By Gary Evans, Senior Staff Writer
U.S. healthcare workers who survived Ebola after acquiring it from patients have suffered a wide variety of symptoms and maladies, with only one survivor considered symptom-free at five months after discharge, according to the Centers for Disease Control and Prevention (CDC).1
Though it is not completely clear in all cases if post-Ebola symptoms are the result of damage inflicted during infection or reflect some lingering presence of the virus, none of the healthcare workers are considered an infectious threat to patients or the public and most have returned to work or other activities.
However, Ebola clearly does not end at discharge, as survivors report a panoply of recurrent pains, aches, nerve tingling, hearing and vision problems, extreme fatigue, anxiety, and depression. For example, one of the U.S. nurses occupationally infected with Ebola described nightmares and fears about a future recurrence of the virus or some unintended consequences of novel treatment.2
“There are many unanswered questions about post-Ebola virus disease symptoms,” says Tim Uyeki, MD, MPH, a CDC epidemiologist who has co-authored several papers on the Ebola response. “Prospective, longitudinal research studies of Ebola virus disease survivors — along with a comparison group of persons who did not have Ebola virus disease — are needed to better understand the frequency, severity, duration, and pathogenesis of the complications, sequelae, and symptoms experienced by Ebola survivors.”
In one of the more shocking cases, a Scottish nurse who had been successfully treated for Ebola in January 2015 was readmitted last October for meningitis thought to be caused by surviving virus in her brain.3 She recovered again, but joins the cases of Ebola viral persistence in the eyes, semen, and other so-called “immune privileged” body sites which may have evolved to mitigate collateral damage during an inflammatory immune response.
In one of the U.S. cases included in the CDC report, a physician who had completed treatment and was discharged from Emory University Hospital in Atlanta later developed vision problems and almost went blind in his left eye. He eventually recovered, but not before the affected iris actually changed color from blue to green and the virus was recovered in mutated form from the infected eye.
When compared to the Ebola in the patient’s blood during hospitalization, the virus sequenced from ocular fluid by researchers4 “identified a single nonsynonymous mutation, as well as two silent mutations and two mutations in noncoding regions. The significance of these mutations is unknown. However, these findings are in contrast to results that showed no changes in viral consensus sequences acquired over several days from a single patient.5 All personal protective equipment and materials that were used during paracentesis and laboratory testing were sterilized by means of autoclaving before disposal.”
Overall, 11 patients with Ebola were treated in U.S. hospitals and nine survived. The dead include Thomas Duncan, a Liberian man who developed symptoms after arriving in the U.S. from Africa. He died Oct. 8, 2014, in a Dallas hospital after infecting two nurses who survived. The other fatality was Martin Salia, MD, a surgeon who was a native of Sierra Leone and a U.S. citizen. He died Nov. 17, 2014, at the University of Nebraska biocontainment unit. The two deaths among the 11 U.S. cases translate to a 15% mortality rate, nearly four-fold less than the 58% rate of deaths in healthcare workers who acquired Ebola in West Africa and remained there for care. As of Nov. 1, 2015, the World Health Organization reported that a total of 881 healthcare workers have been infected with Ebola during patient care and 513 of them have died. With a few threads of possible transmission still being followed, the WHO reports 28,598 Ebola cases with 11,299 deaths in the outbreak.
8 U.S. SURVIVORS SURVEYED
In a breakdown of the U.S. cases, two healthcare workers acquired Ebola in the U.S.; two — Duncan and a U.S. physician — became symptomatic after travel from West Africa; and the remainder were infected in Africa and became symptomatic before being flown in for treatment.
The U.S. survivors are primarily healthcare workers, but also include a photojournalist and a missionary aid worker who helped disinfect personal protective equipment in West Africa.
“Among the eight U.S. survivors who we surveyed, most reported that their symptoms resolved or improved over time,” says CDC lead author Lauren Epstein, MD, an officer in the Epidemic Intelligence Service. “However, only one survivor reported complete resolution of all symptoms at the time we conducted the survey in March 2015. We did not specifically assess whether survivors returned to medical work — however, 75% of the survivors returned to normal daily activities within eight weeks after discharge.”
The CDC administered a questionnaire by telephone or in person to the U.S. survivors about symptoms, diagnostic testing, and treatment occurring any time during the recovery period. Medical records were not reviewed and the CDC determined that the survey did not meet the definition of human research that would require oversight by an institutional review board.
The median interval from hospital discharge and survey administration was five months. All survivors reported having had at least one symptom during the recovery period. These symptoms ranged from mild to more severe complications requiring rehospitalization or treatment. The most frequently reported symptoms were lethargy or fatigue, joint pain, and alopecia, an autoimmune disease that causes hair loss. Five patients (63%) reported having eye problems, including pain, discomfort, or blurriness. Of these patients, four underwent ophthalmologic evaluation, and two were treated for unilateral uveitis, an inflammation of the iris or other parts of the eye that can cause blindness. They were diagnosed with uveitis from two weeks to eight weeks after hospital discharge for Ebola treatment.
Six patients (75%) reported having psychological or cognitive symptoms, including short-term memory loss, insomnia, and depression or anxiety, the CDC reported. Three patients (38%) reported having paresthesia or a tingling sensation in the peripheral nerves, and one received treatment for peripheral neuropathy nerve damage. Two patients (25%) were rehospitalized briefly for febrile illness that was not related to Ebola.
SURVIVORS NEED SPECIALTY CARE
Given the findings, some Ebola survivors “may benefit from psychological and subspecialty assessment — rheumatologic, musculoskeletal, neurologic and ophthalmologic — in addition to primary care,” Epstein says.
Hospital Employee Health asked Uyeki if there are any particular precautions or special measures that Ebola survivors who are healthcare workers need to take to return to patient care?
“Our survey did not address these issues,” he says. “However, persons who have recovered from Ebola virus disease who are asymptomatic do not pose any risk of Ebola virus transmission to the general public or to close contacts.”
In light of a study6 finding that Ebola can persist in semen for at least nine months, the CDC recommends male survivors abstain from unprotected sex until semen tests negative twice.
This next stage of control could be a formidable challenge, as there are tens of thousands of African men among the estimated 18,000 Ebola survivors. The WHO recently reported that a cluster of cases in Liberia were the “result of the re-emergence of Ebola virus that had persisted in a previously infected individual. Although the probability of such re-emergence events is low, the risk of further transmission following a re-emergence underscores the importance of implementing a comprehensive package of services for survivors that includes the testing of appropriate bodily fluids for the presence of Ebola virus RNA.”7
The governments of Liberia and Sierra Leone, with support from partners including WHO and CDC, have implemented voluntary semen screening and counselling programs for male survivors in order to help affected individuals understand their risk and take necessary precautions to protect close contacts. In addition, the Ministry of Health of Liberia and the U.S. National Institute of Allergy and Infectious Diseases are conducting a five-year study of thousands of survivors in Liberia and their close contacts. The findings and other research might change the treatment and follow-up of healthcare workers or other Ebola survivors, possibly developing ways to stave off or mitigate the aftershocks through interventions earlier in the course of treatment.
REFERENCES
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Epstein L, Wong KK, Kallen AJ, et al. Centers for Disease Control and Prevention. Post-Ebola Signs and Symptoms in U.S. Survivors. N Engl J Med 2015; 373:2484-2486December 17, 2015DOI: 10.1056/NEJMc1506576.
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Lupkin, S. Life After Ebola: Nurse Nina Pham Says She Has Nightmares, Aches, Hair Loss. ABC News Mar 2, 2015.
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Paddock, C. British nurse Pauline Cafferkey defeats Ebola — again. MNT Nov. 13 2015: http://www.medicalnewstoday.com/.
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Varkey JB, Shantha JG, Crozier I, et al. Persistence of Ebola virus in ocular fluid during convalescence. N Engl J Med 2015;372:2423-2427.
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Gire SK, Goba A, Anderson KG, et al. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science 2014;345:1369-1372.
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Deen GF, Knust B, Broutet, et al. Ebola RNA Persistence in Semen of Ebola Virus Disease Survivors — Preliminary Report. N Engl J Med. October 14, 2015 DOI: 10.1056/NEJMoa1511410.
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WHO. Ebola Situation Report — 16 December 2015:http://bit.ly/1YMz16y.
