Dengue Virus and Its Risk to the U.S. Blood Supply Blood Products Advisory Committee December 14,...
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Transcript of Dengue Virus and Its Risk to the U.S. Blood Supply Blood Products Advisory Committee December 14,...
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
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
Genus
Flavivirus WNV, Dengue, Yellow Fever, TBE
Pestivirus Bovine Viral Diarrhea Viruses
Hepacivirus Hepatitis C
Flaviviridae Family
Dengue Viruses
Structural Proteins Nonstructural (NS) Proteins
C prM E NS1 AA B B
NS2
NS3 NS5
NS4Core
Pre-Membrane
Envelope
• 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
Urbanization
Population migration
Population growth
Global travel
Climate change
Ineffective mosquito control
DENV has expanded its range and increased worldwide
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
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
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
NS1
IgM
NS1
IgM
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
Rapid increase in IgG to higherlevels within 2 weeks.
Secondary DENV infection: Immune response
NS1
IgM
IgG
Rapid increase in IgG to higherlevels within 2 weeks.
Lower or absent IgM
Secondary DENV infection: Immune response
NS1
IgM
IgG
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
NS1
IgM
IgG
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
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:
• 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:
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:
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
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:
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:
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:
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:
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:
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:
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