Critical evaluation of FDA-approved respiratory multiplex assays for public health surveillance

Abstract

Clinical management and identification of respiratory diseases has become more rapid and increasingly specific due to widespread use of PCR(polymerase chain reaction) multiplex technologies. Although significantly improving clinical diagnosis, multiplexed PCR assays could have a greater impact on local and global disease surveillance. The authors wish to propose methods of evaluating respiratory multiplex assays to maximize diagnostic yields specifically for surveillance efforts. Areas covered: The authors review multiplexed assays and critically assess what barriers have limited these assays for disease surveillance and how these barriers might be addressed. The manuscript focuses specifically on the case study of using multiplexed assays for surveillance of respiratory pathogens. The authors also provide a method of validation of specific surveillance measures. Expert commentary: Current commercially available respiratory multiplex PCR assays are widely used for clinical diagnosis; however, specific barriers have limited their use for surveillance. Key barriers include differences in testing phase requirements and diagnostic performance evaluation. In this work the authors clarify phase testing requirements and introduce unique diagnostic performance measures that simplify the use of these assays on a per target basis for disease surveillance.

Enterovirus D68 – The New Polio?

“…Similarly, the GenMark eSensor respiratory viral panel (Carlsbad, California, United States) was found to pick up low-positive rhinoviruses which were later found to be EV-D68 in 67% of samples, with a 94% sensitivity and 88% specificity rate ( McAllister et al, 2015 ). This was subsequently noted due to cross-reactivity with rhinoviruses ( McAllister et al, 2015 ; Diaz-Decaro et al, 2018 ).…”

Identification of Pathogens from the Upper Respiratory Tract of Adult Emergency Department Patients at High Risk for Influenza Complications

“…The value and meaningfulness of applying multiplex molecular methods for respiratory viruses aside from influenza virus has been under debate. 27,28 For influenza virus, and in some cases RSV, studies utilizing point-of-care (POC) diagnostic tests for these specific organisms have shown value in terms of patient management, patient cohorting and droplet precautions, and appropriate anti-viral therapy. [29][30][31] However, for large, molecular multiplex methods, it is unclear whether or not they should be employed broadly for general surveillance purposes, or restricted to specific populations, i.e., pediatric patients, high risk ED patients, and the immunocompromised.…”

“…27 It has been noted that there are various barriers to utilizing these methods for general surveillance and specific diagnosis. These include difference in testing phase requirements, 28 cost to the laboratory, the patient and insurer, 27 and level of complexity for the multiplex method. 27 Strategies have been suggested to mitigate some of these barriers.…”

“…27 Strategies have been suggested to mitigate some of these barriers. 28 Surveillance of non-influenza viruses in these populations can aid in differentiating the cause of illness, which can be potentially antibiotic sparing. 7,13,[18][19][20] Newly developed multiplex diagnostic technologies can aid in non-influenza surveillance and expand the etiology of URIs beyond influenza.…”

Viral Respiratory Infections: New Tools for a Rapid Diagnosis

“…Numerous commercial multiplex respiratory virus assays exist: some of them, such as Luminex NxTAG RPP, Verigene RP Flex, eSensor RVP, and FilmArray RP are FDA-cleared 74 ( Table 2 ). Significant differences between the various multiplex assays lie in the number of targets detected, which affect the method of nucleic acid amplification used, and the time of sample analysis.…”