NPR

“…..What does the center look like?

It’s our standard set-up for an Ebola treatment center. Tents are the most rapid thing we can put up. They are very large, 47-square-meter tents, divided into different zones, with toilets, showers, orange fencing. It’s a very nice structure.

Do you run a test to see if someone who’s sick actually has Ebola before admitting them to the center?

We don’t wait for test results. We start treating [suspected Ebola] patients as soon as they enter the treatment center.

What kind of treatments?

We give anti-malaria treatment, antibiotics and then symptomatic treatment as well as hydration, fever and nausea management. With Ebola you give the maximum you can in terms of supportive care. If the person gets a negative result [from the lab test] and is not an Ebola case and they’re still sick, we send them to the hospital for proper care…..

The taking of the sample is exactly the same as for any nurse who does a blood sample anywhere — but be very, very careful with the needle. Make sure you have all your materials with you before start, then just take a normal blood sample. What’s different is the way we send it to the lab.

What’s the procedure?

First when we take the blood [container] and decontaminate it — spray it with chlorine, then put it in another container sprayed with chlorine, then put it in a third container that’s sprayed before it goes to the lab.

When it gets to the lab, the lab technician is in the low-risk zone, sitting behind plexiglass. And in the plexiglass are two gloves that go into high-risk zone. So the lab tech’s hands go into the gloves and they’re manipulating [the blood sample] in the high-risk zone………”

BBC

“…..The name Novichok means “newcomer” in Russian, and applies to a group of advanced nerve agents developed by the Soviet Union in the 1970s and 1980s.

They were known as fourth-generation chemical weapons and were developed under a Soviet programme codenamed Foliant….

These nerve agents were designed to escape detection by international inspectors…..

One of the group of chemicals known as Novichoks – A-230 – is reportedly five to eight times more toxic than VX nerve agent…..

A number of variants of A-230 have been manufactured. One of these experimental chemicals – A-232 – was reportedly used by the Russian military as the basis for a chemical weapon known as Novichok-5.

Russia’s ambassador to the UK, Alexander Yakovenko, has suggested British authorities have identified the variant used in the Skripal attack as A-23…..

“Based on public sources, A-234 is one of the Novichok family of agents… Little is known about it but the symptoms track closely with those eyewitnesses attributed to Sergei and Yulia Skripal – as do other similar nerve agents…….

While some Novichok agents are liquids, others are thought to exist in solid form. This means they could be dispersed as an ultra-fine powder.

Some of the agents are also reported to be “binary weapons“, meaning the nerve agent is typically stored as two less toxic chemical ingredients that are easier to transport, handle and store.

When these are mixed, they react to produce the active toxic agent……..

Novichoks were designed to be more toxic than other chemical weapons, so some versions would begin to take effect rapidly – in the order of 30 seconds to two minutes.

The main route of exposure is likely to be through inhalation, though they could also be absorbed through the skin.

However, in powder form an agent might take longer to cause a reaction……

Novichok agents have similar effects to other nerve agents – they act by blocking messages from the nerves to the muscles, causing a collapse of many bodily functions.

Dr Mirzayanov told BBC Russian that the first sign to look out for was miosis, the excessive constriction of the pupils.

A larger dose could cause convulsions and interrupted breathing…..”

BBC

“…..Dr Stephen Jukes, an intensive care consultant at the hospital, said: “When we first were aware this was a nerve agent, we were expecting them not to survive.

“We would try all our therapies. We would ensure the best clinical care. But all the evidence was there that they would not survive.”

Both Skripals were heavily sedated which allowed them to tolerate the intrusive medical equipment they were connected to, but also helped to protect them from brain damage, a possible consequence of nerve agent poisoning.

Over time, the sedation was reduced and the ventilation switched from the mouth to the trachea, as shown by the vivid scar seen on Yulia Skripal’s neck in the TV statement she gave after she was released.

Once the patients became more conscious, staff had to carefully consider what they could tell them without prejudicing the police investigation, and decide on the right moment to allow questioning by detectives.

Medical director Dr Christine Blanshard explained: “Those are very difficult decisions, because on the one hand you want to provide reassurance to the patients that they are safe and they are being looked after, and on the other hand you don’t want to give them information that might cause difficulties with subsequent police interviews.”

It was the doctors and nurses that, out of concern for their patients, insisted that international inspectors obtain a court order before they would be allowed to take blood samples from the Skripals.

Dr Jukes explained: “These are vulnerable patients, they needed some form of advocate and without a court order we could not allow things to happen to them without their consent.”

Once the Skripals were stable and able to speak, the key concern for medical staff was how their production of the key enzyme acetylcholinesterase – needed to re-establish their normal body functions – could be stimulated.

The body will do this naturally after nerve agent poisoning, but the process can take many months.

In trying combinations of drugs, Dr Murray says the hospital received input from “international experts”, some of them from Porton Down.

The laboratory, internationally known for its chemical weapons expertise, processed tests and offered advice on the best therapies.

New approaches to well-known treatments were tried. Dr Jukes said that the speed of the Skripals’ recovery came as a very pleasant surprise that he cannot entirely explain……”

History

PLOS

Hotez PJ, Damania A (2018) India’s neglected tropical diseases. PLoS Negl Trop Dis 12(3): e0006038. https://doi.org/10.1371/journal.pntd.0006038

NIAID

Friday, May 18, 2018

Experimental MERS treatments enter clinical trial

NIH-sponsored trial to test two human monoclonal antibodies.

Color-enhanced scanning electron micrograph of cells infected with Middle East respiratory syndrome coronavirus (MERS-CoV).NIAID

Enrollment has begun in an early-stage clinical trial testing the safety of two human monoclonal antibodies (mAbs) designed to treat people infected with Middle East respiratory syndrome coronavirus (MERS-CoV). The trial is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and is funded in part by the Biomedical Advanced Research and Development Authority, part of the Office of the Assistant Secretary for Preparedness and Response, Department Health and Human Services.

The first recognized case of MERS was reported in Jordan in 2012. Since then, MERS-CoV has spread to 27 countries. As of May, 2,206 laboratory-confirmed cases have been reported to the World Health Organization. Those cases include 787 deaths, a fatality rate of about 36 percent.

“Currently, we lack specific treatments for MERS,” said NIAID Director Anthony S. Fauci, M.D. “Having targeted therapeutics available to treat this unpredictable and frequently fatal respiratory disease would help us reduce MERS-associated deaths and control future outbreaks.”

The mAbs, REGN3048 and REGN3051, were discovered and developed by scientists at the biotechnology company Regeneron, headquartered in Tarrytown, New York.

Subsequently, researchers at Regeneron and the University of Maryland School of Medicine demonstrated the ability of the antibodies to neutralize MERS-CoV in a mouse model of MERS.

The new NIAID trial is the first to test these mAbs in people.

The study will enroll 48 healthy adults between the ages of 18 and 45 years at WCCT Global, a clinic in Cypress, California. Participants will be divided into six groups of eight, with two people in each group receiving an inactive placebo and the remaining six receiving both experimental mAbs delivered intravenously. The study is blinded, meaning neither the study staff nor the participants will know whether a placebo or the mAb is being administered. Participants in the initial cohort will receive the lowest dosage of the experimental antibodies, 1.5 milligrams (mgs) of each mAb per kilogram (kg) of the volunteer’s weight. Participants in successive cohorts will receive increasing dosages until the highest dosage (75 mg/kg of each mAb) is reached in the sixth group.

Decisions to continue the trial and to administer the escalating doses of mAbs will be made by an independent safety review committee (SRC) whose members will have access to safety and tolerability data throughout the trial. The SRC will meet at regularly scheduled intervals to determine if any pre-established criteria have been met that would require the trial to be halted. If there are no safety concerns, the trial will proceed to enroll participants into the next higher dosage cohort. The study is expected to be completed by June 2019.

Additional information about the trial is available at clinicaltrials.gov, using the identifier NCT03301090. The trial is funded through contract HHSN272201500005I.

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH

“Scientists have identified a molecule found on human cells and some animal cells that could be a useful target for drugs against chikungunya virus infection and related diseases, according to new research published in the journal Nature. A team led by scientists at Washington University School of Medicine in St. Louis conducted the research, which was funded in part by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Chikungunya, an alphavirus, is transmitted to humans by the bite of an infected mosquito. Currently no specific treatment is available for chikungunya virus infection, which can cause fever and debilitating joint pain and arthritis. Small, sporadic outbreaks of chikungunya occurred in Africa, Asia, Europe, and the Indian and Pacific Oceans after the virus was identified in the 1950s. In 2013, the virus spread to the Americas and has since caused a widespread and ongoing epidemic.

In this study, scientists aimed to better understand which traits make humans susceptible to chikungunya virus infection. Using the gene-editing tool CRISPR-Cas9, they performed a genome-wide screen that identified the molecule Mxra8 as a key to the entry of chikungunya virus and related viruses into host cells. In the laboratory, scientists were able to reduce the ability of chikungunya virus to infect cells by editing the human and mouse genes that encode Mxra8. The researchers also administered anti-Mxra8 antibodies to mice and infected the mice with chikungunya virus or O’nyong-nyong virus, another alphavirus. The antibody-treated mice had significantly lower levels of virus infection and related foot swelling as compared with a control group.

These findings, along with future studies to better understand how chikungunya virus interacts with Mxra8, could help inform development of drugs to treat diseases caused by alphaviruses, according to the authors.

Article

R Zhang et al. Mxra8 is a receptor for multiple arthritogenic alphaviruses. Nature DOI: 10.1038/s41586-018-0121-3 (2018).

Who

NIAID Director Anthony S. Fauci, M.D., is available for comment. Patricia M. Repik, Ph.D., program officer for Emerging Viral Diseases in the Virology Branch of NIAID’s Division of Microbiology and Infectious Diseases, is also available for comment.

Contact

To schedule interviews, please contact Jennifer Routh, (301) 402-1663, NIAIDNews@niaid.nih.gov (link sends e-mail).

This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process — each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health^®”

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