Baseline and multinormal distribution of ex vivo susceptibilities of Plasmodium falciparum to methylene blue in Africa, 2013-18.
J Antimicrob Chemother
; 75(8): 2141-2148, 2020 08 01.
Article
em En
| MEDLINE
| ID: mdl-32407538
ABSTRACT
BACKGROUND:
Plasmodium falciparum resistance to most antimalarial compounds has emerged in Southeast Asia and spread to Africa. In this context, the development of new antimalarial drugs is urgent.OBJECTIVES:
To determine the baseline in vitro activity of methylene blue (Proveblue®) on African isolates and to determine whether parasites have different phenotypes of susceptibility to methylene blue.METHODS:
Ex vivo susceptibility to methylene blue was measured for 609 P. falciparum isolates of patients hospitalized in France for malaria imported from Africa. A Bayesian statistical analysis was designed to describe the distribution of median effective concentration (EC50) estimates.RESULTS:
The EC50 ranged from 0.16 to 87.2 nM with a geometric mean of 7.17 nM (95% CI = 6.21-8.13). The 609 EC50 values were categorized into four components A (mean = 2.5 nM; 95% CI = 2.28-2.72), B (mean = 7.44 nM; 95% CI = 7.07-7.81), C (mean = 16.29 nM; 95% CI = 15.40-17.18) and D (mean = 38.49 nM; 95% CI = 34.14-42.84). The threshold value for in vitro reduced susceptibility to methylene blue was estimated at 35 nM using the geometric mean of EC50 plus 2 SDs of the 609 isolates. This cut-off also corresponds to the lower limit of the 95% CI of the methylene blue EC50 of component D. Thirty-five isolates (5.7%) displayed EC50 values above this threshold.CONCLUSIONS:
Methylene blue exerts a promising efficacy against P. falciparum and is a potential partner for triple combinations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Malária Falciparum
/
Antimaláricos
Limite:
Humans
País/Região como assunto:
Africa
/
Europa
Idioma:
En
Revista:
J Antimicrob Chemother
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
França