Advice

The technology

The technology

The FebriDx test (Lumos Diagnostics) is a single-use, portable, in vitro diagnostic test. It is intended to give point-of-care semi-quantitative measurement of C-reactive protein (CRP) and qualitative measurement of myxovirus resistance protein A (MxA) in human peripheral whole blood.

CRP is a non-specific indicator for the presence of acute inflammation, which can be raised when there is bacterial infection. MxA is a protein marker that is raised in the blood when there is acute viral infection. Simultaneous measurement of MxA and CRP in people with acute febrile respiratory infections is designed to help differentiate between viral and bacterial infections. This can then guide appropriate use of antibiotics. Tests that improve clinical decision making in antibiotic prescription at the point of care could support antimicrobial stewardship.

FebriDx is a self-contained, portable, all-in-one test device, which both collects and analyses the blood sample. It consists of a single strip test card, a buffer solution activated by an integrated push button, lancet and collection tube. No extra equipment is needed.

The FebriDx test card has a single lateral-flow test strip with monoclonal anti‑MxA and anti-CRP antibodies. The lancet punctures the skin and the first drop of blood is discarded. After this, a 5 microlitre blood sample is collected at a 45‑degree angle using the blood collection tube. The blood is transferred into the blood transfer zone when the collection tube is full, and the buffer solution is applied by fully depressing the buffer release button. The test is left to develop for 10 minutes on a flat surface before the results are analysed and displayed in the result window.

Innovations

Point-of-care CRP tests could change current practice by helping clinicians to make decisions about whether to prescribe antibiotics for people with symptoms of respiratory tract infections during a primary care consultation. The addition of the MxA biomarker in the FebriDx test is designed to increase specificity compared with CRP alone. It is claimed that FebriDx eliminates the 'grey zone' of 20 mg to 100 mg per millilitre CRP by accurately differentiating viral from bacterial infection. This means that rapid and accurate antibiotic prescribing decisions can be made (if a diagnosis is unclear, antibiotic prescribing should be based on a point-of-care CRP test level of more than 100 mg per litre. Prescribing antibiotics should be delayed at levels between 20 mg and 100 mg per litre). It could also help identify and isolate people with suspected COVID‑19, by differentiating viral and bacterial respiratory infections when they enter a healthcare setting.

Current care pathway

Respiratory infections (mainly consisting of otitis media, sore throat, sinusitis, pharyngitis, acute bronchitis and pneumonia) are one of the most common reasons for oral antibiotic prescriptions in the NHS (Del Mar 2016). Bacterial and viral respiratory tract infections clinically present similarly and are frequently misdiagnosed. The decision to prescribe antibiotics for a suspected respiratory bacterial infection in primary care is generally made by a GP or nurse practitioner. This decision is based on medical history, clinical examination and assessment of risk. The 2018 English surveillance programme for antimicrobial utilisation and resistance (ESPAUR), reported that 81% of all antibiotics prescribed in England in 2017 were from a primary care setting. This was equal to about 654 prescriptions for every 1,000 people. A recent study on antibiotic prescribing in English primary care suggested that approximately 9% to 23% of antibiotics used in secondary care were inappropriate (Smieszek et al. 2018).

Point-of-care testing should be considered in primary care for people with suspected lower respiratory tract infections. Point-of-care CRP tests should be considered for people with symptoms of respiratory tract infection in primary care, if a diagnosis is unclear after clinical assessment. Antibiotic prescribing should be based on the results. Immediate antibiotic treatment should be offered if the CRP level is more than 100 mg per litre and a delayed prescription should be considered at levels between 20 mg and 100 mg per litre.

Antibiotics can be prescribed at the time of the patient's first clinical examination, or postponed until a later date if the symptoms continue.

Point-of-care CRP tests are not yet widely used in primary care. Standard laboratory analysis for CRP and MxA is typically only done by collecting a venous blood sample. These are sent off for laboratory analysis, with the results available 1 to 2 days later. Because of this delay, CRP and MxA testing are not typically used to assess acute respiratory infections in primary care. FebriDx uses 2 biomarkers with MxA used to confirm a negative test for CRP.

To help stop bacteria becoming resistant to antibiotics, it is important to prescribe antibiotics in line with the principles of antimicrobial stewardship. These include only prescribing them when needed (and not for self-limiting mild infections such as colds and most coughs, sinusitis, earache and sore throats) and to review the continued need for them.

NICE is aware of the following CE-marked devices that appear to have some of the functions that FebriDx has, but none include a viral biomarker and all need bench-top analysers:

The following publications have been identified as relevant to this care pathway:

Population, setting and intended user

The FebriDx test would usually be used for people with suspected acute febrile respiratory tract infections presenting in primary or secondary care. It could also be used in community care and in out-of-hours facilities. It would be done as a point-of-care test by clinicians during a consultation. It would be used together with a clinical examination and clinical judgement, to help clinicians to make the decision to prescribe antibiotics. This is because a negative result would not preclude a respiratory tract infection.

During the COVID‑19 pandemic or pandemics of a similar nature, the technology could also be a way to initially test, triage and isolate individuals presenting to hospital with symptoms associated with the pandemic.

Costs

Technology costs

The cost of each single-use FebriDx test is £12.75 per test (excluding VAT). The company has advised that it offers volume discounts on this price. No extra equipment is needed.

The company, through its UK distributor, provides training to NHS users. This is included in the cost of the test and is free of charge.

Costs of standard care

Standard care for people who present to primary care with symptoms of a respiratory tract infection would be a consultation with a primary care clinician. This would not include point-of-care tests to help the diagnosis. The clinician would make the clinical decision about whether to prescribe antibiotics. The unit cost of a GP consultation, excluding antibiotic prescriptions, ranges from £27 to £36, for an average consultation time of 9.22 minutes. This depends on the GP's qualification and direct care staff costs (Personal Social Services Research Unit, 2016). The average cost of a course of amoxicillin is about £1.49. A course of erythromycin costs about £3.05.

Resource consequences

The FebriDx test would be an extra cost compared with a standard primary care consultation, adding test cost and staff time. These extra costs may be offset if it reduces repeat appointments, helps to avoid unnecessary antibiotic prescribing and reduces adverse events associated with this. An economic evaluation by Schneider et al. (2020), using a UK NHS perspective, suggests that FebriDx could save the NHS £88 million every year. This is through avoiding unnecessary antibiotic prescription and related adverse events.

Antimicrobial stewardship is an important issue in healthcare and a number of guidelines have been published related to this: