Experimental Ebola Serum Likely Treating Sick Americans
Thom Lang / Corbis
May 14, 2012 -
Recent controversial experiments and a research paper that detailed how to make an airborne version of the H5N1 avian influenza virus made some people nervous. The fear is that somebody, be it a terrorist group or unethical government, could create a superbug and use it as a biological weapon. But even it the recipe for avian flu hadn't been published, there are still plenty of other viruses to choose from. To be a good biological weapon, a pathogen should be transmitted from person to person, have an incubation or contagious period long enough that the infected patient can spread it and either incapacitate or kill.
Centers for Disease Control
Smallpox Top of the list is smallpox. Historically it's had a mortality rate of 30 to 35 percent, although it was much higher, sometimes 90 percent, in populations that were never exposed to it, such as Native Americans. Smallpox is an airborne virus, which means it can be caught easily from infected people who cough or sneeze, but can also be transmitted through touch. The disease creates a fever, malaise, head and body aches and sometimes vomiting. Two to four days later, a rash develops in the mouth and throat and sores break out on the skin. This is the most contagious period. Usually the rash spreads to the entire body in 24 hours. Ironically, most people feel better at this point. The rash becomes the classic pox after about three days, in which bumps are filled with fluid. The fever rises again at this time. Over the course of another week or two the pustules scab over, and when the last one is gone, the patient is no longer contagious. Smallpox has four varieties; three are often fatal. The last naturally occurring case of the disease was in 1975, in Bangladesh. However, the virus is still in cold storage at two labs, one in the United States and the other in Russia. For now, most people in their 20s and 30s might have no immunity at all. This is especially true in developing nations whose populations are generally younger. "A new outbreak in India or South Africa, for example, would be beyond terrible," said Tara Smith, an assistant professor of epidemiology at the University of Iowa.
Michael Abbey / Visuals Unlimited / Corbis
Resistant Bacteria Diseases that have been historically treated with antibiotics are good candidates for biological weapons because many strains have become resistant to the antibiotics. Methicillin-resistant staph, or MRSA, is one of the more well-known, and is spread by physical contact. MRSA usually stays in the skin, but in some people, it infects vital organs like the heart. Some varieties have caused necrotizing fasciitis, "flesh eating disease." A drug-resistant MRSA that was immune to all of the currently known antibiotics would cause many deaths. Tuberculosis is another that has evolved drug-resistant strains. The first totally drug-resistant form was identified in 2007 in Italy and by 2010, 8.8 million people had contracted it, with 1.4 million dying. Tuberculosis is the second biggest killer behind HIV/AIDS, according to the World Health Organization. It's spread person-to-person by coughing. The bacteria multiplies in the lungs, and patients die from respiratory failure or an excess of fluid in the lungs. Artificially breeding drug-resistant bacteria is no longer that complicated, Smith said. "Antibiotic resistance genes are easy to add to almost any bug, and some plasmids already carry resistance genes for multiple classes of drugs."
Centers for Disease Control
Bubonic Plague The Black Death or bubonic plague -- officially known as Yersina pestis -- killed a third of Europe's population in the 14th century, and it still exists in some parts of the world today. It has a long history as a bioweapon: accounts of the Mongol siege of the Crimean city of Caffa in 1347 say the invaders catapulted the corpses of infected people over the walls. And it isn't just a medieval phenomenon; the last major outbreak in the United States was in 1900 in San Francisco and involved 121 people of which 113 died; cases have appeared sporadically since. The plague is transmitted by fleas, which incubate the bacterium in their gullets. The multiplying Yersina block blood from getting to the fleas' stomachs, and the starving fleas start to feed more aggressively and try to clear the blockage by regurgitating the bacteria. That transmits the disease to hosts, including humans. Symptoms appear in two to six days. The infection causes the lymph nodes to swell (the "buboes"), but sometimes the bacteria invades the bloodstream directly and causes flu-like symptoms, without the swollen lymph nodes. In either case, mortality rates can be 40 to 60 percent if untreated. Infection of the lungs is the most serious form. The patient will cough up bloody sputum and droplets that help spread the disease person-to-person, and unless treated quickly mortality can approach 100 percent. The Black Death is treatable with antibiotics such as streptomycin now, but a resistant strain could be a serious public health problem.
Centers for Disease Control
Anthrax Anthrax is spread by spores, and those spores can survive in many environments, sometimes for years. There are three ways anthrax infects: breathing the spores, eating infected meat or having the spores get into cuts on the skin. Infection through inhalation is the most likely to kill, but anthrax is still quite dangerous. As the bacteria multiply in a person, they release toxins into the blood and tissues that cause swelling and cell death. Fatality rates are high, approaching 50 percent, even with treatment by antibiotics and 90 percent without that. It's not contagious, but a bomb can be made to spread the spores and infect many people at once. The spores can even be sent in the mail, as in the 2001 anthrax attacks. In those cases, envelopes containing anthrax spores were sent to several media outlets and the offices of two senators. Five people died and another 17 were infected. "Anthrax is great from the point of view that it is stable and not usually a suspect until it's too late to treat," Smith said. Anthrax produces symptoms that look like flu and unless there is a reason to think a person is infected, a doctor might not know to test for it. For a bioweapons manufacturer, however, the lack of person-to-person transmission means it needs to be released repeatedly. Anthrax is also vulnerable to antibiotics if caught early, though drug-resistant forms of it were experimented with in the United States until 1972 and the former USSR until the projects were abandoned in 1992. In 1942 the British government tested a strain of anthrax on an island in Scotland; decontamination didn't happen until 1990.
Sion Touhig / Corbis
Agricultural Pathogens As bad as pathogens are that kill people, those that attack animals or agriculture can have effects just as devastating. Rinderpest, which was declared wiped out in 2011, killed cattle at mortality rates of 100 percent, if the population had never been exposed previously. Hoof-and-mouth disease, caused by a virus in the genus Aphthovirus, remains active. It can infect cows, pigs, sheep and goats, and causes lesions on the feet and in the mouth. The mouth lesions sometimes keep animals from eating and the foot lesions can cause lameness. Some animals die from heart inflammation. It can be spread via contact with contaminated farming equipment, vehicles, clothing or feed. It also is carried by predators. During the 2001 outbreak in the United Kingdom, anyone traveling to the United States and Europe from there was asked to step onto a disinfectant pad to decontaminate their shoes, and livestock imports from Britain to the European Union were banned. The results were millions of animals being culled and billions of dollars in containment and lost business. To create mayhem, a terrorist could spray aerosols with the virus and devastate herds. "If someone would spray every herd he/she sees from a highway going from New York to San Francisco and then driving North-South (in the middle of the country), that would do it," said Peter Palese, chair of the department of Microbiology at the Mt. Sinai School of Medicine in New York. Other diseases could also become a problem, including H5N1 avian influenza, which infects the respiratory tracts and has a high mortality rate among chickens and poultry.
An American doctor working in West Africa and another health care worker, also American, who contracted Ebola there have both received experimental treatments for the deadly viral disease, according to news reports.
Nancy Writebol, a worker with the charity Samaritan's Purse, received an experimental serum, and Dr. Kent Brantly, from the same charity, received a blood transfusion from a patient who recovered from Ebola, according to NBC News. One or both of the health care workers are also being flown to an isolation unit in an American hospital for treatment, according to news reports.
Watch "Ebola: Are We Next?" on Thursday, Sep. 18, starting at 9/8c on both Discovery Channel and Discovery Fit & Health.
Though there are conflicting reports, and no one is saying exactly what the experimental serum is, its likely that both of the reported methods contained antibodies to the Ebola virus, said Dr. William Schaffner, a professor of preventive medicine and infectious diseases at Vanderbilt University Medical Center in Nashville, Tenn. Delivering antibodies to a patient could slow the virus's replication, and give the immune system time to recover.
"There is a long tradition of using immune serum as treatment," Schaffner told Live Science. "You give the person antibodies, and you would hope that those antibodies would then bind the viruses and interfere with their multiplication."
No current treatments
This Ebola outbreak is the largest in history and has so far claimed 729 lives in Sierra Leone, Guinea and Liberia. Doctors without Borders has said that the crisis is "out of control." Sierra Leone has declared a national emergency, closed all of its schools and is quarantining disease hot spots. [2014 Ebola Outbreak (Infographic)]
There are no treatments or vaccines available for Ebola, though several are in the pipeline. A study in Nature this year reported that one drug improved survival in monkeys who were exposed to a closely related virus, called Marburg virus. Public Health Canada is testing another antibody-based treatment and the company Tekmira Pharmaceuticals has developed an experimental drug that uses a process called RNA interference to block the virus' replication, Forbes reported.
As for the American health-care workers, one possibility is that Writebol was given a concentrated form of antibodies to the virus from someone who survived, Schaffner said. To make such a treatment, researchers would have to separate and concentrate the antibodies from a survivor's blood.
If Writebol did receive such an immune serum, it would almost certainly have to have been created at the site of the outbreak and have come from someone infected with the same strain of Ebola that she has, said Thomas Geisbert, a virologist at the University of Texas Medical Branch in Galveston, who has helped develop potential Ebola drugs. There are several species of Ebola virus; the current outbreak is caused by one called the Zaire species.
Brantly is reportedly receiving a transfusion of whole blood from a 14-year-old patient who survived the disease.
In an Ebola infection, the virus first disables some of the immune system's frontline cells and then replicates almost unchecked. It then bursts out of cells throughout the body and damages them, eventually causing multi-organ failure.
Both experimental treatments, if they work, would need to lower the viral load by binding to the virus and preventing it from replicating, which would give the immune system enough time to regenerate its cells and fight the disease, Geisbert said.
However, such treatments likely have limitations. In the last stages of the disease, in a process known as a cytokine storm, the immune system goes haywire and inflammatory molecules called cytokines attack the body's own tissue.
At that point, "if you're 24 to 72 hours from death and you've got a full blown case of Ebola hemorrhagic fever, there's probably nothing on the planet that's going to save you," Geisbert told Live Science.
The Ebola virusCDC/Cynthia Goldsmith/Public Health Image Library
Will it work?
It's not clear that using antibodies from recovering patients would work. In a 1995 outbreak, eight patients were given serum from recovering patients and only one died, according to a 1999 study in the Journal of Infectious Diseases. However, those patients may have been given the drug when they were already on the road to recovery, Geisbert said.
When Geisbert and his colleagues tested a treatment made from human antibodies in monkeys injected with Ebola, the antibodies failed to protect rhesus macaques from infection and death, according to a 2007 study in PLOS Pathogens.
However, a cocktail of engineered Ebola antibodies called MB-003 developed by Mapp Biopharmaceuticals seemed to protect monkeys exposed to the virus, a 2013 study in Science reported. In animal models, some of the newer antibody treatments seem to be more effective at combating the disease, perhaps because they are more targeted, Geisbert said.
In the current outbreak, about 40 percent of victims have survived even without treatments, making it hard to gauge any treatment's effectiveness, Geisbert said.
To assess if a treatment was helping, doctors would need to measure the amount of virus in multiple patients' blood and bodily fluids before treatment, and then frequently afterwards. If the treatment worked, they would expect to see a steep drop in the number of virus particles circulating in the body soon after injection, not a gradual decay, Schaffner said.
But even then, it would be hard to say whether a treatment worked, Geisbert said.
"My fear is that they're going to give it to somebody that's almost ready to die and then blame the treatment, and I don't think that's fair," Geisbert said.
More from LiveScience.com