Showing posts with label EBOLA. Show all posts
Showing posts with label EBOLA. Show all posts

Thursday, July 9, 2015

Ebola is back in Liberia more than a month after the country thought it was rid of the virus.
A 17-year-old man died on June 29 of a fever illness that was being treated as malaria. As part of Liberia’s Ebola surveillance, swabs from the young man were collected by a safe burial team. Tests revealed that the young man died of Ebola, the World Health Organization (WHO)announced July 3.
Two of the nearly 200 people who came in contact with the young man have also developed Ebola symptoms and have been found to carry the virus. Other contacts are being monitored.
Liberia was declared Ebola-free on May 9 after 42 days without a new case. It is not known how the young man became infected.
To date 27,573 people have contracted Ebolaand 11,246 have died. Most of the cases have occurred in Sierra Leone, Liberia and Guinea.
report issued July 7 by a panel that analyzed the global response to the Ebola outbreak says the WHO and its member states were ill-equipped to handle the epidemic and must make changes to safeguard public health.

New cases of Ebola emerge in Liberia

Friday, June 5, 2015

Zoloft and another drug keep most mice alive after infection with the virus

UNLIKELY CANDIDATE  The antidepressant drug Zoloft and another approved medication might fight the Ebola virus (shown). 

C. Bickel/Science Translational Medicine

The fearsome Ebola virus may itself fall victim to two already approved medications — the antidepressant drug Zoloft and a drug for patients with heart problems.

Researchers tested roughly 2,600 compounds and found 30 approved drugs with some capacity to fight the virus in lab-dish tests. The team tested several of these drugs in mice and found that Zoloft, also called sertraline,and the heart drug marketed as Vascor protected the animals best. Seven of 10 mice exposed to the virus and inoculated with Zoloft one hour later survived, as did all 10 given Vascor, a calcium channel blocker also called bepridil. The drugs block viral entry into cells, the team reports in the June 3 Science Translational Medicine.

The researchers plan to further test the drugs against Ebola, which has a high fatality rate and no known cure.

Citations

L. M. Johansen et al. A screen of approved drugs and molecular probes identifies therapeutics with anti-Ebolavirus activityScience Translational Medicine. Vol. 7, June 3, 2015, p. 290ra89.

An antidepressant may protect against Ebola

Monday, May 11, 2015

After Nearly Claiming His Life, Ebola Lurked in a Doctor’s Eye
Before he contracted Ebola, Dr. Ian Crozier had two blue eyes. After he was told he was cured of the disease, his left eye turned green. Credit Emory Eye Center Emory Eye Center
ATLANTA — When Dr. Ian Crozier was released from Emory University Hospital in October after a long, brutal fight with Ebola that nearly ended his life, his medical team thought he was cured. But less than two months later, he was back at the hospital with fading sight, intense pain and soaring pressure in his left eye.
Test results were chilling: The inside of Dr. Crozier’s eye was teeming with Ebola.
His doctors were amazed. They had considered the possibility that the virus had invaded his eye, but they had not really expected to find it. Months had passed since Dr. Crozier became ill while working in an Ebola treatment ward in Sierra Leone as a volunteer for the World Health Organization. By the time he left Emory, his blood was Ebola-free. Although the virusmay persist in semen for months, other body fluids were thought to be clear of it once a patient recovered. Almost nothing was known about the ability of Ebola to lurk inside the eye.
Despite the infection within his eye, Dr. Crozier’s tears and the surface of his eye were virus-free, so he posed no risk to anyone who had casual contact with him.
More than a year after the epidemic in West Africa was recognized, doctors are still learning about the course of the disease and its lingering effects on survivors. Information about the aftermath of Ebola has been limited because past outbreaks were small: no more than a few hundred cases, often with death rates of 50 percent to 80 percent. But now, with at least 10,000 survivors in Guinea, Liberia and Sierra Leone, patterns are emerging.
A Secondary Problem
Dr. Crozier, 44, ruefully calls himself a poster child for “post-Ebola syndrome”: Besides eye trouble, he has had debilitating joint and muscle pain, deep fatigue and hearing loss. Similar problems are being reported in West Africa, but it is not clear how common, severe or persistent they are. There have even been reports of survivors left completely blind or deaf, but these accounts are anecdotal and unconfirmed.
Doctors say the eye problems, because they threaten sight, are the most worrisome part of the syndrome and most urgently need attention. Dr. Crozier’s condition, uveitis — a dangerous inflammation inside the eye — has also been diagnosed in West Africans who survived Ebola.
At the height of the epidemic, health workers were too overwhelmed with the sick to worry much about survivors. But as the outbreak wanes, the World Health Organization has begun to gather information to help those who have not fully recovered, said Dr. Daniel Bausch, a senior consultant to the W.H.O. and an infectious-disease specialist at Tulane University. He added that the reports of eye trouble were of particular concern.
“It’s a major thing we need to study and provide support for,” Dr. Bausch said. But there are hardly any ophthalmologists in West Africa, and only they have the skills and equipment to diagnose conditions like uveitis that affect the inner chambers of the eye.
At ELWA Hospital in Monrovia, Liberia, run by the missionary group SIM, Dr. John Fankhauser, the medical director, said chronic pain, headaches and eye trouble were the most common physical problems among the hundred or so people attending a special clinic for Ebola survivors. Some have such severe pain that they find it hard to walk, he said. About 40 percent have eye pain, inflammation,blurred vision and blind spots in their visual fields. Some have uveitis.
“We’re seeing symptoms in patients who’ve been out of the treatment unit for up to nine months,” Dr. Fankhauser said. “They’re still very severe and impacting their life every day.” These patients will need medical care for months and maybe years, he predicted.
Dr. Fankhauser said he hoped that specialists in ophthalmology, rheumatology and rehabilitation medicine would visit.
Dr. Crozier's eyes were examined again on March 27 by Dr. Yeh at Emory Eye Center in Atlanta. Eye troubles are common among Ebola survivors. Credit Kevin Liles for The New York Times Kevin Liles for The New York Times
“If they see enough patients, they can help us with the trends of what they are seeing, and that may help direct some of our therapy in the future, even after the team’s gone,” he said.
In Sierra Leone, the picture is much the same, according to Dr. John S. Schieffelin, a physician from the Tulane University School of Medicine who volunteered there. He said a strong, well-organized survivor group met regularly in Kenema.
“The main problems they’re telling me about are lots of body and joint pains, chronic headaches and women who stopped having menstrual periods, and for some it’s been several months,” Dr. Schieffelin said. “There’s quite a bit of vision problems.”
He added, “I have met one former patient that does appear to be deaf.”
The hearing loss could result from brain inflammation or very low blood pressure for an extended period, both caused by Ebola, Dr. Schieffelin said.
Alarming Test Results
When Dr. Crozier’s eye trouble began, he and the Emory team suspected that Ebola had weakened his immune system and left him vulnerable to some other virus that had invaded his eye, maybe one that would be treatable with an antiviral drug.
So Dr. Steven Yeh, an ophthalmologist, pierced Dr. Crozier’s eye with a hair-thin needle, drew a few drops of fluid from its inner chamber and sent them to the lab. The results came as a shock.
For Dr. Crozier, it was deeply unsettling to learn that he was still occupied by something that seemed alien and malevolent. “It felt almost personal that the virus could be in my eye without me knowing it,” he said.
Dr. Steven Yeh, an ophthalmologist, examined Dr. Ian Crozier in March, five months after Dr. Crozier's initial recovery from Ebola. Credit Kevin Liles for The New York Times Kevin Liles for The New York Times
Uveitis had been reported in some Ebola survivors from previous outbreaks, and a related virus, Marburg, had been recovered from one patient’s eye. But those cases had seemed uncommon.
A report about Dr. Crozier’s eye condition waspublished on Thursday in The New England Journal of Medicine.
The inside of the eye is mostly shielded from the immune system to prevent inflammation that could damage vision. The barriers are not fully understood, but they include tightly packed cells in minute blood vessels that keep out certain cells and molecules, along with unique biological properties that inhibit the immune system. But this protection, called immune privilege, can sometimes turn the inner eye into a sanctuary for viruses, where they can replicate unchecked. The testes are also immune-privileged, which is why Ebola can persist in semen for months.
Finding Ebola in Dr. Crozier’s eye threw his doctors off balance. Dr. Yeh had worn a protective gown, gloves and a mask but no goggles when he drew the fluid. Doctors wear more protective gear when treating patients known to have Ebola. He could not rule out the possibility that he had been infected, so he slept in the guest room at home and avoided touching his infant son for three weeks, the incubation period of the disease.
Another concern was the examining room where Dr. Yeh had taken the fluid sample. As soon as they got the results, he and several Emory colleagues rushed back there, verified that no one else had used the room, and disinfected every surface.
Additional tests showed that Dr. Crozier’s tears and the outer surface of his eye were Ebola-free, so he posed no danger to others. But his case suggests that doctors performing eye surgery on Ebola survivors could be at risk. It is not known how long the virus can persist within the eye.
The big question was whether the doctors could save Dr. Crozier’s sight. They worried about both eyes, because ailments in one eye can sometimes spread to the other. But there was no antiviral drug proven to work against Ebola, and even if there were, there was no precedent for treating an eye full of the virus.
In addition, the severe inflammation suggested that the barriers that normally protect the eye from the immune system had been breached. So what was damaging Dr. Crozier’s eye? The virus, the inflammation or both? They could not be sure.
The usual treatment for inflammation is steroids. But they can make an infection worse.
Dr. Crozier's left eye regained its blue color following treatment. Read more about what can cause an eye to change color. Credit Kevin Liles for The New York Times Kevin Liles for The New York Times
“What if it unleashed the virus?” Dr. Crozier said. “We were on a tightrope.”
Maybe an experimental antiviral drug would help, the doctors thought.
Weeks of Fear
Though Dr. Crozier was the patient, he was also part of his own medical team, and his focus on the scientific details helped counter his mounting fear that he was going blind.
As he and his physicians struggled to balance treating the inflammation with fighting the infection, his eyesight continued to deteriorate. They tried high doses of a steroid, prednisone. The drug caused mood swings like a teenager’s, ravenous hunger, weight gain, high blood pressure and insomnia. And still his sight worsened. It was like looking through brambles, he said. He reached a point where all he could see was movement when Dr. Yeh waggled his fingers.
He also had significant hearing loss on the same side. “The whole left side of your life is gone,” he said. “It was a very dark and depressing time.”
He spent Christmas in the hospital with his younger brother Mark, who had stayed with him constantly throughout his illness and recovery.
The pressure inside his eye, which had been dangerously elevated, began to drop — too much. The eye became doughy to the touch, as if it were turning to mush.
“The eye felt dead to me,” Dr. Crozier said.
Dr. Crozier with children at an Ebola treatment unit in Sierra Leone in September 2014.
The biggest shock came one morning about 10 days after his symptoms started, when he glanced in the mirror and saw that his eye had actually changed color. His iris, normally bright blue, had turned a vivid green. Rarely, severe viral infections can cause such a color change, and it is usually permanent.
“It was like an assault,” he said. “It was so personal.”
As the days passed with no sign of improvement, Dr. Crozier and the Emory team began to think he had little to lose. Dr. Jay Varkey, an infectious-disease specialist who had handled much of Dr. Crozier’s care, got special permission from the Food and Drug Administration to use an experimental antiviral drug taken in pill form. (The doctors declined to name it, preferring to save that information for future publication in a medical journal.) They were not even sure that the drug would find its way into Dr. Crozier’s eye.
To add to the treatment for inflammation, Dr. Yeh also gave Dr. Crozier a steroid injection above his eyeball that would slowly release the drug into his eye.
Receding Darkness
At first, there seemed to be no effect. But one morning a week or so later, Dr. Crozier realized that if he turned his head this way and that, he could find “portals” and “wormholes” through the obstructions in his eye and could see his brother Mark, who was sitting on the end of his bed.
Gradually, over the next few months, his sight returned. Surprisingly, his eye turned blue again. A video shows him excitedly calling out letters on an eye chart as he works his way down to smaller and smaller type, with his brother and the doctors standing by, laughing.
Was it the antiviral drug? He cannot be sure, but he thinks so.
“I think the cure was Ian’s own immune system,” Dr. Varkey said, explaining that he suspected the treatments had reduced Dr. Crozier’s symptoms and helped preserve his sight long enough for his immune system to kick in and clear out the virus — just as supportive care during the worst phase of his initial illness had kept him alive until his natural defenses could take over.
Dr. Crozier believes information from his case may help prevent blindness in Ebola survivors in West Africa. On April 9, he headed to Liberia with Dr. Yeh and several other Emory physicians to see patients who had recovered from Ebola and examine their eyes.
“Maybe we can change the natural history of the disease for survivors,” Dr. Crozier said. “I want to start that conversation.”

EBOLA the life of survivors

Thursday, February 5, 2015

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

 
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