Laboratory demonstration of a prozone-like effect in HRP2-detecting malaria rapid diagnostic tests: implications for clinical management

Malaria Journal

Research

Vicente Belizario¹  James S McCarthy²  Sheila Alcantara³  Jennifer Luchavez³  Qin Cheng⁴  Joanne Baker⁴  David Bell⁵ 

[1] Department of Developmental Biology, The University of Texas Southwestern Medical Center, Dallas, TX, USA;Department of Parasitology, Research Institute for Tropical Medicine, Alabang, Muntinlupa City, Philippines;Department of Parasitology, Research Institute for Tropical Medicine, Alabang, Muntinlupa City, The Philippines;Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Australia;Queensland Institute of Medical Research, University of Queensland, Brisbane, Australia;

关键词: Malaria;    Rapid Diagnostic Test;    Parasite Density;    Antigen Concentration;    Malaria Rapid Diagnostic Test;   

DOI  :  10.1186/1475-2875-10-286

 received in 2011-05-21, accepted in 2011-09-29,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundMalaria 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.MethodsIn 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.ResultsA 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.ConclusionsThese 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.

【 授权许可】

Unknown   
© Luchavez et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.