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.)

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

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

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

Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in children in Sierra Leone: a randomised, double-blind, controlled trial

Background—Children account for a substantial proportion of cases and deaths from Ebola virus disease. We aimed to assess the safety and immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vectorbased vaccine, encoding glycoproteins from the Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in a paediatric population in Sierra Leone. Methods—This randomised, double-blind, controlled trial was done at three clinics in Kambia district, Sierra Leone. Healthy children and adolescents aged 1–17 years were enrolled in three age cohorts (12–17 years, 4–11 years, and 1–3 years) and randomly assigned (3:1), via computer-generated block randomisation (block size of eight), to receive an intramuscular injection of either Ad26.ZEBOV (5 × 1010 viral particles; first dose) followed by MVA-BN-Filo (1 × 108 infectious units; second dose) on day 57 (Ebola vaccine group), or a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo (second dose) on day 57 (control group). Study team personnel (except for those with primary responsibility for study vaccine preparation), participants, and their parents or guardians were masked to study vaccine allocation. The primary outcome was safety, measured as the occurrence of solicited local and systemic adverse symptoms during 7 days after each vaccination, unsolicited systemic adverse events during 28 days after each vaccination, abnormal laboratory results during the study period, and serious adverse events or immediate reportable events throughout the study period. The secondary outcome was immunogenicity (humoral immune response), measured as the concentration of Ebola virus glycoprotein-specific binding antibodies at 21 days after the second dose. The primary outcome was assessed in all participants who had received at least one dose of study vaccine and had available reactogenicity data, and immunogenicity was assessed in all participants who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response. This study is registered at ClinicalTrials.gov, NCT02509494. Findings—From April 4, 2017, to July 5, 2018, 576 eligible children or adolescents (192 in each of the three age cohorts) were enrolled and randomly assigned. The most common solicited local adverse event during the 7 days after the first and second dose was injection-site pain in all age groups, with frequencies ranging from 0% (none of 48) of children aged 1–3 years after placebo injection to 21% (30 of 144) of children aged 4–11 years after Ad26.ZEBOV vaccination. The most frequently observed solicited systemic adverse event during the 7 days was headache in the 12–17 years and 4–11 years age cohorts after the first and second dose, and pyrexia in the 1–3 years age cohort after the first and second dose. The most frequent unsolicited adverse event after the first and second dose vaccinations was malaria in all age cohorts, irrespective of the vaccine types. Following vaccination with MenACWY, severe thrombocytopaenia was observed in one participant aged 3 years. No other clinically significant laboratory abnormalities were observed in other study participants, and no serious adverse events related to the Ebola vaccine regimen were reported. There were no treatment-related deaths. Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second dose of the Ebola virus vaccine regimen were observed in 131 (98%) of 134 children aged 12–17 years (9929 ELISA units [EU]/mL [95% CI 8172–12 064]), in 119 (99%) of 120 aged 4–11 years (10 212 EU/mL [8419–12 388]), and in 118 (98%) of 121 aged 1–3 years (22 568 EU/mL [18 426–27 642]). Interpretation—The Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen was well tolerated with no safety concerns in children aged 1–17 years, and induced robust humoral immune responses, suggesting suitability of this regimen for Ebola virus disease prophylaxis in children

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.</p

Impact of COVID-19 on Tuberculosis Case Detection and Treatment Outcomes in Sierra Leone

The COVID-19 pandemic has adversely affected tuberculosis (TB) care delivery in high burden countries. We therefore conducted a retrospective study to assess the impact of COVID-19 on TB case detection and treatment outcomes at the Chest Clinic at Connaught Hospital in Freetown, Sierra Leone. Overall, 2300 presumptive cases were tested during the first three quarters of 2020 (intra-COVID-19) versus 2636 in 2019 (baseline), representing a 12.7% decline. Testing declined by 25% in women, 20% in children and 81% in community-initiated referrals. Notwithstanding, laboratory-confirmed TB cases increased by 37.0% and treatment success rate was higher in 2020 (55.6% vs. 46.7%, p = 0.002). Multivariate logistic regression analysis found that age &lt; 55 years (aOR 1.74, 95% CI (1.80, 2.56); p = 0.005), new diagnosis (aOR 1.69, 95% CI (1.16, 2.47); p = 0.007), pulmonary TB (aOR 3.17, 95% CI (1.67, 6.04); p &lt; 0.001), HIV negative status (aOR 1.60, 95%CI (1.24, 2.06); p &lt; 0.001) and self-administration of anti-TB drugs through monthly dispensing versus directly observed therapy (DOT) (aOR 1.56, 95% CI (1.21, 2.03); p = 0.001) independently predicted treatment success. These findings may have policy implications for DOTS in this setting and suggest that more resources are needed to reverse the negative impact of the COVID-19 pandemic on TB program activities in Sierra Leone

Hepatitis B Virus and Tuberculosis Are Associated with Increased Noncommunicable Disease Risk among Treatment-Naïve People with HIV: Opportunities for Prevention, Early Detection and Management of Comorbidities in Sierra Leone

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