The Ebola connection
The Ebola connection
By Michael Howell
The front cover of a recent issue of Bloomsberg Businessweek declared in red letters that looked something like smeared blood, “EBOLA IS COMING.”
Dr. Vincent Racaniello, Professor of Virology at Columbia University Medical Center, blogged soon after, “Although the article presents a good analysis of the hurdles in developing antibody therapy for Ebola virus infection, the cover is overstated. Why does Businessweek think that Ebola virus is coming to the US?”
We may not know why Businessweek thought Ebola was coming to the U.S., but now that Thomas Duncan has landed in Dallas, we do know it was correct.
The Star recently spoke with scientists at the Rocky Mountain Laboratory in Hamilton where research and development of an Ebola vaccine has been in the works for several years.
Ebola jumped from the hotbed of its latest outbreak in West Africa to the U.S. when Duncan, who traveled to Dallas from Liberia, was found to have Ebola. The Centers for Disease Control (CDC) and Prevention reported the incident on September 30.
According to a Q&A article in the New York Times, Duncan was screened for fever before boarding the plane – a standard airport procedure in Liberia – and showed no symptoms at that time. He arrived in Dallas on September 20. By September 24, he was developing symptoms and the next day went to the hospital. He was sent home but returned on the 28th and was placed in isolation. On the 30th, the CDC issued a statement saying he had tested positive for Ebola. As of Monday, Duncan was in critical condition in a Dallas hospital and it was being reported that his condition was worsening.
According to the NYT article, “Ebola spreads through direct contact with body fluids. If an infected person’s blood or vomit gets in another person’s eyes, nose or mouth, the virus may be transmitted. Ebola does not invade through healthy skin, but skin must be sanitized after potential contact to avoid spreading the virus by touch. Although Ebola does not cause respiratory problems, a cough from a sick person could infect someone who has been sprayed with saliva. Because of that, being within three feet of a patient for a prolonged time without protective clothing is considered to be direct contact. ” The virus can survive for several hours on surfaces, so any object contaminated with bodily fluids, like a latex glove or a hypodermic needle, may spread the disease. According to the CDC, the virus can survive for a few hours on dry surfaces like doorknobs and countertops. But it can survive for several days in puddles or other collections of body fluid at room temperature. Bleach solutions can kill it. “In the current outbreak, most new cases are occurring among people who have been taking care of sick relatives or who have prepared an infected body for burial. Health care workers are at high risk, especially if they have not been properly equipped with protective gear or correctly trained to use and decontaminate it,” reports the NYT.
Will the events in Dallas lead to a bloody scourge in this country, as the cover of Businessweek suggests? Probably not, according to the experts. Ebola is a form of hemorrhagic fever and, at its worst, may end in the kind of uncontrollable bleeding that has sparked fear and panic in the public. But it is not as easily transmissible as some other deadly diseases that can move through the air. Instead, it takes contact with the body fluid of an infected person. Simple hygiene measures, such as washing hands with bleach, which kills the virus, and the use of personal protective equipment, such as gloves and masks, do work as effective countermeasures. You could add to this not messing with bats, not eating jungle meat which may be contaminated by bat droppings or saliva, and not touching anyone who is infected. It is because of the proven effectiveness of these simple countermeasures that experts do not expect the disease to sweep through the U.S. like it has in West Africa, since most U.S. cities are better prepared to implement the necessary countermeasures to contain the disease. Health officials from CDC have said they are confident that standard procedures for controlling an infection will contain Ebola in the United States.
The problem in West Africa has been in implementing some of the simplest countermeasures, in the face of widespread ignorance, fear, even hysteria, related to the disease.
As was stated in the NYT article, “In some parts of West Africa, there is a belief that simply saying ‘Ebola’ aloud makes the disease appear. Such beliefs have created major obstacles for physicians trying to combat the outbreak. Some people have even blamed physicians for the spread of the virus, opting to turn to witch doctors for treatment instead. Their skepticism is not without a grain of truth: In past outbreaks, hospital staff members who did not take thorough precautions became unwitting travel agents for the virus.”
Another problem with containing the disease in West Africa has been the customary burial practices that involve contact with the dead person’s body.
Although many people’s eyes are riveted on the unfolding developments in West Africa and now in Texas, there are several pairs of eyes here in Hamilton that have been looking closely at the Ebola virus for several years.
Because of its high case fatality rate and the absence of licensed vaccines or treatments, work on this virus is restricted to a few high containment laboratories worldwide. The little city of Hamilton happens to be home to one of those labs.
Ebola first came to Rocky Mountain Lab in Hamilton soon after the new Bio-safety Level 4 lab was built. It arrived in a major way in 2008 when Dr. Heinz Feldmann, an expert in viral hemorrhagic fevers and emerging viruses, and a team of associated researchers relocated here from Winnipeg, Canada. They brought in vials of Ebola, one focus of their varied research, to Hamilton. The vials are, of course, contained within the super-sealed walls of a state-of-the-art Bio-safety Level 4 maximum containment facility. The doctors don’t live in fear of contracting the disease and they don’t believe that it has much chance of getting out of the lab.
Dr. Feldmann and some of his colleagues, including Dr. Andrea Marzi who we interviewed for this story, are at the cutting edge in the development of a vaccine against the virus. They have been performing experimental trials for over six years at RML and announced in January 2013 that a vaccine had been developed that can protect nonhuman primates from Ebola infection.
According to an NIH news release at the time, several research groups had developed experimental vaccine approaches that would protect nonhuman primates from Ebola virus and the closely related Marburg virus. But how the vaccines were working remained a lingering question. Were they boosting an immune response to attack the virus? Or were they eliciting antibodies that block the infection?
The results, published by A. Marzi et al in 2013, showed that important immune cells had a minimal role in providing protection, while antibodies induced by the vaccine appeared critical to protecting the animals.
The next step would be clinical experiments on humans, but that step was slow in coming. A phase I clinical trial with the vaccine only began last month, in part due to the unprecedented proportions of the current outbreak in West Africa.
Ebola has been around in the animal reservoir, primarily in fruit bats, for thousands of years, but once transferred to a human it is fatal in anywhere from 60% to 90% of cases depending on the outbreak. It was first identified as the culprit in a fairly large outbreak in the Democratic Republic of Congo and Sudan in 1976 in which a little over 300 people were infected and most of them died. This was followed by outbreaks in Sudan in 1979 and, after a long lull, in Gabon in 1994. Infection rates were very low in comparison, but death rates among the infected were high. Between 1976 and 2012, twenty outbreaks in different Central African countries were reported. Most involved less than 100 infections before the outbreak subsided.
Then came 2013 and the current outbreak in West Africa and the numbers are going off the chart. According to the World Health Organization’s Ebola Response Roadmap Update, the current outbreak, which started in the village of Meliandou, Guinea, when a two year old child was infected in December 2013, had spread to over 3,000 people by August 27, 2014 and 1,400 of them had died. By September 26, the number of infected had grown to 6,553 infections, 3,083 resulting in death. As of September 23, 375 health care workers were known to have been infected. Overall total infections as of the end of the month were close to 7,400 and 3,400 had died.
It is currently estimated that the number of infections is doubling every three weeks. In August the WHO projected that the outbreak could ultimately affect up to 20,000 people. By the end of September they were estimating 20,000 as a best case scenario and the worst case scenario had grown to a potential 1.4 million infections over the next four months.
CDC Director Dr.Thomas R. Frieden said, “My gut feeling is, the actions we’re taking now are going to make that worst-case scenario not come to pass. But it’s important to understand that it could happen.”
Since proving the efficacy of the vaccine on nonhuman primates, Dr. Feldmann and his co-workers have had to wait for years to have it tested on humans. But due to the small number of people ultimately being affected in the historical outbreaks, it was hard to get the pharmaceutical companies, who were looking at a huge expense with little chance for profit, interested in producing the vaccine. Government funding was also difficult to come by for the same reasons.
But times are changing. The numbers are mounting and the outbreak is now getting world attention and the first clinical trials were finally funded in the last month. But still, it is very unlikely that the vaccine could be produced in the quantities and the speed needed to address the current outbreak.
In a recent article published by BMC Biology, “Ebolavirus in West Africa, and the use of experimental therapies or vaccines” [Hoenen T and Feldmann H. Ebolavirus in West Africa, and the use of experimental therapies or vaccines. BMC Biolgy 2014 12:80], Dr. Feldmann, despite the long years of frustration at not getting any clinical trials funded, advises against using the vaccine or other untested therapies in the current crisis until those trials are complete.
Feldmann notes that the World Health Organization has made a declaration to ethically approve the use of the experimental treatments and vaccines under certain circumstances.
“However, one needs to remain realistic regarding what can be done during the current outbreak, given both the extremely limited amount of clinical grade material that is available and the lack of human safety data for any of the promising experimental drugs and vaccines.
“Clearly, improving the chances of survival of an infected patient is highly desirable. Improved survival might also help to change a perception in the population that isolation wards are death traps rather than medical care facilities… However, because of the general lack of human safety and efficacy data for these experimental drugs and vaccines there is a risk of adverse effects and/or ineffectiveness, which could result in the perception that developed countries are experimenting on African patients.”
So, if it is not possible to rush in with treatments and vaccines, what can be done?
The main strategy for outbreak management focuses on the reduction of secondary transmission by isolating infected individuals, the implementation of safe burial practices, contact tracing to disrupt infection chains, and education of the local population regarding risk reduction.
“From a public safety perspective, this strategy is paramount,” state Hoenen and Feldmann.
Rocky Mountain Laboratory is helping to implement that strategy and, since the end of August, has been sending three-person teams on three week stints to provide on-the-ground services, which amount to trying to isolate the infected, keep them alive, and take lots of blood samples to look for positive or negative results for Ebola.
This is what Dr. Andrea Marzi did on a recent team visit to Liberia, analyzing anywhere from 30 to 70 blood samples a day for 20 days straight. She worked in a tent clinic provided by Doctors Without Borders.
Dr. Marzi said that the huge distrust of foreign health care workers that was so evident at the beginning of the outbreak was getting better. She said in the beginning people didn’t believe there was any Ebola, they took it as a hoax. But she believes the educational campaign to convince the people that Ebola is real has been working. As has the campaign to institute strict hygiene and other highly successful countermeasures as well as an increased supply and access to personal protection equipment, such as protective gloves and masks.
Officials have emphasized that people are infectious only if they have symptoms of Ebola. There is no risk of transmission from people who have been exposed to the virus but are not yet showing symptoms. Dr. Thomas R. Frieden, director of the Centers for Disease Control and Prevention, said the odds of contracting Ebola in the United States were still extremely low. Marzi is looking forward to her next trip to West Africa.
“For me personally, it’s very rewarding,” she said. She said that she has been working on Ebola for a long time to create a vaccine that could be very useful in handling future outbreaks, “but this is a chance to do what I can to make a little bit of difference on the ground right now.” She called being there on the ground “the experience of a lifetime.”
She recalled the experience she had with an Ebola victim who survived and was declared clean when his blood test came back negative. They held a celebration and gave him an “Ebola-free” certificate as part of a new program aimed at helping Ebola survivors reintegrate into their family and society.
Marzi said that in the beginning of the epidemic people who got infected were often shunned and ostracized by their community and not allowed to return. She said the new program of giving out official certificates designating the holder as guaranteed Ebola-free was having some positive effect. She said the educational campaign about the effectiveness of simple hygiene like washing hands with bleach and by providing washstands all over the place was also having some positive effect, in her view.
She also witnessed some incredible acts of bravery and devotion. One woman, whose two children had tested positive for Ebola while her own blood test had come back negative, refused to leave her children. She said the woman was given gloves, mask and a gown and washed often. After two follow up blood tests she was still showing negative and still caring for her children when Dr. Marzi’s three-week stint came to an end.
Dr. Marshall Bloom, Associate Director for Scientific Management, clarified that RML does not assign doctors to travel overseas and fight infections. Each person from the lab that is involved is a highly qualified individual volunteering to work for a sponsoring entity, such as the World Health Organization or Doctors Without Borders.
As far as being able to deal with an Ebola outbreak if one should occur here in Hamilton, RML has the good fortune of having three highly secure quarantine rooms available at St. Patrick’s hospital in Missoula.
“The facility at St. Pat’s is the Cadillac version of what’s required,” said Bloom, “but any community hospital in America would be capable of safely caring for a patient.” He said cases of similar, but not identical, infections have been successfully handled at community hospitals in the state and around the country.
As far as the volunteer work some of his associates are doing in West Africa, he said, “A large number of people have asked about RML’s involvement in the recent outbreak. Uniformly, people are taking pride in the fact that our community is able to assist in this unprecedented outbreak and attendant humanitarian crisis.”
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