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. In this study, we characterize humoral immune responses in EVD survivors and their contacts in Eastern Sierra Leone. We found high levels of EBOV IgG in EVD survivors and lower yet substantial antibody levels in household contacts, suggesting subclinical transmission. Neutralizing antibody function was prevalent but variable in EVD survivors, raising questions about the durability of immune responses from natural infection with EBOV. Additionally, we found that certain discrete symptoms-ophthalmologic and auditory-are associated with EBOV IgG seropositivity, while an array of symptoms are associated with the presence of neutralizing antibody.

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. We collected demographic and clinical characteristics and calculated each participant´s respiratory symptom severity. Nose and throat swabs were collected at enrollment. Total nucleic acid was purified and tested for multiple respiratory viruses. Statistical analysis was performed using R version 4.2.0 software. 502 children less than two-years of age were enrolled. 376 (74.9%) had at least one respiratory virus detected. The most common viruses isolated were HRV/EV (28.2%), RSV (19.5%) and PIV (13.1%). Influenza and SARS-CoV-2 were identified in only 9.2% and 3.9% of children, respectively. Viral co-detection was common. Human metapneumovirus and RSV had more than two-fold higher odds of requiring O2 therapy while hospitalized. Viral pathogen prevalence was high (74.9%) in our study population. Despite this, 100% of children received antibiotics, underscoring a need to expand laboratory diagnostic capacity and to revisit clinical guidelines implementation in these children. Continuous surveillance and serologic studies among more diverse age groups, with greater geographic breadth, are needed in Sierra Leone to better characterize the long-term impact of COVID-19 on respiratory virus prevalence and to better characterize the seasonality of respiratory viruses in Sierra Leone.

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. The aims of this study were to describe the antibiotic prescribing practices for children less than 24 months of age with symptoms of ARI, that were admitted to Kenema Government Hospital (KGH) in the Eastern Province of Sierra Leone, and to identify the number of children empirically prescribed antibiotics who were admitted to hospital with ARI, as well as their clinical signs, symptoms, and outcomes. METHODS: We conducted a prospective study of children < 24 months of age admitted to the KGH pediatric ward with respiratory symptoms between October 1, 2020 and May 31, 2022. Study nurses collected data on demographic information, medical and medication history, and information on clinical course while hospitalized. RESULTS: A total of 777 children were enrolled. Prior to arrival at the hospital, 224 children (28.8%) reported taking an antibiotic for this illness without improvement. Only 15 (1.9%) children received a chest radiograph to aid in diagnosis and 100% of patients were placed on antibiotics during their hospital stay. CONCLUSIONS: Despite the lives saved, reliance on clinical decision-support tools such as IMCI and ETAT + for pediatric ARI, is resulting in the likely over-prescribing of antibiotics. Greater uptake of implementation research is needed to develop strategies and tools designed to optimize antibiotic use for ARI in LMIC settings. Additionally, much greater priority needs to be given to ensuring clinicians have the basic tools for clinical diagnosis, as well as greater investments in essential laboratory and radiographic diagnostics that help LMIC clinicians move beyond the sole reliance on algorithm based clinical decision making.

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. Exposure to LASV is usually through contact with rodent excreta. After an incubation period of 1-3 weeks, initial symptoms such as fever, headache, and fatigue develop that may progress to sore throat, retrosternal chest pain, conjunctival injection, vomiting, diarrhea, and abdominal pain. Severe illness, including hypotension, shock, and multiorgan failure, develops in a minority of patients. Patient demographics and case fatality rates are distinctly different in Sierra Leone and Nigeria. Laboratory diagnosis relies on the detection of LASV antigens or genomic RNA. LASV-specific immunoglobulin G and M assays can also contribute to clinical management. The mainstay of treatment for Lassa fever is supportive care. The nucleoside analog ribavirin is commonly used to treat acute Lassa fever but is considered useful only if treatment is begun early in the disease course. Drugs in development, including a monoclonal antibody cocktail, have the potential to impact the management of Lassa fever.

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. However, a significant amount of work now needs to be undertaken to ensure that future trials for LF can be conducted consistently and reliably to facilitate the efficient generation of evidence. METHODOLOGY: We convened a consultation group to establish the position of clinicians and researchers on the core components of future trials. A Core Eligibility Criteria (CEC), Core Case Definition (CCD), Core Outcome Set (COS) and Core Data Variables (CDV) were developed through the process of a multi-stakeholder consultation that took place using a modified-Delphi methodology. RESULTS: A consensus position was achieved for each aspect of the framework, which accounts for the inclusion of pregnant women and children in future LF clinical trials. The framework consists of 8 core criteria, as well as additional considerations for trial protocols. CONCLUSIONS: This project represents the first step towards delineating the clinical development pathway for new Lassa fever therapeutics, following a period of 40 years without advancement. Future planned projects will bolster the work initiated here to continue the advancement of LF clinical research through a regionally-centred, collaborative methodology, with the aim of delineating a clear pathway through which LF clinical trials can progress efficiently and ensure sustainable investments are made in research capacity at a regional level.

Emergency Triage Assessment and Treatment Plus (ETAT+): adapting training to strengthen quality improvement and task-sharing in emergency paediatric care in Sierra Leone.

BACKGROUND: Over the past 25 years Sierra Leone has made progress in reducing maternal and child mortality, but the burden of preventable paediatric deaths remains high. Further progress towards achieving the Sustainable Development Goals will require greater strengthening of the health care system, including hospital care for perinatal and paediatric conditions. Emergency Triage Assessment and Treatment Plus (ETAT+) may offer a useful tool. METHODS: The five-day ETAT+ course was adapted as a six-month programme of in-situ training and mentoring integrated with patient flow and service delivery improvements in 14 regional and district government hospitals across the country. Nurses were trained to carry out the initial resuscitation and assessment of the sick paediatric patient, and to administer the first dose of medication per protocol. The course was for all clinical staff; most participants were nurses. RESULTS: The intervention was associated with an improvement in the quality of paediatric care and a reduction in mortality. In 2017 mortality decreased by 33.1%, from 14.5% at baseline to 9.7% after six months of the intervention. Mortality at the start of the 2018 intervention was 8.5% and reduced over six months to 6.5%. Care quality indicators showed improvement across the two intervention periods, with some evidence of sustained effect. CONCLUSIONS: These results suggest that adapted ETAT+ training with in-situ mentoring alongside improved patient flow and service delivery supports improvements in the quality of paediatric care in Sierra Leonean hospitals. ETAT+ may provide an affordable framework for improving the quality of secondary paediatric care in Sierra Leone and a model of nurse-led resuscitation may allow for prompt and timely emergency paediatric care in Sierra Leonean hospitals where there are fewer physicians and other resources for care.

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. Results were compared to COVID-19 subjects and healthy blood donors from the United States. Prior to the pandemic, Sierra Leoneans had more frequent exposures than Americans to coronaviruses with epitopes that cross-react with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), SARS-CoV, and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). The percentage of Sierra Leoneans with antibodies reacting to seasonal coronaviruses was also higher than for American blood donors. Serological responses to coronaviruses by Sierra Leoneans did not differ by age or sex. Approximately a quarter of Sierra Leonian pre-pandemic blood samples had neutralizing antibodies against SARS-CoV-2 pseudovirus, while about a third neutralized MERS-CoV pseudovirus. Prior exposures to coronaviruses that induce cross-protective immunity may contribute to reduced COVID-19 cases and deaths in Sierra Leone.

Space-Time Trends in Lassa Fever in Sierra Leone by ELISA Serostatus, 2012-2019.

Lassa fever (LF) is a viral hemorrhagic disease found in Sub-Saharan Africa and is responsible for up to 300,000 cases and 5000 deaths annually. LF is highly endemic in Sierra Leone, particularly in its Eastern Province. Kenema Government Hospital (KGH) maintains one of only a few LF isolation facilities in the world with year-round diagnostic testing. Here we focus on space-time trends for LF occurring in Sierra Leone between 2012 and 2019 to provide a current account of LF in the wake of the 2014-2016 Ebola epidemic. Data were analyzed for 3277 suspected LF cases and classified as acute, recent, and non-LF or prior LF exposure using enzyme-linked immunosorbent assays (ELISAs). Presentation rates for acute, recent, and non-LF or prior LF exposure were 6.0% (195/3277), 25.6% (838/3277), and 68.4% (2244/3277), respectively. Among 2051 non-LF or prior LF exposures, 33.2% (682/2051) tested positive for convalescent LF exposure. The overall LF case-fatality rate (CFR) was 78.5% (106/135). Both clinical presentations and confirmed LF cases declined following the Ebola epidemic. These declines coincided with an increased duration between illness onset and clinical presentation, perhaps suggesting more severe disease or presentation at later stages of illness. Acute LF cases and their corresponding CFRs peaked during the dry season (November to April). Subjects with recent (but not acute) LF exposure were more likely to present during the rainy season (May to October) than the dry season (p < 0.001). The findings here suggest that LF remains endemic in Sierra Leone and that caseloads are likely to resume at levels observed prior to the Ebola epidemic. The results provide insight on the current epidemiological profile of LF in Sierra Leone to facilitate LF vaccine studies and accentuate the need for LF cohort studies and continued advancements in LF diagnostics.

Lassa Fever among Children in Eastern Province, Sierra Leone: A 7-year Retrospective Analysis (2012-2018).

Pediatric Lassa fever (LF) usually presents as a nonspecific febrile illness, similar to other endemic diseases in countries like Sierra Leone, where LF is considered to be hyperendemic. The nonspecificity of presentation and lack of research have made it difficult to fully understand best practices for pediatric management. We aim to describe clinical characteristics of hospitalized pediatric patients suspected or diagnosed with LF and assess factors associated with hospital outcomes among those with LF antigen-positive results. We conducted a 7-year retrospective cohort study using routine data for all children younger than 18 years admitted at the Kenema Government Hospital's LF ward. A total of 292 children with suspected or confirmed LF were analyzed. Overall, mortality was high (21%). Children with antigen-positive results had a high case fatality rate of 63% (P < 0.01). In univariate analyses, children who presented with unexplained bleeding (odds ratio [OR]: 3.58; 95% CI: 1.08-11.86; P = 0.040) and confusion (altered sensorium) (OR: 5.37; 95% CI: 1.34-21.48; P = 0.020) had increased odds of death. Abnormal serum levels of alanine aminotransferase (P = 0.001), creatinine (P = 0.004), and potassium (P = 0.003) were associated with increased likelihood of death in these children. Treatment with ribavirin was not significantly associated with survival (P = 0.916). Our findings provide insights into current pediatric LF clinical presentation and management. More evidence-based, high-quality research in creating predictive algorithms of antigen-positivity and hospital outcomes is needed in the management of pediatric LF.

Assessing communication between oncology professionals and their patients.

BACKGROUND: Effective communication with cancer patients continues to be an elusive goal for health care professionals (HCPs) and cancer educators. METHODS: We posted a survey on the ConversationsInCare.com Web site to collect information from oncology HCPs regarding attitudes, effectiveness, and specific patient communication skills. RESULTS: The 291 respondents agreed that good communication enhances patient satisfaction (76%) and treatment compliance (88%). Only 34% of respondents felt comfortable discussing complementary or alternative therapies, and approximately half of all respondents felt they lack the skills to help patients maintain hope. CONCLUSIONS: Oncology HCPs believe that good communication is important and wish to improve their skills. Implications for cancer educators are discussed.

Physically correct theoretical prism waveguide coupler model.

We develop new generalized four-wave-model-based waveguide mode equations for both isotropic and anisotropic systems by taking into account the influence of the incident light. These new mode equations eliminate the inherent deficiency in the conventional waveguide model, in which the action of incident light was neglected. Further, a peak-value-search (PVS) numerical method is developed to solve the four-wave-model-based mode equations. The PVS method has significant advantages in that accurate refractive index and thickness can be obtained without prior knowledge of the thickness of the air gap.