How Cutting-Edge Medicine Might Have Spared Us the Ebola Epidemic
The promise of technical end-runs around government ineptitude
The first person diagnosed with Ebola in the United States died in Texas on Wednesday. Also on Wednesday, a nurse who contracted Ebola from a missionary priest being treated for the disease in Spain became the first known case ever of Ebola transmission outside of the West Africa hot zone.
In the meantime, the number of people infected with Ebola in the West Africa outbreak now exceeds 8,000; 3,857 have died of the disease. Computer disease model estimates by Eurosurveillance suggest that the number of people with the illness could grow by an additional 77,181, to 277,124 cases by the end of 2014. The U.S. Centers for Disease Control and Prevention (CDC) calculates that if the rate at which infected people are isolated is not substantially increased, the number of cases could swell to somewhere between 555,000 and 1.4 million cases by mid-January.
It could have been otherwise.
The current outbreak apparently began in December in the Gueckedou province of Guinea. On March 10, regional officials alerted the Ministry of Public Health and the local Medecins sans Frontieres (MSF) about patients suffering from a mysterious high-fatality rate illness characterized by fever, diarrhea, and vomiting. Guinean and MSF health care workers reached the region by March 18. On March 30, the World Health Organization (WHO) confirmed that 112 people, of whom 70 had already died, had been infected with the Ebola virus. Only two cases were reported in neighboring Sierra Leone and just three in Liberia.
Rapid response teams were dispatched to begin the standard process of controlling a disease outbreak by isolating infected patients and tracking their contacts. Evidently, the rapid response was not rapid enough. By July 1, the number of reported cases in all affected countries had risen to 759, of whom 467 had died. On August 6, the WHO declared the outbreak a "public health emergency of international concern" and announced that "a coordinated international response is deemed essential to stop and reverse the international spread of Ebola."
On September 4, the WHO reported 3,685 cases and 1,841 deaths. The public health measures that had successfully quelled earlier epidemics in rural areas were overwhelmed when the disease reached densely populated cities. Patients were not isolated because hospitals and clinics lacked sufficient space, adequate protective equipment, and trained personnel. In addition, years of political repression and civil war have sown deep distrust toward the region's governments. As a result, many of those exposed to infected patients evaded government attempts at quarantine and rebuffed public health officials' efforts to track their contacts.
In an October 9 article for The New England Journal of Medicine, the National Institute of Allergy and Infectious Diseases virologist Heinz Feldmann observed that "it is still not possible to administer vaccines or treatments to the at-risk population or medical aid teams. If we are to practice cutting-edge medicine, rather than simply outbreak control, we need to advance leading approaches toward approval and licensing. This gap should close over the next several years—if we can continue making progress before Ebola (or a related virus) strikes again."
Feldmann is all too sadly right. It is not possible to "administer vaccines or treatments" to people suffering from Ebola virus disease. Let us imagine a world where cutting-edge medicine had actually been encouraged to advance.
Right now, one of the chief problems with controlling the epidemic is that the current method of diagnosing patients takes hours, often days, to yield a result. The RT-PCR test was a genuine breakthrough a decade and half ago, but considerable progress has been made since then in molecular techniques for diagnosing illnesses. Back in 2003, researchers developed a diagnostic test that could identify a specific Ebola protein in a patient's blood. They even speculated that it could "become a very useful tool for obtaining an accurate diagnosis in the field, limiting the risk of laboratory infections." In 2007, the German biotech company Senova reported that it had developed a similar rapid cheap field test for Ebola virus.
Eleven years later, driven by the current crisis, the Colorado-based biotech company Corgenix is rushing to validate a rapid diagnostic test based on the 2003 finding. If this process works as planned, a health care worker will apply a drop of blood from a patient to a test strip. The test will work much like a pregnancy test, with a dark line appearing to indicating infection. The results will be available in 10 minutes. Using such a test on would-be airline passengers suspected of being infected would certainly be more effective than taking their temperatures.
As Feldmann further notes, "There is currently no licensed prophylaxis or treatment for any ebolavirus or marburgvirus infection; therefore, treatment is merely supportive." It didn't have to be that way. In 2007, researchers reported that mice given antibody treatments that attack the virus two days after the mouse is exposed to it survived the infection. In 2012, Canadian researchers showed that treating macaque monkeys with a combination of three monoclonal antibodies one day after exposure to the virus resulted "complete survival." This research led to the creation of the ZMapp cocktail of antibodies administered in August to the infected U.S. missionaries Kent Brantly and Nancy Writebol, both of whom survived.
Another approach is to disrupt the proliferation of the virus in an infected patient. Researchers have developed several effective antiviral compounds. One of the more promising anti-Ebola treatments is favipiravir, developed as anti-influenza drug by Japanese researchers in 2002. In May, German researchers reported that all the mice given doses of favipiravir six days after infection survived. Similarly, research in 2010 found that treatments using small interfering RNAs protected macaque monkeys exposed to the virus. This compound is being developed into an Ebola therapeutic by the Canadian company Tekmira.
Of course, the best way to disrupt and prevent future Ebola epidemics is to develop a vaccine. In the August 2003 Lancet, Feldmann and his colleagues wrote: "The rare appearance of EBOV haemorrhagic fever and the remote locations of the outbreaks did not favour vaccine development. Development of effective vaccines requires industrial support and this did not seem to be feasible, knowing that there would not be a market for the vaccine." They added, "This view has changed with the existing threat from bioterrorism."
In 2000, Nature reported the development of Ebola vaccine using an adenovirus that prevented all of the inoculated macaque monkeys from becoming infected. In a 2005 study, researchers developed another vaccine by adding a gene from the Ebola virus to a weakened livestock pathogen called vesicular stomatitis virus (VSV). The vaccine completely protected immunized macaque monkeys from Ebola infection.
So all of the elements for plausibly stopping an Ebola epidemic existed years before the current outbreak: fast diagnostics, post-exposure treatments, and vaccines. Public health bureaucracies have now finally been panicked into getting their acts together. Yesterday it was announced that a clinical trial of the adenovirus-based vaccine has begun in Africa, and enough of the VSV vaccine for up to 100,000 doses is expected be shipped to the WHO shortly. A clinical trial testing the efficacy of favipiravir may be launched in Guinea in November. The drug apparently saved a French nurse who caught the disease while working in Africa. In September, Senova sent 2,000 of its fast diagnostic kits to Guinea to assess its accuracy against the slower standard RT-PCR diagnostic.
But cutting-edge medical innovation was not permitted to flourish. Outmoded regulations significantly boosted development costs for new medicines, which in turn further eroded the already meager economic incentives for pharmaceutical and biotech companies to pursue their development. In one particularly clueless moment, the U.S. Food and Drug Administration put a clinical hold on Tekmira's Ebola therapeutic just as the West African epidemic was exploding. A month later, fortunately, the agency did an about-face and lifted the hold, having realized that the risks of dying of Ebola are far greater than any safety risks posed by the therapy. The Nebraska Medical Center in Omaha was therefore able to treat medical missionary Rick Sacra with Tekmira's medicine. Sacra survived.
Now we must hope that public health measures will eventually work. The CDC calculates that the chain of infection in West Africa can be broken if the isolation of infected patients in Ebola treatment units at clinics or at home could be ramped up to 70 percent by late December. In that optimistic scenario, the number of patients that would need to be isolated at any one time would peak at 1,335, and the epidemic could be over by January 20, 2015.
If the epidemic is allowed to rage unchecked, on the other hand, the CDC calculates that the number of patients that would need to be isolated in Ebola treatment units would peak that month at nearly 26,000. That's a figure too scary to contemplate.