Introduction: Plasmodium falciparum (P. falciparum) is a deadly protozoan that is accountable for malaria and chloroquine was the first-line antimalarial drug before its withdrawal and replaced by artemisinin. To date, several studies showed that P. falciparum had regained its sensitivity towards chloroquine after its withdrawal for decades. By understanding the basic principle and mechanism of chloroquine resistance in P. falciparum, at the molecular level, it would be valuable prior to the re-introduction of chloroquine as a first-line anti-malarial drug for malaria treatment. Thus, this study was conducted to determine the chloroquine resistance level of long preserved lab-adapted P. falciparum strain. Methodology: By using 14 years (2006-2020) cryopreserved chloroquine-sensitive (3D7) and chloroquine-resistant (W2) lab-adapted P. falciparum strains, the strains were subjected to continuous culture for three months before in vitro drug susceptibility assay and single nucleotide polymorphisms (SNP) analysis on Pfcrt and Pfmdr-1 gene for both strains. Results: This study shows the IC50 chloroquine of lab-adapted P. falciparum 3D7 and W2 strains were at 32.98 nM and 691.21 nM, respectively and both strains showed 3-fold higher IC50 when compared to their susceptibility before cryopreserved (3D7; 13.84nM and W2; 208.27 nM). The SNPs result showed a consistent amino acid substitution at position 76 (K to T) on PfCRT and 86 (N to Y) in Pfmdr-1 gene which concordance with other studies before preservation. Conclusion: Thus, this study shows that long cryopreserved of lab-adapted P. falciparum increases the chloroquine resistance level but not exhibited any change in susceptibility.
Malaria is a disease that causes enormous human morbidity and mortality. One feature of mature Plasmodium falciparum-infected erythrocytes leading to the development of severe malaria is thought to be cytoadherence and blockage of the microvasculature. Therefore, an understanding of mechanisms that mediate parasite adhesion leading to malaria pathology is needed to yield new treatments for malaria. However, to date, cytoadherence-associated pathology is still under debate. Is cytoadherence needed to develop severe malaria? This review will discuss the available information on associations of cytoadherence with the development of severe malaria.
Fluoxetine (FLX), a P-glycoprotein inhibitor with antimalarial activity, is promising candidate for reversing chloroquine/mefloquine (CQ/MQ) resistance. The Dd2 strain of CQ- and MQ-resistant Plasmodium falciparum was synchronized and assayed with various concentrations of CQ/MQ individually and in combination with FLX or verapamil (VPL). Our results indicated the 50% inhibitory concentration values of CQ and MQ were greatly lowered when FLX was used simultaneously. Isobolograms indicated that CQ-FLX combinations are more synergistic (mean fractional inhibitory concentration [FIC] index 0.55) than MQ-FLX (mean FIC index 0.64), and their synergistic effect was better than or at par with CQ-VPL (mean FIC index 0.88) and MQ-VPL (mean FIC index 0.60) combinations. We conclude that the FLX potentiates the CQ and MQ response on multidrug-resistant P. falciparum at clinically achievable concentrations.