NIH Ebola Response

Ebola-Infected Nurse Discharged

A key element in the mission of the Intramural Research Program is to respond to public-health emergencies and this certainly has been realized in the Ebola epidemic. Beyond having had an Ebola vaccine ready for clinical trial before the onset of the recent West African outbreak, the NIH Clinical Center has long been prepared to accept Ebola patients. Its Special Clinical Studies Unit (SCSU) was recently called into action to treat Nina Pham, the Ebola-infected nurse who recovered from her illness and was discharged on Friday, October 24, 2014.

several people walking out of the Clinical Center

ERNIE BRANSON

NIH Director Francis Collins led the way as NIAID Director Anthony Fauci walked recovered Ebola patient Nina Pham out of the Clinical Center to a press conference on the day of her discharge, Friday, October 24, 2014. Pham’s mother, Diana (left), and sister Catherine (right) were close behind.

Pham works at Texas Health Presbyterian Hospital (Dallas) and was one of two nurses who became infected with the virus while caring for Thomas Eric Duncan, a Liberian national and the first Ebola patient diagnosed in the United States. He died on October 8, 2014. Pham was being treated at Texas Presbyterian until she was transferred to NIH on Thursday, October 16. The other nurse, Amber Vinson, was transferred from Texas Presbyterian to Emory University Hospital (Atlanta) and has also recovered.

Reporters and NIH staff, who had gathered for a press conference outside the Clinical Center, applauded and cheered when the 26-year-old Pham walked out of the building with Anthony Fauci and other members of her health-care team.

“I feel fortunate and blessed to be standing here today,” she read from a prepared statement. She expressed her thanks to God, to her family and friends, and to everyone involved in her care. “As a nurse, I have a special appreciation for the care I have received from so many people.”

Although Pham declined to take questions, the reporters had plenty for Fauci, who is the director of the National Institute of Allergy and Infectious Diseases (NIAID).
“How do you know that she’s virus-free?” asked one of the reporters. “What did you do while she was here at NIH?”

“We know she is virus-free because we now have five consecutive negative PCRs,” said Fauci, referring to a test called a PCR (polymerase chain reaction), which detects bits of the virus’s RNA and is used to confirm an Ebola diagnosis. “We did five because this is a research institution. But that’s not the norm.”

Fauci went on to describe the kind of treatment Pham and other Ebola patients receive. It is important to “give them the kind of general medical support to allow their own body to be able to fight off the virus and essentially get rid of [it],” he said.

Supportive care includes providing intravenous fluids and electrolytes; maintaining blood oxygenation and blood pressure; and treating secondary infections if they occur. Pham also received plasma from Kent Brantly, the first person to be treated for and recover from Ebola in the United States—he was treated at Emory University Hospital. People who recover from Ebola develop antibodies against the particular strain of the virus that infected them. It is not known, however, whether the transfusion played a role in Pham’s recovery.

“When you have so many separate factors at the same time going into the care of this patient, it is virtually impossible to say that this is the thing that did it,” said Fauci. Clinical studies are needed to evaluate the efficacy of plasma transfusions containing anti-Ebola antibodies.

Another reporter wanted to know why, if the World Health Organization (WHO) reports that “70 percent of the people in West Africa die because of this virus, what explains the speedy recovery of someone like Nina Pham?”

“We don’t know,” said Fauci. “But I can tell you, as a physician, what goes into a patient’s getting better. It is anything from she’s young and very healthy, number one. Number two, she got into a health-care system that was able to give her intensive care early. Number [three], she was transferred to another health-care system that gave her everything she needed.”

The health-care system that gave her “everything she needed” was the NIH Clinical Center’s SCSU.

It didn’t hurt that Pham was cared for in NIH Clinical Center’s SCSU, which can accommodate up to two patients at a time and is designed to provide excellent clinical care and high-level isolation. It is staffed by clinicians trained in infectious diseases and/or critical care and in strict infection-control practices. The unit has the facilities necessary to provide multiple levels of care, from routine to state-of-the-art intensive care. In terms of isolation, many redundant systems and precautions are in place such as special air-handling systems; cardkey restricted access; separate entrance and exit pathways for staff, including a shower prior to exit; and detailed protocols for clinical care and the handling of waste. Staff in direct contact with Ebola patients or specimens from them have received rigorous training in the use of personal protective equipment (PPE) and follow strict protocols for putting it on and taking it off.

Pham was the second patient exposed to Ebola to be cared for at NIH. The first was an American physician who, while volunteering in an Ebola treatment unit in Sierra Leone, was potentially exposed and later developed a fever. He was admitted to NIH for observation on Sunday, September 28, 2014, tested negative for Ebola, and released on Tuesday, October 7, 2014.

The 2014 Ebola epidemic is the largest in history and is centered in the West African countries Sierra Leone, Liberia, and Guinea. The outbreak—of the Zaire species of Ebola virus, which is the most virulent—began in Guinea in December 2013, and spread mostly to Liberia and Sierra Leone. The number of cases reported in the West Africa epidemic has exceeded the total of all previously reported cases since the discovery of Ebola in 1976. As of October 25, 2014, WHO and the Centers for Disease Control and Prevention reported 10,141 suspected cases (5,692 are laboratory-confirmed) and 4,922 deaths. According to WHO, there may actually be as many as three times more than the number of reported cases (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/index.html).

In West Africa, the likely animal reservoir for Ebola is bats, Fauci told NIHers in a presentation at Clinical Center Grand Rounds on October 22. “We’re not sure how it goes from bats to nonhuman primates,” he said. “Humans get it by contact with the [infected] animals, killing, eating, [and] butchering them and cutting themselves.”

The Ebola virus spreads in humans as a result of direct contact with blood or other body fluids (sweat, feces, vomit, semen, and saliva) from an infected, symptomatic person, contact with the body of a person who has recently died from Ebola, or through exposure to objects that have been contaminated with infected body fluids or secretions.

“When somebody gets exposed, the incubation period averages eight to 10 days, but the range is two to 21,” said Fauci. The problem is, in early stages, Ebola is “virtually indistinguishable” from the flu: fever, chills, muscle pains, and malaise.

After about five days, patients may develop gastrointestinal symptoms such as severe watery diarrhea, nausea, vomiting, and abdominal pain. Even though Ebola is known as one of the viral hemorrhagic fevers, hemorrhage occurs in a minority of cases. In the late stage of the disease, there may be organ-system failure.

In addition to be being able to care for Ebola-infected patients, NIH is conducting clinical trials on two Ebola vaccines, one of which was co-developed by NIAID and GlaxoSmithKline (Hanover, Pennsylvania), and will begin a third trial soon with another investigational Ebola vaccine that was developed in Canada. In addition, NIH intramural and NIAID-supported extramural researchers have also been developing diagnostics and therapeutics such as ZMapp, which has been administered experimentally to several Ebola-infected patients.

According to the CDC, the most effective way to stop the current Ebola outbreak in West Africa is meticulous work in finding Ebola cases; isolating and caring for those patients; tracing contacts to stop the chain of transmission; conducting safe burials; and having health-care workers strictly follow infection-control procedures in hospitals.

“Although I no longer have Ebola, I know it may be a while before I have my strength back,” said Pham. Fauci hugged her as she left the press conference. Before heading home, she made a stop at the White House, where even President Obama gave her a hug.

To see a videocast of the press briefing, go to http://videocast.nih.gov/launch.asp?18690. For a videocast of the Clinical Center Grand Rounds (10/22/14), which features Fauci; NIH physician Daniel Chertow, who described his work volunteering at an Ebola clinic in Liberia; and NIH bioethicist David Wendler, who talked about the ethics of Ebola research, go to http://videocast.nih.gov/launch.asp?18685.


What NIH is Doing

Vaccines

NIH is conducting clinical trials to test two vaccines at the Clinical Center. In September, clinical trials began at NIH for testing an Ebola vaccine candidate that was co-developed by NIAID and GlaxoSmithKline (Hanover, Pennsylvania). In October, NIAID researchers began evaluating the VSV-ZEBOV vaccine for safety and ability to generate an immune response in healthy adults who receive two intramuscular doses. The Walter Reed Army Institute of Research (Silver Spring, Maryland) is simultaneously testing the vaccine candidate as a single dose.

Additionally, NIH will collaborate with the Department of Defense and NewLink Genetics Corp. (Ames, Iowa) on Phase 1 human safety studies of another investigational Ebola vaccine candidate, which was developed by and licensed from the Public Health Agency of Canada. Other vaccine candidates are in earlier stages of development in animal models.

Therapeutics

NIH intramural and NIAID-supported extramural researchers have also been developing diagnostics and therapeutics. For example, NIAID has supported and collaborated with Mapp Biopharmaceutical, Inc. (San Diego) in its development of ZMapp, which has been administered experimentally to several Ebola-infected patients. While it is not possible at this time to determine whether ZMapp benefited these patients, NIAID is supporting a broader effort to advance development and clinical testing of ZMapp to determine whether it is safe and effective.

In addition, the U.S. Biodefense Advanced Research and Development Agency has announced plans to optimize and accelerate the manufacturing of ZMapp, which is in limited supply, to enable clinical safety testing to proceed as soon as possible.

NIAID is also supporting the development of other potential treatments. Among them is BCX4430, a drug that Biocryst Pharmaceuticals (Research Triangle Park, North Carolina) plans to enter into a phase 1 human clinical trial by early 2015. Another potential drug, brincidofovir, developed by Chimerix (Durham, North Carolina), has been evaluated in more than 1,000 patients for two non–Ebola viruses (cytomegalovirus, adenovirus). Brincidofovir has shown some ability to suppress Ebola viruses in cell cultures and was recently administered to several patients with Ebola.

For more information, go to the NIH Director’s blog, which also has links to other resources: http://directorsblog.nih.gov/2014/10/14/nih-ebola-update-working-toward-treatments-and-vaccines.


SPECIAL CLINICAL CENTER GRAND ROUNDS

On October 22, 2014, Anthony Fauci (director, National Institute of Allergy and Infectious Diseases), NIH physician Daniel Chertow, who volunteered in an Ebola clinic in Liberia, and NIH bioethicist David Wendler presented a special Clinical Center Grand Rounds that was an update on Ebola.

five men standing in front of the podium in Masur Auditoriam

ERNIE BRANSON

A special Clinical Center Grand Rounds—held on Wednesday, October 22, 2014, in Building 10’s Masur Auditorium—provided an update on NIH’s response to Ebola and featured remarks by NIH bioethicist David Wendler, NIAID Director Anthony Fauci, Clinical Center Director John Gallin, NIH physician Daniel Chertow who volunteered to help Ebola patients in Liberia, and NIH Director Francis Collins.

Fauci described Ebola as “the perfect storm because we now have a perfect storm of a true globally important outbreak and perfect storm of misinformation that has gone around.” In West Africa, there are “porous borders, poor people, no good health-care structure, and customs in the country [that] allow one to embrace and try and take care of their own sick people, which is the natural thing to do as well as [to] bury them.” He went on to discuss the causes of Ebola and how it is spread, diagnosed, and treated (see main article).

Chertow (assistant clinical investigator in the Viral Pathogenesis and Evolution Section in NIAID’s Laboratory of Infectious Diseases) spoke—and showed a National Geographic video—about his experiences diagnosing and treating Ebola patients in Liberia.

“The first principle of care in an Ebola treatment unit is to establish a safe environment for local and international staff,” being sure they wear their PPE properly while treating patients, decontaminate frequently, and have their temperature checked regularly as well as have access to the clinic and paid sick leave. In addition, “expat staff are subject to restricted movement in designated vehicles between a local hotel for lodging and the treatment unit,” said Chertow. “The second principle…is to avoid nosocomial transmission. Policies [are] in place to limit disease spread [among] patients while they await initial…PCR testing.”

“When we’re talking about an epidemic like this…there’s an ethical obligation on all of us to do the best job we can to take it seriously,” said Wendler, who’s head of the Unit on Vulnerable Populations in the Clinical Center’s Department of Bioethics. Dealing with a crisis like this requires a lot of capacity, trained clinicians, and health-care infrastructure as well as a lot of trust and capacity on the part of the communities and the people involved.

“These are things that take time to develop. So we need to develop these in times independent of a crisis and try to do the best job that we can.”
Wendler focused on three ethical questions raised by research designs: “Is it ethical to offer unproven interventions for Ebola?”; “If you provide untested or unproven intervention, should you require that it be done in a study?”; and “Is it ethical to use control arms and randomization?”

To see a videocast of the Grand Rounds, go to http://videocast.nih.gov/launch.asp?18685