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Peer reviewedOpen accessMalaria

The effect of mefloquine dose on outcome of uncomplicated falciparum malaria treated with artesunate-mefloquine: a WWARN systematic review and individual patient data meta-analysis

Malaria Journal·

Elizabeth A. Ashley, Emmanuel Baron, Marielle K. Bouyou-Akotet, Rebekah Burrow, Gwenaelle Carn, Verena I. Carrara, Emmanuelle Comets, Chantal Csajka, Umberto D’Alessandro, Nicholas P. Day, Abdoulaye A. Djimde, Arjen Dondorp, Stephan Duparc, MAbul Faiz, Marcelo Urbano Ferreira, Lawrence Fleckenstein, Oumar Gaye, Blaise Genton, Philippe J. Guerin, Eva Maria Hodel, Georgina S. Humphreys, Peter G. Kremsner, Srivicha Krudsood, Simone Ladeia-Andrade, Gilbert Lefèvre, Rashid Mansoor, Mayfong Mayxay, Paul N. Newton, Francois Nosten, Aung Pyae Phyo, Ric N. Price, Sasithon Pukrittayakamee, Michael Ramharter, Ronnatrai Rueangweerayut, Issaka Sagara, Sodiomon B. Sirima, Frank M. Smithuis, Kasia Stepniewska, Walter R. J. Taylor, Innocent Valéa, Neena Valecha, Ingrid V. F. van den Broek, Rob W. van der Pluijm, Michèle van Vugt, Stephen A. Ward, Nicholas J. White

DOI
10.1186/s12936-026-05963-4
PMID
42638106
PMCID
OpenAlex
Study type
Systematic review
Publisher
Springer Science and Business Media LLC
Article type
journal-article
Integrity
current

Why this research matters now

The results indicate that while the regimen remains effective, age-specific tolerability issues may constrain dosing adjustments in young children.

01

Structured evidence summary

Research question

What impact does varying mefloquine dosage have on clinical outcomes and tolerability in patients receiving artesunate-mefloquine therapy?

Study design

The investigation utilizes an individual patient data meta-analysis combined with a systematic review of thirty-one clinical trials.

Population and setting

The cohort comprises 6,761 individuals diagnosed with uncomplicated falciparum malaria, primarily recruited from Asian sites, with a median participant age of eighteen years.

Main findings

Three-day combination therapy achieved low parasite recurrence rates prior to the emergence of drug resistance. Pediatric patients in Asia experienced a substantially greater likelihood of treatment failure than adults, whereas increased mefloquine quantities corresponded to improved outcomes in that region. Gastrointestinal adverse events following administration were most prevalent among children between one and five years old.

Public-health relevance

The results indicate that while the regimen remains effective, age-specific tolerability issues may constrain dosing adjustments in young children.

Important limitations

The dataset aggregates historical trial results gathered before widespread drug resistance developed, potentially reducing contemporary relevance. Geographic representation heavily favors Asian populations, limiting broader extrapolation.

GIDS interpretation

This synthesis consolidates historical trial data into a searchable format, facilitating literature mapping for researchers investigating antimalarial pharmacokinetics and pediatric safety thresholds.

02

Related GIDS surveillance

Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.

03

Evidence relationships

This article has 11 auditable classifier relationships to diseases, places, topics, and study design.

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