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Recent evidence indicates that systemic glucose treatment enhances memory while producing a corresponding increase in hippocampal acetylcholine (ACh) output. The present experiments examined whether unilateral intrahippocampal infusions of glucose would enhance spontaneous alternation performance and whether there would be a corresponding increase in ACh output in the ipsilateral and contralateral hippocampus. Extracellular ACh was assessed in samples collected at 12 min intervals using in vivo microdialysis with HPLC with electrochemical detection. Twelve minutes after a unilateral infusion of artificial cerebrospinal fluid (CSF) or glucose (6.6 mM), rats were tested in a cross maze for spontaneous alternation behavior with concurrent microdialysis collection. In two experiments, glucose infusions significantly increased alternation scores (67.5 and 59%) compared with CSF controls (42.4 and 39.5%, respectively). In both experiments, behavioral testing resulted in increased ACh output in the hippocampus. Glucose administration at the time of alternation tests enhanced ACh output beyond that of behavioral testing alone both ipsilateral (+93.8%) and contralateral (+85%) to the infusion site, as compared with ACh output (+36.1% and +55.5%) of CSF controls. Glucose infusions did not affect hippocampal ACh output in rats kept in a holding chamber. These results suggest that glucose may enhance alternation scores by modulating ACh release. The findings also indicate that unilateral glucose infusions increase hippocampal ACh output both ipsilateral and contralateral to the site of injection. Furthermore, glucose increased ACh output only during maze testing, suggesting that specific behavioral demands, perhaps requiring activation of cholinergic neurons, determine the efficacy of glucose in modulating ACh release.

Globally, national pharmacovigilance systems rely on spontaneous reporting in which suspected adverse drug reactions (ADRs) are reported to a national coordinating centre by health professionals, manufacturers or patients. Spontaneous reporting systems are the easiest to establish and the cheapest to run but suffer from poor-quality reports and underreporting. It is difficult to estimate rates and frequencies of ADRs through spontaneous reporting. Public health programmes need to quantify and characterize risks to individuals and communities from their medicines, to minimize harm and improve use, to sustain public confidence in the programmes, and to track problems due to medication errors and poor quality medicines. Additional methods are therefore needed to monitor the quantitative aspects of medicine safety, to better identify specific risk factors and high-risk groups, and to characterize ADRs associated with specific medicines and in specific populations. The present paper introduces two methods, cohort event monitoring and targeted spontaneous reporting, that are being implemented by the WHO, in its public health programmes, to complement spontaneous reporting. The advantages and disadvantages of these methods and how each can be applied in clinical practice are discussed.

This study has helped identify some of the special challenges and barriers to promoting pharmacovigilance in low- and middle-income countries. A pharmacovigilance strategy in these settings needs to help build health systems that can serve the purpose of multiple health conditions. It needs to identify and implement feasible systems, governance, infrastructures, human resource, training and capacity building, sustainable methodologies and innovations in pharmacovigilance; a key component will be the dissemination of medicines safety information to policy makers and regulators and knowledge sharing with healthcare professionals through high quality informatics and learning tools, with rational use of medicines and patient safety as the ultimate goal of pharmacovigilance.

This study provides a comprehensive review on the methods used in patient reporting of ADRs. Although there are some differences in the way various countries handle patient reports of ADRs, the importance of giving the public the opportunity to report and the additional scientific value of the collected data is widely recognized by the countries who participated in this survey.

Summary Background Seasonal malaria chemoprevention (SMC) aims to prevent malaria in children during the high malaria transmission season. The Achieving Catalytic Expansion of SMC in the Sahel (ACCESS-SMC) project sought to remove barriers to the scale-up of SMC in seven countries in 2015 and 2016. We evaluated the project, including coverage, effectiveness of the intervention, safety, feasibility, drug resistance, and cost-effectiveness. Methods For this observational study, we collected data on the delivery, effectiveness, safety, influence on drug resistance, costs of delivery, impact on malaria incidence and mortality, and cost-effectiveness of SMC, during its administration for 4 months each year (2015 and 2016) to children younger than 5 years, in Burkina Faso, Chad, The Gambia, Guinea, Mali, Niger, and Nigeria. SMC was administered monthly by community health workers who visited door-to-door. Drug administration was monitored via tally sheets and via household cluster-sample coverage surveys. Pharmacovigilance was based on targeted spontaneous reporting and monitoring systems were strengthened. Molecular markers of resistance to sulfadoxine–pyrimethamine and amodiaquine in the general population before and 2 years after SMC introduction was assessed from community surveys. Effectiveness of monthly SMC treatments was measured in case-control studies that compared receipt of SMC between patients with confirmed malaria and neighbourhood-matched community controls eligible to receive SMC. Impact on incidence and mortality was assessed from confirmed outpatient cases, hospital admissions, and deaths associated with malaria, as reported in national health management information systems in Burkina Faso and The Gambia, and from data from selected outpatient facilities (all countries). Provider costs of SMC were estimated from financial costs, costs of health-care staff time, and volunteer opportunity costs, and cost-effectiveness ratios were calculated as the total cost of SMC in each country divided by the predicted number of cases averted. Findings 12 467 933 monthly SMC treatments were administered in 2015 to a target population of 3 650 455 children, and 25 117 480 were administered in 2016 to a target population of 7 551 491. In 2015, among eligible children, mean coverage per month was 76·4% (95% CI 74·0–78·8), and 54·5% children (95% CI 50·4–58·7) received all four treatments. Similar coverage was achieved in 2016 (74·8% [72·2–77·3] treated per month and 53·0% [48·5–57·4] treated four times). In 779 individual case safety reports over 2015–16, 36 serious adverse drug reactions were reported (one child with rash, two with fever, 31 with gastrointestinal disorders, one with extrapyramidal syndrome, and one with Quincke's oedema). No cases of severe skin reactions (Stevens-Johnson or Lyell syndrome) were reported. SMC treatment was associated with a protective effectiveness of 88·2% (95% CI 78·7–93·4) over 28 days in case-c...

IntroductionFollowing the start of the World Health Organization (WHO) Programme for International Drug Monitoring (PIDM) by 10 member countries in 1968, it took another 24 years for the first two African countries to join in 1992, by which time the number of member countries in the PIDM had grown to 33. Whilst pharmacovigilance (PV), including the submission of individual case safety reports (ICSR) to VigiBase®, the WHO global ICSR database, is growing in Africa, no data have been published on the growth of ICSR reporting from Africa and how the features of ICSRs from Africa compare with the rest of the world (RoW).ObjectiveThe objective of this paper was to provide an overview of the growth of national PV centres in Africa, the reporting of ICSRs by African countries, and the features of ICSRs from Africa, and to compare ICSRs from Africa with the RoW.MethodsThe search and analysis interface of VigiBase®—VigiLyze®—was used to characterise ICSRs submitted by African countries and the RoW. The distribution of ICSRs by African countries was listed and characterised by anatomic therapeutic chemical (ATC) code, Medical Dictionary for Regulatory Activities (MedDRA®) system organ class (SOC) classification, and patient age and sex. The case-defining features of ICSRs between Africa and the RoW were also compared.ResultsThe number of African countries in the PIDM increased from 2 in 1992 to 35 at the end of September 2015, and African PIDM members have cumulatively submitted 103,499 ICSRs (0.88 % of global ICSRs) to VigiBase®. The main class of products in African ICSRs are nucleoside and nucleotide reverse transcriptase inhibitors (14.04 %), non-nucleoside reverse transcriptase inhibitors (9.09 %), antivirals for the treatment of HIV infections (5.50 %), combinations of sulfonamides and trimethoprim (2.98 %) and angiotensin-converting enzyme (ACE) inhibitors (2.42 %). The main product classes implicated in ICSRs from the RoW are tumour necrosis factor-α (TNFα) inhibitors (5.29 %), topical nonsteroidal anti-inflammatory preparations (2.26 %), selective immunosuppressants (2.08 %), selective serotonin reuptake inhibitors (2.04 %) and HMG CoA reductase inhibitors (1.85 %). The main SOCs reported from Africa versus the RoW include skin and subcutaneous tissue disorders (31.14 % vs. 19.58 %), general disorders and administration site conditions (20.91 % vs. 30.49 %) and nervous system disorders (17.48 % vs. 19.13 %). The 18–44 years age group dominated ICSRs from Africa, while the 45–64 years age group dominated the RoW. Identical proportions of females (57 % Africa and the RoW) and males (37 % Africa and the RoW) were represented.ConclusionsAs at the end of September 2015, 35 of 54 African countries were Full Member countries of the PIDM. Although the number of ICSRs from Africa has increased substantially, ICSRs from Africa still make up <1 % of the global total in VigiBase®. The features of ICSRs from Africa differ to those from the RoW in relation to the classes of products as well as age group of patients affected. Th...

The thalidomide tragedy in the late 1950s and early 1960s served as a wakeup call and raised questions about the safety of medicinal products. The developed countries rose to the challenge putting in place systems to ensure the safety of medicines. However, this was not the case for low-resource settings because of prevailing factors inherent in them. This paper reviews some of these features and the current status of pharmacovigilance in Africa. The health systems in most of the 54 countries of Africa are essentially weak, lacking in basic infrastructure, personnel, equipment and facilities. The recent mass deployment of medicines to address diseases of public health significance in Africa poses additional challenges to the health system with notable safety concerns. Other safety issues of note include substandard and counterfeit medicines, medication errors and quality of medicinal products. The first national pharmacovigilance centres established in Africa with membership of the World Health Organization (WHO) international drug monitoring programme were in Morocco and South Africa in 1992. Of the 104 full member countries in the programme, there are now 24 African countries with a further nine countries as associate members. The pharmacovigilance systems operational in African countries are based essentially on spontaneous reporting facilitated by the introduction of the new tool Vigiflow. The individual case safety reports committed to the WHO global database (Vigibase) attest to the growth of pharmacovigilance in Africa with the number of reports rising from 2695 in 2000 to over 25,000 in 2010. There is need to engage the various identified challenges of the weak pharmacovigilance systems in the African setting and to focus efforts on how to provide resources, infrastructure and expertise. Raising the level of awareness among healthcare providers, developing training curricula for healthcare professionals, provisions for paediatric and geriatric pharmacovigilance, engaging the pharmaceutical industries as well as those for herbal remedies are of primary concern.