Zika virus infection laboratory findings
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D., Nate Michalak, B.A., Serge Korjian M.D., Yamuna Kondapally, M.B.B.S[2]
Overview
The diagnosis of Zika virus infection is usually made by detection of elevated IgM and IgG Zika virus antibodies by ELISA or viral RNA by RT-PCR. Non-specific lab findings include elevated markers of inflammation, mild neutropenia, normal leukocyte count or mild leukocytosis with normal platelet count and liver function tests. State health departments are requested to report laboratory-confirmed Zika virus infections to CDC.
How soon to get tested
- Zika virus usually remains in the blood of an infected person for about a week. The following are the conditions where you have to consult your healthcare provider:
- Once a person has been infected, he or she is likely to be protected from future infections.
Laboratory Findings
- State health departments are requested to report laboratory-confirmed Zika virus infections to the CDC.
- Priority for diagnostic testing is given for individuals who are symptomatic and asymptomatic pregnant women with possible exposure to Zika virus.[1]
- The diagnosis of Zika virus infection is usually made by detection of elevated IgM and IgG Zika virus antibodies by ELISA or viral RNA by RT-PCR.
- According to WHO, routine semen testing for Zika virus is not recommended except for aymptomatic and symptomatic men returning from areas where transmission of Zika virus is known to occur.
- Patients with Zika virus may also have the following non-specific lab findings.
Non-Specific Laboratory Findings
- Elevated markers of inflammation and acute phase reactants (e.g. ESR, C-reactive protein, ferritin)
- Elevated lactate dehydrogenase (LDH)
- Mild neutropenia
- Normal leukocyte count / mild leukocytosis
- Platelet count and liver function tests (LFTs) are usually normal (vs. thrombocytopenia and elevated LFTs in Dengue fever)
ELISA
- ELISA can be used to detect virus-specific IgM (anti-ZIKV-IgM) and neutralizing antibodies toward the end of the first week of illness.
- Cross-reaction with related flaviviruses (e.g., Dengue and West Nile viruses) is common and may be difficult to discern.
- Plaque-reduction neutralization testing can be performed to measure virus-specific neutralizing antibodies and discriminate between cross-reacting antibodies in primary flavivirus infections.[2]
- According to the CDC, serologic assays should be used for testing of serum collected 14 days to 12 weeks after symptom onset and for RT-PCR negative serum collected within 14 days of illness onset.
PCR
- During the first week after onset of symptoms, Zika virus may be diagnosed by performing reverse transcriptase-polymerase chain reaction (RT-PCR) on serum.
- According to the CDC, RT-PCR testing of serum and urine is recommended less than 14 days after symptom onset.
WHO Interim Guidance For Laboratory Testing
According to WHO, the interim guidelines includes information on current testing strategies for Zika virus infection.[3]
Specimens
- The specimens collected for laboratory testing include:
- Whole blood (also serum and plasma)
- Urine
- Cerebrospinal fluid
- Amniotic fluid
- Semen
- Saliva
- Zika virus is present for longer periods in urine and semen than in whole blood or saliva.
- A blood or urine test can confirm ZIKV infection.
- Patient information on specimen should include:
- Contact with Zika virus cases and type of contact such as breastfeeding and sexual contact
- Symptoms, date of onset, and duration of symptoms
- Travel history (date, place, and duration of visit)
- Vaccination history (Flaviviruses including yellow fever virus, Japanese encephalitis virus, and dengue viruses)
- Groups that have to be prioritized for specimen collection and testing include:
- Patient with sexual contact with a confirmed or probable case
- Patients who meet the case definition of a suspected case with neurological disorders
- Pregnant women with a history of travel to endemic areas and/or sexual contact with a confirmed probable case
- Neonates with microcephaly or neurological abnormalities born in areas with ongoing Zika transmission or born to women with a history of travel to a Zika-affected area during pregnancy
- Infants with mothers diagnosed with Zika virus, especially if they are breastfeeding
- Still births or spontaneous abortions from women who have lived in or travelled to a Zika-affected area during the pregnancy
Nucleic acid testing (NAT)
- Done in patients presenting with onset of symptoms ≤7 days.
- The specimen for nucleic acid testing include whole blood, serum collected in a dry tube and/or urine.
Serology (IgM detection)
- Done in patients presenting with onset of symptoms ≥7days.
- The specimen for serology include whole blood and serum collected in a dry tube.
- First serum specimen should be ideally collected during the first 5 days of illness.
- Paired serum specimens should be collected at least 2-3 weeks apart.
Testing strategy
Nucleic acid amplification test (NAT)
Nucleic acid amplification test such as RT-PCR is preferred in cases with onset of symptoms <7 days
Serology and/or NAT
- Serology and/or NAT is preferred in cases with onset of symptoms ≥7 days.
- Serology is the preferred method in patients with onset of symptoms >7 days as negative NAT does not rule out infection because viremia drops rapidly 7 days after onset of symptoms and may not be detected by the test at the lower end of sensitivity.
- Recommended serological assays:
- Enzyme immunoassays (EIAs)
- Immunofluorescence assays (IFA)
- Plaque-reduction neutralization tests (PRNT)
Specimen processing and testing
- It is recommended that specimens are kept refrigerated at 2-8°C and tested within 48 hours.
- If the sample is delayed for more than 48 hours before testing, serum is separated and stored separately.
- Storage of samples:
- <7 days: Specimens are frozen at -20°C
- >7 days: Specimens are frozen at -70°C
References
- ↑ Laboratory tests http://apps.who.int/iris/bitstream/10665/204671/1/WHO_ZIKV_LAB_16.1_eng.pdf?ua=1 (March 23, 2016) Accessed on September 20, 2016
- ↑ For HealthCare Providers: Diagnostic Testing. Center for Disease Control and Prevention (June 1, 2015). http://www.cdc.gov/zika/hc-providers/diagnostic.html Accessed December 21, 2015.
- ↑ WHO Laboratory Guidelines http://apps.who.int/iris/bitstream/10665/204671/1/WHO_ZIKV_LAB_16.1_eng.pdf?ua=1 (March, 2016) Accessed on 21 September, 2016