Upload
michael-wang
View
223
Download
0
Embed Size (px)
Citation preview
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
1/29
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
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
2/29
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
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
3/29
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/
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
4/29
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
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
5/29
http://www.cdc.gov/flu/weekly/
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
6/29
http://www.cdc.gov/flu/weekly/
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
7/29
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*Unpublished data compiled according to the Centers for Medicare and Medicaid Service(CMS) Current Procedural Terminology (CPT) codes
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
8/29
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
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
9/29
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
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
10/29
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
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
11/29
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
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
12/29
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
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
13/29
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
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
14/29
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
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
15/29
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
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
16/29
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.
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
17/29
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.aspx7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
18/29
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
Outcomes of 2010 Stakeholder Meeting:
Better Guidance
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
19/29
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
Outcomes of 2010 Stakeholder Meeting:
Better Tests
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
20/29
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
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
21/29
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
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
22/29
New Challenges for RIDTs
Influenza H7
Influenza H5
Influenza H3N2v
Seasonal influenza
Phylogenetic analysis of nucleoprotein genes of influenza viruses from various hosts
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
23/29
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
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
24/29
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
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
25/29
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
26/29
New Challenges for RIDTs
Influenza H7
Influenza H5
Influenza H3N2v
Seasonal influenza
Phylogenetic analysis of nucleoprotein genes of influenza viruses from various hosts
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
27/29
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
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
28/29
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
7/28/2019 Public Health Challenges in Influenza Diagnostics.pdf
29/29
Thank you