Histidine-rich protein 2 (<i>pfhrp2</i>) and <i>pfhrp3</i> gene deletions in <i>Plasmodium falciparum</i> isolates from select sites in Brazil and Bolivia

<div><p>More than 80% of available malaria rapid diagnostic tests (RDTs) are based on the detection of histidine-rich protein-2 (PfHRP2) for diagnosis of <i>Plasmodium falciparum</i> malaria. Recent studies have shown the genes that code for this protein and its paralog, histidine-rich protein-3 (PfHRP3), are absent in parasites from the Peruvian Amazon Basin. Lack of PfHRP2 protein through deletion of the <i>pfhrp2</i> gene leads to false-negative RDT results for <i>P</i>. <i>falciparum</i>. We have evaluated the extent of <i>pfhrp2</i> and <i>pfhrp3</i> gene deletions in a convenience sample of 198 isolates from six sites in three states across the Brazilian Amazon Basin (Acre, Rondonia and Para) and 25 isolates from two sites in Bolivia collected at different times between 2010 and 2012. <i>Pfhrp2</i> and <i>pfhrp3</i> gene and their flanking genes on chromosomes 7 and 13, respectively, were amplified from 198 blood specimens collected in Brazil. In Brazil, the isolates collected in Acre state, located in the western part of the Brazilian Amazon, had the highest percentage of deletions for <i>pfhrp2</i> 25 (31.2%) of 79, while among those collected in Rondonia, the prevalence of <i>pfhrp2</i> gene deletion was only 3.3% (2 out of 60 patients). In isolates from Para state, all parasites were <i>pfhrp2</i>-positive. In contrast, we detected high proportions of isolates from all 3 states that were <i>pfhrp3</i>-negative ranging from 18.3% (11 out of 60 samples) to 50.9% (30 out of 59 samples). In Bolivia, only one of 25 samples (4%) tested had deleted <i>pfhrp2</i> gene, while 68% (17 out of 25 samples) were <i>pfhrp3</i>-negative. Among the isolates tested, <i>P</i>. <i>falciparum pfhrp2</i> gene deletions were present mainly in those from Acre State in the Brazilian Amazon. These results indicate it is important to reconsider the use of PfHRP2-based RDTs in the western region of the Brazilian Amazon and to implement appropriate surveillance systems to monitor <i>pfhrp2</i> gene deletions in this and other parts of the Amazon region.</p>