Monitoring the safety of Seasonal Malaria Chemoprevention during large scale implementation through the ACCESS-SMC project 2015-16.

By 2014 Seasonal Malaria Chemoprevention (SMC) programmes had started in several countries on a relatively small scale. The UNITAID-funded ACCESS-SMC project (2014-2017), managed by Malaria Consortium with Catholic Relief Services, aimed to overcome barriers to scaling-up SMC, by implementing on a large scale in seven countries and demonstrating the feasibility, safety and effectiveness and cost-effectiveness of the intervention on this scale. The project implemented SMC in Chad, Burkina Faso, Nigeria, Niger, Mali, Guinea and The Gambia. During the first SMC campaign season in 2015, about 12 million treatments were administered to about 3.2 million children. In 2016, this number more than doubled to about 25 million treatments administered to about 6.4 million children. SMC distribution in the areas covered by ACCESS-SMC in 2016 was subsequently continued or expanded in 2017, through funding from the Global Fund and other sources, while the ACCESS-SMC project continued to implement in Chad, Burkina Faso and Nigeria during the 2017 season. By 2017, a total of 12 countries had SMC programmes. The total number of children eligible for SMC in these 12 countries is estimated by the national programmes to be 29.3million, of these the number treated in 2017 was about 15.7million, about 60million doses of sulfadoxine-pyrimethamine plus amodiaquine having been administered in that year. SMC is highly effective against malaria and has been associated with substantial reductions in malaria cases and malaria deaths when it has been introduced. At the start of the ACCESS-SMC project two of the countries had no formal PV system, and the other countries with the exception of Nigeria, had relatively little experience of investigating and reporting adverse drug reactions. To strengthen monitoring of drug safety for the ACCESS-SMC project, a consultation was held between national PV coordinators and malaria control programme managers of all SMC countries to develop the approaches to be used, and training programmes were then organised for pharmacovigilance staff and staff in the national malaria control programme from each country, in collaboration with WHO Special Programme for Research and Training (TDR) and the WHO Safety and Vigilance Department in Geneva, and the WHO Collaborating Centre for Strengthening Pharmacovigilance practices in Rabat, Morocco. PV training was included in the cascade training sessions organised by Malaria Consortium and Catholic Relief Services to train health facility staff and community health workers to administer SMC; job-aids were developed to explain how to recognise the known side-effects of SMC drugs, these were distributed as posters and fliers to health facilities; PV reporting forms were printed and distributed to all public and private health facilities; and a number of strategies were developed to raise awareness about safety monitoring and reporting of adverse events, including sending SMS reminders to health staff in Mali, radio programmes to raise awareness in the community about the importance of reporting drug reactions in The Gambia, and, in Nigeria, training community health workers in administering SMC to children to document adverse events during the previous month. An international committee was convened to review reports of serious adverse events associated with SMC and to provide advice about safety monitoring for SMC, which reported their findings to the WHO Advisory Committee on the Safety of Medicines and Medicinal Products (ACSoMP), the committee which advises WHO on the safety of medicines. As of April 2017, a total of 1721 individual case safety reports (ICSRs) related to SMC treatment up to the end of 2016, had been submitted to Vigibase, the WHOs international drug safety database, and an additional 65 cases were notified to ACCESS-SMC staff. A total of 46 cases were serious (requiring or prolonging hospitalization). Only three cases of severe skin reactions had been reported (two Stevens Johnson syndrome and one Lyell syndrome), six children with extra-pyramidal reactions, and two cases of anaphylactic shock. Of mild and moderate side effects, vomitting was the most common, occurring in from 10 to 50 children per 1000 treated. In the 2017 campaign, one child died, due to suffocation from inhaling SMC medicine following administration when the child was not fully awake. The case was investigated promptly, and the findings communicated to all SMC countries so that mitigation actions could be put in place to avoid such cases in future. A review of SMC safety undertaken by the SMC Safety Committee was presented to ACSoMP in April 2017, who endorsed the activities undertaken to support the safe implementation of SMC concluded that the benefit-risk profile of SMC was positive. However, PV systems need further strengthening, the quality and completeness of reports was variable, and reports were often delayed in reaching the national PV centre. Strategies to simplify and expedite reporting are needed; PV centres need resources to review reports and assess causality; and National technical committees need strengthening to ensure reports are validated.