• Nazmul Islam, Sophie Wright, Colleen L Lau, DoiSuhail A RSARDepartment of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, PO BOX 2713, Qatar., Deborah J Mills, Justin Clark, ClementsArchie C AACAFaculty of Health Sciences, Curtin University, Perth, WA 6102, Australia., and Luis Furuya-Kanamori.
• Department of Public Health, College of Health Sciences, QU Health, Qatar University, Doha, PO BOX 2713, Qatar.
• J Travel Med. 2021 Jul 7; 28 (5).

BackgroundChemoprophylaxis with weekly doses of tafenoquine (200 mg/day for 3 days before departure [loading dose], 200 mg/week during travel and 1-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.MethodsFour databases were searched in November 2020 for randomized controlled trials (RCTs) that assessed efficacy and/or safety of tafenoquine for chemoprophylaxis. Network meta-analysis using the generalized pair-wise modelling framework was utilized 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.ResultsNine RCTs (1714 participants) were included. In long-term travellers, compared to mefloquine, tafenoquine with maintenance doses (OR = 1.05; 95% confidence interval [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.ConclusionsFor 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.RegistrationThe meta-analysis was registered in PROSPERO (CRD42021223756).HighlightTafenoquine is the latest approved drug for malaria chemoprophylaxis. A loading dose of tafenoquine (200 mg/day for 3 days before departure) is as effective in preventing malaria in short-term (≤28 days) travellers as chemoprophylaxis schedules of tafenoquine or mefloquine with maintenance doses, allowing travellers to have a 'drug-free holiday'.© International Society of Travel Medicine 2021. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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