Eight months ago, an outbreak of Ebola was declared in the Democratic Republic of the Congo’s (DRC) North Kivu province and the disease has now spread to the city of Bunia. According to the World Health Organization (WHO). Ebola is a rare and highly infectious virus, with a death rate of up to 90 percent.
Health workers in the DRC are describing a “bleak situation” as the Ebola virus tears through the conflict-ridden region in what has been deemed the second-worst outbreak since the virus was first discovered within the country’s borders in 1976.
In Nov. 2018, Centers for Disease Control and Prevention (CDC) Director Robert R. Redfield concluded it may not be possible to control the spread of the disease. By February 2019, the disease had claimed 510 lives, or 63 percent of the 811 confirmed cases.
As reported, the highly contagious Ebola hemorrhagic virus causes infected patients to become violently ill, and as it progresses, internal bleeding into areas like the intestines is coupled with external bleeding out of the body’s orifices, leading eventually to death, often from shock.
Public health officials in the region, as well as those who have been dispatched to affected areas, must contend with security risks and preexisting armed conflict, as well as widespread mistrust of medical authorities.
At the same time, a new arsenal of tools has been made available thanks to recent strides in biopharmaceutical research with animals. To fight the country’s tenth Ebola outbreak, a multidrug clinical trial is now underway to test the safety and efficacy of four therapies—three antibody treatments, and an antiviral—all proven successful in studies with macaque monkeys.
Additional research with animal models has yielded crucial information about the potential for zoonotic transmission of the Ebola virus (from animals to humans) through routes that were not previously understood.
In 2014, an 18-month-old boy was infected with the Zaire strain of the Ebola virus (Zaire ebolavirus) by a greater long-fingered bat. Next-generation sequencing, applied to the animals’ genomes, revealed the bat species is a natural carrier for a strain of the virus nearly identical to that which has been identified in the ongoing outbreak among people in Democratic Republic of the Congo.
The findings, published in late Jan. 2019, do not confirm bats are the source of transmission, but “This discovery is a major step forward in understanding how Ebola outbreaks happen,” explained Lead Study Investigator Jonathan Epstein of the USAID-PREDICT project.
Meanwhile, for patients already infected, health workers hope clinical trials will determine which of the four new drug therapies is most effective. Each of the promising pharmacological candidates have been identified in studies with macaques.
When administered intravenously to the nonhuman primates for 12 consecutive days, Remdesivir, the antiviral—a pharmacologically active nucleoside triphosphate—effectively reached the “sanctuary sites” of viral replication in the animals: the testes, eyes, and brain. One-hundred percent were protected against lethal doses of the Ebola virus, and the drug ameliorated “clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two out of six treated animals.”
It will now be tested in people for the first time, along with the three antibody therapies that have already proven safe and effective in human patients.
Antibody treatments work by equipping the immune system with blood proteins specifically designed to, in these cases, attack the Ebola virus antigen. Of those three, the first, mAb114, was originally cloned from a sample procured from an Ebola survivor. In a 2016 study, it was administered to four macaque monkeys exposed to a lethal dose of the Ebola virus, and to three animals five days after exposure, all of which survived.
Researchers working with mAb114 determined the therapy shows potential for protection against the disease for human patients either alone or in combination with other related antibodies.
A pair of drug cocktails, REGN-EB3 and ZMapp, each of which includes three antibodies, are now being tested alongside mAb114 for patients infected with the Ebola virus. These therapies were pioneered by harvesting the antibodies from humanized mouse models that were exposed to proteins from the virus, which were then pharmacologically combined and studied with non-human primate models.
For health workers and the public at large, the availability of experimental therapies developed through animal research represents the promise of hope, amid a crisis that that continues to grow more dire with each passing day.