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The irrational use of antibiotics to treat infections in children is a crucial contributing factor to bacterial antimicrobial resistance (AMR), which can have economic and health consequences, such as morbidity and mortality. This study aims to evaluate antibiotic use and AMR in children under five years of age in Sierra Leone. This study will be conducted in three hospitals: Ola During Children, Kenema Government, and Magburaka Government Hospitals in Sierra Leone, among healthcare professionals and patients. A mixed-method (qualitative and quantitative) approach will be used to evaluate paediatric health professionals' knowledge, perceptions, and antibiotic prescription practices. Additionally, two cross-sectional sub-studies will assess inpatient and outpatient trends in antibiotic use and consumption in children, and a cross-sectional observational sub-study will investigate bacterial profiles and AMR among children with bloodstream infections. The anatomical therapeutic chemical (ATC) and the World Health Organisation Access, Watch and Reserve (WHO AWaRe) classifications, days of therapy per 1,000 patient days (DOT/1000PDs), and days of therapy per 100 bed days (DOT/100BDs) will be used to determine the use and consumption. The DOT/1,000PDs and DOT/100BDs will be compared with the defined daily dose/1,000 patient days (DDD/1000PDs) and defined daily dose/100 bed days (DDD/100BDs), respectively. A pre-tested interview guide, interviewer-administered questionnaire and data collection tools adapted from previous studies will be employed for data collection. The sample sizes will be determined, and appropriate sampling methods will be used. Data will be analysed thematically using NVivo 15, and descriptive and inferential statistics using the R software. The results of this study will inform policymakers and healthcare professionals in developing and/or implementing policies, guidelines, and educational initiatives that will promote antibiotic stewardship among children in Sierra Leone.

The 2013-2016 Ebola virus disease (EVD) epidemic resulted in more infections and deaths than all prior outbreaks in the 40-year history of this virus combined. This study examines how experiences of EVD infection, and preventive measures such as social distancing, were linked to experiences of stigma and social exclusion among those reintegrating into their communities. Key informant interviews (n = 42) and focus group discussions (n = 27) were conducted in districts with a high prevalence of EVD and representing geographical and ethnic diversity (n = 228 participants). The final sample was composed of adults (52%) and children (48%) who were EVD-infected (46%) and -affected (42%) individuals, and community leaders (12%). Data were coded using a Grounded Theory approach informed by Thematic Content Analysis, and analyzed using NVivo. Interrater reliability was high, with Cohen's κ = 0.80 or higher. Participants described two main sources of EVD-related stress: isolation from the community because of social distancing and other prevention measures such as quarantine, and stigma related to infected or affected status. Participants linked experiences of social isolation and stigma to significant distress and feelings of ostracization. These experiences were particularly pronounced among children. Sources of support included community reintegration over time, and formal community efforts to provide education and establish protection bylaws. This study found that social distancing and EVD-related stigma were each prominent sources of distress among participants. These results suggest that isolation because of infection, and the enduring stigmatization of infected individuals and their families, demand coordinated responses to prevent and mitigate additional psychosocial harm. Such responses should include close engagement with community leaders to combat misinformation and promote community reintegration.

Lassa fever (LF) is an acute viral hemorrhagic illness endemic in West Africa, representing significant public health challenges, particularly for pregnant persons and children who experience higher morbidity and mortality. Although several vaccine candidates are being developed, no LF vaccine has been licensed yet. We conducted a living systematic review (LSR) of the literature to evaluate the safety, efficacy, effectiveness, and immunogenicity of LF vaccines. We performed biweekly searches in major biomedical databases, trial registries, preprint servers, and other sources. Eligible studies included preclinical studies, clinical trials, and observational studies published from January 2014 to April 2025. Reviewer pairs screened studies extracted data (REDCap), and assessed risk of bias independently. Data synthesis involved random-effects pairwise and proportion meta-analyses (R software), with GRADE assessment of evidence certainty. PROSPERO registries: (CRD42024514513; CRD42024516754). Searches retrieved 1423 records, including 51 studies, 2 clinical trials in adults involving 88 vaccinated persons, and 49 preclinical studies of 30 vaccine candidates. Trials evaluated Recombinant Measles-Vectored (MV-LASV) and Recombinant Vesicular Stomatitis Virus-based (rVSVΔG-LASV-GPC) LF vaccine candidates. No published clinical trials were found to evaluate LF vaccines in special populations such as pregnant persons, infants, children, or adolescents. Although injection site reactogenicity was reported, no vaccine-related serious adverse events (SAEs) were reported in study participants. Immunogenicity was robust in adults, with vaccines achieving around 95% seroconversion at 30 days. Preclinical data evaluated nine different platforms. Findings are disseminated via an interactive online dashboard (https://safeinpregnancy.org/living-systematic-review-lassa/). Currently, two LF vaccine candidates that have advanced to clinical trials exhibit high immunogenicity, but the safety profile in healthy adults is still limited. Clinical evidence in pregnant persons, infants, children, and adolescents is absent. Vaccine platforms of interest have been identified in preclinical studies, providing information on those that could advance to clinical studies.

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. The core protocol described here harmonises key study components, such as eligibility criteria, case definitions, outcome measures, and laboratory tests, which will maximise the comparability of data for between-country analyses. We are conducting a prospective cohort study in Benin, Guinea, Liberia, Nigeria (three sites), and Sierra Leone from 2020 to 2023, with 24 months of follow-up. Each site will assess the incidence of LASV infection, LF disease, or both. When both incidences are assessed the LASV cohort (nmin = 1000 per site) will be drawn from the LF cohort (nmin = 5000 per site). During recruitment participants will complete questionnaires on household composition, socioeconomic status, demographic characteristics, and LF history, and blood samples will be collected to determine IgG LASV serostatus. LF disease cohort participants will be contacted biweekly to identify acute febrile cases, from whom blood samples will be drawn to test for active LASV infection using RT-PCR. Symptom and treatment data will be abstracted from medical records of LF cases. LF survivors will be followed up after four months to assess sequelae, specifically sensorineural hearing loss. LASV infection cohort participants will be asked for a blood sample every six months to assess LASV serostatus (IgG and IgM). Data on LASV infection and LF disease incidence in West Africa from this research programme will determine the feasibility of future Phase IIb or III clinical trials for LF vaccine candidates.

A considerable amount of disease is transmitted from animals to humans and many of these zoonoses are neglected tropical diseases. As outbreaks of SARS, avian influenza and Ebola have demonstrated, however, zoonotic diseases are serious threats to global public health and are not just problems confined to remote regions. There are two fundamental, and poorly studied, stages of zoonotic disease emergence: 'spillover', i.e. transmission of pathogens from animals to humans, and 'stuttering transmission', i.e. when limited human-to-human infections occur, leading to self-limiting chains of transmission. We developed a transparent, theoretical framework, based on a generalization of Poisson processes with memory of past human infections, that unifies these stages. Once we have quantified pathogen dynamics in the reservoir, with some knowledge of the mechanism of contact, the approach provides a tool to estimate the likelihood of spillover events. Comparisons with independent agent-based models demonstrates the ability of the framework to correctly estimate the relative contributions of human-to-human vs animal transmission. As an illustrative example, we applied our model to Lassa fever, a rodent-borne, viral haemorrhagic disease common in West Africa, for which data on human outbreaks were available. The approach developed here is general and applicable to a range of zoonoses. This kind of methodology is of crucial importance for the scientific, medical and public health communities working at the interface between animal and human diseases to assess the risk associated with the disease and to plan intervention and appropriate control measures. The Lassa case study revealed important knowledge gaps, and opportunities, arising from limited knowledge of the temporal patterns in reporting, abundance of and infection prevalence in, the host reservoir.

We aimed to investigate sociodemographic factors associated with self-reported COVID-19 infection. The study population was a prospective multicenter cohort of adult volunteers recruited from healthcare systems located in the mid-Atlantic and southern United States. Between April 2020 and October 2021, participants completed daily online questionnaires about symptoms, exposures, and risk behaviors related to COVID-19, including self-reports of positive SARS CoV-2 detection tests and COVID-19 vaccination. Analysis of time from study enrollment to self-reported COVID-19 infection used a time-varying mixed effects Cox-proportional hazards framework. Overall, 1,603 of 27,214 study participants (5.9%) reported a positive COVID-19 test during the study period. The adjusted hazard ratio demonstrated lower risk for women, those with a graduate level degree, and smokers. A higher risk was observed for healthcare workers, those aged 18-34, those in rural areas, those from households where a member attends school or interacts with the public, and those who visited a health provider in the last year. We identified subgroups within healthcare network populations defined by age, occupational exposure, and rural location reporting higher than average rates of COVID-19 infection for our surveillance population. These subgroups should be monitored closely in future epidemics of respiratory viral diseases.

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. 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. Participants who had undetectable CD8+ T cell response underwent further analysis using a 10-day T cell proliferation assays to evaluate for low T cell precursor frequency. Forty-five of the 93 LF survivors did not have a Lassa virus specific CD8+ T cell response. Of those with responses and a known date of onset of LF (N = 11), 9 had LF within the last ten years. Most participants without a measurable CD8+ T cell response were more than 10 years removed from a clinical history of LF (N = 14/16). Fourteen of 21 patients (67%) with undetectable CD8+ T cell response had a measurable Lassa virus specific CD8+ T cell response with the 10-day assay. Despite reports of strong CD8+ T cell responses during acute Lassa virus infection, circulating Lassa virus-specific CD8+ T cells declined to undetectable levels in most Lassa fever survivors after ten years when evaluated with an 18-hour T cell stimulation. However, when Lassa virus-specific T cells were expanded prior to restimulation, a Lassa virus-specific CD8+ T cell response could be detected in many if the samples that were negative in the 18-hour stimulation assay, suggesting that prolonged cellular immunity does exist in Lassa fever survivors at low frequencies.

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.

Lassa fever (LF) causes multisystem disease and has a fatality rate <70%. Severe cases exhibit abnormal coagulation, endothelial barrier disruption, and dysfunctional platelet aggregation but the underlying mechanisms remain poorly understood. In Sierra Leone during 2015-2018, we assessed LF patients' day-of-admission plasma samples for levels of proteins necessary for coagulation, fibrinolysis, and platelet function. P-selectin, soluble endothelial protein C receptor, soluble thrombomodulin, plasminogen activator inhibitor 1, ADAMTS-13, von Willebrand factor, tissue factor, soluble intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 were more elevated in LF patients than in controls. Endothelial protein C receptor, thrombomodulin, intercellular adhesion molecule 1, plasminogen activator inhibitor 1, D-dimer, and hepatocyte growth factor were higher in fatal than nonfatal LF cases. Platelet disaggregation occurred only in samples from fatal LF cases. The impaired homeostasis and platelet dysfunction implicate alterations in the protein C pathway, which might contribute to the loss of endothelial barrier function in fatal infections.

BACKGROUND: Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions. METHODOLOGY/PRINCIPAL FINDINGS: Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost [Formula: see text] of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals ('super-spreaders'), as we found only [Formula: see text] of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) [Formula: see text], with a maximum value up to [Formula: see text]. CONCLUSIONS/SIGNIFICANCE: This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.