Genetic variability of Plasmodium falciparum histidine-rich proteins 2 and 3 in Central America.

BACKGROUND: Malaria is an important disease in many tropical countries. Rapid diagnostic tests (RDTs) are valuable tools for diagnosing malaria in remote areas. The majority of RDTs used for the diagnosis of Plasmodium falciparum are based on the detection of the specific histidine-rich proteins (PfHRP2 and PfHRP3). During the last decade, the threat posed by the lack of expression of these antigens and the variability of the proteins on the diagnosis of malaria has been widely discussed. The aim of this study was to evaluate the genetic diversity of pfhrp2 and pfhrp3 of P. falciparum isolates collected in three Central American countries.

METHODS: DNA samples were amplified and sequenced to assess the diversity of nucleotides and amino acids. A search for known epitopes within the amino acid sequence was carried out, and the sensitivity of the sequences was evaluated according to a predictive model. A phylogenetic analysis was carried out including homologous sequences from different regions of the world. Protein structures were predicted in silico.

RESULTS: Five different patterns for PfHRP2 and one pattern for PfHRP3 were identified. Isolates from Central America show a high level of genetic diversity in pfhrp2; however, the amino acid sequences seem to contain enough motifs to be detected by the RDTs currently available.

CONCLUSION: It is unlikely that the variability of the pfhrp2 and pfhrp3 genes has a significant impact on the ability of the RDTs to detect the PfHRP antigens in Central America.