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Zika-- Information for ELR CDC Vocabulary Team, 2016-0217 CDC has updated the lab testing algorithm Zika,, and viruses: http://www.cdc.gov/zika/state-labs/index.html Contents of this document 1. Lab tests and LOINC codes Testing during the first week of illness IgM antibody testing Confirmation by plaque-reduction neutralization (PRNT) 2. Test results and SNOMED codes Zika virus results for CDC serology tests SNOMED codes for Zika,, and viruses SNOMED codes for qualitative results 3. Links to VADS value sets for Zika,, and 4. For more information Lab tests and LOINC codes Testing during the first week of illness During the first 7 days of these illnesses, viral RNA can often be identified in serum, and RT-PCR is the preferred test for Zika, chikungunya, and dengue viruses. In addition, for dengue viruses, NS1 antigen can be detected by ELISA in acute phase specimens but this assay is not widely available in the US. Because viremia decreases over time, a negative RT-PCR collected 5-7 days after symptom onset does not exclude flavivirus infection and serologic testing should be performed. LOINC codes for Zika, and PCRs are shown below.

Virus Zika virus Concept Concept Name 79190-5 ZIKV RNA XXX Ql PCR 60260-7 CHIKV RNA SerPl Ql PCR 51664-1 CHIKV RNA XXX Ql PCR 60262-3 DENV1 RNA Ser Ql PCR 60420-7 DENV2 RNA Ser Ql PCR 60419-9 DENV3 RNA Ser Ql PCR 60418-1 DENV4 RNA Ser Ql PCR 7855-0 DENV1+2+3+4 RNA Ser Ql PCR 77958-7 DENV 1+2+3+4 RNA CSF Ql PCR 75377-2 DENV NS1 Ag SerPlBld Ql EIA.rapid Preferred Name Zika virus RNA [Presence] in Unspecified specimen by Probe and target amplification method virus RNA [Presence] in Serum or Plasma by Probe and target amplification method virus RNA [Presence] in Unspecified specimen by Probe and target amplification method virus 1 RNA [Presence] in Serum by virus 2 RNA [Presence] in Serum by virus 3 RNA [Presence] in Serum by virus 4 RNA [Presence] in Serum by virus 1+2+3+4 RNA [Presence] in Serum by Probe and target amplification method virus 1 and 2 and 3 and 4 RNA [Presence] in Cerebral spinal fluid by Probe and target amplification method virus NS1 Ag [Presence] in Serum, Plasma or Blood by Rapid immunoassay System ICD-10 PCS CPT MedlinePlus Connect Topic IgM antibody testing Virus-specific IgM antibodies may be detectable >4 days after onset of illness. However, serum collected within 7 days of illness onset may not have detectable virus-specific IgM antibodies. IgM antibodies against Zika virus, dengue viruses, and other flaviviruses have strong cross- reactivity which may generate false positive results in serological tests. The table below contains some LOINC codes for Zika,, and virus IgM in serum or CSF.

Virus Zika virus Concept Concept Name 80618-2 ZIKV IgM CSF EIA-aCnc 80619-0 ZIKV IgM Ser EIA-aCnc Preferred Name Zika virus IgM Ab [Units/volume] in Cerebral spinal fluid by Immunoassay Zika virus IgM Ab [Units/volume] in Serum by Immunoassay 57934-2 CHIKV IgM Ser Ql virus IgM Ab [Presence] in Serum 56131-6 CHIKV IgM SerPl Ql IF virus IgM Ab [Presence] in Serum or Plasma by Immunofluorescence 56130-8 CHIKV IgM Titr SerPl IF virus IgM Ab [Titer] in Serum or Plasma by Immunofluorescence 56131-6 CHIKV IgM SerPl Ql IF virus IgM Ab [Presence] in Serum or Plasma by Immunofluorescence 56130-8 CHIKV IgM Titr SerPl IF virus IgM Ab [Titer] in Serum or Plasma by Immunofluorescence 57934-2 CHIKV IgM Ser Ql virus IgM Ab [Presence] in Serum 23992-1 DENV IgM Ser EIA-aCnc virus IgM Ab [Units/volume] in Serum by Immunoassay 23968-1 DENV IgM Ser-aCnc virus IgM Ab [Units/volume] in Serum 29663-2 DENV IgM Ser Ql EIA virus IgM Ab [Presence] in Serum by Immunoassay 6812-2 DENV IgM Titr Ser virus IgM Ab [Titer] in Serum 25338-5 DENV IgM Ser Ql virus IgM Ab [Presence] in Serum 34721-1 DENV IgM CSF Ql virus IgM Ab [Presence] in Cerebral spinal fluid System ICD-10 PCS Notes: 1. Currently there is no LOINC code for virus IgM in serum or CSF by EIA (quantitative). 2. Currently there is no LOINC code for virus IgM in CSF by EIA (quantitative). (CNS dengue infection is rare but it can occur.) CPT MedlinePlus Connect Topic Confirmation by plaque-reduction neutralization (PRNT) Due to serological cross-reactivity between flaviviruses, current IgM antibody assays cannot reliably distinguish between Zika and dengue virus infections. Therefore, an IgM positive result in a dengue or Zika IgM ELISA test should be considered indicative of a recent flavivirus infection.

Plaque-reduction neutralization tests (PRNT) can be performed to measure virus-specific neutralizing antibodies and may be able to determine the cause of primary flavivirus infection. In patients who have received yellow fever or Japanese encephalitis vaccination or infected with another flavivirus in the past, cross-reactive antibodies in both the IgM and neutralizing antibody assays may make it difficult to identify which flavivirus is causing the patient's current illness. The table below shows some LOINCs for neutralization tests. Virus Zika virus Concept Concept Name Preferred Name 80620-8 ZIKV NAb Titr Ser Nt Zika virus neutralizing antibody [Titer] in Serum by Neutralization test 80621-6 ZIKV NAb Titr CSF Nt Zika virus neutralizing antibody [Titer] in Cerebral spinal fluid by Neutralization test The LOINCs below can be used for paired specimens 80622-4 ZIKV NAb sp1 Titr Ser Nt Zika virus neutralizing antibody [Titer] in Serum by Neutralization test --1st specimen 80623-2 ZIKV NAb sp2 Titr Ser Nt Zika virus neutralizing antibody [Titer] in Serum by Neutralization test --2nd specimen 80624-0 ZIKV NAb sp1 Titr CSF Nt Zika virus neutralizing antibody [Titer] in Cerebral spinal fluid by Neutralization test --1st specimen 80625-7 ZIKV NAb sp2 Titr CSF Nt Zika virus neutralizing antibody [Titer] in Cerebral spinal fluid by Neutralization test --2nd specimen 43064-5 CHIKV Ab Titr Ser virus Ab [Titer] in Serum 55438-6 DENV Ab Titr Ser Nt 50036-3 DENV Ab XXX Ql Nt virus Ab [Titer] in Serum by Neutralization test virus Ab [Presence] in Unspecified specimen by Neutralization test System ICD-10 PCS CPT MedlinePlus Connect Topic Notes: 1. Currently there is no LOINC code for virus antibodies in serum or CSF by neutralization. For now 43064-5 (above) can be used for the serum antibodies by neutralization assay. 2. Currently there is no LOINC code yet for virus antibodies in CSF by neutralization. For now, 50036-3 (above) can be used, although it is a qualitative result. ( infection of the CNS is rare but it can occur.)

Lab test result codes Zika virus IgM ELISA results For CDC's Zika virus IgM ELISA, the result is a number without units. A result <2 is Negative; 2-3 is Equivocal (or presumed false positive); >3 is Positive. Example results: 1.3, 8.5, 23.2, etc. Zika virus PRNT results Units and reference range: A titer < 1:10 is normal (negative test). Example results: <1:10, 1:80, 1:320, 1:2560, etc. Titer results might also be expressed as simple numbers (<10, 80, 320, 2560, etc.) SNOMED codes All of the tests in the tables above have either numeric or qualitative results. Some other ELR messaging situations might require SNOMED codes for Zika virus, virus, and virus. These are shown in the table below. Virus Concept Concept Name Preferred Name System MedlinePlus Connect Topic Zika virus disease 50471002 Zika virus (organism) Zika virus SCT 2423009 virus (organism) virus SCT 34348001 virus (organism) virus SCT 60588009 virus, type 1 (organism) virus, type 1 SCT 41328007 virus, type 2 (organism) virus, type 2 SCT 8467002 virus, type 3 (organism) virus, type 3 SCT 36700002 virus, type 4 (organism) virus, type 4 SCT Qualitative results: The table below contains some qualitative results that might be used for Zika,, and testing. Result type Snomed ID Snomed FullySpecifiedName Snomed PreferredTerm system Positive 260373001 Detected (qualifier value) Detected SCT Positive 10828004 Positive (qualifier value) Positive SCT Positive 11214006 Reactive (qualifier value) Reactive SCT Inconclusive 42425007 Equivocal (qualifier value) Equivocal SCT

Result type Snomed ID Snomed FullySpecifiedName Snomed PreferredTerm system Inconclusive 82334004 Indeterminate (qualifier value) Indeterminate SCT Inconclusive 419984006 Inconclusive (qualifier value) Inconclusive SCT Negative 260385009 Negative (qualifier value) Negative SCT Negative 260415000 Not detected (qualifier value) Not detected SCT Negative 131194007 Non-Reactive (qualifier value) Non-Reactive SCT Links to the complete value sets in VADS: Condition Value Set Name Link to value set Zika virus disease Lab Result (Zika virus) https://phinvads.cdc.gov/vads/viewvalueset.action?oid=2.16.840.1.114222.4.11.7479 Lab Test Name (Zika virus) https://phinvads.cdc.gov/vads/viewvalueset.action?oid=2.16.840.1.114222.4.11.7480 Lab Result ( virus) https://phinvads.cdc.gov/vads/viewvalueset.action?oid=2.16.840.1.114222.4.11.7343 Lab Test Name ( virus) https://phinvads.cdc.gov/vads/viewvalueset.action?oid=2.16.840.1.114222.4.11.7339 Lab Result () https://phinvads.cdc.gov/vads/viewvalueset.action?oid=2.16.840.1.114222.4.11.4025 Lab Test Name () https://phinvads.cdc.gov/vads/viewvalueset.action?oid=2.16.840.1.114222.4.11.4141 Qualitative results Qual Lab Result Positive (Reportable Conditions) https://phinvads.cdc.gov/vads/viewvalueset.action?oid=2.16.840.1.114222.4.11.7234 Qual Lab Result Negative (Reportable Conditions) https://phinvads.cdc.gov/vads/viewvalueset.action?oid=2.16.840.1.114222.4.11.7235 Qual Lab Result Inconc (Reportable Conditions) https://phinvads.cdc.gov/vads/viewvalueset.action?oid=2.16.840.1.114222.4.11.7236 For more information CDC's lab testing algorithm Zika,, and viruses: http://www.cdc.gov/zika/state-labs/index.html CDC Zika virus home page: http://www.cdc.gov/zika/index.html