Susceptibilidad in vitro de aislamientos colombianos de Plasmodium falciparum a diferentes antipalúdicos Translated title: In vitro susceptibility of Colombian Plasmodium falciparum isolates to different antimalarial drugs

Abstract

Introducción. Los estudios de susceptibilidad in vitro de Plasmodium falciparum a los medicamentos antipalúdicos son herramientas importantes para vigilar la utilidad de esos medicamentos; tales estudios son escasos en Colombia. Objetivo. Evaluar la susceptibilidad in vitro de aislamientos colombianos de P. falciparum a cloroquina, amodiaquina, mefloquina, quinina y artesunato. Materiales y métodos. Se obtuvieron aislamientos clínicos de P. falciparum en varias regiones colombianas. De cada antipalúdico se probaron siete diluciones dobles seriadas, por duplicado, con la técnica HRP-2 y las cepas FCB2 (resistente a cloroquina) y NF54 (sensible a cloroquina) como controles. Se utilizaron las concentraciones inhibitorias 50 (CI50) mayor de 100, 80, 64, 500 y 10,5 nM como puntos de corte para clasificar la resistencia a cloroquina, amodiaquina, mefloquina, quinina y artesunato, respectivamente. Resultados. Se evaluaron 25 aislamientos: 72% de Urabá, 8% de Bajo Cauca y 20% de la Costa Pacífica. Las CI50 promedio de cloroquina, amodiaquina, mefloquina, quinina y artesunato fueron 422,9; 131,4; 56,3; 269,7 y 1,88 nM, respectivamente, y la proporción de aislamientos resistentes fue, en el mismo orden, 76%, 16%, 32%, 24% y 4%. Conclusiones. La baja sensibilidad a la cloroquina concuerda con otros estudios in vitro y con la baja eficacia terapéutica in vivo. Aunque 96% de los aislamientos fueron sensibles a artesunato, éste y otros estudios han observado aislamientos con disminución de la sensibilidad a las artemisininas (CI50>10,5 nM), lo que sugiere que el uso indiscriminado de estos medicamentos pone en riesgo su efectividad y podría dejarnos sin opciones para el tratamiento del paludismo por P. falciparum.

Translated abstract

Introduction. The in vitro assays for susceptibility of Plasmodium falciparum to antimalarial drugs are important tools for monitoring drug resistance, however few such studies have been undertaken in Colombia. Objective. P. falciparum isolates were obtained from several municipalities in western Colombia (Urabá, Bajo Cauca, Pacific Coast) and characterized for their in vivo susceptibility to chloroquine (CQ), amodiaquine (AQ), mefloquine (MQ), quinine (QN) and artesunate (AS). Material and methods. Patients with only P. falciparum infection (parasitemia=1,000 rings/µl) were included. Each antimalaria drug was tested with 7 dilutions, two-fold doses, with 2 replications and its effect evaluated using the histidine-rich protein (HRP-2) antigen detection method. Controls included FCB2 (chloroquine-resistant) and NF54 (chloroquine-sensitive) strains. IC50>100, 80, 64, 500 and 10.5 nM were used as the threshold criteria of resistance to CQ, AQ, MQ, QN and AS, respectively. Results. Twenty-five isolates were evaluated from Urabá (18), Bajo Cauca (2) and the Pacific Coast (5). The mean IC50 obtained with CQ, AQ, MQ, QN and AS were 422.9; 131.4; 56.3; 269.7 and 1.9 nM, respectively, and the number of resistant isolates for these drugs was 19 (76%), 4 (16%), 8 (32%), 6 (24%) and 1 (4%), respectively. Conclusions. The low sensitivity to CQ found here agrees with both in vitro and in vivo studies in Colombia. Ninety-six percent of the isolates were sensitive to AS. However, this study and previous reports have found isolates with low sensitivity to artemisinines (IC50>10.5 nM). This suggests that the indiscriminate use of these drugs put their efficacy at risk and eventually leave no options for falciparum malaria treatment.