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

Abstract

Microscopic diagnosis and species identification of Plasmodium in areas of nonendemicity provide a robust method for malaria diagnosis but are technically challenging. A prospective study was conducted to measure the performance of BinaxNOW compared to microscopy (the gold standard) in a U.S. teaching hospital. Overall, BinaxNOW was 84.2% sensitive and 99.8% specific. Excluding patients on antimalarial therapy, the sensitivity was 92.9%. Importantly, BinaxNOW initially misclassified a case of Plasmodium falciparum malaria as non-falciparum. These results support the judicious use of BinaxNOW in screening of individuals suspected of having malaria in areas of nonendemicity. T he accurate diagnosis of malaria by microscopy in the UnitedStates is complicated by a number of factors, including lack of experienced technologists, variable methodology and quality of smears, and partial morphological overlap between Plasmodium falciparum and other Plasmodium species (12,14). Although the incidence of malaria in returned febrile travelers is approximately 21%, only 1,300 cases were reported in the United States in 2008, in comparison to 243 million cases worldwide during the same period (15,19,20). The development of rapid diagnostic tests (RDTs) has aided diagnosis of malaria in resource-poor settings, but these tests have limited capability for species identification, as they were originally designed to distinguish P. falciparum from other Plasmodium species that cause disease in humans. Numerous studies have demonstrated the utility of RDTs, which have sensitivity and specificity comparable to those of microscopy while offering rapid diagnosis, in Africa and Asia (1, 16). The performance of RDTs in areas of low malaria prevalence is less well investigated. 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).Here, we report on the performance of the BinaxNOW in a major U.S. academic medical center, describe a unique case of misidentification of P. falciparum by BinaxNOW, and discuss the advantages and disadvantages of using BinaxNOW as a screening tool in the United States. MATERIALS AND METHODSFrom July 2008 to March 2012, 484 BinaxNOW Malaria tests, on 407 unique patients, were performed concurrently with thin and thick blood smears in the Stanford Hospital Clinical Hematology Laboratory on consecutive blood samples from patients with suspected malaria. For each sample, one thick and two thin smears were prepared from venous ED...

Use of the Rapid BinaxNOW Malaria Test in a 24-Hour Laboratory Associated with Accurate Detection and Decreased Malaria Testing Turnaround Times in a Pediatric Setting Where Malaria Is Not Endemic

“…These cases highlighted the utility of molecular diagnostics, when available, to resolve discordance between RDT and microscopy. We did not observe any cases of P. falciparum malaria misidentified by RDT as non-falciparum malaria as reported by DiMaio et al (8).…”

Use of Rapid Diagnostic Tests for Diagnosis of Malaria in the United States

“…n the September issue of this journal, performance of BinaxNOW for the diagnosis of malaria in a major U.S. academic medical center was reported (1). Herein, we report performance of this test in a second large academic medical center in the United States.…”

“…Clinical ramifications of reporting false-negative results are of most pressing concern, in particular because many patients seen in the United States with P. falciparum malaria will have low-level parasitemia that is below the limit of detection of BinaxNOW. False-negative results may also be obtained at high-level parasitemia due to the prozone phenomenon or possibly a mutation in histidinerich protein 2 (HRP-2) antigen detected by the test (1,5).…”

Prozone-like phenomenon in travellers with fatal malaria: report of two cases

“…These tests detect Plasmodium antigens in blood by antigen-antibody interaction on a nitrocellulose test strip and can target antigens specific of P. falciparum like the histidine-rich protein 2 (HRP-2) and lactate dehydrogenase (Pf-pLDH) or parasite antigens considered pan-specific (pLDH and aldolase). More than 200 tests are on the market, but only BinaxNow Malaria (Binax, Scarborough, USA) a combination assay with antibodies for detection of HRP2 and aldolase, has been approved by the US Food and Drug Administration [2]. Their global sensitivities are around 95% for detection of Plasmodium falciparum, however, false negative results may occur, with the majority of cases being related to low parasite densities (below 100 asexual parasites/l or <0.002% of parasitized red blood cells (RBC) or non-falciparum-infections, for which the RDTs are less sensitive [3].…”