Facts, numbers, present challenges and predictions. In which direction is the Ebola epidemic going?
Text: Iskra Pollak Dorocic & Sergio Scro Petualang
Infographics: Jakub Lewicki
It’s impossible to not have heard of the ongoing and unprecedented Ebola epidemic in West Africa, with its steady escalation and horrifyingly high death count over the past six months. Every day there are reports of more and more people contracting the disease, with the US Centre for Disease Control predicting the number of cases could surpass 1 million by the end of the year if drastic measures are not taken. As the affected countries are scrambling, so far unsuccessfully, to gain control of the outbreak, the rest of the world has for the most part stood idly by. Medicor spoke to several experts, as well as people in the affected region, and in the following pages takes an in-depth look at the disease – from virology to public health issues.
Ebola viral fever (Ebola VF) is one of several viral haemorrhagic fevers. The Ebola type produces a severe and often fatal disease affecting both humans and nonhuman primates (such as monkeys, gorillas, and chimpanzees). When infection occurs, symptoms usually begin abruptly. The first Ebola virus species was discovered in 1976 in what is now the Democratic Republic of the Congo, near the Ebola River. Since then, outbreaks have appeared sporadically.
The natural reservoir host of Ebola viruses remains unknown. However, on the basis of available evidence and the nature of similar viruses, researchers believe that the virus is animal-borne, with bats being the most likely reservoir. Four of the five subtypes occur in an animal host native to Africa. Symptoms of Ebola VF include high fever, severe headache, muscle pain, diarrhoea, vomiting and abdominal pain. Symptoms may appear anywhere from 2 to 21 days after exposure to the virus. Someone who becomes sick with Ebola could be able to recover. However, patients who die usually have not developed a significant immune response to the virus at the time of death.
When an infection does occur in humans, the virus can be spread throughdirect contact with a sick person’s blood or body fluids (urine, saliva, faeces, vomit, and semen), objects (such as needles) that have been contaminated with infected body fluids and infected animals. Healthcare workers and family and friends in close contact with Ebola VF patients are thus at the highest risk of getting sick.
During outbreaks of Ebola VF, the disease can spread quickly within healthcare settings (such as a clinic or hospital). Exposure to Ebola viruses can occur in healthcare settings if the hospital staff is not wearing appropriate protective equipment such as masks, gowns and gloves. Unfortunately, these relatively cheap basic medical materials are often not available in poor settings. Proper cleaning and disposal of instruments such as syringes is also important. If instruments are not disposable, they must be sterilized before being re-used. Without adequate sterilization of the instruments, virus transmission can continue and amplify an outbreak. No specific vaccine or medicine (e.g., antiviral drug) has been proven to be effective against Ebola.
Wreaking havoc in the body
What exactly makes the Ebola VF virus so deadly? When the virus enters the body, it quickly infects various cells of the immune system, including monocytes, macrophages, and dendritic cells. These then spread via the blood to the lymph, spleen, and the liver where they infect more cells dispersing the virus throughout the whole body. In a normal case, immune cells fight back by producing antibodies against the pathogen. However, Ebola VF manages to evade the immune system by inactivating certain defence genes and disrupting the function of interferon, an important antiviral protein.
This is when the real problem starts. The infected cells induce a ‘cytokine storm’, an exaggerated response of the immune system to a new pathogen, resulting in recruitment of more and more of the small molecules which the immune system uses for communication – the cytokines. Too many cytokines can eventually cause tissue damage, organ destruction and death. This is exactly what is seen in later stages of an Ebola VF infection, when the strong immune response causes blood vessels to leak and result in internal and external bleeding. This haemorrhaging is what in most cases ultimately leads to the patient’s death.
Tracking the outbreak
Past Ebola outbreaks have occurred since Ebola records began in 1976 in the Democratic Republic of the Congo (DRC), Gabon, South Sudan, Ivory Coast, Uganda, Republic of the Congo (ROC) and South Africa (imported). The current Ebola outbreak is occurring in Guinea, Liberia, Sierra Leone, Nigeria and DRC.
How exactly did the current outbreak begin? To begin answering that question, scientists have sequenced and analysed the genomes of Ebola virus samples from 78 people who were the first ones diagnosed with the disease at a hospital in north-eastern Sierra Leone, near the borders with Liberia and Guinea. Sierra Leone’s initial outbreak of Ebola in the early summer has now been traced back to a single event – a traditional healer’s funeral at which 14 women were infected. Geneticists at the Broad Institute of M.I.T. and Harvard who sequenced the virus from blood of the patients found that all 78 had virus traceable to funeral guests, and also showed that the West African Ebola strain is different from a strain that has been circulating thousands of miles away in Central Africa since 1976. These two strains are thought to have diverged in 2004 and the West African outbreak originated in a single event in which the virus passed from an animal to a person.
The DNA sequences have shed light on how much the virus is changing throughout the outbreak and will be used to improve diagnostic tests, which are currently developed for the older strain of the virus and not the current one. Eventually, the genetic information will be useful in order to develop vaccines. On a tragic side note, five of the researchers that were involved in this research and co-authors of the study died of Ebola before the publication came out in Science in August, once again underscoring the danger that the health care professionals working with the disease are in.
Fast-track for a cure
Arguably, the biggest obstacle to the current prevalence has been the lack of vaccine or treatment against the disease. The usual containment measures of isolation of patients have failed and the outbreak seems to be out of control. This reality has finally mobilized authorities to push for a fast-tracked development of drugs. A number of infected health care workers, for the most part from outside of Africa, have successfully been treated with the experimental drug ZMapp, containing a cocktail of three monoclonal antibodies. Trials in monkeys have also shown a positive effect of the drug. The drug is, however, in a very limited and exhausted supply and production of more will take months. Time is also a factor in testing and producing a number of potential vaccines. Companies producing the vaccines still need to confront the technical challenges of boosting production. It seems that a lack of interest in developing preventative measures is coming back to haunt authorities, who are now approving development and trials with an unprecedented speed.
A last desperate measure has been proposed to slow down the fatalities. WHO announced that blood from recovered Ebola patients should be used to treat the infected ones. This strategy has been used in several patients during a previous much smaller Ebola outbreak in 1995, with apparent success. It cannot be denied that time is of the utmost importance in battling the current Ebola outbreak. The longer the virus is on the loose, the more genetic mutations it is acquiring, making it more likely to mutate into a form that is even more dangerous than the current one.
Researching the virus
Studying the Ebola VF virus is no easy task. Medicor spoke to Dr. Ali Mirazimi, Associate Professor at the Department of Microbiology, Tumour and Cell Biology at KI, who is working at with Folkhälsomyndigheten (Public Health Agency of Sweden). Dr. Mirazimi specifically studies the Crimean-Congo Haemorrhagic Fever virus, which also causes haemorrhagic fever disease and requires the same highest level biosecurity laboratory to handle it.
Today relatively little research has been devoted to studying the specific mechanisms of the Ebola virus. There is an obvious discrepancy in the scientific literature between research on Ebola versus other types of pathogens, with less than 2,000 scientific papers on Ebola VF, compared to the widely-researched HIV which covers almost 300,000 publications. Aside from this scarcity of basic research, do pharmaceutical companies have incentives to invest in Ebola VF drug development? “There is of course several aspects to consider”, says Dr. Mirazimi, “First of all, HIV is a much, much bigger health problem than Ebola VF, in Africa as well as many other parts of the world, including Western countries. This is why there is more research being done on HIV, malaria, tuberculosis.” HIV and tuberculosis kill 1.6 and 1.3 million people each year respectively, exponentially more than any Ebola outbreak thus far. “Secondly, usually the industry’s interests lie towards money, and the profit is larger where there are more patients.”
Then there are the other limitations, including the high-level biosafety laboratories. “Keep in mind that studying these viruses is very expensive as you need high-containment laboratories and the maintenance of these laboratories has a huge cost”, says Dr. Mirazimi. Only about a handful of these highest biosafety level facilities exists in Europe (including one at Folkhälsomyndigheten), while Africa has only one, located in South Africa. “So generally speaking, there is a limitation in number of these facilities, there is limitation in priority of how this disease is seen in correlation with other public health problems, and how much money the industry is interested in investing. These issues make the research on diseases like Ebola VF really limited in comparison to other pathogens.”
On the ground
Medicor also interviewed Anneli Eriksson, a Swedish nurse and Médecins Sans Frontières (MSF) staff member. She worked in Monrovia, Liberia during August 2014 in an Ebola hospital set up by MSF. She considers the outbreak in Liberia “out of control”. Many staff members and health personnel have been infected by Ebola VF and have subsequently died; many of the country’s hospitals and healthcare centres have been closed or perform their activities in a very limited way in order to avoid the spread of Ebola VF within the hospital premises. Eriksson also adds that the peculiarity of the outbreak in Liberia is that no clusters or hotspots have been identified. Infected patients come from all over Monrovia and all over the country. The MSF Ebola centre in Monrovia is currently run by approximately 300 national staff members and 60 international. They have an availability of 200 beds and the centre is overcrowded. Their admission policy is to only admit patients that have strong symptoms, and thus high viremia, with the aim of isolating the most infectious patients in order to limit the spread.
Furthermore, Medicor approached Dr. Johan von Schreeb, a disaster medicine specialist and Associate Professor at Karolinska Institutet, where he lead research and training on health response following disasters. During the last 25 years he has on a regular basis worked for MSF and World Health Organization (WHO). He recently returned from Sierra Leone where he was deployed on behalf of WHO to coordinate the foreign medical teams’ response to the Ebola outbreak. “The situation in Sierra Leone is out of control”, says also Dr. von Schreeb. He emphasizes the need of supporting the existing health staff, primarily nurses. “They need to be ensured a substantial risk allowance, have access to treatments if they are infected, in addition to an insurance package that protects their families in case of death. They are courageous and take risks, it is our duty to support them, without them this epidemic will continue to ravage”. Beside case management, an additional four essential pillars must be in place to control Ebola VF: epidemiologic surveillance to monitor the evolution of the epidemic, contact tracing and follow up of persons in contact with the sick, safe burials of suspected Ebola VF deaths and finally and the most challenging, community sensitization. This means building trust and confidence with the population at risk, convincing them to follow guidelines and avoiding contact with sick. Discouragingly, none of the pillars mentioned above are working properly in Sierra Leone, according to Dr. von Schreeb.
EU on high-alert
At the European level, the European Centre for Disease Control (ECDC) is facing the Ebola outbreak in a number of ways. As public health professionals, the ECDC staff is working hard on keeping the outbreak under control and protect the health of EU citizens and residents, according to the ECDC’s press department. They have produced a first Rapid Risk Assessment in March 2014 that has been updated periodically as the outbreak evolves. In an interview with them, they state that the ECDC is considering three main risks for EU/EEA: “risks for someone from the EU being infected in the affected countries; risk of importation of Ebola VF virus into Europe and the risk of onward transmission, should it be imported”.
The most obvious option to decrease the risk of importation from affected areas is to advise travellers to defer their travel to these affected countries until the outbreak is controlled there. Twenty-four EU/EEA countries have recommended this option for their citizens of which twenty have recommended avoiding or postponing non-essential travel and four advising against all travel in the affected areas. Should any infected person enter the EU, the transmission within the EU should be prevented and controlled. To achieve this, preparatory activities are on-going, to ensure that all Member States are well aware and prepared for this eventuality.
Finally, it seems as though the rest of the world is taking notice of the severity of the outbreak and jumping into action. US president Obama announced on September 16th that the US will be sending 3,000 military troops to set up treatment centres with 1,700 beds. China and Cuba are also sending medical personnel and equipment, as are a number of other countries in smaller quantities. The last day of September also saw the first diagnosis of Ebola VF outside of West Africa, brought by a traveller to the United States. The struggle is a race against time, as the longer the virus is on the loose, the more deaths there will be and the more difficult and expensive will it be to contain the epidemic.