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BRIEF RESEARCH REPORT article

Front. Trop. Dis
Sec. Major Tropical Diseases
Volume 5 - 2024 | doi: 10.3389/fitd.2024.1454252

Efficacy of Artesunate-Mefloquine Combination Therapy on Survival in Plasmodium berghei-Infected Mice: A Time-To-Event Analysis

Provisionally accepted
Valdeene Vieira Santos Valdeene Vieira Santos 1,2Laiz Campos Pereira Laiz Campos Pereira 1,2Aline L. dos Santos Miranda Aline L. dos Santos Miranda 2Helenita Quadros Helenita Quadros 3Diogo Magalhães Moreira Diogo Magalhães Moreira 2Francine Johansson Azeredo Francine Johansson Azeredo 4*
  • 1 Faculty of Pharmacy, Federal University of Bahia (UFBA), Salvador, Bahia, Brazil
  • 2 Gonçalo Moniz Institute (IGM), Salvador, Bahia, Brazil
  • 3 Independent researcher, Juazeiro, Brazil
  • 4 Center for Pharmacometrics & Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, United States

The final, formatted version of the article will be published soon.

    Artesunate-mefloquine combination therapy (AR-MQ) is a standard therapy for treating uncomplicated malaria by Plasmodium falciparum. Time-to-event (TTE) analysis is used to describe the occurrence and timing of events by yielding information about the risk of an event occurring during a specific period. Therefore, the aim of the present study is to evaluate the efficacy of AR-MQ combination therapy on the survival time of Plasmodium berghei-infected mice using TTE analysis. Here, TTE analysis was used to analyze P. berghei-infected mice receiving a single oral dose of 100 mg/kg artesunate and 55 mg/kg mefloquine or dose-matched artesunate monotherapy. Median survival was higher for AR-MQ than for monotherapy. A survival analysis to evaluate the influence of treatment on survival was performed using MonolixSuite™. The Weibull model best described the mortality time of the animals. Subsequent analysis identified that AR-MQ had a significant influence on population survival time (Te_pop), estimated at 13.66 days, population parameter for curve fitting (p_pop) at 4.39, and survival time under AR-MQ treatment (beta Te_AR-MQ) at 0.77 days. The probability of survival 7, 15, and 30 days after treatment with AR-MQ was 94.4%, 88.9%, and 14.9%, respectively. The experimental and modeling data both found that AR-MQ combination therapy yielded increased survival of infected animals.

    Keywords: Survival analysis1, malaria2, Plasmodium berghei3, Plasmodium falciparum4, antimalarial drug combination5

    Received: 24 Jun 2024; Accepted: 10 Sep 2024.

    Copyright: © 2024 Vieira Santos, Campos Pereira, dos Santos Miranda, Quadros, Magalhães Moreira and Johansson Azeredo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Francine Johansson Azeredo, Center for Pharmacometrics & Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, 32827-7400, Florida, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.