Publications by authors named "Ian Crozier"

We performed monkeypox virus genome sequencing on clinical samples from Liberia, yielding 5 clade IIa genomes. Our analysis found no evidence of sustained human-to-human transmission, suggesting independent zoonotic spillovers from a diverse viral lineage. Public health officials should continue monitoring and sequencing efforts to identify emerging monkeypox virus lineages.

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Unlabelled: A cocktail of human monoclonal antibodies 1C3 and 1C11 previously protected macaques from a lethal exposure to either Ebola virus (EBOV) or Sudan virus (SUDV). 1C3 is of particular interest because its paratope strongly binds with unique stoichiometry to the glycoprotein head of several orthoebolaviruses, resulting in neutralization of EBOV and SUDV. Therefore, we evaluated the protective activity of 1C3 as a standalone therapeutic in macaques exposed to either EBOV or SUDV.

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The 2013-2016 Western African outbreak of the Ebola virus disease (EVD), the largest recorded outbreak since the discovery of Ebola virus (EBOV) in 1976, destabilized local health systems and left thousands of survivors at risk for post-acute sequelae, including vision-threatening uveitis. In an EVD survivor with severe panuveitis, the detection of persistent EBOV in the aqueous humor, long after clearance of acute viremia, focused clinical and research attention on the host-EBOV interaction in the unique terrain of ocular immune-privilege. Despite the recognition that uveitis is common and consequential in EVD survivors, our understanding of pathogenesis is extremely limited, including the contributions of viral persistence and ocular-specific and systemic immune responses to disease expression.

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Importance: Both myocardial infarction (MI) and anemia have deleterious effects on health-related quality of life (QOL). Red blood cell (RBC) transfusion may improve QOL after MI by relieving symptoms and/or increasing functional capacity.

Objective: To evaluate whether a liberal transfusion strategy compared with a more restrictive transfusion strategy affects QOL in patients with MI and anemia.

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This report describes the ocular manifestations in a cohort of patients with Clade I mpox evaluated in the Democratic Republic of the Congo (DRC) from 2007 to 2011, as well as the clinical course of a pediatric patient with mpox associated with ocular disease. Among 216 patients, ocular manifestations were observed in 8.3% of the patients, including conjunctivitis, eyelid lesions, eyelid swelling, eye pain, orbital swelling, keratitis, and corneal staphyloma.

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The dysregulated production of reactive oxygen species (ROS) during viral infections may lead to immune cell death and ineffective host responses. ROS dynamics have been under-investigated in severe Ebola virus disease (EVD), a condition in which hyperinflammation and excessive immune cell death are well described but poorly understood. Through ex vivo immunohistochemistry and in vivo ROS-sensitive magnetic resonance imaging (MRI) we demonstrate significant ROS-related oxidative changes in the spleens of domestic ferrets exposed to Ebola virus (EBOV).

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Background: Tecovirimat is available for the treatment of mpox (formerly known as monkeypox) in Europe and the United States, on the basis of findings from efficacy studies in animals and safety evaluations in healthy humans. Evidence from randomized, controlled trials of safety and efficacy in patients with mpox is lacking.

Methods: We conducted a double-blind, randomized, placebo-controlled trial of tecovirimat in patients with mpox in the Democratic Republic of Congo (DRC).

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Background: The extravascular implantable cardioverter-defibrillator (EV-ICD) with substernal lead placement has been shown to terminate ventricular arrhythmias safely and effectively while being outside the vasculature. The performance of the EV-ICD system with a novel inappropriate shock-reducing algorithm in a real-world setting has yet to be investigated.

Objective: The objective of the Enlighten Study: the EV-ICD Post-Approval Registry is to provide a comprehensive measure of the safety and performance of the EV-ICD system in real-world clinical practice over the lifetime of the device.

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Background: Premarket clinical trials have shown the extravascular implantable cardioverter-defibrillator (EV-ICD) system to provide effective therapy with a low complication rate, but its performance in the real world is unknown.

Objective: We report on the periprocedural safety and performance of the EV-ICD system from the postmarket Enlighten (EV-ICD Post-Approval Registry) Study.

Methods: Enlighten is an ongoing, global, prospective, postmarket registry study, enrolling patients guideline indicated for an ICD with a planned implantation of the Aurora EV-ICD system (Medtronic, Mounds View, MN).

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Monoclonal antibodies (mAbs) against Ebola virus (EBOV) glycoprotein (GP) are the standard of care for Ebola virus disease (EVD). Anti-GP mAbs targeting the stalk and membrane proximal external region (MPER) potently neutralize EBOV in vitro and are protective in a mouse model of EVD. However, their neutralization mechanism is poorly understood because they target a GP epitope that has evaded structural characterization.

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Background: The robustness and persistence of vaccine antigen-induced antibodies are often used as proxy indicators of vaccine efficacy, but immune responses to vaccine vectors are typically less well-defined. Our study considered the kinetics of immunoglobulin (IgG) responses against the vector (vesicular stomatitis Indiana virus [VSIV]) nucleoprotein (N) and the inserted antigen (Ebola virus [EBOV]) glycoprotein (GP1,2) components of the rVSVΔG-ZEBOV-GP (rVSV-ZEBOV) vaccine and evaluated their use as biomarkers to confirm self-reported vaccination status.

Methods: From the Partnership for Research on Ebola Virus in Liberia (PREVAIL) I clinical trial (NCT02344407), we randomly selected 212 participants who received rVSV-ZEBOV (n=107) or placebo (n=105).

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Purpose: To characterize corneal and conjunctival abnormalities (CCAs) and their impact on visual acuity in a cohort of survivors from the Western African Ebola virus disease (EVD) outbreak.

Design: A post hoc analysis of 121 patients, who had previously undergone screening for the Ebola Virus Persistence in Ocular Tissues and Fluids study, was performed.

Methods: Patients underwent a comprehensive ophthalmic exam at the Lowell and Ruth Gess Eye Hospital in Freetown, Sierra Leone.

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Article Synopsis
  • * A study involving 521 EVD survivors in Sierra Leone found that significant eye conditions such as cataracts, uveitis, and dry eyes were present, highlighting the prevalence of visual impairments in this population even years after recovery.
  • * EVD survivors with certain eye conditions, like cataracts and uveitis, were at greater risk of having vision impairment, underscoring the importance of ongoing eye care for those affected by the disease.
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Background/objectives: Ebola virus disease (EVD) survivors develop post-acute ophthalmic sequelae, including a high prevalence of uveitis that may be complicated by vision-threatening cataract. After the non-detection of Ebola virus (EBOV) RNA in sampled ocular fluid, vision impairment due to cataract can be treated safely and effectively via manual small incision cataract surgery (MSICS). However, the long-term ocular visual outcomes and assessment of ocular tissues, including for genomic RNA, have been infrequently or not reported in Western African survivors.

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Introduction: Substernal extravascular defibrillators (EV ICDs) have been shown to be effective and safe for patients at risk of sudden cardiac death, however, there is little evidence around the safety of extracting chronic devices.

Methods And Results: We present a 50-year-old patient in whom a Medtronic EV ICD system was successfully removed without specialist extraction tools, 186 weeks after implantation, by an operator experienced in transvenous lead extraction but without formal training in EVICD implantation.

Conclusion: The successful extraction of an EV ICD system is possible without specialised tools at least 3.

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Article Synopsis
  • - Lassa virus (LASV) leads to hundreds of thousands of infections in Western Africa annually, with about 20% progressing to Lassa fever, a serious disease that has a high fatality rate.
  • - Currently, there are no approved vaccines or treatments for Lassa fever, but researchers have been working on recombinant LASVs (rLASVs) that show promising results as vaccines in animal models.
  • - The new vaccine candidate, rLASV/IGR-CD, demonstrated high safety and effectiveness in guinea pigs, offering complete protection against lethal LASV exposure and advancing the development of a live-attenuated vaccine for Lassa fever.
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Article Synopsis
  • * It involves a subgroup analysis of over 3,100 participants from the MINT clinical trial conducted across multiple countries between 2017 and 2023, with a 30-day follow-up period and primary outcomes related to death or recurrent MI.
  • * Results indicated that 34.3% of participants had acute anemia, and the researchers explored the link between anemia type and post-MI outcomes, assessing various secondary complications as well.
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Objective: To describe a simple therapeutic intervention for persistent congestion in an advanced heart failure patient using a continuous intravenous furosemide infusion in the home setting with a non-powered elastomeric pump that can be managed by the patient.

Key Steps: Patient selected as a known intravenous furosemide responder with a supportive home environment. Shared care decision making with patient, cardiologist, heart failure nurse practitioner, palliative care physician, and general practitioner.

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During the last decade, global health security has been threatened by major Ebola virus disease outbreaks in Western Africa (2014 to 2016) and in eastern Democratic Republic of the Congo (2018 to 2020). Particularly in Western Africa, the outbreak initially overwhelmed health care capacity in already fragile health systems. Thousands of survivors were at risk of newly recognized postacute ocular complications, and their need for urgent ophthalmic care challenged national vision health systems with scarce eye care services.

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Article Synopsis
  • - The Ebola virus disease (EVD) was first identified in the Democratic Republic of the Congo (DRC) in 1976, and a significant outbreak occurred between 2018 and 2020, complicated by security issues and high case numbers across a wide area.
  • - A program was initiated to provide eye care for EVD survivors, involving partnerships with health authorities, where 237 survivors were screened and a significant percentage reported ocular symptoms like itchy eyes and eye pain.
  • - The findings revealed various eye issues such as retinal scarring, uveitis, and cataracts among survivors, highlighting the need for ongoing monitoring and multidisciplinary care to address these post-EVD health challenges.
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A range of challenges exists regarding vitreoretinal (VR) surgical services in resource-limited settings, including Sierra Leone. As a result, retinal pathologies may contribute to vision loss and blindness. In the wake of the 2013 to 2016 outbreak of Ebola virus disease in West Africa, gaps in ophthalmic care were underscored as survivors were experiencing a constellation of sequelae, including uveitis and VR disease.

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