Long-term Complications of Ebola Virus Disease: Prevalence and Predictors of Major Symptoms and the Role of Inflammation.

BACKGROUND: Cohort studies have reported a high prevalence of musculoskeletal, neurologic, auditory, and visual complications among Ebola virus disease (EVD) survivors. However, little is known about the host- and disease-related predictors of these symptoms and their etiological mechanisms. METHODS: The presence and patterns of 8 cardinal symptoms that are most commonly reported following EVD survival were assessed in the 326 EVD survivors who participated in the ongoing longitudinal Liberian EVD Survivor Study. At quarterly study visits, symptoms that developed since acute EVD were recorded and blood was collected for biomarkers of inflammation and immune activation. RESULTS: At baseline (mean 408 days from acute EVD), 75.5% of survivors reported at least 1 new cardinal symptom since surviving EVD, which in 85.8% was rated as highly interfering with life. Two or more incident symptoms were reported by 61.0% of survivors, with pairings of joint pain, headache, or fatigue the most frequent. Women were significantly more likely than men to report headache, while older age was significantly associated with musculoskeletal and visual symptoms. In analyses adjusted for multiple comparisons, no statistically significant association was found between any symptom and 26 markers of inflammation and immune activation. Symptom frequency remained largely unchanged during study follow-up. CONCLUSIONS: Post-EVD complications occur in a majority of survivors and remain present more than 4 years after acute infection. An association between markers of inflammation and immune activation and individual symptoms was not found, suggesting an alternative etiology for persistent post-EVD symptomatology.

Anti-Ebola Virus Antibody Levels in Convalescent Plasma and Viral Load After Plasma Infusion in Patients With Ebola Virus Disease.

Background: Ebola virus (EBOV) neutralizing antibody in plasma may reduce viral load following administration of plasma to patients with Ebola virus disease (EVD), but measurement of these antibodies is complex. Methods: Anti-EBOV antibody was measured by 2 neutralization and 2 enzyme-linked immunosorbent assays (ELISAs) in convalescent plasma (ECP) from 100 EVD survivor donors in Liberia. Viral load was assessed repetitively in patients with EVD participating in a clinical trial of enhanced standard of care plus ECP. Results: All 4 anti-EBOV assays were highly concordant for detection of EBOV antibody. Antibodies were not detected in plasma specimens obtained from 15 of 100 donors, including 7 with documented EBOV-positive reverse-transcription polymerase chain reaction during EVD. Viral load was reduced following each dose in the 2 clinical trial participants who received ECP with higher antibody levels but not in the 2 who received ECP with lower antibody levels. Conclusions: Recovery from EVD can occur with absence of detectable anti-EBOV antibody several months after disease onset. ELISAs may be useful to select ECP donors or identify ECP units that contain neutralizing antibody. ECP with higher anti-EBOV antibody levels may have greater effect on EBOV load-an observation that requires further investigation. Clinical Trials Registration: NCT02333578.

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

Sexual transmission of Ebola virus (EBOV) is well established and has been implicated in multiple resurgences during the West African Ebola epidemic. Given the persistence of viral RNA in semen, guidelines from the World Health Organization (WHO) recommend abstinence or condom use for at least 1 year or until two semen PCR tests are negative. To better understand the impact of semen testing on sexual behavior, male EVD survivors were surveyed regarding their sexual behavior before and after semen testing. Of the 171 men who enrolled, 148 reported being sexually active following discharge from an ETU with 59% reporting episodes of condomless sex. At least one semen sample for testing was provided by 149 men and 13 of these men had EBOV RNA detected in their semen. When comparing sexual behaviors before and after semen testing, a positive semen test result had limited impact on behavior. Of those with seminal EBOV RNA detected, 61% reported no change in behavior pre- and post-semen testing with 46% engaging in condomless sex before and after testing and only 1 adopted safer sex behaviors following receipt of a positive result. Similarly, among men with undetectable EBOV in their semen, 66% reported no change in sexual behaviors with semen testing, with 55% forgoing condoms during sex. In only 11% was a negative semen result followed by abandoning condoms. There were no known sexual transmission events of Ebola virus in this cohort despite viral presence in semen during periods of condomless sex. This highlights the need to better understand the infectious potential of viral RNA persistence and determine what constitutes effective counseling for survivors and their partners.

Stigma and Ebola survivorship in Liberia: Results from a longitudinal cohort study.

BACKGROUND: Survivors of the 2014-2016 West Africa Ebola epidemic have been reported to suffer high levels of stigmatization after return to their communities. We sought to characterize the stigma encountered by a cohort of Ebola survivors in Liberia over time. METHODS: Ebola-related stigma was assessed from June 2015 to August 2017 in 299 adolescent and adult Liberian Ebola Survivor Cohort participants at three month intervals using adapted HIV stigma scales scored from 0 to 10 according to the proportion of answers indicating stigmatization. FINDINGS: The median time from Ebola Virus Disease (EVD) to study entry was 393 days (IQR 336-492). Participants (43% female) had a median age of 31 (IQR 25-40) years. Mean self-reported stigma levels were greater at baseline (6.28 ± 0.15 [IQR: 4.38-8.75]) compared to the first post-baseline visit (0.60 ± 0.10 [IQR: 0-0]; p<0.0001). During follow-up, stigma levels were stable. Baseline stigma significantly increased during enrollment and following clusters of Ebola re-emergence in Liberia. Survivors encountered primarily enacted and perceived external stigma rather than internalized stigma. CONCLUSIONS: Ebola-related stigma was prevalent among Liberian survivors more than a year after EVD recovery. Self-reported stigma was greater in the period before cohort enrollment; however, some degree of stigmatization persisted years after EVD. Transient rises in stigma were observed following episodic Ebola re-emergence of EVD in Liberia. During future EVD outbreaks, enhanced public health interventions designed to prevent and mitigate Ebola-related stigma that is enacted and external should be implemented to support survivor recovery and community re-integration.

Ebola Virus Ribonucleic Acid Detection in Semen More Than Two Years After Resolution of Acute Ebola Virus Infection.

Among 149 men who survived Ebola virus disease (EVD) and donated semen 260-1016 days after EVD onset, Ebola virus (EBOV) ribonucleic acid (RNA) was detected in 13 (9%). Of 137 men who donated semen 2 years after EVD onset, 11 (8%) had an EBOV RNA-positive specimen. The mechanism underlying the persistence of EBOV RNA in semen is unclear, and it is unclear whether the detection of viral RNA represents the presence of infectious virus.