Ebola Drug Trial Has Encouraging Early Results, and Questions Follow

An Ebola treatment center run by the Alliance for International Medical Action has tested the drug favipiravir. Credit Sylvain Cherkaoui/Cosmos for ALIMA Sylvain Cherkaoui/Cosmos for ALIMA

For the first time, a drug is showing promising signs of effectiveness in Ebola patients participating in a study. The medicine, which interferes with the virus’s ability to copy itself, seems to have halved mortality — to 15 percent, from 30 percent — in patients with low to moderate levels of Ebola in their blood, researchers have found. It had no effect in patients with more virus in their blood, who are more likely to die.

The drug, approved as an influenza treatment in Japan last year, was generally well tolerated.

“The results are encouraging in a certain phase of the disease,” Dr. Sakoba Keita, director of disease control for the Guinean Ministry of Health, said in a telephone interview. The drug is being tested in Guinea, one of the three West African countries most affected by the Ebola crisis.

The early findings have not yet been announced, but they raise questions about which patients, if any, outside the study should be offered treatment with the drug, favipiravir. “These are very difficult, agonizing decisions,” said Susan Ellenberg, a professor of biostatistics at the University of Pennsylvania’s Perelman School of Medicine, who was not involved in the research. She cautioned that early results were sometimes not borne out.

Avigan, a drug approved as an anti-influenza drug in Japan, is showing promise in treating ebola. Credit Issei Kato/Reuters Issei Kato/Reuters

The drug has been provided on an emergency basis to Ebola patients in European countries, but not in Africa. The Japanese maker of the drug announced in October that it had 20,000 courses of treatment in stock. The epidemic is now ebbing but is not over. The World Health Organization on Wednesdayreported 124 new cases in Guinea, Sierra Leone and Liberia in the week that ended on Sunday, warning of an increased geographical spread in Guinea and a rise in new cases in all three countries for the first time this year.

Early reports of the interim results of the drug trial have created unanticipated complications, delaying the testing of at least one other therapy as researchers reconsidered plans and some doctors pressed to make favipiravir more widely available.

Researchers and health authorities have been quietly debating whether and when to release the preliminary results of the study. The dilemmas they face echo those from the early years of the AIDS epidemic. Because mortality was so high in a disease with no proven treatment, there was demand to provide experimental therapies to everyone.

The results for the drug favipiravir are based on an analysis of 69 patients older than 14 who have received it at two sites in Guinea since December. The survival rates of those with low to moderate levels of virus in their blood were significantly better than those of patients previously treated at a center run by Doctors Without Borders in Guéckédou, Guinea.

Caroline Guele, 31, a rice farmer who lost two children and her husband to Ebola, received the drug in January at the site run by the Alliance for International Medical Action soon after she developed symptoms. She said she believed it contributed to her survival. “When I heard I could take the medicine, I actually prayed to God it would help me,” she said in a telephone interview Wednesday.

In a typical drug study, participants would be randomly assigned to take the drug or not, and the outcomes would be compared to see if the drug made a difference. However, because Ebola is so deadly and there is no known treatment aside from supportive care, all patients in the study were provided with the treatment. Fluctuating death rates during the current epidemic have complicated researchers’ efforts to assess whether the new drug should be credited with the reduced mortality.

The drug was expected to be most effective in patients receiving it within two to three days of showing symptoms, similar to antiviral treatments for influenza. However, most study participants arrived at the Ebola treatment units later in their illnesses, a median of five days after their symptoms began, so results were analyzed instead in terms of the approximate levels of virus in the blood.

Independent boards charged with monitoring the drug trial detected the encouraging findings and recommended that they be made public. Results were submitted for review to the Conference on Retroviruses and Opportunistic Infection, which will take place in Seattle at the end of the month. A draft of an abstract of the findings was reviewed by The New York Times.

“With Ebola, there’s precious little good news,” said Dr. Susan Shepherd, who served as medical coordinator at a treatment unit run by the Alliance for International Medical Action, one of two sites where the drug was tested. (The other was a facility run by Doctors Without Borders.)

Dr. Shepherd added, “There will, I think, be an enormous pressure and desire to offer the treatment more broadly.”

A patient is treated at the ALIMA ebola treatment center in Nzerekore, Guinea. Credit Sylvain Cherkaoui/Cosmos for ALIMA Sylvain Cherkaoui/Cosmos for ALIMA

The trial is sponsored by the French public research institute Inserm, with support from the European Union, and is run by a consortium of organizations and the Guinean government. The drug, also known by the trade name Avigan, was developed by the Japanese company Toyama Chemical, part of Fujifilm Group, and approved for influenza treatment in that country last March after safety testing.

The company has said it would produce more doses of the drug in anticipation of the trial. It has also provided the tablets on an emergency basis to several Ebola patients in Europe, according to a company spokeswoman, Kana Matsumoto. She said that the drug had never been provided on that basis to patients in any African country, and that the company had no comment as to whether it would do so in the future given the new findings.

“With a medication that seems to be safe, you really don’t have a leg to stand on in terms of this person gets it and this person doesn’t,” Dr. Shepherd said. “The problem we seem to have is it doesn’t help at all for people who have high viral loads.”

Researchers hope that some patients’ lives might be saved by bolstering the immune system, including through transfusions of serum extracted from the blood of Ebola survivors, which contains virus-fighting antibodies.

However, expectations around favipiravir have contributed to a delay in a trial of serum transfusions, also known as convalescent plasma therapy, in Guinea’s capital, according to Roeland Scholtalbers, the head of communications for the Institute of Tropical Medicine in Antwerp, Belgium, the study’s sponsor.

Some doctors are urging that if favipirivir has a positive effect and seems safe, it should be given to everyone with the virus.

If patients getting the serum transfusions also get favipiravir, it would probably be more difficult to discern whether the serum had an effect. Mr. Scholtalbers said that just because early results for favipiravir came first did not mean that researchers or the public should “put more hope on that solution than any other solution.”

“There are pretty good arguments to think that plasma can give good impact,” she continued. “It will be a shame if we don’t manage as a scientific community to test it.”

Dr. Xavier Anglaret, the lead investigator of the favipiravir trial in Guinea, said that he and his colleagues agreed that the other study was important. “The plasma trial should start as early as possible,” he said.

Both trials are all the more important because of the abrupt cancellation last Friday of a study testing a third therapy, the anti-viral drug brincidofovir, after the manufacturer found an insufficient number of Ebola patients in Liberia, where the trial had been planned, to determine the effectiveness of the drug.

Dr. Anglaret said researchers had expected to have results from all three studies around the same time. Instead, one study advanced ahead of the others, with early results that are encouraging but not definitive. As of Tuesday, Dr. Anglaret said, the favipiravir trial had enrolled 101 patients in the continuing study.

The complications of managing the Ebola trials are a sign that more needs to be done to prioritize research in future outbreaks, said Dr. Bernard Lo, a bioethicist and president of the Greenwall Foundation in New York City.

Ebola Drug Trial Has Encouraging Early Results, and Questions Follow

8:48 AM DRUG FOR EBOLA, EBOLA, EBOLA cure, Preventing Ebola

EBOLA treatment: Convalescent plasma therapy (CPT) Gaining Momentum

Convalescent plasma therapy (CPT)

This is not new but old techniques, but seriously discussing and researching now a day. A couple of days back NPG reported about the ongoing clinical research in CPT. The CPT, earlier really helped to reduce the fatality of N1H1 victims. Now the same approach is trying with EBOLA victims. 

Clinical trials of convalescent plasma therapy (CPT) have started in the past few weeks in Liberia, and are due to begin soon in Guinea and Sierra Leone. If the therapy saves lives, the approach could quickly be scaled up. 

Success would also raise awareness of CPT’s potential to treat other new and emerging infectious diseases for which there are no readily available effective drugs or vaccines, such as SARS, avian influenza and Middle East respiratory syndrome (MERS). “Clinical trials of convalescent plasma should be considered in other emerging infections,” says David Heymann, an infectious-disease researcher at the London School of Hygiene and Tropical Medicine, and chair of Public Health England. 

What is Convalescent plasma therapy (CPT) ?

Basically this is a plasma transfusion treatment. The plasma will be collected from patients who recovered from the infection. Only plasma with a high neutralizing antibody will e used. The treatment involved an infusion of 500 mL of plasma over a four-hour period on day two of the stay in the intensive care unit. To the extent possible, the treatment and control groups were matched by age, sex, comorbidities, and disease severity at ICU admission. 

Nonetheless, patients in the treatment group had more risk factors for severe disease, including a lower lymphocyte count, greater prevalence of obesity, and presentation with more severe symptoms. 

Convalescent plasma therapy, which is safer now than in the early half of the 20th century because of donor screening, virological and microbiological testing, and apheresis, may have some advantages over antivirals.

Collecting convalescent plasma presents some feasibility issues during the course of an epidemic because the plasma will not be available at the beginning of the outbreak.

Convalescent plasma therapy (CPT) Gaining Momentum

Many scientists have long argued that CPT has been wrongly neglected, both as a therapy for emerging diseases and in preparation for future unknown threats. Today, the approach is gaining ground. Trials of convalescent plasma are beginning for the treatment of patients with MERS, which has infected 938 people and killed 343 of them since it was discovered in 2012. And an international protocol aimed at removing hurdles to quickly rolling out trials of convalescent plasma has recently been drafted.

CPT Where and When ?

Convalescent plasma was found to effectively treat diphtheria and tetanus at the end of the nineteenth century, and was widely used in the first half of the twentieth century to treat diseases such as measles, mumps and pneumonia. But it fell off the radar after the development of antibiotics, antiviral drugs and vaccines. (An exception was the adoption of CPT in Argentina for Argentine hemorrhagic fever after a successful controlled trial in the 1970s.)

When available , vaccines and drugs are the best option. CPT is a lengthy and risky procedure, and may be not able to cover a large population with ease. In other case , drugs and vaccine can be mass produced and easily applied during and out break.

CPT is more complicated — it requires collecting survivors’ blood, screening it for pathogens and then organizing patient transfusion. And standardizing batches of plasma is difficult, because antibody levels in donated blood can vary widely.

But an epidemic or pandemic of a new pathogen turns that logic on its head. As in the case of the Ebola epidemic, there are typically no drugs or vaccines available, and developing these usually takes years. By contrast, “convalescent plasma is one of the few things you can get up and running quickly”, says Calum Semple, a paediatrician and clinical virologist at the University of Liverpool, UK, who is involved in the Guinea Ebola trial. Trials for Ebola and other emerging diseases “should have happened years ago”, he adds. He points out that the therapy is often considered old-fashioned and that there are neither big profits to be made nor cutting-edge-science interests at stake. “Convalescent plasma is not attractive to pharma, or the modern model of academia,” he says.

Adequate screening for pathogens in donated blood can be an issue in poorer countries. In the CPT Ebola trials, a chemical is being added to the donated blood. When the mixture is exposed to ultra­violet light, the compound irreversibly crosslinks the DNA and RNA of pathogens, preventing their replication.

Hope advancement in CPT may bring control over new epidemic outbreaks. Hope the human race may gain the ability to stand with their own mistakes.

EBOLA treatment: Convalescent plasma therapy (CPT) Gaining Momentum

12:26 PM Convalescent plasma therapy (CPT), CPT, EBOLA cure, MERS, plasma therapy

Ebola Gorilla Vaccine Could Prevent Human Outbreak

Ebola The Deadly Virus

In a podcast on today 13^th Oct 2014 on Scientific America by David Biello, stating the possibility of preventing Ebola outbreaks in Human by vaccinating Gorilla against Ebola. The first line of statement is little odd but on continue listening, I understood the meaning behind the statement.

Vaccination For Ebola

Humans are not only the victim of deadly Ebola virus. Chimps and Gorillas are also susceptible to the disease.  He stated that, the current Ebola epidemic may have started with the butchering of an infected          fruit bat.  But we cannot avoid the possibility from Chimpanzee, which found dead in the forest and eaten by people, who cannot afford to pass up a free meat.

Connection Between Ebola And Apes

Ebola has killed thousands of great apes. Some 95 percent of gorillas who become infected die. Several previous outbreaks of Ebola in central Africa stemmed from dead gorillas or chimps found in the forest and butchered for food. All it takes to start an epidemic is infected blood getting in a person’s eye, mouth or open wound.

That's why veterinarians from the Wildlife Conservation Society and other conservation organizations may prove to be the front line for defending humans against Ebola.

  

Like their physician counterparts, vets are hoping to develop a vaccine, perhaps to be administered orally. At the very least, monitoring Ebola outbreaks in apes could provide early warning for potential human outbreaks. By saving the apes we may be saving ourselves.

Ebola Gorilla Vaccine Could Prevent Human Outbreak

4:58 PM EBOLA cure, Ebola Vaccination, Preventing Ebola

Artificial Biospleen to Filter the Blood

Biospleen to Filter the Blood

The recent issue of Nature reported the development of a high-tech methodology to clean up the body from infection even if the causative pathogen is unknown. This device inspired by the Spleen to clean up the blood quickly and easily. This can be mentioned as an ‘artificial Biospleen’ to clean up the blood.

Knowing about Spleen

The spleen is the organ that is responsible for purifying the blood as well as storing blood cells. It is positioned in the superior abdomen, and is the largest lymphatic organ in the body. The spleen serves a valuable role in immune function because it purifies the blood and helps the immune system with recognize and attack foreign antibodies and disease. The spleen is composed of the red and white pulp. The white pulp produces and grows immune cell as well as blood cells. On the other hand, the red pulp is responsible for purifying the blood and removing dead or old blood cells.

Application of Artificial Biospleen

Infection in blood is difficult to identify and cure. Usually more than 50% of time physicians treat this by antibiotic which attack on broad range of pathogens. This approach is not always effective, and can lead to antibiotic resistance in bacteria.

In search of a way to clear any infection, a team led by Donald Ingber, a bioengineer at the Wyss Institute for Biologically Inspired Engineering in Boston, Massachusetts, developed an artificial 'biospleen' to filter blood.

The filtering technology

Scientist used modified version of Mannose binding Lectin (MBL). a protein found in humans that binds to sugar molecules on the surfaces of more than 90 different bacteria, viruses and fungi, as well as to the toxins released by dead bacteria that trigger the immune overreaction in sepsis.

The researchers coated magnetic nanobeads with MBL. As blood enters the Biospleen device, passes by the MBL-equipped nanobeads, which bind to most pathogens. A magnet on the Biospleen device then pulls the beads and their quarry out of the blood, which can then be routed back into the patient.

Testing of the Biospleen in infected rats showed that 90% of pathogens cleaned by the device in 5 hours. The researchers then tested whether the Biospleen could handle the volume of blood in an average adult human — about 5 litres. They ran human blood containing a mixture of bacteria and fungi through the Biospleen at a rate of 1 litre per hour, and found that the device removed most of the pathogens within five hours.

The Biospleen could also help to treat viral diseases such as HIV and Ebola, in which survival depends on lowering the amount of virus in the blood to a negligible level. This may be a future breakthrough device to save human life. 

Artificial Biospleen to Filter the Blood

3:10 PM Artificial spleen, Biospleen, Blood cleaning, Blood filtration, Disease treatment, EBOLA cure, HIV cure, Pathogen, spleen