Point-of-care testing for respiratory viruses in adults: The current landscape and future potential

doi:10.1016/j.jinf.2015.07.008

Journal of Infection

Volume 71, Issue 5, November 2015, Pages 501-510

https://doi.org/10.1016/j.jinf.2015.07.008 Get rights and content

Highlights

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There is a large burden of respiratory virus infection in hospitalised adults.
•
Replacing empirical antimicrobials with pathogen directed use is a global priority.
•
Molecular platforms now exist with potential for use as point-of-care tests (POCT).
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Potential benefits of POCT include a reduction in unnecessary antibiotic use.
•
High quality trials evaluating clinically relevant outcomes are urgently needed.

Summary

Respiratory viruses are responsible for a large proportion of acute respiratory illness in adults as well as children, and are associated with a huge socio-economic burden worldwide. Development of accurate point-of-care tests (POCT) for respiratory viruses has been listed as a priority by the World Health Organisation and replacing the current paradigm of empirical antimicrobial use with directed use is a listed goal of the movement for reduction in antimicrobial resistance. POCTs for respiratory viruses have previously been limited by the poor sensitivity of antigen detection based tests and by a limited range of detectable viruses. Highly accurate molecular platforms are now able to test for a comprehensive range of viruses, can be operated by non-laboratory staff and can generate a result in approximately 1 h, making them potentially deployable as POCTs. The potential clinical benefits of POC testing for respiratory viruses in adults include a reduction in unnecessary antibiotic use, improved antiviral prescribing for influenza and rationalisation of isolation facilities. We review here the burden of disease, the currently available molecular platforms with potential for POCT use and the existing evidence for clinical and economic benefits of testing for respiratory viruses in adults.

Introduction

Acute respiratory tract infections are responsible for an estimated 4.25 million deaths each year and are the third most common cause of death worldwide.¹ Although bacteria have previously been considered to be the principal aetiological agents of severe respiratory infection, the global importance of respiratory viruses in all age groups has been increasingly recognised in recent years.2, 3, 4 Diagnostic technology for respiratory virus detection has evolved rapidly over the last two decades from viral culture and immunofluorescence to the current standard of molecular detection by polymerase chain reaction (PCR). This review focuses on the currently available molecular diagnostic platforms for respiratory virus detection with potential for use as point-of-care tests (POCT) and explores the current landscape for POCT in adults.

Section snippets

Respiratory viruses: clinical and economic burden of disease

Improvements in the sensitivity of diagnostic testing for respiratory viruses with the widespread use of nucleic amplification techniques such as PCR have helped to accurately define the burden of viral disease over the past two decades. In children respiratory viruses have been detected by molecular diagnostic techniques in 43–67% of cases of community acquired pneumonia (CAP),⁵ over 90% of infants with bronchiolitis,⁶ and approximately 85% of asthma exacerbations.⁷ In adults approximately

Laboratory PCR

Nucleic acid amplification techniques such as PCR have now largely superseded cell culture and direct fluorescent antibody testing as the method of choice for routine diagnostic testing for respiratory viruses, due to their superior diagnostic accuracy and faster turnaround time. PCR is highly sensitive and specific but generally has a turnaround time of at least 24 h and requires specialist laboratory facilities and expertise.54, 55

Rapid antigen detection tests for respiratory viruses

There are several commercially available FDA approved and CE

Alere i Influenza A&B

The Alere i Influenza A&B (Alere, San Diego, CA, USA) is an FDA approved and CE marked isothermal nucleic acid amplification-based system that uses a fluorescence-based molecular signal to detect influenza A and B. Results are generated within 15 min, with around 2 min of “hands on” time. The testing kits and analyser have been specifically designed to be used by non-laboratory clinical staff in an acute care environment and it is the only molecular platform that is FDA approved specifically as

Respiratory virus point-of-care testing in the wider context

The UK Department of Health commissioned report into UK pathology services in 2006 noted the importance of developing clinically relevant point-of-care diagnostic tests to reduce turnaround times and improve patient pathways.⁷⁸ Despite this POCT for infectious diseases in the UK and globally have not advanced far beyond dipstick testing for urinary tract infection with in vitro diagnostic tests for infection remaining confined to large centralised laboratories. The associated slow turnaround

Reduction in antibiotic use

The current culture of empirical antimicrobial use in patients with suspected infection is no longer considered sustainable due the emergence and proliferation of antibiotic resistance. Antibiotic use in hospitalised patients with acute respiratory illness is near universal despite the predominance of viruses and the low frequency of detectable bacteria in much of this patient group. Fig. 1 shows antibiotic use by detected pathogen in a large study of hospitalised adults from the UK.⁴

Conclusion

The current global priority of replacing empirical antimicrobial use with pathogen directed therapy to help combat resistance, coupled with the recent development of rapid, accurate and easy-to-use molecular test platforms for respiratory viruses, sets the scene for rolling out a point-of-care testing strategy in patients presenting with acute respiratory illness. The potential benefits of such a strategy include a reduction in unnecessary antibiotic use, improved use of directed antiviral

Author contributions

NJB, HFS and TWC were all involved in the design, literature search and writing the manuscript, including the final version submitted.

Funding source

None.

Conflicts of interest

None declared for all authors.

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Antiviral treatment with neuraminidase inhibitors is recommended for all patients admitted to hospital with suspected and proven influenza by UK and US national guidelines8,9 and evidence suggests that earlier use is associated with better outcomes.10,11 New rapid molecular point-of-care tests (mPOCTs) using PCR for influenza are highly accurate, easy to use, and can generate a result in less than 1 h,12–15 compared with the current turnaround time of approximately 24 h for laboratory-based PCR testing.7 Routinely testing patients for influenza at the point of care might improve influenza detection and use of antivirals and isolation facilities by allowing confident real-time decision making.7,16–20
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ReviewPoint-of-care testing for respiratory viruses in adults: The current landscape and future potential

Highlights

Summary

Introduction

Section snippets

Respiratory viruses: clinical and economic burden of disease

Laboratory PCR

Rapid antigen detection tests for respiratory viruses

Alere i Influenza A&B

Respiratory virus point-of-care testing in the wider context

Reduction in antibiotic use

Conclusion

Author contributions

Funding source

Conflicts of interest

J Infect

Lancet

Chest

Chest

Vaccine

J Infect

Lancet Infect Dis

Lancet Infect Dis

J Clin Virol

Lancet Infect Dis

J Clin Virol

Lancet

Clin Ther

Clin Microbiol Infect

J Clin Virol

J Clin Virol

J Clin Virol

Diagn Microbiol Infect Dis

J Clin Virol

J Clin Virol

J Clin Virol

Lab Med

J Clin Virol

J Clin Virol

Diagn Microbiol Infect Dis

Lancet Infect Dis

Lancet Respir Med

Lancet Infect Dis

Lancet

Lancet

Lancet Infect Dis

Acute respiratory infections Atlas

Community-acquired pneumonia requiring hospitalization among U.S. children

N Engl J Med

Beyond malaria – causes of fever in outpatient Tanzanian children

N Engl J Med

Prospective multicenter study of viral etiology and hospital length of stay in children with severe bronchiolitis

Arch Pediatr Adolesc Med

Community study of role of viral infections in exacerbations of asthma in 9–11 year old children

BMJ

Incidence and characteristics of viral community-acquired pneumonia in adults

Thorax

Etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods

Clin Infect Dis

Improved diagnosis of the etiology of community-acquired pneumonia with real-time polymerase chain reaction

Clin Infect Dis

Viruses and bacteria in acute asthma exacerbations – a GA2LEN-DARE* systematic review

Allergy

Prevalence of viral infection detected by PCR and RT-PCR in patients with acute exacerbation of COPD: a systematic review

Respirology

A role for Streptococcus pneumoniae in virus-associated pneumonia

Nat Med

Human rhinovirus infection during naturally occurring COPD exacerbations

Eur Respir J

The co-pathogenesis of influenza viruses with bacteria in the lung

Nat Rev Microbiol

Respiratory syncytial virus infection in elderly and high-risk adults

N Engl J Med

Circulating influenza virus, climatic factors, and acute myocardial infarction: a time series study in England and Wales and Hong Kong

J Infect Dis

Association of influenza vaccination with reduced risk of venous thromboembolism

Thromb Haemost

Influenza, influenza-like symptoms and their association with cardiovascular risks: a systematic review and meta-analysis of observational studies

Int J Clin Pract

The influence of oseltamivir treatment on the risk of stroke after influenza infection

Review
Point-of-care testing for respiratory viruses in adults: The current landscape and future potential