Public Health Challenges in Influenza Diagnostics.pdf

7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf

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Public Health Challenges in Influenza Diagnostics

J ulie Villanueva, PhD

Acting Chief, Virus Surveillance and Diagnosis Branch,Influenza Division, NCIRD

Centers for Disease Control and Prevention

J une 13, 2013


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Outline

Influenza: Impact in the U.S.

Characteristics and challenges of rapid influenza

diagnostic test (RIDT) use

2010 public health initiative to improve RIDT use

New challenges for RIDTs


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Hospitalizations Attributable to Influenza (U.S.)

Average of >200,000 influenza-relatedhospitalizations/year

Estimated by modeling studies using retrospective data andinfluenza surveillance data

Children High rates in young children 65 years

High rates in persons with chronic illness

http://www.cdc.gov/flu/weekly/


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Seasonal Influenza-associated Mortality (U.S.)

Estimated average of severity is variable

3,349 to 48,614 influenza-attributable deaths/year (1976-2007)

Highest mortality rates

Persons >65 years

Persons with chronic pulmonary and cardiac disease; otherchronic conditions

Mortality data limited for chi ldren

Estimated average of 92 influenza-related deaths among

children aged


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Medicare reimbursement claims from 2000-2011 for

influenza diagnostic tests

*Unpublished data compiled according to the Centers for Medicare and Medicaid Service(CMS) Current Procedural Terminology (CPT) codes


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Influenza Diagnostic Dilemma

RIDTs(CLIA-waived)

RIDTs & DFA(in central clinical lab)

PCR, ViralCulture

(in central clinical lab)

PCR, ViralCulture

(in public healthlaboratory orreference lab)

Clinical assessment &preliminary clinical

diagnosis of ILI

Lab-confirmeddiagnosis

at public healthlab or CDC

specimens results


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Rapid Influenza Diagnostic Test Characteristics

Detection of influenza nucleoprotein (NP) using specificantibodies/antibody combinations

Can obtain results within 15 min. and are available to

clinicians during the time of a patients office visit

Extremely variable performance reported Sub-optimal sensitivity reports in previous years

2012 Meta-analysis of 159 studies that compared RIDTs to a

reference standard (RT-PCR or culture)

Sensitivity 62.3% - highly heterogeneous

Specif ici ty 98.2%

More sensit ive for influenza A than influenza B

Lower sensitivity in adults than in children

Chartrand et al., Annals of Internal Medicine 2012, 156: 500-511


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Use of RIDTs

Clinical decisions Testing decisions are linked directly to clinical decisions

related to antiviral treatment and clinical management of

individual patients

Outpatient, Emergency Room settings; Hospitalized

patients Decisions to initiate antiviral treatment

Decisions to pursue other diagnostic testing

Decisions on infection control needed

Public Health

Control of suspected outbreaks in semi-closed settings Decisions to in itiate prevention and control measures for acute

respiratory disease outbreaks of suspected influenza


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Challenges with RIDT Use

Clinicians may not access or uti lize influenzasurveillance data on the prevalence of inf luenza

activity in their patient populations

Clinicians may lack understanding of key test

parameters that influence RIDT results Sensitivity and specificity

Prevalence

Major determinant of predictive values of inf luenza tests

Posit ive Predictive Value is highest and Negative Predictive

Value is lowest during peak influenza activity

Negative Predictive Value is highest and Posit ive Predictive

Value is lowest during low influenza activity


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RIDT Use and Antiviral Prescript ions in

Outpatient Settings

Survey of healthcare providers in outpatient facilityproviders (OFP) in 2008 and 2010 to assess their RIDT

testing practices, the use of confirmatory testing, and the

impact of RIDT results on subsequent treatment

decisions.A positive RIDT result was a major reason among greater

than two thirds of participants for prescribing antiviral

medications

This was >3 times higher than the % OFP that ordered antiviral

medications based upon other lab-based influenza tests.

OFP relied on RIDT for antiviral and antibiot ic treatment

decisions

Unpublished results 2011 CDC and J oint Commission


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Confirmatory Test Ordering from Outpatient

Facility Providers

0%10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

CHCs

2008

CHCs

2010

EDs

2008

EDs

2010

POs

2008

POs

2010

Positive Specimens

Negative specimens

Outbreak Settings (2010 only)

Do not use Confirmatory

Testing

Emergency Departments (ED)

Community Health Centers (CHC)

Physicians Offices (PO)

Unpublished results 2011 CDC and J oint Commission


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View from the Clinician 2009 PandemicCunha, Thekkel, Cohan. Infect Contro l Hosp Epidemiol 2010;31:102-4

SUNY Stony Brook - Mineola, NY (adjacent to Queens NYC)

Emergency Department inundated with swine flu requests

Many patients admitted from the ED with an ILI/pneumonia

were not put on influenza precautions because the rapid

influenza A test was negative HCWs, pts & visitors exposed

The most crit ical problem was the inability to get RT-PCRperformed by the Health Department

Overdiagnosing and misdiagnosing, quickly became

apparent

Health Department overwhelmed, results took more than a

week Began using clinical criteria for infection control and clinical

management


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2010 Public Health Init iatives

Stakeholder meeting was held in September 2010 tohelp identify tools and resources for achieving:

Better practices for optimal use of RIDTs

Better guidance with relevant information forclinicians and laboratories

Better tests available to clinicians and laboratories

Goal: To improve the use of RIDTS for clinical

management and public health practice


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2010 Public Health Init iatives

Better Practice Presentation of data collected by JCAHCO and CDC.

Discuss how all can facilitate optimal use of currently available

RIDTs for clinical management of patients.

HHS, FDA, CDC; Professional organizations; Manufacturers

Better Guidance

Presentation of draft updates to CDC test guidance.

Discuss ways to improve and disseminate guidance to clinic ians.

Better Tests

Identify factors which can lead to improved RIDTs.

What are the incentives and support needed from CDC, BARDA,

FDA, professional societies, manufacturers, and others.


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Outcomes of 2010 Stakeholder Meeting:

Better Practice

Created specimen col lection training resources Continuing education course: Strategies for Improving

Rapid Influenza Testing in Ambulatory Settings:

http://www.jointcommission.org/siras.aspx

1519 participants to date

YouTube channel for Strategies for Improving Rapid

Influenza Testing in Ambulatory Settings featuring

instructional videos:http://www.youtube.com/playlist?list=PLNQfL_CJ36fK08KEPjxu1Z

KJn7GuFtn-N&feature=plcp

7950 views of specimen collection videos to date
http://www.jointcommission.org/siras.aspxhttp://www.youtube.com/playlist?list=PLNQfL_CJ36fK08KEPjxu1ZKJn7GuFtn-N&feature=plcphttp://www.youtube.com/playlist?list=PLNQfL_CJ36fK08KEPjxu1ZKJn7GuFtn-N&feature=plcphttp://www.youtube.com/playlist?list=PLNQfL_CJ36fK08KEPjxu1ZKJn7GuFtn-N&feature=plcphttp://www.youtube.com/playlist?list=PLNQfL_CJ36fK08KEPjxu1ZKJn7GuFtn-N&feature=plcphttp://www.youtube.com/playlist?list=PLNQfL_CJ36fK08KEPjxu1ZKJn7GuFtn-N&feature=plcphttp://www.youtube.com/playlist?list=PLNQfL_CJ36fK08KEPjxu1ZKJn7GuFtn-N&feature=plcphttp://www.jointcommission.org/siras.aspx


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Added new algorithms and narratives to CDC

Influenza website

Flowcharts with testing algorithms:

When influenza is circulating

When influenza is NOT circulating

In outbreak investigation in inst itut ions

Guidance on molecular diagnostics

Updated lists of FDA-cleared RIDTs and molecular assays


Better Guidance


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Evaluate clinical performance of current FDA-cleared

tests in defined practice settings and communicate

results effectively to the practice community on an

annual basis

Support development and implementation of new or

significantly improved RIDTs:

Research and development by manufacturers

Regulatory process innovations


Better Tests


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BARDA/CDC/MCW study

With CDC, the Biological Advanced Research and DevelopmentAuthority (BARDA) and the Medical College of Wisconsin (MCW)

performed an analytical evaluation using RIDTs

All 11 commerc iall y available FDA-cleared RIDTs (201011 influenza season)

23 recent influenza viruses to allow for a more finely detailed characterization of test

performance

The analytical sensit ivity of the evaluation varied across tests and with

different influenza viruses

Each inf luenza virus had variable levels of positivi ty with RIDTs, suggesting that

several viruses of each type and subtype should be evaluated with each RIDT on a

regular basis These findings do not reflect performance in clinical settings

Performance of any one test ki t may appear more or less sensitive depending on the

predominance of virus subtype during a clinical evaluation

Beck et al., MMWR 2012, Nov 2: 61(43); 873-876


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Benefits of Annual Analytical Assessment

Determine that recent circulating influenza viruses

are detected

Determine an estimated level of analytical sensitivity

Utilize a standard set of fully characterized influenzavirus preparations

Provide mechanisms for evaluating analytical

reactivity with emerging influenza viruses


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New Challenges for RIDTs

Influenza H7

Influenza H5

Influenza H3N2v

Seasonal influenza

Phylogenetic analysis of nucleoprotein genes of influenza viruses from various hosts


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Influenza H3N2v in Humans 2005-2011

12

43

21

1

1

2 6

12

0

2

4

6

8

10

12

14

16

2005 2006 2007 2008 2009 2010 2011

H3N2v MH3N2v

H1N2v

H1N1v

Numberofhumancases


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Influenza A(H3N2)v: 2005 - September 2012

0

50

100

150

200

250

300

350

2005 2006 2007 2008 2009 2010 2011 2012

H3N2v MH3N2v

H1N2v

H1N1v

306

Numberofhumancases


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New Challenges for RIDTs

Influenza H7

Influenza H5

Influenza H3N2v

Seasonal influenza

Phylogenetic analysis of nucleoprotein genes of influenza viruses from various hosts


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Benefits of Reclassification to Public Health

Standardization of reference methods Performance measurement equality

Monitoring of performance as seasonal influenza

evolves Early indication of potential performance issues

Mechanism to assess tests as novel inf luenza

viruses emerge

Expeditious method to inform public health and clin ical

community in an emergency


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Benefits of Reclassification to Public Health

Heightened performance

Minimum performance criteria to reduce sensitivity issues

Introduction of advanced technologies

Encourage manufacturers to develop new methods and

techniques to assist the clinician in making an informed

decision regarding patient management


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Thank you

Documents

Public Health Challenges in Influenza Diagnostics.pdf