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Negative RT-PCR result doesn’t exclude Zika infection

Blood sample collection

Photo by Jeremy L. Grisham

The Centers for Disease Control and Prevention (CDC) has issued an interim guidance on how to interpret results of the Zika virus antibody test.

Over the past few weeks, the FDA has authorized the use of new Zika tests, including RealStar® Zika Virus RT-PCR Kit U.S., Zika Virus RNA Qualitative Real-Time RT-PCR test, and the Trioplex Real-time RT-PCR Assay.

The CDC is now updating its guidance, since a negative real time reverse transcription-polymerase chain reaction (rRT-PCR) test does not necessarily rule out Zika infection.

In these cases, the CDC recommends immunoglobulin (Ig) M and neutralizing antibody testing, which can identify additional recent Zika virus infections.

The Zika antibody test, however, is difficult to interpret because of cross-reactivity with other flaviviruses. Zika is a mosquito-borne flavivirus that is closely related to dengue, West Nile, Japanese encephalitis, and yellow fever viruses.

The cross-reactivity can preclude identification of the specific infecting virus, particularly if a person was previously infected with or vaccinated against a related flavivirus. And appropriate clinical management is dependent upon proper identification of the virus.

If IgM test results are positive, equivocal, or inconclusive, the CDC recommends performing a plaque reduction neutralization test (PRNT) to confirm the diagnosis.

However, in people who have been previously infected with or vaccinated against a related flavivirus, even a 4-fold higher titer by PRNT may not be able to discriminate between anti-Zika virus antibodies and cross-reacting antibodies.

Therefore, the CDC now recommends an even more conservative approach to interpreting PRNT results to reduce the possibility of missing the diagnosis of either Zika or dengue virus infection.

The US Food and Drug Administration issued in February an Emergency Use Authorization for the CDC Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA) for antibody testing.

It is used to detect Zika virus IgM antibodies in serum or cerebrospinal fluid from people with suspect Zika virus disease.

Presumptive positive results should be confirmed with PRNT against Zika, dengue, and other flaviviruses.

Equivocal and inconclusive results that are not resolved by re-testing should also have PRNT performed to rule out false-positive results.

For more information on interpretation of the Zika virus antibody test results, see the CDC’s Interim Guidance published as part of the Morbidity and Mortality Weekly Report for 31 May 2016.

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Blood sample collection

Photo by Jeremy L. Grisham

The Centers for Disease Control and Prevention (CDC) has issued an interim guidance on how to interpret results of the Zika virus antibody test.

Over the past few weeks, the FDA has authorized the use of new Zika tests, including RealStar® Zika Virus RT-PCR Kit U.S., Zika Virus RNA Qualitative Real-Time RT-PCR test, and the Trioplex Real-time RT-PCR Assay.

The CDC is now updating its guidance, since a negative real time reverse transcription-polymerase chain reaction (rRT-PCR) test does not necessarily rule out Zika infection.

In these cases, the CDC recommends immunoglobulin (Ig) M and neutralizing antibody testing, which can identify additional recent Zika virus infections.

The Zika antibody test, however, is difficult to interpret because of cross-reactivity with other flaviviruses. Zika is a mosquito-borne flavivirus that is closely related to dengue, West Nile, Japanese encephalitis, and yellow fever viruses.

The cross-reactivity can preclude identification of the specific infecting virus, particularly if a person was previously infected with or vaccinated against a related flavivirus. And appropriate clinical management is dependent upon proper identification of the virus.

If IgM test results are positive, equivocal, or inconclusive, the CDC recommends performing a plaque reduction neutralization test (PRNT) to confirm the diagnosis.

However, in people who have been previously infected with or vaccinated against a related flavivirus, even a 4-fold higher titer by PRNT may not be able to discriminate between anti-Zika virus antibodies and cross-reacting antibodies.

Therefore, the CDC now recommends an even more conservative approach to interpreting PRNT results to reduce the possibility of missing the diagnosis of either Zika or dengue virus infection.

The US Food and Drug Administration issued in February an Emergency Use Authorization for the CDC Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA) for antibody testing.

It is used to detect Zika virus IgM antibodies in serum or cerebrospinal fluid from people with suspect Zika virus disease.

Presumptive positive results should be confirmed with PRNT against Zika, dengue, and other flaviviruses.

Equivocal and inconclusive results that are not resolved by re-testing should also have PRNT performed to rule out false-positive results.

For more information on interpretation of the Zika virus antibody test results, see the CDC’s Interim Guidance published as part of the Morbidity and Mortality Weekly Report for 31 May 2016.

Blood sample collection

Photo by Jeremy L. Grisham

The Centers for Disease Control and Prevention (CDC) has issued an interim guidance on how to interpret results of the Zika virus antibody test.

Over the past few weeks, the FDA has authorized the use of new Zika tests, including RealStar® Zika Virus RT-PCR Kit U.S., Zika Virus RNA Qualitative Real-Time RT-PCR test, and the Trioplex Real-time RT-PCR Assay.

The CDC is now updating its guidance, since a negative real time reverse transcription-polymerase chain reaction (rRT-PCR) test does not necessarily rule out Zika infection.

In these cases, the CDC recommends immunoglobulin (Ig) M and neutralizing antibody testing, which can identify additional recent Zika virus infections.

The Zika antibody test, however, is difficult to interpret because of cross-reactivity with other flaviviruses. Zika is a mosquito-borne flavivirus that is closely related to dengue, West Nile, Japanese encephalitis, and yellow fever viruses.

The cross-reactivity can preclude identification of the specific infecting virus, particularly if a person was previously infected with or vaccinated against a related flavivirus. And appropriate clinical management is dependent upon proper identification of the virus.

If IgM test results are positive, equivocal, or inconclusive, the CDC recommends performing a plaque reduction neutralization test (PRNT) to confirm the diagnosis.

However, in people who have been previously infected with or vaccinated against a related flavivirus, even a 4-fold higher titer by PRNT may not be able to discriminate between anti-Zika virus antibodies and cross-reacting antibodies.

Therefore, the CDC now recommends an even more conservative approach to interpreting PRNT results to reduce the possibility of missing the diagnosis of either Zika or dengue virus infection.

The US Food and Drug Administration issued in February an Emergency Use Authorization for the CDC Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA) for antibody testing.

It is used to detect Zika virus IgM antibodies in serum or cerebrospinal fluid from people with suspect Zika virus disease.

Presumptive positive results should be confirmed with PRNT against Zika, dengue, and other flaviviruses.

Equivocal and inconclusive results that are not resolved by re-testing should also have PRNT performed to rule out false-positive results.

For more information on interpretation of the Zika virus antibody test results, see the CDC’s Interim Guidance published as part of the Morbidity and Mortality Weekly Report for 31 May 2016.

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