New Ebola treatments have been tested in the area of ​​the Congo outbreak

In the middle of the second biggest Ebola outbreak of all time, the search for a life-saving treatment is underway. A clinical trial of patients taking place in the Congo is gathering evidence on experimental therapies, to provide a proven option when the deadly virus inevitably emerges again.

The first multidrug clinical study of the Ebola therapies, which began enrolling patients in November, will compare the efficacy of three antibody treatments and an antiviral drug. A therapy tested briefly during the 2014-2016 epidemic in West Africa, the largest ever, has already shown promising results.

With the trial data, however, "we will be able to say, ideally, that this drug or that drug really works, we not only think or hope it works," says Richard Davey, a leading investigator and vice clinical director at the National Institute of Allergy and Infectious Diseases of the United States in Bethesda, Maryland.

The Ebola virus causes serious illnesses, including fever, vomiting, diarrhea and bleeding. Mortality rates range from 25 to 90 percent, depending on the epidemic. During the current Congo epidemic – the tenth country and its largest since Ebola was discovered within its borders in 1976 – about 63% of those infected died, or 510 out of 811 cases reported starting from February 9th. Stop the epidemic, which began August 1 was difficult due to the security risks and armed conflicts in the region, as well as public mistrust of the medical response, according to the World Health Organization .

28 days of treatment

The drug trial started at a treatment unit in the northeastern Congolese city of Beni, with the intention of adding further units. Registered patients will receive one of four test therapies, in addition to standard supportive care including liquids, electrolytes and painkillers.

Researchers will compare mortality rates between each group of patients enrolled after 28 days of treatment to determine the efficacy of each drug. All four trial treatments were studied on animals. The three antibody treatments were considered safe for human use, while antiviral safety tests are being performed in people.

Antibody treatments "basically start the immune system to have an immediate presence of antibodies against the virus," says Davey. One, called mAb114, was cloned from a sample taken from an Ebola survivor at 11 years from a person's infection in 1995. This treatment targets a protein on the surface of the Ebola virus and somehow hinders the infection. entry of the virus into the cells. All macaques that received a lethal dose of Ebola and treated with mAb114 survived even when the drug was administered five days after infection, the researchers said in Science in 2016.

While mAb114 is composed of a single antibody, two others – REGN-EB3 and ZMapp – are cocktails, each containing three different antibodies. In a study that assessed different doses of REGN-EB3, some dosing regimens prevented death in all or most of the macaques that had been infected by Ebola, according to a 2018 study published in the Journal of Infectious Diseases.

I hope in a bleak situation

Meanwhile, ZMapp appeared to benefit some patients in a clinical study conducted at the end of the epidemic in West Africa. Eight of the 36 patients who received the drug and supportive care died, compared to 13 out of 35 patients who received only supportive care, the researchers reported in the New England Journal of Medicine in 2016. But that previous study had not enough patients to provide statistically significant evidence that the drug works better than supportive care alone.

The only non-antibody treatment studied in the study is an antiviral drug called remdesivir, or GS-5734, which seems to aim for a step in the "owner's manual" of the virus to make copies of itself. The replication of the virus was suppressed by the drug and, at certain doses, helped survive the infected macaques from ebola, the researchers reported in Nature in 2016.

All the treatments under examination are already used in this outbreak according to the "compassionate use" protocols established by the WHO. In Congolese treatment units participating in the clinical trial, patients will be randomly assigned to receive one of the drugs, with an equal number of patients in each group. If the study does not register enough patients to obtain statistically significant results, it will remain open to patients in future outbreaks.

Meanwhile, people not yet exposed to Ebola but considered high risk in the Congo and surrounding countries are receiving an experimental vaccine called rVSV-ZEBOV to prevent infection. More than 73,000 people have obtained the preventive hit so far. The Congo has vaccinated health workers, family members of patients and other contacts. The neighboring regions of Uganda and South Sudan are also vaccinating health workers and others at risk. Rwanda intends to follow the example.

"The only silver lining in the entire dark cloud" of this epidemic is the availability of the vaccine and the therapies, says the epidemiologist of the infectious disease Mosoka Fallah of the National Institute of public health of Liberia in Monrovia. He thinks that the deployment of the vaccine and the therapies have prevented the epidemic from becoming much worse than it already is.

"Although it is a bleak situation, it is full of hope," says Fallah.

– Scientific news