Ebola: A Message from Kenneth Kaushansky, M.D.
A Landmark Time for American Medicine
The events of the past several months will almost certainly be noted as a landmark
in American public health, the arrival of patients infected with the Ebola virus.
The Ebola virus was first identified in 1976 as causing an outbreak of hemorrhagic fever near the Ebola River in Zaire, now known as the Democratic Republic of Congo (DRC). This first outbreak claimed 318 victims, of which 280 died. Study of this “new virus” commenced soon after the very first epidemic in Africa. But why had we never seen a case of Ebola hemorrhagic fever prior to 1976? New infectious agents of humans are emerging continuously, and the Ebola virus is a prime example. The virus capable of infecting humans almost certainly emerged from animals, likely bats or non-human primates. Ebola is extremely infectious, since as little as a single virus can lead to a full-blown infection, but it is not highly contagious, as unlike influenza or measles, the Ebola virus does not aerosolize and so cannot be spread by the most contagious route, respiratory droplets. Rather, human-to-human transmission requires the direct contact of broken skin or mucous membranes with blood or body fluids of an infected, symptomatic person. After an incubation period of 2 to 21 days the newly infected individual experiences fever, headache, muscle aches and gastrointestinal symptoms, such as nausea and diarrhea.
The current outbreak in the western African countries of Guinea, Liberia, Nigeria and Sierra Leone likely began in December 2013, with infection of a 2-year-old Guinean child. As of October 19th, the World Health Organization (WHO) and US Centers for Disease Control and Prevention (CDC) report the occurrence of 1540 cases in Guinea, 4665 in Liberia, 20 in Nigeria and 3706 in Sierra Leone, making the 2014 western Africa Ebola outbreak the largest (by far) in history. It should also be noted that a seemingly separate outbreak is also occurring today in DRC, with about 100 infected individuals. Overall, the death rate during the current outbreak in western Africa is approximately 70%, although mortality in the US, with earlier diagnosis and better supportive care, is likely to be lower.
Human Ebola virus infections are not strangers to Africa. Since the initial cases in 1976 there have been numerous outbreaks of Ebola hemorrhagic fever, with those affecting greater than 100 individuals occurring in the DRC in 1995, in Uganda in 2000-2001, in Gabon in 2001-2002, and in 2003 and 2007 in the DRC. Like many other devastating outbreaks of disease in the developing world, humanitarian help arrived in western Africa in the form of many non-African healthcare workers, who worked side by side with their African counterparts. Two American healthcare workers helping to control the current African Ebola outbreak were infected in the course of their work and were brought to the US in August, to be treated (successfully) at Emory University Hospital, without sacrificing the health or normal flow of the hospital staff or other patients; two months later another American, a photojournalist, was successfully treated at the University of Nebraska Hospital, again without incident to others. Those two hospitals had been preparing to receive highly infectious patients for years, and their staff had been drilled repeatedly in the processes necessary to provide outstanding patient care, while protecting themselves from secondary infection. But when a non-healthcare worker arrived at the Texas Health Presbyterian Hospital Emergency Room in Dallas, their unprepared staff mistook his symptoms for influenza (needless to say, far more common in the US than Ebola) and sent him home. Moreover, when the patient was finally admitted two days later, their staff was likely not sufficiently drilled in the proper protective protocols, nor did they don the very best protective equipment (although their equipment was advised to be adequate at the time), and two nurses became secondarily infected. And on Friday, an American physician working for Doctors Without Borders and caring for Guinean patients with Ebola, became sickened after returning to the US, and was diagnosed with Ebola virus infection and admitted to Bellevue Hospital in New York City.
Biomedical scientists have intensely studied the human Ebola virus over its near 40-year existence. A search of PubMed yesterday, using the term “ebola virus”, yielded 1839 publications. We know that it is a single stranded RNA virus that binds to the surface of endothelial cells, macrophages and hepatocytes via the virus surface protein termed GP1,2. Once the virus enters the target cell it is transcribed into messenger RNA that encodes 7 protein products. One viral product, sGP, is secreted and acts to blunt the host immune response to the virus and to reduce vascular integrity. Once the virus replicates the thousands of new viral particles destroy their host cell, which releases cytokines that cause fever, and the progeny viruses spread throughout the host to infect additional cells. Damage to endothelial cells causes blood vessels to leak, and damage to the liver causes a failure in blood coagulation, which together cause the widespread bleeding leading to the phrase “hemorrhagic fever virus”, and which ultimately causes death of the patient. Based on our rather detailed understanding of the virus, a number of viral targets for treatment have emerged, as have attempts at vaccine development, many of which are ready for human testing.
Over the past few months, triggered in large measure by the magnitude of the 2014 epidemic, and coupled to greatly expanded travel between the US and western Africa, American hospitals have begun to sense urgency in preparing to handle patients who might be infected with the Ebola virus. And since JFK International Airport is the single most common point of arrival of airline flights to the US from western Africa, New Yorkers have been particularly anxious.
It is my strong and abiding belief that the Stony Brook University Hospital has the people and the technology to manage the Ebola challenge, should it come to Suffolk County. This is why we volunteered to serve as one of eight hospitals in New York State to care for such patients. That the New York State Department of Health has assigned us this role is a testament to their faith in our skill and preparedness, as is the reliance on Stony Brook of the Suffolk County Department of Health, in preparing county-wide health facilities to transport suspected patients to designated care facilities. And because Stony Brook University and Stony Brook Medicine students and faculty travel the world to pursue advanced scholarly and educational missions, our hospital and clinical facilities must be prepared to evaluate and care for members of our own community.
A few days ago several of the leaders of Stony Brook Medicine met with faculty and staff from the day, the evening and the midnight shifts at University Hospital to discuss our procedures for dealing with patients suspected and proven to harbor Ebola virus. Signage in English and French (the native language of many from West Africa) asks that all patients coming into our clinics, maternity suite, and emergency department identify whether they have a fever and have travelled from western Africa in the past month. Such patients are immediately isolated and staff and family protected from potential spread by sophisticated barrier methods. Specific rooms in the Emergency Department and University Hospital have been set up to care for such patients by designated teams of attending Emergency Medicine- and Critical Care Medicine-trained physicians, experienced Emergency Department and ICU nurses, and other healthcare professionals. Staff likely to encounter a patient with Ebola will work in teams (the buddy system was embraced at SBUH prior to being adopted by the CDC), have already been trained, and will continue to repeat their training frequently, so they maintain the skills necessary to deliver our two top priorities, delivering the best possible supportive patient care and protecting the health of our staff. The leaders of Stony Brook Medicine have been in constant consultation with the State and County Departments of Health, the CDC, and the other 7 hospitals designated by the New York State DOH to care for patients with Ebola to be certain we have the very most current recommendations for care and staff protection. We have pledged to our healthcare professionals that we will only disseminate information that we are certain is correct, that we will provide them with the very best equipment and skills, always seeking to utilize protocols for care that meet or exceed those recommended by governmental healthcare agencies for the care of Ebola patients. Moreover, we will use this tragedy as an opportunity to re-double our investment in the public health measures needed to control an infection such as Ebola until specific and effective therapy becomes available. And while I am confident in our ability to protect our healthcare workers against secondary infection, we must face the prospect that the best available supportive care still carries a greater than 60% mortality rate, at least in Africa, as effective anti-Ebola treatments do not currently exist. This is the crux of the problem, and the source of the tremendous anxiety in the residents of our state and our nation.
For the past two hundred years we have begun to win the war on infectious agents of humans. The work of Edward Jenner, on small pox vaccination, and Alexander Fleming on penicillin, began the human counterassault on the microbial world. The development of the polio vaccine by Jonas Salk and then Albert Sabin virtually eliminated a disease that routinely crippled or killed tens of thousands of children every year in the US. The hepatitis B vaccine has greatly reduced what used to be the primary cause of liver failure in the US and the world. The development of antimicrobials against HIV has turned an epidemic that claimed the lives of tens of thousands of previously healthy Americans into a very manageable chronic condition. And the recent development of new drugs that cure 95% of patients with chronic hepatitis C virus infection, currently the most common cause of cirrhosis, liver failure and liver cancer, are testament to the ability of biomedical research and pharmaceutical ingenuity to forge successful partnerships that overcome major public health threats.
At Stony Brook Medicine we strive to help overcome the major maladies of humans, both for individuals and populations. Infectious and immunological diseases are a major focus of our strategic plan, which is why we have recruited new leaders to our infectious disease division, continue to invest in one of the very best departments of microbiology in the country, and are building a high level infectious disease research laboratory on the health sciences campus. Fueled by these and other investments, Stony Brook Medicine successes are many, including the discovery of the causative agent of Lyme disease, the first chemical synthesis of the polio virus and a myriad of studies of hemorrhagic fever viruses, the category of infectious agents to which Ebola belongs. But we cannot overcome Ebola virus, and all of the emerging infections certain to come, without help.
Each of the major accomplishments highlighted above (except the work of Jenner, in 1796, and Flemming, in 1928) was catalyzed by research grants provided by the National Institutes of Health, during a period of sustained growth in American support for biomedical research. Over the past decade, funding for biomedical research has been stagnant, which because of inflation, has meant a 25% loss in the ability to provide the kind of breakthrough research required to overcome such a formidable opponent. Our current understanding of the Ebola virus should be sufficient to conquer this infection; in fact, many Ebola vaccines and targeted therapies developed by academic collaborations are available, but have not been tested in humans. Why? Dr. Francis Collins, Director of the National Institutes of Health recently stated that an effective vaccine for Ebola could have been available for the 2014 epidemic if NIH funding had not been cut. What about other sources of research and development support? The Pharmaceutical Industry (Pharma) has been quite successful in developing new antibiotics and vaccines for infectious agents common in the US: diphtheria, tetanus, hepatitis, influenza, pneumococcus, and other viruses and bacteria have come under control over the past several decades. But Pharma only pursues vaccines or drugs for which a successful business plan can be developed, and thus far, a successful business plan has not been constructed when the recipients of the new medication or vaccine live primarily in the developing world. One only need look at the very slow progress towards better treatments for malaria to see a similar story. This is where Americans must step up; we must demand that our governments and industries re-invest in biomedicine, to allow the biomedical and clinical scientists at Stony Brook, and many more like them throughout our academic and Pharma communities across the country, to unleash their incredible creativity and technical skill towards what will hopefully become another victory over a formidable microbial foe.
Kenneth Kaushansky, MD, MACP, is Dean of the School of Medicine and Senior Vice President of Health Sciences at Stony Brook University.