Long-term visual outcomes and histopathologic findings after cataract surgery in Ebola virus disease survivors in the Ebola virus RNA persistence in ocular tissues and fluids (EVICT) study.

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.

Long-term physical and mental health outcomes of Ebola Virus Disease survivors in Kenema District, Sierra Leone: A cross-sectional survey.

The 2013-2016 Ebola Virus Disease (EVD) epidemic in West Africa was the deadliest in history, with over 28,000 cases. Numerous physical and mental health symptoms have been reported in EVD survivors, although there is limited prior research on how the health of survivors compares to the general population. We conducted a survey of EVD survivors in Kenema District, Sierra Leone and a population-based sample of community members who lived in EVD-affected areas but were not diagnosed with EVD, and compared resulting data about self-reported symptoms, duration, and severity between EVD survivors and community members through multivariate regression models.

Ebola Virus-Specific Neutralizing Antibody Persists at High Levels in Survivors 2 Years After Resolution of Disease in a Sierra Leonean Cohort.

Ebola virus (EBOV) infection results in Ebola virus disease (EVD), an often severe disease with a nonspecific presentation. Since its recognition, periodic outbreaks of EVD continue to occur in sub-Saharan Africa. The 2013-2016 West African EVD outbreak was the largest recorded, resulting in a substantial cohort of EVD survivors with persistent health complaints and variable immune responses.

Upper Airway Epithelial Tissue Transcriptome Analysis Reveals Immune Signatures Associated with COVID-19 Severity in Ghanaians.

The immunological signatures driving the severity of coronavirus disease 19 (COVID-19) in Ghanaians remain poorly understood. We performed bulk transcriptome sequencing of nasopharyngeal samples from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected Ghanaians with mild and severe COVID-19, as well as healthy controls to characterize immune signatures at the primary SARS-CoV-2 infection site and identify drivers of disease severity. Generally, a heightened antiviral response was observed in SARS-CoV-2-infected Ghanaians compared with uninfected controls.

Emergency care capacity in Sierra Leone: A multicentre analysis.

Background: The Disease Control Priorities Project estimates that over 50 % of annual mortality in low- and middle-income countries can be addressed by improved emergency care. Sierra Leone's Ministry of Health and Sanitation has highlighted emergency care as a national priority. We conducted the first multicentre analysis of emergency care capacity in Sierra Leone, using the Hospital Emergency Unit Assessment Tool (HEAT) to analyse 14 government hospitals across the country.

Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever.

Infection with Lassa virus (LASV) can cause Lassa fever, a haemorrhagic illness with an estimated fatality rate of 29.7%, but causes no or mild symptoms in many individuals. Here, to investigate whether human genetic variation underlies the heterogeneity of LASV infection, we carried out genome-wide association studies (GWAS) as well as seroprevalence surveys, human leukocyte antigen typing and high-throughput variant functional characterization assays.

Respiratory virus surveillance in hospitalized children less than two-years of age in Kenema, Sierra Leone during the COVID-19 pandemic (October 2020- October 2021).

Globally, viral pathogens are the leading cause of acute respiratory infection in children under-five years. We aim to describe the epidemiology of viral respiratory pathogens in hospitalized children under-two years of age in Eastern Province of Sierra Leone, during the second year of the SARS-CoV-2 pandemic. We conducted a prospective study of children hospitalized with respiratory symptoms between October 2020 and October 2021.

Antibiotic prescribing practices for acute respiratory illness in children less than 24 months of age in Kenema, Sierra Leone: is it time to move beyond algorithm driven decision making?

Background: Lower respiratory tract infections are the leading cause of mortality in young children globally. In many resource-limited settings clinicians rely on guidelines such as IMCI or ETAT + that promote empiric antibiotic utilization for management of acute respiratory illness (ARI). Numerous evaluations of both guidelines have shown an overall positive response however, several challenges have also been reported, including the potential for over-prescribing of unnecessary antibiotics.

Lassa Fever Natural History and Clinical Management.

Lassa fever is caused by Lassa virus (LASV), an Old World Mammarenavirus that is carried by Mastomys natalensis and other rodents. It is endemic in Sierra Leone, Nigeria, and other countries in West Africa. The clinical presentation of LASV infection is heterogenous varying from an inapparent or mild illness to a fatal hemorrhagic fever.

A prospective, multi-site, cohort study to estimate incidence of infection and disease due to Lassa fever virus in West African countries (the Enable Lassa research programme)-Study protocol.

Background: Lassa fever (LF), a haemorrhagic illness caused by the Lassa fever virus (LASV), is endemic in West Africa and causes 5000 fatalities every year. The true prevalence and incidence rates of LF are unknown as infections are often asymptomatic, clinical presentations are varied, and surveillance systems are not robust. The aim of the Enable Lassa research programme is to estimate the incidences of LASV infection and LF disease in five West African countries.

Seroprevalence of anti-Lassa Virus IgG antibodies in three districts of Sierra Leone: A cross-sectional, population-based study.

Background: Lassa virus (LASV), the cause of the acute viral hemorrhagic illness Lassa fever (LF), is endemic in West Africa. Infections in humans occur mainly after exposure to infected excrement or urine of the rodent-host, Mastomys natalensis. The prevalence of exposure to LASV in Sierra Leone is crudely estimated and largely unknown.

Expansion of CD8+ T cell population in Lassa virus survivors with low T cell precursor frequency reveals durable immune response in most survivors.

Introduction: Lassa virus is a priority pathogen for vaccine research and development, however the duration of cellular immunity and protection in Lassa fever (LF) survivors remains unclear.

Methods: We investigated Lassa virus specific CD8+ T cell responses in 93 LF survivors. Peripheral blood mononuclear cells from these individuals were infected with recombinant vesicular stomatitis virus encoding Lassa virus antigens and virus specific T cell responses were measured after 18-hour incubation.

Predicting the evolution of the Lassa virus endemic area and population at risk over the next decades.

Lassa fever is a severe viral hemorrhagic fever caused by a zoonotic virus that repeatedly spills over to humans from its rodent reservoirs. It is currently not known how climate and land use changes could affect the endemic area of this virus, currently limited to parts of West Africa. By exploring the environmental data associated with virus occurrence using ecological niche modelling, we show how temperature, precipitation and the presence of pastures determine ecological suitability for virus circulation.

Evaluation of Three Clinical Prediction Tools to Predict Mortality in Hospitalized Patients with Lassa Fever.

Lassa fever is a viral hemorrhagic illness with a case fatality rate for hospitalized patients as high as 69%. Identifying cases before they progress to serious illness can lead to earlier treatment and improved clinical outcomes. Three existing clinical prediction tools were evaluated on their ability to predict the in-hospital mortality in Lassa fever: the quick Sequential Organ Failure Assessment (qSOFA), the Modified Early Warning System (MEWS), and the Universal Vital Assessment (UVA).

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.

A standardised Phase III clinical trial framework to assess therapeutic interventions for Lassa fever.

Background: Only one recommendation currently exists for the treatment of Lassa fever (LF), which is ribavirin administered in conjunction with supportive care. This recommendation is primarily based on evidence generated from a single clinical trial that was conducted more than 30 years ago-the methodology and results of which have recently come under scrutiny. The requirement for novel therapeutics and reassessment of ribavirin is therefore urgent.

Cross-Reactive Antibodies to SARS-CoV-2 and MERS-CoV in Pre-COVID-19 Blood Samples from Sierra Leoneans.

Many countries in sub-Saharan Africa have experienced lower COVID-19 caseloads and fewer deaths than countries in other regions worldwide. Under-reporting of cases and a younger population could partly account for these differences, but pre-existing immunity to coronaviruses is another potential factor. Blood samples from Sierra Leonean Lassa fever and Ebola survivors and their contacts collected before the first reported COVID-19 cases were assessed using enzyme-linked immunosorbent assays for the presence of antibodies binding to proteins of coronaviruses that infect humans.

Health seeking behavior after the 2013-16 Ebola epidemic: Lassa fever as a metric of persistent changes in Kenema District, Sierra Leone.

Background: The West African Ebola epidemic of 2013-2016 killed nearly 4,000 Sierra Leoneans and devastated health infrastructure across West Africa. Changes in health seeking behavior (HSB) during the outbreak resulted in dramatic underreporting and substantial declines in hospital presentations to public health facilities, resulting in an estimated tens of thousands of additional maternal, infant, and adult deaths per year. Sierra Leone's Kenema District, a major Ebola hotspot, is also endemic for Lassa fever (LF), another often-fatal hemorrhagic disease.

Implementation of the Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) study: Lessons learned for vision health systems strengthening in Sierra Leone.

Background: Following the West African Ebola virus disease (EVD) outbreak of 2013-2016 and more recent EVD outbreaks in the Democratic Republic of Congo, thousands of EVD survivors are at-risk for sequelae including uveitis, which can lead to unremitting inflammation and vision loss from cataract. Because of the known risk of Ebola virus persistence in ocular fluid and the need to provide vision-restorative, safe cataract surgery, the Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) Study was implemented in Sierra Leone. During implementation of this multi-national study, challenges included regulatory approvals, mobilization, community engagement, infection prevention and control, and collaboration between multiple disciplines.

Development of a qualitative real-time RT-PCR assay for the detection of SARS-CoV-2: a guide and case study in setting up an emergency-use, laboratory-developed molecular microbiological assay.

Developing and deploying new diagnostic tests are difficult, but the need to do so in response to a rapidly emerging pandemic such as COVID-19 is crucially important. During a pandemic, laboratories play a key role in helping healthcare providers and public health authorities detect active infection, a task most commonly achieved using nucleic acid-based assays. While the landscape of diagnostics is rapidly evolving, PCR remains the gold-standard of nucleic acid-based diagnostic assays, in part due to its reliability, flexibility and wide deployment.

A Fc engineering approach to define functional humoral correlates of immunity against Ebola virus.

Protective Ebola virus (EBOV) antibodies have neutralizing activity and induction of antibody constant domain (Fc)-mediated innate immune effector functions. Efforts to enhance Fc effector functionality often focus on maximizing antibody-dependent cellular cytotoxicity, yet distinct combinations of functions could be critical for antibody-mediated protection. As neutralizing antibodies have been cloned from EBOV disease survivors, we sought to identify survivor Fc effector profiles to help guide Fc optimization strategies.