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Similar to VIRUSES AND ANTIMICROBIAL USE_17NOV2016__MACKAY
Similar to VIRUSES AND ANTIMICROBIAL USE_17NOV2016__MACKAY (20)
VIRUSES AND ANTIMICROBIAL USE_17NOV2016__MACKAY
- 1. Ian M. Mackay, PhD Public and Environmental Health – Virology Forensic & Scientific Services | Health Support Queensland Department of Health and Associate Professor, The University of Queensland Ian.Mackay@health.qld.gov.au Opinions expressed here are my own; product images are not endorsements; references available upon request Point of Care Testing (POCT) for ARIs
- 3. 3 Acute Respiratory Illnesses (ARIs) • ARIs include • common colds cough, sore throat • flu-like illnesses fever and respiratory signs and symptoms • bronchitis, bronchiolitis • exacerbations – asthma, chronic obstructive pulmonary disease • Most ARIs are caused by virus infections • Young, elderly, immunosuppressed • Virus identification depends on testing… • detection window, sample type/collection, test selection, testing at all AMRQLD NOV 2016
- 4. • Virus infections occur over our entire life • Usually self-limiting • Often mild or asymptomatic • Exposure to viruses changes over a lifetime • Children are virus factories 4AMRQLD NOV 2016 Acute Respiratory Illnesses (ARIs)
- 5. 5 Respiratory Virus Infections Start from Birth • From a QLD birth cohort study • ORChID cohort • neonates birth to 4 weeks • 29/157 (18%) neonates were virus positive ≥1 • first virus positives from day 2 • 45% of infected neonates were symptomatic AMRQLD NOV 2016
- 6. 6 Acute Respiratory Illnesses (ARIs) • Often a non-specific clinical illness • Upper respiratory tract infections (URTIs) • Lower RTIs (LRTIs) AMRQLD NOV 2016
- 7. 7AMRQLD NOV 2016 Acute Respiratory Illnesses (ARIs) • >50% of GPs prescribe antibiotics for an URTI • despite most being caused by a known virus • primary care, hospital facilities and residential aged care • Bacteria do directly cause ARI, but infrequently • URTI or LRTI, can precede or follow a viral infection • may complicate post-viral infection e.g. pneumonia • virus infection can impact on epithelial surface o damage, exposure or cells/receptors o perturb respiratory microbiome • viruses can look like neonatal sepsis • need to quickly differentiate
- 8. 8 (not always) Acute Respiratory Illnesses (ARIs) • Protracted bacterial bronchitis or bronchiectasis • Adenovirus C & Haemophilus influenzae • Moraxella catarrhalis or Streptococcus pneumoniae • Pneumonia, acute, bacterial, viral • viruses - particularly in the extremes of age, prematurity – o RSV, influenza A or B viruses, parainfluenza viruses, rhinoviruses, adenoviruses, coronaviruses • Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella spp AMRQLD NOV 2016
- 9. 9 Acute Respiratory Illnesses (ARIs) • What is a pathogen, what is a passenger in the airways? • many viruses, many bacteria = permutationpalooza • no simple yes / no answers • one reason for limited point-of-care test development / uptake • Severe ARIs early on can lead to chronic effects on… • …immune memory and regulatory cells – atopy over antiviral • …tissues - damage and remodelling • predispose to future exacerbations after infection e.g. asthma AMRQLD NOV 2016
- 10. 10 Acute Respiratory Illnesses (ARIs) • Knowing virus may not change management but may… • …contain emerging virus outbreak / epidemic • …guide cohorting of infectious patients • …limit nosocomial infections • …reduce unnecessary / invasive exploratory testing • …guide decisions on infant hospitalization vs. treatment as an outpatient • …limit use of antibiotics – or identify a need to use them AMRQLD NOV 2016
- 11. 11 Respiratory Viruses • Majority are endemic human viruses • h2h spread • Spread via droplets and surfaces • inhaled infectious droplets • self-inoculation • acquired at home, school, transport, healthcare.. • Usually RNA viruses • Often mild infections • testing is for more severe symptomatic episodes AMRQLD NOV 2016
- 12. 12 Respiratory Virus Diversity • There are many viruses • they don’t disappear • influenza viruses (Flu) • respiratory syncytial virus (RSV) • rhinoviruses • enteroviruses • human metapneumovirus • human coronaviruses • parainfluenza viruses • bocaviruses, adenoviruses… AMRQLD NOV 2016 RNA DNA
- 13. “Pathology test results inform diagnostic and treatment decisions that affect health outcomes” In vitro Diagnostic Tests, Australia • In vitro diagnostic (IVD) • In Australia, IVDs are a subset of medical devices • Subject to regulation under Therapeutic Goods Act 13AMRQLD NOV 2016 From “Guidelines for point-of-care testing”, 1st edition National pathology accreditation advisory council (NPAAC)
- 14. 14 Detection of Respiratory Viruses • Clinical: signs and symptoms • modest to poor sensitivity • poor specificity • expertise • Culture: cell death, fluorescent assays • laborious and time-consuming • can be insensitive • non-specific • specialized reagents • expertise AMRQLD NOV 2016
- 15. 15 Detection of Respiratory Viruses • Molecular: lab-based, more sensitive • ..than animal / tissue / cell culture • gold standard • detect more viruses, more often • detect viral nucleic acids - not infectious • positive result implies virus presence • (RT) polymerase chain reaction ([RT-]PCR) –based tests • cost per specimen perceived as very high – but not so • specialized laboratory, experienced staff AMRQLD NOV 2016 The PCR
- 16. • Increased sensitivity • A fifth of tests can yield 2 or more detections • co-detections • symptomatic infection + end of a past infection • symptomatic infection + beginning of a new infection • two concurrent symptomatic infections • synergistic impact – better or worse outcome? 16AMRQLD NOV 2016 Detection of Multiple Viruses
- 17. 17 Respiratory Virus Interactions • Different virus epidemics may clash & interact • virus:virus interference (population level) • Queensland data • influenza virus appears to ‘clear out’ other viruses AMRQLD NOV 2016
- 18. 18 Respiratory Virus Seasonality • Different viruses peak at different times of the year • temperature and humidity • cooler ‘shoulders’ • winter • some viruses occur every other year • respiratory viruses do occur outside expected peaks AMRQLD NOV 2016
- 19. 19 Respiratory Virus Therapeutics & Vaccines • Treatments drive testing • limited options for treatments / preventions for airway virus infections • manage the inflammation • Existence of antivirals drives need / desire for testing • test results can be responded to • disease in presence of therapeutic may suggest resistance • antivirals Flu; MAb for RSV • Vaccines open up new areas in need of surveillance • resistance, vaccine escape & disease re-emergence • targets for vaccination or study of vaccine; Flu vaccine AMRQLD NOV 2016
- 21. 21 Point-of-care testing (POCT) • Ultimate goal to improve patient outcomes • Definition of a POC test based on… • the function of the test or device • how and where the test or device is used • Portable and easy use • at the patient’s location e.g. bedside, pharmacy, remote medical services, specialist community health services, GP’s office • POCT doesn’t need permanent testing space but… o …can be used in a lab…can do lab testing at the POC AMRQLD NOV 2016
- 22. 22 Point-of-care testing (POCT) • Mostly qualitative (yes/no) lateral flow strips • rapid antigen test (RAT), rapid antigen detection test (RADT), rapid diagnostic test (RDT) • Often less sensitive than molecular methods • negative results need confirmation • usually good specificity AMRQLD NOV 2016
- 23. Point-of-care testing (POCT) • Simple, performed outside a laboratory • e.g. chemistry tests (glucose), pregnancy tests, HIV test • Can be great for resource-poor regions • if battery operated • thermal stability of reagents • humidity resistant • long shelf-life • can remove access barriers to pathology tests • simpler sample collection and pre-analytical processes 23AMRQLD NOV 2016
- 24. 24 Point-of-care testing (POCT) • Speedy result, <30min • POCT removes need to transport patient to collection site or specimen to lab • POCT results within the time of the usual patient encounter o reduced delays in support/treatment due to shorter TAT • cohort infectious patients (infection control), enhance contact tracing • good for 1 or few specific/known targets-seasonal virus, disaster, bioterror – full workup not needed • in common with any testing… o result stops search for a cause o better understand circulating viruses - PH messaging, resourcing & policy o reduce antibiotic usage / hospital procedures / staff hours / equipment use AMRQLD NOV 2016
- 25. • Mostly one technology, until recently • Lateral flow immunochromatographic method • antigen or antibody detection from human swab/fluids • combines thin-layer paper chromatography with ELISA • Limited ARI range: RSV, IFAV, IFBV, Strep • improve upon culture and microscopy • strip reader can help interpret weak positives • may still need further test to confirm and quantify 25AMRQLD NOV 2016 Point-of-care testing (POCT) POCT 1.0
- 26. 26 Molecular Diagnostics (MDx) POCT 1.5 • Nucleic acid amplification strips • isothermal • influenza A(H1N1pdm09) • Paper gene circuits • CRISPR-based • isothermal RNA amplification & detection • ~3h TAT - quick & easy to design and manufacture, 1y shelf-life @ 20C • Ebola virus, Zika virus • no respiratory viruses AMRQLD NOV 2016
- 27. • Appropriate training still needed • 'sample-in, result-out‘ – oversimplified • Expertise still important for… • …testing • …function and maintenance of any equipment • …storage of specimens, reagents and consumables • …counselling • …result reporting • …record keeping • …waste disposal 27AMRQLD NOV 2016 Point-of-care testing (POCT)
- 28. • Summary • immunochromatographic tests are simple & have been the POCT mainstay • potential of the speed is high • benefits of testing in common with any testing • great for remote areas • range of tests is limited by lack of treatments / preventions • sensitivity issues remain 28AMRQLD NOV 2016 Point-of-care testing (POCT)
- 30. 30 Molecular Diagnostics (MDx) POCT 2.0 • Emerged in past few years & address sensitivity issues • US Clinical Laboratory Improvement Amendments (CLIA) • waived first MDx POCT, April 2015 (FluA/B, Strep A) • now defined as simple tests, not complex • Can require more complex equipment, 1 test at a time • mostly faster than culture/PCR – 15-60min vs days (culture) hour(s) (rtPCR) • Some leading examples include… AMRQLD NOV 2016
- 31. 31 Molecular Diagnostics (MDx) POCT 2.0 • Pneumonia POCT • Curetis Unyvero system, semi-automated • separate sample “lysator”, cartridge based, mPCR, ~4h • community-acquired pneumonia (CAP) • hospital-acquired pneumonia (HAP) • ventilator acquired pneumonia (VAP) • healthcare-associated pneumonia (hCAP) AMRQLD NOV 2016
- 32. 32 Molecular Diagnostics (MDx) POCT 2.0 • AlereTM i system semi-automated • isothermal, ≤13min • cartridge-based, no extraction needed • Alere i RSV • Alere i FluA/B • Alere i Strep A AMRQLD NOV 2016
- 33. 33 Molecular Diagnostics (MDx) POCT 2.0 • AlereTM q system, fully automated • rtPCR-based, <60min • battery powered • cartridge-based, no extraction needed • no respiratory virus tests yet AMRQLD NOV 2016
- 34. 34 Molecular Diagnostics (MDx) POCT 2.0 • Cepheid GeneXpert systems, fully automated • cartridge-based, no extraction needed • Xpert® Flu/RSV, ~60min • Xpert® Xpress Flu/RSV, ~30min • Omni [2017] POC / emerging markets / developing world o battery, phone, rtPCR AMRQLD NOV 2016 GeneXpert Omni GeneXpert I GeneXpert II GeneXpert IV GeneXpert XVI
- 35. 35 Molecular Diagnostics (MDx) POCT 2.0 • Roche cobas® automated Liat® system • RT-rtPCR-based, ~20min, mains power • cobas® Influenza A/B • cobas® Influenza A/B and RSV • cobas® Strep A AMRQLD NOV 2016
- 36. 36 POCT costs • Cost per test (varies worldwide) • POCT fares well AMRQLD NOV 2016 Test Cost per test Unit Viral culture $15-$30 AUD/USD POCT 1.0 strips $5-$12 AUD/USD/€ PCR-based lab test $10-$140 AUD/USD/€ MDx POCT 2.0 $10-$70 USD
- 37. 37 Horizon scanning – what might be coming? • Multiplexed POCT • account for more pathogens and co-infections • Wish-list POCT • virus vs. bacteria in ARI would be a great help • Unbiased / deep / next gen sequencing at the POC • complexity, >6h, bioinformatics-heavy, friendly interface-light • interpretation • laptop, power AMRQLD NOV 2016
- 38. 38 Summary: ARIs are overwhelmingly viral #antibiotics4bacteria • MDx POCT has arrived • ARIs are usually self-limiting • includes those due to more worrisome Flu and RSV • Most ARIs are due to untreatable viruses • POCT product range likely reflects this • POCT options for ARIs are scant • impact on antibiotic stewardship AMRQLD NOV 2016