Research
Laboratory demonstration of a prozone-like effect in HRP2-detecting malaria rapid diagnostic tests: implications for clinical management
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* Corresponding author: David Bell david.bell@finddiagnostics.org
1 Department of Parasitology, Research Institute for Tropical Medicine, Alabang, Muntinlupa City, The Philippines
2 Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Australia
3 Department of Developmental Biology, The University of Texas Southwestern Medical Center, Dallas, TX, USA; formerly Department of Parasitology, Research Institute for Tropical Medicine, Alabang, Muntinlupa City, Philippines
4 Queensland Institute of Medical Research, University of Queensland, Brisbane, Australia
5 Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland; formerly World Health Organization - Regional Office for the Western Pacific, Manila, The Philippines
Malaria Journal 2011, 10:286 doi:10.1186/1475-2875-10-286
Published: 29 September 2011Abstract
Background
Malaria rapid diagnostic tests (RDTs) are now widely used for prompt on-site diagnosis in remote endemic areas where reliable microscopy is absent. Aberrant results, whereby negative test results occur at high parasite densities, have been variously reported for over a decade and have led to questions regarding the reliability of the tests in clinical use.
Methods
In the first trial, serial dilutions of recombinant HRP2 antigen were tested on an HRP2-detectiing RDT. In a second trial, serial dilutions of culture-derived Plasmodium falciparum parasites were tested against three HRP2-detecting RDTs.
Results
A prozone-like effect occurred in RDTs at a high concentration of the target antigen, histidine-rich protein-2 (above 15,000 ng/ml), a level that corresponds to more than 312000 parasites per μL. Similar results were noted on three RDT products using dilutions of cultured parasites up to a parasite density of 25%. While reduced line intensity was observed, no false negative results occurred.
Conclusions
These results suggest that false-negative malaria RDT results will rarely occur due to a prozone-like effect in high-density infections, and other causes are more likely. However, RDT line intensity is poorly indicative of parasite density in high-density infections and RDTs should, therefore, not be considered quantitative. Immediate management of suspected severe malaria should rely on clinical assessment or microscopy. Evaluation against high concentrations of antigen should be considered in malaria RDT product development and lot-release testing, to ensure that very weak or false negative results will not occur at antigen concentrations that might be seen clinically.