This briefing describes the regulated use of the technology for the indication specified, in the setting described, and with any other specific equipment referred to. It is the responsibility of healthcare professionals to check the regulatory status of any intended use of the technology in other indications and settings.
The AdenoPlus test is an in vitro diagnostic medical device for which the manufacturer (Rapid Pathogen Screening) received a CE mark in June 2011. The CE mark was revised in October 2012 when the product name was changed from Adeno Detector to AdenoPlus. The current UK distributor is Nicox Pharma SNC.
AdenoPlus is a single use, point‑of‑care diagnostic test for adenoviral conjunctivitis. All human adenovirus serotypes contain the hexon protein that is detected by AdenoPlus. The test takes around 10 minutes to return a result. According to the instructions for use, the test is recommended for use within 7 days of the person developing a red eye with signs and symptoms of infectious conjunctivitis. AdenoPlus has a detection limit of 6 ng/ml adenovirus hexon protein.
All the necessary components of the AdenoPlus test are contained in a single test kit. This includes a sterile sample collector with sampling fleece attached to the tip, a test cassette and a buffer vial. The sampling fleece is made of Dacron, which may cause allergic reactions for some people. If both eyes are affected by conjunctivitis, the test should be done using tear samples from the most recently affected eye. To do the test, tear fluid is collected from the person's inferior palpebral fornix conjunctiva (the area between the lower eyelid and the eyeball). This is exposed by pulling the lower eyelid downwards. The sampling fleece is dabbed across the conjunctiva 6 to 8 times in total, and is then rested against the conjunctiva for an additional 5 seconds. If the person experiences discomfort during the sampling procedure, a topical anaesthetic can be used, and the sample collected 5 minutes after applying the anaesthetic. The anaesthetic does not interfere with the test results.
The protective cap is then removed from the test cassette, revealing a sample transfer window and an absorbent tip. The sample collector is placed on the test cassette with the sampling fleece tip inserted into the sample transfer window, and the 2 components are then clipped together. To run the test, the absorbent tip of the test cassette is immersed into the buffer vial for at least 20 seconds. Once the absorbent tip is removed from the buffer vial, the protective cap is replaced on the test cassette and the test placed horizontally on a flat surface for at least 10 minutes. The test cassette also contains a result window. A purple fluid wave will move across the background of the result window while the test is running. Once the background of the result window is white and 10 minutes have elapsed, the test can be read.
The results of the test are indicated by 2 lines: a blue control line and a red result line, which appear in the result window in their respective zones (the control zone and the result zone). The blue control line indicates that the test result is valid. A red line in the result zone indicates a positive result – the presence of adenovirus antigens in the tear fluid. A red line that is faint or uneven in colour or incomplete over the width of the test strip may happen because of an uneven distribution of eye fluid in the sampling fleece, but this should also be interpreted as a positive result. A single blue control line with no red result line indicates that the test has worked but the result is negative, that is, adenovirus antigens are not present in the tear fluid or are below the 6 ng/ml detection limit of the test. If a blue control line does not appear, the test result may be invalid. In this case, the absorbent tip should be re‑immersed in the buffer vial for an additional 10 seconds. If a blue line still does not appear after 10 minutes, the test should be discarded and the person retested using a new AdenoPlus test kit. If a further test is needed, additional samples from the same eye may have fewer adenoviral antigens, so if both eyes are equally affected, the second sample should be collected from the other eye. In patients with only one eye affected, the sample collection may be repeated 30 minutes later. The test cassette should be used within 1 hour of opening, and the test run within 24 hours of taking a sample and assembling the test. The result should be read within 12 hours of completing the test.
The AdenoPlus test is intended for use by healthcare professionals to help in the rapid differential diagnosis of acute conjunctivitis in people of any age, to reduce the unnecessary prescribing of antibiotics for viral infections. It is designed for use in any healthcare setting where people with eye conditions present, such as primary care, urgent care services or secondary care ophthalmology services.
A diagnosis of conjunctivitis is usually made by GPs by assessing symptoms and examining the eyes. People should be referred to an ophthalmology clinic if they have reduced vision or if they do not respond to treatment. People who wear contact lenses may need to be referred to an optometrist to check the cornea for keratitis (NHS Oxfordshire 2010). Further tests (such as a swab test) may be needed if the conjunctivitis is persistent, does not respond to treatment or to help decide what treatment to use (NICE clinical knowledge summary on infective conjunctivitis). The swab from the affected eye is sent to a laboratory to determine the cause of the conjunctivitis. Cell culture with immunofluorescence detection is considered reliable but may take 1 to 2 weeks; polymerase chain reaction (PCR) assays can identify adenovirus, enterovirus, herpes simplex virus or herpes zoster virus in less time (Public Health England 2014).
NICE is not aware of any other CE‑marked devices with a similar function to the AdenoPlus test.
AdenoPlus costs £150 (excluding VAT) for a box of 10 tests. There are no additional consumables or maintenance requirements. Both the AdenoPlus test cassette and the buffer are stable until the expiry dates marked on their outer packaging and containers. The shelf life is 2 years.
AdenoPlus would be used as an alternative to existing laboratory tests to identify the type of infection in people with infectious conjunctivitis.
Two specialist commentators stated that AdenoPlus is fairly easy and quick to use at the point of care. However, 2 of the specialist commentators noted that the process of swabbing might be difficult, particularly in people with sore or severely inflamed eyes, and is likely to be impractical in children.
One specialist commentator mentioned that AdenoPlus is cheaper than the current gold standard PCR test (if swab and laboratory costs are taken into account), although PCR is not commonly used because the results are not available in time to guide first‑line management. One specialist commentator stated that the current management options for conjunctivitis are either no treatment or treating with antibiotics (usually chloramphenicol eye drops) and that both options are cheaper than using AdenoPlus (about £1.50 compared with £15). One specialist commentator noted that the need for steroid treatment for the acute condition or for adenoviral keratitis, which may occur as a complication of certain serotypes of the virus, is based on the symptoms of the patient. They added that although it is reassuring to know that the patient definitely has adenovirus, it is not necessary for ongoing management.
One specialist commentator stated that using AdenoPlus in an acute setting or GP practice is cost and time effective. Another specialist commentator stated that they do not consider AdenoPlus to be clinically necessary and that it does not offer sufficient utility to warrant its routine use in infectious conjunctivitis. They did note that it would be 'nice to have', particularly in primary care settings without access to a slit lamp, and for atypical cases, such as those where only one eye is affected. The specialist commentator stated that, assuming the conjunctivitis is viral, no harm would come to the person by not doing any tests, giving no antibiotics and waiting for a few days. They also said that this strategy would not cause side effects related to antibiotic usage and would also minimise expense. The specialist commentator noted that even if they have a positive test using AdenoPlus, patients also need to be checked by a healthcare professional with a slit lamp if they have a lot of pain, blurred vision or sensitivity to bright lights (photophobia) because they might need topical steroid treatment.
One specialist commentator stated that AdenoPlus was cheaper than the current gold standard PCR test, which is not commonly used because the results are not available to guide first‑line management. They noted that although PCR can detect atypical cases of chlamydia conjunctivitis as well as other viruses such as herpes simplex virus and varicella‑zoster virus, which all have specific treatments, they considered PCR to be a waste of resources unless chlamydia was the likely cause. The specialist commentator raised a concern that AdenoPlus could give false reassurance in people with both adenovirus and chlamydia. This might lead to under‑treatment of chlamydia, which has far greater potential complications for the person and their sexual partner.
Two specialist commentators stated that antibiotics are often prescribed because people find their symptoms distressing, although most cases of conjunctivitis seen by GPs are mild conditions that may get better with no treatment, and are likely to be of viral origin. Two specialist commentators suggested that it would be more cost effective to target public health messages (for example, in school and nursery health education and policies) to reduce the pressure on GPs to prescribe antibiotics for conjunctivitis. One specialist commentator noted that there are currently no real‑world data to support the idea that antibiotic prescribing would decrease by using AdenoPlus. The commentator stated that it would be useful to see more studies on AdenoPlus to confirm if regular use of the test reduces the numbers of people requesting antibiotics from GPs, as well as reducing the number of antibiotic prescriptions.
One specialist commentator stated that the AdenoPlus test itself would not reduce the number of working days and school days lost as a result of conjunctivitis, because the test will not affect the course of the condition or the symptoms. However, replacing PCR tests with AdenoPlus could decrease the number of unnecessary GP appointments and days off work or school needed to get the results, reducing health‑related anxiety and additional expenses for the person.
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