Malaria is a major public health problem worldwide, particularly in sub-Saharan Africa, where the burden remains highest [1] - [3] . According to the WHO, around 94% of global cases (233 million cases) of malaria and 95% of global deaths (580,000 deaths) due to malaria were recorded in Africa in 2022 [4] .

In Benin, malaria accounted for 21.7% of consultations or pathologies diagnosed in health centers, according to health statistics for 2021. The people most affected were children under 5 and pregnant women. Among infants under one year of age, the overall incidence was 39%, while among children aged 1 to 5 years, the trend was upwards, with an overall incidence of 44% [5] . Malaria remains the main reason for consultation in health services, accounting for 49.5% of cases in children under 5, with a specific death rate of 21.4% [6] .

In order to reduce the burden of malaria, since 2012 the WHO has recommended the chemoprevention of seasonal malaria (SMC) in children under the age of 5 (7). This approach consists of a complete three-day course of treatment with Sulfadoxine pyrimethamine (SP) and Amodiaquine (AQ). The eligible children receive SP on the first day in the presence of a health worker. The next day and on day 3, a child receives AQ from a health worker or community health worker [7] [8] . SMC reduces the number of cases of uncomplicated malaria by at least 80% and severe malaria by 70% [1] [9] [10] .

Benin has started implementing SMC in two health zones in 2019, and the positive results have led to the extension of the intervention to 4 other health zones in 2021. Each year, a mass SMC treatment campaign is organised in the health zones of Malanville-Karimama (MK), Kandi-Gogounou-Ségbana (KGS), Banikoara (BNK), Tanguiéta-Matéri-Cobly (TMC), Natitingou-Boukombé-Toucountouna (NBT), and Kouandé Kérou Péhunco (2KP) [8] [11] .

The fact that dispensing agents did not inquire whether the child had recently been treated for malaria, or whether he or she had previously been allergic to SMC treatment, favored the occurrence of AEs in children targeted by SMC [12] . This often led to cessation [13] or misperception of SMC by the populations, to the detriment of the program, hence the importance of an effective AR monitoring system. However, Benin’s surveillance system, like that of other sub-Saharan African countries, is characterized by low AEs notification rates [14] .

The WHO recommends strengthening or implementing pharmacovigilance in order to detect, understand and prevent any risks associated with the use of SPAQ during SMC, with the aim of supporting the program with reliable efficacy and safety data, and guaranteeing the sustainability of the strategy [15] .

The aim of this study is to describe the AEs reported during SMC and to determine the frequency of discontinuation of SMC administration in children under the age of 5 in 2023.

A total of 3115 children had received at least one dose of SPC out of 3573 included in the study, representing a coverage rate of at least one dose of 87.2%.

SMC campaigns contribute to the increase in AEs reporting in Benin. The prevalence of SMC-related AEs observed in this study was 18.6%, which is consistent with data available in the scientific literature [16] . The AEs presented in this study are mentioned in the summary of product characteristics used for SMC and mentioned in other studies [1] [3] [17] - [20] . Vomiting was the most frequent AE, both in our study and in the literature. Ndiaye et al., in Senegal in 2016 [20] and Ouoba et al. in 2023 in Burkina [18] , also identified vomiting as a common reaction. This similarity may be attributed to amodiaquine, which is known to cause nausea and vomiting. The high prevalence of vomiting suggests that it may be beneficial to explore alternative formulations or administration strategies to reduce this adverse reaction. Fever was the second most frequent adverse reaction in our study. Dicko et al., also reported similar rates of fever, highlighting that this reaction may be due to a normal immune response or a reaction to the drug [17] . Proactive management of side effects, including fever and diarrhea, is essential to improve acceptability and adherence to treatment.

Children in rural areas appear to be more affected by AEs, which could be attributed to environmental and nutritional conditions, which are often less favorable in rural areas and may play a role in increased susceptibility to AEs. Cairns et al., found that malnutrition and micronutrient deficiencies, more common in rural areas, can exacerbate drug side effects [21] . Furthermore, Druetz et al., noted that limited access to health services and medical care in rural areas could delay the detection and management of AEs, thereby increasing their prevalence and severity [22] .

The fact that only 34.8% of children with AEs were referred to a health center may indicate various challenges in the healthcare system. Studies such as that by Druetz et al., in 2015 highlighted that gaps in AEs monitoring and management are common in many parts of sub-Saharan Africa [22] . In rural areas, limited access to healthcare services and adequate infrastructure may explain low referral rates to health center. Families may be reluctant to seek care due to distance, cost or perceived severity of symptoms [21] [23] .

The rate of children whom discontinued SMC due to AEs is relatively low, suggesting that most children and their parents are willing to continue treatment despite the occurrence of minor AEs. This was consistent with the findings of several studies, which have shown that the overall tolerability of SMC is acceptable, and that discontinuations are rare [1] [8] [13] .

The absence of a significant association between the proportion of children discontinuing SMC after vomiting and the proportion discontinuing SMC for other reasons indicates that vomiting is not a primary reason for discontinuation. Studies such as that by Meremikwu et al. have also observed that vomiting, although a common side effect, does not often lead to treatment discontinuation, probably due to the effective management of this symptom by caregivers [19] .

Children referred for treatment at a health center were less likely to discontinue treatment than those who were not treated at a health center. This underlines the importance of appropriate medical management in the management of AEs and the prevention of treatment discontinuation. Researchers have shown that early and appropriate interventions by healthcare professionals can improve adherence to treatment by reducing the perceived severity of AEs [20] [24] . The geographical variation in treatment discontinuation highlights the need for targeted awareness programs to inform communities about AEs management and the importance of treatment continuity. The implementation of continuous monitoring and follow-up systems is crucial to detect and manage AEs rapidly, in order to minimize treatment interruptions.

Although the prevalence of AEs is notable, most children continue SMC despite these effects, underscoring acceptable treatment tolerance. Adequate medical management plays a crucial role in managing AEs and reducing treatment discontinuation. Regional variations in treatment discontinuation highlight the need for targeted interventions to improve access to care and AEs management. By strengthening health systems and raising community awareness, it is possible to improve treatment adherence and maximize the benefits of SMC in children.