Late last month, the head of the Therapeutic Goods Administration, John Skerritt, announced Australians would be able to purchase rapid antigen tests from pharmacies and convenience stores from November 1.

The TGA has already approved more than 130 tests and is working on a new regulation to allow manufacturers to supply their self-tests for domestic use.

While rapid antigen tests might be new for Australians, they rely on old, established technology and have been widely used overseas for many months. Yet concerns remain around their use for self-testing in the Australian context, mostly to do with how reliable the tests are.

Most of us have become accustomed to the polymerase chain reaction (PCR) Covid-19 test. Many of us have had it at least once in the past 20 months.

“In Australia, a very large part of our success so far has been the widespread access to reputable laboratory-based PCR testing,” says Associate Professor Paul Griffin, an infectious diseases physician and microbiologist at the University of Queensland and director of infectious diseases at Mater Health Services.

PCR tests and rapid antigen tests (RATs) are fundamentally different. Both require a nasal swab, although saliva RATs exist. But while a PCR test looks for the virus’s genetic material to confirm the presence of the pathogen, an RAT detects viral proteins.

PCR acts like a genetic microphone. First, the genetic material from any virus present in the swab is isolated. It follows a thermal process that separates the virus’s DNA double helix into two single DNA strands. These then undergo an amplification process. An enzyme called Taq polymerase duplicates the DNA strands multiple times to create millions of exact replicas of the original DNA segment, which allows the identification of the pathogens present in the swab.

The whole process can take hours and requires sophisticated laboratory equipment and specialised staff, but results are almost 100 per cent accurate. In an RAT, the swab is mixed into a buffer solution that breaks the virus apart, freeing pieces of viral proteins. The buffer is then dropped onto a paper strip that contains antibodies tailored to bind to the antigens – viral proteins that cause our immune system to produce antibodies against them – and detect their presence in the buffer.

RATs deliver the result within 10 to 20 minutes as a coloured band on the paper strip, similar to a home pregnancy test.

Antigen levels rise and fall within the first few days of infection, so RATs are most suitable for screening people within five to seven days of contracting the virus.

RATs have several advantages compared with PCR tests – they are quick, relatively cheap and amenable to self-testing. But speed and convenience come at the cost of accuracy.

Professor Deborah Williamson, a clinical microbiologist and deputy director of the Microbiological Diagnostic Unit Public Health Laboratory at the Doherty Institute, says RATs are “inherently less sensitive than PCR”. That means RATs are more likely to miss cases or return false positives than PCR tests.

Accuracy, she said, depends on a variety of factors. Each brand comes with a different degree of accuracy. The ability of the user to collect a sample, operate the test, and read and interpret it, also plays a significant role in effectiveness, Williamson explained.

In March, Williamson and her colleagues tested the Panbio kit, one of the RATs licensed in Australia. They tested 2435 people, of which 22 had been shown to be positive for Covid-19 in a PCR test.

They found that the Panbio test had a specificity – the likelihood of a positive result if someone was not infected with Covid-19 – of 99.96 per cent, which means that for every 10,000 tests, four could return a false-positive result.

In Australia, where Covid-19 prevalence remains low, most positive results could be likely to represent false positives even with such high specificity.

But a more serious issue was the kit’s sensitivity – the likelihood of a positive result if someone was infected with Covid-19 – among asymptomatic people.

The Panbio kit picked up 100 per cent of positive cases among people who experienced symptoms in the previous seven days. But its sensitivity plunged to 77 per cent among those who did not experience symptoms, which equates to missing 23 positive cases in every 100.

Data on the performance of RATs in asymptomatic people is conflicting. A Cochrane review, which looked at several studies, found that sensitivity could vary from 40 per cent to 74 per cent.

However, RATs’ accuracy drastically improves when tests are repeated, compared with a one-off test. A study from the United States National Institutes of Health showed that sensitivity was comparable to PCR tests when people repeated the rapid test at least every three days.

“Given this accuracy issue, they’re not going to be appropriate for every situation,” Williamson said. “It depends very much on the appetite for risk.”

For example, in Western Australia, currently sitting on zero cases, missing even one case would be a huge deal. But in New South Wales and Victoria, RATs could add an extra layer of protection during the reopening phase.

“The rapid antigen testing is going to be a very useful adjunct to laboratory testing,” said UQ’s Paul Griffin. “In no way was it designed to replace PCR testing. But it’s designed to be a useful additional screen, provided we’re aware of some of those limitations.”

While RATs have been used primarily in pilot studies in Australia, they have been implemented in various settings to complement PCR testing overseas.

In Britain, for example, RATs were used in schoolchildren who were close contacts of a Covid-19 case. The study showed that daily testing was an acceptable alternative to self-isolation to prevent transmission while allowing children to continue attending face-to-face classes.

In Australia, self-testing could find its place in hospitals and healthcare facilities to screen staff and patients. It could facilitate border control, allowing incoming vaccinated people to self-test for a few days upon arrival, reducing the need for extended quarantine.

RATs could also be used to screen people before attending mass gatherings such as concerts, festivals and sports events.

People could self-test to monitor the occurrence of infection after a known exposure or before visiting family and friends.

“Anywhere that is high-risk, all those environments where we don’t want to see a positive person go, using RATs as a screening test, in addition to our usual processes, will be useful,” said Griffin.

But not everyone has welcomed with enthusiasm the use of RATs for self-testing.

In a statement released last August, the Royal College of Pathologists of Australasia recognised the need for RATs for surveillance testing in “defined circumstances” in addition to PCR tests, but remained concerned about their uncontrolled use while Covid-19 prevalence remains low in the country.

Professor Bill Rawlinson, a medical virologist at Sydney Adventist Hospital and RCPA member, said RATs “are not appropriate for every setting, and then they’re also not needed in every setting”.

He said RATs might be helpful in highly remote areas of Australia where people don’t have immediate access to PCR tests. But where more reliable testing is available, RATs might be redundant.

Rawlinson also pointed out that if people were to self-test at home, it would be crucial to have systems to help them perform and interpret the test and to provide medical support for dealing with a positive result. “You’ve got to have access to education, whether that’s an online GP, on the telephone, by email, by text messages. You come up with different clever ways of doing it.”

Deborah Williamson said we “should assume that people have a working knowledge”, but agreed the TGA must ensure users have access to support, that kits are fit for purpose and that there are clear instructions on how to use them.

She added that vaccination and all other public health measures that lower the risk of spread should still be a priority, but RATs might play an important role in getting us through the pandemic.

“As we transition to learning to live with Covid, I’d certainly welcome the added benefit that these tests provide as an additional screen,” Griffin said. “They will help us moving forward as we try to open up.”

Share this article