Ebola survivors face health issues long after recovery
In June, WHO declared an end to the second largest Ebola outbreak ever, surpassed in size only by the West African Ebola epidemic.
Although that outbreak in the eastern Democratic Republic of the Congo (DRC) is over, another one on the other side of the country has begun, hitting 100 cases in 100 days. Even after Ebola outbreaks are brought under control, the fight continues for survivors who face the prospect of long-term health effects from the illness, research has shown.
“Survivors of Ebola have significant mental and physical health issues. What they go through before, during and after being admitted to the Ebola treatment units (ETUs) forever changes them,” Majid Sadigh, MD, director of global health for the Western Connecticut Health Network and the University of Vermont Larner College of Medicine, told Infectious Disease News.
“Their bodies and souls have been shattered and broken down incredibly suddenly. Diseases like leprosy grant its victims the privilege of time to adjust to the tragedy. Ebola does not,” said Sadigh, who was the chief medical officer for an American-built ETU in Liberia during the West African epidemic.
Studies have shown that Ebola survivors experience significantly reduced life expectancy, eye and kidney problems, and stigma from being infected, which can result in loss of employment and social difficulties for not just the survivor but their families.
“Many Ebola survivors have had difficulty resuming work and normal life for many different reasons — physical, psychological and social,” said Kevin M. De Cock, MD, senior advisor to the CDC’s Center for Global Health.
Infectious Disease News spoke with experts about the long-term impact of Ebola on survivors and how their lives change after being designated as “recovered.”
Higher risk for mortality
According to Anne W. Rimoin, PhD, MPH, FASTMH, professor of epidemiology and director of both the Center for Global and Immigrant Health and the UCLA-DRC Health Research and Training Program at the UCLA Fielding School of Public Health, since the West African Ebola epidemic, researchers have learned a lot about the long-term consequences of Ebola infection, including reduced life expectancy.
“It’s very likely that the burden of these long-term health effects would impact overall quality of life,” Rimoin said.
In a retrospective cohort study published last year in The Lancet Infectious Diseases, researchers collected data from 1,130 Ebola survivors who were discharged from ETUs in Guinea. Overall, the study showed that the survivors had a more than fivefold increased risk for mortality compared with the general population up to Dec. 31, 2015 (age-standardized mortality ratio = 5.2; 95% CI, 4-6.8), after a mean follow-up of 1 year from discharge. From Jan. 1, 2016, to Sept. 30, 2016, mortality did not differ between survivors and the general population (age-standardized mortality ratio = 0.6; 95% CI, 0.2-1.4).
Of these survivors, 59 deaths were reported, with 37 being attributed to renal failure, according to the researchers, who called the findings “alarming” and said that future studies should investigate the role of renal failure in late deaths among Ebola survivors.
“Although evidence was weak for most patients, renal failure is a biologically plausible cause of death in survivors of Ebola virus disease,” the researchers wrote. “The virus is often detected in urine samples during the acute phase of the disease because it can infect the kidney, and some patients with Ebola virus develop acute kidney injury, which can lead to longer term renal failure and increased mortality even after initial apparent recovery.”
The study also found that stays in ETUs that were equal to or longer than the median stay were associated with an increased risk for late death compared with shorter stays (adjusted HR = 2.62; 95% CI, 1.43-4.79).
“The high case fatality associated with Ebola virus infection, together with the long-term sequelae and late mortality associated with the infection, highlight the importance of preventive and early therapeutic clinical interventions against severe acute infections,” Hugues Fausther-Bovendo, PhD, and Gary Kobinger, PhD, researchers at the Infectious Disease Research Center at Laval University in Quebec, wrote in a related editorial.
Based on preliminary evidence, there has not been an increase in mortality among survivors of the recent eastern DRC outbreak up to 1 year from discharge, according to Anaïs Legand, MPH, a technical officer for WHO’s viral haemorrhagic fevers team and the WHO Health Emergencies Programme.
“A research protocol similar to Guinea is being implemented and data are being collected and analyzed,” she said.
‘Persistence of ocular disorders’
Among the lasting health effects experienced by Ebola survivors, “of particular importance is the persistence of ocular disorders as a result of uveitis after recovery,” Rimoin said.
According to WHO, around 20% of survivors from the West African Ebola epidemic experienced some form of eye problem.
The scale of the epidemic — 28,652 cases and 11,325 deaths — “has enabled the study of large numbers of survivors, facilitating the characterization of post-Ebola syndrome,” researchers wrote in a 2017 paper in Emerging Infectious Diseases that characterized novel retinal lesions among survivors from Sierra Leone that they said appear to be specific to Ebola survivors.
According to other studies, 13% to 34% of convalescing survivors of the West African epidemic experienced uveitis.
In the PREVAIL III cohort study, which enrolled nearly 1,000 survivors and more than 2,300 Ebola antibody-negative close contacts in Liberia to study the long-term health consequences of survivors, significantly more survivors reported urinary frequency (14.7% vs. 3.4%), headache (47.6% vs. 35.6%), fatigue (18.4% vs. 6.3%), muscle pain (23.1% vs. 10.1%), memory loss (29.2% vs. 4.8%) and joint pain (47.5% vs. 17.5%) compared with controls. Survivors also were more likely to have abdominal, chest, neurological and musculoskeletal findings and uveitis.
However, during follow-up, the prevalence of all these conditions declined, except for uveitis, which increased from rates of 26.4% vs. 12.1% at baseline to 33.3% vs. 15.4% at 1 year for survivors and controls, respectively.
“During an Ebola virus infection, the virus is attacking all organs of the patient, including some immune-privileged sites such as the anterior chamber of the eye where the virus is not neutralized by antibodies produced by the patients or by therapeutics,” Legand explained. “Therefore, eye problems look prevalent.”
Legand said the prevalence of eye problems could also be due to residents of these regions having pre-existing eye conditions before Ebola infection. She explained that these conditions may not be treated as they should be and could be reactivated during Ebola infection to appear as an apparent highly prevalent outcome.
“Eye care should be provided to Ebola survivors, as part of an Ebola survivor care program to diagnose and treat possible complications in a timely manner and mitigate the possible risk of vision impairment,” Legand said. “To be noted, in most countries that have reported Ebola outbreaks, overall health systems remain suboptimal and with limited capacities to provide ophthalmologic care. Efforts should be dedicated to strengthen health systems.”
In addition to the eyes, Ebola virus can remain in other immunologically privileged sites such as the testes and central nervous system, which are shielded from survivors’ immune systems, Sadigh said.
Because of this, Ebola transmission could potentially occur after recovery. Although unproven, sexual transmission of Ebola by men “is a strong possibility,” according to WHO, which said sexual transmission by females is “less probable, but theoretically possible.”
In an opinion piece, William A. Fischer II, MD, associate professor of pulmonology and critical care medicine at the University of North Carolina at Chapel Hill, and David Wohl, MD, co-lead of the UNC Viral Hemorrhagic Fever Research Working Group, analyzed several studies that demonstrated that Ebola virus could be detected in the semen and vaginal fluid of survivors following clearance of viremia.
According to their analysis, Ebola virus was detected in 12 of 15 (80%) men and in one of 26 (4%) women. It has been detected in semen for months after infection.
“Evidence that the virus persists in genital fluids and can be sexually transmitted, along with the potential for lingering virus in other body compartments to permit recrudescence of [Ebola virus disease], has shaken our thinking of what it takes to achieve lasting control of an Ebola epidemic,” they wrote. “A comprehensive response to the threat of persistence and sexual transmission of Ebola is required and should build on accessible longitudinal medical care of survivors and accurate genital fluid testing for Ebola. Control of [...] Ebola outbreaks will depend on our ability to recognize and respond to this persistence of the virus in those who survive.”
In 2015, Liberia launched the Men’s Health Screening Program for male Ebola survivors aged at least 15 years, which provided regular semen testing, safe sex counseling, condoms and referrals to health care services to help gather data and support survivors. Data from the program showed that 11% of the 228 participants enrolled at the 6-month mark had produced at least one positive sample and four participants had recorded two consecutive negative samples.
A later study demonstrated the long-term presence of Ebola RNA in breast milk and semen samples from survivors of the West African epidemic, including almost 10% of male survivors testing positive in at least one semen sample. Researchers calculated the probability of semen remaining positive for Ebola to be 93.02% and 60.12% after 3 and 6 months, respectively, while Ebola RNA was detectable in breast milk from a woman 1 month after she gave birth, which was 500 days after she was discharged from the Ebola treatment unit.
“In support of the view that Ebola virus can be transmitted via semen, a single instance of heterosexual transmission of the related Marburg filovirus, from a male survivor to a female partner, was reported during an outbreak in 1967,” Sadigh said.
He said another example occurred in March 2015 when a woman in Monrovia, Liberia, died from Ebola after likely contracting it from unprotected sexual intercourse with an Ebola survivor. De Cock, who co-authored the report of that case in MMWR, said they used “cautious language” in their summary but “the case was pretty [ironclad] and more than probable.”
“Despite these observations and clinical anecdotes, we have not seen any outbreaks originating from this mode of transmission,” Sadigh said.
Although the risk for transmission may be low, WHO recommends that male Ebola survivors be offered semen testing 3 months after disease onset — or even earlier if possible — and every month thereafter to those who test positive until semen tests come back negative twice, with at least a 1-month interval between tests. Additionally, according to Sadigh, until two negative Ebola tests have been achieved, WHO recommends abstaining from all intercourse or engaging in safer sex through proper and consistent use of condoms.
‘A crippling problem’
The risk for further spread and many other uncertainties surrounding Ebola transmission from survivors contributes to stigma and complicates the recovery process, making assimilation back to “normal life” difficult for survivors, experts said.
“There is no question that verbal abuse and fear of contagion lead to self-sequestration and social isolation of survivors, particularly in the early days of returning home,” Sadigh said.
He said his personal experience in Liberia was no different.
“The major reason behind stigmatization was, of course, fear of acquiring the virus through daily interaction with the survivors,” Sadigh explained. “I witnessed the attempts of community health workers, social workers and mental health counselors to overcome this major barrier by requesting community elders to accompany survivors to their homes, as well as by educating villagers and answering their questions on arrival.”
Lawrence O. Gostin, JD, director of the O’Neill Institute for National and Global Health at Georgetown University, said “stigma is a crippling problem for survivors.”
“It is bad enough to suffer the long-term consequences of this disease, but to live with stigma and discrimination is a great hardship and affects every aspect of their lives,” Gostin told Infectious Disease News.
De Cock said the stigma faced by Ebola survivors can vary by location, underscoring the importance of limiting misinformation.
“We know that stigma is a common experience among Ebola survivors when they return home, but the experience of stigma is going to vary from province to province, country to country. It even varies in the same place at a different time as beliefs, knowledge and attitudes change,” De Cock said. “It’s important to provide accurate, timely information to the survivor and communities about how to protect themselves from this possibility in order to avoid misinformation that contributes to stigmatization.”
During the recently ended Ebola outbreak in eastern DRC, frequent violence that included armed attacks on Ebola centers hindered treatment and vaccination efforts and likely prolonged the outbreak.
It likely had other consequences, too.
“An Ebola outbreak is complicated under any circumstance. An outbreak in a conflict zone makes it even more so,” Rimoin said. “Misperceptions tend to stoke fear in the affected communities. Fear can inhibit effective Ebola outbreak control. If fear leads to poor response during an outbreak, we can assume that endemic issues that stoke fear and stigma will likewise harm survivors.”
Support for survivors
Despite the many challenges faced by Ebola survivors, they can be supported as they navigate back to normal life.
“The care program for Ebola virus survivors is a good example of what can be done to alleviate suffering and stigma,” Legand told Infectious Disease News.
According to Legand, the program has been operating in the DRC since 2018 following the outbreak in Equateur Province and is being used in the Eastern DRC outbreak. It was based on and adapted from research and programs conducted in West Africa.
According to Legand, “Most of the survivors enrolled in the program are able to go back to their normal life and work should they receive adequate support.”
“However, something they must go through is how to return to their community, which could trigger loss of employment, rejection from their community and other issues that make their life complicated,” Legand said.
The program — which has offered enrollment to 1,164 Ebola survivors in the DRC from the provin ces of Ituri, North Kivu and South Kivu — has five clinics in the towns of Beni, Butembo, Goma, Mambasa and Mangina. According to WHO, each of the clinics is equipped with a physician, a psychologist, two laboratory technicians, a nurse, two hygienists, two psychosocial assistants and a representative of Ebola survivors to help engage more survivors. The clinics offer examinations and care, psychological evaluation and care, counseling on safer sex practices and sample analysis. Additionally, an ophthalmologic clinic has been set up in Butembo.
Data on the program provided by WHO demonstrated that Ebola survivors trust the program, with a monthly follow-up rate of 90% and more than 11,000 clinical and psychological consultations performed. Additionally, WHO said efforts are ongoing to find people who might not have been seen in monthly follow-up visits to offer enrollment.
“We hope this program has a positive impact on increasing the level of trust and positively influencing or changing to correct some misinformation and generate trust,” Legand said.
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- WHO. Eye care for Ebola survivors. https://www.who.int/news-room/feature-stories/detail/eye-care-for-ebola-survivors. Accessed August 25, 2020.
- For more information:
- Kevin M. De Cock, MD, can be reached at email@example.com.
- Lawrence O. Gostin, JD, can be reached at firstname.lastname@example.org.
- Anaïs Legand, MPH, can be reached at email@example.com.
- Anne Rimoin, PhD, MPH, can be reached at firstname.lastname@example.org.
- Majid Sadigh, MD, can be reached at email@example.com.
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