U.S. biosafety experts watch every step in care of Ebola patients

[Buster's Uncle]

Tobacco-derived 'plantibodies' enter the fight against Ebola
Reuters
By Sharon Begley  7 hours ago



NEW YORK, Aug 6 (Reuters) - Drugmakers' use of the tobacco plant as a fast and cheap way to produce novel biotechnology treatments is gaining global attention because of its role in an experimental Ebola therapy.

The treatment, which had been tested only in lab animals before being given to two American medical workers in Liberia, consists of proteins called monoclonal antibodies that bind to and inactivate the Ebola virus.

For decades biotech companies have produced such antibodies by growing genetically engineered mouse cells in enormous metal bioreactors. But in the case of the new Ebola treatment ZMapp, developed by Mapp Pharmaceuticals, the antibodies were produced in tobacco plants at Kentucky Bioprocessing, a unit of tobacco giant Reynolds American.

The tobacco-plant-produced monoclonals have been dubbed "plantibodies."

"Tobacco makes for a good vehicle to express the antibodies because it is inexpensive and it can produce a lot," said Erica Ollmann Saphire, a professor at The Scripps Research Institute and a prominent researcher in viral hemorrhagic fever diseases like Ebola. "It is grown in a greenhouse and you can manufacture kilograms of the materials. It is much less expensive than cell culture."

In the standard method of genetic engineering, DNA is slipped into bacteria, and the microbes produce a protein that can be used to combat a disease.

A competing approach called molecular "pharming" uses a plant instead of bacteria. In the case of the Ebola treatment, Mapp uses the common tobacco plant, Nicotiana benthanmianas.

The process is very similar. A gene is inserted into a virus that is then used to infect the tobacco plant. The virus acts like a micro-Trojan Horse, ferrying the engineered DNA into the plant.

Cells infected with the virus and the gene it is carrying produce the target protein. The tobacco leaves are then harvested and processed to extract the protein, which is purified.

ZMapp's protein is a monoclonal antibody, which resembles ordinary disease-fighting antibodies but has a highly specific affinity for particular cells, including viruses such as Ebola. It attaches itself to the virus cells and inactivates them.


APPROVAL PROCESS

The drug so far has only been produced in very small quantities, but interest in it is stoking debate over whether it should be made more widely available to the hundreds of people stricken with Ebola in Africa while it remains untested.

"We want to have a huge impact on the Ebola outbreak," Mapp CEO Kevin Whaley said in an interview at company headquarters in San Diego. "We would love to play a bigger role."

Whaley said he was not aware of any significant safety issues with the serum. He would not discuss whether the company has been contacted about providing the drug overseas.

But he did note the novel manufacturing process carries its own risk, and would have to be cleared by the U.S. Food and Drug Administration as part of the approval process.

The FDA would, for example, have to be satisfied that the plant extraction process had not led to contamination of the resulting drug.

The tobacco plant grows quickly, said Reynolds spokesman David Howard, and "it takes only about a week (after the genes are introduced) before you can begin extracting the protein."

He declined to say how much medication each plant can yield or whether Kentucky Bioprocessing is in a position to produce ZMapp in significant quantities.

Scripps' Saphire said it can still take anywhere from one to three months to produce the ZMapp serum for wider use given the complexities of the process.


PENTAGON FUNDING

In 2007, Kentucky Bioprocessing entered into an agreement with Mapp Biopharmaceutical and the Biodesign Institute of Arizona State University to refine the tobacco-plant approach. The approach attracted funding support from the Pentagon's Defense Advanced Research Projects Agency (DARPA).

For all the hope, however, the plant technique has delivered few commercial products. In 2012 the FDA okayed a drug for the rare genetic disorder Gaucher disease from Israel's Protalix BioTherapeutics and Pfizer. Called Elelyso, it is made in carrot cells, and is the only such drug to reach the market.

Other companies have fallen far short, though it is not clear if the technique was to blame. Calgary-based SemBioSys Genetics Inc, which used safflowers to produce an experimental diabetes drug, folded in 2012 before it finished clinical trials.

Even Kentucky Bioprocessing, which at one point was developing monoclonal antibodies against HIV (the virus that causes AIDS), C. difficile bacterial infection, and the human papillomavirus, has dropped the last two projects, Howard said.

Last year Mitsubishi Tanabe Pharma Corp acquired a majority share of Quebec City-based Medicago, which is developing influenza and other vaccines using the tobacco-plant technology. The other 40 percent is owned by tobacco giant Philip Morris International.

(Reporting by Sharon Begley, Toni Clarke and Deena Beasley; Editing by Michele Gershberg and Martin Howell)


http://news.yahoo.com/tobacco-derived-plantibodies-enter-fight-110000526.html

[Buster's Uncle]

U.S. biosafety experts watch every step in care of Ebola patients
Reuters
By Julie Steenhuysen  August 5, 2014 3:01 PM



COLUMBIA Mo. (Reuters) - A U.S. hospital caring for two Americans carrying the deadly Ebola virus has tapped biosafety experts to ensure doctors, nurses and other staff do everything needed to prevent the virus from escaping from an isolation ward in Atlanta.

The two patients, humanitarian aid workers who became infected with Ebola in West Africa, are believed to be the first Ebola patients ever to be treated on U.S. soil after being flown separately to Emory University hospital.

Sean Kaufman, an Emory biosafety expert, has been advising hospital staff on the steps needed to protect themselves as they care for Dr Kent Brantly of the North Carolina-based Christian organization Samaritan's Purse and missionary Nancy Writebol of the SIM USA group.

"We are sitting in the anteroom. We're watching them interact with the patient and we're making sure every single thing they do is by the book," he said in a videoconference to a biosafety meeting in Columbia, Missouri.

In this case, the book is rather elaborate.

Kaufman said his team ran through the proper methods of putting on and taking off protective suits, gloves, booties and breathing systems required to keep employees safe while working with the Ebola patients. Now they are focused on making sure medical staff comply with those procedures.

The contagious disease, concentrated in Africa, has killed nearly 900 people since February and has no proven cure. The death rate in the current epidemic is about 60 percent, experts say.

Kaufman described the steps taken just to address a small spill of contaminated fluids from Brantly, who arrived at the hospital in a white biohazard suit on Saturday. Writebol arrived on Tuesday.

Staff wearing protective gear set up a perimeter where the spill and any droplets might have landed.

To make sure they do not track the spill outside of that area, staff replaced their protective booties and removed outer gloves that might have been contaminated. They washed their inner gloves, then put on new gloves and booties.

For the spill, the team soaked towels in a special disinfectant, then placed the towels on the spill working from the outside of the spill in. The towels were left there for a period of time to kill any potential virus.

During that waiting period, the staff again replaced gloves and booties. When the disinfectant had enough time to work, the team removed the towels, placed them in biocontainment bags, tied them up tightly, cleaned the outside of the bags with bleach, then repeated the whole process with a second biocontainment bag which they cleaned with bleach.

After that, they placed the material in an autoclave bag, where it will be kept until it can be destroyed. After the bag was removed, the staff members mopped up the spill, and once again changed their protective gear.

Emory University is just a stone's throw from the offices of the U.S. Centers for Disease Control and Prevention, which last month came under the spotlight after announcing the accidental release of anthrax and bird flu pathogens. Kaufman, who is also president of Behavioral-Based Improvement Solutions LLC, testified before U.S. lawmakers on the incidents.

Kaufman said he understands the negative public perception about bringing the patients to the United States, noting that just being a part of this process has affected his own life.

"My kids won't hug me until I take a shower," he said, adding that his wife is "a nervous wreck."

(Reporting by Julie Steenhuysen; Editing by Michele Gershberg and Grant McCool)


http://news.yahoo.com/u-biosafety-experts-watch-every-step-care-ebola-190133079.html

[Buster's Uncle]

Ebola mortality rate expected to rise as outbreak runs its deadly course
Reuters
By Kate Kelland  August 5, 2014 3:21 PM



The possibility that the deadly virus may be in New York City has caused concern



LONDON (Reuters) - The death rate so far in the world's worst outbreak of Ebola is not as extreme as recorded in the past, but experts expect it to prove no less virulent in the end, once more victims succumb and the grim data is tallied up.

Latest figures from the World Health Organization (WHO) record 1,603 cases of Ebola in the West African outbreak and 887 deaths - giving a death rate of just over 55 percent.

That is well below the 78.5 percent average death rate over 14 past outbreaks of the same virus - called the "Zaire strain" after the former name of the Democratic Republic of Congo where it was first detected in 1976. In some outbreaks the rate was up to 90 percent, according to WHO data.

Experts say death rates for Ebola outbreaks can rise as the disease runs its course, which is what they now expect.

"This is partly a statistical thing about collecting death events, and also partly about the maturity of the outbreak," said Derek Gatherer, a virologist at Britain's University of Lancaster who has been following the outbreak since it started in February.

"The nearer we get to the end of the epidemic, the closer we would expect the fatality rate to correspond to the Zaire Ebola average of 80 percent," he told Reuters.



The first of two Americans infected in Africa with the Ebola virus arrived at a hospital in Atlanta Sunday, reports Vicente Arenas. Back in West Africa, the death toll from the outbreak has now climbed well above 700


Ebola can take up to a month to kill its victims, said Ben Neuman, an expert in viruses at Britain's Reading University.

Already, the death rate in Guinea, where the infection was first detected, has reached 74 percent. The overall regional outbreak mortality figure is brought down by lower death rates in countries that were more recently hit: 54 percent in Liberia and around 42 percent in Sierra Leone.

"It will take a few weeks until we see the outcome of a wave of new cases like this one," Neuman said. "(The) Ebola fatality rates look particularly low in Sierra Leone at the moment compared to Guinea, because the virus only recently arrived."

There is still some hope that the rise in death rates can be slowed through medical care. Neuman noted that when doctors are able to begin treatment soon after infection, the survival rates from Ebola can increase significantly.

But even at 50 to 60 percent mortality, no other human disease comes close to Ebola's ability to kill those it infects, specialists say.

The corner of West Africa stricken by Ebola is among the poorest areas in the world and government hospitals in the region often lack even basic equipment, with dirty and overcrowded rooms.

Fear of being left to die in isolation and suspicion of doctors in masks and full body protective suits is driving some patients to evade treatment altogether, meaning they can go uncounted in the data whether they live or die.


NO CURE

Ebola has no proven cures and there is no vaccine to prevent infection, so the best treatment is focused on alleviating symptoms such as fever, vomiting and diarrhea - all of which can contribute to severe dehydration.

Patients often need oral rehydration with solutions containing electrolytes, or intravenous fluids. Severely ill patients need intensive care.

But languishing in the bottom part of the U.N. Human Development Index, Guinea, Sierra Leone and Liberia have some of the weakest health systems in the world. This, combined with porous borders, poor sanitation and local ignorance of the disease have helped its spread.

Nigeria said on Tuesday it had eight suspected cases linked to a confirmed fatal case in a man who traveled to Lagos from Liberia last week. Saudi Arabia's health ministry said it was also testing a suspected case in a man returning from Sierra Leone.

Two American aid workers who contracted Ebola while working in West Africa have been flown home for treatment are likely to have a better than average chance of survival due to higher standards of healthcare.

Guinea, where the outbreak started in rural forest areas in the east, had the lowest ratio of hospital beds per capita in a World Bank survey of 68 nations in 2011, with just three beds per 10,000 people.

Outside the main cities, rural healthcare clinics are rudimentary with healthcare experts saying even basic equipment like plastic gloves is unavailable.

Although malaria and other fevers are regularly treated at hospitals and clinics in the three countries, their facilities were not prepared for a disease as deadly as Ebola. Health authorities and medical NGOs had to scramble to set up makeshift isolation units - often a collection of tents - in rural areas.

Neuman said there was some hope that public relations efforts to get more people to seek treatment for Ebola would pay dividends in lower death rates.

"While improvements in care will undoubtedly continue to increase the Ebola survival rate, there will unfortunately be more casualties from among those who have already caught the virus," he said.



As of August 1, 2014, the cumulative number of cases attributed to EVD in the four countries stands at 1,603 including 887 deaths. (WHO/Yahoo News)


(Additional reporting by Daniel Flynn in Dakar; Editing by Peter Millership and Peter Graff)


http://news.yahoo.com/ebola-mortality-rate-expected-rise-outbreak-runs-deadly-192146284.html

[Buster's Uncle]

Ebola 'Experimental Serum' in Limited Supply, CDC Says
LiveScience.com
By Rachael Rettner, Senior Writer  5 hours ago



The "experimental serum" that doctors gave to two American patients with Ebola is in very limited supply, and will not be available for general use, according to the Centers for Disease Control and Prevention.

Doctors reportedly gave the serum to two American health care workers who contracted the deadly virus while working to combat the Ebola outbreak in West Africa. The humanitarian organization Samaritan's Purse, which employs one of the patients, arranged to have the experimental treatment flown to Liberia, the CDC said. Both patients have since been brought back to the United States for treatment.

The experimental Ebola treatment is called ZMapp, and is being developed by the San Diego company Mapp Biopharmaceutical, Inc. The serum contains three monoclonal antibodies, which are molecules that bind to a protein of a foreign object — in this case, the Ebola virus, the CDC said.

Mapp Biopharmaceutical has been planning to conduct clinical trials to test ZMapp, but the company currently does not have the capacity to make large quantities of the treatment, the CDC said. [5 Things You Should Know About Ebola]

"The manufacturer reports that there is a very limited supply, so it cannot be purchased and is not available for general use," the agency said in a recently posted "Questions and Answers" page on the experimental treatment.

And although some news reports have said that the treatment "likely saved" the two American patients, the CDC said it is too early to know if ZMapp is effective. "Some patients infected with Ebola virus do get better spontaneously or with supportive care," the CDC said. In most previous outbreaks of Ebola, between 10 percent and 50 percent of infected people have survived, according to the World Health Organization.

ZMapp still needs to undergo trials in people to test whether it is safe and works to treat Ebola, the CDC said.

Currently, there is no specific treatment or cure for Ebola. The standard treatment for infected people calls for supporting them by providing fluids, maintaining their blood pressure, treating them for other infections and providing additional supportive care.

Doctors also lack a vaccine to prevent infection with Ebola, but the National Institutes of Health is working to develop such a vaccine, aiming to conduct a trial of it in the fall, the CDC said.


http://news.yahoo.com/ebola-experimental-serum-limited-supply-cdc-says-170349590.html

[Buster's Uncle]

Ebola mortality rate expected to rise as outbreak runs its deadly course
Reuters
By Kate Kelland, Health and Science Correspondent  14 hours ago



Volunteers carry bodies in a centre run by Medecins Sans Frontieres for Ebola patients in Kailahun August 2, 2014. Hundreds of troops were deployed in Sierra Leone and Liberia on Monday to quarantine communities hit by the deadly Ebola virus, as the death toll from the worst-ever outbreak reached 887 and three new cases were reported in Nigeria. Picture taken August 2, 2014. REUTERS/WHO/Tarik Jasarevic/Handout via Reuters



LONDON, Aug 5 (Reuters) - The death rate so far in the world's worst outbreak of Ebola is not as extreme as recorded in the past, but experts expect it to prove no less virulent in the end, once more victims succumb and the grim data is tallied up.

Latest figures from the World Health Organization (WHO) record 1,603 cases of Ebola in the West African outbreak and 887 deaths - giving a death rate of just over 55 percent.

That is well below the 78.5 percent average death rate over 14 past outbreaks of the same virus - called the "Zaire strain" after the former name of the Democratic Republic of Congo where it was first detected in 1976. In some outbreaks the rate was up to 90 percent, according to WHO data.

Experts say death rates for Ebola outbreaks can rise as the disease runs its course, which is what they now expect.

"This is partly a statistical thing about collecting death events, and also partly about the maturity of the outbreak," said Derek Gatherer, a virologist at Britain's University of Lancaster who has been following the outbreak since it started in February.

"The nearer we get to the end of the epidemic, the closer we would expect the fatality rate to correspond to the Zaire Ebola average of 80 percent," he told Reuters.

Ebola can take up to a month to kill its victims, said Ben Neuman, an expert in viruses at Britain's Reading University.

Already, the death rate in Guinea, where the infection was first detected, has reached 74 percent. The overall regional outbreak mortality figure is brought down by lower death rates in countries that were more recently hit: 54 percent in Liberia and around 42 percent in Sierra Leone.

"It will take a few weeks until we see the outcome of a wave of new cases like this one," Neuman said. "(The) Ebola fatality rates look particularly low in Sierra Leone at the moment compared to Guinea, because the virus only recently arrived."

There is still some hope that the rise in death rates can be slowed through medical care. Neuman noted that when doctors are able to begin treatment soon after infection, the survival rates from Ebola can increase significantly.

But even at 50 to 60 percent mortality, no other human disease comes close to Ebola's ability to kill those it infects, specialists say.

The corner of West Africa stricken by Ebola is among the poorest areas in the world and government hospitals in the region often lack even basic equipment, with dirty and overcrowded rooms.

Fear of being left to die in isolation and suspicion of doctors in masks and full body protective suits is driving some patients to evade treatment altogether, meaning they can go uncounted in the data whether they live or die.


NO CURE

Ebola has no proven cures and there is no vaccine to prevent infection, so the best treatment is focussed on alleviating symptoms such as fever, vomiting and diarrhoea - all of which can contribute to severe dehydration.

Patients often need oral rehydration with solutions containing electrolytes, or intravenous fluids. Severely ill patients need intensive care.

But languishing in the bottom part of the U.N. Human Development Index, Guinea, Sierra Leone and Liberia have some of the weakest health systems in the world. This, combined with porous borders, poor sanitation and local ignorance of the disease have helped its spread.

Nigeria said on Tuesday it had eight suspected cases linked to a confirmed fatal case in a man who travelled to Lagos from Liberia last week. Saudi Arabia's health ministry said it was also testing a suspected case in a man returning from Sierra Leone.

Two American aid workers who contracted Ebola while working in West Africa have been flown home for treatment are likely to have a better than average chance of survival due to higher standards of healthcare.

Guinea, where the outbreak started in rural forest areas in the east, had the lowest ratio of hospital beds per capita in a World Bank survey of 68 nations in 2011, with just three beds per 10,000 people.

Outside the main cities, rural healthcare clinics are rudimentary with healthcare experts saying even basic equipment like plastic gloves is unavailable.

Although malaria and other fevers are regularly treated at hospitals and clinics in the three countries, their facilities were not prepared for a disease as deadly as Ebola. Health authorities and medical NGOs had to scramble to set up makeshift isolation units - often a collection of tents - in rural areas.

Neuman said there was some hope that public relations efforts to get more people to seek treatment for Ebola would pay dividends in lower death rates.

"While improvements in care will undoubtedly continue to increase the Ebola survival rate, there will unfortunately be more casualties from among those who have already caught the virus," he said.


http://news.yahoo.com/ebola-mortality-rate-expected-rise-outbreak-runs-deadly-080858661.html

[Buster's Uncle]

How Do People Survive Ebola?
LiveScience.com
By Rachael Rettner, Senior Writer  22 hours ago



Ebola virus



Ebola is a frightening, highly lethal virus — in the current outbreak in West Africa, about 60 percent of people infected with the pathogen have died. Although in the minority, some people do recover from infection.

Doctors don't know for certain who will survive Ebola, and there is no specific treatment or cure for the disease. But studies suggest there are some biological markers linked with a higher chance of surviving Ebola, experts say.

When a person becomes infected with Ebola, the virus depletes the body's immune cells, which defend against infection, said Derek Gatherer, a bioinformatics researcher at Lancaster University in the United Kingdom, who studies viral genetics and evolution. In particular, the Ebola virus depletes immune cells called CD4 and CD8 T lymphocytes, which are crucial to the function of the immune system, Gatherer said.

But if a person's immune system can stand up to this initial attack — meaning their immune cells are not as depleted in the first stages of infection — then studies suggest they are more likely to survive the disease.

"The patients that survive it best are the ones who don't get such a bad [immune] deficiency," Gatherer told Live Science.

But if the body is not able to fend off this attack, then the immune system becomes less able to regulate itself, Gatherer said. This means the immune system is more likely to run out of control and release a "storm" of inflammatory molecules, which cause tiny blood vessels to burst, leading in turn to a drop in blood pressure, multi-organ failure and eventually death.

The current Ebola outbreak — which is in Guinea, Sierra Leone and Liberia — has infected at least 1,603 people, including 887 who have died, according to the World Health Organization, making it the largest outbreak in history.

Another marker linked with people's ability to survive Ebola is a gene called human leukocyte antigen-B, which makes a protein that is important in the immune system. A 2007 study found that people with certain versions of this gene, called B*07 and B*14, were more likely to survive Ebola, while people with other versions, called B*67 and B*15, were more likely to die.

Finally, some people may be resistant to Ebola infection entirely, if they have a mutation in a gene called NPC1. Studies show that, when researchers take cells from people with the NPC1 mutation and try to infect them with Ebola in a laboratory dish, these cells are resistant to the virus.

In European populations, about 1 in 300 to 1 in 400 people have this mutation, Gatherer said. But in some populations, this mutation is more common: in Nova Scotia, between 10 and 26 percent of people have this mutation, Gatherer said. But the frequency of this mutation in African populations is not known, he said.

However, because these studies on Ebola resistance were done in a lab, it's not known for certain if carriers of the NPC1 are truly resistant to Ebola.

Gatherer said that, hopefully, samples are being collected in the current outbreak so that researchers can conduct studies to better understand the virus and how to survive it.


http://news.yahoo.com/people-survive-ebola-233906237.html

[Buster's Uncle]

Are Experimental Ebola Treatments Ethical?
LiveScience.com
By Rachael Rettner, Senior Writer  4 hours ago



Ebola virus



The ethics of using experimental Ebola treatments — which have unknown risks, and unproven benefits —  will be discussed next week by a panel of experts, in light of the ongoing outbreak of the deadly virus in West Africa, according to the World Health Organization.

The panel is being convened by WHO following reports that two American patients with Ebola received an experimental treatment for the disease, called ZMapp (developed by Mapp Biopharmaceutical Inc. in San Diego). The news has raised questions about whether experimental treatments that have not yet been shown to be safe or effective should be used and, if so, who should receive such treatments, WHO said.

The Centers for Disease Control and Prevention has said that there is a very limited supply of ZMapp, and the treatment will not be available for general use.

"We are in an unusual situation in this outbreak. We have a disease with a high fatality rate without any proven treatment or vaccine," Dr. Marie-Paule Kieny, assistant director-general at the World Health Organization, said in a statement. "We need to ask the medical ethicists to give us guidance on what the responsible thing to do is."

The current Ebola outbreak — which is in Guinea, Sierra Leone and Liberia — is the largest in history, and has killed at least 932 of the more than 1,700 people infected to date, according to the World Health Organziation.


http://news.yahoo.com/experimental-ebola-treatments-ethical-212737188.html

[Buster's Uncle]

Obama says lacks sufficient data to fast-track Ebola drug
Reuters
3 hours ago



S. President Barack Obama delivers remarks at the first Leaders Session of the U.S.-Africa Leaders Summit at the State Department in Washington, August 6, 2014. REUTERS/Larry Downing



WASHINGTON (Reuters) - President Barack Obama said on Wednesday he lacks enough information to green-light a promising drug to treat the deadly Ebola virus and that the initial response should focus on public health measures to contain the outbreak.

"We've got to let the science guide us and I don't think all the information is in on whether this drug is helpful," the president said at a media conference. "The Ebola virus both currently and in the past is controllable if you have a strong public health infrastructure in place."

Public health officials should do all they can to contain the outbreak, and during the course of that process, authorities can assess whether new drugs or treatments can be effective, he said.

"We're focusing on the public health approach right now, but I will continue to seek information about what we're learning about these drugs going forward," he said.

(Reporting By Mark Felsenthal; Editing by Sandra Maler)


http://news.yahoo.com/obama-says-lacks-sufficient-data-fast-track-ebola-224218799.html