External Quality Assessment for Zika Virus Molecular Diagnostic Testing, Brazil

Baylis, Sally A.; Blümel, Johannes

doi:10.3201/eid2410.180360

Cited by 1 publication

(1 citation statement)

References 5 publications

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“…These primers are employed by clinical and research laboratories and are included in the CDC Trioplex real-time RT-PCR assay [25]. Similar findings have been reported by Baylis et al which evaluated the sensitivity of a French Polynesian standard for use in the WHO ZIKV RT-PCR [55,56]. Here, multiple labs reported increased sensitivity for MR−766 and closely related French Polynesian isolates that contain the A266V mutation but reduced sensitivity for Cambodian and Puerto Rican isolates that lack the mutation [56].…”

Section: Discussionsupporting

confidence: 56%

Strain-Dependent Activity of Zika Virus and Exposure History in Serological Diagnostics

et al. 2020

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Zika virus (ZIKV) circulates as two separate lineages, with significant genetic variability between strains. Strain-dependent activity has been reported for dengue virus, herpes simplex virus and influenza. Strain-dependent activity of subject specimens to a virus could be an impediment to serological diagnosis and vaccine development. In order to determine whether ZIKV exhibits strain-dependent activity when exposed to antibodies, we measured the neutralizing properties of polyclonal serum and three monoclonal antibodies (ZKA185, 753(3)C10, and 4G2) against three strains of ZIKV (MR−766, PRVABC59, and R103454). Here, MR−766 was inhibited almost 60% less by ZKA185 than PRVABC59 and R103454 (p = 0.008). ZKA185 enhanced dengue 4 infection up to 50% (p = 0.0058). PRVABC59 was not inhibited by mAb 753(3)C10 while MR−766 and R103453 were inhibited up to 90% (p = 0.04 and 0.036, respectively). Patient serum, regardless of exposure history, neutralized MR−766~30%−40% better than PRVABC56 or R103454 (p = 0.005−0.00007). The most troubling finding was the significant neutralization of MR−766 by patients with no ZIKV exposure. We also evaluated ZIKV antibody cross reactivity with various flaviviruses and found that more patients developed cross-reactive antibodies to Japanese encephalitis virus than the dengue viruses. The data here show that serological diagnosis of ZIKV is complicated and that qualitative neutralization assays cannot discriminate between flaviviruses.Trop. Med. Infect. Dis. 2020, 5, 38 2 of 14 with ZIKV, dengue virus (DENV) and other endemic flaviviruses is recommended by the Centers for Disease Control and Prevention ( CDC) to confirm diagnosis when RT-PCR is negative, and IgM ELISA is "not negative" [7]. Unfortunately, even PRNT can be problematic for diagnosis with over half of patients exhibiting significant neutralization of ZIKV, DENV, and other flaviviruses when positive for ZIKV IgM [9].ZIKV co-circulates with other flaviviruses, including DENV, West Nile virus (WNV), Japanese Encephalitis virus (JEV) and Yellow Fever virus (YFV). Antibody-based assays can be problematic as serological cross-reactivity can confound results [10][11][12]. Furthermore, previous exposures and co-infections can further complicate diagnostic tests [13][14][15]. Additional difficulties arise when diagnosing clinical samples in different locations as reference virus and antigen sources can produce divergent results in response to locally circulating viral isolates [16].Prior to the 2016 outbreak, there were very few ZIKV isolates available for use, which included the prototype MR−766 isolate as well as IbH 30656 a Nigerian isolate and DAK AR 41524 from Senegal (BEIResources.org). MR−766 had been extensively characterized prior to the outbreak and was the reference strain used by many researchers in the early days following emergence [6,[17][18][19][20]. Within a year of emergence, the CDC prototype PRVABC59 was released for use through BEI resources and many labs began using this modern isolate for their research and dia...

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