Point of care testing for respiratory ... - Ministry of Health

Point of care testing for respiratory virusesJen KokMedical VirologistCentre for Infectious Diseases and Microbiology Laboratory ServicesPathology West ICPMR Westmead [email protected]

Outline

• rationale for testing, testing methods and

impact of testing

• factors affecting performance of tests

– sample, transport, age of patient, novel virus

• examples of platforms

• surveillance

icpmrCentre for Infectious Diseases and Microbiology, Westmead Hospital

Why test those meeting clinical case

definition of ILI (fever + cough/sore throat)?

• individual patient management

– antivirals

– obviates unnecessary tests and treatments

– infection control measures

• epidemiological purposes

– emerging pathogens

– monitoring of secular trends of existing pathogens

– pandemic preparedness planning


Respiratory virus diagnostic methods


Type of test Sensitivity

Turn

around

time

Advantages Disadvantages

POCT/RIDT 18-77%15-30

mins

Rapid

Simple

No need for

specialised

laboratory

Influenza A and

B typing

possible

Expensive

Limited shelf life

Lower sensitivity

False positives

and negatives

Specimen quality

important

Nucleic acid

detection ~98 - 100% ~4 hours

Sensitive

Typing and

subtyping

possible

Can detect

viable and non-

viable virus

Requires

technical

expertise and

specialised

equipment

Expensive

Clinician’s perspective: which diagnostic

method?


24/7

Menu

Accurate

TAT

Cost

Laboratory’s perspective: which diagnostic

method?


Menu

Workflow

Automation

Throughput

Random access

TAT

Complexity

Expertise

Instruments

Cost*

*reagents, labor,

instruments, QAP,

transport

A positive RIDT alters outpatient

pediatrician practices in ILIs


Jennings IORV 2009

Clearview Exact Influenza A + Bo increase antiviral therapyo reduce antibiotic therapy

Impact of RIDT in EDs


Bonner Pediatrics 2003

MD aware RIDT positive (n=96)

MD unaware RIDT positive

(n=106)P value

CBC 0 13 (12%) <0.001

BC 0 11 (13%) <0.001

Urinalysis 2 (2%) 12 (11%) 0.011

CXR 7 (7%) 26 (25%) 0.001

Charge/patient $15.65 $92.37 <0.001

Antibioticprescription

7 (7%) 26 (25%) <0.001

Antiviralprescription

18 (19%) 7 (7%) 0.02

Mean time from exam to discharge

25 minutes 49 minutes <0.001

Impact of RIDT on hospital inpatients

RIDT negative (n=80)

RIDT positive (n=86)

P value

Antibiotic use 79 (99%) 74 (86%) 0.002

Antiviral use 6 (8%) 63 (73%) <0.001

Antibiotics ceased because of influenza

2 (2%) 12 (14%) 0.004

Discharged from hospital whilst on

antibiotics51 (64%) 38 (44%) 0.006

Length of stay 7.9 ± 4.2 days 9.6 ± 10 days 0.16

icpmrCentre for Infectious Diseases and Microbiology, Westmead Hospital Falsey Arch Intern Med 2007

multivariate analysis for discontinuing antibioticspositive RIDT OR of 6.90 (95% CI 2.0 – 32.70) p=0.005

Detection of influenza virus in samples collected, stored

and transported using media at different temperatures

icpmrCentre for Infectious Diseases and Microbiology, Westmead Hospital Druce J Clin Microbiol 2012

4OC 22OC

37OC

Liquid Amies

Rate of detection of respiratory viruses differs

according to age and samples tested

Recoveryusing flocked

swabs

Recoveryusing

comparator

p values andΔ in CT values

(flocked swab –comparator)

DeByleJ Virol Methods 2012 (n=314 children < 3 years)

79 – 89% (nasopharyngeal)

69 – 94% (nasal wash)

p=0.069 – 1.00.6 – 7.0

MunywokiJ Clin Microbiol2011 (n=299 children < 13 years)

89.6% (nasopharyngeal)

79.2% (nasal wash)

p=0.0043-1 – -2

HernesEur J Clin MicrobiolInfect Dis 2011 (n=223 adults)

78% (nasopharyngeal)

63% (oropharyngealflocked swabs)

p <0.01-5.75

Sensitivity of antigen tests stratified according to

age groups in 2009 (n=2274)


Unpublished data

Age group

RIDTpH1N1 Non-pH1N1

IFApH1N1 Non-pH1N1

0-1 years (n=65 RIDT, 46 IFA)

87.5% 100% 86.7% 90%


70% 87.5% 100% 100%


69.3% 71.9% 86.7% 83.3%

≥16 years (n=1503 RIDT, 389 IFA)

42.4% 72.1% 39.8% 56.7%

Kok ASID 2010

Important to test lower respiratory tract in critically

ill (adult) patients with influenza


RIDT (QuickVue) and IFA vs NAT

• 21 patients with severe A(H1N1)pdm09 infection requiring

respiratory support with paired URT / LRT samples

• Nose and/or throat swabs: RIDT

• BAL/mini BAL: IFA

• All samples: NAT

*** ***p < 0.01

Blyth N Engl J Med 2009

***

Reduced sensitivity of RIDT (QuickVue) for newly

circulating pandemic influenza virus


Kok J Clin Microbiol 2010

Should RIDT be performed “in the lab”

or “in the field”?

• parallel testing of RIDT using NAT/viral

culture as gold standard (n=124 samples)

• transported at 4OC, tested within 24h

• inter-operator variability (WYD 2008)


OperatorSensitivity

(%)

Specificity

(%)PPV (%) NPV (%)

Trained

(n=59)60* 96.6 94.7 70

Untrained

(n=65)34.6* 89.7 69.2 67.3

Foo J Clin Virol 2009

*p > 0.05

RIDT : Rapid (15 - 20 minutes)

Rapid respiratory virus diagnostic tests

Turnaround times (minutes)

Sensitivity Specificity

Lateral flow immunochromatography (BinaxNOW)

15 minutesInfluenza A: 44%Influenza B: 25%

RSV: 63 – 65%

Influenza A: 100%Influenza B: 100%

RSV: 100%

Fluorescent immunoassay(Sofia)

15 minutesInfluenza A: 71.4%Influenza B: 33.3%

RSV: 92.9%

Influenza A: 98.2%Influenza B: 99.5%

RSV: 100%

Loop mediated isothermalamplification (Alere i)

15 minutesInfluenza A: 77.8%Influenza B: 75%


Photon fluorescent excitation(mariPOC)

20 minutesInfluenza A: 71%Influenza B: 86%

RSV: 89%


RSV: 100%

Hazelton J Med Virol 2014, IORV 2015; Ivaska J Clin Virol 2013

PPV and NPV of RIDT depends on

prevalence of flu


If flu prevalence is…

and specificity is…

then PPV is…

very low (2.5%) good (98%) poor (39 – 56%)

moderate (20%) good (98%) good (86 - 93%)

If flu prevalence is…

and sensitivity is…

then NPV is…

moderate (20%) poor (50%) moderate (86 –89%)

high (40%) poor (50%) very good (93 –94%)

RIDT : Rapid (20 minutes – 4 hours)

Rapid respiratory virus diagnostic tests

Turnaround times (minutes)

Sensitivity Specificity

Cobas Liat Influenza A/B (Roche Diagnostics)

20 minutesInfluenza A: 99.2%Influenza B: 100%


Xpert Flu (Cepheid) 40 – 75 minutesInfluenza A: 97.8%Influenza B: 100%

RSV: 90.6%

Influenza A: 100%Influenza B: 99.4%

RSV: 99.4%

FilmArray RP (BioFire/bioMerieux)

1 hour17 viruses

Up to 100%17 viruses

Up to 100%

Simplexa Flu A/B + RSV Direct (Focus Diagnostics)

1 – 4 hours

Influenza A: 91.7 -100%

Influenza B: 97.5 -100%

Influenza A: 99.4 -100%

Influenza B: 98.1 -99.4%

Binnicker J Clin Microbiol 2015, Popowitch J Clin Microbiol 2015, Babady Expert Rev Mol Diagn 2013, KoJ Med Virol 2013

San Diego

Wireless transmission of influenza

surveillance data

icpmrCentre for Infectious Diseases and Microbiology, Westmead Hospital courtesy of John Tamerius

San Diego

CDC, Atlanta

WI

Daily at midnight (optional)

Daily

Dept. of Hygiene, Madison


Feedback of data to Wisconsin State Department of

Hygiene and CDC Atlanta

courtesy of John Tamerius

Laboratory surveillance of influenza

icpmrCentre for Infectious Diseases and Microbiology, Westmead Hospital NSW Health 2015

Novel antiviral agents for respiratory viruses


Virus Existing agentsNovel agents in development

Influenza

Amantadine, Rimantidine

Zanamivir, Laninamivir, Oseltamivir, Peramivir

Favipiravir

DAS181 (Fludase®)CR6261CR8020

AVI-7100VX-787

RSVRibavirin

PalivizumabMotavizumab

GS-5806ALS-008176

RI-001ALN-RSV01TMC353121

MDT-637ALX-0171

Novel antiviral agents for respiratory viruses


Virus Existing agents Novel agents in development

Parainfluenza virus - DAS181 (Fludase®)

Rhinovirus -Vapendavir

(BTA798)SNG001 (IFN-β)

Adenovirus CidofovirBrincidofovir

(CMX001)

Conclusions

• laboratory diagnosis of viral infections

important

– impact of availability of rapid test result

– novel antivirals for specific viruses

• technological advances

– multi-analyte rapid molecular based tests

– real-time surveillance

• quality and regulatory aspects

• costs


Point of care testing for respiratory ... - Ministry of Health

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