Modelling the dynamics of Plasmodium falciparum histidine-rich protein 2 in human malaria to better understand malaria rapid diagnostic test performance

A model of PfHRP2 production and decay was developed to mimic the kinetics of PfHRP2 antigenaemia during infections. Data from two human infection studies was used to fit the model, and to investigate PfHRP2 kinetics. Four malaria RDTs were assessed in the laboratory to determine the minimum detectable concentration of PfHRP2.Fitting of the PfHRP2 dynamics model indicated that in malaria na？ve hosts, P. falciparum parasites of the 3D7 strain produce 1.4 × 10-13 g of PfHRP2 per parasite per replication cycle. The four RDTs had minimum detection thresholds between 6.9 and 27.8 ng/mL. Combining these detection thresholds with the kinetics of PfHRP2, it is predicted that as few as 8 parasites/μL may be required to maintain a positive RDT in a chronic infection.The results of the model indicate that good quality PfHRP2-based RDTs should be able to detect parasites on the first day of symptoms, and that the persistence of the antigen will cause the tests to remain positive for at least seven days after treatment. The duration of a positive test result following curative treatment is dependent on the duration and density of parasitaemia prior to treatment and the presence and affinity of anti-PfHRP2 antibodies.Plasmodium falciparum causes the most severe form of malaria, and contributes to high morbidity and mortality in areas of the world where malaria is endemic. Accurate diagnostics are paramount for efficient treatment of falciparum malaria. In this context, the popularity of malaria rapid diagnostic tests (RDTs) has increased due to the WHO recommendation for parasitological confirmation of suspected malaria cases prior to treatment [1]. Compared to microscopy, RDTs are easier to use, do not require well-maintained microscopes and skilled microscopists, and provide a timely result. The majority of P. falciparum specific RDTs function by detecting a water soluble protein produced by P. falciparum, namely histidine-rich protein 2 (PfHRP2). Detection is accomplished usin