Genetic characterization of pfhrp2/3 and its implications for the use of Plasmodi

University Of California, San Diego, La Jolla CA

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Abstract

While Plamodium vivax is the most common cause of malaria in the Amazon region, Plasmodium falciparum accounts for 20-30% of all cases and has higher rates of mortality. Most of the currently available commercial rapid diagnostic tests kits (RDTs) for detection of Plasmodium falciparum use Histidlne Rich Protein 2 (HRP2) as the target antigen. The tests provide point of care diagnosis with the potential to replace microscopy, and so could have global impact. The anfibodies used in these kits recognize HRP2 antigen and may also cross react with another member of the HRP gene family called HRP3. We have found that up to 1/2 of light microscopy-positive P. falciparum cases were negative by this RDT in Peru and Colombia, explained by the absence of HRP2 and HRP3 genes. In Peru, 4 1% of P. falciparum parasites were missing the HRP2 gene, while 70% were missing HRP3. 20% of P. falciparum parasites lacked both genes. Because most ofthe RDTs used to diagnose malaria target HRP2 due to its greater sensitivity, delefions of HRP2 and HRP3 may compromise the ability of RDTs based on these antigens to detect the presence of parasites in pafient samples. Countries throughout South America have received global funds to acquire and purchase RDTs to use in malaria control programs. Because ofthe high proportion of parasites missing HRP2/HRP3 in Peru, it is important to undertake a comprehensive molecular surveillance to determine the possible origin and extent ofthese gene delefions in other areas of Peru and also in other countries in South America to guide Malaria Control Programs for the procurement and implementafion of malaria rapid diagnostic tests (RDTs). It is also important to understand the additional implicafions ofthese delefions in the parasite genotype and phenotype. To assess the origin and extent of HRP2/HRP3 gene deletions we propose to conduct a cross-secfional surveillance in areas from Peru not included in previous studies (Puerto Maldonado) and in other countries in South America, specifically Southern Brazil, near Puerto Maldonado. In collaboration with our partners, we will use molecular and serological methods to determine and characterize the deletions in HRP2/HRP3 and examine their funcfional significance.