Adverse Events Of Atovaquone-Proguanil Compared With Mefloquine as Malaria Chemoprophylaxis Used By Visitors Of Malaria Endemic Country : A Systematic Review And Meta Analysis

Introduction: Chemoprophylaxis plays a crucial role in preventing malaria among travellers to endemic regions. Atovaquone-proguanil and mefloquine are two of the main chemoprophylactic agents recommended by the WHO and CDC to prevent malaria. Both are effective in malaria prophylaxis but are associated with distinct adverse events that can influence their use in travellers. Method: Literature search was conducted in ScienceDirect, and PubMed databases until 2025 without language constraints. Inclusion criteria focused on studies assessed the use of both atovaquone-proguanil and mefloquine as malaria prophylaxis in visitors to malaria-endemic countries. The risk of bias was evaluated using TheNewcastle-Ottawa Scale and Cochrane "RoB" tool. Discussion: A total of 10 studies were included and resulting in 15 categories of adverse events. Reported events were diarrhea (RR 1.07; 95% CI; p = 0.72) mouth ulcers (RR 2.88; 95% CI; p = 0,32), indigestion (RR 1.17; 95% CI; p = 0.80), abdominal pain (RR 1.41; 95% CI; p = 0.10), vomiting & Nausea (RR 0.64; 95% CI; p = 0.16), insomnia (RR 0.25; 95% CI; p = 0.007), dizziness/vertigo (RR 0.41; 95% CI; p = 0.02), tinnitus (RR 0.70, 95% CI; p < 0.00001), anxiety (RR 0.13; 95% CI; p < 0.00001), depression (RR 0.20; 95% CI; p < 0.00001), nightmares (RR 0.18; 95% CI; p = 0.001), headaches (RR 0.47; 95% CI; p = 0.003), dermatological effects (RR 0.89; 95% CI; p = 0.74), eye disorders (RR 0.42; 95% CI; p = 0.02), and a pooled analysis along with events not specifically mentioned (RR 0.38; 95% CI; p = 0.33). Heterogeneity among included studies was generally low to moderate. Conclusion: Practically, mefloquine is suitable for long-term weekly prophylaxis except for those with psychiatric disorders, whereas atovaquone-proguanil is preferred for short-term travel with the recommendation to administer it with food.