Persistent intraocular Ebola virus RNA is associated with severe uveitis in a convalescent rhesus monkey.

Despite increasing evidence that uveitis is common and consequential in survivors of Ebola virus disease (EVD), the host-pathogen determinants of the clinical phenotype are undefined, including the pathogenetic role of persistent viral antigen, ocular tissue-specific immune responses, and histopathologic characterization. Absent sampling of human intraocular fluids and tissues, these questions might be investigated in animal models of disease; however, challenges intrinsic to the nonhuman primate model and the animal biosafety level 4 setting have historically limited inquiry. In a rhesus monkey survivor of experimental Ebola virus (EBOV) infection, we observed and documented the clinical, virologic, immunologic, and histopathologic features of severe uveitis. Here we show the clinical natural history, resultant ocular pathology, intraocular antigen-specific antibody detection, and persistent intraocular EBOV RNA detected long after clinical resolution. The association of persistent EBOV RNA as a potential driver of severe immunopathology has pathophysiologic implications for understanding, preventing, and mitigating vision-threatening uveitis in EVD survivors.

Fractional-Order Ebola-Malaria Coinfection Model with a Focus on Detection and Treatment Rate.

Coinfection of Ebola virus and malaria is widespread, particularly in impoverished areas where malaria is already ubiquitous. Epidemics of Ebola virus disease arise on a sporadic basis in African nations with a high malaria burden. An observational study discovered that patients in Sierra Leone's Ebola treatment centers were routinely infected with malaria parasites, increasing the risk of death. In this paper, we study Ebola-malaria coinfections under the generalized Mittag-Leffler kernel fractional derivative. The Banach fixed point theorem and the Krasnoselskii type are used to analyse the model's existence and uniqueness. We discuss the model stability using the Hyers-Ulam functional analysis. The numerical scheme for the Ebola-malaria coinfections using Lagrange interpolation is presented. The numerical trajectories show that the prevalence of Ebola-malaria coinfections ranged from low to moderate depending on memory. This means that controlling the disease requires adequate knowledge of the past history of the dynamics of both malaria and Ebola. The graphical dynamics of the detection rate indicate that a variation in the detection rate only affects the following compartments: individuals that are latently infected with the Ebola, Ebola virus afflicted people who went unnoticed, individuals who have been infected with the Ebola virus and have been diagnosed with the disease, and persons undergoing Ebola virus therapy.

The prevalence of Post-Ebola Syndrome hearing loss, Sierra Leone.

BACKGROUND: Globally, hearing loss is the second leading cause of disability, affecting approximately 18.7% of the world's population. However, the burden of hearing loss is unequally distributed, with the majority of affected individuals located in Asia or Sub-Saharan Africa. Following the 2014 West African Ebola Outbreak, disease survivors began to describe hearing loss as part of the constellation of symptoms known as Post-Ebola Syndrome. The goal of this study was to more fully characterize hearing loss among Ebola Virus Disease (EVD) survivors. METHODOLOGY AND PRINCIPAL FINDINGS: EVD survivors and their household contacts were recruited (n = 1,12) from Eastern Sierra Leone. Each individual completed a symptom questionnaire, physical exam, and a two-step audiometry process measuring both air and bone conduction thresholds. In comparison to contacts, EVD survivors were more likely to have complaints or abnormal findings affecting every organ system. A significantly greater percentage of EVD survivors were found to have hearing loss in comparison to contacts (23% vs. 9%, p < 0.001). Additionally, survivors were more likely to have bilateral hearing loss of a mixed etiology. Logistic regression revealed that the presence of any symptoms of middle or inner ear (p < 0.001), eye (p = 0.005), psychiatric (p = 0.019), and nervous system (p = 0.037) increased the odds of developing hearing loss. CONCLUSIONS AND SIGNIFICANCE: This study is the first to use an objective and standardized measurement to report hearing loss among EVD survivors in a clinically meaningful manner. In this study it was found that greater than 1/5th of EVD survivors develop hearing loss. The association between hearing impairment and symptoms affecting the eye and nervous system may indicate a similar mechanism of pathogenesis, which should be investigated further. Due to the quality of life and socioeconomic detriments associated with untreated hearing loss, a greater emphasis must be placed on understanding and mitigating hearing loss following survival to aid in economic recovery following infectious disease epidemics.

Comparative effectiveness of intracranial hypertension management guided by ventricular versus intraparenchymal pressure monitoring: a CENTER-TBI study.

OBJECTIVE: To compare outcomes between patients with primary external ventricular device (EVD)-driven treatment of intracranial hypertension and those with primary intraparenchymal monitor (IP)-driven treatment. METHODS: The CENTER-TBI study is a prospective, multicenter, longitudinal observational cohort study that enrolled patients of all TBI severities from 62 participating centers (mainly level I trauma centers) across Europe between 2015 and 2017. Functional outcome was assessed at 6 months and a year. We used multivariable adjusted instrumental variable (IV) analysis with "center" as instrument and logistic regression with covariate adjustment to determine the effect estimate of EVD on 6-month functional outcome. RESULTS: A total of 878 patients of all TBI severities with an indication for intracranial pressure (ICP) monitoring were included in the present study, of whom 739 (84%) patients had an IP monitor and 139 (16%) an EVD. Patients included were predominantly male (74% in the IP monitor and 76% in the EVD group), with a median age of 46 years in the IP group and 48 in the EVD group. Six-month GOS-E was similar between IP and EVD patients (adjusted odds ratio (aOR) and 95% confidence interval [CI] OR 0.74 and 95% CI [0.36-1.52], adjusted IV analysis). The length of intensive care unit stay was greater in the EVD group than in the IP group (adjusted rate ratio [95% CI] 1.70 [1.34-2.12], IV analysis). One hundred eighty-seven of the 739 patients in the IP group (25%) required an EVD due to refractory ICPs. CONCLUSION: We found no major differences in outcomes of patients with TBI when comparing EVD-guided and IP monitor-guided ICP management. In our cohort, a quarter of patients that initially received an IP monitor required an EVD later for ICP control. The prevalence of complications was higher in the EVD group. PROTOCOL: The core study is registered with ClinicalTrials.gov , number NCT02210221, and the Resource Identification Portal (RRID: SCR_015582).

Clinical sequelae among individuals with pauci-symptomatic or asymptomatic Ebola virus infection and unrecognised Ebola virus disease in Liberia: a longitudinal cohort study.

BACKGROUND: Whether or not individuals with pauci-symptomatic or asymptomatic Ebola virus infection and unrecognised Ebola virus disease develop clinical sequelae is unknown. We assessed current symptoms and physical examination findings among individuals with pauci-symptomatic or asymptomatic infection and unrecognised Ebola virus disease compared with Ebola virus disease survivors and uninfected contacts. METHODS: Between June 17, 2015, and June 30, 2017, we studied a cohort of Ebola virus disease survivors and their contacts in Liberia. Surveys, current symptoms and physical examination findings, and serology were used to characterise disease status of reported Ebola virus disease, unrecognised Ebola virus disease, pauci-symptomatic or asymptomatic Ebola virus infection, or no infection. We pre-specified findings known to be differentially prevalent among Ebola virus disease survivors versus their contacts (urinary frequency, headache, fatigue, muscle pain, memory loss, joint pain, neurological findings, chest findings, muscle findings, joint findings, abdominal findings, and uveitis). We estimated the prevalence and incidence of selected clinical findings by disease status. FINDINGS: Our analytical cohort included 991 reported Ebola virus disease survivors and 2688 close contacts. The median time from acute Ebola virus disease onset to baseline was 317 days (IQR 271-366). Of 222 seropositive contacts, 115 had pauci-symptomatic or asymptomatic Ebola virus infection and 107 had unrecognised Ebola virus disease. At baseline, prevalent findings of joint pain, memory loss, muscle pain, and fatigue were lowest among those with pauci-symptomatic or asymptomatic infection or no infection, higher among contacts with unrecognised Ebola virus disease, and highest in reported survivors of Ebola virus disease. Joint pain was the most prevalent finding, and was reported in 434 (18%) of 2466 individuals with no infection, 14 (12%) of 115 with pauci-symptomatic or asymptomatic infection, 31 (29%) of 107 with unrecognised Ebola virus disease, and 476 (48%) of 991 with reported Ebola virus disease. In adjusted analyses, this pattern remained for joint pain and memory loss. Survivors had an increased odds of joint pain compared with unrecognised Ebola virus disease contacts (adjusted odds ratio [OR] 2·13, 95% CI 1·34-3·39); unrecognised Ebola virus disease contacts had an increased odds of joint pain compared with those with pauci-symptomatic or asymptomatic infection and uninfected contacts (adjusted OR 1·89, 95% CI 1·21-2·97). The adjusted odds of memory loss was more than four-times higher among survivors than among unrecognised Ebola virus disease contacts (adjusted OR 4·47, 95% CI 2·41-8·30) and two-times higher among unrecognised Ebola virus disease contacts than in those with pauci-symptomatic or asymptomatic infection and uninfected contacts (adjusted OR 2·05, 95% CI 1·10-3·84). By 12 months, prevalent findings had decreased in the three infected groups. INTERPRETATION: Our findings provide evidence of post-Ebola virus disease clinical sequelae among contacts with unrecognised Ebola virus disease but not in people with pauci-symptomatic or asymptomatic Ebola virus infection. FUNDING: National Cancer Institute and National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

Risk factors for postresection shunting in children with suprasellar tumor: a retrospective analysis of 124 patients.

OBJECTIVE: Hydrocephalus is one of the most significant comorbidities of pediatric suprasellar tumors. Up to 37.5-68.0% of patients were diagnosed with hydrocephalus at admission. However, after surgical resection of the tumor, 9.3-51.4% of the hydrocephalus will persist and require a ventriculoperitoneal shunt (VPS) surgery. The purpose of this study was to identify the risk factors associated with postresection shunting in children with suprasellar tumors. METHODS: We conducted a retrospective analysis of children who underwent surgery for suprasellar tumors at our department from February 2011 to December 2020. We used univariate and multivariate analysis to screen the factors that might be correlated with postoperative shunt placement, taking into account patients' characteristics, tumor histology/size/calcification, the severity of preoperative hydrocephalus, the involvement of ventricles, external ventricular drainage (EVD) placement, postoperative intraventricular hematoma, the extent of resection, and other surgical details. RESULTS: A total of 124 children who underwent surgery for suprasellar tumors were included in our study. Hydrocephalus was present in 55 patients (44.3%) at admission; 23 patients (18.5%) received VPS implantation after tumor removal. Univariate analysis showed that the involvement of ventricles (p = 0.002), moderate/severe preoperative hydrocephalus (p = 0.001), postoperative intraventricular hematoma (p = 0.005), and EVD implantation (p = 0.001) were significantly associated with postoperative VPS. Multivariate analysis confirmed that only ventricle involvement (p = 0.002; OR = 5.6; 95%CI 1.8-17.2) and intraventricular hematoma (p = 0.01; OR = 10.7; 95%CI 1.8-64.2) were independent risk factors for postresection shunting. CONCLUSION: Ventricle involvement and intraventricular hematoma can be identified as independent predictors for postoperative shunting in pediatric suprasellar tumors.

PTSD, depression and anxiety in Ebola virus disease survivors in Beni town, Democratic Republic of the Congo.

BACKGROUND: Ebola Virus Disease (EVD) is a deadly and feared infectious disease, which can be responsible of debilitating physical and psychological sequelae in survivors including depression and anxiety disorders. Unfortunately, there are scarce data on survivor sequelae in Democratic Republic of the Congo. So this study assessed PTSD, depression and anxiety symptoms among EVD survivors enrolled in the follow-up program of the psychosocial care team of Beni town's general hospital. METHODS: A cross-sectional study used consecutive sampling to recruit 144 Ebola virus disease survivors who came for follow up from October 23 to November 13; 2019. Basic socio-demographic data, presence of headache and short-term memory function were assessed. The Post-traumatic Checklist Scale and Hospital Anxiety and Depression Scale were used to assess psychological burden among participants. Descriptive statistics were used to summarized data and Pearson's or likelihood chi-square were used to test association between psychiatric disorders and associated factors. RESULTS: The prevalence of PTSD, depression and anxiety was 24.3, 24.3 and 33.3% respectively. Being male (OR = 0.42, 95% CI: 0.16, 0.95, p = 0.049), suffering from persistent headache (OR = 2.62, 95% CI: 1.12, 6.14, p = 0.014), losing a loved one because of EVD (OR: 2.60, 95% CI: 1.11, 6.15, p = 0. 015) and being young - 18-24 years - (OR: 0. 261, 95% CI: 0. 08, 0.82, p = 0,026) were statistically associated with PTSD diagnosis. Having short-term memory impairment and suffering from persistent headache were statistically associated with depression and anxiety diagnoses (OR = 2.44, 95% CI: 1.03, 5.82, p = 0.026); (OR = 2.24, 95% CI: 1.04, 4.85, p = 0.025); (OR = 2.62, 95% CI: 1.12, 6.14, p = 0.014); (OR = 2.31, 95% CI: 1.06, 5.01, p = 0.020). CONCLUSION: The prevalence of PTSD, depression and anxiety is high among EVD survivors. Development of specialized psychiatric services to sustain psychiatric and psychological health amongst survivors in the cultural context of the Eastern part of the DRC should be considered by the teams fighting against EVD in the DRC.

Post-Ebola Syndrome Presents With Multiple Overlapping Symptom Clusters: Evidence From an Ongoing Cohort Study in Eastern Sierra Leone.

BACKGROUND: Following the 2013-2016 West African Ebola outbreak, distinct, persistent health complaints were recognized in Ebola virus disease (EVD) survivors. Here we provide an in-depth characterization of post-Ebola syndrome >2.5 years after resolution of disease. Additionally, we report subphenotypes of post-Ebola syndrome with overlapping symptom clusters in survivors from Eastern Sierra Leone. METHODS: Participants in Eastern Sierra Leone were identified by the Sierra Leone Association of Ebola survivors. Survivors and their contacts were administered a questionnaire assessing self-reported symptoms and a physical examination. Comparisons between survivors and contacts were conducted using conditional logistic regression. Symptom groupings were identified using hierarchical clustering approaches. Simplified presentation of incredibly complex evaluations (SPICE), correlation analysis, logistic regression, and principal component analysis (PCA) were performed to explore the relationships between symptom clusters. RESULTS: Three hundred seventy-five EVD survivors and 1040 contacts were enrolled into the study. At enrollment, EVD survivors reported significantly more symptoms than their contacts in all categories (P < .001). Symptom clusters representing distinct organ systems were identified. Correlation and logistic regression analysis identified relationships between symptom clusters, including stronger relationships between clusters including musculoskeletal symptoms (r = 0.63, P < .001; and P < .001 for correlation and logistic regression, respectively). SPICE and PCA further highlighted subphenotypes with or without musculoskeletal symptoms. CONCLUSIONS: This study presents an in-depth characterization of post-Ebola syndrome in Sierra Leonean survivors >2.5 years after disease. The interrelationship between symptom clusters indicates that post-Ebola syndrome is a heterogeneous disease. The distinct musculoskeletal and non-musculoskeletal phenotypes identified likely require targeted therapies to optimize long-term treatment for EVD survivors.

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.

Efficacy and Safety Outcomes of Cataract Surgery in Survivors of Ebola Virus Disease: 12-Month Results From the PREVAIL VII Study.

Purpose: In survivors of Ebola virus disease (EVD), intraocular viral persistence raises questions about the timing and safety of cataract surgery. To the best of our knowledge, this is the first controlled study evaluating Ebola virus persistence and cataract surgery safety and outcomes in EVD survivors. Methods: Seropositive EVD survivors and seronegative controls with vision worse than 20/40 from cataract and without active intraocular inflammation were enrolled. Aqueous humor from survivors was tested with reverse transcription-polymerase chain reaction for Ebola viral RNA. Participants underwent manual small-incision cataract surgery and 1 year of follow-up examinations. Results: Twenty-two eyes of 22 survivors and 12 eyes of eight controls underwent cataract surgery. All of the aqueous samples tested negative for Ebola viral RNA. Median visual acuity improved from 20/200 at baseline to 20/25 at 1 year in survivors and from count fingers to 20/50 in controls (overall, P < 0.001; between groups, P = 0.07). After a 1-month course of topical corticosteroids, 55% of survivors and 67% of controls demonstrated at least 1+ anterior chamber cell. Twelve months after surgery, optical coherence tomography revealed a median increase in macular central subfield thickness of 42 µm compared with baseline (overall, P = 0.029; between groups, P = 0.995). Conclusions: EVD survivors and controls demonstrated significant visual improvement from cataract surgery. The persistence of intraocular inflammation highlights the importance of follow-up. The absence of detectable intraocular Ebola viral RNA provides guidance regarding the safety of eye surgery in Ebola survivors. Translational Relevance: These findings demonstrate the safety and efficacy of cataract surgery in Ebola survivors and will inform ocular surgery guidelines in this population.

Assessing anxiety, depression and insomnia symptoms among Ebola survivors in Africa: A meta-analysis.

BACKGROUND: During health disaster events such as the current devastating havoc being inflicted on countries globally by the SARS-CoV-19 pandemic, mental health problems among survivors and frontline workers are likely concerns. However, during such health disaster events, stakeholders tend to give more precedence to the socio-economic and biomedical health consequences at the expense of mental health. Meanwhile, studies show that regardless of the kind of disaster/antecedent, all traumatic events trigger similar post-traumatic stress symptoms among survivors, families, and frontline workers. Thus, our study investigated the prevalence of anxiety, depression and insomnia symptoms among survivors of the 2014-2016 Ebola virus disease that plagued the West African sub-region. METHODS: We systematically retrieved peer-reviewed articles published between 1970 and 2019 from seven electronic databases, including Google Scholar, MEDLINE, PsychInfo, PubMed, Scopus, Springer Link, Web of Science on Ebola and post-traumatic stress disorder symptoms. A comprehensive hand search complemented this literature search. Of the 87 articles retrieved, only 13 met the inclusion criteria for this meta-analysis. RESULTS: After heterogeneity, influence, and publication bias analysis, our meta-analysis pooled proportion effects estimates showed a moderate to a high prevalence of anxiety (14%; 99% CI: 0.05-0.30), depression (15%; 99% CI: 0.11-0.21), and insomnia (22%; 99% CI: 0.13-0.36). Effect estimates ranging from (0.13; 99% CI: 0.05, 0.28) through to (0.11; 99% CI: 0.05-0.22), (0.15; 99% CI: 0.09-0.25) through to (0.13; 99% CI: 0.08-0.21) and (0.23; 99% CI: 0.11-0.41) to (0.23; 99% CI: 0.11-0.41) were respectively reported for anxiety, depression and insomnia symptoms. These findings suggest a significant amount of EVD survivors are struggling with anxiety, depression and insomnia symptoms. CONCLUSION: Our study provided the first-ever meta-analysis evidence of anxiety, depression, and insomnia symptoms among EVD survivors, and suggest that the predominant biomedical health response to regional and global health disasters should be complemented with trauma-related mental health services.

Characterization of Ebola Virus-Associated Eye Disease.

Importance: Survivors of Ebola virus disease (EVD) may experience ocular sequelae. Comparison with antibody-negative individuals from the local population is required to characterize the disease. Objective: To assess features of ophthalmic disease specific to EVD. Design, Setting, and Participants: This baseline cross-sectional analysis of survivors of EVD and their close contacts was conducted within PREVAIL III, a 5-year, longitudinal cohort study. Participants who enrolled at John F. Kennedy Medical Center in Liberia, West Africa from June 2015 to March 2016 were included in this analysis. Close contacts were defined as household members or sex partners of survivors of EVD. Data were analyzed from July 2016 to July 2020. Exposures: All participants, both survivors and close contacts, underwent testing of IgG antibody levels against Ebola virus surface glycoprotein. Main Outcomes and Measures: Ocular symptoms, anterior and posterior ophthalmologic examination findings, and optical coherence tomography images were compared between antibody-positive survivors and antibody-negative close contacts. Results: A total of 564 antibody-positive survivors (320 [56.7%] female; mean [SD] age, 30.3 [14.0] years) and 635 antibody-negative close contacts (347 [54.6%] female; mean [SD] age, 25.8 [15.5] years) were enrolled in this study. Survivors were more likely to demonstrate color vision deficit (28.9% vs 19.0%, odds ratio [OR], 1.6; 95% CI, 1.2-2.1) and lower intraocular pressure (12.4 vs 13.5 mm Hg; mean difference, -1.2 mm Hg; 95% CI, -1.6 to -0.8 mm Hg) compared with close contacts. Dilated fundus examination revealed a higher percentage of vitreous cells (7.8% vs 0.5%; OR, 16.6; 95% CI, 5.0-55.2) and macular scars (4.6% vs 1.6%; OR, 2.8; 95% CI, 1.4-5.5) in survivors than in close contacts. Uveitis was present in 26.4% of survivors and 12.1% of close contacts (OR, 2.4; 95% CI, 1.8-3.2). Among all participants with uveitis, survivors were more likely than close contacts to have intermediate uveitis (34.2% vs 6.5% of all cases; OR, 7.8; 95% CI, 3.1-19.7) and had thicker mean central subfield thickness on optical coherence tomography (222 vs 212 µm; mean difference, 14.4 µm; 95% CI, 1.9-26.9 µm). Conclusions and Relevance: In this cross-sectional study, survivors of EVD had a distinct spectrum of ocular and neuro-ophthalmologic findings compared with close contacts that potentially require medical and surgical treatment.

[Ocular manifestations of viral diseases]. / Atteintes ophtalmologiques des infections virales.

Viral infections may involve all ocular tissues and may have short and long-term sight-threatening consequences. Among them, ocular infections caused by herpesviruses are the most frequent. HSV-1 keratitis and kerato-uveitis affect approximately are the leading cause of infectious blindness in the Western world, mainly because of corneal opacification caused by recurrences. For this reason, they may warrant long-term antiviral prophylaxis. Herpes zoster ophthalmicus, accounts for 10 to 20% of all shingles locations and can be associated with severe ocular involvement (keratitis, kerato-uveitis) of which a quarter becomes chronic/recurrent. Post herpetic neuralgias in the trigeminal territory can be particularly debilitating. Necrotizing retinitis caused by herpesviruses (HSV, VZV, CMV) are seldom, but must be considered as absolute visual emergencies, requiring urgent intravenous and intravitreal antiviral treatment. Clinical pictures depend on the immune status of the host. Adenovirus are the most frequent cause of infectious conjunctivitis. These most often benign infections are highly contagious and may be complicated by visually disabling corneal lesions that may last over months or years. Some arboviruses may be associated with inflammatory ocular manifestations. Among them, congenital Zika infections may cause macular or optic atrophy. Conjunctivitis is frequent during the acute phase of Ebola virus disease. Up to 15% of survivors present with severe chronic inflammatory ocular conditions caused by viral persistence in uveal tissues. Finally, COVID-19-associated conjunctivitis can precede systemic disease, or even be the unique manifestation of the disease. Utmost caution must be taken because of viral shedding in tears.

Review of Ebola virus disease in children - how far have we come?

Ebola virus (EBOV) causes an extremely contagious viral haemorrhagic fever associated with high mortality. While, historically, children have represented a small number of total cases of Ebolavirus disease (EVD), in recent outbreaks up to a quarter of cases have been in children. They pose unique challenges in clinical management and infection prevention and control. In this review of paediatric EVD, the epidemiology of past EVD outbreaks with specific focus on children is discussed, the clinical manifestations and laboratory findings are described and key developments in clinical management including specific topics such as viral persistence and breastfeeding while considering unique psychosocial and anthropological considerations for paediatric care including of survivors and orphans and the stigma they face are discussed. In addition to summarising the literature, perspectives based on the authors' experience of EVD outbreaks in the Democratic Republic of the Congo (DRC) are described.Abbreviations: ARDS: acute respiratory distress syndrome; aOR: adjusted odds ratio; ALT: alanine transferase; ALIMA: Alliance for International Medical Action; AST: aspartate transaminase; BUN: blood urea nitrogen; CNS: central nervous system; CUBE: chambre d'urgence biosécurisée pour épidémie; COVID-19: coronavirus disease 2019; Ct: cycle threshold; DRC: Democratic Republic of Congo; ETC: ebola treatment centre; ETU: ebola treatment unit; EBOV: ebola virus; EVD: ebolavirus disease; FEAST: fluid expansion as supportive therapy; GP: glycoprotein; IV: intravenous; MEURI: monitored emergency use of unregistered interventions; NETEC: National Ebola Training and Education Centre; NP: nucleoprotein; ORS: oral rehydration solution; PALM: Pamoja Tulinde Maisha; PREVAIL: Partnership for Research on Ebola Virus in Liberia; PPE: personal protective equipment; PCR: polymerase chain reaction; PEP: post-exposure prophylaxis; RDTs: rapid diagnostic tests; RT: reverse transcriptase; RNA: ribonucleic acid; UNICEF: United Nations International Children's Emergency Fund; USA: United States of America; WHO: World Health Organization.

Short communication: expanding the range of services to the survivors of Ebola virus disease in the Democratic Republic of the Congo.

BACKGROUND: The objectives of the article are to assess the role of a strategic response in the prevention and control of the disease and the need for extending supports to the survivors of disease. INTRODUCTION: Since the start of the August last year, a new outbreak of Ebola virus disease has been reported in provinces of the Democratic Republic of the Congo. METHODS: As of now, close to 1170 cases and 740 deaths have been attributed to the diseases due to the associated complications in the region.As of now, close to 1170 cases and 740 deaths have been attributed to the diseases due to the associated complications in the region. RESULT: In order to effectively respond to the outbreak, a wide range of strategies have been proposed. It is a fact that the survivors of the disease outbreak face multiple challenges, the task of organizing eye clinics to promote early detection of the problems among the survivors has been initiated. CONCLUSION: In conclusion, Ebola virus disease is a life threatening disease and is linked with a wide range of complications, including those involving eyes. Thus, the need of the hour is to formulate a strategic response comprising of different strategies which not only aim to reduce the incidence of the disease, but also to extend quality assured care to the survivors.

Long-lasting severe immune dysfunction in Ebola virus disease survivors.

Long-term follow up studies from Ebola virus disease (EVD) survivors (EBOV_S) are lacking. Here, we evaluate immune and gene expression profiles in 35 Guinean EBOV_S from the last West African outbreak, a median of 23 months (IQR [18-25]) after discharge from treatment center. Compared with healthy donors, EBOV_S exhibit increases of blood markers of inflammation, intestinal tissue damage, T cell and B cell activation and a depletion of circulating dendritic cells. All survivors have EBOV-specific IgG antibodies and robust and polyfunctional EBOV-specific memory T-cell responses. Deep sequencing of the genes expressed in blood reveals an enrichment in 'inflammation' and 'antiviral' pathways. Integrated analyses identify specific immune markers associated with the persistence of clinical symptoms. This study identifies a set of biological and genetic markers that could be used to define a signature of "chronic Ebola virus disease (CEVD)".

Peripheral Neuronopathy Associated With Ebola Virus Infection in Rhesus Macaques: A Possible Cause of Neurological Signs and Symptoms in Human Ebola Patients.

Neurological signs and symptoms are the most common complications of Ebola virus disease. However, the mechanisms underlying the neurologic manifestations in Ebola patients are not known. In this study, peripheral ganglia were collected from 12 rhesus macaques that succumbed to Ebola virus (EBOV) disease from 5 to 8 days post exposure. Ganglionitis, characterized by neuronal degeneration, necrosis, and mononuclear leukocyte infiltrates, was observed in the dorsal root, autonomic, and enteric ganglia. By immunohistochemistry, RNAscope in situ hybridization, transmission electron microscopy, and confocal microscopy, we confirmed that CD68+ macrophages are the target cells for EBOV in affected ganglia. Further, we demonstrated that EBOV can induce satellite cell and neuronal apoptosis and microglial activation in infected ganglia. Our results demonstrate that EBOV can infect peripheral ganglia and results in ganglionopathy in rhesus macaques, which may contribute to the neurological signs and symptoms observed in acute and convalescent Ebola virus disease in human patients.

Pregnancy and breastfeeding in the context of Ebola: a systematic review.

The outbreaks of Ebola virus between 2014 and 2020 have drawn attention to knowledge gaps related to Ebola virus disease in pregnant women. The aim of this study was to systematically evaluate available data on pregnant and lactating women with acute Ebola virus disease or following recovery. We searched MEDLINE, Embase, Cochrane Library (CENTRAL), Web of Science Core Collection, CINAHL, POPLINE, Global Health, and WHO Global Index Medicus, in addition to grey literature, for relevant articles. Studies of all types and published between database inception and Aug 19, 2019, were eligible (PROSPERO 129335). We identified 1060 records, of which 52 studies met our inclusion criteria. Overall, mortality in 274 pregnant women with Ebola virus disease was 72% (197 women died); mortality for pregnant women with Ebola virus disease were not higher than those in the general population of patients with Ebola virus disease. Nearly all women with Ebola virus disease had adverse pregnancy outcomes. Among survivors, Ebola virus RNA was detected by RT-PCR in amniotic fluid up to 32 days after maternal clearance of Ebola virus from the blood and in breastmilk 26 days after symptom onset. A risk of transmission of Ebola virus from pregnancy-related fluids and breastmilk probably exists, and precautions should be taken.