Understanding Long-term Evolution and Predictors of Sequelae of Ebola Virus Disease Survivors in Guinea: A 48-Month Prospective, Longitudinal Cohort Study (PostEboGui).
Ontology highlight
ABSTRACT: Background
Longitudinal analyses are needed to better understand long-term Ebola virus disease (EVD) sequelae. We aimed to estimate the prevalence, incidence, and duration of sequelae and to identify risk factors associated with symptom occurrence among EVD survivors in Guinea.Methods
We followed 802 EVD survivors over 48 months and recorded clinical symptoms with their start/end dates. Prevalence, incidence, and duration of sequelae were calculated. Risk factors associated with symptom occurrence were assessed using an extended Cox model for recurrent events.Results
Overall, the prevalence and incidence of all symptoms decreased significantly over time, but sequelae remained present 48 months after Ebola treatment center discharge with a prevalence of 30.68% (95% confidence interval [CI] 21.40-39.96) for abdominal, 30.55% (95% CI 20.68-40.41) for neurologic, 5.80% (95% CI 1.96-9.65) for musculoskeletal, and 4.24% (95% CI 2.26-6.23) for ocular sequelae. Half of all patients (50.70%; 95% CI 47.26-54.14) complained of general symptoms 2 years' postdischarge and 25.35% (95% CI 23.63-27.07) 4 years' post-discharge. Hemorrhage (hazard ratio [HR], 2.70; P = .007), neurologic (HR 2.63; P = .021), and general symptoms (HR 0.34; P = .003) in the EVD acute phase were significantly associated with the further occurrence of ocular sequelae, whereas hemorrhage (HR 1.91; P = .046) and abdominal (HR 2.21; P = .033) symptoms were significantly associated with musculoskeletal sequelae.Conclusions
Our findings provide new insight into the long-term clinical complications of EVD and their significant association with symptoms in the acute phase, thus reinforcing the importance of regular, long-term follow-up for EVD survivors.
SUBMITTER: Diallo MSK
PROVIDER: S-EPMC8677527 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundThere are limited data regarding the long-term health effects of child survivors of the 2013-2016 West African Ebola virus disease (EVD) outbreak. Here, we assess post-Ebola sequelae among EVD child survivors by comparing the self-reported symptoms between EVD child survivors and their close household contacts over one year after the end of the outbreak.MethodsEVD child survivors(n=159) and their close contacts(n=303) were enrolled in Western and Eastern Sierra Leone. Demographics and self-reported symptoms data were collected using an interviewer-administered questionnaire. We compared a list of self-reported symptoms between EVD child survivors and their close household contacts using backward stepwise logistic regression.ResultsEVD child survivors were more likely to be orphans compared to their close contacts. Musculoskeletal, ocular, auditory and neurological symptoms were more prevalent among Ebola child survivors than their close contacts (p<0.001). Joint pain and headache were the most common self-reported symptoms in EVD child survivors and their close contacts. Joint pain (AOR=2.633; 95 % CI:1.31-5.28, p=0.006), eye pain (AOR=4.56;95 %CI: 2.16-9.64, p<0.001), hearing loss (AOR=3.85; 95 %CI: 1.15-12.87, p=0.029), memory impairment (AOR=7.76;0.95 %CI: 1.34-45.01 p=0.022), mood changes (AOR=5.07; 95 %CI: 2.35-10.94, p<0.001) were more common among survivors than their contacts.ConclusionsOur data suggest that EVD child survivors have higher odds than their close contacts of suffering from musculoskeletal, ophthalmic, auditory and neurological impairment more than a year after the end of the EVD outbreak. Routine screening, treatment and monitoring of these symptoms is required to prevent long-term disability among EVD child survivors.
| S-EPMC8556876 | biostudies-literature
Project description:BackgroundEbola virus disease (EVD) outbreaks in West Africa (2013-2016) and the Democratic Republic of Congo (2018-2020) have resulted in thousands of EVD survivors who remain at-risk for survivor sequelae. While EVD survivorship has been broadly reported in adult populations, pediatric EVD survivors are under-represented. In this cross-sectional study, we investigated the prevalence of eye disease, health-related quality-of-life, vision-related quality-of-life, and the burden of mental illness among pediatric EVD survivors in Sierra Leone.MethodsTwenty-three pediatric EVD survivors and 58 EVD close contacts were enrolled. Participants underwent a comprehensive ophthalmic examination and completed the following surveys: Pediatric Quality of Life Inventory Version 4.0, Effect of Youngsters Eyesight on Quality-of-Life, and the Revised Child Anxiety and Depression Scale.FindingsA higher prevalence of uveitis was observed in EVD survivor eyes (10·8%) cohort compared to close contacts eyes (1·7%, p=0·03). Overall, 47·8% of EVD survivor eyes and 31·9% of close contact eyes presented with an eye disease at the time of our study (p=0·25). Individuals diagnosed with an ocular complication had poorer vision-related quality-of-life (p=0·02).InterpretationBoth health related quality-of-life and vision-related quality-of-life were poor among EVD survivors and close contacts. The high prevalence of eye disease associated with reduced vision health, suggests that cross-disciplinary approaches are needed to address the unmet needs of EVD survivors.FundingNational Institutes of Health R01 EY029594, K23 EY030158; National Eye Institute; Research to Prevent Blindness (Emory Eye Center); Marcus Foundation Combating Childhood Illness; Emory Global Health Institute; Stanley M. Truhlsen Family Foundation.
| S-EPMC9167858 | biostudies-literature
Project description:BackgroundMultiple 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.MethodsWe 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.ResultsA 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.ConclusionsA 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.).
| S-EPMC6478393 | biostudies-literature
Project description:BackgroundDuring the 2014-15 Ebola Virus Disease (EVD) epidemic, thousands of people in Sierra Leone were infected with the devastating virus and survived. Years after the epidemic was declared over, stigma toward EVD survivors and others affected by the virus is still a major concern, but little is known about the factors that influence stigma toward survivors. This study examines how key personal and ecological factors predicted EVD-related stigma at the height of the 2014-2015 epidemic in Sierra Leone, and the personal and ecological factors that shaped changes in stigma over time.MethodsUsing three waves of survey data from a representative sample in the Western Urban and Western Rural districts of Sierra Leone, this study examines factors associated with self-reported personal stigma toward Ebola survivors (11 items, α = 0.77) among 1008 adults (74.6% retention rate) from 63 census enumeration areas of the Western Rural and Western Urban districts of Sierra Leone. Participants were randomly sampled at the height of the EVD epidemic and followed up as the epidemic was waning and once the epidemic had been declared over by the WHO. Three-level mixed effects models were fit using Stata 16 SE to examine cross-sectional associations as well as predictors of longitudinal changes in stigma toward EVD survivors.ResultsAt the height of the EVD epidemic, female sex, household wealth, post-traumatic stress, EVD-related fear and perceived infection risk are a few of the factors which predicted higher levels of stigma toward survivors. On average, stigma toward EVD survivors decreased significantly as the epidemic declined in Sierra Leone, but female sex, EVD fear, and risk perceptions predicted a slower rate of change.ConclusionThis study identified key individual and psychosocial characteristics which may predict higher levels of stigma toward infectious disease survivors. Future studies should pursue a better understanding of how personal characteristics and perceptions, including psychosocial distress, fear, and perceived infection risk serve as pathways for stigma in communities affected by infectious disease.
| S-EPMC8581958 | biostudies-literature
Project description:Background:The Eternal Love Winning Africa (ELWA) Clinic was the first clinic to provide free, comprehensive care to Ebola virus disease (EVD) survivors in Liberia. The objectives of this analysis were to describe the demographics and symptoms of EVD survivors at ELWA from January 2015 through March 2017 and to identify risk factors for development of sequelae. Methods:Patients' demographic and clinical information was collected by chart review in June 2016 and March 2017. Associations with clinical sequelae were analyzed using the chi-square test, t test, and multivariate logistic regression. Results:From January 2015 to March 2017, 329 EVD survivors were evaluated at ELWA. Most survivors experienced myalgia/arthralgia (73%; n = 239) and headache (53%; n = 173). The length of time from Ebola Treatment Unit (ETU) discharge to first clinic visit ranged from 0 to 30 months. Many visits (30%) occurred 24 or more months after ETU discharge. The proportion of visits for headache, weight loss, joint pain, visual problems, insomnia, fatigue, memory loss, decreased libido, depression, and uveitis decreased over time. More men than women had visits for depression; however, these differences were not significant. Symptom prevalence differed in adults and children; significantly more adults experienced myalgia/arthralgia (77% vs 44%), visual problems (41% vs 12%), post-EVD-related musculoskeletal pain (42% vs 15%), and insomnia (17% vs 2%). Conclusions:EVD survivors frequented ELWA for EVD-related symptoms many months after ETU discharge, indicating a long-term need for care. Reported symptoms changed over time, which may reflect eventual resolution of some sequelae.
| S-EPMC6202424 | biostudies-literature
Project description:Background:With the increasing frequency and impact of Ebola virus disease (EVD) outbreaks illustrated by recent epidemics, a good understanding of the extent of viral persistance or ribonucleic acid (RNA) detection in body fluids from survivors is urgently needed. Methods:Ebola viral RNA shedding was studied with molecular assays in semen (n = 1368), urine (n = 1875), cervicovaginal fluid (n = 549), saliva (n = 900), breast milk (n = 168), and feces (n = 558) from EVD survivors in Guinea (PostEbogui cohort, n = 802) at a regular base period until 40 months after inclusion. Results:Twenty-seven of 277 (9.8%) male survivors tested positive for Ebola RNA in at least 1 semen sample. The probability of remaining positive for Ebola RNA in semen was estimated at 93.02% and 60.12% after 3 and 6 months. Viral RNA in semen was more frequent in patients with eye pain (P = .036), joint pain (P = .047), and higher antibody levels to Ebola virus antigens (nucleoprotein [P = .001], glycoprotein [P = .05], and viral protein-40 [P = .05]). Ebola RNA was only rarely detected in the following body fluids from EVD survivors: saliva (1 of 454), urine (2 of 593), breast milk (2 of 168), cervicovaginal secretions (0 of 273), and feces (0 of 330). Ribonucleic acid was detected in breast milk 1 month after delivery but 500 days after discharge of Ebola treatment unit (ETU) in 1 woman who became pregnant 7 months after discharge from the ETU. Conclusions:The frequency and potential long-term presence of viral RNA in semen confirmed that systematic prevention measures in male survivors are required. Our observation in breast milk suggests that our knowledge on viral reservoir in immune-privileged sites and its impact are still incomplete.
| S-EPMC7047953 | biostudies-literature
Project description:BackgroundEbola virus (EBOV) disease has killed thousands of West and Central Africans over the past several decades. Many who survive the acute disease later experience post-Ebola syndrome, a constellation of symptoms whose causative pathogenesis is unclear.MethodsWe investigated EBOV-specific CD8+ and CD4+ T-cell responses in 37 Sierra Leonean EBOV disease survivors with (n = 19) or without (n = 18) sequelae of arthralgia and ocular symptoms. Peripheral blood mononuclear cells were infected with recombinant vesicular stomatitis virus encoding EBOV antigens. We also studied the presence of EBOV-specific immunoglobulin G, antinuclear antibodies, anti-cyclic citrullinated peptide antibodies, rheumatoid factor, complement levels, and cytokine levels in these 2 groups.ResultsSurvivors with sequelae had a significantly higher EBOV-specific CD8+ and CD4+ T-cell response. No differences in EBOV-specific immunoglobulin G, antinuclear antibody, or anti-cyclic citrullinated peptide antibody levels were found. Survivors with sequelae showed significantly higher rheumatoid factor levels.ConclusionEBOV-specific CD8+ and CD4+ T-cell responses were significantly higher in Ebola survivors with post-Ebola syndrome. These findings suggest that pathogenesis may occur as an immune-mediated disease via virus-specific T-cell immune response or that persistent antigen exposure leads to increased and sustained T-cell responses.
| S-EPMC7529037 | biostudies-literature
Project description:Antibodies that mediate non-neutralizing functions play an important role in the immune response to Ebola virus (EBOV) and are thought to impact disease outcome. EBOV has also been associated with long term sequelae in survivors, however, the extent to which antibodies that mediate non-neutralizing functions are associated with the development of these sequelae is unknown. Here, the presence of antibodies mediating different effector functions and how they relate to long-term sequelae two years after the 2007 Bundibugyo Ebola virus (BDBV) outbreak was investigated. The majority of survivors demonstrated robust antibody effector functional activity and demonstrated persistent polyfunctional antibody profiles to the EBOV glycoprotein (GP) two years after infection. These functions were strongly associated with the levels of GP-specific IgG1. The odds of developing hearing loss, one of the more common sequelae to BDBV was reduced when antibodies mediating antibody dependent cellular phagocytosis (ADCP), antibody dependent complement deposition (ADCD), or activating NK cells (ADNKA) were observed. In addition, hearing loss was associated with increased levels of several pro-inflammatory cytokines and levels of these pro-inflammatory cytokines were associated with lower ADCP. These results are indicating that a skewed antibody profile and persistent inflammation may contribute to long term outcome in survivors of BDBV infection.
| S-EPMC8173169 | biostudies-literature
Project description:INTRODUCTION:During the 2014 Ebola Virus Disease (EVD) epidemic, the Ebola-Tx trial evaluated the use of convalescent plasma (CP) in Guinea. The effectiveness of plasmapheresis trials depends on the recruitment of plasma donors. This paper describes what motivated or deterred EVD survivors to donate CP, providing insights for future plasmapheresis trials and epidemic preparedness. METHODS:This qualitative study, part of Ebola-Tx, researched and addressed emergent trial difficulties through interviewing, participant observation and focus group discussions. Sampling was theoretical and retroductive analysis was done in NVivo 10. RESULTS:Willingness or hesitance to participate in plasma donation depended on factors at the interface of pre-existing social dynamics; the impact of the disease and the consequent emergency response including the trial set-up. For volunteers, motivation to donate was mainly related to the feeling of social responsibility inspired by having survived EVD and to positive perceptions of plasmapheresis technology despite still unknown trial outcomes. Conversely, confidentiality concerns when volunteering due to stigmatization of survivors and perceived decrease in vital strength and in antibodies when donating, leading to fears of loss in protection against EVD, were main deterrents. The dynamic (dis)trust in Ebola Response Actors and in other survivors further determined willingness to participate and lead to the emergence/decline of rumours related to blood stealing and treatment effectiveness. Historic inter-ethnic relations in the health care setting further defined volunteering along socio-economic and ethnic lines. Finally, lack of follow-up and of dedicated care further impacted on motivation to volunteer. CONCLUSIONS:Ebola-Tx was the first trial to solicit and evaluate blood-product donation as an experimental treatment on a large scale in Sub-Saharan Africa. An effective donation system requires directly engaging with emergent social barriers and providing an effective ethical response, including improved and transparent communication, effective follow-up after donation, assuring confidentiality and determining ethical incentives.
| S-EPMC6219816 | biostudies-literature
Project description:BackgroundPersistence of Ebola virus (EBOV) in semen remains of deep concern, as sexual transmission of EBOV seems plausible up to 6 months after acute phase of Ebola virus disease (EVD). Favipiravir, a broad spectrum antiviral product, has been evaluated in reducing EVD mortality in Guinea in 2014-2015 in the JIKI trial, the pharmacokinetic results of which suggest that an increase of dose might be necessary to achieve a therapeutically relevant exposure. In FORCE trial, we aimed at evaluating the tolerance and activity of high doses of favipiravir in male EVD survivors with EBOV RNA detection in semen in Guinea.CaseIn 2016, we launched a phase IIa open-labeled multicenter dose escalation study. Male survivors of EVD with EBOV RT-PCR positive on semen received a loading dose of 2400 mg BID of favipiravir on day 1 then a maintenance dose of 1800 mg BID from day 2-14. The primary outcome was the tolerance, assessed daily during period treatment and up to day 90. Unfortunately only two participants were included and the trial was stopped for lack of recruitment. No clinical adverse event of grade 3/4 was reported for both patients. One patient experienced a grade 3 hypocalcemia at day 10 and 14.ConclusionsHigh doses of favipiravir were well tolerated in these two participants. Better characterized tolerance and pharmacokinetics of high doses of favipiravir are of utmost importance considering that favipiravir is a candidate treatment for a variety of emerging severe viral diseases with poor prognosis.
| S-EPMC8808076 | biostudies-literature