Evaluation of Histidine-Rich Proteins 2 and 3 Gene Deletions in <i>Plasmodium falciparum</i> in Endemic Areas of the Brazilian Amazon

• Main Authors: Leandro Góes, Nathália Chamma-Siqueira, José Mário Peres, José Maria Nascimento, Suiane Valle, Ana Ruth Arcanjo, Marcus Lacerda, Liana Blume, Marinete Póvoa, Giselle Viana
• Format: Article
• Language: English
• Published: MDPI AG 2021-12-01
• Series: International Journal of Environmental Research and Public Health
• Subjects: <i>Plasmodium falciparum</i>; rapid diagnostic tests (RDTs); <i>pfhrp2</i>; <i>pfhrp3</i>; gene deletion
• Online Access: https://www.mdpi.com/1660-4601/18/1/123
• ISSN: 1661-7827; 1660-4601

Histidine-rich proteins 2 and 3 gene (<i>pfhrp2</i> and <i>pfhrp3</i>) deletions affect the efficacy of rapid diagnostic tests (RDTs) based on the histidine-rich protein 2 (HRP2), compromising the correct identification of the <i>Plasmodium falciparum</i> species. Therefore, molecular surveillance is necessary for the investigation of the actual prevalence of this phenomenon and the extent of the disappearance of these genes in these areas and other South American countries, thus guiding national malaria control programs on the appropriate use of RDTs. This study aimed to evaluate the <i>pfhrp2</i> and <i>pfhrp3</i> gene deletion in <i>P. falciparum</i> in endemic areas of the Brazilian Amazon. Aliquots of DNA from the biorepository of the Laboratory of Basic Research in Malaria, Evandro Chagas Institute, with a positive diagnosis for <i>P. falciparum</i> infection as determined by microscopy and molecular assays, were included. Monoinfection was confirmed by nested-polymerase chain reaction assay, and DNA quality was assessed by amplification of the merozoite surface protein-2 gene (<i>msp2).</i> The <i>pfhrp2</i> and <i>pfhrp3</i> genes were amplified using primers for the region between exons 1 and 2 and for all extension of exon 2. Aliquots of DNA from 192 <i>P. falciparum</i> isolates were included in the study, with 68.7% (132/192) from the municipality of Cruzeiro do Sul (Acre) and 31.3% (60/192) from Manaus (Amazonas). Of this total, 82.8% (159/192) of the samples were considered of good quality. In the state of Acre, 71.7% (71/99) showed <i>pfhrp2</i> gene deletion and 94.9% (94/99) showed <i>pfhrp3</i> gene deletion, while in the state of Amazonas, 100.0% (60/60) of the samples showed <i>pfhrp2</i> gene deletion and 98.3% (59/60) showed <i>pfhrp3</i> gene deletion. Moreover, 79.8% (127/159) of isolates displayed gene deletion. Our findings confirm the presence of a parasite population with high frequencies of <i>pfhrp2</i> and <i>pfhrp3</i> gene deletions in the Brazilian Amazon region. This suggests reconsidering the use of HRP2-based RDTs in the Acre and Amazonas states and calls attention to the importance of molecular surveillance and mapping of <i>pfhrp2/pfhrp3</i> deletions in this area and in other locations in the Amazon region to guarantee appropriate patient care, control and ultimately contribute to achieving <i>P. falciparum</i> malaria elimination.