Uveitis and Systemic Inflammatory Markers in Convalescent Phase of Ebola Virus Disease.
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ABSTRACT:
SUBMITTER: Chancellor JR
PROVIDER: S-EPMC4734519 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC9644391 | biostudies-literature
Project description:During the 2018-2020 Ebola virus disease (EVD) outbreak in North Kivu province in the Democratic Republic of Congo, EVD was diagnosed in a patient who had received the recombinant vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) (Merck). His treatment included an Ebola virus (EBOV)-specific monoclonal antibody (mAb114), and he recovered within 14 days. However, 6 months later, he presented again with severe EVD-like illness and EBOV viremia, and he died. We initiated epidemiologic and genomic investigations that showed that the patient had had a relapse of acute EVD that led to a transmission chain resulting in 91 cases across six health zones over 4 months. (Funded by the Bill and Melinda Gates Foundation and others.).
| S-EPMC7888312 | biostudies-literature
Project description:BackgroundIn the wake of the recent outbreak of Ebola virus disease (EVD) in several African countries, the World Health Organization prioritized the evaluation of treatment with convalescent plasma derived from patients who have recovered from the disease. We evaluated the safety and efficacy of convalescent plasma for the treatment of EVD in Guinea.MethodsIn this nonrandomized, comparative study, 99 patients of various ages (including pregnant women) with confirmed EVD received two consecutive transfusions of 200 to 250 ml of ABO-compatible convalescent plasma, with each unit of plasma obtained from a separate convalescent donor. The transfusions were initiated on the day of diagnosis or up to 2 days later. The level of neutralizing antibodies against Ebola virus in the plasma was unknown at the time of administration. The control group was 418 patients who had been treated at the same center during the previous 5 months. The primary outcome was the risk of death during the period from 3 to 16 days after diagnosis with adjustments for age and the baseline cycle-threshold value on polymerase-chain-reaction assay; patients who had died before day 3 were excluded. The clinically important difference was defined as an absolute reduction in mortality of 20 percentage points in the convalescent-plasma group as compared with the control group.ResultsA total of 84 patients who were treated with plasma were included in the primary analysis. At baseline, the convalescent-plasma group had slightly higher cycle-threshold values and a shorter duration of symptoms than did the control group, along with a higher frequency of eye redness and difficulty in swallowing. From day 3 to day 16 after diagnosis, the risk of death was 31% in the convalescent-plasma group and 38% in the control group (risk difference, -7 percentage points; 95% confidence interval [CI], -18 to 4). The difference was reduced after adjustment for age and cycle-threshold value (adjusted risk difference, -3 percentage points; 95% CI, -13 to 8). No serious adverse reactions associated with the use of convalescent plasma were observed.ConclusionsThe transfusion of up to 500 ml of convalescent plasma with unknown levels of neutralizing antibodies in 84 patients with confirmed EVD was not associated with a significant improvement in survival. (Funded by the European Union's Horizon 2020 Research and Innovation Program and others; ClinicalTrials.gov number, NCT02342171.).
| S-EPMC5856332 | biostudies-literature
Project description:The clinical evaluation of convalescent plasma (CP) for the treatment of Ebola virus disease (EVD) in the current outbreak, predominantly affecting Guinea, Sierra Leone, and Liberia, was prioritized by the World Health Organization in September 2014. In each of these countries, nonrandomized comparative clinical trials were initiated. The Ebola-Tx trial in Conakry, Guinea, enrolled 102 patients by 7 July 2015; no severe adverse reactions were noted. The Ebola-CP trial in Sierra Leone and the EVD001 trial in Liberia have included few patients. Although no efficacy data are available yet, current field experience supports the safety, acceptability, and feasibility of CP as EVD treatment. Longer-term follow-up as well as data from nontrial settings and evidence on the scalability of the intervention are required. CP sourced from within the outbreak is the most readily available source of anti-EVD antibodies. Until the advent of effective antivirals or monoclonal antibodies, CP merits further evaluation.
| S-EPMC4678103 | biostudies-other
Project description:Background:Ebola virus (EBOV) neutralizing antibody in plasma may reduce viral load following administration of plasma to patients with Ebola virus disease (EVD), but measurement of these antibodies is complex. Methods:Anti-EBOV antibody was measured by 2 neutralization and 2 enzyme-linked immunosorbent assays (ELISAs) in convalescent plasma (ECP) from 100 EVD survivor donors in Liberia. Viral load was assessed repetitively in patients with EVD participating in a clinical trial of enhanced standard of care plus ECP. Results:All 4 anti-EBOV assays were highly concordant for detection of EBOV antibody. Antibodies were not detected in plasma specimens obtained from 15 of 100 donors, including 7 with documented EBOV-positive reverse-transcription polymerase chain reaction during EVD. Viral load was reduced following each dose in the 2 clinical trial participants who received ECP with higher antibody levels but not in the 2 who received ECP with lower antibody levels. Conclusions:Recovery from EVD can occur with absence of detectable anti-EBOV antibody several months after disease onset. ELISAs may be useful to select ECP donors or identify ECP units that contain neutralizing antibody. ECP with higher anti-EBOV antibody levels may have greater effect on EBOV load-an observation that requires further investigation. Clinical Trials Registration:NCT02333578.
| S-EPMC6927845 | biostudies-literature
Project description:The 2013-2016 Ebola Zaire virus (EBV) outbreak in West Africa resulted in over 28,000 cases and 11,000 deaths. Ebola virus disease (EVD) is a highly virulent systemic disease with a high case fatality rate of ~ 50%. EVD results in hemorrhagic fever marked by an exaggerated systemic inflammatory response, and impaired vascular and coagulation systems. The immune response of patients who either survived or died is characterized by strong differences. Notably, fatalities showed a diminished capacity to mount an appropriate immune response, resulting in high viremia and increased pro-inflammatory cytokine production. In this study, we analyzed 38 sequential samples collected from 12 patients: 8 survivors and 4 fatalities. Our analytical strategy combined three protein-based platforms covering three different fractions of the plasma proteome: the undepleted classical plasma proteome, the depleted plasma proteome, and cytokines/chemokines, using LC/MS- and antibody-based assays, resulting in over 1000 quantified host and pathogen proteins. For depletion of the most abundant plasma proteins, we advanced a perchloric acid-based precipitation method. This method is low cost, high-throughput and robust.
2022-03-29 | PXD030260 | Pride
Project description:Spondyloarthritis (Spa), Behçet's disease (BD) and sarcoidosis are major systemic inflammatory diseases worldwide. They are all multisystem pathologies and share a possible ocular involvement, especially uveitis. We hereby describe selected cases who were referred by ophthalmologists to our internal medicine department for unexplained uveitis. Physical examination and/or the use of laboratory and imaging investigations allowed to make a diagnosis of a systemic inflammatory disease in a large proportion of patients. In our tertiary referral center, 75 patients have been diagnosed with Spa (n = 20), BD (n = 9), or sarcoidosis (n = 46) in the last two years. There was a significant delay in the diagnosis of Spa-associated uveitis. Screening strategies using Human Leukocyte Antigen (HLA)-B27 determination and sacroiliac magnetic resonance imaging in patients suffering from chronic low back pain and/or psoriasis helped in the diagnosis. BD's uveitis affects young people from both sexes and all origins and usually presents with panuveitis and retinal vasculitis. The high proportion of sarcoidosis in our population is explained by the use of chest computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography CT that helped to identify smaller hilar or mediastinal involvement and allowed to further investigate those patients, especially in the elderly. Our results confirm how in these sight- and potentially life-threatening diseases a prompt diagnosis is mandatory and benefits from a multidisciplinary approach.
| S-EPMC7828680 | biostudies-literature
Project description:Ebola virus disease (EVD) is a severe and frequently lethal disease caused by Ebola virus (EBOV). EVD outbreaks typically start from a single case of probable zoonotic transmission, followed by human-to-human transmission via direct contact or contact with infected bodily fluids or contaminated fomites. EVD has a high case-fatality rate; it is characterized by fever, gastrointestinal signs and multiple organ dysfunction syndrome. Diagnosis requires a combination of case definition and laboratory tests, typically real-time reverse transcription PCR to detect viral RNA or rapid diagnostic tests based on immunoassays to detect EBOV antigens. Recent advances in medical countermeasure research resulted in the recent approval of an EBOV-targeted vaccine by European and US regulatory agencies. The results of a randomized clinical trial of investigational therapeutics for EVD demonstrated survival benefits from two monoclonal antibody products targeting the EBOV membrane glycoprotein. New observations emerging from the unprecedented 2013-2016 Western African EVD outbreak (the largest in history) and the ongoing EVD outbreak in the Democratic Republic of the Congo have substantially improved the understanding of EVD and viral persistence in survivors of EVD, resulting in new strategies toward prevention of infection and optimization of clinical management, acute illness outcomes and attendance to the clinical care needs of patients.
| S-EPMC7223853 | biostudies-literature
Project description:BackgroundThe current West Africa Ebola virus disease (EVD) outbreak has resulted in multiple individuals being medically evacuated to other countries for clinical management.MethodsWe report two patients who were transported from West Africa to the United States for treatment of EVD. Both patients received aggressive supportive care measures, as well as an investigational therapeutic (TKM-100802) and convalescent plasma.ResultsWhile one patient experienced critical illness with multi-organ failure requiring mechanical ventilation and renal replacement therapy, both patients recovered without serious long-term sequelae to date.ConclusionsIt is unclear what role the experimental drug and convalescent plasma had in the recovery of these patients. Prospective clinical trials are needed to delineate the role of investigational therapies in the care of patients with EVD.
| S-EPMC4542597 | biostudies-literature
Project description:As of 20 May 2016 there have been 28,646 cases and 11,323 deaths resulting from the West African Ebola virus disease (EVD) outbreak reported to the World Health Organization. There continue to be sporadic flare-ups of EVD cases in West Africa.EVD presentation is nonspecific and characterized initially by onset of fatigue, myalgias, arthralgias, headache, and fever; this is followed several days later by anorexia, nausea, vomiting, diarrhea, and abdominal pain. Anorexia and gastrointestinal losses lead to dehydration, electrolyte abnormalities, and metabolic acidosis, and, in some patients, acute kidney injury. Hypoxia and ventilation failure occurs most often with severe illness and may be exacerbated by substantial fluid requirements for intravascular volume repletion and some degree of systemic capillary leak. Although minor bleeding manifestations are common, hypovolemic and septic shock complicated by multisystem organ dysfunction appear the most frequent causes of death.Males and females have been equally affected, with children (0-14 years of age) accounting for 19 %, young adults (15-44 years) 58 %, and older adults (?45 years) 23 % of reported cases. While the current case fatality proportion in West Africa is approximately 40 %, it has varied substantially over time (highest near the outbreak onset) according to available resources (40-90 % mortality in West Africa compared to under 20 % in Western Europe and the USA), by age (near universal among neonates and high among older adults), and by Ebola viral load at admission.While there is no Ebola virus-specific therapy proven to be effective in clinical trials, mortality has been dramatically lower among EVD patients managed with supportive intensive care in highly resourced settings, allowing for the avoidance of hypovolemia, correction of electrolyte and metabolic abnormalities, and the provision of oxygen, ventilation, vasopressors, and dialysis when indicated. This experience emphasizes that, in addition to evaluating specific medical treatments, improving the global capacity to provide supportive critical care to patients with EVD may be the greatest opportunity to improve patient outcomes.
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