Drug Resistance Molecular Markers of Plasmodium falciparum and Severity of Malaria in Febrile Children in the Sentinel Site for Malaria Surveillance of Melen in Gabon: Additional Data from the Plasmodium Diversity Network African Network

Abstract

The objective of this study was to analyze the relationship between the frequency of artemisinin-based combination (ACT) drug resistance molecular markers and clinical forms of P. falciparum malaria and parasitemia. A cross-sectional study was carried out between January and April 2014 at the Operational Clinical Research Unit of Melen in febrile children aged 12 to 240 months with a Plasmodium sp. infection. A total of 3 mL of peripheral blood collected from an EDTA tube was used for leukocyte depletion. DNA mutation detection was performed by next generation sequencing (NGS). A total of 1075 patients were screened for malaria. Among them, 384 had a Plasmodium infection. P. falciparum mono-infection was found in 98.9% of the patients. Pfcrt-326T mutation was found in all isolates, while 37.9% had Pfmdr2-484I mutant allele. The highest median parasite densities were found in patients infected by parasites carrying the CVIET haplotype of the Pfcrt gene. The different genetic profiles found here, and their variations according to clinical and biological signs of severe malaria, are additional arguments for the surveillance of P. falciparum strains.

Keywords: ART resistance; Gabon; Plasmodium falciparum; malaria clinical forms; molecular markers; parasitaemia.

Figure 1

Profile of outcomes obtained before sequencing.

Figure 2

Frequency of molecular markers of amino-4-quinoleine resistance (Pfcrt-72-76 + Pfmdr1-86-184-1246). (a) Frequency of Pfcrt mutations related to amino-4-quinoleines resistance; (b) Frequency of Pfmdr1 mutations related to AQ and lumefantrine resistance; (c) Frequency of haplotypes of Pfcrt gene, Pfmdr1 gene and Pfcrt + Pfmdr1 genes. YYY: 86Y-184Y-1246Y; YYD: 86Y-184Y-D1246; NYD: N86-184Y-D1246; YFD: 86Y-F184-D1246; NFD: N86-F184-D1246; CVMNK: 72C-73V-74M-75N-76K; CVIET: 72C-73V-74I-75E-76T; CVIET/CVMNK: mixed infection.