UNC Institute for Global Health & Infectious Diseases (IGHID) has shared insightful news and information about the organization’s efforts to save lives and improve quality of healthcare at a global level. The following content was created by the organization and borrowed from its quarterly e-newsletter.
Morag MacLachlan, Communications Director for IGHID, wrote this story and produced the accompanying video (https://youtu.be/f3NIPU5mh7g). To learn more about the IGHID, visit http://globalhealth.unc.edu. And click here to read a blog post by Chris Evans, RN, ANP-BC, who works in UNC’s Division of Infectious Diseases and who also traveled to Liberia to work on the following studies of the Ebola virus from March-June 2015.
Fear and poverty. These are the main factors two UNC clinician-researchers feel have fueled the reoccurring outbreaks of Ebola in West Africa over the past 40 years. The most recent outbreak was the worst to date with more than 27,000 people infected and more than 11,000 dead. What is known about the virus is that it spreads quickly and those stricken suffer immensely. Instead of remaining safely stateside with their families and medical practices in Chapel Hill, William Fischer, MD, and David Wohl, MD, headed to the Ebola epicenter.
“It’s a legitimate question about why someone who is involved in the HIV epidemic would find themselves in the throes of the Ebola epidemic of this last year and a half,” says Wohl, Associate Professor of Medicine, Division of Infectious Diseases, UNC School of Medicine. “But on the other hand, I think who else would be perfectly suited to respond to an emerging, viral, infectious disease that is fatal, that is surrounded with a lot of sociological aspects, including stigma and fear. There are not a whole lot of Ebola-ologists out there. The last outbreak was around 400 people. There isn’t this reserve of veterans who know a lot about clinical management, or about infectious diseases in general, who could respond to this outbreak. So I asked myself, could I be helpful there? Could I respond? And if the answer is yes, I need to go.”
A message spray painted to a wall in Liberia. Photo credit: Chris Evans
And go he did along with Fischer, who had been asked by the World Health Organization (WHO) in May 2014 to travel to its headquarters in Geneva to discuss drafting guidelines for the collection of respiratory specimens for a number of emerging infections, including Ebola in West Africa, avian influenza in China and Middle East Respiratory Syndrome (MERS). Yet upon his arrival, WHO officials informed him there had been a change of plans. His experience as a pulmonary and critical care physician, who spoke French and had served in resource-constrained environments made him a perfect first responder to travel to Guéckédou, Guinea – the African town hardest hit by Ebola at that time.
“I called my wife and she was not happy,” says Fischer, an Assistant Professor of Medicine, Division of Pulmonary and Critical Care Medicine, UNC School of Medicine. “But there was such urgency about the situation. And this is exactly what I do. I focus on severe viral infections. I focus on delivery of care in resource-constrained environments. And I am a critical care physician. So it was all of these worlds that I am passionate about that really came together. There was no way I wasn’t going to go. But the thing that really got me, the hook that made it something I could not turn down, was the focus. For 40 years the way Ebola has been treated is by isolating the people who are sick. But this time, the WHO, from the very beginning, said we have got to do better than we have done responding to past Ebola outbreaks. The goal was twofold – can we learn how to better treat people fighting Ebola and can we improve clinical outcomes now.”
Fischer’s experience in Guinea showed him how people being treated for Ebola in the US and Europe had very different treatment plans and usually better clinical outcomes than people fighting the virus in West Africa. The shear volume of patients in West Africa and the lack of electricity and running water compounded the problem of getting the virus under control. Then came a call from Clinical Research Management (ClinicalRM), a company based in Ohio with a robust clinical trial presence in Africa. ClinicalRM approached Fischer and Wohl about designing a study to test a treatment strategy in Liberia with funding secured from the Bill and Melinda Gates Foundation.
“We were introduced to David and Billy through mutual contacts at UNC about a year ago,” says Claudia Christian of ClinicalRM. “We immediately started collaborating on the Ebola efforts, and in short time, the duo rose to a leadership role in our partnership and agreed to travel to Liberia together to personally launch and oversee our clinical trials. Combined, they formed the perfect scientific leadership –Dr. Wohl bringing his significant clinical experience and Dr. Fischer bringing his significant Africa experience.”
The trial, the first implemented during an Ebola outbreak, began in December 2014 at ELWA Hospital in Monrovia, Liberia.
Stopping the Virus: Convalescent Plasma, Fluids and Lab Tests
This first trial synergized Fischer’s critical care strengths and knowledge from his experience treating people battling Ebola in Guinea with Wohl’s clinical and research expertise in treating another communicable infectious disease – HIV with ClinicalRM’s established clinical trial foundation in West Africa. The theory to be tested was the use of convalescent plasma or using the blood from survivors to treat people fighting the infection.
David Wohl, MD, has traveled to West Africa many times since the most recent Ebola virus outbreak began to provide clinical care and conduct research.
“That’s a therapeutic intervention that has been used in most people who have been infected and repatriated back home. So people from Europe and the US who worked in West Africa and got infected, or the very few cases of health care workers being infected in the US, all received convalescent plasma and recovered,” says Wohl. “The idea being that antibodies in that plasma give you a head start to treating Ebola. We do not know if that is the case and we went over to try and figure that out. We wanted to know once and for all – is this something that is worthwhile, is there something different about these antibodies, and do you need a certain concentration of these antibodies to be effective?”
In addition to receiving convalescent plasma, a more aggressive and ambitious clinical care strategy was also implemented. Providing each patient with fluids intravenously to combat dehydration and drawing labs to monitor levels, such as the amount of potassium in the blood, greatly improved the health of patients battling Ebola in the developed world. In the US or Europe, Fischer says the ratio of healthcare providers to patients is 30 to 50 clinicians for every one patient. In the field, like Liberia, the ratio of providers to patients is one clinician for every 60 patients. With the odds stacked against them, Fischer, Wohl, ClinicalRM and their Liberian counterparts still managed to improve survival rates.
“We reduced mortality rates from 75 percent to between 43-50 percent with just supportive care when I was working in Guinea at the beginning of the epidemic for the WHO,” Fischer says. “That is why I knew supportive care had to be a part of this trial in Liberia. Historically, people have been very hesitant to place IV’s because of the risk associated with a needle stick. But people suffering from Ebola can have up to 10 liters of diarrhea a day. So we decided to be more aggressive in placing IV’s in Guinea and people’s health improved. We needed to give the healthcare providers in West Africa the tools to provide better service or the kind of care available in resource-rich countries. So in the trial in Liberia, everyone got IV’s. Everyone received lab support. The whole idea behind this is combining service and clinical research. If our research operation fails, meaning if the intervention doesn’t work, we are still providing better clinical care to patients than they would have received otherwise. So that was our first trial.”
This trial has since been stopped because the number of new cases of Ebola in Liberia has waned. Wohl says getting research started in a resource-constrained area is challenging and he wished the group could’ve gotten up and running back in the summer of 2014 when Médecins Sans Frontières (Doctors Without Borders) began predicting the humanitarian crisis coming down the pike.
“I felt like we did a great job, but it was too late to really answer that question of does convalescent plasma improve clinical outcomes this time,” Wohl says.
Ebola Survivors: After Effects and Sexual Transmission
Wohl, Fischer and ClinicalRM have now turned their attention to the thousands of Ebola survivors. With further funding from the Gates Foundation, they are investigating the ongoing clinical complaints from people who have recovered from Ebola. The team is also focused on learning whether or not those who have no trace of the virus in their blood stream may still shed the virus elsewhere in the body.
“The team on the ground became aware of the hardships being faced by Ebola survivors through the course of collecting plasma from survivors as a potential therapeutic and daily interactions on the ELWA campus with survivors as we pass through the waiting area of the survivor clinic,” says Melissa Jones Reyes of ClinicalRM. “Many have lost their homes and families, lives are turned upside down and economic livelihood lost. The stories are heart wrenching, but survivors are also plagued with continued health issues such as arthritis, malaise and eye problems to name a few. Additionally, women are unsure about the safety of conceiving and nursing. We are just trying to find a way to give them their lives back through research and possible interventions for their health issues.”
Wohl says eye drops to help with ocular issues and steroids to counter muscle pain are two ways the survivors’ clinic at ELWA Hospital in Monrovia is trying to equip those Liberians who beat Ebola with tools to combat these lingering issues from the virus. As far as viral shedding, which would put a recovered Ebola survivor at risk for transmitting the virus to an uninfected person, there has been at least one confirmed case of sexual transmission of Ebola. Thirty days after the last case of Ebola was reported in Liberia, a 40-year-old woman died of Ebola, Wohl says. Her boyfriend was a survivor and the genetic makeup of her virus was the same as his.
“Ebola as a sexually transmitted disease is something Billy and I have been very concerned about for a long time. While this is the first confirmed case, we do not believe this is the first time this has happened. In the midst of an outbreak, we believe sexual transmission of Ebola has probably just been subsumed by common contact, like cleaning a body or bodily fluids,” says Wohl. “UNC has a long history of studying sexually transmitted diseases and also understanding how there is compartmentalization within our bodies of viruses and the immune response to those viruses. So we know from HIV, where we have been a pioneer in this work, the virus in the blood can be different than the virus in the genital secretion, which can be different from the virus in the cerebral spinal fluid that bathes the brain. And the immune system reacts differently to the virus in each of theses places. The quantity of virus and the duration of infection can therefore be different depending on if the virus is in the blood or if it is in genital secretions. We know people who were infected with Ebola do clear the virus from their blood. However, there is documented evidence that they do still have it in their genital secretions and their eyes. So that is concerning because that means there are these sanctuaries in the body where the immune system was not able to eradicate the virus.”
After the initial case of sexual transmission in Liberia, Fischer says the Ministry of Health and the WHO recommended avoiding unsafe sex until semen had tested negative twice. However, testing is not widely available in Liberia, and there were no recommendations for women. Thus, Fischer, Wohl, ClinicalRM and ELWA Hospital designed their latest study to provide free testing for survivors and to couple this service with clinical research to provide evidence behind future recommendations. Wohl and Fischer are hopeful that further analysis of these samples will allow them to give survivors a timetable as to how long they will have to practice safe sex with their loved ones and could lead to interventions that penetrate the virus in genital secretions in much the same way as has been discovered in HIV.
It’s Not Over: Stigma, Future Outbreaks and the Plane Ride Effect
Continued health problems and precautions with having sex aside, Ebola survivors face another hardship – stigma.
A sign in Liberia pleading for Ebola to stop. Photo credit: Chris Evans
“Like anything, there are news cycles and Ebola has faded. To some degree, that is appropriate, but it is not over. There are still some Ebola cases in Sierra Leone and Guinea. It is not a matter of if, but when the next Ebola outbreak will happen. We now know it is endemic to the forests in this part of Africa and it will happen again. We just have to prepare for that and be better able to respond to that,” Wohl says. “And secondly, there are a lot of survivors. There are more than 1,000 survivors in Liberia alone and they are suffering. They don’t have their jobs any more. They are stigmatized. These are people whose homes were burned and whose possessions were thrown away because people were afraid. Many of them were health care workers and they cannot go back to health care because many of these settings don’t want them or don’t need them now. So we are really trying very hard to support these clinics like the one at ELWA. We are not just studying plasma and then saying we are going to leave. We have a commitment to be here for the longer run and continue to provide care for people who survived Ebola.”
Fischer says what has struck him the most about his time tackling Ebola are the similarities he has noticed between basic human compassion in the resource-constrained and developed countries, but how these same actions can have such devastatingly different outcomes.
“What we have learned is that you can reduce mortality with aggressive care and you can do that during an outbreak,” Fischer says. “But Ebola, like many diseases, is a disease of poverty. There is such disparity in health care across the globe. If my son is sick with diarrhea, I will give him a hug to comfort him and I will clean him up. I can then wash my hands and I will be fine. That is exactly what people in West Africa did, but the difference is that they do not have access to the resources that keep them safe. They do not have access to the soap, water and alcohol-based hand sanitizers we have. And that is the only thing they did differently. Fundamentally, the problem is poverty.”
Yet, Fischer also points out that people can’t just watch the news and think that Ebola is a West Africa problem. Plane travel has made any disease any place in the world something each person should care about.
“The world is changing. These tropical diseases that occur in these resource-constrained, isolated environments no longer exist. We are now a plane ride away from every corner of the world. So if we let poverty accelerate, as we’re doing right now, then it’s only a matter of time before these diseases spread to other countries,” Fischer says. “I think the most frustrating thing we heard was people saying ‘we should quarantine all of West Africa.’ I think that is exactly the wrong response. Quarantines have never worked. It just causes an outbreak to spiral out of control. So I think the right way to do this is to respond to an epidemic at the source and fix the underlying problem of poverty by increasing equitably access to lifesaving interventions.”