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Three Part Question

In [recent travelers or migrants with fever and a history of exposure to malaria endemic areas] does the [BinaxNOW malaria rapid diagnostic test] have [adequate diagnostic accuracy to guide initial treatment decisions]?

Clinical Scenario

A 28-year-old female presents to the emergency department with fever, influenza-like symptoms and diarrhea. History reveals she recently returned from a two week trip to rural Kenya. You consider malaria in your differential and wonder if using the Binax NOW malaria rapid diagnostic test (RDT) has sufficient accuracy to guide your treatment decision and hasten disposition.

Search Strategy

Ovid MEDLINE(R) 1950 to August Week 3 2010; Embase 1980 to 2010 Week 13
(exp malaria) AND (binax* OR 'now ICT' or 'now malaria').mp). Limit to English language; The Cochrane Library August 2010: Binax* ti, ab.

Search Outcome

Seventeen, 28 and two results, respectively, for each search of the above databases. Of these results, a total of 12 unique relevant papers were found. Two were excluded from review as they are ‘brief reports’ with limited methods detail, two were excluded as they are letters to the editor, and finally three were excluded for either retrospective design, not being clinically based, or of insufficient quality Three remaining high-quality studies were included in this review

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
De Monbrison F et al, 2004, France	Patients with suspected malaria presenting to 3 hospitals in France between 3/2002 and 8/2002. 557 consecutive patients underwent Binax NOW RDT and microscopy gold standard with blinded test interpreters. Disease incidence in population was 19.6%.	Prospective observational study	RDT detection of any Plasmodium spp (CIs):		Grouped bedside and laboratory performed RDTs together when calculating test statistics.
			Sensitivity	0.96 (0.90-0.99)
			Specificity	0.99 (0.97-1.0)
			PPV	0.95 (0.89-0.98)
			NPV	0.99 (0.98-1.0)
			LR (+)	86 (36-206)
			LR (-)	0.03 (0.01–0.09)
Gatti S et al, 2007, Italy	Convenience sample of 306 patients with suspected malaria presenting to 13 northern Italy hospitals during an unknown time period. Blood samples were tested in the lab with the Binax NOW RDT and microscopy gold standard and interpreted blindly. Disease incidence in population was 47.2%.	Prospective observational study	RDT detection of P. falciparum (CIs):		Evaluates RDT under laboratory conditions, not bedside. Not a consecutive sample of patients. Unknown time period of patient enrolement. No likelihood ratios. High incidence of disease in population limits generalizability.
			Sensitivity	1.0 (1.0-1.0)
			Specificity	0.93 (0.88-0.98)
			RDT detection of non-P. falciparum:
			Sensitivity	0.93
			Specificity	0.91
Wiese L et al, 2008, Denmark	Patients with suspected malaria presenting to 7 hospitals in Denmark between 8/2003 and 10/2004. 542 consecutive patients underwent Binax NOW RDT (bedside & in lab) and microscopy gold standard with blinded test interpreters. Disease incidence in population was 14.9%.	Prospective observational study	RDT detection of P. falciparum:		Only 376 patients received all three tests with 121 missing the bedside RTD and 45 missing the lab RDT. No confidence intervals or likelihood ratios reported.
			Sensitivity (Bedside; Lab)	0.88; 0.95
			Specificity (Bedside; Lab)	1.00; 0.99
			PPV (Bedside; Lab)	0.98; 0.95
			NPV (Bedside; Lab)	1.00; 1.00
			RDT detection for non-P. falciparum:	Results very poor, i.e. Sn: 0.41

Comment(s)

All studies included compared the index test with the ‘gold standard’ of blood smear microscopy in a blinded way. Evidence to date shows that the BinaxNOW Malaria RDT has reasonable sensitivity (0.88–1.0) and specificity (0.93–1.0) for the detection of Plasmodium falciparum in symptomatic patients. The one study that reported likelihood ratios had impressive results with LR(+) of 86 and LR(−) of 0.03 for diagnosis of any plasmodium spp. However, Gatti et al (2007) and Wiese et al (2006) both demonstrated that, for mixed infections or infections limited to non-P falciparum spp., the test characteristics deteriorate markedly. Wiese et al (2006) supports limiting use of the BinaxNOW Malaria RDT to the controlled conditions of the laboratory and not bedside. They point out that training is necessary to gain proficiency. Low frequency of use in non-endemic settings and high turnover of clinical staff contributed to their increased rate of inconclusive and false results with bedside testing. An approach that considers a BinaxNOW Malaria RDT positive result for P falciparum infection to be trustworthy for treatment purposes is appropriate based on the evidence, especially in facilities without rapid access to parasitologists proficient in malaria thick and thin smears. However, for purposes of establishing parasite burden, diagnosing mixed infection, and ruling out relapse, blood smears should still be obtained in these patients as soon as possible. Negative results, or results positive only for non-P falciparum spp., are less reliable and need follow-up by serial microscopy.

Clinical Bottom Line

In facilities located in non-endemic countries and with delayed access to microscopists experienced in the diagnosis of malaria, a positive result from the BinaxNOW Malaria RDT for P falciparum infection is sufficiently accurate to initiate treatment for this potentially life-threatening disease in appropriately selected patients. Other test results (inconclusive, negative entirely, or positive only for non-P falciparum) should be interpreted with caution and treatment decisions made on a clinical basis or after pursuing serial blood smear microscopy.

References

1. De Monbrison F, Gerome P, Chaulet JF, et al. . Comparative diagnostic performance of two commercial rapid tests for malaria in a non-endemic area. Eur J Clin Microbiol Infect Dis 2004; 23:784-786
2. Gatti S, Gramegna M, Bisoffi Z, et al. A comparison of three diagnostic techniques for malaria: a rapid diagnostic test (NOWH Malaria), PCR and microscopy. Ann Trop Med Parasitol 2007;101:195–204.
3. Wiese L, Bruun B, Baek L, et al. Bedside diagnosis of imported malaria using the Binax Now malaria antigen detection test. Scand J Infect Dis 2006;38:1063–8.