Experimental Serum Probably Saved Ebola Patients

Three top secret, experimental vials stored at subzero temperatures were flown into Liberia last week in a final effort to save two American missionary workers who had contracted Ebola, according to a source familiar with details of the treatment.

On July 22, 2014 Dr. Kent Brantly woke up feeling feverish. Fearing the worst, Brantly immediately isolated himself. Nancy Writebol's symptoms started three days later. A rapid field blood test confirmed the infection in both of them after they had become ill with fever, vomiting, and diarrhea.

It's believed both Brantly and Writebol, who worked with the aid organization Samaritan's Purse, contracted Ebola from another health care worker at their hospital in Liberia, although the official Centers for Disease Control and Prevention (CDC; Atlanta, GA, USA) case investigation has yet to be released.

A representative from the National Institutes of Health contacted Samaritan's Purse in Liberia and offered the experimental treatment, known as ZMapp, for the two patients, according to the source. The drug was developed by the biotech firm Mapp Biopharmaceutical Inc (San Diego, CA, USA).The patients were told that this treatment had never been tried before in a human being but had shown promise in small experiments with monkeys.

According to company documents, four monkeys infected with Ebola survived after being given the therapy within 24 hours after infection. Two of four additional monkeys that started therapy within 48 hours after infection also survived. One monkey that was not treated died within five days of exposure to the virus.

Mr. Brantly and Ms. Writebol were aware of the risk of taking a new, little understood treatment; informed consent was obtained from both Americans, according to two sources familiar with the care of the missionary workers. In the monkeys, the experimental serum had been given within 48 hours of infection. Mr. Brantly didn't receive it until he'd been sick for nine days.

The medicine is a three-mouse monoclonal antibody; i.e., mice were exposed to fragments of the Ebolavirus and then the antibodies generated within the mice's blood were harvested to create the medicine. It works by preventing the virus from entering and infecting new cells.

Ebolavirus causes viral hemorrhagic fever, which refers to a group of viruses that affect multiple organ systems in the body and are often accompanied by bleeding. Early symptoms include sudden onset of fever, weakness, muscle pain, headaches, and a sore throat. This, later progresses to vomiting, diarrhea, impaired kidney and liver function, and sometimes internal and external bleeding.

The ZMapp vials reached the hospital in Liberia where Mr. Brantly and Ms. Writebol were being treated Thursday morning. Doctors were instructed to allow the vials to thaw naturally without any additional heat. It was expected that it would be eight to 10 hours before the medicine could be given, according to a source familiar with the process.

Brantly asked that Writebol be given the first dose because he was younger and he thought he had a better chance of fighting it, and she agreed. However, as the first vial was still thawing, Brantly's condition took a sudden turn for the worse.

Brantly began to deteriorate and developed labored breathing. He told his doctors he thought he was dying, according to a source with firsthand knowledge of the situation.

Knowing his dose was still frozen, Brantly asked if he could have Writebol's now-thawed medication. It was brought to his room and administered through an IV. Within an hour of receiving the medication, Brantly's condition dramatically improved. He began breathing easier; the rash over his trunk faded away. One of his doctors described the events as "miraculous."

By the next morning, Brantly was able to take a shower on his own before getting on a specially designed Gulfstream air ambulance jet to be evacuated to the United States.

Writebol also received a vial of the medication. Her response was not as remarkable, according to sources familiar with the treatment. However, doctors on Sunday administered Writebol a second dose of the medication, which resulted in significant improvement.

She was stable enough to be evacuated back to the United States and is expected to arrive before noon Tuesday.

ZMapp has not been approved for human use, and has not even gone through the clinical trial process, which is standard to prove the safety and efficacy of a medication. The process by which the medication was made available to Brantly and Writebol is highly unusual. It may have fallen under the US Food and Drug Administration's (FDA; Silver Spring, MD, USA) "compassionate use" regulation, which allows access to investigational drugs outside clinical trials.

Getting approval for compassionate use is often long and laborious, but in the case of Brantly and Writebol, they received the medication within 7 to 10 days of their exposure to the Ebolavirus.

On July 30, 2014, the Defense Threat Reduction Agency, an arm of the military responsible for any chemical, biological, radiological, nuclear, and high-yield explosive threats, had allotted additional funding to MAPP Biopharmaceutical due to "promising results."

Related Links:
CDC 
Mapp Biopharmaceutical Inc.
US Food and Drug Administration