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. (Funded by the National Institute of Allergy and Infectious Diseases and the National Eye Institute; PREVAIL III ClinicalTrials.gov number, NCT02431923.).

Figure 1.. Enrollment, Follow-up, and Antibody Measurements in the Study Population.

Panel A shows a flow diagram for the generation of the analysis cohort. Panel B shows a kernel-density plot of the distribution of log₁₀ antibody concentrations among the Ministry of Health–reported survivors and the survivor-reported close contacts. The black vertical line indicates the antibody concentration cutoff for determining Ebola virus seropositivity or seronegativity. EU denotes enzyme-linked immunosorbent assay units.

Figure 2.. Frequency of Semen Samples Testing Positive for Ebola Virus RNA since the Time of Acute Infection.

Data points represent model-based estimates of the probability of testing positive for individual samples; vertical bars represent 95% confidence intervals for the probability of a sample being positive, based on samples grouped into 25-day bins; and the piecewise linear black curve shows the sample proportions in these bins. The red curve represents a model-based population trend for the probability of a sample testing positive for Ebola virus RNA.