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 andWHO 2009mutation 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 48months. 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.Xunta Galicia-Fondo Social Europeo | Ref. IN606A-2016/023Case Western Reserve University | Ref. NIH NIAID T32 AI07024Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional-FEDER | Ref. RD16/0025/002

Characterizing HIV-1 genetic subtypes and drug resistance mutations among children, adolescents and pregnant women in Sierra Leone

Human immunodeficiency virus (HIV) drug resistance (HIVDR) is widespread in sub-Saharan Africa. Children and pregnant women are particularly vulnerable, and laboratory testing capacity remains limited. We, therefore, used a cross-sectional design and convenience sampling to characterize HIV subtypes and resistance-associated mutations (RAMs) in these groups in Sierra Leone. In total, 96 children (age 2–9 years, 100% ART-experienced), 47 adolescents (age 10–18 years, 100% ART-experienced), and 54 pregnant women (>18 years, 72% ART-experienced) were enrolled. Median treatment durations were 36, 84, and 3 months, respectively, while the sequencing success rates were 45%, 70%, and 59%, respectively, among children, adolescents, and pregnant women. Overall, the predominant HIV-1 subtype was CRF02_AG (87.9%, 95/108), with minority variants constituting 12%. Among children and adolescents, the most common RAMs were M184V (76.6%, n = 49/64), K103N (45.3%, n = 29/64), Y181C/V/I (28.1%, n = 18/64), T215F/Y (25.0%, n = 16/64), and V108I (18.8%, n = 12/64). Among pregnant women, the most frequent RAMs were K103N (20.6%, n = 7/34), M184V (11.8%, n = 4/34), Y181C/V/I (5.9%, n = 2/34), P225H (8.8%, n = 3/34), and K219N/E/Q/R (5.9%, n = 2/34). Protease and integrase inhibitor-RAMs were relatively few or absent. Based on the genotype susceptibility score distributions, 73%, 88%, and 14% of children, adolescents, and pregnant women, respectively, were not susceptible to all three drug components of the WHO preferred first-line regimens per 2018 guidelines. These findings suggest that routine HIVDR surveillance and access to better ART choices may improve treatment outcomes in Sierra Leone.This research was funded by the Roe Green Travel Medicine and Global Health Award 2019 (Award Number J0628), University Hospitals Cleveland Medical Center (G.A.Y.), Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional-FEDER, Red Española de Investigación en SIDA (RD16/0025/0026) (E.P.), Xunta Galicia-Fondo Social Europeo (IN606A-2016/023) (E.P.) and Fundación Biomédica Galicia Sur (E.P.)

How Well Are Hand Hygiene Practices and Promotion Implemented in Sierra Leone? A Cross-Sectional Study in 13 Public Hospitals.

From Europe PMC via Jisc Publications RouterHistory: ppub 2022-03-01, epub 2022-03-23Publication status: PublishedFunder: World Health Organization; Grant(s): 001Healthcare-associated infections (HAIs) result in millions of avoidable deaths or prolonged lengths of stay in hospitals and cause huge economic loss to health systems and communities. Primarily, HAIs spread through the hands of healthcare workers, so improving hand hygiene can reduce their spread. We evaluated hand hygiene practices and promotion across 13 public health hospitals (six secondary and seven tertiary hospitals) in the Western Area of Sierra Leone in a cross-sectional study using the WHO hand hygiene self-Assessment framework in May 2021. The mean score for all hospitals was 273 ± 46, indicating an intermediate level of hand hygiene. Nine hospitals achieved an intermediate level and four a basic level. More secondary hospitals 5 (83%) were at the intermediate level, compared to tertiary hospitals 4 (57%). Tertiary hospitals were poorly rated in the reminders in workplace and institutional safety climate domains but excelled in training and education. Lack of budgets to support hand hygiene implementation is a priority gap underlying this poor performance. These gaps hinder hand hygiene practice and promotion, contributing to the continued spread of HAIs. Enhancing the distribution of hand hygiene resources and encouraging an embedded culture of hand hygiene practice in hospitals will reduce HAIs

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

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

How Well Are Hand Hygiene Practices and Promotion Implemented in Sierra Leone? A Cross-Sectional Study in 13 Public Hospitals

From MDPI via Jisc Publications RouterHistory: accepted 2022-03-17, pub-electronic 2022-03-23Publication status: PublishedHealthcare-associated infections (HAIs) result in millions of avoidable deaths or prolonged lengths of stay in hospitals and cause huge economic loss to health systems and communities. Primarily, HAIs spread through the hands of healthcare workers, so improving hand hygiene can reduce their spread. We evaluated hand hygiene practices and promotion across 13 public health hospitals (six secondary and seven tertiary hospitals) in the Western Area of Sierra Leone in a cross-sectional study using the WHO hand hygiene self-Assessment framework in May 2021. The mean score for all hospitals was 273 ± 46, indicating an intermediate level of hand hygiene. Nine hospitals achieved an intermediate level and four a basic level. More secondary hospitals 5 (83%) were at the intermediate level, compared to tertiary hospitals 4 (57%). Tertiary hospitals were poorly rated in the reminders in workplace and institutional safety climate domains but excelled in training and education. Lack of budgets to support hand hygiene implementation is a priority gap underlying this poor performance. These gaps hinder hand hygiene practice and promotion, contributing to the continued spread of HAIs. Enhancing the distribution of hand hygiene resources and encouraging an embedded culture of hand hygiene practice in hospitals will reduce HAIs

Research on Emerging Infections Offers an Opportunity for Public Health Intelligence on Non-Communicable Diseases: Hypertension Prevalence in Volunteers for an Ebola Vaccine Trial in Northern Sierra Leone

Introduction: The West African Ebola outbreak of 2014–2016 necessitated clinical trials in communities with limited health data. The EBOVAC-Salone Ebola vaccine trial is ongoing in the largely rural Kambia District in northern Sierra Leone. To gain a baseline insight into our local noncommunicable disease (NCD) epidemiology, we examined screening blood pressure (BP) measurements in trial volunteers. Methods: BP involved taking multiple readings using an Omron M6 sphygmomanometer in rested individuals. We classified BP by the European 2018 ESC/ESH guidelines: optimal BP, normal or high-normal BP, or hypertension (systolic ≥ 140 mmHg ± diastolic ≥ 90 mmHg) with Grade 1, 2, or 3 (G1HT, G2HT, G3HT) severity levels. Results: Of 870 volunteers, 220 (25.3%) had optimal BP, 236 (27.13%) had normal BP, and 250 (28.7%) had high-normal BP. The remaining 164 (18.9%) were hypertensive. By gender, 16.5% (109/668) of males and 27.2% (55/202) of females were hypertensive. Among hypertensives, 62.2% had G1HT, 18.3% had G2HT, and 19.5% had G3HT. Twenty-two (13.4%) were previously diagnosed, with eight on treatment. Forty-one had isolated systolic hypertension. The prevalence significantly increased with age (p &lt; 0.0001), with 5.3% (27/514) in the age-category 18–29 y, 18.6% (29/156) in 30–39 y, 49.4% (84/170) in 40–59 y, and 80% (24/30) in ≥60 y. The severity also increased with age, with 54.9% of G1HT, 76.7% of G2HT, and 90.7% of G3HT being aged ≥ 40 y. In total, 36.6% (60/164) of hypertensives were overweight or obese. Discussion: In an economically disadvantaged, Ebola-affected rural West African community where NCD might not traditionally be thought prevalent, almost one in five adults were found to be hypertensive and were mostly unaware. Additionally, nearly one in three had high-normal BP. Together, these findings portend a potent, largely silent, and potentially growing NCD threat, and illustrate that infectious disease (ID) studies could provide opportunities for pragmatic NCD data. As both ID and NCD are putatively promoted by overlapping pro-inflammatory and poverty-driven factors, a cross-paradigmatic “multiplex” approach, whereby ID studies prospectively incorporate NCD-related sub-studies (and vice versa), might optimize limited research resources for enhanced public health benefit

Stroke in Sierra Leone: Case fatality rate and functional outcome after stroke in Freetown

Background: There is limited information on long term outcomes after stroke in Sub-Saharan Africa (SSA). Current estimates of case fatality rate (CFR) in SSA are based on small sample sizes with varying study design and report high heterogeneity. Aims: We report CFR and functional outcomes from a large, prospective, longitudinal cohort of stroke patients in Sierra Leone and describe factors associated with mortality and functional outcome. Methods: A prospective longitudinal stroke register was established at both adult tertiary government hospitals in Freetown, Sierra Leone. It recruited all patients ≥18 years with stroke, using the World Health Organization definition, from May 2019 until October 2021. To reduce selection bias onto the register all investigations were paid by the funder and outreach conducted to raise awareness of the study. Sociodemographic data, National Institute of Health Stroke Scale (NIHSS) and Barthel Index (BI) was collected on all patients on admission, at seven days, 90 days, one year and two years post stroke. Cox proportional-hazards models were constructed to identify factors associated with all-cause mortality. A binomial logistic regression model reports odds ratio (OR) for functional independence at one year. Results: 986 patients with stroke were included, of which 847 (85.9%) received neuroimaging. Follow up rate was 81.5% at one year, missing item data was &lt;1% for most variables. Stroke cases were equally split by sex and mean age was 58.9 (SD: 14.0) years. 625 (63%) were ischaemic, 206 (21%) primary intracerebral haemorrhage, 25 (3%) subarachnoid haemorrhage and 130 (13%) were of undetermined stroke type. Median NIHSS was 16 (9-24). CFR at 30 days, 90 days, 1 year and 2 years was 37.1%, 44.4%, 49.7% and 53.2% respectively. Factors associated with increased fatality were male sex HR:1.28 (1.05-1.56), previous stroke HR:1.34 (1.04-1.71), atrial fibrillation HR:1.58(1.06-2.34), subarachnoid haemorrhage HR:2.31 (1.40-3.81), undetermined stroke type HR: 3.18(2.44-4.14) and in-hospital complications HR: 1.65 (1.36-1.98). 93% of patients were completely independent prior to their stroke, declining to 19% at one year after stroke. Functional improvement was most likely to occur between 7 and 90-days post stroke with 35% patients improving, and 13% improving between 90 days to one year. Increasing age OR: 0.97(0.95-0.99), previous stroke OR: 0.50 (0.26-0.98), NIHSS OR 0.89 (0.86-0.91), undetermined stroke type OR:0.18 (0.05-0.62) and ≥1 in hospital complication OR:0.52 (0.34-0.80) were associated with lower OR of functional independence at one year. Whilst hypertension OR:1.98 (1.14-3.44) and being the primary breadwinner of the household OR:1.59 (1.01-2.49) were associated with functional independence. Discussion: Stroke in Sierra Leone affected younger people, and resulted in high rates of fatality and functional impairment relative to global averages. Key clinical priorities for reducing fatality include preventing stroke-related complications through evidence-based stroke care; improved detection and management of atrial fibrillation, and increasing coverage of secondary prevention. Further research into care pathways and interventions to encourage care seeking for less severe strokes should be prioritized. Data availability: Requests for access to anonymized data for academic use should be made to the SISLE team https://www.kcl.ac.uk/research/stroke

Safety and immunogenicity of an Ad26.ZEBOV booster dose in children previously vaccinated with the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen: an open-label, non-randomised, phase 2 trial.

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 × 1010 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

A prospective stroke register in Sierra Leone: Demographics, stroke type, stroke care and hospital outcomes

Introduction Stroke is the second most common cause of adult death in Africa. This study reports the demographics, stroke types, stroke care and hospital outcomes for stroke in Freetown, Sierra Leone. Methods A prospective observational register recorded all patients 18 years and over with stroke between May 2019 and April 2020. Stroke was defined according to the WHO criteria. Pearson’s chi squared test was used to examine associations between categorical variables and unpaired t-tests for continuous variables. Multivariable logistic regression,to explain in-hospital death, was reported as odds ratios (OR) and 95% confidence intervals. Results 385 strokes were registered, 315 (81.8%) were first in a lifetime events. Mean age was 59.2 (SD 13.8) and 187 (48.6%) were male. 327 (84.9%) of strokes were confirmed by CT scan. 231 (60.0%) were ischaemic, 85 (22.1%) intracerebral haemorrhage, 11 (2.9%) subarachnoid haemorrhage and 58 (15.1%) undetermined stroke type. The median National Institute of Health Stroke Scale on presentation was 17 (IQR 9-25). Haemorrhagic strokes compared to ischaemic strokes were more severe, 20 (IQR 12-26) vs 13 (IQR 7-22) (p<0.001), and occurred in a younger population, mean age 52.3 (SD 12.0) vs 61.6 (SD 13.8) (p<0.001), with a lower level of educational attainment 28.2% vs 40.7% (p=0.04). The median time from stroke onset to arrival at the principal referral hospital was 25 hours (IQR 6-73). Half the patients (50.4%) sought care at another health provider prior to arrival. 151 patients died in hospital (39.5%). 43 deaths occurred within 48 hours of arriving at hospital with median time to death of 4 days (IQR 0-7 days). 49.6% of patients had ≥1 complication, 98 (25.5%) pneumonia, 33 (8.6%) urinary tract infection. Male gender (OR 3.33,1.65 - 6.75), pneumonia (OR 3.75, 1.82 – 7.76), subarachnoid haemorrhage (OR 43.1, 6.70-277.4) and undetermined stroke types (OR 6.35, 2.17– 18.60), were associated with higher risk of in-hospital death. Discussion We observed severe strokes occurring in a young population with high in hospital mortality. Further work to deliver evidence-based stroke care is essential to reduce stroke mortality in Sierra Leone