The spread of Ebola in West Africa reveals two truths: The disease is swift, and it is devastating. But amid the chaos of deadly outbreak, researchers say another truth may exist: The disease might be quietly inoculating a significant portion of the population who are exposed to the virus but never succumb to it or show symptoms of being infected.
If this is true, experts say it would have significant ramifications for outbreak projections — how many more infections and deaths will we see in the coming weeks and months — and could lead to improvements in Ebola control strategies.
More than 10,000 cases of Ebola have been confirmed in the 2014 outbreak, with about half resulting in death. The three hardest-hit countries — Guinea, Sierra Leone, and Liberia — account for the vast majority of these cases, but the disease has now spread to six different African countries plus the United States and Spain. Mali, which shares a border with Guinea, confirmed their first case of Ebola on Thursday and the World Health Organization (WHO) has warned that “many people” had “high-risk exposures” to the patient, a two-year-old child who traveled on a bus from Guinea through several towns in Mali and spent two hours riding the bus in the capital, Bamako.
Leading international health authorities have warned that without a large-scale, prompt global response, the Ebola crisis in West Africa will continue to spiral out of control as fragile local health systems collapse under the strain of the disease. A few weeks ago, the US Centers for Disease Control and Prevention (CDC) released a new prediction model estimating that by early 2015, the number of Ebola cases could exceed half a million or more if effective prevention and control measures were not implemented promptly. The model suggested the number of cases was doubling every 20-40 days.
But as the virus continues to infect and kill thousands, scientists say it may also be silently immunizing an unknown number of others.
Asymptomatic Ebola infection may trigger immune response
When a person is exposed to a virus, like Ebola, their immune system produces antibodies that linger in their blood long after the infection subsides. Antibody blood tests can therefore be used to deduce past infections. Following several prior Ebola outbreaks in Central Africa, such tests showed that large numbers of people who remained healthy during an outbreak had antibodies to the virus.
In one study, 71 percent of individuals with positive Ebola antibody tests had not gotten sick; in another, 46 percent of close contacts of infectious Ebola patients who remained healthy tested positive for Ebola antibodies. The latter study also found minute concentrations of Ebola virus in these individuals’ blood, suggesting that their antibodies could not be explained by their exposure to dead virus, but that rather they had truly been infected by live virus.
Above, researchers from the French Institut de recherche pour le développement (IRD) collect epidemiological data on Ebola immunity in a Gabon village.
It’s not unheard of for some people to develop natural immunity to devastating diseases. In Peru, one in ten people in a study appeared to have survived rabies, which is a virus that was believed to be 100 percent fatal. Earlier this year, reports announced that researchers discovered rare immunity to malaria in six percent of children they studied in Tanzania.
The best evidence that some people may be immune to Ebola is research that was done in 1996 during an Ebola outbreak in Gabon. Researchers monitored two dozen contacts of known Ebola patients. These study participants never got sick even though they were in close contact with patients. Eleven of those monitored ended up having antibodies to Ebola, but they had never been symptomatic.
Fourteen years later, during a 2010 outbreak in Gabon, researchers tested the blood of nearly 4,000 people from 220 randomly selected villages in Gabon and found that antibodies for the Ebola virus were present in over 15 percent of the samples; this figure increased to almost 20 percent in the country’s forested areas. The study participants had no history of illness or exposure to people infected with Ebola infected, leading the researchers to surmise that they had developed antibodies to Ebola after coming in contact with the virus by eating fruit contaminated by the saliva of bats.
Naturally immune people could be key to stopping transmission
If individuals with Ebola antibodies but no history of infection have indeed acquired a type of immunity to Ebola, the implications could be game-changing for the fight against Ebola.
Epidemics are fueled by susceptible people; the more there are, the bigger an epidemic can become. Immunization of any kind — via vaccine or natural infection — makes people resistant and thereby slows transmission. If asymptomatic or subclinical Ebola infections actually protect against future re-infection, then Ebola is acting as its own vaccine, leaving a large wake of uninfectable people in its path. Importantly, this wake is likely to include healthcare workers who frequently contact patients and are at considerable risk for future exposure. If so, Ebola is simultaneously killing some individuals while protecting others within the population subgroup at highest priority for interventions, such as future vaccines.
If individuals with natural immunity can be identified, they could end up serving a crucial role in reducing transmission of Ebola, particularly among healthcare workers, as they could work in otherwise high-risk settings without a personal risk of infection.
Widespread acquired immunity would therefore have three important implications. First, outbreak forecasts that do not consider this phenomenon will overestimate the future extent of the outbreak. Second, naturally acquired immunity will amplify the effects of disease control measures, including vaccination. Third, if scientists can reliably detect immune individuals, then they can safely take on risky health care tasks and thereby prevent spread to non-immune caregivers.
Antibodies could be used to treat Ebola patients
Importantly, it may also be possible to utilize the blood of naturally immune individuals to develop treatments for Ebola patients. Scientists have long known that people who survive infectious diseases develop varying degrees of immunity to future infection, and that their blood contains antibodies that can boost the immune response of infected individuals. Blood from survivors of diseases including bird flu and anthrax has been used in the past when doctors ran out of options and seems to work best in diseases where there’s a toxin, such as anthrax and tetanus.
The rationale behind the approach is that blood from recovered patients contains antibodies and other components that may help the transfused patient fight off the virus. Antibodies are produced by the body’s immune system to fend off harmful things such as viruses. They remain in the blood ready to fight off any future infections by the same foreign substance. This type of treatment — called serotherapy – has been used on isolated patients in the 2014 Ebola outbreak. Kent Brantly, the American missionary doctor who contracted Ebola in Africa, received a transfusion from a 14-year-old survivor while in Africa. After Dr. Brantly was evacuated to the U.S. for treatment and recovered, he donated his own plasma to at least three patients.
Scientists are already investigating the effectiveness of serotherapy using antibodies from the blood of Ebola survivors. If individuals with silent immunity turn out to be truly immune to future Ebola infection, it may be possible to use their blood to produce mass quantities of convalescent serum to treat Ebola patients.
The evidence on serotherapy is limited, but scientists announced this week that they will soon start testing whether treatment with antibodies from the blood of Ebola survivors can help infected patients fight off the deadly disease. A clinical trial is expected to start by the end of the year in Guinea. If effective, the blood products of survivors — called convalescent serum — could be scaled up quickly as a short-term intervention while work continues to develop drugs and vaccines. And if scientists determine that so-called ‘naturally immune’ individuals — those who show immunological evidence of being exposed to Ebola yet never fell ill — are indeed immune to future Ebola infection, the antibodies found in their blood may able to be used in the same way.
Harnessing natural immunity could change the course of the epidemic
In a recent letter published in The Lancet, a team of infectious disease specialists urged scientists to fast-track research on natural immunity, suggesting that the findings could change the way the rest of the outbreak unfolds. “We want to know whether people who are infected without getting sick become immune,” said Dr. Juliet Pulliam, one of the letter’s authors and an assistant professor of biology at the University of Florida and UF’s Emerging Pathogens Institute. “If these people are protected from future infections, this would open up new opportunities for controlling the disease.”
The team, led by Dr. Steven Bellan at The University of Texas at Austin, reviewed the evidence on asymptomatic Ebola infection and concluded that natural immunity may be even more prevalent than once thought, making it a particularly promising avenue to explore. “We propose that launching of an immediate investigation of asymptomatic immunity, by coupling serological testing to ongoing intervention efforts in west Africa, is warranted and feasible, and might ultimately save lives,” the authors wrote.
The investigation needs to be as soon as possible, not only in order for any findings to have the chance to make a difference and save lives in the current outbreak, but because you can only be sure of finding individuals that are immune during an outbreak, as the authors explain:
” … the extent of protective immunity after asymptomatic infection and the identification of serological markers for protective immunity can only be definitively addressed in settings with ongoing transmission risk.”
Experts say further investigation of natural immunity should be a top research priority, given the potential for immediate — and possibly life-saving — findings.
Knowing more about silent infections will improve outbreak projections and potentially lead to life-saving advances in Ebola control measures. At the same time, given the limited resources and dire situation in West Africa, public health agencies must prioritize treating patients and preventing further infection via case isolation and contact tracing. Diverting resources to this project could mean fewer beds for treatment or a smaller budget for personal protective equipment. Moreover, surveillance for silent infection requires regular blood draws from seemingly healthy contacts of Ebola patients, which could place healthcare workers at risk of accidental transmission.
Still, said Dr. Pulliam, the potential benefits cannot be overlooked “If we can take advantage of natural immunity within the affected communities, we may be able impact the course of the epidemic even before a vaccine becomes available.”