Adverse Events Following Immunization with Novel Oral Polio Vaccine Type 2, and the Experience and Challenges of Reporting in Sierra Leone.

Background: The manifestation and spread of neuroinvasive circulating vaccine-derived polioviruses (cVDPVs) across several countries, which led to the emergency use of the novel oral polio vaccine type 2 (nOPV2), raised concerns about adverse events following immunization (AEFI) surveillance. We assessed the attributes of AEFI with nOPV2 and examined stakeholder experiences and challenges in AEFI surveillance in Sierra Leone. Methods: Using a mixed method approach, we retrospectively reviewed passive data collected during a 2021 immunization campaign, and conducted semi-structured, interviews with vaccinators, district AEFI focal persons, and key stakeholders at the national Expanded Program on Immunization and the National Medicines Regulatory Authority. AEFI were categorized using the Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms (PTs) and System Organ Class (SOC). Outcomes were stratified as recovered or not, with preventability and causality assessed using the Schumock and Thornton and World Health Organization (WHO) algorithms, respectively. Results: A total of 528 suspected AEFI were documented, predominantly affecting children aged 28 days to 23 months (63.3%). Most reported AEFI were administration site conditions and general disorders, with pyrexia being the predominant PT. Of 80 serious cases, 78 recovered, with 74 having an inconsistent causal relationship with the vaccine. Most serious cases (78) were deemed non-preventable, with only two being probably preventable. AEFI reporting was not routinely carried out across the group of people interviewed. AEFI reporting was not consistently performed, with discrepancies in defining reportable events and confusion over responsibility. Challenges with the open data kit (ODK) platform were noted, along with perceived inadequacies in training. Conclusion: While the nOPV2 is relatively new, the majority of AEFI were not serious, and most serious cases were not causally linked to the vaccine. Participants exhibited variations in experience and awareness of AEFI reporting.

An Assessment of Medication Errors Among Pediatric Patients in Three Hospitals in Freetown Sierra Leone: Findings and Implications for a Low-Income Country.

Background: Pediatric patients are prone to medicine-related problems like medication errors (MEs), which can potentially cause harm. Yet, this has not been studied in this population in Sierra Leone. Therefore, this study investigated the prevalence and nature of MEs, including potential drug-drug interactions (pDDIs), in pediatric patients. Methods: The study was conducted in three hospitals among pediatric patients in Freetown and consisted of two phases. Phase one was a cross-sectional retrospective review of prescriptions for completeness and accuracy based on the global accuracy score against standard prescription writing guidelines. Phase two was a point prevalence inpatient chart review of MEs categorized into prescription, administration, and dispensing errors and pDDIs. Data was analyzed using frequency, percentages, median, and interquartile range. Kruskal-Wallis H and Mann-Whitney U-tests were used to compare the prescription accuracy between the hospitals, with p<0.05 considered statistically significant. Results: Three hundred and sixty-six (366) pediatric prescriptions and 132 inpatient charts were reviewed in phases one and two of the study, respectively. In phase one, while no prescription attained the global accuracy score (GAS) gold standard of 100%, 106 (29.0%) achieved the 80-100% mark. The patient 63 (17.2%), treatment 228 (62.3%), and prescriber 33 (9.0%) identifiers achieved an overall GAS range of 80-100%. Although the total GAS was not statistically significant (p=0.065), the date (p=0.041), patient (p=<0.001), treatment (p=0.022), and prescriber (p=<0.001) identifiers were statistically significant across the different hospitals. For phase two, the prevalence of MEs was 74 (56.1%), while that of pDDIs was 54 (40.9%). There was a statistically positive correlation between the occurrence of pDDI and number of medicines prescribed (r=0.211, P=0.015). Conclusion: A Low GAS indicates poor compliance with prescription writing guidelines and high prescription errors. Medication errors were observed at each phase of the medication use cycle, while clinically significant pDDIs were also reported. Thus, there is a need for training on prescription writing guidelines and medication errors.

Antibiotic use among hospitalised patients in Sierra Leone: a national point prevalence survey using the WHO survey methodology.

OBJECTIVE: Inappropriate use of antibiotics is a major driver of antibiotic resistance. A few studies conducted in Africa have documented that about half of hospitalised patients who receive antibiotics should not have received them. A few hospital-based studies that have been conducted in Sierra Leone have documented a high usage of antibiotics in hospitals. Therefore, we conducted a nationwide point prevalence survey on antibiotic use among hospitalised patients in Sierra Leone. DESIGN: We conducted a hospital-based, cross-sectional survey on the use of antibiotics using the WHO point prevalence survey methodology. SETTING: The study was conducted in 26 public and private hospitals that are providing inpatient healthcare services. PARTICIPANTS: All patients admitted to paediatric and adult inpatient wards before or at 08:00 on the survey date were enrolled. OUTCOME MEASURES: Prevalence of antibiotic use, antibiotics Access, Watch and Reserve (AWaRe) categorisation, indication for antibiotic use prevalence and proportion of bacteria culture done. RESULTS: Of the 1198 patient records reviewed, 883 (73.7%, 95% CI 71.1% to 76.2%) were on antibiotics. Antibiotic use was highest in the paediatric wards (306, 85.7%), followed by medical wards (158, 71.2%), surgical wards (146, 69.5%), mixed wards (97, 68.8%) and lowest in the obstetrics and gynaecology wards (176, 65.7%). The most widely prescribed antibiotics were metronidazole (404, 22.2%), ceftriaxone (373, 20.5%), ampicillin (337, 18.5%), gentamicin (221, 12.1%) and amoxicillin (90, 5.0%). Blood culture was only done for one patient and antibiotic treatments were given empirically. The most common indication for antibiotic use was community-acquired infection (484, 51.9%) followed by surgical prophylaxis (222, 23.8%). CONCLUSION: There was high usage of antibiotics in hospitals in Sierra Leone as the majority of patients admitted received an antibiotic. This has the potential to increase the burden of antibiotic resistance in the country. We, therefore, recommend the establishment of hospital antimicrobial stewardship programmes according to the WHO core components.

Quality of Reporting of Adverse Drug Reactions to Antimicrobials Improved Following Operational Research: A before-and-after Study in Sierra Leone (2017-2023).

Background: The quality of pharmacovigilance data is important for guiding medicine safety and clinical practice. In baseline and follow-up studies after introducing interventions to improve the quality of reporting of Individual Case Safety Reports (ICSRs) in Sierra Leone, we compared (a) timeliness and completeness of reporting and (b) patient outcomes classified as 'recovering'. Methods: Baseline (January 2017-December 2021) and follow-up (June 2022-April 2023) studies of ICSRs in the national pharmacovigilance database. Interventions introduced following recommendations from the baseline study included: updating standard operating procedures and guidelines, setting performance targets follow-up of patient outcomes, and training. Results: There were 566 ICSRs in the baseline study and 59 in the follow-up study. Timelines (reporting < 30 days) improved by five-fold (10% at baseline to 47% in follow-up). For the completeness of variables in ICSRs (desired threshold ≥ 90%),this was 44% at baseline and increased to 80% in the follow-up study. 'Recovering' outcomes reduced from 36% (baseline study) to 3% (follow-up study, p < 0.001). Conclusions: Significant improvements in timeliness, completeness, and validation of ICSRs were observed following operational research in Sierra Leone. While enhancing pharmacovigilance and patient safety, this study highlights the important synergistic role operational research can play in improving monitoring and evaluation systems.

Antibiotic use and consumption in Freetown, Sierra Leone: A baseline report of prescription stewardship in outpatient clinics of three tertiary hospitals.

Objective: As there are no country-representative data on bacterial sensitivities to guide antimicrobial stewardship (AMS) interventions, an AMS programme was established in the outpatient clinics of three tertiary hospitals in Freetown, Sierra Leone. Methods: The study employed a cross-sectional design to collect antibiotic prescribing data from 370 pregnant women and lactating mothers, 314 children and 229 regular patients in the outpatient clinics of the Princess Christian Maternity Hospital (PCMH), Ola During Children's Hospital and Connaught Hospital (CH), respectively, in April 2022. All data were analysed using Stata Version 16. Results: Of 913 patients, most were female (n=635, 69.5%), treated at PCMH (n=370, 40.5%) and had a bacterial infection (n=661, 72.4%). The indication for prescribing antibiotics was inappropriate in 252 (27.6%) patients. Of the 1236 prescriptions, 393 (31.8%) were made at CH. The duration of antibiotic use was not stated in 230 (18.6%) prescriptions. Overall antibiotic consumption was 55.3 defined daily doses per 1000 outpatient-days. Conclusion: Gaps in antibiotic prescriptions were identified in the outpatient clinics of three national referral hospitals in Sierra Leone. In order to combat antimicrobial resistance, AMS interventions are needed to reduce the prescription of antibiotics for inappropriate indications or without specified duration.

Regulating clinical trials in a resource-limited setting during the Ebola public health emergency in Sierra Leone.

Clinical trials during public health emergencies of novel medical products such as therapeutics and vaccines in resource-limited settings are daunting due to the limited capacity for regulatory assessment. Regulating clinical trials during the Ebola outbreak in Sierra Leone required expedited evaluation to identify medical products that could be promptly introduced to combat the epidemic in the absence of approved treatment or prevention. This article explored the decisions taken by the Pharmacy Board of Sierra Leone through its Expert Committee on Medicine Safety and Clinical Trials regarding clinical trials oversight during the Ebola epidemic and the lessons learned. This independent expert committee assessed and provided scientific opinions to the Pharmacy Board of Sierra Leone to inform approval of all clinical trials within 10-15 working days. We also requested for assisted review from the African Vaccine Regulatory Forum and support from the US Food and Drug Administration through a unilateral recognition and reliance memorandum of understanding. In addition, the Agency-ensured structures and systems were in place for reporting and reviewing adverse events and serious adverse events, management of biological samples, submission and review of progress reports, and good clinical practice inspections. Unfortunately, the Ebola epidemic revealed many weaknesses in the country's clinical trials regulatory structure and processes. Government and partners should further offer more resources to build the clinical trial structures and systems so that the Agency will be better poised to handle future public health emergencies.

Leveraging WHO's Global Benchmarking Tool to strengthen capacity in clinical trials oversight for public health emergencies: the GHPP VaccTrain model.

BACKGROUND: A stable, well-functioning and integrated national medicines regulatory system is a core component of health systems resilient against infectious disease outbreaks. In many low- and middle-income countries, however, sizable gaps exist in the emergency preparedness framework of national regulatory authorities (NRAs). RegTrain-VaccTrain is a project of Germany Ministry of Health's Global Health Protection Programme that contributes to global efforts aimed at strengthening such regulatory systems by providing technical support and advice to partner NRAs. In this study, we probed the outputs of our capacity-strengthening activities for clinical trials oversight (CTO) to take stock of progress made and examine remaining priorities in order to provide specialized technical assistance in addressing them to improve operational readiness for emergencies. METHOD: Data validated from NRA self-benchmarking results in 2017 and worksheet records of November 2021 were utilized to assess the emergency preparedness capacity for CTO in three VaccTrain partner NRAs (Liberia, Sierra Leone, The Gambia) before and after interventional capacity-strengthening partnership, using specific public health emergency-related (sub-)indicators of the WHO Global Benchmarking Tool. RESULTS: A generally weak and vulnerable structural framework for CTO characterized the emergency preparedness capacity in all three partner NRAs at baseline, thus putting their operational readiness for public health emergencies at risk. VaccTrain's collaborative work was successful at supporting individual NRAs to develop the full spectrum of operational structures (including (draft) regulations, guidelines, and standard operating procedures) required to improve regulatory preparedness. A gap in the formal approval and implementation of developed legal documents in two of three NRAs still remains. Notwithstanding, a robust emergency framework now exists and the NRAs stand better prepared to respond to (future) locally-concerning health emergencies, during which time clinical trials activity was observed to heighten. CONCLUSIONS: These results exemplify a north-south capacity-strengthening partnership model that effectively contributes in developing structures to enhance regulatory oversight and support expeditious product development in response to crises. They further underscore the equally critical role local/national processes play in facilitating the full implementation of developed structures.

Inconsistent Country-Wide Reporting of Adverse Drug Reactions to Antimicrobials in Sierra Leone (2017-2021): A Wake-Up Call to Improve Reporting.

Background: Monitoring of adverse drug reactions (ADRs) to antimicrobials is important, as they can cause life-threatening illness, permanent disabilities, and death. We assessed country-wide ADR reporting on antimicrobials and their outcomes. Methods: A cross-sectional study was conducted using individual case safety reports (ICSRs) entered into the national pharmacovigilance database (VigiFlow) during 2017−2021. Results: Of 566 ICSRs, inconsistent reporting was seen, with the highest reporting in 2017 and 2019 (mass drug campaigns for deworming), zero reporting in 2018 (reasons unknown), and only a handful in 2020 and 2021 (since COVID-19). Of 566 ICSRs, 90% were for antiparasitics (actively reported during mass campaigns), while the rest (passive reporting from health facilities) included 8% antibiotics, 7% antivirals, and 0.2% antifungals. In total, 90% of the reports took >30 days to be entered (median = 165; range 2−420 days), while 44% had <75% of all variables filled in (desired target = 100%). There were 10 serious ADRs, 18 drug withdrawals, and 60% of ADRs affected the gastrointestinal system. The patient outcomes (N-566) were: recovered (59.5%), recovering (35.5%), not recovered (1.4%), death (0.2%), and unknown (3.4%). There was no final ascertainment of 'recovering' outcomes. Conclusions: ADR reporting is inconsistent, with delays and incomplete data. This is a wake-up call for introducing active reporting and setting performance targets.

Pharmacovigilance systems in resource-limited settings: an evaluative case study of Sierra Leone.

Few low and middle-income countries (LMIC) have fully operational pharmacovigilance structures, systems and legal framework to collect and collate safety data and evaluate the risks and benefits by active and passive approaches. However, in a LMIC such as Sierra Leone, the capacity to manage the risks by taking appropriate preventative actions to help inform therapeutic decisions, promote rational use of medicines, guide risk management and communications is gradually growing but yet to be fully optimized. This study sought to assess the current status of pharmacovigilance in Sierra Leone since it became the 87th member of the World Health Organisation International Drug Monitoring Programme. This study evaluated the pharmacovigilance system in Sierra Leone through a comprehensive and system-based approach that covered the national medicines regulatory authority, health facilities and public health programmes. A descriptive cross-sectional study design was employed. Using a convenience sampling method, 14 respondents from the national medicines regulatory authority, six health facilities and six public health programmes were interviewed. Data were collected using a validated metric instrument: Indicator-Based Pharmacovigilance Assessment Tool. A scoring system was used for the quantification of assessment results with a score greater than 60% indicating that an organization has structural and policy frameworks to collect and collate safety data in a national database and evaluate the risks and benefits by both active and passive approaches. The study findings showed that the national medicines regulatory authority scored 79% and thus met the standard requirements of pharmacovigilance. On the other hand, the health facilities and public health programmes scored less than 60% indicating the need to fully operationalise pharmacovigilance frameworks at these levels. The study further demonstrated that the national medicine regulatory authority which hosts the national pharmacovigilance centre had functional pharmacovigilance structures and processes with potential to providing leadership in the implementation of pharmacovigilance in Sierra Leone.

Antinutritional factors, toxic elements and phytochemicals present in jatropha curcas fruits, kernels, seeds and ethanol seed extract

Jatropha curcas (J. curcas) seeds have been exploited as a source of biodiesel and for its ethnomedicinal uses and agro feed potential, however, toxic properties have been associated with the seeds. The study was aimed at determining the toxic constituents present in J. curcas fruits, seeds and kernels and ethanol seed extract. Standard methods were employed in the investigations, including those of the Association of Analytical Chemists and Trease and Evans. J. curcas fruits, seeds and kernels from Sierra Leone contained cyanogenic glycosides (in mg/100g) of 7.10, 5.10 and 16.96 while the corresponding values for the Nigeria samples were 11.60, 10.15 and 15.92; all greatly above the maximum permissible limits of 0.05-0.35. Similarly, the tannin contents of the fruits, seeds and kernels from Sierra Leone (1.66, 1.46, and 1.80) and of the seeds and kernels from Nigeria (1.40, 1.48) approximated the maximum permissible limits of 1.5 mg/100g or were higher. In contrast, the phytates and saponins which ranged from 1.78-2.14 and 1.64-2.42 for both sources of J. curcas were significantly below the maximum permissible levels of 500 mg/100g (for phytates) and 100 mg/100g (for saponins). Heavy metals like cadmium, copper, chromium and lead were also detected, but their concentrations were below the maximum permissible limits. These constituents were mostly similar regardless of the country source of Jatropha. Ethanol extract of J. curcas seeds was found to contain toxic phytochemicals and heavy metals. J. curcas as food cannot be ruled out especially for animals since cooking, fermentation and heat treatment can significantly reduce some of these antinutritional factors