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Efficacy and safety of tafenoquine for malaria chemoprophylaxis (1998-2020): A systematic review and meta-analysis


Maier, Julian D; Siegfried, Sandra; Gültekin, Nejla; Stanga, Zeno; Baird, J Kevin; Grobusch, Martin P; Schlagenhauf, Patricia (2021). Efficacy and safety of tafenoquine for malaria chemoprophylaxis (1998-2020): A systematic review and meta-analysis. Travel Medicine and Infectious Disease, 39:101908.

Abstract

BACKGROUND

In 2018, tafenoquine was approved for malaria chemoprophylaxis. We evaluated all available data on the safety and efficacy of tafenoquine chemoprophylaxis.

METHODS

This systematic review followed the PRISMA guidelines and was registered on PROSPERO (CRD42019123839). We searched PubMed, Embase, Scopus, CINAHL and Cochrane databases. Two authors (JDM, PS) screened all papers.

RESULTS

We included 44 papers in the qualitative and 9 in the quantitative analyses. These 9 randomized, controlled trials included 2495 participants, aged 12-60 years with 27.3% women. Six studies were conducted in Plasmodium spp.-endemic regions; two were human infection studies. 200 mg weekly tafenoquine and higher dosages lead to a significant reduction of Plasmodium spp. infection compared to placebo and were comparable to 250 mg mefloquine weekly with a protective efficacy between 77.9 and 100% or a total risk ratio of 0.22 (95%-CI: 0.07-0.73; p = 0.013) in favour of tafenoquine. Adverse events (AE) were comparable in frequency and severity between tafenoquine and comparator arms. One study reported significantly more gastrointestinal events in tafenoquine users (p ≤ 0.001). Evidence of increased, reversible, asymptomatic vortex keratopathy in subjects with prolonged tafenoquine exposures was found. A single, serious event of decreased macular sensitivity occurred.

CONCLUSION

This systematic review and meta-analysis of trials of G6PD-normal adults show that weekly tafenoquine 200 mg is well tolerated and effective as malaria chemoprophylaxis focusing primarily on Plasmodium falciparum but also on Plasmodium vivax. Our safety analysis is limited by heterogenous methods of adverse events reporting. Further research is indicated on the use of tafenoquine in diverse traveller populations.

Abstract

BACKGROUND

In 2018, tafenoquine was approved for malaria chemoprophylaxis. We evaluated all available data on the safety and efficacy of tafenoquine chemoprophylaxis.

METHODS

This systematic review followed the PRISMA guidelines and was registered on PROSPERO (CRD42019123839). We searched PubMed, Embase, Scopus, CINAHL and Cochrane databases. Two authors (JDM, PS) screened all papers.

RESULTS

We included 44 papers in the qualitative and 9 in the quantitative analyses. These 9 randomized, controlled trials included 2495 participants, aged 12-60 years with 27.3% women. Six studies were conducted in Plasmodium spp.-endemic regions; two were human infection studies. 200 mg weekly tafenoquine and higher dosages lead to a significant reduction of Plasmodium spp. infection compared to placebo and were comparable to 250 mg mefloquine weekly with a protective efficacy between 77.9 and 100% or a total risk ratio of 0.22 (95%-CI: 0.07-0.73; p = 0.013) in favour of tafenoquine. Adverse events (AE) were comparable in frequency and severity between tafenoquine and comparator arms. One study reported significantly more gastrointestinal events in tafenoquine users (p ≤ 0.001). Evidence of increased, reversible, asymptomatic vortex keratopathy in subjects with prolonged tafenoquine exposures was found. A single, serious event of decreased macular sensitivity occurred.

CONCLUSION

This systematic review and meta-analysis of trials of G6PD-normal adults show that weekly tafenoquine 200 mg is well tolerated and effective as malaria chemoprophylaxis focusing primarily on Plasmodium falciparum but also on Plasmodium vivax. Our safety analysis is limited by heterogenous methods of adverse events reporting. Further research is indicated on the use of tafenoquine in diverse traveller populations.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Epidemiology, Biostatistics and Prevention Institute (EBPI)
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Public Health, Environmental and Occupational Health
Health Sciences > Infectious Diseases
Language:English
Date:1 January 2021
Deposited On:26 Jan 2021 09:08
Last Modified:24 Jun 2024 01:44
Publisher:Elsevier
ISSN:1477-8939
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.tmaid.2020.101908
PubMed ID:33227500
  • Content: Published Version
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)