ArticleMalaria journal2019
In vivo compartmental kinetics of Plasmodium falciparum histidine-rich protein II in the blood of humans and in BALB/c mice infected with a transgenic Plasmodium berghei parasite expressing histidine-rich protein II.
Article in Malaria journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 14 citations in OpenAlex.
- Slow clearance of histidine-rich protein-2 in Gabonese with uncomplicated malaria.Microbiology spectrum · 2024Observational
- The in-vivo dynamics of Plasmodium falciparum HRP2: implications for the use of rapid diagnostic tests in malaria elimination.Malaria journal · 2022Article
- HRP2 and HRP3 cross-reactivity and implications for HRP2-based RDT use in regions with Plasmodium falciparum hrp2 gene deletions.Malaria journal · 2021Article
- Changes in mammalian copper homeostasis during microbial infection.Metallomics : integrated biometal science · 2020Article
- Clearance dynamics of lactate dehydrogenase and aldolase following antimalarial treatment for Plasmodium falciparum infection.Parasites & vectors · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe Plasmodium falciparum histidine-rich protein II (PfHRP2) is a common biomarker used in malaria rapid diagnostic tests (RDTs), but can persist in the blood for up to 40 days following curative treatment. The persistence of PfHRP2 presents a false positive limitation to diagnostic interpretation. However, the in vivo dynamics and compartmentalization underlying PfHRP2 persistence have not been fully characterized in the plasma and erythrocyte (RBC) fraction of the whole blood.
methodsThe kinetics and persistence of PfHRP2 in the plasma and RBC fractions of the whole blood were investigated post-treatment in human clinical samples and samples isolated from BALB/c mice infected with a novel transgenic Plasmodium berghei parasite engineered to express PfHRP2 (PbPfHRP2).
resultsPfHRP2 levels in human RBCs were consistently 20-40 times greater than plasma levels, even post-parasite clearance. PfHRP2 positive, DNA negative, once-infected RBCs were identified in patients that comprised 0.1-1% of total RBCs for 6 and 12 days post-treatment, even post-atovaquone-proguanil regimens. Transgenic PbPfHRP2 parasites in BALB/c mice produced and exported tgPfHRP2 to the RBC cytosol similar to P. falciparum. As in humans, tgPfHRP2 levels were found to be approximately 20-fold higher within the RBC fraction than the plasma post-treatment. RBC localized tgPfHRP2 persisted longer than tgPfHRP2 in the plasma after curative treatment. tgPfHRP2 positive, but DNA negative once-infected RBCs were also detected in mouse peripheral blood for 7-9 days after curative treatment.
conclusionsThe data suggest that persistence of PfHRP2 is due to slower clearance of protein from the RBC fraction of the whole blood. This appears to be a result of the presence PfHRP2 in previously infected, pitted cells, as opposed to PfHRP2 binding naïve RBCs in circulation post-treatment. The results thus confirm that the extended duration of RDT positivity after parasite clearance is likely due to pitted, once-infected RBCs that remain positive for PfHRP2.
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