Efficacy of a 3-day pre-travel schedule of Tafenoquine for malaria chemoprophylaxis: A network meta-analysis.

BACKGROUND Chemoprophylaxis with weekly doses of tafenoquine (200 mg/day for 3 days before departure [loading dose], 200 mg/week during travel and one-week post-travel [maintenance doses]) is effective in preventing malaria. Effectiveness of malaria chemoprophylaxis drugs in travellers is often compromised by poor compliance. Shorter schedules that can be completed before travel, allowing 'drug-free holidays', could increase compliance and thus reduce travel-related malaria. In this meta-analysis, we examined if a loading dose of tafenoquine alone is effective in preventing malaria in short-term travellers. METHODS Four databases were searched in November 2020 for randomised controlled trials (RCTs) that assessed efficacy and/or safety of tafenoquine for chemoprophylaxis. Network meta-analysis using the generalised pair-wise modelling framework was utilised to estimate the odds ratio (OR) of malaria infection in long-term (>28 days) and short-term (≤28 days) travellers, as well as adverse events (AEs) associated with receiving loading dose of tafenoquine alone, loading dose of tafenoquine followed by maintenance doses, loading dose of mefloquine followed by maintenance doses, or placebo. RESULTS Nine RCTs (1714 participants) were included. In long-term travellers, compared to mefloquine, tafenoquine with maintenance doses (OR = 1.05; 95%CI:0.44-2.46) was equally effective in preventing malaria, while there was an increased risk of infection with the loading dose of tafenoquine alone (OR = 2.89; 95%CI:0.78-10.68) and placebo (OR = 62.91; 95%CI:8.53-463.88). In short-term travellers, loading dose of tafenoquine alone (OR = 0.98; 95%CI:0.04-22.42) and tafenoquine with maintenance doses (OR = 1.00; 95%CI:0.06-16.10) were as effective as mefloquine. The risk of AEs with tafenoquine with maintenance doses (OR = 1.03; 95%CI:0.67-1.60) was similar to mefloquine, while loading dose of tafenoquine alone (OR = 0.58; 95%CI:0.20-1.66) was associated with lower risk of AEs, although the difference was not statistically significant. CONCLUSIONS For short-term travellers, loading dose of tafenoquine alone was equally effective, had possibly lower rate of AEs, and likely better compliance than standard tafenoquine or mefloquine chemoprophylaxis schedules with maintenance doses. Studies are needed to confirm if short-term travellers remain free of infection after long-term follow-up. Registration: The meta-analysis was registered in PROSPERO (CRD42021223756).