“It’s (Ebola) different than SARS or H1N1 influenza, as spread is by contact.  However, if you can treat someone with norovirus and feel protected, why can’t you treat someone with Ebola and feel protected.  If you let your guard down, which is common, you can also infect yourself easily.  So, you try to marry those two things and keep people safe:  proper PPE use and treating patients.  They go hand in hand.”  Fowler witnessed a remarkable transformation by the end of 2014.  “You had in Africa, in endemic areas, patients receiving ventilation and dialysis where, just months or a year before, just putting an iv in and delivering fluids would have been a remarkable achievement.  It was fascinating to work through that process, using the simplest form of epidemiology anyone could have pulled from a textbook, and see it transform clinical outcomes.”  Fowler and his team witnessed the same fear, and then transformation, that gripped healthcare workers during the AIDS epidemic.  A disease that was considered transmissible and universally fatal.  With blood and body fluid precautions, and with the advent of triple anti-retroviral therapy, fears and stigma started to dampen, and comfort levels of working with the disease started to change for the better.

“From the outset, we saw this was a disaster in evolution.  WHO is not an operational unit clinically.  They don’t do clinical care in the way MSF does.  Plus, we are not credentialled to practice medicine in Guinea, obviously.  We’re just an ID doc and an ICU doc visiting at the pleasure of the Ministry of Health through the WHO.  “In the end, they all said, “Okay, you can be doctors.”  We still did what we were supposed to be doing from an epidemiologic perspective, but during the day, from morning to night, we were just regular doctors.  Because there were never enough people around to do what needed to be done.  To do what was necessary.  But from WHO perspective, it was not what we were supposed to be doing there.” 

Fowler discusses dealing with and overcoming initial fears.  “I remember the first IV I put into an Ebola patient.  It was in Conakry, and I was sweating.  I was in PPE but it was hot!  And the patients agitated, and he’s dehydrated.  As a matter of principle, I thought he should have an iv.  So, I put one in, or I tried to put one in.  I completely muffed that iv and I had to admit to myself, that was not good.  You need to get a little calmer and to just sort of take charge of your emotions and settle down.  Yeah, that first iv, I admit, was a botch.  I had to go back to him, and I think he was an anesthesiologist, and he was pissed at me for missing it the first time.  And I wanted to say, “Dude, we know you have Ebola, and you jerked your arm, and I’m not prepared in the way I usually would be.  We transferred him to the treatment unit and he got better.  He did ok and lived.  I mean, it would be nuts if I said I wasn’t afraid.  Here I am in PPE for hours at a time, sweating, and I know all these patients have Ebola.  Then you are running around to other patients, hanging iv’s, drawing blood, with blood backing up into the tubing.  And for someone who’s never had an iv before, and see’s this in their arm, and see’s their blood backing up into the iv tubing, they’d be confused and reaching to pull those iv’s right out of there.  Then you must go and put a new iv into them, this time with a better explanation, and tell them when this happens, don’t pull it out, because you’re making my job more difficult.  There are so many contextual things you are doing and learning in a new environment.”  Fowler found the experience both trying and overwhelming.

Ebola starts with a prodromal illness that is nonspecific.  Malaise, fatigue, headache, myalgia’s; a sense that something is not quite right.  “There is no way to know in those first few days if someone has Ebola, or if they have malaria, or something else.  In the latter part of the first week, they begin to have gastrointestinal symptoms.  Fever develops, followed by nausea, vomiting, and a transition to diarrhea.  Now you’ve got a full-on GI focus of this initial viral illness.  And that could still be something else entirely.  As patients can’t keep anything down, they naturally get very dehydrated, and electrolyte abnormalities develop and possibly renal insufficiency.  Metabolic acidosis develops and liver enzymes may rise.”

The critical juncture in supportively treating Ebola Virus Disease is to limit the extent of dehydration by volume resuscitation, and correcting electrolyte abnormalities.  If you prevent the patient’s from getting sicker by correcting the reversible complications under your control, you can positively affect the outcome.  “You have a chance of pulling back a large number of folks from a poor outcome.  Certainly, the very old and the very, very young.  The outcomes of infants and newborns are very poor without supportive intervention.  But most people are going to survive if you can get them through that phase where eventually people start to develop immunity to Ebola.  You develop antibodies and you knock it out of your system, but it takes support to get people to that phase.  Some patients will require dialysis to get there.  Others will require vasopressors.  Every once in a while, they will need a ventilator.  A number of colleagues of mine have gotten Ebola, and without that intensive ICU type treatment, available mostly outside of Africa, they would be dead.  To limit the damage of Ebola, you need to be able to treat people through severe illness over time.  Otherwise, it will kill for sure.”

Ebola often causes thrombocytopenia, sometimes severe.  If can affect the normal function of the liver by causing intense inflammation, and this can sometimes cause the INR and PTT to go up.  Fibrinogen can drop and a state of Disseminated Intravascular Coagulation, or DIC, can occur.  Bleeding occurs as a result.  Likely, the cause is multifactorial, gastritis and stress ulceration in the stomach, low platelets, DIC, etc.  Studies showing why and where hemorrhage occurs are not available, and not likely to be, given the transmissibility of Ebola and the countries in which it has occurred to date.  In Africa, stress ulcer prevention with proton pump inhibitors or H2 blockers may not be available.  If a patient is already malnourished before being stricken with Ebola, and illness progresses to DIC without proper supportive care, hemorrhage can more easily ensue.  There is often no one pathognomonic feature that you can look at to say this person has Ebola Virus.  All the symptoms and signs must be taken into context.  “The most important thing is that you are in the middle of an outbreak, and someone presents with the right sort of presentation, which is typically a prodromal illness, followed by a GI phase with non-bloody diarrhea and other GI related symptoms, in the setting of an already known existing outbreak.”  In other words, there is no tell-tale sign you are dealing with Ebola Virus without using your clinical intuition in the absence of a known outbreak.  There is a plethora of disease states that can mimic Ebola Virus.  It takes history, logic, intuition, and locale to put the pieces of the puzzle together in the right order.  “You may see some subconjunctival hemorrhages, in addition to some petechiae from being severely thrombocytopenic, evidence of a coagulopathy, if it gets to that point, and a bit of icteric sclera.  With the right history, including prodrome, GI phase, and clinical course, you may be able to make a presumptive diagnosis.”

In addition to the Ebola Virus, Fowler had to fight the superstitions and beliefs of the patients and surrounding community.  “There was one day I went out into the community with an MSF group to try to bring back a patient that we knew was sick and was still at home.  We knew she was sick because she was implicated in contact with other people who had Ebola and she was reportedly getting sicker.  People were caring for her and we knew she was going to transmit the virus to more people the sicker she got.  And so, I went out into the community, in some PPE, with a local doctor, and MSF doctor, and a nurse, to this densely populated community, knowing this was not my country and our beliefs.  It was optimistic to think we were going to be able to coax this woman back to our treatment facility, where people were worried, you were going to get sicker there or die anyway.  It took a long time to get there.  By the time we got to speak to her, the sun was going down and dusk was present.  We spoke with the patient, with the help of a local community leader, but the patient wouldn’t come in.  When we returned, my colleague, the United Kingdom doctor, an ex-military type, looked at me and asked where the patient was.  Strong of will, Fletcher went himself the next day but encountered the same resistance and returned empty-handed.  Eventually, with the patient growing sicker, she relented and end up in the treatment facility shortly thereafter.  But in that community, having foreigners, especially white foreigners come to your home and try to convince someone to get care in a facility where people had heard bad things or weren’t sure they were going to come out of, it was not viewed as the best option by many.”

The virus is most transmissible from the GI phase, usually through contamination of the mucous membranes of the eyes, nose, and mouth.  “It’s fecal-oral, or GI-oral, or contact with the mucous membranes of another person.  If you get a needle stick, your risk increases exponentially.  But if you can avoid GI contents coming into contact with the eyes, nose, or mouth, then you can generally be safe, but that is very hard to do in the real world.”

After a while, the response from the developed world started to materialize and, when the population of the effected countries started to present for care and engage in the epidemiologic defense against the outbreak, the tide started to turn and the outbreak slowly petered out.  “This had little to do with US aide or WHO response.  It was mostly when the country began to “own” the outbreak, and take charge, and the local community engaged in the effort, things began to change.  The outbreak grew to 30,000 affected at its height.  There was a lot of mistrust and uncertainty based on stories from the old colonial times.”  Certainly, there was also local superstition and custom that needed to be overcome, also. 

“In Sierra Leone, in the summer of 2014, they had one treatment facility in Kenema, that was essentially a Lassa Fever facility, many hours’ drive from Freetown.  All the patients with Ebola were being sent there from around the country under the guise that they wanted to centralize care.  But in fact, it was also because nobody wanted Ebola in their backyard.  So, given the extent of the drive, some of the patients would arrive alive and some dead.  Everything was being sent there, and the place was overwhelmed and clinicians got infected early on and they lost their clinical staff, essentially.  There were no more local doctors at that facility, and we were asked to re-populate the facility with clinicians.  So that was a big part of the summer of 2014 for me.  But by the end of the year, things were changing, the people engaged, and the NGO’s set up other facilities to help and things started to turn around.  By 2015, my role was becoming more administrative and supportive, as the African Union was sending people in from other countries and my job was more training them to do the clinical care, rather than doing it myself and there was money flowing in by that part.”

Fowler was also involved in the second largest Ebola outbreak, in the Democratic Republic of Congo, in 2018.  “It occurred in North Kivu, and it was a very difficult situation to work in.  The government of the day doesn’t pay a lot of attention to that part of the country.  It’s a zone of conflict with clashes between two or three different para-military factions, and in the middle of that occurs an Ebola outbreak.  It was difficult to get from one place to the other as there were obstacles because of the military presence of these factions, or you were locked in your hotel because people were shooting up the outside of the hotel or because the treatment center had been burned down the day before.  And you thought, “my gosh, how is this ever going to get under control in this kind of setting?”  But by that time, it had been realized that better clinical care would lead to better outcomes.  But implementing that care was a challenge operationally in that environment.”

A clinical trial was undertaken that encompassed the beginning of the West African outbreak and the end of the Congo outbreak.  The trial was an enormous success in helping doctors and scientists understand the pharmacologic or immunologic therapy for Ebola.  “It looked at three monoclonal antibodies and an anti-viral therapy.  Where the baseline mortality is high, you often have an opportunity to make big gains. The mortality benefit from treating someone with monoclonal antibodies was about 20 percentage points.  You could never move the needle that much in our own treatments, typically, for cardiovascular disease or cancer.”

Fowler states one of the monoclonal antibodies had its origins years before in a Canadian national microbiology lab, targeting certain antigens on the outer shell of the virus.  “Two others were developed in more contemporary context during the Congo outbreak that were tested against the one developed in Canada.  And the fourth component of the study, was the anti-viral Remdesivir, that was subsequently used against Covid.  In Guinea, in 2014, there was an attempt at a very small trial using a monoclonal antibody called Z-MAP that looked promising, but the trial was too small to make recommendations or conclusions from.  And so, Z-MAP was incorporated into this trial with the two other more locally derived antibodies and with Remdesivir.  The two other monoclonal antibodies in the study were shown to have great efficacy, one from Regeneron and the other called MAP114.  It’s important to give these antibodies early, to staunch the viral replication process, so the antibodies weren’t directed against the cytokine cascade or anything.”  Fowler credits the pharmaceutical companies who helped innovate these treatment methods, given that their ultimate dissemination is quite limited due to outbreaks that, to date, have been small and isolated.  “We tend the criticize the pharmaceutical companies for overpricing medications before they become generic, yet they are also developing therapeutics for diseases so uncommon you may never see them.”

Dr. Fowler thinks it’s inevitable in this era of global travel, that Ebola, or Marburg Virus, for that matter, will leave the forests of Africa and be transported via an undiagnosed patient into the US, Canada, or Europe.  However, the unfolding situation is likely to be vastly different, given that supportive care in well-stocked modern hospitals, complete with dialysis machines and ventilators and instantaneous laboratory data, on top of effective public health containment policies, are likely to limit the mortality and extent of any outbreak, compared to our brethren in Africa currently.  Conceding however, that initial diagnosis, especially in the earlier stages of disease, are likely to be challenging in the absence of a known outbreak. 

Rob Fowler has proven to us that, although Ebola Virus is still unquestionably a deadly disease, having the resources and availability of even the most basic supportive care can have an astounding impact on overall survival.  Dr. Fowler continues to be active in international health and has pushed the envelope further by serving on the Therapeutics for Ebola Virus Disease Guideline Development Group sponsored by the WHO, in addition to donating his energy and skill in surveying a Marburg Virus outbreak in Rwanda.  He has come a long way from the carefree life of exploring the woods in New Brunswick as a child.  In fact, Rob Fowler has grown to embody the very qualities that physicians aspire to yet rarely realize.  He has demonstrated a bottomless capacity for self-sacrifice for the greater good and he has had the mettle to stand in harm’s way, at great personal risk, and under the most deplorable conditions, while displaying both skill and compassion, and emerging from the experience not only having done well for the patient, but increasing our foundational knowledge and treatment of Ebola Virus Disease in the process.  As a physician, he has truly made a difference in our world.