The online version of this article (doi:10.1186/1475-2875-11-74) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
LM developed the model, conducted the analysis and drafted the manuscript. AB performed the laboratory testing of RDTs and ELISA assays. JMC participated in the design of the study. MLG participated in the design of the study, reviewed the model output and helped draft the manuscript. All authors read and approved the final manuscript.
Effective diagnosis of malaria is a major component of case management. Rapid diagnostic tests (RDTs) based on Plasmodium falciparum histidine-rich protein 2 (Pf HRP2) are popular for diagnosis of this most virulent malaria infection. However, concerns have been raised about the longevity of the Pf HRP2 antigenaemia following curative treatment in endemic regions.
A model of Pf HRP2 production and decay was developed to mimic the kinetics of Pf HRP2 antigenaemia during infections. Data from two human infection studies was used to fit the model, and to investigate Pf HRP2 kinetics. Four malaria RDTs were assessed in the laboratory to determine the minimum detectable concentration of Pf HRP2.
Fitting of the Pf HRP2 dynamics model indicated that in malaria naïve hosts, P. falciparum parasites of the 3D7 strain produce 1.4 × 10-13 g of Pf HRP2 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 Pf HRP2, 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 Pf HRP2-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-Pf HRP2 antibodies.
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- Modelling the dynamics of Plasmodium falciparum histidine-rich protein 2 in human malaria to better understand malaria rapid diagnostic test performance
James S McCarthy
Michelle L Gatton
- BioMed Central
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