Post-Ebola Symptoms 7 Years After Infection: The Natural History of Long Ebola.

BACKGROUND: Lingering symptoms have been reported by survivors of Ebola virus disease (EVD). There are few data describing the persistence and severity of these symptoms over time. METHODS: Symptoms of headache, fatigue, joint pain, muscle pain, hearing loss, visual loss, numbness of hands or feet were longitudinally assessed among participants in the Liberian Ebola Survivors Cohort study. Generalized linear mixed effects models, adjusted for sex and age, were used to calculate the odds of reporting a symptom and it being rated as highly interfering with life. RESULTS: From June 2015 to June 2016, 326 survivors were enrolled a median of 389 days (range 51-614) from acute EVD. At baseline 75.2% reported at least 1 symptom; 85.8% were highly interfering with life. Over a median follow-up of 5.9 years, reporting of any symptom declined (odds ratio for each 90 days of follow-up = 0.96, 95% confidence interval [CI]: .95, .97; P < .0001) with all symptoms declining except for numbness of hands or feet. Rating of any symptom as highly interfering decreased over time. Among 311 with 5 years of follow-up, 52% (n = 161) reported a symptom and 29% (n = 47) of these as highly interfering with their lives. CONCLUSIONS: Major post-EVD symptoms are common early during convalescence and decline over time along with severity. However, even 5 years after acute infection, a majority continue to have symptoms and, for many, these continue to greatly impact their lives. These findings call for investigations to identify the mechanisms of post-EVD sequelae and therapeutic interventions to benefit the thousands of effected EVD survivors.

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.

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.

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.