HRP2: Transforming Malaria Diagnosis, but with Caveats. Issue 2 (February 2020)

• Record Type: Journal Article
• Authors: Poti, Kristin E.; Sullivan, David J.; Dondorp, Arjen M.; Woodrow, Charles J.
• Is Part Of: Trends in parasitology. Volume 36:Issue 2(2020)
• Page Start: 112
• Page End: 126
• Publication Date: 2020-02
• Subjects: HRP2 -- rapid diagnostic test -- Plasmodium falciparum -- diagnosis -- severe malaria -- deletion; Parasitology -- Periodicals; Parasitology -- Periodicals; Biology -- Periodicals; Parasitology; Biology; Parasitologie -- Périodiques; Online resources; 571.999
• DOI: 10.1016/j.pt.2019.12.004
• Languages: English
• ISSNs: 1471-4922

Abstract

Abstract : The major growth in point-of-care malaria diagnosis over the past decade has been based on immunochromatographic malaria rapid diagnostic tests (mRDTs), which generally detect Plasmodium falciparum via its abundant histidine-rich protein 2 (HRP2). Here, we review the discovery and biology of HRP2, as well as the strengths and weaknesses of HRP2-based diagnosis compared with alternative antigens. We highlight recent studies describing HRP2 deletion in Latin America, Eritrea, and possibly other regions, and the methodological challenges of confirming deletion of the pfhrp2 gene. We also discuss the mechanism of persistent HRP2 positivity after effective antimalarial treatment, along with other emerging HRP2-based applications, including detection of submicroscopic malaria and diagnosis of severe malaria. Highlights: HRP2 detection forms the basis of the most sensitive mRDTs currently available, and HRP2-based mRDTs have been the central element in the scale-up of mRDTs over the last decade, allowing malaria diagnosis even in remote areas in sub-Saharan African. Over 1 billion mRDTs have been sold so far. Parasites with HRP2 deletion were first reported from the Amazon region (Peru and neighbouring countries) in 2010 and, more recently, at high prevalence in Eritrea. Persistence of HRP2 in the circulation for several weeks following successful antimalarial treatment is now understood to be due to splenic pitting, and HRP2 measurement can be used to predict postartesunate-delayed haemolysis. The concentration of HRP2 can be used to define severe malaria (plasma) and quantify in vitro growth (laboratory culture). There is increasing interest in ultrasensitive HRP2 detection to detect asymptomatic malaria in low-transmission areas, potentially allowing public health-level interventions.