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Specific treatments targeting Ebola virus are crucial in managing Ebola virus disease. To support the development of clinical practice guidelines on medications for Ebola virus disease, we aimed to evaluate the efficacy and safety of therapies for patients with Ebola virus disease.In this systematic review and network meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, Global Health, African Index Medicus, World Health Organization Global Index Medicus, the Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, Epistemonikos, bioRxiv, medRxiv, and SSRN without language restrictions for randomised controlled trials (RCTs) published between database inception and Jan 1, 2022, comparing at least one therapeutic agent for Ebola virus disease against standard care or another therapeutic agent for Ebola virus disease. Two reviewers assessed study eligibility and extracted summary data independently using a standardised form. Our outcomes of interest were mortality, adverse maternal outcomes, risk of onward transmission, duration of admission to a health-care facility, functional status after Ebola virus disease, serious adverse events from medication, adverse perinatal outcomes, time to symptom resolution, and time to viral clearance. We did frequentist network meta-analyses to estimate the effect of all interventions and applied the Grading of Recommendations Assessment, Development and Evaluation approach to rate the certainty of the evidence. We registered the protocol with PROSPERO, CRD42022296539.We identified 7840 records through database searches, of which two RCTs with a total of 753 patients proved eligible. Only data on mortality, the duration of admission, serious adverse events, and time to viral clearance were available for meta-analysis. Compared with standard care, REGN-EB3 (relative risk [RR] 0·40, 95% CI 0·18 to 0·89; moderate certainty) and mAb114 (0·42, 0·19 to 0·93; moderate certainty) probably reduce mortality. Whether ZMapp (0·60, 0·28 to 1·26; very low certainty) and remdesivir (0·64, 0·29 to 1·39; very low certainty) reduce mortality compared with standard care is uncertain. With high certainty, REGN-EB3 reduces mortality compared with ZMapp (0·67, 0·52 to 0·88) and remdesivir (0·63, 0·49 to 0·82). With high certainty, mAb114 also reduces mortality compared with ZMapp (0·71, 0·55 to 0·91) and remdesivir (0·66, 0·52 to 0·84). Compared with standard care, REGN-EB3, mAb114, ZMapp, and remdesivir might have little or no effect on the time to viral clearance (mean difference ranged from -0·25 days to -1·14 days; low certainty). ZMapp might reduce the duration of admission compared with standard care (mean difference -2·02 days, 95% CI -4·05 to 0·01; low certainty). Findings for all comparisons suggested that there might be little or no difference in the prevalence of serious adverse events, but certainty was low or very low in all comparisons but one.REGN-EB3 and mAb114 separately reduce mortality compared with ZMapp, remdesivir, or standard care in patients with Ebola virus disease. These findings suggest that health-care workers should prioritise the use of REGN-EB3 and mAb114 for patients with Ebola virus disease during future outbreaks.WHO.

Chiyembekezo Kachimanga,1,2 Anu Jegede Williams,3 Musa Bangura,1 Marta Lado,4 Sahr Kanawa,5 Daniel Lavallie,5 Michael Mhango,1 Haja Isatta Wurie,6 Marta Patiño Rodriguez1 1Partners in Health Sierra Leone, Koidu City, Sierra Leone; 2Partners in Health Malawi, Neno, Malawi; 3Central Public Health Reference Laboratory, Ministry of Health and Sanitation, Freetown, Sierra Leone; 4World Health Organization, Geneva, Switzerland; 5Koidu Government Hospital, Ministry of Health and Sanitation, Koidu City, Sierra Leone; 6Laboratory Science Unit, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra LeoneCorrespondence: Chiyembekezo Kachimanga Tel +265 887247777Email chembekachimanga@yahoo.co.ukIntroduction: Currently, there are no data on prevalence and associated risk factors of chronic kidney disease (CKD) among patients with hypertension in rural Sierra Leone.Purpose: To estimate the prevalence and associated risk factors of CKD in rural Sierra Leone.Patients and Methods: A cross-sectional study of hypertension patients aged between 18 and 75 years attending a non-communicable disease clinic at Koidu Government Hospital, Kono District, Sierra Leone was conducted between February and December 2020. Using systematic random sampling, a structured questionnaire, which comprised of questions on social demographic characteristics and past and current clinical history, was administered followed by measurement of creatinine and urinary protein and glucose. Estimated glomerular filtration rate (eGFR) was estimated using CKD-epidemiology formula without race as a factor. Baseline eGFR between 60– 89 min/mL/1.73m2 and < 60 min/mL/1.73m2 defined reduced eGFR and renal impairment, respectively. Estimated GFR less than 60 min/mL/1.73m2 measured two times at least 3 months apart was used to define CKD.Results: Ninety-six percent (n = 304) patients out of 317 patients were included in the study. Among all included patients, only 3.9% (n = 12) had eGFR of 90 min/mL/1.73m2 and above. The prevalence of renal impairment and CKD was 52% (158/304, CI 46.2– 57.7) and 29.9% (91/304, CI 24.8– 34.5), respectively. In adjusted logistic regression analysis, currently taking herbal medications as treatment of hypertension (OR 4.11 (CI 1.14– 14.80), p = 0.03) and being overweight and/or obese (OR 2.16 (CI 1.24– 3.78), p < 0.001) was associated with CKD. Additionally, receiving some education was associated with a 48% (OR 0.52 (CI 0.29– 0.91), p = 0.02) reduced likelihood of CKD.Conclusion: The prevalence of renal impairment and CKD is high among hypertensive patients in rural Sierra Leone. CKD was associated with current history of taking herbal medications and being overweight and/or obese. Additionally, CKD was associated with reduced likelihood in patients who received some education.Keywords: hypertension, non-communicable diseases, CKD, renal impairment, screening, Sierra Leone

This study is an evaluation of the first cohort of patients enrolled in an outpatient non-communicable disease clinic in Kono, Sierra Leone. In the first year, the clinic enrolled 916 patients. Eight months after the enrollment of the last patient, 53% were still active in care, 43% had been lost to follow-up (LTFU) and 4% had defaulted. Of the LTFU patients, 47% only came for the initial enrollment visit and never returned. Treatment outcomes of three patient groups [HTN only (n = 720), DM only (n = 51), and HTN/DM (n = 96)] were analyzed through a retrospective chart review. On average, all groups experienced reductions in blood pressure and/or blood glucose of approximately 10% and 20%, respectively. The proportions of patients with their condition controlled also increased. As NCDs remain underfunded and under-prioritized in low-income countries, the integrated program in Kono demonstrates the possibility of improving outpatient NCD care in Sierra Leone and similar settings.

Objectives: In Sierra Leone, very little data are available on hepatitis B virus (HBV) and hepatitis C virus (HCV) prevalence. Blood donor screening permits estimation of the prevalence of transfusion transmissible infections in a general open population. We analyzed blood donor data in Sierra Leone to estimate national viral hepatitis prevalence and identify risk factors for hepatitis infection among the donor population. Methods: We conducted a retrospective data analysis in five government hospitals. We collected HBV and HCV screening results, donor demographics, and donation type (family replacement or voluntary donor; first-time or repeat). Univariate and multivariate analyses were performed to determine associations between infections and socio-demographic factors. Results: The number of donors screened was 29,713. The overall prevalence was: 10.8% (3200) for HBV and 1.2% (357) for HCV. HBV infection was most strongly associated with male sex (p

Background Treating critical illness in resource-limited settings during disease outbreaks is feasible and can save lives. Lack of trained healthcare workers is a major barrier to COVID-19 response. There is an urgent need to train healthcare workers to manage COVID-19. The World Health Organization and International Committee of the Red Cross’s Basic Emergency Care course could provide a framework to cross-train personnel for COVID-19 care while strengthening essential health services. Methods We conducted a prospective cohort study evaluating the Basic Emergency Care course for healthcare workers from emergency and inpatient units at two hospitals in Sierra Leone, a low-income country in West Africa. Baseline, post-course, and six month assessments of knowledge and confidence were completed. Questions on COVID-19 were added at six months. We compared change from baseline in knowledge scores and proportions of participants “very comfortable” with course skills using paired Student’s t-tests and McNemar’s exact tests, respectively. Results We enrolled 32 participants of whom 31 completed pre- and post-course assessments. Six month knowledge and confidence assessments were completed by 15 and 20 participants, respectively. Mean knowledge score post-course was 85% (95% CI: 82% to 88%), which was increased from baseline (53%, 48% to 57%, p-value p-value 0.001). The percentage of participants who were “very comfortable” performing skills increased from baseline for 27 of 34 skills post-training and 13 skills at six months. Half of respondents strongly agreed the course improved ability to manage COVID-19. Conclusions This study demonstrates the feasibility of the Basic Emergency Care course to train emergency and inpatient healthcare workers with lasting impact. The timing of the study, at the beginning of the COVID-19 pandemic, provided an opportunity to illustrate the strategic overlap between building human resource capacity for long-term health systems strengthening and COVID-19. Future efforts should focus on integration with national training curricula and training of the trainers for broader dissemination and implementation at scale.

Background: This study aimed at describing the changes in the completeness of documentation and changes in decision to incision time interval of emergency cesarean sections after an audit and feedback project a rural hospital in Sierra Leone. Methods: We documented and monitored the decision and incision times for emergency cesarean sections over the course of two years. Year one focused on the introduction of the project and year two focused on the continuous monitoring of the project. We compared the completeness of decision to incision data and used the 30-min benchmark as target for the decision to incision time interval. Results: A total of 762 emergency cesarean sections were included. While the completion of decision time data (72%) did not change between the two reporting periods, documentation of incision time increased from 95% to 98% (p &lt, 0.001). Complete documentation for both decision and incision time was available for 540 (70.9%) emergency cesarean sections. The decision to incision time interval decreased from 105 min to 42 min (p &lt, 0.001). The proportion of cesarean sections started within 30 min increased from 8.5% to 37% (p &lt, 0.001). Conclusion: Although not all cesarean sections were performed within the 30-min threshold, the decision to incision interval decreased significantly. Improvements in documentation and routine reporting of the decision to incision time interval is recommended.

This is the twelfth version (eleventh update) of the living guideline, replacing earlier versions (available as data supplements). New recommendations will be published as updates to this guideline.What is the role of drugs in the treatment of patients with covid-19?The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and under way. The emerging SARS-CoV-2 variants (such as omicron) and subvariants are also changing the role of therapeutics. This update provides updated recommendations for remdesivir, addresses the use of combination therapy with corticosteroids, interleukin-6 (IL-6) receptor blockers, and janus kinase (JAK) inhibitors in patients with severe or critical covid-19, and modifies previous recommendations for the neutralising monoclonal antibodies sotrovimab and casirivimab-imdevimab in patients with non-severe covid-19.• Remdesivir: a conditional recommendation for its use in patients with severe covid-19; and a conditional recommendation against its use in patients with critical covid-19. • Concomitant use of IL-6 receptor blockers (tocilizumab or sarilumab) and the JAK inhibitor baricitinib: these drugs may now be combined, in addition to corticosteroids, in patients with severe or critical covid-19. • Sotrovimab and casirivimab-imdevimab: strong recommendations against their use in patients with covid-19, replacing the previous conditional recommendations for their use.When moving from new evidence to updated recommendations, the Guideline Development Group (GDG) considered a combination of evidence assessing relative benefits and harms, values and preferences, and feasibility issues. For remdesivir, new trial data were added to a previous subgroup analysis and provided sufficiently trustworthy evidence to demonstrate benefits in patients with severe covid-19, but not critical covid-19. The GDG considered benefits of remdesivir to be modest and of moderate certainty for key outcomes such as mortality and mechanical ventilation, resulting in a conditional recommendation. For baricitinib, the GDG considered clinical trial evidence (RECOVERY) demonstrating reduced risk of death in patients already receiving corticosteroids and IL-6 receptor blockers. The GDG acknowledged that the clinical trials were not representative of the world population and that the risk-benefit balance may be less advantageous, particularly in patients who are immunosuppressed at higher risk of opportunistic infections (such as serious fungal, viral, or bacteria), those already deteriorating where less aggressive or stepwise addition of immunosuppressive medications may be preferred, and in areas where certain pathogens such as HIV or tuberculosis, are of concern. The panel anticipated that there would be situations where clinicians may opt for less aggressive immunosuppressive therapy or to combine medications in a stepwise fashion in patients who are deteriorating. The decision to combine the medications will depend on their availability, and the treating clinician's perception of the risk-benefit balance associated with combination immunosuppressive therapy, particularly in patient populations at risk of opportunistic infections who may have been under-represented in clinical trials. When making a strong recommendation against the use of monoclonal antibodies for patients with covid-19, the GDG considered in vitro neutralisation data demonstrating that sotrovimab and casirivimab-imdevimab evaluated in clinical trials have meaningfully reduced neutralisation activity of the currently circulating variants of SARS-CoV-2 and their subvariants. There was consensus among the panel that the absence of in vitro neutralisation activity strongly suggests absence of clinical effectiveness of these monoclonal antibodies. However, there was also consensus regarding the need for clinical trial evidence in order to confirm clinical efficacy of new monoclonal antibodies that reliably neutralise the circulating strains in vitro. Whether emerging new variants and subvariants might be susceptible to sotrovimab, casirivimab-imdevimab, or other anti-SARS-CoV-2 monoclonal antibodies cannot be predicted.• Recommended for patients with severe or critical covid-19—strong recommendations for systemic corticosteroids; IL-6 receptor blockers (tocilizumab or sarilumab) in combination with corticosteroids; and baricitinib as an alternative to IL-6 receptor blockers, in combination with corticosteroids. • Recommended for patients with non-severe covid-19 at highest risk of hospitalisation—a strong recommendation for nirmatrelvir/ritonavir; conditional recommendations for molnupiravir and remdesivir. • Not recommended for patients with non-severe covid-19—a conditional recommendation against systemic corticosteroids; a strong recommendation against convalescent plasma; a recommendation against fluvoxamine, except in the context of a clinical trial; and a strong recommendation against colchicine. • Not recommended for patients with non-severe covid-19 at low risk of hospitalisation—a conditional recommendation against nirmatrelvir/ritonavir. • Not recommended for patients with severe or critical covid-19—a recommendation against convalescent plasma except in the context of a clinical trial; and a conditional recommendation against the JAK inhibitors ruxolitinib and tofacitinib. • Not recommended, regardless of covid-19 disease severity—a strong recommendations against hydroxychloroquine and against lopinavir/ritonavir; and a recommendation against ivermectin except in the context of a clinical trial.This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The GDG typically evaluates a therapy when the WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resource implications, acceptability, feasibility, equity, and human rights. This guideline was developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for Guideline Development and according to a pre-approved protocol (planning proposal) by the Guideline Review Committee (GRC). A box at the end of the article outlines key methodological aspects of the guideline process. MAGIC Evidence Ecosystem Foundation provides methodological support, including the coordination of living systematic reviews with network meta-analyses to inform the recommendations. The full version of the guideline is available online in MAGICapp and in PDF, with a summary version here in The BMJ. These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact.Recommendations on anticoagulation are planned for the next update to this guideline.

The Corona Virus Disease 2019 (COVID-19) pandemic has rapidly spread in Africa, with a total of 474,592 confirmed cases by 11thJuly 2020. Consequently, all policy makers and health workers urgently need to be trained and to access the most credible information to contain and mitigate its impact. While the need for rapid training and information dissemination has increased, most of Africa is implementing public health social and physical distancing measures. Responding to this context requires broad partnerships and innovative virtual approaches to disseminate new insights, share best practices, and create networked communities of practice for all teach, and all learn. The World Health Organization (WHO)-Africa region, in collaboration with the Extension for Community Health Outcome (ECHO) Institute at the University of New Mexico Health Sciences Center (UNM HSC), the West Africa college of nurses and the East Central and Southern Africa college of physicians, private professional associations, academia and other partners has embarked on a virtual training programme to support the containment of COVID-19. Between 1stApril 2020 and 10thJuly 2020, about 7,500 diverse health professionals from 172 locations in 58 countries were trained in 15 sessions. Participants were from diverse institutions including: central ministries of health, WHO country offices, provincial and district hospitals and private medical practitioners. A range of critical COVID-19 preparedness and response interventions have been reviewed and discussed. There is a high demand for credible information from credible sources about COVID-19. To mitigate the“epidemic of misinformation”partnerships for virtual trainings and information dissemination leveraging existing learning platforms and networks across Africa will augment preparedness and response to COVID-19.

Purpose Hepatitis B virus (HBV) infection is considered a major public health concern for Sierra Leone. Although medical students are at increased occupational risk for HBV infection, little is known about the burden of HBV infection amongst medical students in Sierra Leone. Methods As part of a screening and vaccination campaign, a cross-sectional study on prevalence of HBV among medical students in Freetown was conducted in December 2019. Antigen point of care test was used for HBV screening and data on students' risk history and demographics were collected. Additionally, for students diagnosed positive with HBV, linkage to care and initial assessment data after diagnosis was collected from the HBV clinic they were linked to. Results One hundred and fifty-seven medical students (77.3%) from year three to six were screened for HBV infection. Almost all students (98.1%) had never been vaccinated against HBV and more than half (56.7%) reported a history of needle stick injuries. The prevalence of HBV infection (Hepatitis B surface antigen (HBsAg) positivity) was 10.2% (n = 16). Among HBsAg positive students, 75% (n = 12) were successfully enrolled at chronic HBV clinic within three months of diagnosis. Only one student had evidence of liver cirrhosis and was started on treatment with Tenofovir diproxil fumarate. Conclusion The prevalence of HBV infection is high among medical students in Sierra Leone. Despite the high prevalence, most of the students linked to care had no evidence of severe liver disease., Public health; Hepatobiliary system; Virology; Clinical research; Sierra Leone; Hepatitis B virus infection; Screening

Background Sepsis is a major contributor to global mortality with an estimated 700, 000 sepsis-related deaths annually. As sepsis is an acute complication of COVID-19, the ongoing pandemic can increase its global burden. Despite this, there is still limited research evidence on COVID-19 and sepsis. In this scoping review, we described the research data on sepsis and septic shock among patients with COVID-19. Methods We adapted Arksey and O’Malley framework by reviewing relevant studies published on medRxiv, PubMed, and Google Scholar between January 01, 2020, and April 16, 2020, on sepsis and septic shock with the publication language restriction to English. The findings included the prevalence and outcome of COVID-19 patients with sepsis or septic shock, sepsis criteria, laboratory data, and the treatment given to COVID patients. Results Of the 16 eligible articles included in this review, 13 (81.2%) were conducted in China. With the exception of one article, the research work for all the articles was conducted in adult patients. The articles were retrospective studies (12, 75%), case reports (3, 18.8%) and prospective observational studies (1,6.2%). The estimated prevalence of sepsis and septic shock range from 6.8–100% and 4–28.9%, respectively. Serum lactate, platelets, C-reactive protein, white cell counts, and procalcitonin were elevated in 24.5%, 6.2%, 31.2%, 62.5%, 43.8% and 37.5% of the articles, respectively. Bacterial cultures were documented in 4(25%) of the eligible articles. 12 (75%) and 11 (68.8%) articles documented the use of antivirals and antibiotics, respectively. Other antimicrobials used among COVID-19 patients were hydroxychloroquine (1,6.3%), chloroquine (1, 6.3%), and unspecified antifungal drugs (2, 12.5%). Supportive therapies like oxygen therapy, mechanical ventilation, and fluid therapy were documented in 12(75%), 13 (81.3%), and 2 (12.5%) articles, respectively. The highest and lowest mortality among the study participants is 29.8% (134) and 5.4% (12), respectively. Conclusion There is a paucity of data in the literature on sepsis in COVID-19 despite its high burden among the COVID-19 patient population resulting in a high rate of antimicrobial use that is not backed by clearly documented microbiology laboratory support. Research is needed to understand the burden of sepsis in COVID-19.

We describe a case series of 35 Ebola virus disease (EVD) survivors during the epidemic in West Africa who had neurologic and accompanying psychiatric sequelae. Survivors meeting neurologic criteria were invited from a cohort of 361 EVD survivors to attend a preliminary clinic. Those whose severe neurologic features were documented in the preliminary clinic were referred for specialist neurologic evaluation, ophthalmologic examination, and psychiatric assessment. Of 35 survivors with neurologic sequelae, 13 had migraine headache, 2 stroke, 2 peripheral sensory neuropathy, and 2 peripheral nerve lesions. Of brain computed tomography scans of 17 patients, 3 showed cerebral and/or cerebellar atrophy and 2 confirmed strokes. Sixteen patients required mental health follow-up; psychiatric disorders were diagnosed in 5. The 10 patients who experienced greatest disability had co-existing physical and mental health conditions. EVD survivors may have ongoing central and peripheral nervous system disorders, including previously unrecognized migraine headaches and stroke.

Objectives A central pillar in the response to the 2014 Ebola Virus Disease (EVD) epidemic in Sierra Leone was the role of Ebola Holding Units (EHUs). These units isolated patients meeting a suspect case definition, tested them for EVD, initiated appropriate early treatment, and discharged negative patients to onward inpatient care or home. Positive patients were referred to Ebola Treatment Centres. We aimed to estimate the risk of nosocomial transmission within these EHUs. Methods We followed up a cohort of 543 patients discharged with a negative EVD-test from five EHUs in the Western Area, Sierra Leone, and examined all line-listed subsequent EVD-tests from any facility in the Western Area to see if the patient was re-tested within 30 days, matching by name, age and address. We defined possible readmissions as having the same name and age but uncertain address, and confirmed readmissions where name, age and address matched. Results We found a positive readmission rate of 3.3% (18 cases), which included 1.5% confirmed readmissions (8 cases) and 1.8% possible readmissions (10 cases). This is lower than rates previously reported. We cannot ascertain if EVD was acquired within the EHUs or from re-exposure in the community. No demographic or clinical variables were identified as risk factors for positive readmission, likely due to our small sample size. Conclusions These findings support the EHU model as a safe method for isolation of suspect EVD patients and their role in limiting the spread of EVD. This article is protected by copyright. All rights reserved.

The Ebola virus and the Marburg virus together form the family of Filoviridae. The Filoviruses are thread-like RNA viruses that cause fever and haemorrhagic complications. The Filoviruses cause severe disease in humans and non-human primates (gorillas, chimpanzees and monkeys) with an extremely high case fatality rate in humans ranging from 25 to 90% depending on the subtype and the availability of medical care.

The long-term effects of the Ebola virus and the care needed by survivors is an evolving area and in the coming years we have much opportunity to learn about the late complications of the disease. In this chapter, we will first outline some of the proposed pathways for sequalae of EVD, then focus on the body systems in which some of these problems occur, and structure these around the time-frame in which they happen. Within the broad range of complications, the most common and potentially manageable relate to the psychosocial and ophthalmological sequelae, and viral persistence in semen with the accompanying risk of disease transmission—greatest attention is paid to these areas. Finally, we provide an approach to the Ebola survivor and outline future direction for care and research.

During this Ebola outbreak, there have been many different names used to describe Ebola Isolation units, including ‘Holding Units’, ‘Isolation Units’, ‘Care Units’ and ‘Care Centres’. For the purposes of this book we use the phrase Ebola Holding Unit to mean a site which: Isolates patients who are screened or otherwise identified as suspected cases of Ebola Virus Disease (EVD) Provides initial clinical care for suspected EVD patients Undertakes laboratory testing to confirm the status of suspected EVD cases Refers positive EVD patients to an Ebola Treatment Centre (ETC/ETU) as soon as is possible Can safely store corpses of suspected or positive EVD patients pending collection by a burial team Is ideally co-located with other general health services

The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision.

The chapter explores the role of health partnerships in delivering services throughout the West African Ebola Virus Disease epidemic, including the creation of the Ministry of Health and Sanitation, Sierra Leone, Ebola Holding Unit models, command and control structures, research into diagnostics and care pathways, and general medical care. It will highlight how this provided resilience during the Ebola response, and how this will aid health systems strengthening going forward.

Fundamento y objetivo Analizar las tendencias de utilizacion de gammagrafia de ventilacion-perfusion (gammaV/Q), tomografia computarizada helicoidal (TCH) y arteriografia pulmonar para el diagnostico de embolia pulmonar (EP) en Espana, considerando los datos del Sistema Nacional de Salud (SNS) y el Registro RIETE y examinar las analogias diagnosticas de la gammaV/Q y la TCH en RIETE, con especial referencia a la gammaV/Q de probabilidad intermedia/indeterminada (GV/QPI). Material y metodo Se examinaron las tendencias anuales en pruebas de imagen para diagnosticar EP en 5.678 pacientes espanoles incluidos en el Registro RIETE (2001 a 2005) y se compararon con los pertenecientes al SNS (periodo 1999-2003). En el RIETE se compararon los resultados analogos entre los casos con gammaV/Q y TCH concomitantes y arteriografia y gammaV/Q o TCH. Resultados Hubo una tendencia creciente en la utilizacion de TCH, que supero en 2002 (RIETE) y en 2003 (SNS) a la gammaV/Q. En 732 casos con ambas pruebas, se obtuvieron resultados analogos en el 53%. En 116 casos con gammaV/QPI, la TCH disponible fue positiva a EP en un 87%. Cuando ademas habia signos clinicos de EP, la TCH fue positiva en un 95%. En 29 casos con angiografia pulmonar (AP) y TCH, los resultados fueron analogos en un 83% y en 31 casos con arteriografia y gammaV/Q, en un 77%. Conclusiones Actualmente, en Espana, la TCH es el metodo mas utilizado para el diagnostico de EP, aunque siguen realizandose numerosos estudios con gammaV/Q. En los resultados de gammaV/QPI es aconsejable estudiar la posible trombosis venosa profunda y, si la hay, los resultados del RIETE permiten asegurar la coexistencia de EP en un 87-95% de casos.

The 2014-2015 West African outbreak of Ebola Virus Disease (EVD) claimed the lives of more than 11,000 people and infected over 27,000 across seven countries. Traditional approaches to containing EVD proved inadequate and new approaches for controlling the outbreak were required. The Ministry of Health & Sanitation and King’s Sierra Leone Partnership developed a model for Ebola Holding Units (EHUs) at Government Hospitals in the capital city Freetown. The EHUs isolated screened or referred suspect patients, provided initial clinical care, undertook laboratory testing to confirm EVD status, referred onward positive cases to an Ebola Treatment Centre or negative cases to the general wards, and safely stored corpses pending collection by burial teams. Between 29th May 2014 and 19th January 2015, our five units had isolated approximately 37% (1159) of the 3097 confirmed cases within Western Urban and Rural district. Nosocomial transmission of EVD within the units appears lower than previously documented at other facilities and staff infection rates were also low. We found that EHUs are a flexible and effective model of rapid diagnosis, safe isolation and early initial treatment. We also demonstrated that it is possible for international partners and government facilities to collaborate closely during a humanitarian crisis.

Summary Background The size of the west African Ebola virus disease outbreak led to the urgent establishment of Ebola holding unit facilities for isolation and diagnostic testing of patients with suspected Ebola virus disease. Following the onset of the outbreak in Sierra Leone, patients presenting to Connaught Hospital in Freetown were screened for suspected Ebola virus disease on arrival and, if necessary, were admitted to the on-site Ebola holding unit. Since demand for beds in this unit greatly exceeded capacity, we aimed to improve the selection of patients with suspected Ebola virus disease for admission by identifying presenting clinical characteristics that were predictive of a confirmed diagnosis. Methods In this retrospective cohort study, we recorded the presenting clinical characteristics of suspected Ebola virus disease cases admitted to Connaught Hospital's Ebola holding unit. Patients were subsequently classified as confirmed Ebola virus disease cases or non-cases according to the result of Ebola virus reverse-transcriptase PCR (EBOV RT-PCR) testing. The sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio of every clinical characteristic were calculated, to estimate the diagnostic accuracy and predictive value of each clinical characteristic for confirmed Ebola virus disease. Results Between May 29, 2014, and Dec 8, 2014, 850 patients with suspected Ebola virus disease were admitted to the holding unit, of whom 724 had an EBOV RT-PCR result recorded and were included in the analysis. In 464 (64%) of these patients, a diagnosis of Ebola virus disease was confirmed. Fever or history of fever (n=599, 83%), intense fatigue or weakness (n=495, 68%), vomiting or nausea (n=365, 50%), and diarrhoea (n=294, 41%) were the most common presenting symptoms in suspected cases. Presentation with intense fatigue, confusion, conjunctivitis, hiccups, diarrhea, or vomiting was associated with increased likelihood of confirmed Ebola virus disease. Three or more of these symptoms in combination increased the probability of Ebola virus disease by 3·2-fold (95% CI 2·3–4·4), but the sensitivity of this strategy for Ebola virus disease diagnosis was low. In a subgroup analysis, 15 (9%) of 161 confirmed Ebola virus disease cases reported neither a history of fever nor a risk factor for Ebola virus disease exposure. Interpretation Discrimination of Ebola virus disease cases from patients without the disease is a major challenge in an outbreak and needs rapid diagnostic testing. Suspected Ebola virus disease case definitions that rely on history of fever and risk factors for Ebola virus disease exposure do not have sufficient sensitivity to identify all cases of the disease. Funding None.

The response to the fatal EVD outbreak in West Africa has not been properly analyzed yet and it may take us a long time to be able to identify all the weaknesses and mistakes that have happened and contributed to make of this EVD outbreak the worst in history. But definitely, it is clear that it was not only the virulence and lethality of the virus what led this outbreak to such an unexpected level; it involved many other environmental, resource and social factors which helped to the spread of the disease all over these three countries in such an exponential way.

Background Neurological and psychiatric sequelae in survivors of Ebola virus disease have been noted in previous epidemics, but few details have been documented. One case-report reported abnormal CT brain findings in one survivor. We aimed to document full neurological history and clinical examination findings, psychiatric screening, and the need for brain imaging in people who survived Ebola virus disease. Methods Adults (>16 years) in Sierra Leone who had survived Ebola virus disease with defined criteria of confirmed disease and one major or two minor symptoms were invited to attend clinic. Patients underwent full history, neurological examination, and psychiatric screening. Patients were referred, as necessary, to a tertiary neurology and psychiatric clinic, where brain CT scans were requested. Findings 87 (25%) of 354 patients in the initial cohort fitted the defined criteria. 38 of 45 patients who were contactable attended our screening clinic (24 women [63%], median age 34 years [IQR 25–43]). Median length of initial stay in hospital during Ebola virus disease was 21 days (13–28) and median time to our screening clinic post discharge was 431 days (402–497). 17 (45%) of the 38 clinic attenders reported loss of consciousness and seven (18%) reported seizures during their acute phase. In the screening clinic, 14 (50%) of 28 patients with headache reported eye symptoms (eye pain, itching, redness, blurred vision, or altered vision), seven (25%) photophobia, six (21%) intermittent fevers, five (18%) dizziness or vertigo, two (7%) tinnitus, and two (7%) scotoma. Headaches were usually intermittent and localised as frontal, unilateral, or band-like. 23 (61%) of the clinic attenders were offered referral to a tertiary neurological and psychiatric clinic, and 17 (42%) required CT brain scanning. At the screening clinic, psychiatric symptoms included insomnia (21/38, 55%), depression (12/38, 32%), and anxiety (11/38, 29%). Interpretation A broad range of important neurological and psychiatric sequelae were present in our selected group of Ebola virus disease survivors over a year after initial discharge. Intermittent headaches, associated with photophobia, intermittent fever, and dizziness or vertigo, were the most frequent neurological features. Common psychiatric symptoms included insomnia, depression, and anxiety. Our experience suggests that there is a need for tertiary level neurological and psychiatric clinics. Funding JTS is supported by the Wellcome Trust. MGS is supported by the UK National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections. This project is supported by the Enhancing Research Activity in Epidemic Situations.

Alcohol advertising correlates with consumption, particularly in young people. We studied the evolution of the amounts spent on alcoholic beverages advertising and on advertising as a whole in conventional media in Spain during the period 1995-2005.We analyzed the amounts spent on advertising in total and on alcoholic beverages advertising by studying the annual INFOADEX Survey on Advertising Investment in Spain in conventional media (TV, radio, the press, billboards and Internet). The results were subdivided into the periods 1995-2000 and 2001-2005.In the period 1995-2000 there was an increase (Delta) in alcoholic beverages advertising expenditure, from 268 to 347 million euro (Delta=29.5%), but a decrease in its percentage of advertising as a whole (from 7.6% to 6.1%). In the period 2001-2005 there was a rise in alcohol advertising expenditure from 145 to 186 million euro(Delta=28.0%), and also in its percentage of total advertising (from 2.7% to 2.8%). In 2001-2005, spending by Regional governments on preventive advertising increased from 22 to 52 million euro (Delta=136%).Alcohol advertising expenditure remains high in Spain, with young people as a primary target. In contrast, there is only modest investment in preventive advertising. Regulatory measures are necessary with a view to protecting populations especially susceptible to uncontrolled consumption.

To analyze the trends in the utilization of ventilation/perfusion pulmonary scintigraphy (V/QSc), spiral CT (sCT) and pulmonary angiography for diagnosis of pulmonary embolism (PE) in Spain, taking in account the information from the National System of Health (NSH) and RIETE Registry. To examine the diagnostic conformities of V/QSc and sCT in RIETE, with special reference to V/QSc of intermediate/indeterminate probability (V/QScIP).We examined annual trends of diagnostic imaging for PE in 5,678 Spanish patients included in RIETE (period 2001-2005) and in those of the NHS Databases (1999-2003 period). In RIETE the agreement between diagnostics was compared in cases with both V/QSc and sCT and angiography and V/QSc or sCT.We observed an increasing trend in sTC use, which overcame to V/QSc in 2002 (RIETE) and 2003 (NHS). In 732 cases with both techniques there was a diagnostic conformity of 53%. In 116 cases with V/QScIP a concomitant sTC was + for PE in 87%. If clinical signs of PE were present, then sTC was + in 95% of cases. In 29 cases with sCT and angiography agreement was 83% and in 31 cases with angiography and V/QSc was 77%.Nowadays in Spain the sTC is the most utilized method to diagnose EP. However, V/QSc studies are also broadly used. In studies V/QScIP it is advisable to look for deep venous thrombosis and, if present, the results of RIETE allow to assure EP coexistence in 87-95% of cases.

Background The Ebola virus disease epidemic in West Africa has infected 28 457 people and claimed more than 11 000 lives. Many more people may have died from the indirect effects of the epidemic and closure of normal health-care facilities. Unlike other facilities in West Africa, the emergency department in Connaught Hospital, Freetown, Sierre Leone, protected by an onsite Ebola holding unit, continued to provide emergency care throughout the outbreak. We aimed to assess the effect of the outbreak on emergency department attendance and presentation. We also analysed emergency care capacity across Freetown. Methods Attendance data from the emergency department and Ebola holding unit at Connaught Hospital were collected from June 1, 2014, to June 1, 2015. Severity of presentation was derived from South African Triage Score (SATS) assigned at first presentation to the emergency department. A mean severity score was calculated by dividing the number of presentations with a SATS of 1–2 by the total number of presentations. Local prevalence of the disease was counted as RT-PCR positive cases at the Ebola holding unit. Emergency care capacity was assessed at the seven principal hospitals in Freetown in May, 2013, and in April, 2015, with a standardised tool, the Emergency Care Capacity Score (ECCS), specifically designed for the low-income setting. All data were collected in Excel (2013). Stata (version 13) was used for statistical analysis. Findings 8935 patients presented to the emergency department; mean attendance was 172 patients per week (95% CI 153–191), with attendance varying from 41 patients in the week beginning July 28, 2014, to 284 patients in the week beginning May 11, 2015. Emergency department attendance had a negative correlation with local prevalence of Ebola virus disease (r=–0·640, p appendix ). The proportion of severe cases also varied from a peak of 26·5% in week 40 of 2014 (a period of high local prevalence, 74·6%) to 3·2% in week 28 of 2014 before any case had occurred in Freetown. The mean severity of presentation was 11·9% (95% CI 10·3–13·4). The ECCS was reduced across all domains except the systems domain ( appendix ). Total ECCS for all seven hospitals decreased by 10% from 2013 to 2015, and all facilities showed a decrease in their individual ECCS score. Interpretation The reduction in attendance probably demonstrates both a change in health-seeking behaviour—ie, great public fear of hospitals because of the perceived risk of nosocomial transmission of the virus—and a reduction in access to care. The decrease in emergency care capacity was expected and reflects the closure of many health services other than those for Ebola virus disease. Overall, this is an important case study of the impact of an infectious disease outbreak on a tertiary referral hospital in a low-income setting. Funding None.

Following an expert meeting convened in November, 2014, by the UK Chief Medical Officer, Michael Jacobs and colleagues argue there is “no evidence that addition of ventilatory or renal support would result in substantial overall benefit for patients who receive the optimum supportive care” for Ebola. Critical care support for volunteers who treat Ebola will therefore not be routinely provided in Sierra Leone or through repatriation to the UK. This recommendation contradicts our experience and that of colleagues in Germany and the USA who have managed Ebola and provided both ventilation and dialysis to patients who required it. It also goes against expert opinion from the fi eld which suggests many acutely unwell patients, and some recovering from viraemia, become anuric. Much sudden death might be attributed to renal failure and subsequent electrolyte imbalance in addition to respiratory compromise. Though priority should lie on staff safety and immediate basic care, many healthy individuals deteriorate rapidly and might undoubtedly die without organ support. As of December 2014—when we wrote this Correspondence—22 Ebola cases had been treated outside west Africa. To our knowledge where critical care support was provided, fi ve out of eight made a complete recovery. The two US and one German patients who died received late critical care intervention. As Bruce Ribner—who leads the team at Emory University Hospital Atlanta—stated: “[they] can get sick enough to need those interventions and [they] can still walk out of the hospital”. The Centers for Disease Control and Prevention and international nephrologists have produced guidelines for safe provision of haemodialysis in Ebola care. Importantly, no virus was detected in dialysis effl uent. Though ideally we would want critical care to be available for all Ebola patients, we argue that there is no medical reason against providing intensive organ support in Ebola-induced organ failure to all international volunteers whose home countries can provide it.