Detection of Specific ZIKV IgM in Travelers Using a Multiplexed Flavivirus Microsphere Immunoassay
Abstract
:1. Introduction
2. Materials and Methods
2.1. Bead Coupling to Monoclonal Antibody for FlaviMIA
2.2. Production of Purified Whole Virus Antigen Preparations for FlaviMIA
2.3. Binding of Flavivirus Preparations to Monoclonal Antibody-Coupled Microspheres for FlaviMIA
2.4. Reference Sera
2.5. Flavivirus Screening Assays
2.6. Flavivirus-Specific IgM Serology—FlaviMIA
2.7. ZIKV PRNT
3. Results
3.1. FlaviMIA Validation
3.2. Analysis of Patient Samples
3.3. Patients with Recent Primary ZIKV Infections
3.4. Patients with Recent Secondary ZIKV Infections
3.5. Patients with Past ZIKV Infection
3.6. Patients with ZIKV/DENV IgM
4. Discussion
Supplementary Materials
Author Contributions
Acknowledgments
Conflicts of Interest
References
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Group Reference Number | Laboratory Reference No. | Sex | Age | Flavivirus IgG ELISA Result | Flavivirus IgG ELISA Results | FlaviMIA Result | FlaviMIA Result | SI | RT-PCR Result | PRNT Result | Year/Travel Region |
---|---|---|---|---|---|---|---|---|---|---|---|
1st Sample | 2nd Sample | 1st Sample | 2nd Sample | ||||||||
Group 1: recent ZIKV infection—primary | |||||||||||
#1 | 1 | M | 40 | Negative | Positive | Negative | Positive (ZIKV specific) | 19 | Not detected | Positive | 2013 Thailand |
#2 | 2 | M | 34 | Negative | Positive | Negative | Positive (ZIKV specific) | 14 | Not detected | Positive | 2013 Vietnam |
#3 | 3 | M | 30 | Negative | nss | Negative | nss | n/a | ZIKV RNA detected | Insufficient | 2014 Cook Islands |
#4 | 7 | M | 58 | Negative | Positive | Negative | Positive (ZIKV specific) | 6 | ZIKV RNA detected | Positive | 2014 Cook Islands |
#5 | 9 | M | 32 | Negative | nss | Negative | nss | n/a | ZIKV RNA detected | Negative | 2014 Cook Islands |
#6 | 12 | M | 38 | Negative | nss | Negative | nss | n/a | ZIKV RNA detected | Insufficient | 2014 Cook Islands |
#7 | 13 | M | 79 | Negative | nss | Negative | nss | n/a | ZIKV RNA detected | Insufficient | 2014 Cook Islands |
#8 | 14 | M | 24 | Negative | Negative | Negative | Positive (ZIKV specific) | 4 | ZIKV RNA detected | Negative | 2014 Cook Islands |
#9 | 15 | F | 7 | Negative | Positive | Negative | Positive (ZIKV specific) | 35 | Not detected | Positive | 2014 Country of travel not identified |
#10 | 16 | F | 37 | Negative | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 15 | Not detected | Positive | 2014 Country of travel not identified |
#11 | 19 | F | 42 | Negative | Positive | Negative | Positive (cross-reactive) | 19 | ZIKV RNA detected | Positive | 2014 Vanuatu |
#12 | 20 | F | 43 | Negative | Positive | Negative | Positive (ZIKV specific) | 16 | Not detected | Positive | 2015 Bali |
#13 | 26 | M | 48 | Negative | nss | Negative | nss | n/a | ZIKV RNA detected | Negative | 2015 Solomon Islands |
#14 | 27 | M | 45 | Negative | nss | Negative | nss | n/a | ZIKV RNA detected | Negative | 2015 Solomon Islands |
#15 | 29 | M | 33 | Negative | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 15 | ZIKV RNA detected | Positive | 2015 Solomon Islands |
#16 | 30 | M | 52 | Negative | nss | Positive (ZIKV specific) | nss | n/a | Not detected | Positive | 2015 Solomon Islands |
#17 | 32 | M | 29 | Negative | Positive | Negative | Positive (ZIKV specific) | 91 | Not detected | Positive | 2015 Solomon Islands |
#18 | 33 | F | 22 | Negative | Positive | Negative | Positive (ZIKV specific) | 10 | ZIKV RNA detected | Positive | 2015 Vanuatu |
#19 | 34 | F | 33 | Negative | nss | Positive (ZIKV specific) | nss | n/a | ZIKV RNA detected | Positive | 2015 Vanuatu |
#20 | 47 | F | 30 | Negative | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 14 | ZIKV RNA detected | Positive | 2016 Fiji |
#21 | 52 | F | 22 | Negative | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 17 | Not detected | Positive | 2016 Fiji |
#22 | 53 | F | 62 | Negative | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 16 | Not detected | Positive | 2016 Fiji |
#23 | 57 | F | 17 | Negative | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 24 | Not detected | Positive | 2016 Fiji/Samoa |
#24 | 60 | M | 50 | Negative | nss | Negative | nss | n/a | ZIKV RNA detected | Insufficient | 2016 Guyana |
#25 | 61 | M | 30 | Negative | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 26 | ZIKV RNA detected | Positive | 2016 Jamaica |
#26 | 64 | F | 33 | Negative | nss | Positive (ZIKV specific) | nss | n/a | ZIKV RNA detected | Negative | 2016 Mexico |
#27 | 65 | F | 33 | Negative | Positive | Negative | Positive (ZIKV specific) | 14 | Not detected | Positive | 2016 Mexico |
#28 | 68 | M | 37 | Negative | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 8 | Not detected | Positive | 2016 Mexico |
#29 | 69 | F | 42 | Negative | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 21 | Not detected | Positive | 2016 Mexico |
#30 | 71 | F | 21 | Negative | nss | Positive (ZIKV specific) | nss | n/a | Not detected | Positive | 2016 Nicaragua |
#31 | 74 | F | 28 | Negative | Positive | Negative | Positive (ZIKV specific) | 16 | ZIKV RNA detected | Positive | 2016 Samoa |
#32 | 76 | F | 2 | Negative | nss | Positive (ZIKV specific) | nss | n/a | ZIKV RNA detected | Positive | 2016 Samoa |
#33 | 81 | F | 28 | Negative | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 15 | Not detected | Positive | 2016 Solomon Is |
#34 | 84 | F | 43 | Negative | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 14 | Not detected | Positive | 2016 Thailand |
#35 | 86 | F | 37 | Negative | nss | Negative | Positive (ZIKV specific) | 46 | ZIKV RNA detected | Positive | 2016 Tonga |
#36 | 88 | F | 52 | Negative | nss | Negative | nss | n/a | ZIKV RNA detected | Negative | 2016 Tonga |
#37 | 89 | F | 23 | Negative | Positive | Positive (cross-reactive) | Positive (ZIKV specific) | 14 | Not detected | Positive | 2016 Tonga |
#38 | 92 | M | 41 | Negative | Negative | Positive (ZIKV specific) | Positive (ZIKV specific) | 11 | Not detected | Positive | 2016 Tonga |
#39 | 94 | M | 43 | Negative | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 94 | ZIKV RNA detected | Positive | 2016 Vanuatu/Fiji |
#40 | 95 | F | 56 | Negative | nss | Negative | nss | n/a | ZIKV RNA detected | Negative | 2016 Vietnam |
#41 | 97 | F | 71 | Negative | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 12 | Not detected | Positive | 2017 Country of travel not identified |
#42 | 99 | F | 49 | Negative | nss | Negative | nss | n/a | Not detected | Positive | 2017 Cuba |
#43 | 100 | M | 33 | Negative | Positive | Negative | Positive (ZIKV specific) | 20 | ZIKV RNA detected | Positive | 2017 Cuba |
Group 2: recent ZIKV infection—secondary | |||||||||||
#1 | 4 | F | 42 | Positive | nss | Positive (cross-reactive) | nss | n/a | ZIKV RNA detected | Positive | 2014 Cook Islands |
#2 | 5 | M | 30 | Positive | nss | Positive (ZIKV specific) | nss | n/a | ZIKV RNA detected | Negative | 2014 Cook Islands |
#3 | 6 | F | 43 | Positive | nss | Positive (cross-reactive) | nss | n/a | ZIKV RNA detected | Insufficient | 2014 Cook Islands |
#4 | 8 | F | 65 | Positive | Positive | Positive (DENV-4 specific) | Positive (ZIKV specific) | 23 | ZIKV RNA detected | Positive | 2014 Cook Islands |
#5 | 10 | F | 38 | Positive | Positive | Negative | Positive (DENV-2 specific) | 20 | ZIKV RNA detected | Positive | 2014 Cook Islands |
#6 | 11 | M | 31 | Positive | Positive | Positive (DENV-2 specific) | Positive (cross-reactive) | 23 | ZIKV RNA detected | Positive | 2014 Cook Islands |
#7 | 23 | F | 51 | Positive | Positive | Negative | Positive (cross-reactive) | 30 | ZIKV RNA detected | Positive | 2015 El Salvador |
#8 | 24 | M | 55 | Positive | Positive | Negative | Positive (ZIKV specific) | 25 | Not detected | Positive | 2015 Samoa |
#9 | 25 | M | 46 | Positive | nss | Negative | nss | n/a | ZIKV RNA detected | Insufficient | 2015 Solomon Islands |
#10 | 28 | F | 26 | Positive | nss | Negative | nss | n/a | ZIKV RNA detected | Positive | 2015 Solomon Islands |
#11 | 36 | M | 54 | Positive | Positive | Negative | Positive (cross-reactive) | 13 | ZIKV RNA detected | Positive | 2016 Bali |
#12 | 38 | M | 25 | Negative | nss | Positive (YFV specific) | nss | n/a | ZIKV RNA detected | Negative | 2016 Colombia |
#13 | 45 | M | 42 | Positive | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 15 | ZIKV RNA detected | Positive | 2016 El Salvador |
#14 | 46 | F | 45 | Positive | Positive | Negative | Positive (ZIKV specific) | 13 | ZIKV RNA detected | Positive | 2016 Fiji |
#15 | 62 | F | 25 | Positive | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 14 | ZIKV RNA detected | Positive | 2016 Mexico |
#16 | 63 | M | 34 | Positive | nss | Positive (ZIKV specific) | nss | n/a | ZIKV RNA detected | Negative | 2016 Mexico |
#17 | 75 | M | 52 | Positive | nss | Positive (ZIKV specific) | nss | n/a | ZIKV RNA detected | Positive | 2016 Samoa |
#18 | 82 | F | 60 | Positive | Positive | Negative | Positive (ZIKV specific) | 22 | ZIKV RNA detected | Positive | 2016 Solomon Islands |
#19 | 83 | F | 30 | Negative | Positive | Positive (YFV specific) | Positive (ZIKV specific) | 18 | ZIKV RNA detected | Positive | 2016 Thailand |
#20 | 85 | F | 71 | Positive | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 13 | ZIKV RNA detected | Positive | 2016 Tonga |
#21 | 87 | M | 34 | Positive | nss | Negative | nss | n/a | ZIKV RNA detected | Insufficient | 2016 Tonga |
Group 3: patients with past ZIKV infection | |||||||||||
#1 | 18 | M | 77 | Positive | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 11 | Not detected | Positive | 2014 Papua New Guinea |
#2 | 21 | M | 43 | Positive | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 30 | Not tested | Positive | 2015 Brazil |
#3 | 37 | F | 68 | Positive | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 9 | Not tested | Positive | 2016 Caribbean |
#4 | 39 | F | 23 | Positive | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 26 | Not detected | Positive | 2016 Colombia |
#5 | 40 | M | 35 | Positive | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 22 | Not detected | Positive | 2016 Country of travel not identified |
#6 | 41 | F | 39 | Positive | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 14 | Not detected | Positive | 2016 Country of travel not identified |
#7 | 43 | F | 61 | Positive | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 17 | Not detected | Positive | 2016 Curacao |
#8 | 51 | F | 23 | Positive | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 17 | Not detected | Positive | 2016 Fiji |
#9 | 67 | M | 48 | Positive | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 28 | Not detected | Positive | 2016 Mexico |
#10 | 72 | M | 88 | Positive | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 9 | Not detected | Positive | 2016 No recent travel |
#11 | 73 | M | 82 | Positive | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 20 | Not detected | Positive | 2016 No recent travel |
#12 | 80 | M | 73 | Positive | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 36 | Not detected | Positive | 2016 Solomon Is |
#13 | 90 | M | 27 | Positive | Positive | Positive (cross-reactive) | Positive (ZIKV specific) | 14 | Not detected | Positive | 2016 Tonga |
#14 | 91 | F | 27 | Positive | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 10 | Not detected | Positive | 2016 Tonga |
Group 4: patients with ZIKV/DENV IgM | |||||||||||
#1 | 17 | F | 43 | Positive | nss | Positive (ZIKV specific) | nss | n/a | Not detected | Positive | 2014 Maldives |
#2 | 22 | M | 78 | Positive | Positive | Positive (ZIKV specific) | Positive (ZIKV/DENV) | 16 | Not tested | Positive | 2015 Burma |
Group 5: patients with recent or past ZIKV infection | |||||||||||
#1 | 31 | M | 37 | Positive | nss | Positive (ZIKV specific) | nss | n/a | Not detected | Positive | 2015 Solomon Islands |
#2 | 35 | F | 34 | Positive | nss | Positive (ZIKV specific) | nss | n/a | Not tested | Positive | 2015 Vanuatu |
#3 | 42 | M | 31 | Positive | nss | Positive (ZIKV specific) | nss | n/a | Not detected | Positive | 2016 Country of travel not identified |
#4 | 44 | F | 57 | Positive | Positive | Positive (ZIKV specific) | Positive (ZIKV specific) | 6 | Not detected | Positive | 2016 Dominican Republic |
#5 | 48 | F | 25 | Positive | nss | Positive (ZIKV specific) | nss | n/a | Not detected | Positive | 2016 Fiji |
#6 | 49 | M | 56 | Positive | nss | Positive (ZIKV specific) | nss | n/a | Not detected | Positive | 2016 Fiji |
#7 | 50 | F | 41 | Positive | nss | Positive (ZIKV specific) | nss | n/a | Not detected | Positive | 2016 Fiji |
#8 | 54 | M | 12 | Positive | nss | Positive (ZIKV specific) | nss | n/a | Not detected | Positive | 2016 Fiji |
#9 | 55 | F | 31 | Positive | nss | Positive (ZIKV specific) | nss | n/a | Not tested | Positive | 2016 Fiji |
#10 | 58 | M | 54 | Positive | nss | Positive (ZIKV specific) | nss | n/a | Not detected | Positive | 2016 Fiji/Tonga |
#11 | 59 | F | 30 | Positive | nss | Positive (ZIKV specific) | nss | n/a | Not tested | Positive | 2016 Guatemala/Belize |
#12 | 66 | F | 25 | Positive | nss | Positive (ZIKV specific) | nss | n/a | Not detected | Positive | 2016 Mexico |
#13 | 70 | F | 36 | Positive | nss | Positive (ZIKV specific) | nss | n/a | Not detected | Positive | 2016 Mexico |
#14 | 78 | M | 73 | Positive | nss | Positive (ZIKV specific) | nss | n/a | Not detected | Positive | 2016 Samoa |
#15 | 79 | F | 27 | Positive | nss | Positive (ZIKV specific) | nss | n/a | Not detected | Positive | 2016 Solomon Is |
#16 | 93 | F | 31 | Positive | nss | Positive (ZIKV specific) | nss | n/a | Not detected | Positive | 2016 Tonga |
#17 | 96 | M | 32 | Positive | nss | Positive (ZIKV specific) | nss | n/a | Not detected | Positive | 2016 Vietnam/Myanmar |
#18 | 98 | F | 20 | Positive | nss | Positive (ZIKV specific) | nss | n/a | Not detected | Positive | 2017 Country of travel not identified |
#19 | 101 | F | 36 | Positive | nss | Positive (ZIKV specific) | nss | n/a | Not tested | Positive | 2017 Fiji |
Group 6: patients with unconfirmed ZIKV infection/false positives | |||||||||||
#1 | 56 | M | 16 | Negative | Negative | Positive (ZIKV specific) | Positive (ZIKV specific) | 12 | Not detected | Negative | 2016 Fiji |
#2 | 77 | F | 52 | Negative | nss | Positive (ZIKV specific) | nss | n/a | Not detected | Negative | 2016 Samoa |
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Taylor, C.T.; Mackay, I.M.; McMahon, J.L.; Wheatley, S.L.; Moore, P.R.; Finger, M.J.; Hewitson, G.R.; Moore, F.A. Detection of Specific ZIKV IgM in Travelers Using a Multiplexed Flavivirus Microsphere Immunoassay. Viruses 2018, 10, 253. https://doi.org/10.3390/v10050253
Taylor CT, Mackay IM, McMahon JL, Wheatley SL, Moore PR, Finger MJ, Hewitson GR, Moore FA. Detection of Specific ZIKV IgM in Travelers Using a Multiplexed Flavivirus Microsphere Immunoassay. Viruses. 2018; 10(5):253. https://doi.org/10.3390/v10050253
Chicago/Turabian StyleTaylor, Carmel T., Ian M. Mackay, Jamie L. McMahon, Sarah L. Wheatley, Peter R. Moore, Mitchell J. Finger, Glen R. Hewitson, and Frederick A. Moore. 2018. "Detection of Specific ZIKV IgM in Travelers Using a Multiplexed Flavivirus Microsphere Immunoassay" Viruses 10, no. 5: 253. https://doi.org/10.3390/v10050253