Influenza Diagnostics Development and Distribution:

Responding to Emerging Threats

Michael W. Shaw, PhDInfluenza DivisionNational Center for Immunization and Respiratory Diseases

Actions for Diagnostic Preparedness:

• Develop New Diagnostic Tests and Improved Diagnostic Capabilities

• Improve Surge Capacity• Implement Challenge and Proficiency Testing• Develop Regulatory Preparedness• Improve Access to Tests and Reagents• Provide Guidance for Clinicians• Improve Virologic Surveillance

Serology(AntibodyDetection)

Immunofluorescence (Virus Detection)

WHO(GISRS)

Outpatient& Clinic

HospitalLab

ReferralLab

PublicHealth

Lab

Virus Culture

Immunoassay(Virus Detection)

CU

RR

ENT

TEST

S

Real-time RT-PCR(Identification of Virus)

Improved Point-of-Care

Influenza Tests

Laboratory Influenza Test

TEST

S IN

D

EVEL

OPM

ENT

Rapid Influenza Immunity Test

TEST

SE

TTIN

GS

Antiviral Resistance Influenza Test

What Tests are Needed and Where Do We Use Them?Antigenic Characterization(Determine Vaccine Match)

Gaps in Influenza Diagnostic Testing

• No simple, rapid test available for use in point-of-care clinical setting to differentiate novel influenza from seasonal strains• Confirmation of subtype requires submission of

specimens to a laboratory capable of running high-complexity tests

• Current rapid tests are not easily adaptable for inclusion of new, variant strains

• No tests available for antiviral resistance suitable for patient care decisions

Real-Time RT-PCR for InfluenzaReal-Time RT-PCR for Influenza

• Based on CDC Assay cleared by FDA for domestic US use

• Capable of detecting all influenza A and B• Identifies Influenza A subtypes:

• Seasonal H1 and H3• Novel subtypes as needed

• H5• H7

• Internal Controls to test quality of specimen and proper test conditions – ensures test is valid

High-complexity assay only suitable for labs with appropriate equipment and trained personnel

• Based on CDC Assay cleared by FDA for domestic US use

• Capable of detecting all influenza A and B• Identifies Influenza A subtypes:

• Seasonal H1 and H3• Novel subtypes as needed

• H5• H7

• Internal Controls to test quality of specimen and proper test conditions – ensures test is valid

High-complexity assay only suitable for labs with appropriate equipment and trained personnel

The Influenza Reagent Resource (IRR):A global CDC resource for public health laboratories

• Goals:• Support global influenza surveillance by

supplying high quality test kits for the detection and characterization of influenza

• Ensure high quality reagents are the standard for influenza research and the development of new influenza diagnostics, vaccines, and therapeutics

IRR

VirusSurveillance

Researchand

Development

Registrants order reagents through an email box (FluOrder@CDC.Gov) or web

(http://influenzareagentresource.org)

As of Summer, 2013, the CDC IRR has distributed over 16,000 reagents to 665

laboratories in 161 countries

New diagnostic tests and reagents are developed and distributed as needed

when new virus variants appear.

April 15First caseIdentifiedA/California/4/2009

April 29First DiagnosticKits Shipped toState Labs

May 3First DiagnosticKits Shipped toWHO Network

May 23Vaccine StrainShipped toManufacturers

First cases in Mexico: Late February–Early March

April 15First caseIdentifiedA/California/4/2009

April 29First DiagnosticKits Shipped toState Labs

May 3First DiagnosticKits Shipped toWHO Network

May 23Vaccine StrainShipped toManufacturers

March 31Novel Virus Identified,Sequences Made PublicBy China CDC

April 11First H7N9 VirusShipped to CDCBy China CDC

April 25First DiagnosticKits Shipped

May 2Vaccine StrainShipped toManufacturers

Timeline for Response to 2013 H7N9 Outbreak:

Timeline for Response to 2009 H1N1 Pandemic:

CDC H7 rRT-PCR Kit Shipments(As of 26 July, 2013)

# of US Domestic Requests

# of US Domestic Labs

# of International Requests

# of International 

Labs

# of Countries

Shipped 109 108 78 73 69Pending 1 1 11 11 11Total 110 109 89 84 80

CDC Protocol Availability

• CDC protocols including all primer and probe sequences posted on WHO website(http://www.who.int/influenza/resources/en/):• Real-time RT-PCR diagnosis influenza• Pyrosequencing for markers of antiviral

sensitivity/resistance• Full genome sequencing of influenza viruses• REGULAR UPDATES AS PROTOCOLS

MODIFIED TO IMPROVE PERFORMANCE

• Laboratories worldwide have used these to develop their own testing protocols

The IRR stocks many influenza specific reagents

• rRT-PCR kits and reagents• WHO test kits to identify influenza• Reference influenza viruses • Antibodies to detect influenza• Virus and antibody assay reagents• Sequencing reagents• Standards for test development

Who can receive IRR reagents?• Qualified public health laboratories and WHO National

Influenza Centers• Non-NIC public health and other non-profit

laboratories are considered on a case-by-case basis

How are reagents distributed to users?

• All products are provided free of charge, the IRR does not cover customs fees

• International shipments are delivered within 2 weeks to most locations

• Customer support is available at Contact@InfluenzaReagentResource.org• Customer support is managed by CDC and ATCC

• Technical support for rRT-PCR diagnostics is available at FluSupport@CDC.gov• Technical support is managed by CDC

• Technical support for other reagents is available by contacting CDC subject matter experts

Conclusions

Influenza is both a recurrent, seasonal disease and a proven, emergent threat requiring constant international surveillance.

The natural variation of influenza viruses means diagnostic tests must be updated frequently to detect newly emergent strains.

Because influenza can spread rapidly both in human and animal hosts, public health laboratories need access to the most current tests as quickly as possible.

Thank You

www.cdc.gov.1‐800‐CDC‐INFO

Michael W. ShawMShaw1@cdc.gov