Quality of life and factors associated among caregivers of adolescent and young adult Ebola survivors in Democratic Republic of the Congo, a cross-sectional study.

BACKGROUND: Ebola virus disease is a medical condition whose consequent effects on quality of life of patients. In the history of infectious diseases, there have been pathologies that have had significant repercussions for caregivers, healthcare providers and the community. OBJECTIVES: This study investigate determinants of quality of life among caregivers of adolescent and young adult Ebola survivors in Democratic Republic of the Congo. METHODS: This was a cross sectional study. The study sites were the two health districts of Beni and Katwa, in North-Kivu province in the Eastern part of Democratic Republic of the Congo. The study period was from April to August 2022. Participants of the study were caregivers of adolescents and young adult Ebola virus survivors. Simple random sampling technique was used to select the 68 study participants. A questionnaire was administered. Data was collected using pretested questionnaire of WHO quality of life Bref (WHOQOL-BREF) and CommCare by Dimagi.Inc. lastest Version 2.52.1 and  a sum of score of 78 or higher indicated a high level of life quality. To determine the quality of life of caregivers of adolescents and young adult EVD survivors, descriptive analysis was used. The Pearson correlation coefficient was utilized to check whether the predictor variables are multicollinear. The regression analysis produced the crude odds ratio (COR), adjusted odds ratio (aOR), 95% confidence interval (CI), and p-value. Statistical significance was defined as a p-value 0.05. The final multivariate model contained variables that were significant in the bivariate analysis. Prior to data collection, a research permit from National Ethical Committee of Research in Democratic Republic of the Congo was obtained. Written informed consents from literate or illiterate caregivers of adolescent and young adult Ebola survivors were obtained. Throughout the study, participants' privacy and confidentiality were respected. RESULTS: A total of 68 care givers participated in the study, with a majority 54/68(79.41%) having poor quality of life. Men were 3.17 times more likely to record good quality of life than women (p = 0.02); OR:(95% CI), 3.17: (1.2 - 8.36), With regards to place of residence, caregivers who lived in town were less likely to have good quality of life compared to those in rural (p = 0.01); OR: (95%CI), 0.25: (0.09 - 0.72). CONCLUSION: The quality of life of caregivers of adolescent and young adult Ebola survivors in Democratic Republic of the Congo is poor. To be woman caregiver and to live in town are determinants associated with poor quality of life among caregivers of adolescent and young adult Ebola survivors.

Health-related quality of life among Ebola survivors in Sierra Leone: the role of socio-demographic, health-related and psycho-social factors.

BACKGROUND: Evidence of how social factors affect the health-related quality of life (HRQoL) of Ebola virus disease (EVD) survivors is limited. Our study explores the association between socio-demographic, health-related and psycho-social (stigma) factors and EVD survivors' health-related quality of life (HRQoL) in Sierra Leone. METHODS: We conducted a nationwide cross-sectional study among 358 EVD survivors between January and August 2018. We used a multistage sampling method to recruit EVD survivors, and the RAND 36-Item Health Survey item was used to assess the HRQoL. Data were analysed using descriptive statistics and multiple linear regression. RESULTS: When comparing by each dimension in relation to their respective summary scores, role limitation physical [0.00 (50.00)] and role limitation emotional [0.00 (33.33)] were the most affected physical health and mental health domains among EVD survivors respectively. EVD survivors who were older (ß = - 3.90, 95% CI - 6.47 to - 1.32, p = 0.003), had no formal education (ß = - 2.80, 95% CI - 5.16 to - 0.43, p = 0.021), experienced a unit increase in the number of post-Ebola symptoms (ß = - 1.08, 95% CI - 1.74 to - 0.43, p < 0.001) and experienced a unit increase in enacted stigma (ß = - 2.61, 95% CI - 4.02 to - 1.20, p < 0.001) were more likely to report a decreased level of physical health. EVD survivors who experienced a unit increase in the time spent in the Ebola treatment centre (ß = - 0.60, 95% CI - 0.103 to - 0.18, p = 0.006) and those who experienced a unit increase in enacted Stigma were more likely to report decreased levels of mental health (ß = - 1.50, 95% CI - 2.67 to - 0.33, p = 0.012). CONCLUSION: Sociodemographic, health-related, and psycho-social factors were significantly associated with decrease levels of HRQoL. Our findings improve our understanding of the factors that might influence the HRQoL and suggest the need for EVD survivors to be provided with a comprehensive healthcare package that caters for their physical and mental health needs.

Characteristics of Ebola Virus Disease Survivor Blood and Semen in Liberia: Serology and Reverse Transcription Polymerase Chain Reaction (RT-PCR).

INTRODUCTION: Ebola virus (EBOV), species Zaire ebolavirus, may persist in the semen of male survivors of Ebola virus disease (EVD). We conducted a study of male survivors of the 2014-2016 EVD outbreak in Liberia and evaluated their immune responses to EBOV. We report here findings from the serologic testing of blood for EBOV-specific antibodies, molecular testing for EBOV in blood and semen, and serologic testing of peripheral blood mononuclear cells (PBMCs) in a subset of study participants. METHODS: We tested for EBOV RNA in blood by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and for anti-EBOV-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies by enzyme-linked immunosorbent assay (ELISA) for 126 study participants. We performed PBMC analysis on a subgroup of 26 IgG-negative participants. RESULTS: All 126 participants tested negative for EBOV RNA in blood by qRT-PCR. The blood of 26 participants tested negative for EBOV-specific IgG antibodies by ELISA. PBMCs were collected from 23/26 EBOV IgG-negative participants. Of these, 1/23 participants had PBMCs that produced anti-EBOV-specific IgG antibodies upon stimulation with EBOV-specific glycoprotein (GP) and nucleoprotein (NP) antigens. CONCLUSIONS: The blood of EVD survivors, collected when they did not have symptoms meeting the case definition for acute or relapsed EVD, is unlikely to pose a risk for EBOV transmission. We identified 1 IgM/IgG negative participant who had PBMCs that produced anti-EBOV-specific antibodies upon stimulation. Immunogenicity following acute EBOV infection may exist along a spectrum, and absence of antibody response should not be exclusionary in determining an individual's status as a survivor of EVD.

Understanding Long-term Evolution and Predictors of Sequelae of Ebola Virus Disease Survivors in Guinea: A 48-Month Prospective, Longitudinal Cohort Study (PostEboGui).

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.

PREVAIL IV: A Randomized, Double-Blind, 2-Phase, Phase 2 Trial of Remdesivir vs Placebo for Reduction of Ebola Virus RNA in the Semen of Male Survivors.

BACKGROUND: Ebola virus RNA persists in the semen of male Ebola survivors for months to years after the acute infection, and male-to-female sexual transmission of the virus is well documented. We investigated whether remdesivir can safely reduce persistence of seminal Ebola virus RNA. METHODS: We recruited men with persistent seminal Ebola RNA in Liberia and Guinea. Participants were randomized 1:1 to receive intravenous remdesivir (GS-5734; Gilead Sciences) or matching placebo administered once daily by intravenous infusion over 1 hour on 5 consecutive days. Stratification was by country and number of positive (1 or 2) preenrollment semen tests. We evaluated the difference in mean assay negativity rate (ANR), that is, the proportion of negative tests for each participant in each group in the treatment (days 1-28) and follow-up (months 2-6) phases on an intention-to-treat basis. RESULTS: We enrolled 38 men from July 2016 through June 2018. The mean treatment phase ANRs were 85% (standard deviation [SD] = 24%) and 76% (SD = 30%) in the remdesivir and placebo arms, respectively (P = .270). The mean follow-up phase ANRs were 96% (SD = 10%) and 81% (SD = 29%) in the remdesivir and placebo arms, respectively (P = .041). The 5-day remdesivir regimen was well tolerated with no safety concerns. CONCLUSIONS: In this small trial, remdesivir 100 mg/day for 5 days safely reduced the presence of Ebola virus RNA in the semen of Ebola survivors 2 to 6 months after administration. A larger follow-up study is necessary to confirm results. Clinical Trials Registration . NCT02818582.

Post-Ebola sequelae among Ebola child survivors in Sierra Leone.

BACKGROUND: There 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. METHODS: EVD 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. RESULTS: EVD 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. CONCLUSIONS: Our 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.

Post-Ebola psychosocial experiences and coping mechanisms among Ebola survivors: a systematic review.

OBJECTIVE: A myriad of physical and psychosocial sequelae have been reported among Ebola survivors from previous Ebola virus disease (EVD) outbreaks, including the most recent in West Africa. This review examines the various forms of psychological distress experienced by EVD survivors, family and community reactions to EVD survivors and EVD survivors' coping mechanisms. METHODS: We conducted a literature search of original articles employing Medline (Ovid), PubMed, Web of Science, Scopus, CINAHL, EBSCO host academic search complete, PsycINFO (EBSCO) and Embase databases. RESULTS: Our search identified 1890 articles of which 24 met our inclusion criteria. Various forms of psychological distress were prevalent among EVD survivors including depression, anxiety, anger, grief, guilt, flashbacks, sadness, worthlessness, substance addiction, suicidal tendencies and self-stigmatisation. Family and community responses to EVD survivors ranged from acceptance to rejection, isolation, stigmatisation and discrimination. EVD survivors' coping strategies included engagement with religious faith, EVD survivors associations and involvement in EVD prevention and control interventions. CONCLUSION: Psychological distress, including that resulting from family and community stigma and discrimination, appears common among EVD survivors. Community-based mental health and psychosocial interventions integrated within a broader package of care for EVD survivors that also recognises the physical health challenges are required. Well-designed longitudinal studies can provide clear insights on the nature and trajectory of the psychosocial issues currently experienced by EVD survivors.

OBJECTIF: Une myriade de séquelles physiques et psychosociales a été rapportée parmi les survivants d'Ebola lors des épidémies précédentes de la maladie du virus Ebola (MVE) et dans la plus récente en Afrique de l'Ouest. Cette revue examine les différentes formes de détresse psychologique vécue par les survivants de la MVE, les réactions de la famille et de la communauté à l'égard des survivants de la MVE et leurs mécanismes d'adaptation. MÉTHODES: Nous avons effectué une recherche de la littérature dans des articles originaux en utilisant les bases de données Medline (Ovid), PubMed, Web of Science, Scopus, CINAHL, EBSCO host academic search complete, PsycINFO (EBSCO) et Embase. RÉSULTATS: Notre recherche a identifié 1.890 articles dont 24 répondaient aux critères d'inclusion. Diverses formes de détresse psychologique étaient prévalentes parmi les survivants de la MVE, notamment la dépression, l'anxiété, la colère, le deuil, la culpabilité, les flashbacks, la tristesse, le sentiment d'inutilité, la toxicomanie, les tendances suicidaires et l'auto-stigmatisation. Les réactions des familles et des communautés vis-à-vis des survivants de la MVE vont de l'acceptation au rejet, à l'isolement, à la stigmatisation et à la discrimination. Les stratégies d'adaptation des survivants de la MVE comprenaient l'engagement avec la religion, dans les associations de survivants de la MVE et une implication dans des interventions de prévention et de lutte contre la MVE. CONCLUSION: La détresse psychologique, y compris celle résultant de la stigmatisation et de la discrimination familiale et communautaire, semble être fréquente chez les survivants de la MVE. Des interventions communautaires intégrées psychosociales et de santé mentale dans un ensemble plus large de soins pour les survivants de la MVE, qui reconnaît également les problèmes de santé physique sont nécessaires. Des études longitudinales bien conçues peuvent fournir des informations claires sur la nature et la trajectoire des problèmes psychosociaux actuellement rencontrés par les survivants de la MVE.

Utilisation of and Attitude towards Traditional and Complementary Medicine among Ebola Survivors in Sierra Leone.

Background and objectives: In addition to conventional healthcare, Ebola survivors are known to seek traditional and complementary healthcare (T&CM) options to meet their healthcare needs. However, little is known about the general beliefs of Ebola survivors regarding T&CM and the impact of these beliefs in influencing their decisions around T&CM use. This study examines Ebola survivors' attitudes towards T&CM use in Sierra Leone. Materials and Methods: We conducted a nationwide quantitative cross-sectional study of 358 Ebola survivors in Sierra Leone between January and August 2018. We used descriptive analysis, chi-square tests and backward stepwise binary logistic regression for data analysis. Results: Close to half of the survivors (n = 163, 45.5%) had used T&CM since their discharge from an Ebola treatment centre. Survivors who viewed T&CM as boosting their immune system/resistance were 3.89 times (95%CI: 1.57-9.63, p = 0.003) more likely to use T&CM than those who did not view T&CM as boosting their immune system/resistance. Additionally, survivors who viewed T&CM as having fewer side effects than conventional medicine were more likely to use T&CM [OR = 5.03 (95%CI: 1.92-13.19, p = 0.001)]. Ebola survivors were more influenced to use T&CM based on their personal experience of the effectiveness of T&CM than by clinical evidence [OR = 13.72 (95%CI: 6.10-30.84, P < 0.001)]. Ebola survivors who perceived T&CM as providing them with more control than conventional medicine over their health/body were more likely to use T&CM [OR = 4.15 (95%CI: 1.74-9.89, p = 0.001)] as opposed to those who did not perceive T&CM in this way. Conclusions: Considering the widespread use of T&CM, an understanding of Ebola survivors' attitudes/beliefs towards T&CM is useful to healthcare providers and policymakers with regard to public education and practitioner-survivors communication, T&CM regulation and research in Sierra Leone. Ebola survivors appear to turn to T&CM not only for treatment, but also to fill gaps in conventional health care services.

Disability Among Ebola Survivors and Their Close Contacts in Sierra Leone: A Retrospective Case-Controlled Cohort Study.

Ebola survivors (21/27 [77.8%]) suffered more disability than their close contacts (6/54 [11.1%]) (adjusted odds ratio, 23.5 [95% confidence interval, 6.5-85.7]; P < .001) when measured by the Washington Group Disability Extended Questionnaire. Major limitations in vision, mobility, cognition, and affect were observed in survivors 1 year following the 2014-2016 Ebola outbreak, highlighting the need for long-term rehabilitation.

Therapeutic Itineraries during the Ebola Epidemic in the Democratic Republic of Congo.

While treating a disease, patients or their relatives make decisions to pursue different therapeutic options, and various stages are involved in searching for a cure. This paper explored the pattern of health-seeking in the Democratic Republic of Congo (DRC) during the 10th Ebola virus disease (EVD) outbreak. Eight hundred randomly selected adults were surveyed using a questionnaire. Qualitative data were also collected through in-depth interviews with 17 community leaders and 20 focus group discussions with community members. The results showed that modern healthcare facilities are not usually considered the first option for treatment. The therapeutic journey generally begins with the patients, who treat themselves based on the what they know about the disease and the resources they have at their disposal. However, if the disease is not cured through self-medication, then patients or their relatives will visit a pharmacy. Patients request medication they know to be effective in treating the disease, and relatives can also assist in obtaining medication in the case of immobile patients. Pharmacies commonly sell the medication to patients or their relatives without a medical prescription.

High doses of favipiravir in two men survivors of Ebola virus disease carrying Ebola virus in semen in Guinea.

BACKGROUND: Persistence 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. CASE: In 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. CONCLUSIONS: High 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.

Providing healthcare to Ebola survivors: A qualitative exploratory investigation of healthcare providers' views and experiences in Sierra Leone.

Although the experiences of healthcare workers regarding caring for Ebola patients during the West African Ebola outbreak have been explored, little is known about healthcare workers' experiences in providing care to Ebola survivors. We employed a qualitative design to address this gap in the literature. Healthcare providers described the health complaints of Ebola survivors as similar to those of ordinary patients, but disproportionately frequent and severe. During the Ebola outbreak, fear of infection with the Ebola virus affected healthcare providers' confidence to provide care to survivors leading to the provision of symptomatic or no treatment. At the close of the Ebola outbreak, healthcare providers cited previous experience in providing care to Ebola patients, being more knowledgeable, peer support, commitment to professional duty and the implementation of the CPES programme as motivators that helped boost their confidence to providing care. However, healthcare providers described the unavailability of medicines, the inability to undertake laboratory investigations, the lack of access to specialised care and uncoordinated referrals from peripheral health units as their current challenges to providing care. Such enablers and barriers need to be prioritised within the Sierra Leone health system to further strengthen initiatives aimed at improving healthcare delivery to Ebola survivors.

Ebola survivors' healthcare-seeking experiences and preferences of conventional, complementary and traditional medicine use: A qualitative exploratory study in Sierra Leone.

BACKGROUND: and Purpose: This study explores Ebola survivors' healthcare-seeking experiences within the context of Sierra Leone's free healthcare initiative (FHCI) and comprehensive package for Ebola survivors (CPES) program while also exploring the enablers and barriers to their use of informal healthcare. MATERIALS AND METHODS: We employed an inductive, exploratory qualitative approach using focus group discussion with 41 adults Ebola survivors in the four administrative regions of Sierra Leone. RESULTS: Biomedical care was the first choice of treatment option for most survivors immediately following post-ETC discharge. Survivors' healthcare-seeking experience varies before and after their inclusion into FHCI and the establishment of the CPES program. Personal and health system factors influenced survivors' decision to seek multiple healthcare approaches, especially T&CM. CONCLUSION: Our findings suggest the determinants of Ebola survivors' healthcare-seeking experiences should be considered when developing and implementing programs aimed at improving the current health status of Ebola survivors in Sierra Leone.

Traditional and complementary medicine use among Ebola survivors in Sierra Leone: a qualitative exploratory study of the perspectives of healthcare workers providing care to Ebola survivors.

BACKGROUND: Considerable number of patients, including Ebola survivors, in Sierra Leone, are using traditional and complementary medicine (T&CM). Healthcare providers' (HCPs) views about T&CM is crucial in addressing the increased need for T&CM among patients. However, healthcare providers' views about T&CM in Sierra Leone is unknown. Our study explores healthcare providers' knowledge of and perception towards T&CM and how that influence their personal and professional T&CM use, communication with Ebola survivors about T&CM as well as its integration into the healthcare system in Sierra Leone. METHODS: We employed a qualitative exploratory study design using semi-structured interviews to collect data from 15 conveniently sampled HCPs in all four geographical regions of Sierra Leone. We analysed our data using thematic network analysis framework. RESULTS: Healthcare providers perceived their knowledge about T&CM to be low and considered T&CM to be less effective and less safe than conventional medicine as well as not evidence-based. HCPs perception of T&CM as non-scientific and their lack of knowledge of T&CM were the key barriers to HCPs' self-use and recommendation as well as their lack of detailed discussion about T&CM with Ebola survivors. HCPs are open to T&CM integration into mainstream healthcare in Sierra Leone although at their terms. However, they believe that T&CM integration could be enhanced by effective professional regulation of T&CM practice, and by improving T&CM evidenced-based knowledge through education, training and research. CONCLUSION: Changing HCPs' negative perception of and increasing their knowledge about T&CM is critical to promoting effective communication with Ebola survivors regarding T&CM and its integration into the healthcare system in Sierra Leone. Strategies such as educational interventions for HCPs, conducting rigorous T&CM research, proper education and training of T&CM practitioners and effective professional regulation of T&CM practice could help in that direction.

Correspondence of Neutralizing Humoral Immunity and CD4 T Cell Responses in Long Recovered Sudan Virus Survivors.

Robust humoral and cellular immunity are critical for survival in humans during an ebolavirus infection. However, the interplay between these two arms of immunity is poorly understood. To address this, we examined residual immune responses in survivors of the Sudan virus (SUDV) outbreak in Gulu, Uganda (2000-2001). Cytokine and chemokine expression levels in SUDV stimulated whole blood cultures were assessed by multiplex ELISA and flow cytometry. Antibody and corresponding neutralization titers were also determined. Flow cytometry and multiplex ELISA results demonstrated significantly higher levels of cytokine and chemokine responses in survivors with serological neutralizing activity. This correspondence was not detected in survivors with serum reactivity to SUDV but without neutralization activity. This previously undefined relationship between memory CD4 T cell responses and serological neutralizing capacity in SUDV survivors is key for understanding long lasting immunity in survivors of filovirus infections.

Molecular mechanisms of Ebola pathogenesis.

Ebola viruses (EBOVs) and Marburg viruses (MARVs) are among the deadliest human viruses, as highlighted by the recent and widespread Ebola virus outbreak in West Africa, which was the largest and longest epidemic of Ebola virus disease (EVD) in history, resulting in significant loss of life and disruptions across multiple continents. Although the number of cases has nearly reached its nadir, a recent cluster of 5 cases in Guinea on March 17, 2016, has extended the enhanced surveillance period to June 15, 2016. New, enhanced 90-d surveillance windows replaced the 42-d surveillance window to ensure the rapid detection of new cases that may arise from a missed transmission chain, reintroduction from an animal reservoir, or more important, reemergence of the virus that has persisted in an EVD survivor. In this review, we summarize our current understanding of EBOV pathogenesis, describe vaccine and therapeutic candidates in clinical trials, and discuss mechanisms of viral persistence and long-term health sequelae for EVD survivors.