Randomized Trial of Vaccines for Zaire Ebola Virus Disease.

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.).

Impact of COVID-19 on the Utilization of HIV Testing and Linkage Services in Sierra Leone: Experience from Three Public Health Facilities in Freetown.

The COVID-19 pandemic adversely affected the delivery of essential health services globally. In this study, we aimed to assess the impact of the pandemic on HIV testing and linkage services at three public health facilities in Freetown, Sierra Leone. We conducted a retrospective study to assess the impact of COVID-19 on HIV testing and linkage to treatment services (HTS) at Connaught Hospital (CH-tertiary), Lumley Government Hospital (LGH-secondary) and George Brooke Community Health Center (GBC-primary) in Freetown. Statistical analyses were conducted in Stata (16.1, StataCorp LLC, College Station, TX). Intra-pandemic HTS (2020) and HTS during recovery (2021) were compared with pre-pandemic HTS (2019). Of the 8538 people tested for HIV in the three facilities, 4929 (57.5%) visited CH. Only 2249 people were tested for HIV in 2020 compared to 3825 in 2019 (difference: - 41.2%, P < 0.001). Fewer people were also tested in 2021 (difference: - 35.6% P < 0.001). The largest reductions in testing in 2020 occurred in women (- 47.7%), children under 15 (- 95.2%), married people (- 42.6%), and CH (- 46.2%). Overall, 1369 (16.0%) people were positive for HIV; CH (878, 17.9%), LGH (469, 15.6%) and GBC (22, 3.5%). The likelihood of a positive HIV test was 26% lower in 2020 than 2019 (PR 0.74; 95% CI 0.64-0.85; P < 0.001), but 16% higher in 2021 than 2019 (PR 1.16; 95% CI 1.03-1.30; P < 0.05). Of the 1369 HIV diagnosis, 526 (38.4%) were linked to care. We found significant disruptions in HIV testing and linkage services at different levels of service delivery during the COVID-19 pandemic, underscoring the need to strengthen essential health services during public health emergencies.

The feasibility, repeatability, validity and responsiveness of the EQ-5D-3L in Krio for patients with stroke in Sierra Leone.

OBJECTIVES: To assess the feasibility, repeatability, validity and responsiveness of the EQ-5D-3L in Krio for patients with stroke in Sierra Leone, the first psychometric assessment of the EQ-5D-3L to be conducted in patients with stroke in Sub Saharan Africa. METHODS: A prospective stroke register at two tertiary government hospitals recruited all patients with the WHO definition of stroke and followed patients up at seven days, 90 days and one year post stroke. The newly translated EQ-5D-3L, Barthel Index (BI), modified Rankin Scale (mRS) and National Institute of Health Stroke Scale (NIHSS), a measure of stroke severity, were collected by trained researchers, face to face during admission and via phone at follow up. Feasibility was assessed by completion rate and proportion of floor/ceiling effects. Internal consistency was assessed by inter item correlations (IIC) and Cronbach's alpha. Repeatability of the EQ-5D-3L was examined using test-retest, EQ-5D-3L utility scores at 90 days were compared to EQ-5D-3L utility scores at one year in the same individuals, whose Barthel Index had remained within the minimally clinical important difference. Known group validity was assessed by stroke severity. Convergent validity was assessed against the BI, using Spearman's rho. Responsiveness was assessed in patients whose BI improved or deteriorated from seven to 90 days. Sensitivity analyses were conducted using the UK and Zimbabwe value sets, to evaluate the effect of value set, in a subgroup of patients with no formal education to evaluate the influence of patient educational attainment, and using the mRS instead of the BI to evaluate the influence of utilising an alternative functional scale. RESULTS: The EQ-5D-3L was completed in 373/460 (81.1%), 360/367 (98.1%) and 299/308 (97.1%) eligible patients at seven days, 90 days and one year post stroke. Missing item data was low overall, but was highest in the anxiety/depression dimension 1.3% (5/373). Alpha was 0.81, 0.88 and 0.86 at seven days, 90 days and one year post stroke and IIC were within pre-specified ranges. Repeatability of the EQ-5D-3L was moderate to poor, weighted Kappa 0.23-0.49. EQ-5D-3L utility was significantly associated with stroke severity at all timepoints. Convergent validity with BI was strong overall and for shared subscales. EQ-5D-3L was moderately responsive to both improvement Cohen's D 0.55 (95% CI:0.15-0.94) and deterioration 0.92 (95% CI:0.29-1.55). Completion rates were similar in patients with no formal education 148/185 (80.0%) vs those with any formal education 225/275 (81.8%), and known group validity for stroke severity in patients with no formal education was strong. Using the Zimbabwe value set instead of the UK value set, and using the mRS instead of the BI did not change the direction or significance of results. CONCLUSIONS: The EQ-5D-3L for stroke in Sierra Leone was feasible, and responsive including in patients with no formal education. However, repeatability was moderate to poor, which may be due to the study design, but should add a degree of caution in the analysis of repeated measures of EQ-5D-3L over time in this population. Known group validity and convergent validity with BI and mRS were strong. Further research should assess the EQ-5D in the general population, examine test-retest reliability over a shorter time period and assess the acceptability and validity of the anxiety/depression dimension against other validated mental health instruments. Development of an EQ-5D value set for West Africa should be a research priority.

Determinants of incomplete childhood hepatitis B vaccination in Sierra Leone, Liberia, and Guinea: Analysis of national surveys (2018-2020).

Vaccination against hepatitis B virus (HBV) is effective at preventing vertical transmission. Sierra Leone, Liberia, and Guinea are hyperendemic West African countries; yet, childhood vaccination coverage is suboptimal, and the determinants of incomplete vaccination are poorly understood. We analyzed national survey data (2018-2020) of children aged 4-35 months to assess complete HBV vaccination (receiving 3 doses of the pentavalent vaccine) and incomplete vaccination (receiving <3 doses). Statistical analysis was conducted using the complex sample command in SPSS (version 28). Multivariate logistic regression was used to identify determinants of incomplete immunization. Overall, 11,181 mothers were analyzed (4,846 from Sierra Leone, 2,788 from Liberia, and 3,547 from Guinea). Sierra Leone had the highest HBV childhood vaccination coverage (70.3%), followed by Liberia (64.6%) and Guinea (39.3%). Within countries, HBV vaccination coverage varied by socioeconomic characteristics and healthcare access. In multivariate regression analysis, factors that were significantly associated with incomplete vaccination in at least one country included sex of the child, Muslim mothers, lower household wealth index, <4 antenatal visits, home delivery, and distance to health facility vaccination (all p < 0.05). Understanding and addressing modifiable determinants of incomplete vaccination will be essential to help achieve the 2030 viral hepatitis elimination goals.

Antibiotic use and consumption among medical patients of two hospitals in Sierra Leone: a descriptive report.

BACKGROUND: Although one of the main drivers of antimicrobial resistance is inappropriate antibiotic prescribing, there are limited resources to support the surveillance of antibiotic consumption in low-income countries. In this study, we aimed to assess antibiotic use and consumption among medical patients of two hospitals in different geographic regions of Sierra Leone. METHODS: This is a cross-sectional study of adult (18 years or older) patients receiving medical care at two hospitals (34 Military Hospital-MH and Makeni Government Hospital-MGH) between March 2021 and October 2021. After admission to the medical or intensive care unit, patients were sequentially recruited by a nurse from each hospital. Demographic and clinical characteristics and information on the dose of antibiotics, their routes, and frequency of administration and duration were collected using a questionnaire adapted from previous studies and encrypted in EpiCollect software (Epic, Verona WI). A physician reviews and verifies each completed questionnaire. Data analysis was done using STATA version 16. RESULTS: The mean age of the 468 patients evaluated in this study was 48.6 years. The majority were women (241, 51.7%) and treated at MGH (245, 52.0%). Clinical diagnosis of bacterial infection was made in only 180 (38.5%) patients. Regardless of the diagnosis, most (442, 94.9%) patients received at least one antibiotic. Of a total 813 doses of antibiotics prescribed by the two hospitals, 424 (52.2%) were administered in MH. Overall, antibiotic consumption was 66.9 defined daily doses (DDDs) per 100 bed-days, with ceftriaxone being the most commonly used antibiotic (277, 34.1%). The ACCESS and WATCH antibiotics accounted for 18.9 DDDs per 100 bed-days (28.2%) and 48.0 DDDs per 100 bed-days (71.7%), respectively. None of the patients were prescribed a RESERVE antibiotics. The antibiotic consumption was lower in MH (61.3 DDDs per 100 bed-days) than MGH (76.5 DDDs per 100 bed-days). CONCLUSION: Antibiotic consumption was highest with ceftriaxone, followed by levofloxacin and metronidazole. Given the high rate of consumption of antibiotics in the WATCH category of the AWaRe classification, there is a need to initiate surveillance of antibiotic consumption and establish hospital-based antibiotic stewardship in these settings.

"I want to become someone!" gender, reproduction and the moral career of motherhood for women with sickle cell disorders.

In Sierra Leone, motherhood is being transformed into a moral career for women with sickle cell disorders. This qualitative participatory study, conducted in 2018, involved thirty-six semi-structured interviews with female care-givers and women with sickle cell disorders. Mothers argued that medical models of disease, combined with caring practices, are means to morally manage ideas of 'spoiled identity' and rethink the sick role, disability and life-outcomes of a potentially serious condition. Mothers encourage their children with sickle cell to stay in education as a route to access formal employment and careers that will not tax their bodies and ensure reproductive timing. Education and employment are framed temporally to ensure a delay so that girls can develop caring relationships and access motherhood safely. Understanding and encouraging the development of motherhood as a moral career, involving embodied hyper-vigilant caring practices, is valuable for the self-identity of mothers, allowing them to see a future for themselves and their children.

Stroke in Sierra Leone. the stroke risk factors for people with HIV: A prospective case-control study.

BACKGROUND: HIV infection rates are relatively low in Sierra Leone and in West Africa but the contribution of HIV to the risk factors for stroke and outcomes is unknown. In this study, we examined stroke types, presentation, risk factors and outcome in HIV stroke patients compared with controls. METHODS: We used data from the Stroke in Sierra Leone Study at 2 tertiary hospitals in Freetown, Sierra Leone. A case control design was used to compare stroke type, presentation, risk factors and outcome in sero-positive HIV patients with HIV negative stroke controls. Controls were matched for age and gender and a 1:4 ratio cases to controls was used to optimize power. Analysis was performed using the Pearson x2 for categorical variable, Paired-T test and Mann-Whitney U test for continuous variables. A p-value of less than 0.05 was taken as the level of statistical significance. RESULTS: Of 511 (51.8%) stroke patients tested for HIV, 36 (7.1%) were positive. Univariate unmatched analysis showed a stroke mean age of 49 years in HIV-positive versus 58 years in HIV-negative population (p = <0.001). In the case-control group, ischaemic stroke is the major type reported in both populations, HIV-negative population: 77 (53.5%) versus HIV-positive: 25 (69.4%) (p = 0.084). Hypertension is the most prevalent risk factor in both groups, HIV-positive: 23 (63.9%) versus HIV-negative: 409 (86.1%) (p = 0.001). Lower CD4+ count is associated in-hospital mortality (p = <0.001). CONCLUSION: These findings support the current call for timely management of stroke and HIV through integrated care.

Prevalence of sero-markers and non-invasive assessment of liver cirrhosis in patients with Hepatitis B virus infection in Freetown, Sierra Leone: a cross-sectional study.

BACKGROUND: Hepatitis B virus (HBV) is a major global health problem. Although sub-Saharan Africa has a high proportion of the global burden of HBV, the epidemiology and clinical features of HBV in this region are poorly characterized, and access to diagnostic and treatment services remain limited. METHODS: We conducted a retrospective study of HBV-infected children and adults of all age groups who were evaluated at public and private health facilities in Freetown, Sierra Leone between January 2017 and January 2019. We assessed their clinical presentation, HBV sero-markers, stages of liver disease, prevalence of cirrhosis by non-invasive tools, and the proportion of treatment eligible patients using the criteria recommended by the World Health Organization's 2015 treatment guidelines for HBV. Logistic regression was used to identify predictors of liver cirrhosis. RESULTS: 163 HBV patients included in the study, with mean age 32.6 years and 65.0% (106) being males. Most (84.0%) were asymptomatic at presentation. The majority (69.9%) were classified as having HBeAg-negative chronic infection (or inactive HBsAg carrier phase), 24.5% were in the HBeAg-negative immune active phase, 3.1% had HBeAg positive hepatitis, and 2.5% were HBsAg negative. The median Aspartate aminotransferase to Platelet Ratio (APRI) and Fibrosis-4 (FIB-4) scores were 0.37 and 0.80, respectively. The prevalence of cirrhosis was 7.6% and 6.2%, estimated by the APRI and FIB-4 scores, respectively. About 20.0% of patients were eligible for treatment with antiviral agents. Based on APRI scores, the presence of any symptom [adjusted odds ratio (aOR) 20.0, 95% confidence interval (CI) (4.1-85.9); p < 0.001], elevated direct bilirubin [aOR 12.1, 95% CI (1.9-63.0); p = 0.003], and elevated total bilirubin [aOR 16.1, 95% CI (3.2-80.8); p = 0.001] were independent predictors of cirrhosis. CONCLUSION: Although most patients with HBV infection were asymptomatic, the prevalence of liver cirrhosis and proportion of patients requiring antiviral treatment were substantial. This small study from a hyperendemic setting in Sierra Leone suggests that routine population-based screening may increase early detection and linkage of HBV patients to care before development of complications. Larger studies are needed to confirm our findings.

Ebola RNA Persistence in Semen of Ebola Virus Disease Survivors - Final Report.

BACKGROUND: Ebola virus has been detected in the semen of men after their recovery from Ebola virus disease (EVD). We report the presence of Ebola virus RNA in semen in a cohort of survivors of EVD in Sierra Leone. METHODS: We enrolled a convenience sample of 220 adult male survivors of EVD in Sierra Leone, at various times after discharge from an Ebola treatment unit (ETU), in two phases (100 participants were in phase 1, and 120 in phase 2). Semen specimens obtained at baseline were tested by means of a quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay with the use of the target sequences of NP and VP40 (in phase 1) or NP and GP (in phase 2). This study did not evaluate directly the risk of sexual transmission of EVD. RESULTS: Of 210 participants who provided an initial semen specimen for analysis, 57 (27%) had positive results on quantitative RT-PCR. Ebola virus RNA was detected in the semen of all 7 men with a specimen obtained within 3 months after ETU discharge, in 26 of 42 (62%) with a specimen obtained at 4 to 6 months, in 15 of 60 (25%) with a specimen obtained at 7 to 9 months, in 4 of 26 (15%) with a specimen obtained at 10 to 12 months, in 4 of 38 (11%) with a specimen obtained at 13 to 15 months, in 1 of 25 (4%) with a specimen obtained at 16 to 18 months, and in no men with a specimen obtained at 19 months or later. Among the 46 participants with a positive result in phase 1, the median baseline cycle-threshold values (higher values indicate lower RNA values) for the NP and VP40 targets were lower within 3 months after ETU discharge (32.4 and 31.3, respectively; in 7 men) than at 4 to 6 months (34.3 and 33.1; in 25), at 7 to 9 months (37.4 and 36.6; in 13), and at 10 to 12 months (37.7 and 36.9; in 1). In phase 2, a total of 11 participants had positive results for NP and GP targets (samples obtained at 4.1 to 15.7 months after ETU discharge); cycle-threshold values ranged from 32.7 to 38.0 for NP and from 31.1 to 37.7 for GP. CONCLUSIONS: These data showed the long-term presence of Ebola virus RNA in semen and declining persistence with increasing time after ETU discharge. (Funded by the World Health Organization and others.).

Prevalence and mortality of cryptococcal disease in adults with advanced HIV in an urban tertiary hospital in Sierra Leone: a prospective study.

BACKGROUND: The global annual estimate for cryptococcal disease-related deaths exceeds 180,000, with three fourth occurring in sub-Saharan Africa. The World Health Organization (WHO) recommends cryptococcal antigen (CrAg) screening in all HIV patients with CD4 count < 100/µl. As there is no previous published study on the burden and impact of cryptococcal disease in Sierra Leone, research is needed to inform public health policies. We aimed to establish the seroprevalence and mortality of cryptococcal disease in adults with advanced HIV attending an urban tertiary hospital in Sierra Leone. METHODS: A prospective cohort study design was used to screen consecutive adult (18 years or older) HIV patients at Connaught Hospital in Freetown, Sierra Leone with CD4 count below 100 cells/mm3 from January to April 2018. Participants received a blood CrAg lateral flow assay (IMMY, Oklahoma, USA). All participants with a positive serum CrAg had lumbar puncture and cerebrospinal fluid (CSF) CrAg assay, and those with cryptococcal diseases had fluconazole monotherapy with 8 weeks followed up. Data were entered into Excel and analysed in Stata version 13.0. Proportions, median and interquartile ranges were used to summarise the data. Fisher's exact test was used to compare categorical variables. RESULTS: A total of 170 patients, with median age of 36 (IQR 30-43) and median CD4 count of 45 cells/mm3 (IQR 23-63) were screened. At the time of enrolment, 54% were inpatients, 51% were newly diagnosed with HIV, and 56% were either ART-naïve or newly initiated (≤ 30 days). Eight participants had a positive blood CrAg, giving a prevalence of 4.7% (95% CI: 2.4-9.2%). Of those with a positive CrAg, CSF CrAg was positive in five (62.5%). Five (62.5%) CrAg-positive participants died within the first month, while the remaining three were alive and established on ART at 8 weeks. CONCLUSION: A substantial prevalence of cryptococcal antigenaemia and poor outcome of cryptococcal disease were demonstrated in our study. The high mortality suggests a need for the HIV programme to formulate and implement policies on screening and pre-emptive fluconazole therapy for all adults with advanced HIV in Sierra Leone, and advocate for affordable access to effective antifungal therapies.

Prevalence of drug resistance mutations among ART-naive and -experienced HIV-infected patients in Sierra Leone.

OBJECTIVES: The aim of this study was to assess the prevalence of HIV drug resistance (HIVDR) in HIV-infected ART-naive and -experienced patients in Sierra Leone. PATIENTS AND METHODS: We conducted a cross-sectional study of HIV-positive adults aged ≥18 years at Connaught Hospital in Freetown, Sierra Leone in November 2017. Sequencing was performed in the reverse transcriptase, protease and integrase regions, and interpreted using the Stanford HIVDR database and WHO 2009 mutation list. RESULTS: Two hundred and fifteen HIV-infected patients were included (64 ART naive and 151 ART experienced). The majority (66%) were female, the median age was 36 years and the median ART exposure was 48 months. The majority (83%) were infected with HIV-1 subtype CRF02_AG. In the ART-naive group, the pretreatment drug resistance (PDR) prevalence was 36.7% (14.2% to NRTIs and 22.4% to NNRTIs). The most prevalent PDR mutations were K103N (14.3%), M184V (8.2%) and Y181C (4.1%). In the ART-experienced group, 64.4% harboured resistance-associated mutations (RAMs) and the overall prevalence of RAMs to NRTIs and NNRTIs was 85.2% (52/61) and 96.7% (59/61), respectively. The most prevalent RAMs were K103N (40.7%), M184V (28.8%), D67N (15.3%) and T215I/F/Y (15.3%). Based on the genotypic susceptibility score estimates, 22.4% of ART-naive patients and 56% of ART-experienced patients were not susceptible to first-line ART used in Sierra Leone. CONCLUSIONS: A high prevalence of circulating NRTI- and NNRTI-resistant variants was observed in ART-naive and -experienced HIV-1-infected patients in Sierra Leone. This necessitates the implementation of HIVDR surveillance programmes to inform national ART guidelines for the treatment and monitoring of HIV-infected patients in Sierra Leone.

Causes of hospitalization and predictors of HIV-associated mortality at the main referral hospital in Sierra Leone: a prospective study.

BACKGROUND: HIV infection is a growing public health problem in Sierra Leone and the wider West Africa region. The countrywide HIV prevalence was estimated at 1.7% (67,000 people), with less than 30% receiving life-saving ART in 2016. Thus, HIV-infected patients tend to present to health facilities late, with high mortality risk. METHODS: We conducted a prospective study of HIV inpatients aged ≥15 years at Connaught Hospital in Freetown-the main referral hospital in Sierra Leone-from July through September 2017, to assess associated factors and predictors of HIV-related mortality. RESULTS: One hundred seventy-three HIV inpatients were included, accounting for 14.2% (173/1221) of all hospital admissions during the study period. The majority were female (59.5%, 70/173), median age was 34 years, with 51.4% (89/173) of them diagnosed with HIV infection for the first time during the current hospitalization. The most common admitting diagnoses were anemia (48%, 84/173), tuberculosis (24.3%, 42/173), pneumonia (17.3%, 30/173) and diarrheal illness (15.0%, 26/173). CD4 count was obtained in 64.7% (112/173) of patients, with median value of 87 cells/µL (IQR 25-266), and was further staged as severe immunosuppression: CD4 < 100 cells/µL (50%, 56/112); AIDS: CD4 < 200 cells/µL (69.6%, 78/112); and late-stage HIV disease: CD4 < 350 cells/µL (83%, 93/112). Fifty-two patients (30.1%, 52/173) died during hospitalization, 23% (12/52) of them within the first week. The leading causes of death were anemia (23.1%, 12/52), pneumonia (19.2%, 10/52), diarrheal illness (15.4%, 8/52) and tuberculosis (13.6%, 7/52). Neurological symptoms, i.e., loss of consciousness (p = 0.04) and focal limb weakness (p = 0.04); alcohol use (p = 0.01); jaundice (p = 0.02); cerebral toxoplasmosis (p = 0.01); and tuberculosis (p = 0.04) were significantly associated with mortality; however, only jaundice (AOR 0.11, 95% CI [0.02-0.65]; p = 0.01) emerged as an independent predictor of mortality. CONCLUSION: HIV-infected patients account for a substantial proportion of admissions at Connaught Hospital, with a high morbidity and in-hospital mortality burden. These findings necessitate the implementation of specific measures to enhance early HIV diagnosis and expand treatment access to all HIV-infected patients in Sierra Leone.

Health Conditions in an Adult Population in Sierra Leone: Data Reported From the Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE).

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

The Sierra Leone Trial to Introduce a Vaccine Against Ebola: An Evaluation of rVSV∆G-ZEBOV-GP Vaccine Tolerability and Safety During the West Africa Ebola Outbreak.

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

Monitoring Serious Adverse Events in the Sierra Leone Trial to Introduce a Vaccine Against Ebola.

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

Case Series of Severe Neurologic Sequelae of Ebola Virus Disease during Epidemic, Sierra Leone.

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 followup; 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.

A Scoping Review of stroke registers in Sub Saharan Africa.

BACKGROUND: Stroke registers are recommended as a key priority by the Lancet Neurology World Stroke Organisation Commission for Stroke, 2023, and the African Stroke Leaders' Summit, 2022. AIMS: This scoping review aims to map where stroke registers have been implemented in SSA. The article then compares and critiques the methods and definitions used and summarizes key results from the registers. SUMMARY: We identified 42 unique stroke registers from 48 individual studies. The registers were located in 20 countries, with 19 from East Africa, 15 West Africa, six Central Africa and two from Southern Africa. Cumulatively, the registers recruited 12,345 participants with stroke, the median number of participants was 183 (IQR:121-312) and the range was 50-1018. Only one study was a population-based register and 41 were hospital-based registers. Of the hospital-based registers, 29 were single site, 10 were conducted at two sites, and two at three sites. 23 (54.7%) of the registers were located in the capital city of their respective country and only one of the hospital-based registers was in a self-described rural area. Length of recruitment ranged from four months to six years, median length of recruitment was 12 months.Methodology and definitions were heteregenous between the registers. Only seven (19.4%) registers referenced the WHO STEPwise approach to implementing stroke registers. 27 (64.3%) registers used the WHO definition of stroke. Mean neuroimaging rate was 84%, and ranged from 0-100%. Stroke severity was measured using the National Institute of Health Stroke Scale (NIHSS) in 22 (52.4%) registers, four registers used Glasgow Coma Scale (GCS), two registers used the miniNIHSS, one used the Scandanavian stroke scale, one mRS and 11 registers did not report a stroke severity measure. 17 (40.5%) registers used the mRS to measure function, six registers used Barthel Index alone and three registers used both mRS and Barthel Index. Only two registers included a quality of life measure, the EQ-5D. 8 registers included a quality of care measure, 26 (61.9%) registers recorded socioeconomic status or a socioeconomic status proxy, most frequently educational attainment. CONCLUSIONS: This scoping review found high heterogeneity of methods and definitions used by stroke registers, with low uptake of the WHO stepwise method of stroke surveillance. A drive to standardize methodology would improve the comparability of stroke data in SSA. The shared use of educational attainment by registers in our review may enable future meta-analyses of inequities in stroke in SSA. Incorporating health-related quality of life measures, such as EQ-5D, into stroke registers should be encouraged, bringing a patient perspective and allow the estimation of quality-adjusted life years lost to stroke. Agreement on a standardized register methodology or further promotion and uptake of the WHO stepwise method is essential to produce comparable data to improve stroke prevention and care.

Quality of life and quality-adjusted life years after stroke in Sierra Leone.

BACKGROUND: Stroke is a leading cause of mortality and negatively affects health-related quality of life (HRQoL). HRQoL after stroke is understudied in Africa and there are no reports of quality-adjusted life years after stroke (QALYs) in African countries. We determined the impact of stroke on HRQoL after stroke in Sierra Leone. We calculated QALYs at 1 year post-stroke and determined sociodemographic and clinical variables associated with HRQoL and QALYs in this population. METHODS: A prospective stroke register was established at the two-principal adult tertiary government hospitals in Freetown, Sierra Leone. Participants were followed up at 7, 90 days, and 1 year post-stroke to capture all-cause mortality and EQ-5D-3L data. QALYs were calculated at the patient level using EQ-5D-3L utility values and survival data from the register, following the area under the curve method. Utilities were based on the UK and Zimbabwe (as a sensitivity analysis) EQ-5D value sets, as there is no Sierra Leonean or West African value set. Explanatory models were developed based on previous literature to assess variables associated with HRQoL and QALYs at 1 year after stroke. To address missing values, Multiple Imputation by Chained Equations (MICE), with linear and logistic regression models for continuous and binary variables, respectively, were used. RESULTS: EQ-5D-3L data were available for 373/460 (81.1%), 360/367 (98.1%), and 299/308 (97.1%) participants at 7, 90 days, and 1 year after stroke. For stroke survivors, median EQ-5D-3L utility increased from 0.20 (95% CI: -0.16 to 0.59) at 7 days post-stroke to 0.76 (0.47 to 1.0) at 90 days and remained stable at 1 year 0.76 (0.49 to 1.0). Mean QALYs at 1 year after stroke were 0.28 (SD: 0.35) and closely associated with stroke severity. Older age, lower educational attainment, patients with subarachnoid hemorrhage and undetermined stroke types all had lower QALYs and lower HRQoL, while being the primary breadwinner was associated with higher HRQoL. Sensitivity analysis with the Zimbabwe value set did not significantly change regression results but did influence the absolute values with Zimbabwe utility values being higher, with fewer utility values less than 0. CONCLUSION: We generated QALYs after stroke for the first time in an African country. QALYs were significantly lower than studies from outside Africa, partially explained by the high mortality rate in our cohort. Further research is needed to develop appropriate value sets for West African countries and to examine QALYs lost due to stroke over longer time periods. DATA AVAILABILITY: The Stroke in Sierra Leone anonymized dataset is available on request to researchers, see data access section.

All-cause mortality of hospitalised patients with suspected COVID-19 in Sierra Leone: a prospective cohort study.

OBJECTIVES: To study the mortality of patients with COVID-19 in Sierra Leone, to explore the factors associated with mortality during the COVID-19 pandemic and to highlight the complexities of treating patients with a novel epidemic disease in a fragile health system. STUDY DESIGN: A prospective single-centre cohort study. Data were extracted from paper medical records and transferred onto an electronic database. Specific indicators were compared between survivors and non-survivors, using descriptive statistics in Stata V.17. STUDY SETTING: The infectious diseases unit (IDU) at Connaught Hospital in Freetown, Sierra Leone PARTICIPANTS: Participants were all patients admitted to the IDU between March and July 2020. AIMS OF STUDY: The primary outcome of the study was to examine the all-cause mortality of hospitalised patients with suspected COVID-19 in Sierra Leone and the secondary outcome measures were to examine factors associated with mortality in patients positive for COVID-19. RESULTS: 261 participants were included in the study. Overall, 41.3% of those admitted to the IDU died, compared with prepandemic in-hospital mortality of 23.8%. Factors contributing to the higher mortality were COVID-19 infection (aOR 5.61, 95% CI 1.19 to 26.30, p=0.02) and hypertension (aOR 9.30, 95% CI 1.18 to 73.27, p=0.03) CONCLUSIONS: This study explores the multiple factors underpinning a doubling in facility mortality rate during the COVID-19 pandemic in Sierra Leone . It provides an insight into the realities of providing front-line healthcare during a pandemic in a fragile health system.

Prevalence and predictors of Aspergillus seropositivity and chronic pulmonary aspergillosis in an urban tertiary hospital in Sierra Leone: A cross-sectional study.

BACKGROUND: In the World Health Organization Global Tuberculosis (TB) Report 2022, 37% of pulmonary TB patients were clinically diagnosed and thus many people were treated for TB without evidence of the disease. Probably the most common TB misdiagnosis is chronic pulmonary aspergillosis (CPA). In this study, we aimed to assess the prevalence and predictors of Aspergillus seropositivity and CPA in patients with chronic respiratory symptoms in an urban tertiary hospital in Sierra Leone. METHODOLOGY/PRINCIPAL FINDINGS: We used a cross-sectional study design to recruit adults (≥18 years) from the Chest Clinic of Connaught Hospital, Freetown between November 2021 and July 2022. Aspergillus antibody was detected using LDBio Aspergillus IgM/IgG. Logistic regression was performed to assess the independent predictors of Aspergillus seropositivity and CPA. Of the 197 patients with chronic respiratory symptoms, 147 (74.6%) were male. Mean age was 47.1 ± 16.4 years. More than half (104, 52.8%) had been diagnosed with TB in the past, while 53 (26.9%) were on TB treatment at the time of recruitment. Fifty-two (26.4%) patients were HIV positive, 41 (20.8%) were seropositive for Aspergillus and 23 (11.6%) had CPA, 2 (3.8%) with current TB and 18 (17.3%) with past TB. Common radiologic abnormalities reported were localized fibrotic changes 62 (31.5%), consolidation 54 (27.4%), infiltrates 46 (23.4%), hilar adenopathy 40 (20.3%) and pleural effusion 35 (17.85) and thickening 23 (11.7%). Common symptoms were weight loss 144 (73.1%), cough 135 (68.5%), fever 117 (59.4%) and dyspnea 90 (45.7%). Current or past TB infection {aOR 3.52, 95% CI (1.46, 8.97); p = 0.005} was an independent predictor of Aspergillus seropositivity and CPA. CONCLUSIONS/SIGNIFICANCE: We report a high prevalence of Aspergillus antibody seropositivity and CPA, underscoring the need to integrate the prevention and management of pulmonary fungal infections with TB services and asthma care in order to reduce unnecessary morbidity and mortality.