Dengue Virus and Its Risk to the U.S. Blood Supply

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Dengue Virus and Its Risk to the U.S. Blood Supply Blood Products Advisory Committee December 14, 2010 Deborah R. Taylor, Ph.D. Division of Emerging Transfusion Transmitted Diseases Center for Biologics Evaluation and Research

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Dengue Virus and Its Risk to the U.S. Blood Supply. Blood Products Advisory Committee December 14, 2010 Deborah R. Taylor, Ph.D. Division of Emerging Transfusion Transmitted Diseases Center for Biologics Evaluation and Research. Issue. FDA is seeking the advice of the Blood Products - PowerPoint PPT Presentation

Transcript of Dengue Virus and Its Risk to the U.S. Blood Supply

Page 1: Dengue Virus and Its Risk to the U.S. Blood Supply

Dengue Virus and Its Risk to the U.S. Blood Supply

Blood Products Advisory CommitteeDecember 14, 2010

Deborah R. Taylor, Ph.D.

Division of Emerging Transfusion Transmitted DiseasesCenter for Biologics Evaluation and Research

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FDA is seeking the advice of the Blood Products Advisory Committee on:

1. an appropriate strategy, including donor deferral, to mitigate the risk of dengue virus infection in recipients of blood and blood components for transfusion.

2. the potential utility of donor screening either by a nucleic acid-based test (NAT), an antibody test, and/or an antigen test, given the current technological limitations.

Issue

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Genus

Flavivirus WNV, Dengue, Yellow Fever, TBE

Pestivirus Bovine Viral Diarrhea Viruses

Hepacivirus Hepatitis C

Flaviviridae Family

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Dengue Viruses

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Dengue Viruses

Structural Proteins Nonstructural (NS) Proteins

C prM E NS1 AA B B

NS2NS3 NS5

NS4Core

Pre-MembraneEnvelope

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• Threatens 2.5 billion people worldwide • More than 50 million infections occur each year• More than 24,000 deaths per year

Dengue Virus (DENV): Most common vector-borne virus

Dengue

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Urbanization

Population migration

Population growth

Global travel

Climate change

Ineffective mosquito control

DENV has expanded its range and increased worldwide

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Autochthonous DENV in the U.S.

Pacific Islands

Puerto Rico and the U.S. Virgin Islands

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Both important mosquito vectors occur in the U.S.

Aedes albopictusAedes aegypti

2006

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The incubation period can be 15 days withan unknown level and duration of viremia.50-80% of infections are asymptomatic.

Primary DENV infection: Immune response

Viral RNA

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The incubation period can be 15 days with an unknown level and duration of viremia. 50-80% of infections are asymptomatic.

The viral NS1 protein is secreted early in infection and usually correlates with symptom onset/severity.

Primary DENV infection: Immune response

NS1

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The incubation period can be 15 days with an unknown level and duration of viremia. 50-80% of infections are asymptomatic.

The viral NS1 protein is secreted early in infection and usually correlates with symptom onset/severity.

IgM is usually detectable at 3-5 days after infection and declines at 2 weeks.

Primary DENV infection: Immune response

NS1IgM

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NS1IgM

IgG

The incubation period can be 15 days with an unknown level and duration of viremia. 50-80% of infections are asymptomatic.

The viral NS1 protein is secreted early in infection and usually correlates with symptom onset/severity.

IgM is usually detectable at 3-5 days after infection and declines at 2 weeks.

IgG increases after 10 days and is lifelong.

Primary DENV infection: Immune response

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Rapid increase in IgG to higherlevels within 2 weeks.

Secondary DENV infection: Immune response

NS1IgM

IgG

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Rapid increase in IgG to higherlevels within 2 weeks.

Lower or absent IgM

Secondary DENV infection: Immune response

NS1IgM

IgG

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Rapid increase in IgG to higher levels within 2 weeks.

Lower or absent IgM

Persons can acquire a second dengue infection with a different serotype, and secondary infections place them at greater risk for severe dengue.

Secondary DENV infection: Immune response

NS1IgM

IgG

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Transfusion transmitted DENV has been reportedinvolving all blood components:

Fresh Frozen Plasma (FFP) Red Blood Cells (RBC) Platelets

5 reported transmissions from 3 donations

Transfusion-related Transmission

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1) The high proportion of asymptomatic infections

2) The high incidence during outbreaks

3) The unknown duration of viremia

4) Lack of a licensed test

5) Lack of recognition by clinicians

6) Lack of surveillance and reporting

The rate of transmissibility by transfusion may be

inaccurate due to:

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• Currently, there are no FDA approved or licensed tests for diagnosis or screening for DENV.

• DENV can be detected by viral isolation, antigen, and nucleic acid tests.

• Antibody tests may detect a past or present infection.

Potential Screening Methods:

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Nucleic Acid Tests RT-PCR and TMA assays are highly sensitive for detecting viral

RNA from all 4 serotypes early in infection.

Dengue NS1 antigen ELISA NS1 antigen assay may be useful for the detection of the

virus early in infection to identify asymptomatic infected people.

Immunoglobulin IgM or IgG ELISA May not reflect an active infection but may confirm a past or present infection.

Potential Screening Methods:

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K. Tomashek DENV Epidemiology in the U.S. and territories

L. Petersen Risk Model to Define Rate of Infectious Units During

DENV Outbreaks: Endemic vs Nonendemic Areas

M. Rios Dengue Virus Panel Development

M. Busch Overview of Data on Blood Donor Testing and Transfusion Transmission of Dengue Virus

H. Margolis Experience with Dengue Virus Antigen Tests

S. Stramer Recent Experience in Testing Blood Donors in Puerto Rico and Key West, FL

Risk of Dengue Virus Infection: Presentations

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1. Are safety interventions warranted to address the risk of transfusion transmission of Dengue viruses in the US?

2. Do the available scientific data support a temporary deferral for donors living in U.S. non-endemic / non-outbreak areas who have traveled to an outbreak and/or endemic area? If so, what deferral period should FDA consider?

3. Please discuss what interventions, if any, would be appropriate for donors who are residents of endemic or outbreak regions within the U.S. and its territories.

4. Please comment on the potential utility of Dengue virus tests (nucleic acid, antibody and antigen tests) in donor screening.

Questions for the Committee:

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1. Are safety interventions warranted to address the risk of transfusion transmission of Dengue viruses in the US?

2. Do the available scientific data support a temporary deferral for donors living in U.S. non-endemic / non-outbreak areas who have traveled to an outbreak and/or endemic area? If so, what deferral period should FDA consider?

3. Please discuss what interventions, if any, would be appropriate for donors who are residents of endemic or

outbreak regions within the U.S. and its territories.

4. Please comment on the potential utility of Dengue virus tests (nucleic acid, antibody and antigen tests) in donor screening.

Questions for the Committee:

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1. Are safety interventions warranted to address the risk of transfusion transmission of Dengue viruses in the US?

2. Do the available scientific data support a temporary deferral for donors living in U.S. non-endemic / non-outbreak areas who have traveled to an outbreak and/or endemic area? If so, what deferral period should FDA consider?

3. Please discuss what interventions, if any, would be appropriate for donors who are residents of endemic or outbreak regions within the U.S. and its territories.

4. Please comment on the potential utility of Dengue virus tests (nucleic acid, antibody and antigen tests) in donor screening.

Questions for the Committee:

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1. Are safety interventions warranted to address the risk of transfusion transmission of Dengue viruses in the US?

2. Do the available scientific data support a temporary deferral for donors living in U.S. non-endemic / non-outbreak areas who have traveled to an outbreak and/or endemic area? If so, what deferral period should FDA consider?

3. Please discuss what interventions, if any, would be appropriate for donors who are residents of endemic or outbreak regions within the U.S. and its territories.

4. Please comment on the potential utility of Dengue virus tests (nucleic acid, antibody and antigen tests) in donor screening.

Questions for the Committee:

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1. Are safety interventions warranted to address the risk of transfusion transmission of Dengue viruses in the US?

2. Do the available scientific data support a temporary deferral for donors living in U.S. non-endemic / non-outbreak areas who have traveled to an outbreak and/or endemic area? If so, what deferral period should FDA consider?

3. Please discuss what interventions, if any, would be appropriate for donors who are residents of endemic or outbreak regions within the U.S. and its territories.

4. Please comment on the potential utility of Dengue virus tests (nucleic acid, antibody and antigen tests) in donor screening.

Questions for the Committee:

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1. Are safety interventions warranted to address the risk of transfusion transmission of Dengue viruses in the US?

2. Do the available scientific data support a temporary deferral for donors living in U.S. non-endemic / non-outbreak areas who have traveled to an outbreak and/or endemic area? If so, what deferral period should FDA consider?

3. Please discuss what interventions, if any, would be appropriate for donors who are residents of endemic or outbreak regions within the U.S. and its territories.

4. Please comment on the potential utility of Dengue virus tests (nucleic acid, antibody and antigen tests) in donor screening.

Questions for the Committee:

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Potential Interventions

Testing with or without confirmatory test

Import restrictions from endemic areas to nonendemic areas

New questions for donor questionaire

-Deferral for travel

-Deferral for residents of outbreak region

-Deferral for residents of endemic region

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Dengue occurs in many of the same areas as malaria

Dengue

Malaria