Emerging infectious disease laboratory and diagnostic preparedness to accelerate vaccine development

Roberts, Christine C.

Diagnostic assays are often the same style tests as those used in vaccine development, like antibody binding or molecular detection. However, their intended purpose is to accurately identify the infecting pathogen to enable health-care professionals to initiate appropriate treatments and prevent further transmission of disease. Laboratory confirmation of a diagnosis for patient treatment must have sufficient clinical sensitivity and specificity to be useful, the criteria for which may be different than analytical sensitivity and specificity criteria specified by assays for use in vaccine trials. [38] [39] [40] [41] [42] [43] [44] [45] Very few tests have gained Emergency Use Authorization (EUA) from the FDA. There are 2 MERS-CoV diagnostic tests, both molecular-based viral RNA detection, which received EUA in 2013 in response to the recognition of the significant potential for a future public health emergency. 46 For ZIKV, currently, 5 serological kits and 14 viral diagnostic kits have been granted EUA status. 47 For ZIKV in particular, the response to the need for diagnostics was quite rapid with all EUA approvals rolling out over approximately 19 months from February 2016 through September 2017, 46 shortly after the declaration of a public health emergency. Outside the US, the WHO's Emergency Use Assessment and Listing procedures (EUALs) recognizes the need and can grant authorization for use of diagnostic kits in emergency situations. 48 Although no MERS-CoV or ZIKV diagnostic kit, serological or viral, have been fully approved by the FDA to date, the FDA has worked collaboratively with developers to accelerate the approval process when outbreak conditions warrant. 49 A number of published studies have evaluated EUA tests independently for relevant sensitivity and specificity performance or in comparative studies 32, 39, [50] [51] [52] [53] [54] [55] [56] to aid in the selection of appropriate tests for the needs of epidemiological surveillance or public health diagnostics. Details outlining the relevant assay performance characteristics of each of the EUA-approved MERS-CoV and ZIKV assays can also be found on the FDA Medical Countermeasures webpage. 46, 57, 58 In the instance of MERS, EUA diagnostics approvals were limited to use with select respiratory tract specimens from individuals with signs and symptoms of infection with MERS-CoV or with epidemiological risk factors (i.e., contact with probable or confirmed MERS-CoV patient or having a history of travel to locations where MERS-CoV cases occur) for the detection of MERS-CoV. 46 For ZIKV, a number of complications in diagnostic tests such as cross-reactivity of immunological assays and short window of viremia in various bodily fluids required establishment of an algorithm to confirm ZIKV infection. This confirmatory algorithm guidance for health-care providers was based on not only clinical symptoms, risk factors, and diagnostic test results, 59,60 but also specifically for the use and interpretation of EUA diagnostic ZIKV IgM tests to indicate recent exposure with or without accompanying molecular ZIKV test results. 59 The types of specimens and timing of collection of specimens that would provide the most reliable results was also a consideration in the ZIKV diagnosis algorithm.