Abstract
Plasmodium falciparum malaria is widespread in the tropical and subtropical regions of the world. There is ongoing effort to eliminate malaria from endemic regions, and sensitive point-of-care (POC) diagnostic tests are required to support this effort. However, current POC tests are not sufficiently sensitive to detect P. falciparum in asymptomatic individuals. After extensive optimization, we have developed a highly sensitive and robust POC test for the detection of P. falciparum infection. The test is based on upconverting nanophosphor-based lateral flow (UCNP-LF) immunoassay. The developed UCNP-LF test was validated using whole blood reference panels containing samples at different parasite densities covering eight strains of P. falciparum from different geographical areas. The limit of detection was compared to a WHO-prequalified rapid diagnostic test (RDT). The UCNP-LF achieved a detection limit of 0.2-2 parasites/μL, depending on the strain, which is 50- to 250-fold improvement in analytical sensitivity over the conventional RDTs. The developed UCNP-LF is highly stable even at 40 °C for at least 5 months. The extensively optimized UCNP-LF assay is as simple as the conventional malaria RDTs and requires 5 μL of whole blood as sample. Results can be read after 20 min from sample addition, with a simple photoluminescence reader. In the absence of a reader device at the testing site, the strips after running the test can be transported and read at a central location with access to a reader. We have found that the test and control line signals are stable for at least 10 months after running the test. The UCNP-LF has potential for diagnostic testing of both symptomatic and asymptomatic individuals.
Highlights
Plasmodium falciparum malaria is widespread in the tropical and subtropical regions of the world
Plasmodium falciparum malaria caused an estimated 405 000 deaths in 2018.1 Typically, malaria is diagnosed with microscopy or rapid diagnostic tests (RDTs) using the lateral flow (LF) principle
For P. falciparum detection with RDTs, the main analyte is Pf histidine-rich protein 2, Pf HRP2.2 HRP2 is expressed in the parasite’s trophozoite stage, but due to the long half-life of this protein, it can be detected throughout the infection.[3]
Summary
Plasmodium falciparum malaria is widespread in the tropical and subtropical regions of the world. A significant challenge for malaria elimination efforts is that malaria infections are often asymptomatic with a low density of parasitemia, which can persist for a year or longer.[6] It has been shown that these asymptomatic individuals may still transmit the parasite to mosquitoes and are an important reservoir for the malaria parasite.[7] Finding and treating these submicroscopic and asymptomatic infections should have a large impact on preventing transmission, since they can account for 20− 50% of transmission in preelimination and elimination settings.[8] most currently available RDTs do not have sufficient sensitivity to detect asymptomatic or submicroscopic infections where parasite density is below 100 parasites/ μL of blood,[9] and many tests even miss samples with a density of 200 parasites/μL.[10] A target product profile for an RDT for the detection of low-density P. falciparum infections sets the optimal sensitivity requirement at 10 parasites/μL.[11] An RDT with an even lower sensitivity would be important for malaria elimination programs. The detection of asymptomatic infections with parasite load below 2 parasites/
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