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Onome T Abiri,1,2 Alex Ninka,3 Joshua Coker,4 Fawzi Thomas,2,5 Isaac O Smalle,6 Sulaiman Lakoh,4 Foday Umaro Turay,7 James Komeh,2,3 Mohamed Sesay,2,7 Joseph Sam Kanu,8 Ayeshatu M Mustapha,9 Nellie VT Bell,9 Thomas Ansumus Conteh,2,5 Sarah Kadijatu Conteh,10 Alhaji Alusine Jalloh,10 James BW Russell,4 Noah Sesay,3 Mohamed Bawoh,1 Mohamed Samai,1 Michael Lahai7 1Department of Pharmacology and Therapeutics, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone; 2Department of Pharmacovigilance and Clinical Trials, Pharmacy Board of Sierra Leone, Freetown, Sierra Leone; 3Department of Clinical Pharmacy and Therapeutics, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone; 4Department of Internal Medicine, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone; 5Department of Pharmaceutics, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone; 6Department of Surgery, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone; 7Department of Pharmaceutical Chemistry, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone; 8Department of Community Medicine, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone; 9Department of Pediatrics, Ola During Children Hospital, Freetown, Sierra Leone; 10Department of Pediatrics, King Harman Road Maternity and Children Hospital, Freetown, Sierra LeoneCorrespondence: Onome T Abiri, Department of Pharmacology and Therapeutics, College of Medicine and Allied Health Sciences, University of Sierra Leone Freetown, Sierra Leone/Department of Pharmacovigilance and Clinical Trials, Pharmacy Board of Sierra Leone, Freetown, Sierra Leone, Tel +23276370315, Email berylonome@gmail.comBackground: Pediatric patients are prone to medicine-related problems like medication errors (MEs), which can potentially cause harm. Yet, this has not been studied in this population in Sierra Leone. Therefore, this study investigated the prevalence and nature of MEs, including potential drug-drug interactions (pDDIs), in pediatric patients.Methods: The study was conducted in three hospitals among pediatric patients in Freetown and consisted of two phases. Phase one was a cross-sectional retrospective review of prescriptions for completeness and accuracy based on the global accuracy score against standard prescription writing guidelines. Phase two was a point prevalence inpatient chart review of MEs categorized into prescription, administration, and dispensing errors and pDDIs. Data was analyzed using frequency, percentages, median, and interquartile range. Kruskal–Wallis H and Mann–Whitney U-tests were used to compare the prescription accuracy between the hospitals, with p< 0.05 considered statistically significant.Results: Three hundred and sixty-six (366) pediatric prescriptions and 132 inpatient charts were reviewed in phases one and two of the study, respectively. In phase one, while no prescription attained the global accuracy score (GAS) gold standard of 100%, 106 (29.0%) achieved the 80– 100% mark. The patient 63 (17.2%), treatment 228 (62.3%), and prescriber 33 (9.0%) identifiers achieved an overall GAS range of 80– 100%. Although the total GAS was not statistically significant (p=0.065), the date (p=0.041), patient (p=< 0.001), treatment (p=0.022), and prescriber (p=< 0.001) identifiers were statistically significant across the different hospitals. For phase two, the prevalence of MEs was 74 (56.1%), while that of pDDIs was 54 (40.9%). There was a statistically positive correlation between the occurrence of pDDI and number of medicines prescribed (r=0.211, P=0.015).Conclusion: A Low GAS indicates poor compliance with prescription writing guidelines and high prescription errors. Medication errors were observed at each phase of the medication use cycle, while clinically significant pDDIs were also reported. Thus, there is a need for training on prescription writing guidelines and medication errors.Keywords: pediatrics, prescription, medication errors, drug-drug interactions, Sierra Leone

Background: Azithromycin has been shown to be beneficial in preventing infectious diseases, including malaria, infectious diarrhoea and pneumonia. A cluster randomised control trial on azithromycin MDA in children in Niger, Malawi and Tanzania found a reduction in all-cause under-five (U5) mortality in communities who received azithromycin compared to placebo. However, the reduction was largest and statistically significant only in Niger. The purpose of this trial is to evaluate the impact of azithromycin plus intermittent preventive treatment in infants (IPTi), recently renamed by the World Health Organisation as perennial malaria chemoprevention (PMC), with sulfadoxine-pyrimethamine (SP) on all-cause mortality up to 18 months of age in children living in areas of high mortality burden through the Expanded Program on Immunisation (EPI) in Sierra Leone., Methods: The Improving Care through Azithromycin Research for Infants in Africa (ICARIA) trial is a phase III two-arm, individually randomised, double-blinded, placebo-controlled trial administering oral AZI (20 mg/kg bodyweight) at three time points to children attending EPI visits in Sierra Leone. A total of 20,560 infants attending the first EPI contact at around 6 weeks of age are recruited and randomised to AZI or placebo in a 1:1 ratio. The second and third AZI/placebo doses are given at 9 and 15 months of age. The primary outcome of the trial is all-cause mortality rate at 18 months of age assessed through mortality surveillance. Other trial outcomes include the impact on antimicrobial resistance, and on the immune response to certain key routine EPI immunisations, the safety of the intervention, the prevalence of SP resistance markers and the feasibility, and acceptability of adding AZI to the EPI programme., Discussion: The trial will provide the evidence needed to inform policy regarding the adoption and large-scale implementation of AZI in areas of high-mortality burden in sub-Saharan Africa., Trial Registration: ClinicalTrials.gov NCT04235816. Registered on 22 January 2020. Pan-African Clinical Trials Registry PACTR202004540256535. Registered on 14 April 2020., (© 2024. The Author(s).)

Background: Despite the potential foetal and maternal risks of self-medication, studies on self-medication practice and the safety profile of medicines used during pregnancy are scarce in our setting. This study determined the self-medication practice and safety profile of medicines used among pregnant women., Methods: This cross-sectional study was conducted in face-to-face interviews among 345 pregnant women at three hospitals in Sierra Leone. Data were analysed using descriptive statistics and binary logistic regression to determine the prevalence and associated factors of self-medication., Results: A total of 345 pregnant women participated in the study. The prevalence of self-medication prevalence among pregnant women with conventional and/or herbal medicine was 132 (38.3%). Also, 93 (75%) of the conventional medicines (CMs) were categorised as probably safe, of which paracetamol 36 (29.0%) was commonly used, followed by amoxicillin 23 (18.5%) and antimalarials 22 (17.7%) for common illnesses such as headache 30 (25.4%), urinary tract infection 23 (19.4%) and malaria 22 (18.6%). The most common reason for self-medication was previous experience with the disease 24 (27.3%). Luffa acutangula 19 (30.2%) was the most used herbal medicine (HM), and Oedema 30 (47.6%) was the most reported ailment. Among the HM users, 34 (54.0%) believe they are more effective than CMs. Secondary school education (AOR = 2.128, 95%CI = 1.191-3.804, p  = 0.011), tertiary education (AOR = 2.915, 95%CI = 1.104-7.693, p  = 0.031), monthly income of greater than NLe 1,000 (AOR = 4.084, 95% CI = 1.269-13.144, p  = 0.018), and perceived maternal illness (AOR = 0.367, CI = 0.213-0.632, p  = <0.001) were predictors of self-medication., Conclusion: Self-medication practice was highly prevalent and was associated with educational status, monthly income, and perceived maternal illness during pregnancy. Therefore, intervention programmes should be designed and implemented to minimise the practice and risk associated with self-medication among pregnant women., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: The rVSVΔG-ZEBOV-GP vaccine (ERVEBO®) is a single-dose, live-attenuated, recombinant vesicular stomatitis virus vaccine indicated for the prevention of Ebola virus disease (EVD) caused by Zaire ebolavirus in individuals 12 months of age and older., Methods: The Partnership for Research on Ebola VACcination (PREVAC) is a multicenter, phase 2, randomized, double-blind, placebo-controlled trial of 3 vaccine strategies in healthy children (ages 1-17) and adults, with projected 5 years of follow-up (NCT02876328). Using validated assays (GP-ELISA and PRNT), we measured antibody responses after 1-dose rVSVΔG-ZEBOV-GP, 2-dose rVSVΔG-ZEBOV-GP (given on Day 0 and Day 56), or placebo. Furthermore, we quantified vaccine virus shedding in a subset of children's saliva using RT-PCR., Results: In total, 819 children and 783 adults were randomized to receive rVSVΔG-ZEBOV-GP (1 or 2 doses) or placebo. A single dose of rVSVΔG-ZEBOV-GP increased antibody responses by Day 28 that were sustained through Month 12. A second dose of rVSVΔG-ZEBOV-GP given on Day 56 transiently boosted antibody concentrations. In vaccinated children, GP-ELISA titers were superior to placebo and non-inferior to vaccinated adults. Vaccine virus shedding was observed in 31.7% of children, peaking by Day 7, with no shedding observed after Day 28 post-dose 1 or any time post-dose 2., Conclusions: A single dose of rVSVΔG-ZEBOV-GP induced robust antibody responses in children that was non-inferior to the responses induced in vaccinated adults. Vaccine virus shedding in children was time-limited and only observed after the first dose. Overall, these data support the use of rVSVΔG-ZEBOV-GP for the prevention of EVD in at-risk children. Clinical Trials Registration. The study is registered at ClinicalTrials.gov (NCT02876328), the Pan African Clinical Trials Registry (PACTR201712002760250), and the European Clinical Trials Register (EudraCT number: 2017-001798-18)., Competing Interests: Potential conflicts of interest. K. L., M. T. O., L. C., S. D., S. V., A. O., C. W., D .H., S. N., and B.-A. C. G. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ USA, who may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. A. W. L., J. K. S., J. D., and A. M. were employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may own/have owned stock and/or hold/held stock options in Merck & Co., Inc., Rahway, NJ, USA at the time the study was conducted. E. L., B. H., and C. R. report provision of vaccines from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA to the academic sponsors for the PREVAC trial, but no funding directly to themselves or their institution. J. M. reports provision of sample collection kits for the study sites, provision and support of lab software, technical support and supervision of lab activities, and lab data management. S. O. S. reports payments from Leidos to his institution. P. A. reports support for attending meetings and/or travel including Air tickets and accommodations for attending study related meetings during the conduct of the study. D. W.-J reports funding from Innovative Medicines Initiative 2 Joint Undertaking, additionally D. W.-J. reports funding and donations of an HPV vaccine (Gardasil®) from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA for another unrelated study. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Purpose: This review aims to provide an overview of the multiple functions of neutrophils, with the recognition of the inflammatory (N1) and regenerative (N2) phenotypes, in relation to fracture healing., Methods: A literature search was performed using the PubMed database. The quality of the articles was evaluated using critical appraisal checklists., Results: Thirty one studies were included in this review. These studies consistently support that neutrophils exert both beneficial and detrimental effects on bone regeneration, influenced by Tumor Necrosis Factor-α (TNF-α), Interleukin 8 (IL-8), mast cells, and macrophages. The N2 phenotype has recently emerged as one promoter of bone healing. The N1 phenotype has progressively been connected with inflammatory neutrophils during fracture healing., Conclusions: This review has pinpointed various aspects and mechanisms of neutrophil influence on bone healing. The recognition of N1 and N2 neutrophil phenotypes potentially shed new light on the dynamic shifts taking place within the Fracture Hematoma (FH)., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Routine childhood immunisation is one of the most important life-saving public health interventions. However, many children still have inadequate access to these vaccines and millions remain (partially) unvaccinated globally. As the COVID-19 pandemic disrupted health systems worldwide, its effects on immunisation have become apparent. This study aimed to estimate routine immunisation coverage among children under two in Sierra Leone and to identify factors associated with incomplete immunisation during the COVID-19 pandemic., Methods: A cross-sectional household survey was conducted in three districts in Sierra Leone: Bombali, Tonkolili and Port Loko. A three-stage cluster sampling method was followed to enrol children aged 10-23 months. Information regarding immunisation status was based on vaccination cards or caretaker's recall. Using WHO's definition, a fully immunised child received one BCG dose, three oral polio vaccine doses, three pentavalent vaccine doses and one measles-containing vaccine dose. Following the national schedule, full immunisation status can be achieved at 9 months of age. Data were weighted to reflect the survey's sampling design. Associations between incomplete immunisation and sociodemographic characteristics were assessed through multivariable logistic regression., Results: A total of 720 children were enrolled between November and December 2021. Full vaccination coverage was estimated at 65.8% (95% CI 60.3%-71.0%). Coverage estimates were highest for vaccines administered at birth and decreased with doses administered subsequently. Adjusting for age, the lowest estimated coverage was 40.7% (95% CI 34.5%-47.2%) for the second dose of the measles-containing vaccine. Factors found to be associated with incomplete immunisation status were: living in Port Loko district (aOR = 3.47, 95% CI = 2.00-6.06; p-value < 0.001), the interviewed caretaker being Muslim (aOR = 1.94, 95% CI = 1.25-3.02; p-value = 0.015) and the interviewed caretaker being male (aOR = 1.93, 95% CI = 1.03-3.59, p-value = 0.039)., Conclusion: Though full immunisation coverage at district level improved compared with pre-pandemic district estimates from 2019, around one in three surveyed children had missed at least one basic routine vaccination and over half of eligible children had not received the recommended two doses of a measles-containing vaccine. These findings highlight the need to strengthen health systems to improve vaccination uptake in Sierra Leone, and to further explore barriers that may jeopardise equitable access to these life-saving interventions., (© 2023. The Author(s).)

Background: Malaria remains the leading cause of mortality and morbidity in young children in sub-Saharan Africa. To prevent malaria in children living in moderate-to-high malaria transmission areas, the World Health Organization has recommended perennial malaria chemoprevention (PMC). Prior to piloting PMC implementation in southern Togo, a household survey was conducted to estimate malaria infection prevalence in children under 2 years of age (U2)., Methods: A cross-sectional community-based household survey was conducted in the Haho district in the Togo Plateaux region. A three-stage random sampling method was used to select study participants aged 10-23 months whose caretakers gave informed consent. The prevalence of Plasmodium infection, defined as a positive rapid diagnostic test (RDT), was estimated with 95% confidence interval (CI). Clinical malaria was defined as having a positive RDT plus fever (≥ 37.5 °C) or history of fever in the last 24 h. Mixed-effects logistic regression models were used to assess the child's, caretaker's, and household's factors associated with malaria infection., Results: A total of 685 children were included in the survey conducted January-February in 2022 (dry season). Median age was 17 months (interquartile range: 13-21). About 80% of the children slept under a bed net the night before the interview. Malaria infection prevalence was 32.1% (95% CI 27.7-37.0) with significant area variation (cluster range: 0.0-73.3). Prevalence of clinical malaria was 15.4% (95% CI 12.2-19.2). Children whose caretakers were animist (aOR: 1.71, 95% CI 1.19-2.46) and those living in mother-headed households (aOR: 2.39, 95% CI 1.43-3.99) were more likely to have a positive RDT. Living more than 5 km away from the nearest health facility (aOR: 1.60, 95% CI 1.04-2.44) and presence of two or more under-5-years children in the household (aOR: 1.44, 95% CI 1.01-2.07) were also associated with increased risk of infection., Conclusion: One-third of the children U2 who participated in this survey had malaria infection, thus PMC could be a promising strategy to reduce malaria burden in young children in Plateaux region. Reinforcement of outreach services and targeting the poorest households should be prioritized to reduce the inequity in malaria prevention in children exposed to the infection., (© 2023. The Author(s).)

Background: This study assessed the safety and immunogenicity of the Ad26.ZEBOV and MVA-BN-Filo Ebola virus (EBOV) vaccine regimen in infants aged 4-11 months in Guinea and Sierra Leone., Methods: In this phase 2, randomised, double-blind, active-controlled trial, we randomly assigned healthy infants (1:1 in a sentinel cohort, 5:2 for the remaining infants via an interactive web response system) to receive Ad26.ZEBOV followed by MVA-BN-Filo (Ebola vaccine group) or two doses of meningococcal quadrivalent conjugate vaccine (control group) administered 56 days apart. Infants were recruited at two sites in west Africa: Conakry, Guinea, and Kambia, Sierra Leone. All infants received the meningococcal vaccine 8 months after being randomly assigned. The primary objective was safety. The secondary objective was immunogenicity, measured as EBOV glycoprotein-binding antibody concentration 21 days post-dose 2, using the Filovirus Animal Non-Clinical Group ELISA. This study is registered with ClinicalTrials.gov (NCT03929757) and the Pan African Clinical Trials Registry (PACTR201905827924069)., Findings: From Aug 20 to Nov 29, 2019, 142 infants were screened and 108 were randomly assigned (Ebola vaccine n=75; control n=33). The most common solicited local adverse event was injection-site pain (Ebola vaccine 15 [20%] of 75; control four [12%] of 33). The most common solicited systemic adverse events with the Ebola vaccine were irritability (26 [35%] of 75), decreased appetite (18 [24%] of 75), pyrexia (16 [21%] of 75), and decreased activity (15 [20%] of 75). In the control group, ten (30%) of 33 had irritability, seven (21%) of 33 had decreased appetite, three (9%) of 33 had pyrexia, and five (15%) of 33 had decreased activity. The frequency of unsolicited adverse events was 83% (62 of 75 infants) in the Ebola vaccine group and 85% (28 of 33 infants) in the control group. No serious adverse events were vaccine-related. In the Ebola vaccine group, EBOV glycoprotein-binding antibody geometric mean concentrations (GMCs) at 21 days post-dose 2 were 27 700 ELISA units (EU)/mL (95% CI 20 477-37 470) in infants aged 4-8 months and 20 481 EU/mL (15 325-27 372) in infants aged 9-11 months. The responder rate was 100% (74 of 74 responded). In the control group, GMCs for both age groups were less than the lower limit of quantification and the responder rate was 3% (one of 33 responded)., Interpretation: Ad26.ZEBOV and MVA-BN-Filo was well tolerated and induced strong humoral responses in infants younger than 1 year. There were no safety concerns related to vaccination., Funding: Janssen Vaccines & Prevention and Innovative Medicines Initiative 2 Joint Undertaking., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests Janssen Vaccines & Prevention was the vaccine manufacturer and donated the vaccine for this study. BK, WvD, AG, DA, CM, ML, KL, CR, and MD were full-time employees of Janssen Pharmaceuticals at the time of the study and hold stock or stock options in Janssen Pharmaceuticals. All other authors declare funding from the Innovative Medicines Initiative 2 Joint Undertaking., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

We assessed whether the immunogenicity of the two-dose Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen with a 56-day interval between doses was affected by exposure to malaria before dose 1 vaccination and by clinical episodes of malaria in the period immediately after dose 1 and after dose 2 vaccinations. Previous malaria exposure in participants in an Ebola vaccine trial in Sierra Leone (ClinicalTrials.gov: NCT02509494) was classified as low, intermediate, and high according to their antibody responses to a panel of Plasmodium falciparum antigens detected using a Luminex MAGPIX platform. Clinical malaria episodes after vaccinations were recorded as part of the trial safety monitoring. Binding antibody responses against the Ebola virus (EBOV) glycoprotein (GP) were measured 57 days post dose 1 and 21 days post dose 2 by ELISA and summarized as Geometric Mean Concentrations (GMCs). Geometric Mean Ratios (GMRs) were used to compare groups with different levels of exposure to malaria. Overall, 587 participants, comprising 188 (32%) adults (aged ≥ 18 years) and 399 (68%) children (aged 1-3, 4-11, and 12-17 years), were included in the analysis. There was no evidence that the anti-EBOV-GP antibody GMCs post dose 1 and post dose 2 differed between categories of previous malaria exposure. There was weak evidence that the GMC at 57 days post dose 1 was lower in participants who had had at least one episode of clinical malaria post dose 1 compared to participants with no diagnosed clinical malaria in the same period (GMR = 0.82, 95% CI: 0.69-0.98, p -value = 0.02). However, GMC post dose 2 was not reduced in participants who experienced clinical malaria post-dose 1 and/or post-dose 2 vaccinations. In conclusion, the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen is immunogenic in individuals with previous exposure to malaria and in those who experience clinical malaria after vaccination. This vaccine regimen is suitable for prophylaxis against Ebola virus disease in malaria-endemic regions.

Introduction: This study aimed to determine whether the COVID-19 pandemic had an impact on essential primary healthcare services at public primary healthcare facilities., Methods: The number of weekly consultations for antenatal care (ANC), outpatient (OPD), immunisations (EPI), family planning (FP) and HIV services, between January 2018 and December 2020, were collected from 25 facilities in Masaka district, Uganda, 21 in Goma, and 29 in Kambia district, Sierra Leone. Negative binomial regression models accounting for clustering and season were used to analyse changes in activity levels between 2018, 2019 and 2020., Results: In Goma, we found no change in OPD, EPI or ANC consultations, FP was 17% lower in March-July 2020 compared to 2019, but this recovered by December 2020. New diagnoses of HIV were 34% lower throughout 2020 compared to 2019. In Sierra Leone, compared to the same periods in 2019, facilities had 18-29% fewer OPD consultations throughout 2020, and 27% fewer DTP3 doses in March-July 2020. There was no evidence of differences in other services. In Uganda there were 20-35% fewer under-5 OPD consultations, 21-66% fewer MCV1 doses, and 48-51% fewer new diagnoses of HIV throughout 2020, compared to 2019. There was no difference in the number of HPV doses delivered., Conclusions: The level of disruption varied across the different settings and qualitatively appeared to correlate with the strength of lockdown measures and reported attitudes towards the risk posed by COVID-19. Mitigation strategies such as health communications campaigns and outreach services may be important to limit the impact of lockdowns on primary healthcare services., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kasonia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: We assessed the prevalence of immunoglobulin G (IgG) and IgM against four endemic human coronaviruses and two SARS-CoV-2 antigens among vaccinated and unvaccinated staff at health care centers in Uganda, Sierra Leone, and the Democratic Republic of Congo., Methods: The government health facility staff who had patient contact in Goma (Democratic Republic of Congo), Kambia District (Sierra Leone), and Masaka District (Uganda) were enrolled. Questionnaires and blood samples were collected at three time points over 4 months. Blood samples were analyzed with the Luminex MAGPIX Ⓡ ., Results: Among unvaccinated participants, the prevalence of IgG/IgM antibodies against SARS-CoV-2 receptor-binding domain or nucleocapsid protein at enrollment was 70% in Goma (138 of 196), 89% in Kambia (112 of 126), and 89% in Masaka (190 of 213). The IgG responses against endemic human coronaviruses at baseline were not associated with SARS-CoV-2 sero-acquisition during follow-up. Among the vaccinated participants, those who had evidence of SARS-CoV-2 IgG/IgM at baseline tended to have higher IgG responses to vaccination than those who were SARS-CoV-2 seronegative at baseline, controlling for the time of sample collection since vaccination., Conclusion: The high levels of natural immunity and hybrid immunity should be incorporated into both vaccination policies and prediction models of the impact of subsequent waves of infection in these settings., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Intermittent Preventive Treatment of malaria in infants (IPTi) is a malaria control strategy consisting of the administration of an anti-malarial drug alongside routine immunizations. So far, this is being implemented nationwide in Sierra Leone only. IPTi has been renamed as Perennial Malaria Chemoprevention -PMC-, accounting for its recently recommended expansion into the second year of life. Before starting a pilot implementation on PMC, the currently implemented strategy and malaria prevalence were assessed in young children in selected areas of Sierra Leone., Methods: A cross-sectional, community-based, multi-stage cluster household survey was conducted from November to December 2021 in selected districts of the Northern and northwestern provinces of Sierra Leone among 10-23 months old children, whose caretakers gave written informed consent to participate in the survey. Coverage of IPTi and malaria prevalence-assessed with rapid diagnostic tests-were calculated using percentages and 95% confidence intervals weighted for the sampling design and adjusted for non-response within clusters. Factors associated with RDT + and iPTi coverage were also assessed., Results: A total of 720 children were recruited. Coverage of three IPTi doses was 50.57% (368/707; 95% CI 45.38-55.75), while prevalence of malaria infection was 28.19% (95% CI 24.81-31.84). Most children had received IPTi1 (80.26%, 574/707; 95% CI 75.30-84.44), and IPTi2 (80.09%, 577/707; 95% CI 76.30-83.40) and over half of the children also received IPTi3 (57.72%, 420/707; 95% CI 53.20-62.11). The uptake of each IPTi dose was lower than that of the vaccines administered at the same timepoint at all contacts., Conclusion: In Sierra Leone, half of the children received the three recommended doses of IPTi indicating an increase in its uptake compared to previous data of just a third of children receiving the intervention. However, efforts need to be made in improving IPTi coverage, especially in the planned expansion of the strategy into the second year of life following recent WHO guidelines., (© 2023. The Author(s).)

Background: This analysis evaluated the immune response to the two-dose, heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola virus vaccine regimen, administered 56-days apart, from multiple African sites based on results from one analytic laboratory., Methods: Immunogenicity across three trials (EBL2002, EBL2004/PREVAC, EBL3001) conducted in East and West Africa is summarised. Vaccine-induced Ebola glycoprotein-binding antibody concentrations were analysed by Q 2 Solutions laboratory at baseline, 21 days (EBL2002 and EBL3001) or 28 days (EBL2004) post-dose 2 (regimen completion), and 12 months post-dose 1 using the validated Filovirus Animal Nonclinical Group Ebola glycoprotein enzyme-linked immunosorbent assay (ELISA). Responders were defined as those with a >2.5-fold increase from baseline or the lower limit of quantification (LLOQ) if 

Background: Children account for a substantial proportion of cases and deaths during Ebola virus disease outbreaks. We aimed to evaluate the safety and immunogenicity of a booster dose of the Ad26.ZEBOV vaccine in children who had been vaccinated with a two-dose regimen comprising Ad26.ZEBOV as dose one and MVA-BN-Filo as dose two., Methods: We conducted an open-label, non-randomised, phase 2 trial at one clinic in Kambia Town, Sierra Leone. Healthy children, excluding pregnant or breastfeeding girls, who had received the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen in a previous study, and were aged 1-11 years at the time of their first vaccine dose, received an intramuscular injection of Ad26.ZEBOV (5 × 10 10 viral particles) and were followed up for 28 days. Primary outcomes were safety (measured by adverse events) and immunogenicity (measured by Ebola virus glycoprotein-specific IgG binding antibody geometric mean concentration) of the booster vaccine dose. Safety was assessed in all participants who received the booster vaccination; immunogenicity was assessed in all participants who received the booster vaccination, had at least one evaluable sample after the booster, and had no major protocol deviations that could have influenced the immune response. This trial is registered with ClinicalTrials.gov, NCT04711356., Findings: Between July 8 and Aug 18, 2021, 58 children were assessed for eligibility and 50 (27 aged 4-7 years and 23 aged 9-15 years) were enrolled and received an Ad26.ZEBOV booster vaccination, more than 3 years after receiving dose one of the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen. The booster was well tolerated. The most common solicited local adverse event during the 7 days after vaccination was injection site pain, reported in 18 (36%, 95% CI 23-51) of 50 participants. The most common solicited systemic adverse event during the 7 days after vaccination was headache, reported in 11 (22%, 12-36) of 50 participants. Malaria was the most common unsolicited adverse event during the 28 days after vaccination, reported in 25 (50%, 36-64) of 50 participants. No serious adverse events were observed during the study period. 7 days after vaccination, the Ebola virus glycoprotein-specific IgG binding antibody geometric mean concentration was 28 561 ELISA units per mL (95% CI 20 255-40 272), which was 44 times higher than the geometric mean concentration before the booster dose. 21 days after vaccination, the geometric mean concentration reached 64 690 ELISA units per mL (95% CI 48 356-86 541), which was 101 times higher than the geometric mean concentration before the booster dose., Interpretation: A booster dose of Ad26.ZEBOV in children who had received the two-dose Ad26.ZEBOV and MVA-BN-Filo vaccine regimen more than 3 years earlier was well tolerated and induced a rapid and robust increase in binding antibodies against Ebola virus. These findings could inform Ebola vaccination strategies in paediatric populations., Funding: Innovative Medicines Initiative 2 Joint Undertaking., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests Janssen Vaccines and Prevention was the vaccine manufacturer and donated the vaccine for this study. BKe, AG, CM, KL, and CR were full-time employees of Janssen, Pharmaceutical Companies of Johnson & Johnson, at the time of the study. AG, CM, KL, and CR report ownership of shares in Janssen, Pharmaceutical Companies of Johnson & Johnson. All other authors declare funding from the Innovative Medicines Initiative 2 Joint Undertaking., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Leadership by health professionals is key in any health system, but health leadership training programmes are varied in their conceptualisation, learning objectives, and design. This paper describes an undergraduate leadership and management module for health students at the University of Sierra Leone and provides lessons from the design process. Our methods included an initial scoping review and qualitative study, followed by a co-design process of 10 workshops and 17 consultation meetings. The result was a curriculum with learning outcomes emphasising leadership identity, proactiveness, management of people and of change, and the formation of peer relationships. Learning methods included group teaching, team quality improvement projects, mentoring, and reflective practice. Lessons from the design process included the importance of support from university leadership and extensive consultation. Virtual workshops enabled broader participation but limited relationship building. Integrating doctoral research into the process facilitated inclusion of evidence and theory but risked reducing ownership by faculty. The importance of interprofessionalism and management skills in leadership training emerged during the process, illustrating the effectiveness of a co-design approach. Our programme is broadly aligned with other health leadership frameworks and is distinctive due to its undergraduate focus, offering insights for leadership training design in other settings.

Background: Questions remain concerning the rapidity of immune responses and the durability and safety of vaccines used to prevent Zaire Ebola virus disease., Methods: We conducted two randomized, placebo-controlled trials - one involving adults and one involving children - to evaluate the safety and immune responses of three vaccine regimens against Zaire Ebola virus disease: Ad26.ZEBOV followed by MVA-BN-Filo 56 days later (the Ad26-MVA group), rVSVΔG-ZEBOV-GP followed by placebo 56 days later (the rVSV group), and rVSVΔG-ZEBOV-GP followed by rVSVΔG-ZEBOV-GP 56 days later (the rVSV-booster group). The primary end point was antibody response at 12 months, defined as having both a 12-month antibody concentration of at least 200 enzyme-linked immunosorbent assay units (EU) per milliliter and an increase from baseline in the antibody concentration by at least a factor of 4., Results: A total of 1400 adults and 1401 children underwent randomization. Among both adults and children, the incidence of injection-site reactions and symptoms (e.g., feverishness and headache) was higher in the week after receipt of the primary and second or booster vaccinations than after receipt of placebo but not at later time points. These events were largely low-grade. At month 12, a total of 41% of adults (titer, 401 EU per milliliter) and 78% of children (titer, 828 EU per milliliter) had a response in the Ad26-MVA group; 76% (titer, 992 EU per milliliter) and 87% (titer, 1415 EU per milliliter), respectively, had a response in the rVSV group; 81% (titer, 1037 EU per milliliter) and 93% (titer, 1745 EU per milliliter), respectively, had a response in the rVSV-booster group; and 3% (titer, 93 EU per milliliter) and 4% (titer, 67 EU per milliliter), respectively, had a response in the placebo group (P<0.001 for all comparisons of vaccine with placebo). In both adults and children, antibody responses with vaccine differed from those with placebo beginning on day 14., Conclusions: No safety concerns were identified in this trial. With all three vaccine regimens, immune responses were seen from day 14 through month 12. (Funded by the National Institutes of Health and others; PREVAC ClinicalTrials.gov number, NCT02876328; EudraCT numbers, 2017-001798-18 and 2017-001798-18/3rd; and Pan African Clinical Trials Registry number, PACTR201712002760250.)., (Copyright © 2022 Massachusetts Medical Society.)

Objective: Health-related research in sub-Saharan Africa (SSA) has grown over the years. However, concerns have been raised about the state of research ethics committees (RECs). This scoping review examines the literature on RECs for health-related research in SSA and identifies strategies that have been applied to strengthen the RECs. It focuses on three aspects of RECs: regulatory governance and leadership, administrative and financial capacity and technical capacity of members., Design: A scoping review of published literature, including grey literature, was conducted using the Joanna Briggs Institute approach., Data Sources: BioOne, CINAHL, Embase (via Ovid), Education Abstracts, Global Health, Google Scholar, Jstor, OpenEdition (French), Philosopher's Index, PsycINFO, PubMed, Science Citation and Expanded Index (Web of Science), reference lists of included studies and specific grey literature sources., Eligibility Criteria: We included empirical studies on RECs for health-related research in SSA, covering topics on REC leadership and governance, administrative and financial capacity and the technical capacity of REC members. We included studies published between 01 January 2000 and 18 February 2022 and written in English, French, Portuguese or Swahili., Data Extraction and Synthesis: Two independent reviewers screened the records. Data were extracted by one reviewer and cross-checked by another. Owing to the heterogeneity of included studies, thematic analysis was used., Results: We included 54 studies. The findings show that most RECs in SSA work under significant administrative and financial constraints, with few opportunities for capacity building for committee members. This has an impact on the quality of reviews and the overall performance of RECs. Although most countries have national governance systems for RECs, they lack regulations on accountability, transparency and monitoring of RECs., Conclusions: This review provides a comprehensive overview of the literature on RECs for health-related research in SSA and contributes to our understanding of how RECs can be strengthened., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Antiretroviral therapy (ART) is the primary mode of treatment for Human Immunodeficiency Virus (HIV). It slows disease progression and reduces the spread of infection. HIV treatment is also known to require a high level of adherence of over 90% to achieve good treatment outcomes and viral load suppression. In Sierra Leone, about 70% of People Living with HIV (PLHIV) are non-adherent in their first year of treatment. Understanding the reasons behind this high rate of non-adherence from the perspectives of both PLHIV and health workers is critical for developing strategies to improve adherence. This qualitative study is rooted in the field of public health services. It identifies the barriers and facilitators influencing adherence to antiretroviral treatment in Sierra Leone.  METHODS: A qualitative study design using in-depth interviews of four healthcare workers and 16 PLHIV in two districts in Sierra Leone- Freetown and Bo. The interviews were analyzed using a grounded theory approach to identify emerging themes from the data., Results: The study identified several facilitators and barriers to ART adherence at the personal, community, and health system levels. The facilitators included perceived benefits of ART, family support, having an informal caregiver, receiving free ART medicines, and belonging to peer support groups. The identified barriers were stigma and discrimination, frequency of medication, use of traditional medicine, lack of money for food and transport, work barriers, inadequate medicines and test kits, limited health workers, and long distances to clinics., Conclusions: Our study emphasized the need for implementing behavioural change communication programmes and activities to reduce stigma and discrimination in the community. Knowledge of the facilitators and barriers to antiretroviral therapy could provide relevant information for more responsive and equitable programmes supporting adherence implementation in low- and middle-income countries. This study also identifies the vital need for community integration of HIV treatment services., (© 2022. The Author(s).)

Objective: Despite the impact of inappropriate prescribing on antibiotic resistance, data on surgical antibiotic prophylaxis in sub-Saharan Africa are limited. In this study, we evaluated antibiotic use and consumption in surgical prophylaxis in 4 hospitals located in 2 geographic regions of Sierra Leone., Methods: We used a prospective cohort design to collect data from surgical patients aged 18 years or older between February and October 2021. Data were analyzed using Stata version 16 software., Results: Of the 753 surgical patients, 439 (58.3%) were females, and 723 (96%) had received at least 1 dose of antibiotics. Only 410 (54.4%) patients had indications for surgical antibiotic prophylaxis consistent with local guidelines. Factors associated with preoperative antibiotic prophylaxis were the type of surgery, wound class, and consistency of surgical antibiotic prophylaxis with local guidelines. Postoperatively, type of surgery, wound class, and consistency of antibiotic use with local guidelines were important factors associated with antibiotic use. Of the 2,482 doses administered, 1,410 (56.8%) were given postoperatively. Preoperative and intraoperative antibiotic use was reported in 645 (26%) and 427 (17.2%) cases, respectively. The most commonly used antibiotic was ceftriaxone 949 (38.2%) with a consumption of 41.6 defined daily doses (DDD) per 100 bed days. Overall, antibiotic consumption was 117.9 DDD per 100 bed days. The Access antibiotics had 72.7 DDD per 100 bed days (61.7%)., Conclusions: We report a high rate of antibiotic consumption for surgical prophylaxis, most of which was not based on local guidelines. To address this growing threat, urgent action is needed to reduce irrational antibiotic prescribing for surgical prophylaxis., (© The Author(s) 2022.)

Introduction: Recurrent parasitic infections may influence the immune response to vaccines. In the Partnership for Research on Ebola VACcinations extended follow-UP and clinical research capacity build-UP (PREVAC-UP) study being undertaken in Mambolo, northern Sierra Leone, participants are being followed up to assess the potential impact of exposure to malaria and/or helminth infections on long-term immune response to two Ebola vaccines. To support the development of the assays that will be used in this evaluation, a parasitological survey was conducted in Mambolo between November 2019 and February 2020., Methods: Healthy individuals aged ≥1 year who were resident in Mambolo Chiefdom were selected using a stratified sampling approach and questionnaires were administered to explore their sociodemographic characteristics. Microscopy was used to detect malaria parasites, intestinal helminths and urinary schistosome infections. Rapid blood tests were used to detect infections with Onchocerca volvulus and Wuchereria bancrofti. We estimated the overall prevalence of these infections and used adjusted logistic regression models to explore risk factors for malaria and hookworm infection., Results: Eight hundred and fifteen (815) residents, 50.9% of whom were female were surveyed. Overall, 309 (39.1%) of 791 persons tested for malaria had a positive blood slide; Plasmodium falciparum was the dominant species. Helminth infection was detected in 122 (15.0%) of 815 stool samples including three mixed infections. The helminth infections comprised 102 (12.5%) cases of hookworm, 11 (1.3%) cases of Trichuris trichiura, 10 (1.2%) cases of Schistosoma mansoni and two (0.2%) cases of Ascaris lumbricoides. Being male (OR = 2.01, 95% CI 1.15-3.50) and residing in a non-riverine community (OR = 4.02, 95%CI 2.32-6.98) were the factors associated with hookworm infection. Onchocerca volvulus and Wuchereria bancrofti infections were found in 3.3% and 0.4% of participants respectively., Conclusion: Malaria and hookworm are the most prevalent parasite infections and those most likely to influence long-term immune response to Ebola vaccines among the trial participants., Competing Interests: The authors have declared that no competing interests exist.

Noncommunicable diseases (NCDs) are a growing public health concern in low- and middle-income countries and disproportionately affect people living with HIV (PWH). Hepatitis B virus (HBV) and tuberculosis (TB) coinfection are presumed risk factors in endemic settings; however, supporting evidence is conflicting. We analyzed baseline data of newly diagnosed PWH prospectively enrolled in the Sierra Leone HIV Cohort Study in Freetown, Sierra Leone, from March to September 2021. Logistic regression was used to identify associations between NCDs, HBV and TB. A total of 275 PWH aged ≥18 years were studied (55% female, median age 33 years, median CD4 307 cells/mm3, 15.3% HIV/HBV, 8.7% HIV/TB). NCDs were bimodally distributed, with 1 in 4 PWH clustered around liver disease (fibrosis/cirrhosis), diabetes/prediabetes and obesity/preobesity, while 1 in 8 had renal impairment or hypertension (HTN). Overall, 41.5% had ≥1 NCD, while 17.5% were multimorbid (≥2 NCDs). After adjusting for age, sex, sociodemographic factors and CD4 count, liver fibrosis/cirrhosis was strongly associated with HBV (aOR 8.80, 95% CI [2.46−31.45]; p < 0.001) and diabetes/prediabetes (aOR 9.89, 95% CI [1.14−85.67]; p < 0.037). TB independently predicted diabetes/prediabetes (aOR 7.34, 95% CI [1.87−28.74]; p < 0.004), while renal impairment was associated with proteinuria (aOR 9.34, 95% CI [2.01−43.78]; p < 0.004) and HTN (aOR 6.00, 95% CI [1.10−35.39]; p < 0.049). Our findings warrant the implementation of NCD-aware HIV programs for the prevention, early detection and management of comorbidities.

Despite having safe and efficacious vaccines against COVID-19, vaccine hesitancy is widespread. Although a trusted source of information, vaccine hesitancy has been reported among healthcare professionals, yet few studies have explored this phenomenon in sub-Saharan Africa. We conducted a cross-sectional survey of healthcare professionals in Sierra Leone from January to March 2022. Measures included sociodemographic/health-related information and COVID-19-related concerns. From the responses, we constructed a hesitancy (VAX) score, with higher scores implying negative attitudes or unwillingness to vaccinate. Multivariate linear regression was used to access factors associated with vaccine hesitancy. Overall, 592 participants submitted responses (67.2% female, mean age 29 years, 5.6% physicians/pharmacists, 44.3% medical students, 29.2% nurses, 20.9% nursing students). The mean VAX score was 43.27 ± 8.77, with 60.1% of respondents classified as vaccine hesitant (>50th percentile) and 13.8% as highly hesitant (>75th percentile). Worries about unforeseen future effects (76.3%), a preference for natural immunity (59.5%), and profiteering/mistrust of health authorities (53.1%) were the most common concerns. Being a medical student (β = 0.105, p = 0.011) and previously refusing a recommended vaccine (β = 0.177, p < 0.001) were predictors of COVID-19 vaccine hesitancy. Our findings call for addressing vaccine hesitancy among healthcare professionals as an essential component of strategies aimed at increasing COVID-19 vaccine uptake in this setting.

Background: There is limited information on surgical site infections (SSI) and the related antibiotic resistance needed to guide their management and prevention in Sierra Leone. In this study, we aimed to establish the incidence and risk factors of SSI and the related antibiotic resistance among adults attending a tertiary hospital, and a secondary health facility in Freetown, Sierra Leone., Methods: This is a prospective cohort study designed to collect data from adult (18 years or older) patients who attended elective and emergency surgeries at two hospitals in Freetown between February and July, 2021. Data analysis was done using STATA version 16., Results: Of 338 patients, 245 (72.5%) and 93 (27.5%) had their surgeries at the tertiary and secondary hospitals, respectively. Many were males 192 (56.8%), less than 35 years 164 (48.5%), and 39 (11.5%) developed an SSI. Of the 39 patients who acquired an SSI, 7 (17.9%) and 32 (82.1%) had their surgeries at the secondary and tertiary hospitals, respectively. The incidence of SSI is higher in contaminated 17 (43.6%) than in clean-contaminated 12 (30.8%) and clean 10 (25.6%) wounds. Wound swabs were collected in 29 (74.4%) patients, of which 18 (62.1%) had bacterial growth. In total, 49 isolates of 14 different bacteria including gram-negative 41 (83.7%) and gram-positive 8 (16.3%) isolates were identified. Of these, 32 (65.3%) were Enterobacteriaceae, 9 (18.4%) were Non-fermenting gram-negative bacilli and 10 (12.2%) were Enterococci. The most common isolates were Escherichia coli (12, 24.5%), Klebsiella pneumoniae (10, 20.4%), Acinetobacter baumannii (5, 10.2%), Klebsiella oxytoca (4, 8.2%) and Enterococcus faecalis (4, 8.2%). The Enterobacteriaceae were either resistance to carbapenems (4, 8.2%) or were extended-spectrum beta-lactamase (ESBL) producing organisms (29, 59.2%). Male sex [p = 0.031], an ASA score ≥ 2 [p = 0.020), administration of general anaesthesia [p = 0.018] and elevated fasting glucose [p = 0.033] were predictive of SSI., Conclusion: The incidence of SSI in this study is comparable to other low- and middle-income countries, but a substantial proportion of these postoperative wounds have an ESBL-producing Enterobacteriaceae. Therefore, routine surveillance of SSI and related antibiotic resistance is required in resource-limited settings., (© 2022. The Author(s).)

Background: Children account for a substantial proportion of cases and deaths from Ebola virus disease. We aimed to assess the safety and immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vector-based vaccine, encoding glycoproteins from the Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in a paediatric population in Sierra Leone., Methods: This randomised, double-blind, controlled trial was done at three clinics in Kambia district, Sierra Leone. Healthy children and adolescents aged 1-17 years were enrolled in three age cohorts (12-17 years, 4-11 years, and 1-3 years) and randomly assigned (3:1), via computer-generated block randomisation (block size of eight), to receive an intramuscular injection of either Ad26.ZEBOV (5 × 10 10 viral particles; first dose) followed by MVA-BN-Filo (1 × 10 8 infectious units; second dose) on day 57 (Ebola vaccine group), or a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo (second dose) on day 57 (control group). Study team personnel (except for those with primary responsibility for study vaccine preparation), participants, and their parents or guardians were masked to study vaccine allocation. The primary outcome was safety, measured as the occurrence of solicited local and systemic adverse symptoms during 7 days after each vaccination, unsolicited systemic adverse events during 28 days after each vaccination, abnormal laboratory results during the study period, and serious adverse events or immediate reportable events throughout the study period. The secondary outcome was immunogenicity (humoral immune response), measured as the concentration of Ebola virus glycoprotein-specific binding antibodies at 21 days after the second dose. The primary outcome was assessed in all participants who had received at least one dose of study vaccine and had available reactogenicity data, and immunogenicity was assessed in all participants who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response. This study is registered at ClinicalTrials.gov, NCT02509494., Findings: From April 4, 2017, to July 5, 2018, 576 eligible children or adolescents (192 in each of the three age cohorts) were enrolled and randomly assigned. The most common solicited local adverse event during the 7 days after the first and second dose was injection-site pain in all age groups, with frequencies ranging from 0% (none of 48) of children aged 1-3 years after placebo injection to 21% (30 of 144) of children aged 4-11 years after Ad26.ZEBOV vaccination. The most frequently observed solicited systemic adverse event during the 7 days was headache in the 12-17 years and 4-11 years age cohorts after the first and second dose, and pyrexia in the 1-3 years age cohort after the first and second dose. The most frequent unsolicited adverse event after the first and second dose vaccinations was malaria in all age cohorts, irrespective of the vaccine types. Following vaccination with MenACWY, severe thrombocytopaenia was observed in one participant aged 3 years. No other clinically significant laboratory abnormalities were observed in other study participants, and no serious adverse events related to the Ebola vaccine regimen were reported. There were no treatment-related deaths. Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second dose of the Ebola virus vaccine regimen were observed in 131 (98%) of 134 children aged 12-17 years (9929 ELISA units [EU]/mL [95% CI 8172-12 064]), in 119 (99%) of 120 aged 4-11 years (10 212 EU/mL [8419-12 388]), and in 118 (98%) of 121 aged 1-3 years (22 568 EU/mL [18 426-27 642])., Interpretation: The Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen was well tolerated with no safety concerns in children aged 1-17 years, and induced robust humoral immune responses, suggesting suitability of this regimen for Ebola virus disease prophylaxis in children., Funding: Innovative Medicines Initiative 2 Joint Undertaking and Janssen Vaccines & Prevention BV., Competing Interests: Declaration of interests BKe was a full-time employee of Janssen Pharmaceutical Companies of Johnson & Johnson at the time of the study. NG, ML, AG, DH, VB, KL, BC, CR, and MD were full-time employees of Janssen Pharmaceutical Companies of Johnson & Johnson at the time of the study, and declare ownership of shares in Janssen Pharmaceutical Companies of Johnson & Johnson. DW-J reports grants from the Innovative Medicines Initiative and non-financial support from Janssen Vaccines & Prevention BV during the conduct of the study; and grants from the Coalition for Epidemic Preparedness Innovations and non-financial support from Janssen Vaccines & Prevention BV outside the submitted work. HL reports grants from GSK and Merck outside the submitted work. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The Ebola epidemics in west Africa and the Democratic Republic of the Congo highlight an urgent need for safe and effective vaccines to prevent Ebola virus disease. We aimed to assess the safety and long-term immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vector-based vaccine, encoding glycoproteins from Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in Sierra Leone, a country previously affected by Ebola., Methods: The trial comprised two stages: an open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2. The study was done at three clinics in Kambia district, Sierra Leone. In stage 1, healthy adults (aged ≥18 years) residing in or near Kambia district, received an intramuscular injection of Ad26.ZEBOV (5 × 10 10 viral particles) on day 1 (first dose) followed by an intramuscular injection of MVA-BN-Filo (1 × 10 8 infectious units) on day 57 (second dose). An Ad26.ZEBOV booster vaccination was offered at 2 years after the first dose to stage 1 participants. The eligibility criteria for adult participants in stage 2 were consistent with stage 1 eligibility criteria. Stage 2 participants were randomly assigned (3:1), by computer-generated block randomisation (block size of eight) via an interactive web-response system, to receive either the Ebola vaccine regimen (Ad26.ZEBOV followed by MVA-BN-Filo) or an intramuscular injection of a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo on day 57 (second dose; control group). Study team personnel, except those with primary responsibility for study vaccine preparation, and participants were masked to study vaccine allocation. The primary outcome was the safety of the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen, which was assessed in all participants who had received at least one dose of study vaccine. Safety was assessed as solicited local and systemic adverse events occurring in the first 7 days after each vaccination, unsolicited adverse events occurring in the first 28 days after each vaccination, and serious adverse events or immediate reportable events occurring up to each participant's last study visit. Secondary outcomes were to assess Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second vaccine in a per-protocol set of participants (ie, those who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response) and to assess the safety and tolerability of the Ad26.ZEBOV booster vaccination in stage 1 participants who had received the booster dose. This study is registered at ClinicalTrials.gov, NCT02509494., Findings: Between Sept 30, 2015, and Oct 19, 2016, 443 participants (43 in stage 1 and 400 in stage 2) were enrolled; 341 participants assigned to receive the Ad26.ZEBOV and MVA-BN-Filo regimen and 102 participants assigned to receive the MenACWY and placebo regimen received at least one dose of study vaccine. Both regimens were well tolerated with no safety concerns. In stage 1, solicited local adverse events (mostly mild or moderate injection-site pain) were reported in 12 (28%) of 43 participants after Ad26.ZEBOV vaccination and in six (14%) participants after MVA-BN-Filo vaccination. In stage 2, solicited local adverse events were reported in 51 (17%) of 298 participants after Ad26.ZEBOV vaccination, in 58 (24%) of 246 after MVA-BN-Filo vaccination, in 17 (17%) of 102 after MenACWY vaccination, and in eight (9%) of 86 after placebo injection. In stage 1, solicited systemic adverse events were reported in 18 (42%) of 43 participants after Ad26.ZEBOV vaccination and in 17 (40%) after MVA-BN-Filo vaccination. In stage 2, solicited systemic adverse events were reported in 161 (54%) of 298 participants after Ad26.ZEBOV vaccination, in 107 (43%) of 246 after MVA-BN-Filo vaccination, in 51 (50%) of 102 after MenACWY vaccination, and in 39 (45%) of 86 after placebo injection. Solicited systemic adverse events in both stage 1 and 2 participants included mostly mild or moderate headache, myalgia, fatigue, and arthralgia. The most frequent unsolicited adverse event after the first dose was headache in stage 1 and malaria in stage 2. Malaria was the most frequent unsolicited adverse event after the second dose in both stage 1 and 2. No serious adverse event was considered related to the study vaccine, and no immediate reportable events were observed. In stage 1, the safety profile after the booster vaccination was not notably different to that observed after the first dose. Vaccine-induced humoral immune responses were observed in 41 (98%) of 42 stage 1 participants (geometric mean binding antibody concentration 4784 ELISA units [EU]/mL [95% CI 3736-6125]) and in 176 (98%) of 179 stage 2 participants (3810 EU/mL [3312-4383]) at 21 days after the second vaccination., Interpretation: The Ad26.ZEBOV and MVA-BN-Filo vaccine regimen was well tolerated and immunogenic, with persistent humoral immune responses. These data support the use of this vaccine regimen for Ebola virus disease prophylaxis in adults., Funding: Innovative Medicines Initiative 2 Joint Undertaking and Janssen Vaccines & Prevention BV., Competing Interests: Declaration of interests BKe was a full-time employee of Janssen at the time of the study. NG, ML, AG, DH, VB, KL, BC, CR, and MD were full-time employees of Janssen at the time of the study, and declare ownership of shares in Janssen. DW-J reports grants from the Innovative Medicines Initiative and non-financial support from Janssen Vaccines & Prevention BV during the conduct of the study; and grants from the Coalition for Epidemic Preparedness Innovations and non-financial support from Janssen Vaccines & Prevention BV outside the submitted work. HL reports grants from GSK and Merck outside the submitted work. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The effect of malaria infection on the immunogenicity of the recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein (GP) vaccine (rVSVΔG-ZEBOV-GP) (ERVEBO) is unknown., Methods: The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) vaccinated 7998 asymptomatic adults with rVSVΔG-ZEBOV-GP during the 2014-2016 Ebola epidemic. In STRIVE's immunogenicity substudy, participants provided blood samples at baseline and at 1, 6, and 9-12 months. Anti-GP binding and neutralizing antibodies were measured using validated assays. Baseline samples were tested for malaria parasites by polymerase chain reaction., Results: Overall, 506 participants enrolled in the immunogenicity substudy and had ≥1 postvaccination antibody titer. Of 499 participants with a result, baseline malaria parasitemia was detected in 73 (14.6%). All GP enzyme-linked immunosorbent assay (ELISA) and plaque reduction neutralization test (PRNT) geometric mean titers (GMTs) at 1, 6, and 9-12 months were above baseline, and 94.1% of participants showed seroresponse by GP-ELISA (≥2-fold rise and ≥200 ELISA units/mL), while 81.5% showed seroresponse by PRNT (≥4-fold rise) at ≥1 postvaccination assessment. In participants with baseline malaria parasitemia, the PRNT seroresponse proportion was lower, while PRNT GMTs and GP-ELISA seroresponse and GMTs showed a trend toward lower responses at 6 and 9-12 months., Conclusion: Asymptomatic adults with or without malaria parasitemia had robust immune responses to rVSVΔG-ZEBOV-GP, persisting for 9-12 months. Responses in those with malaria parasitemia were somewhat lower., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Although hand hygiene (HH) is the most effective intervention to reduce the spread of infections, there are limited data on HH facilities, policy, and compliance in sub-Saharan Africa. This cross-sectional study is aimed at assessing HH using the WHO HH self-assessment framework, HH technical reference manual, and a modified infection control self-assessment tool in two hospitals in Sierra Leone. Only 10% and 9% of regional and capital city hospitals had running tap water, respectively. Veronica buckets were the resources for HH in 89% of units in the regional hospital and 92% of units in capital city hospital. Constant supply of soap and alcohol-based hand rub was available in 82% and 68%; and 74% and 79% of units in the capital city and regional hospitals, respectively. Only 10% of the units in both hospitals had hand-drying facilities and functional sinks. Overall HH compliance for the two hospitals was 18.6% and was higher in the regional (20.8%) than the capital city (17.0%) hospitals. The HH levels for the capital city and regional hospitals were 277.5 and 262.5 respectively. Despite the COVID-19 pandemic, there are still challenges with HH compliance in Sierra Leone. It is, therefore, necessary to strengthen the HH multi-modal strategy.

Introduction: As of 26 March 2021, the Africa Centres for Disease Control and Prevention had reported 4 159 055 cases of COVID-19 and 111 357 deaths among the 55 African Union member states; however, no country has published a nationally representative serosurvey as of October 2021. Such data are vital for understanding the pandemic's progression on the continent, evaluating containment measures, and policy planning., Methods: We conducted a cross-sectional, nationally representative, age-stratified serosurvey in Sierra Leone in March 2021 by randomly selecting 120 Enumeration Areas throughout the country and 10 randomly selected households in each of these. One to two persons per selected household were interviewed to collect information on sociodemographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. Capillary blood was collected by fingerstick, and blood samples were tested using the Hangzhou Biotest Biotech RightSign COVID-19 IgG/IgM Rapid Test Cassette. Total seroprevalence was estimated after applying sampling weights., Results: The overall weighted seroprevalence was 2.6% (95% CI 1.9% to 3.4%). This was 43 times higher than the reported number of cases. Rural seropositivity was 1.8% (95% CI 1.0% to 2.5%), and urban seropositivity was 4.2% (95% CI 2.6% to 5.7%)., Discussion: Overall seroprevalence was low compared with countries in Europe and the Americas (suggesting relatively successful containment in Sierra Leone). This has ramifications for the country's third wave (which started in June 2021), during which the average number of daily reported cases was 87 by the end of the month:this could potentially be on the order of 3700 actual infections per day, calling for stronger containment measures in a country with only 0.2% of people fully vaccinated. It may also reflect significant under-reporting of incidence and mortality across the continent., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Health research in low-income and middle-income countries, which face the greatest burden of disease, is a vital component of efforts to combat global health inequality. With increased research, there has also been concern about ethical and regulatory issues and the state of research ethics committees, with various attempts to strengthen them. This scoping review examines the literature on ethics committees for health-related research in sub-Saharan Africa, with a focus on regulatory governance and leadership, administrative and financial capacity, and conduct of ethical reviews., Methods and Analysis: We will use the methodological approach proposed by Arksey and O'Malley and adapted by Levac et al and the Joanna Briggs Institute. Inclusion and exclusion criteria are based on the 'Population-Concept-Context' framework. Literature (from January 2000 to December 2020) will be searched in multiple databases including Embase and PubMed and websites of relevant organisations. All records will be screened by applying the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review flowchart: two reviewers will independently screen titles and abstracts, and full text of included records. Using an inductive approach, we will synthesise the literature, identify best practice and gaps in evidence on strengthening research ethics committees., Ethics and Dissemination: Ethical approval is not required as the review will include only published literature. The findings will be published in a peer-reviewed journal and presented at stakeholder meetings and conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Little information exists regarding Ebola vaccine rVSVΔG-ZEBOV-GP and pregnancy. The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) randomized participants without blinding to immediate or deferred (18-24 weeks postenrollment) vaccination. Pregnancy was an exclusion criterion, but 84 women were inadvertently vaccinated in early pregnancy or became pregnant <60 days after vaccination or enrollment. Among immediate vaccinated women, 45% (14/31) reported pregnancy loss, compared with 33% (11/33) of unvaccinated women with contemporaneous pregnancies (relative risk 1.35, 95% CI 0.73-2.52). Pregnancy loss was similar among women with higher risk for vaccine viremia (conception before or <14 days after vaccination) (44% [4/9]) and women with lower risk (conception >15 days after vaccination) (45% [10/22]). No congenital anomalies were detected among 44 live-born infants examined. These data highlight the need for Ebola vaccination decisions to balance the possible risk for an adverse pregnancy outcome with the risk for Ebola exposure.

Background: Preventive chemotherapy was administered to 3.2 million Sierra Leoneans in 13 health districts for lymphatic filariasis, onchocerciasis, and soil transmitted helminthes from October 2008 to February 2009. This paper aims to report the findings of a coverage survey conducted in 2009, compare the coverage survey findings with two reported rates for lymphatic filariasis coverage obtained using pre-mass drug administration (MDA) registration and national census projections, and use the comparison to understand the best source of population estimates in calculating coverage for NTD programming in Sierra Leone., Methodology/principal Findings: Community drug distributors (CDDs) conducted a pre- MDA registration of the population. Two coverage rates for MDA for lymphatic filariasis were subsequently calculated using the reported number treated divided by the total population from: 1) the pre-MDA register and 2) national census projections. A survey was conducted to validate reported coverage data. 11,602 persons participated (response rate of 76.8%). Overall, reported coverage data aggregated to the national level were not significantly different from surveyed coverage (z-test >0.05). However, estimates based on pre-MDA registration have higher agreement with surveyed coverage (mean Kendall's W = 0.68) than coverage calculated with census data (mean Kendall's = 0.59), especially in districts with known large-scale migration, except in a highly urban district where it was more challenging to conduct a pre-MDA registration appropriately. There was no significant difference between coverage among males versus females when the analyses were performed excluding those women who were pregnant at the time of MDA. The surveyed coverage estimate was near or below the minimum 65% epidemiological coverage target for lymphatic filariasis MDA in all districts., Conclusion/significance: These results from Sierra Leone illustrate the importance of choosing the right denominator for calculating treatment coverage for NTD programs. While routinely reported coverage results using national census data are often good enough for programmatic decision making, census projections can quickly become outdated where there is substantial migration, e.g. due to the impact of civil war, with changing economic opportunities, in urban settings, and where there are large migratory populations. In districts where this is known to be the case, well implemented pre-MDA registration can provide better population estimates. Pre-MDA registration should, however, be implemented correctly to reduce the risk of missing pockets of the population, especially in urban settings., Competing Interests: The authors have declared that no competing interests exist.

Background: In an attempt to assess the effects of the Ebola viral disease (EVD) on hospital functions in Sierra Leone, the aim of this study was to evaluate changes in provisions of surgery and non-Ebola admissions during the first year of the EVD outbreak., Methods: All hospitals in Sierra Leone known to perform inpatient surgery were assessed for non-Ebola admissions, volume of surgery, caesarean deliveries and inguinal hernia repairs between January 2014 and May 2015, which was a total of 72 weeks. Accumulated weekly data were gathered from readily available hospital records at bi-weekly visits during the peak of the outbreak from September 2014 to May 2015. The Mann-Whitney U test was used to compare weekly median admissions during the first year of the EVD outbreak, with the 20 weeks before the outbreak, and weekly median volume of surgeries performed during the first year of the EVD outbreak with identical weeks of 2012. The manuscript is prepared according to the STROBE checklist for cross-sectional studies., Results: Of the 42 hospitals identified, 40 had available data for 94% (2719/2880) of the weeks. There was a 51% decrease in weekly median non-Ebola admissions and 41% fewer weekly median surgeries performed compared with the 20 weeks before the outbreak (admission) and 2012 (volume of surgery). Governmental hospitals experienced a smaller reduction in non-Ebola admissions (45% versus 60%) and surgeries (31% versus 53%) compared to private non-profit hospitals. Governmental hospitals realized an increased volume of cesarean deliveries by 45% during the EVD outbreak, thereby absorbing the 43% reduction observed in the private non-profit hospitals., Conclusions: Both non-Ebola admissions and surgeries were severely reduced during the EVD outbreak. In addition to responding to the EVD outbreak, governmental hospitals were able to maintain certain core health systems functions. Volume of surgery is a promising indicator of hospital functions that should be further explored.

Background: As performance-based financing (PBF) has been increasingly implemented in low-income countries, a growing literature has developed, assessing its effectiveness and, more recently, focussing on the political dynamics of PBF introduction and implementation. This study contributes to the latter body of literature by exploring decision-making processes on PBF in Sierra Leone during the 2010-2017 period. Sierra Leone presents an interesting case because of the 'start-stop-start' trajectory of PBF., Methods: The qualitative case study is based on a document review and 25 key informant interviews with national stakeholders and international actors. Documents and interviews were analysed based on a political economy framework focusing on actors and structure, but also making use of concepts drawn from interpretive policy analysis to look at frames., Results: Our analysis describes the process of negotiation and re-negotiation of PBF in Sierra Leone, highlighting the role of different players, both internal and external, their ideas, capacity and power relations, and the shifting narratives around PBF. It is shown that external actors driving the debate make use of 'frames', both actual (i.e., defining the timing and pace of the discussions, the funding available, etc.) and metaphorical (i.e., how PBF is interpreted, defined and understood) to fit in and influence the debate. This is facilitated by the lack of capacity and resources in the fragile setting. Other strategies, such as 'venue shopping' are employed, though they may add to fragmentation in the volatile context., Conclusions: The retrospective view of the study has an analytical advantage, but findings are also relevant to guide practice. Although power relations and rent-seeking issues are difficult to overcome in resource and capacity-constrained settings, more attention could be paid to other elements. In particular, adopting shared frames to ensure a common and inclusive understanding of technical concepts such as PBF may be useful to ensure the political sustainability of reforms. Also, the 'actual frames' which define negotiation and implementation should remain flexible, allowing for disrupting events (e.g., the Ebola epidemic in Sierra Leone) as well as for time to develop national capacity and ownership in order to ensure longer-term political support and better health system integration.

Background/aims During the 2014-2016 West African Ebola epidemic, clinical trials were fast-tracked in order to identify prophylactic vaccines and experimental treatments that might be useful in preventing or treating Ebola. These trials included the ongoing EBOVAC-Salone study, which was established and implemented in Sierra Leone to assess the safety and immunogenicity of the Ad26.ZEBOV/MVA-BN-Filo prime-boost Ebola vaccine regimen. Methods This article describes the experiences of the EBOVAC-Salone research team in setting up and implementing the trial, and provides recommendations for research teams aiming to conduct clinical trials in future outbreak situations. Results Establishing a clinical trial during an outbreak brought some unique challenges, including those related to trial design and the regulatory environment, operational issues, and community engagement. The situation was further complicated by the weak infrastructure and limited experience of clinical trials in Sierra Leone. However, operating in an outbreak context also brought some benefits to the research team, including strong stakeholder support. The EBOVAC-Salone study recruited participants both during and after the outbreak, leading to additional challenges to trial implementation during the post-outbreak transition. Conclusion Many lessons have been learned about setting up and implementing a clinical trial during a devastating Ebola epidemic, and some of the experiences of the EBOVAC-Salone team were mirrored by those of other researchers operating in the region. Common to several of these research groups is a recommendation that research should be more closely incorporated into outbreak response planning, which could expedite the establishment of timely and appropriate research projects. We recommend that the lessons learned by researchers during the West African Ebola epidemic are built into programmes and strategies to improve the responses to future epidemics, wherever they occur.

Currently, the national malaria control programme (NMCP) of Sierra Leone recommends artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) as first- and second-line treatment for uncomplicated malaria, respectively, and artesunate + sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment during pregnancy and for infants. In 2016, the NMCP conducted a study to assess the clinical and parasitological responses of children under five years to ASAQ, AL and dihydroartemisinin-piperaquine (DHA/PPQ) according to the WHO protocol. Day-0 samples were tested for mutations in the Kelch 13 gene (pfk13) and dihydrofolate reductase/dihydropteroate synthase (pfdhfr/pfdhps) genes associated with artemisinin and SP resistance, respectively, and amplification in the pfplasmepsin2 gene for piperaquine resistance. A total of 295 (ASAQ = 128, AL = 64 and DHA/PPQ = 103) eligible children were enrolled at three sites. PCR-corrected 100% adequate clinical and parasitological response and no parasitaemia on day-3 were observed for all patients in each treatment group. Of the 278 samples with interpretable molecular data, only 2.2% carried non-synonymous pfk13 mutants (A578S, I646T), which are not associated with artemisinin resistance. None of the 103 day-0 samples from the DAH/PPQ group had pfplasmepsin2 gene amplification, confirming the absence of piperaquine resistance. The prevalence of the triple pfdhfr mutant (N51I/C59R/S108N) was close to or reached fixation (97.4-100%). For combined pfdhfr/pfdhps mutation, 55-71% carried the quadruple (N51I/C59R/S108N+A437G) mutant and about 10% the quintuple mutant N51I/C59R/S108N+A437G/K540E. Our findings confirm that ASAQ, AL and DHA/PPQ were highly effective for the treatment of uncomplicated malaria in the study areas, and neither pfk13 validated mutations nor pfplasmepsin2 multiple copies were found. The very low prevalence of the quintuple mutant in this study supports the NMCP's decision to introduce intermittent preventive treatment for infants with SP in the districts with high malaria transmission., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE), a phase 2/3 trial of investigational rVSV∆G-ZEBOV-GP vaccine, was conducted during an unprecedented Ebola epidemic. More than 8600 eligible healthcare and frontline response workers were individually randomized to immediate (within 7 days) or deferred (within 18-24 weeks) vaccination and followed for 6 months after vaccination for serious adverse events and Ebola virus infection. Key challenges included limited infrastructure to support trial activities, unreliable electricity, and staff with limited clinical trial experience. Study staff made substantial infrastructure investments, including renovation of enrollment sites, laboratories, and government cold chain facilities, and imported equipment to store and transport vaccine at ≤-60oC. STRIVE built capacity by providing didactic and practical research training to >350 staff, which was reinforced with daily review and feedback meetings. The operational challenges of safety follow-up were addressed by issuing mobile telephones to participants, making home visits, and establishing a nurse triage hotline. Before the Ebola outbreak, Sierra Leone had limited infrastructure and staff to conduct clinical trials. Without interfering with the outbreak response, STRIVE responded to an urgent need and helped build this capacity., Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].