A Longitudinal Study of Ebola Sequelae in Liberia

Abstract

BACKGROUND Multiple health problems have been reported in survivors of Ebola virus disease (EVD). Attribution of these problems to the disease without a control group for analysis is difficult. METHODS We enrolled a cohort of EVD survivors and their close contacts and prospectively collected data on symptoms, physical examination findings, and laboratory results. A subset of participants underwent ophthalmologic examinations. Persistence of Ebola virus (EBOV) RNA in semen samples from survivors was determined. RESULTS A total of 966 EBOV antibody–positive survivors and 2350 antibody-negative close contacts (controls) were enrolled, and 90% of these participants were followed for 12 months. At enrollment (median time to baseline visit, 358 days after symptom onset), six symptoms were reported significantly more often among survivors than among controls: 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%). On examination, more survivors than controls had abnormal abdominal, chest, neurologic, and musculoskeletal findings and uveitis. Other than uveitis (prevalence at enrollment, 26.4% vs. 12.1%; at year 1, 33.3% vs. 15.4%), the prevalence of these conditions declined during follow-up in both groups. The incidence of most symptoms, neurologic findings, and uveitis was greater among survivors than among controls. EBOV RNA was detected in semen samples from 30% of the survivors tested, with a maximum time from illness to detection of 40 months. CONCLUSIONS A relatively high burden of symptoms was seen in all participants, but certain symptoms and examination findings were more common among survivors. With the exception of uveitis, these conditions declined in prevalence during follow-up in both groups. Viral RNA in semen persisted for a maximum of 40 months.

The impact of semen testing for Ebola virus RNA on sexual behavior of male Ebola survivors in Liberia

“…As such, abandonment of abstinence and/or condoms can be expected after negative testing, and while in our study only 15% of men with an undetectable EBOV RNA semen result followed such a pattern, it is important to recognize the limitations of EBOV RNA testing of semen including variability in the lower limit of detection across assays and an incomplete understanding of the threshold below which infection is not possible-information that was shared with participants via post-test counseling with opportunities to ask questions to ensure understanding. We and others have also shown that detection of EBOV RNA in semen can be intermittent and can follow repeatedly undetectable tests [7], [18]. In particular, 5 of the 13 men in our cohort who ultimately tested positive had an initial negative test.…”

Evolving Longitudinal Retinal Observations in a Cohort of Survivors of Ebola Virus Disease

“…A prospective, controlled study of survivors of EVD who had attended the EVD survivors clinic at 34 Military Hospital in Freetown, Sierra Leone, or other medical facilities in the region and reported ophthalmic symptoms since discharge was conducted in 2016. 5 All participants of this study who attended between January 22, 2016, and April 26, 2016, were contacted by telephone and invited to attend the ophthalmology clinic for review 1 year following their baseline examination. The study was approved by the Sierra Leone Ethics and Scientific Review Committee and followed the tenets set forth by the World Medical Association Declaration of Helsinki, seventh revision (2013).…”

“…4 A retinal lesion specific to Ebola was identified in 15% of previously symptomatic survivors. 5,6 Lesions were predominantly nonpigmented, with a pale-gray appearance. Their shapes are variable, but sharp angulations are characteristic.…”

“…7 However, there is a high prevalence of uveitis secondary to other etiologies in West Africa, 8 and therefore recurrent ocular inflammation in survivors of EVD may not necessarily be secondary to Ebola. 9 This study aimed to investigate a cohort of survivors of EVD who underwent detailed ophthalmic evaluation in early 2016 5 by undertaking reexaminations 1 year later to assess for evidence of recurrent uveitis and changes in previously identified areas of DWP. 6…”

Public Health Program for Decreasing Risk for Ebola Virus Disease Resurgence from Survivors of the 2013–2016 Outbreak, Guinea

“…The program aimed to mitigate the risk for EVD reintroduction from exposure to survivors' body fluids. We were able to enroll ≈90% of the survivors in Guinea and test the semen of >90% of the enrolled male survivors >15 years of age, an unprecedented rate compared with other survivor monitoring programs (19)(20)(21)(22)(23)(24)(25).…”