known physician, there was a simple solution.

If someone injected him with tissue from a wart on one of the sick patients and then he got sick, then voilà! Problem solved — there’s the connection. But there was another problem: Those who got the fever generally died.

Carrión was undeterred.

“Once he made the decision that experimentation on a human was necessary, he must have asked himself: On whom?” wrote Lawrence K. Altman, a physician and New York Times reporter in his history of self-experimentation in medicine. “Carrión answered that question in the only way his conscience would allow: Myself.”

He got the fever. And he died.

Altman’s book is titled “Who Goes First?” It’s a question that’s been asked throughout history when scientists have been confronted with a grave new malady such as the novel coronavirus now setting off alarm around the world.

In the race to discover how disease spreads and what treatments might stop it, someone has to be tested first.

That someone is often the doctor in the white coat. Jonas Salk tested the polio vaccine — which contained a nonliving form of the virus — on himself and his children before giving it to strangers. In 1986, Daniel Zagury, a French immunologist, appointed himself to be the first person dosed with an experimental AIDS vaccine.

2012 study identified 465 episodes of doctors’ self-experiments, with 140 of them related to dangerous infectious diseases. Eight self-experiments resulted in death, including physicians and scientists trying to curtail outbreaks of plague, typhus, cholera and yellow fever.

What would posses someone to, say, drink a hearty soup infused with cholera bacteria, as Max Joseph Pettenkofer did in 1892?

“Historically, self experimentation was an important part of the scientific process, allowing medical advances that would have been hard to achieve otherwise,” wrote two researchers in a rollicking 2018 paper titled “Adventures in self experimentation.”

And why?

“Because no sane human would agree to be a research participant and no ethical review board in its right mind would approve the experiment,” the researchers wrote.

Fair enough.

In more modern times, vaccines such as the one being pursued for the novel coronavirus are tested on animals for months and often years before reaching humans. It’s a deliberative process that has frustrated President Trump, who recently asked vaccine manufacturers, “How fast can you get it done?”

Throughout history, though, impatient and desperate scientists have decided to throw their own necks in the ring.

Twelve self-experimenters have won Nobel Prizes for their efforts, including Charles Jules Henri Nicolle, a French scientist who in the early 1900s took lice from typhus-infected chimps, crushed them up and made a vaccine that he tested on himself.

Werner Forssmann, a German, won a Nobel in 1956 for cardiac catheterization, which he first performed on himself, inserting a tube into a vein that he then directed into his heart. (Yes, his heart. Yes, he lived.)

Carrión, of course, didn’t live to see fame. But his bravery is immortal. In Peru, hospitals and soccer stadiums are named after him.

And yet he never authored a single scientific paper.


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Pakistan: Five-day anti-polio campaign kicks off in Khyber Pakhtunkhwa today | The Nation.

[March 08, 2020]

A five-day special anti-polio campaign will be carried out in sixteen districts of Khyber Pakhtunkhwa from tomorrow.

According to Emergency Operation Center Khyber Pakhtunkhwa, the districts where the campaign will be launched includes Peshawar, Buner, Dera Ismail Khan, Lower Dir, Upper Dir, Hangu, Karak, Kohat, Lakki Marwat, Tank, Khyber, Bajaur, Orakzai, Kurram, South Waziristan and North Waziristan districts.

More than three million children up-to five years of age will be administered anti-polio drops during the campaign.

Ten thousand four hundred and eighty-five teams have been constituted which will ensure administering anti-polio vaccine to each and every child.


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India: Everyday Sheroes: How this polio-affected waitress from Assam found a home in Chennai | Edex.

[Published: 07th March 2020]

In our run-up to International Women's Day 2020, we have curated this series of stories of women who aren't extraordinary, but our world may stop going around smoothly if they decided to call it a day.

Frida_Brahma

Frida Brahma.

Blessy Mathew Prasad writes:

It was the year 2015, when a young Frida Brahma packed her bags and left the only place she had ever known --Assam - in search of a better life. Having no idea of what was in store for her, she moved all the way to Chennai without the slightest clue about the culture, language or way of life. 

Five years later, today, she has no regrets about her decision. Working as a waitress at Writer's Cafe, she feels happier than ever. In fact, she's fallen in love with the city and her job. 

Frida grew up in a middle-class family in Assam and wasn't able to afford to finish her school education. She had dreams to study more - she confesses that she was very interested in drama and literature - but there weren't too many opportunities back home. 

When I came to Writer's cafe, I saw many acid attack survivors working here. I was very happy to see that people and especially women are treated without any bias. I felt very comfortable here

Frida Brahma, Waitress

When she landed in Chennai, she found a company where she worked for six months. But it was her second job -- being a waitress at Writer's cafe -- that truly gave her a sense of fulfillment. She says, "For the last four years, I've been working here. I like it very much. I am a victim of polio attack. My left leg has a slight problem. When I came to Writer's cafe, I saw many acid attack survivors working here. I was very happy to see that people and especially women are treated without any bias. I felt very comfortable here." She goes on to say, "I like the people of Chennai very much. I can also understand the language a little bit now."

Frida, who has now been promoted to senior captain takes her job seriously. Her responsibilities include taking orders and overseeing the morning staff. When asked about her best memory at work, she recalls, "It was when I got a raise in my salary. That really helped me and made me feel appreciated." 


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Acute Flaccid Myelitis: A Clinical Review | Seminars in Neurology.

[Pay to View Full Text] [Publication Date: 06 March 2020 (online)]

Abstract.

Acute flaccid myelitis (AFM) is an emerging disorder primarily affecting children that is characterized by acute flaccid paralysis accompanied by abnormalities of the spinal cord gray matter on magnetic resonance imaging. In most cases, prodromal fever or respiratory symptoms occur, followed by acute-onset flaccid limb weakness. Respiratory, axial, bulbar, facial, and extraocular muscles may also be affected. The clinical manifestations have been described as “polio-like,” due to striking similarities to cases of poliomyelitis. The primary site of injury in AFM is the anterior horn cells of the spinal cord, resulting in a motor neuronopathy. Seasonal peaks of cases have occurred in the United States every 2 years since 2012. However, AFM remains a rare disease, which can make it challenging for physicians to recognize and differentiate from other causes of acute flaccid paralysis such as Guillain–Barre syndrome, spinal cord stroke, and transverse myelitis. Epidemiological evidence suggests that AFM is linked to a viral etiology, with nonpolio enteroviruses (in particular enterovirus D68) demonstrating a plausible association. The epidemiology, possible etiological factors, clinical features, differential diagnosis, treatment, and outcomes of AFM are discussed in this review.


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At ICP on way to Kartarpur, a relentless preventive battle against polio | The Indian Express.

[March 7, 2020 11:19:59 pm]

kartarpur corridor punjab, Dera Baba Nanak Integrated Check Post (ICP) kartarpur, polio epidemic, punjab news, latest news, indian express

Gurdwara Darbar Sahib, the final resting place of founder of Sikhism Guru Nanak Dev

Navjeevan Gopal writes:

More than 57,000 and counting. This is the number of pilgrims who have been administered polio vaccination in the form of oral drops at Dera Baba Nanak Integrated Check Post (ICP) ever since it became operational on November 9 and first jatha, led by acting jathedar of Akal Takht, Giani Harpreet Singh, crossed over to Pakistan through Kartarpur Corridor to pay obeisance at Gurdwara Darbar Sahib, the final resting place of founder of Sikhism Guru Nanak Dev in the neighbouring country.

In Pakistan and Afghanistan, polio is categorized as endemic. India, on the other hand, was certified as polio free by the World Health Organisation in 2014 after the last polio case in the country was detected on January 13, 2011.

“We administer drops of polio vaccine to every pilgrim irrespective of their age. The reason is that India is polio free and neighbouring countries Pakistan and Afghanistan are not polio free,” nodal officer dealing with health facilities at Dera Baba Nanak ICP, Dr Lakhwinder Singh Athwal, told The Sunday Express.

Jathedar Harpreet Singh was the first person to be administered two drops of oral polio vaccine on November 9, 2019, Athwal said. Punjab Health Minister Balbir Singh Sidhu had administered the jathedar the drops. All the prominent personalities, who were part of more than 500-strong jatha that crossed over to Pakistan, were administered polio drops. The delegation included former Prime Minister Manmohan Singh, Punjab Chief Minister Capt Amarinder Singh, former chief minister Parkash Singh Badal, Parliamentarians including Sunny Deol, Sukhbir Singh Badal and Harsimrat Kaur Badal, and Punjab ministers and MLAs.

Athwal said that many in the first batch of pilgrims were apprehensive about taking the polio drops saying they had been already immunized. “I informed them why it was necessary even if they had been immunized,” he added.

Children below five years of age are certainly more prone to polio virus, he said, adding that already immunized adults were also being administered drops because if they get infected in Pakistan, there are chances that they may carry the virus back home in India through their fecal matter.

WHO describes polio as “a highly infectious viral disease,” which mainly affects young children.” The virus is transmitted by person-to-person, spread mainly through the faecal-oral route or, less frequently, by a common vehicle (such as contaminated water or food) and multiplies in the intestine, from where it can invade the nervous system and can cause paralysis… the disease causes paralysis, which is often permanent. There is no cure for polio, it can only be prevented by immunization,” as per the WHO.

Already immunized adults, Athwal said, would not contract the disease even if polio virus enters in their bodies. “But the virus can be transmitted through the pass faecal matter. To prevent transmission of virus in this manner from Pakistan, we boost the immunity of the pilgrims with two drops of vaccine,” said Athwal, who is also serving as senior medical officer (SMO) at Kalanaur.

Even if a child has been administered the drops, the authorities administer a supplementary dose at the ICP. “It is mandatory as per WHO guidelines,” said Athwal.

On an average more than 500 pilgrims cross over to Pakistan and come back the same day in the evening after paying obeisance at the Sikh shrine in Kartarpur.

Till February 29, around 57000 pilgrims had visited the gurdwara ever since the corridor became operational.

Apart from administering polio drops, another team of health officials at Dera Baba Nanak ICP are also recording travel history and other signs and symptoms of the visiting pilgrims for coronavirus.


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Pakistan to use polio surveillance teams to contain coronavirus outbreak | The Express Tribune.

[Published: March 2, 2020]

Teams will be trained to deal with cases of highly contagious disease, reads official handout. PHOTO: FILE

Teams will be trained to deal with cases of highly contagious disease, reads official handout. PHOTO: FILE

Razya Khan writes:

ISLAMABAD: In a bid to contain the novel coronavirus outbreak, the federal government has decided to use polio surveillance teams to spread awareness and identify suspected patients across the country.

The decision was made after four people tested positive of COVID-19 virus, setting off alarm bells as authorities scrambled to screen hundreds of people who recently arrived from Iran, a major new hotspot for the virus.

Two of the patients are from Karachi while the other two are from the federal territory, who are believed to have contracted the disease during their visit to Iran.

The decision was taken by the National Emergency Operation Center and a notification in this connection has been forwarded to all the authorities concerned.

According to the communique, the polio teams will be trained to deal with the cases of highly contagious disease “without compromising AFP [Acute Flaccid Paralysis] surveillance”.

The trained polio teams using their expertise will hold orientation sessions at the district level to spread awareness about the mysterious disease and support the government’s focal points established to deal with coronavirus cases, read the notification.

Notification coronavirus

The virus has spread to more than 30 countries, killing over 2,700 and infecting at least 80,000, mostly in China.

But new outbreaks in Europe, the Middle East and in Asia have fanned fears of the contagion taking hold in poor nations that lack the healthcare infrastructure to cope.

There are also growing fears in Pakistan — sandwiched between China and Iran, both hotspots for the disease — over how the country would deal with the outbreak.

The World Health Organisation (WHO), which already declared the outbreak an international health emergency, has updated the global risk level to ‘very high’.


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COVID-19 coronavirus and MS | MS Society UK.

The MS Society’s medical advisors, a group that includes some of the leading neurologists in the UK, have agreed the following joint statement on the COVID-19 coronavirus and MS.

“We have been closely following developments around the COVID-19 coronavirus. This is a rapidly evolving situation with a lot of uncertainty. We have set out our initial advice below based on what we currently know, but we will keep this under continual review as events progress and our knowledge of the virus improves."

Practical advice.

“In line with general public health advice, people with MS should ensure that they wash their hands frequently and where possible avoid being within one metre of people who are coughing and sneezing.

Those with other health conditions in addition to MS (such as cardiovascular disease or diabetes) should be especially careful to observe these recommendations.

If you believe you may have been exposed to COVID-19, in the first instance you should contact the NHS 111 coronavirus service. If you remain concerned you can speak to your GP or neurologist.”

DMTs and coronavirus.

“As of today (6 March 2020) our assessment is that people with MS would not normally need to stop taking a disease-modifying treatment (DMT) as a result of the threat of the virus.

As with many features of MS care, risks can vary widely from person to person. They will depend on a range of factors including the clinical features of your MS, your general health, and any other long-term health conditions you have.

We have set out below an assessment of specific risks regarding different DMTs. These are general guidelines to help people make an initial assessment of their own risk, and decide when to contact healthcare professionals for more detailed advice.”

Copaxone, Aubagio, Tecfidera, beta interferons, and Tysabri.

Glatiramer acetate (brand name: Copaxone), teriflunomide (brand name: Aubagio), dimethyl fumarate (brand name: Tecfidera) and beta-interferons (various brand names) are generally likely to be safer than the other DMTs as they are not considered to be generalised immunosuppressive therapies. We recommend that people with MS who are taking natalizumab (Tysabri) continue as normal, but we will be closely monitoring the developing situation.

Lemtrada, Mavenclad, and Ocrevus.

“If you are taking a course of alemtuzumab (brand name: Lemtrada), cladribine (brand name: Mavenclad), or ocrelizumab (brand name: Ocrevus) you and your neurologist should consider delaying this, as these treatments can hamper your immune system.

The case for waiting could be particularly strong if you are scheduled for a second or third course of treatment of one of these DMTs, where a delay of a few months is relatively unlikely to affect the clinical progression of your MS.

Before cancelling a course of treatment it is important to first discuss this with a neurologist or other healthcare professional. It may be that having understood the risks you feel it is best to continue, or there may be an alternative DMT that would be more suitable for the time being.

Gilenya.

“It is important to note that fingolimod (brand name: Gilenya) may increase your chances of having more severe viral and other infections, including COVID-19.

However if you are already taking fingolimod, stopping can lead to rebound MS disease activity, which in many cases would outweigh the risks of the virus.

If you are considering beginning a course of fingolimod in the near future, you and your neurologist could consider an alternative DMT for the time being."

Mayzent, Arzerra, rituximab, and HSCT.

“Other important points to note regarding specific disease-modifying therapies:

  • Siponimod (brand name: Mayzent), ofatumumab (brand name: Arzerra) and rituximab (various brand names) are not currently available on the NHS, but are available by private prescription in the UK. These could also affect your risk regarding COVID-19 and should be discussed with your neurologist or healthcare professional.
  • Haematopoietic stem cell transplantation (HSCT) is an intense chemotherapy treatment for MS. It aims to stop the damage MS causes by wiping out and then regrowing your immune system, using your stem cells. This treatment greatly hampers your immune system for a period of time and you and your neurologist or healthcare professional should consider delaying this treatment."

“If you are concerned please contact your neurologist or other healthcare professional for more detailed advice.”


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Pakistan: Anti-polio drive to begin from Monday | The Nation.

[March 07, 2020]

PESHAWAR - Khyber Pakhtunkhwa Emergency Operations Centre (EOC) will launch a five-day long anti-polio campaign in 16 districts of Khyber Pakhtunkhwa from Monday in response to the continuous virus circulation and reporting of polio cases from the region.The anti-polio campaign will start from Monday.


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The Coronavirus, by the Numbers | The New York Times.

[Published March 5, 2020; Updated March 6, 2020]

Adam Kucharski, mathematician at the London School of Hygiene and Tropical Medicine. Credit Tom Jamieson for The New York Times
Adam Kucharski, mathematician at the London School of Hygiene and Tropical Medicine. Credit Tom Jamieson for The New York Times

James Gorman writes:

Adam Kucharski studies how diseases spread, but he’s not handling viruses in the lab or treating sick people in the hospital. He’s a mathematician at the London School of Hygiene & Tropical Medicine, and he uses math to understand outbreaks of diseases like Ebola, SARS, influenza and now Covid-19. His goal is to design better ways to control outbreaks.

In an eerie coincidence, he wrote a book called “The Rules of Contagion,” before the current outbreak, which has been published in Britain and will be released in September in the United States. In it he talks about the math of contagion involving not only physical diseases, but also ideas, rumors and even financial crises.

In a recent experiment for the 100th anniversary of the 1918 flu, he worked with another mathematician and BBC presenter, Hannah Fry, of University College London, and collaborators at the University of Cambridge, to create a documentary, “Contagion: The BBC Four Pandemic,” using a phone app to track social contacts and map how an infection might spread.

The news of coronavirus epidemics around the world involves a flood of numbers that are a challenge for any nonscientist to digest. I asked Dr. Kucharski to help us navigate some of these numbers, and to tell us which ones we should pay attention to. We talked on the phone and corresponded by email this week. This is an edited version of our back and forth.

We hear a lot about the percentage of sick people who are dying. Is that the case fatality rate?

The case fatality rate measures the risk that someone who develops symptoms will eventually die from the infection.

And how is that rate calculated?

Ideally, we would monitor a large group of people from the point at which they develop symptoms until they later die or recover, then calculate the proportion of all these cases who had died.

So can we just look at the total number of deaths and the current number of cases?

The problem with just dividing the total number of deaths and total number of cases is that it doesn’t account for unreported cases or the delay from illness to death. The delay is crucial: If 100 people arrive at hospital with Covid-19 on a given day, and all are currently still alive, it obviously doesn’t mean that the fatality rate is 0 percent. We need to wait until we know what happens to them eventually.

Any deaths will be people who got sick two to three weeks ago, so it’s not simply deaths at the moment divided by cases at the moment. Plus some cases might be missed: If you have two deaths from two cases, as happened in Iran last month, that most likely means you’ve missed a bunch of cases.

We’ve seen all sorts of numbers for fatality rates. Does the latest estimate of 3.4 percent globally make sense?

Early on, people looked at total current cases and deaths, which, as I said, is a flawed calculation, and concluded that the case fatality rate must be 2 percent based on China data. If you run the same calculation on yesterday’s totals for China, you get an apparent CFR (case fatality rate) of near 4 percent. People are speculating that something is happening with the virus, where it actually is just this statistical illusion that we’ve known about from Day 1. I’d say on best available data, when we adjust for unreported cases and the various delays involved, we’re probably looking at a fatality risk of probably between maybe 0.5 and 2 percent for people with symptoms.

I had a short Twitter thread explaining this (and predicting the rise) a couple of weeks ago:

Adam Kucharski@AdamJKucharski

If the number of reported confirmed cases of continues to slow down, the 2% fatality rate people have been quoting will appear to rise. But it will be a statistical illusion. Let me explain why.... 1/

411 people are talking about this

What about another number we hear about all the time, R, the reproductive number, or how many people a given patient is likely to infect. Why is it important and what goes into calculating it?

At its simplest, R is the answer to the question: How worried should we be about infection? If R is above one, each case, on average, is giving it to at least one other person. You’re going to see growth.

If it’s less than one, then a group of infected people are generating less infection. From a policy-planning point of view, it gives you a very clear objective. For example, in the Ebola response in 2014, it was a really prominent part of the response. The aim was to get R below one.

That seems very simple and straightforward, but you write that it’s more complicated than it seems. In your book you say that to calculate R you’ve got to know duration, opportunity, transmission probability and susceptibility (the “DOTS”). Let’s take them one by one. What is duration?

How long someone is infectious. If someone is infectious twice as long, then that’s twice as long that they are around to spread infection.

Do we know what the duration is for this coronavirus?

On average, we’d probably be looking at a week or two. Of course, if people get hospitalized, then they’re not in the community spreading infection in the same way.

The second component is opportunity. How do you determine that?

That’s a measure of how many people you come into contact with for every day you’re infectious. With something like flu, you’re not infectious very long but a lot of your interactions could potentially spread it. Whereas with something like HIV, the duration is much longer but the number of sexual partners you have relative to the number of conversations you have is obviously much lower.

And transmission probability?

This is a measure of the chance the infection will get across during an interaction. For example, during a sexual encounter, the virus won’t necessarily get across.

Finally there’s susceptibility. How do you determine that?

Susceptibility measures the chance the person at the other end of the interaction will pick up the infection and become infectious themselves.

Once you’ve got numbers for these four components, what’s the equation to come up with R?

If you multiply them together, you get the reproduction number. So if you scale up or scale down any one of these things, it directly affects the value of R.

How does this knowledge help public health planning?

Generally, susceptibility is the easiest one to reduce if we have things like vaccines. If we don’t, then we have to think about targeting the other aspects of transmission, such as reducing opportunities through social distancing, or probability of transmission during things like handshakes by encouraging hand washing.

What if you’re not in public health, but are thinking about your own personal chances and what your behavior should be?

If you imagine you’ve got a reproduction number of two, each person’s infecting two others, on average. But some situations are more likely to spread infection than others. We’ve found for things like Covid-19, it’s close-knit interactions that seem to be most important.

What we need to think about — and what a lot of our modeling is certainly thinking about — is not just how much transmission is happening, but where is that transmission happening. If you’re going to change your behavior, think how to reduce those risky situations as much as possible.

If you were the average person, what would you pay attention to — in terms of the news and the numbers?

One signal to watch out for is if the first case in an area is a death or a severe case, because that suggests you had a lot of community transmission already. As a back of the envelope calculation, suppose the fatality rate for cases is about 1 percent, which is plausible. If you’ve got a death, then that person probably became ill about three weeks ago. That means you probably had about 100 cases three weeks ago, in reality. In that subsequent three weeks, that number could well have doubled, then doubled, then doubled again. So you’re currently looking at 500 cases, maybe a thousand cases.

I think the other thing that people do need to pay attention to is the risk of severe disease and fatality, particularly in older groups, in the over-70s, over-80s. Over all we’re seeing maybe 1 percent of symptomatic cases are fatal across all ages. There’s still some uncertainty on that, but what’s also important is that 1 percent isn’t evenly distributed. In younger groups, we’re talking perhaps 0.1 percent, which means that when you get into the older groups, you’re potentially talking about 5 percent, 10 percent of cases being fatal.

In thinking about social behavior and thinking about your interactions, the question should be, “How do we stop transmission getting into those groups where the impact could be really severe?”

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James Gorman is a science writer at large and the host and writer of the video series “ScienceTake.” He joined The Times in 1993 and is the author of several books, including “How to Build a Dinosaur,” written with the paleontologist Jack Horner.


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