Diagnostic Performance of Rapid Diagnostic Tests versus Blood Smears for Malaria in US Clinical Practice

Abstract

Background Approximately 4 million U.S. travelers to developing countries are ill enough to seek healthcare with 1,500 malaria cases reported in the U.S. annually. The diagnosis of malaria is frequently delayed due to the time to prepare malaria blood films and lack of technical expertise. An easy, reliable rapid diagnostic test (RDT) with high sensitivity and negative predictive value (NPV), particularly for Plasmodium falciparum, would be clinically useful. The study objective was to determine the diagnostic performance of the FDA-approved NOW® Malaria Test in comparison to traditional thick and thin blood smears for malaria diagnosis. Methods This prospective study tested 852 consecutive blood samples sent for thick and thin smears with blinded, malaria rapid tests at three hospital laboratories during 2003–2006. Polymerase chain reaction (PCR) verified positive tests and discordant results. Results Malaria occurred in 11% (95/852). The rapid test had superior performance than the standard Giemsa thick blood smear (P=.003). The rapid test’s sensitivity for all malaria was 97% (92/95) vs. 85% (81/95) by blood smear, and the RDT had superior NPV of 99.6% vs. 98.2% (P=.001). The P. falciparum performance was excellent with 100% rapid test sensitivity versus only 88% (65/74) by blood smear (P=.003). Conclusions This operational study demonstrates the FDA-approved rapid malaria test is superior to a single set of blood smears performed under routine U.S. clinical laboratory conditions. The most valuable clinical role of the RDT is in the rapid diagnosis or the exclusion of P. falciparum malaria, which is particularly useful in outpatient settings when evaluating febrile travelers.

Performance of BinaxNOW for Diagnosis of Malaria in a U.S. Hospital

“…BinaxNOW is known to have a lower sensitivity for P. ovale at lower parasitemia (5, 9). The current findings are similar to previous reports from the United States, Canada, and France, with 94 to 97% sensitivity for P. falciparum and 67 to 86% sensitivity for non-falciparum malaria using BinaxNOW (4,5,17). As would be expected with qualitative antigen testing, low parasitemia can cause false-negative results, as observed here and in other studies, including one from Canada that showed 75% sensitivity for P. falciparum at a parasitemia of 1 to 100/l (Ͻ0.002%), and 96.2% sensitivity at 101 to 1,000/l (Ͻ0.02%) (5).…”

“…Studies in France have demonstrated 96% sensitivity, 99% specificity, and high negative predictive values (NPV) with certain RDTs but conclude that microscopy is necessary for definitive confirmation (3,4). A similar study in the United States demonstrated 99% overall sensitivity and 99.6% NPV for the diagnosis of malaria with the BinaxNOW Malaria test; sensitivity for P. falciparum was 100% (17). BinaxNOW Malaria, the only U.S. Food and Drug Administration-approved RDT for malaria, qualitatively detects both the histidine-rich protein 2 (HRP-2), specific to P. falciparum, and aldolase, a panmalarial antigen found in all Plasmodium species (11).…”

Real-Time Quantitative Reverse Transcription PCR for Monitoring of Blood-Stage Plasmodium falciparum Infections in Malaria Human Challenge Trials

“…1,2 Rapid diagnostic tests for malarial antigens can sometimes outperform blood smears in developed world settings, 3 but they are less specific in regions of high prevalence and following drug treatment. 4 A variety of molecular methods of malaria parasite detection were developed in the past 20 years and include singlestep and nested polymerase chain reaction (PCR) with gel detection, RNA-specific nucleic acid-based sequence amplification (NASBA), and probe-based real-time PCR and reverse transcription (RT)-PCR (using various combinations of genus-or species-specific primers and TaqMan probes or molecular beacons).…”

Is Serial Testing Required to Diagnose Imported Malaria in the Era of Rapid Diagnostic Tests?

“…A recent report found that Binax NOW RDT had a negative predictive value of 100% for P. falciparum malaria and 98% for all malaria in a U.S. clinical laboratory setting. 9 Despite the excellent capacity of RDTs to exclude malaria, serial testing is generally still recommended. 2 However, fewer tests could dramatically improve patient waiting times, laboratory and hospital efficiency, and costs.…”