Efficacy of artesunate-mefloquine combination therapy on survival in Plasmodium berghei-infected mice: a time-to-event analysis

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 per...

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Bibliographic Details
Published in:Frontiers in Tropical Diseases
Main Authors: Valdeene Vieira Santos, Laiz Campos Pereira, Aline Lorena Lourenço dos Santos Miranda, Helenita Costa Quadros, Diogo Rodrigo Magalhães Moreira, Francine Johansson Azeredo
Format: Article in Journal/Newspaper
Language:English
Published: Frontiers Media S.A. 2024
Subjects:
survival analysis
malaria
Plasmodium berghei
Plasmodium falciparum
antimalarial drug combination
Arctic medicine. Tropical medicine
RC955-962
Arctic
Online Access:https://doi.org/10.3389/fitd.2024.1454252
https://doaj.org/article/a7f439ce4f344c048f468bc12f4b95c2
Description
Summary: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.

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