Organizational capacities of national pharmacovigilance centres in Africa: assessment of resource elements associated with successful and unsuccessful pharmacovigilance experiences.

BACKGROUND: National pharmacovigilance centres (national centres) are gradually gaining visibility as part of the healthcare delivery system in Africa. As does happen in high-income countries, it is assumed that national centres can play a central coordinating role in their national pharmacovigilance (PV) systems. However, there are no studies that have investigated whether national centres in Africa have sufficient organizational capacity to deliver on this mandate and previous studies have reported challenges such as lack of funding, political will and adequate human resources. We conducted interviews with strategic leaders in national centres in 18 African countries, to examine how they link the capacity of their organization to the outcomes of activities coordinated by their centres. Strategic leaders were asked to describe three situations in which activities conducted by their centre were deemed successful and unsuccessful. We analyzed these experiences for common themes and examined whether strategic leaders attributed particular types of resources and relationships with stakeholders to successful or unsuccessful activities. RESULTS: We found that strategic leaders most often attributed successful experiences to the acquisition of political (e.g. legal mandate) or technical (e.g. active surveillance database) resources, while unsuccessful experiences were often attributed to the lack of financial and human resources. Stakeholders that were most often mentioned in association with successful experiences were national government and development partners, whereas national government and public health programmes (PHPs) were often mentioned in unsuccessful experiences. All 18 centres, regardless of maturity of their PV systems had similar challenges. CONCLUSIONS: The study concludes that national centres in Africa are faced with 3 core challenges: (1) over-reliance on development partners, (2) seeming indifference of national governments to provide support after national centres have gained membership of the World Health Organization (WHO) Programme for International Drug Monitoring (PIDM) and (3) engaging public health programmes in a sustainable way.

Assessment of global reporting of adverse drug reactions for anti-malarials, including artemisinin-based combination therapy, to the WHO Programme for International Drug Monitoring.

BACKGROUND: In spite of enhanced control efforts, malaria remains a major public health problem causing close to a million deaths annually. With support from several donors, large amounts of artemisinin-based combination therapy (ACT) are being deployed in endemic countries raising safety concerns as little is known about the use of ACT in several of the settings where they are deployed. This project was undertaken to profile the provenance of the pharmacovigilance reporting of all anti-malarials, including ACT to the WHO adverse drug reaction (ADR) database (Vigibase™) over the past 40 years. METHODS: The WHO Programme for International Drug Monitoring, the Uppsala Monitoring Centre (UMC) provided anonymized extracts of Vigibase™ covering the period 1968-2008. All countries in the programme were clustered according to their malaria control phase and income status. The number of individual case safety reports (ICSRs) of anti-malarials was analyzed according to those clusters. RESULTS: From 1968 to 2008, 21,312 ICSRs suspecting anti-malarials were received from 64 countries. Low-income countries, that are also malaria-endemic (categorized as priority 1 countries) submitted only 1.2% of the ICSRs. Only 60 out of 21,312 ICSRs were related to ACT, 51 of which were coming from four sub-Saharan African countries. Although very few ICSRs involved artemisinin-based compounds, many of the adverse events reported were potentially serious. CONCLUSIONS: This paper illustrates the low reporting of ADRs to anti-malarials in general and ACT in particular. Most reports were submitted by non-endemic and/or high-income countries. Given the current mix of large donor funding, the insufficient information on safety of these drugs, increasing availability of ACT and artemisinin-based monotherapies in public and private sector channels, associated potential for inappropriate use and finally a pipeline of more than 10 new novel anti-malarials in various stages of development, the presence of well functioning national pharmacovigilance systems is vital to ensure safe and responsible scale up of ACT deployment. Bringing together the competencies of national pharmacovigilance centres and various types of organizations in the NGO, academic and private sectors with global coordination to create short- and long-term solutions may help address the lag between rapidly growing ACT use and poor ADR reporting.

Realities of paediatric pharmacotherapy in the developing world.

Diseases causing high mortality in children under 5 years of age in resource limited settings (RLS) could be treated if children in these countries had access to existing medicines. It took 30 years before the WHO Essential Medicines List (EML) considered the issue of medicines for children, with the first EML for children being published in 2007. Recent data indicate that less than half of the key paediatric essential medicines are available in countries of sub-Saharan Africa. Problems include substandard medicines, irrational use of medicines, inefficiency and even possible corruption in pharmaceutical management systems. These are global issues which affect RLS most. Clinical trials in developing countries for the benefit of children are needed but challenging in several ways. In this review, the authors will consider the following areas where progress could improve paediatric pharmacotherapy in RLS: registration and regulation of medicines, rational use of medicines, clinical trials in children and restriction of corruption in pharmaceutical management systems.

Fatal cardiotoxicity related to halofantrine: a review based on a worldwide safety data base.

BACKGROUND: Halofantrine (HF) was considered an effective and safe treatment for multi-drug resistant falciparum malaria until 1993, when the first case of drug-associated death was reported. Since then, numerous studies have confirmed cardiac arrythmias, possibly fatal, in both adults and children. The aim of the study was to review fatal HF related cardiotoxicity. METHODS: In addition, to a systematic review of the literature, the authors have had access to the global safety database on possible HF related cardiotoxicity provided by GlaxoSmithKline. RESULTS: Thirty-five cases of fatal cardiotoxicity related to HF, including five children, were identified. Females (70%) and patients from developing countries (71%) were over-represented in this series. Seventy-four percent of the fatal events occurred within 24 hours of initial exposure to HF. Twenty six patients (74%) had at least one predisposing factor for severe cardiotoxicity, e.g., underlying cardiac disease, higher than recommended doses, or presence of a concomitant QT-lengthening drug. All (100%) of the paediatric cases had either a contraindication to HF or an improper dose was given. In six cases there was no malaria. CONCLUSION: A distinction should be made between common but asymptomatic QT-interval prolongation and the much less common ventricular arrhythmias, such as torsades de pointes, which can be fatal and seem to occur in a very limited number of patients. The majority of reported cardiac events occurred either in patients with predisposing factors or with an improper dose.Therefore, in the rare situations in which HF is the only therapeutic option, it can still be given after carefully checking for contraindications, such as underlying cardiac disease, bradycardia, metabolic disorders, personal or family history of long QT-interval or concomitant use of another QT-prolonging drug (e.g., mefloquine), especially in females.

Self-reported use of anti-malarial drugs and health facility management of malaria in Ghana.

OBJECTIVE: To assess the appropriateness of self-reported use of anti-malarial drugs prior to health facility attendance, and the management of malaria in two health facilities in Ghana. METHOD: A structured questionnaire was used to collect data from 500 respondents who were diagnosed clinically and/or parasitologically for malaria at Agogo Presbyterian Hospital and Suntreso Polyclinic, both in the Ashanti Region of Ghana. Collected information included previous use of anti-malarial drugs prior to attending the health facilities, types of drugs used, how the drugs were used, and the sources of the drugs. In addition, the anti-malarial therapy given and outcomes at the two health facilities were assessed. RESULTS: Of the 500 patients interviewed, 17% had severe malaria, 8% had moderate to severe malaria and 75% had uncomplicated malaria. Forty three percent of the respondents had taken anti-malarial drugs within two weeks prior to hospital attendance. The most commonly used anti-malarials were chloroquine (76%), sulphadoxine-pyrimethamine (9%), herbal preparations (9%) and amodiaquine (6%). The sources of these medicines were licensed chemical sellers (50%), pharmacies (21%), neighbouring clinics (9%) or "other" sources (20%) including left-over medicines at home. One hundred and sixty three (77%) of the 213 patients who had used anti-malarial drugs prior to attending the health facilities, used the drugs inappropriately. At the health facilities, the anti-malarials were prescribed and used according to the national standard treatment guidelines with good outcomes. CONCLUSION: Prevalence of inappropriate use of anti-malarials in the community in Ghana is high. There is need for enhanced public health education on home-based management of malaria and training for workers in medicine supply outlets to ensure effective use of anti-malaria drugs in the country.

A global perspective on vaccine safety and public health: the Global Advisory Committee on Vaccine Safety.

Established in 1999, the Global Advisory Committee on Vaccine Safety advises the World Health Organization (WHO) on vaccine-related safety issues and enables WHO to respond promptly, efficiently, and with scientific rigor to issues of vaccine safety with potential global importance. The committee also assesses the implications of vaccine safety for practice worldwide and for WHO policies. We describe the principles on which the committee was established, its modus operandi, and the scope of the work undertaken, both present and future. We highlight its recent recommendations on major issues, including the purported link between the measles-mumps-rubella vaccine and autism and the safety of the mumps, influenza, yellow fever, BCG, and smallpox vaccines as well as that of thiomersal-containing vaccines.