We need to focus our research on low-cost, accessible, and rapid testing
Bangladesh and its neighbouring country, India, have just begun to see an increase in the number of patients of Covid-19. Developed countries like Italy, Spain, and the US struggled to manage Covid-19 patients at the peak of the epidemic curve with their robust health care systems.
Hence, it is expected that Bangladesh -- an overpopulated country with limited health care resources -- might see devastating outcomes if the infection spreads at a disproportionately high rate. Although the infection has already spread, it is still at an early stage. Therefore, it’s not yet too late to have pandemic preparedness in place to tackle the upcoming challenges.
The recent “zoning” initiative of Bangladesh to minimize the spread of the pandemic is praiseworthy. The first step to reducing the rate of the infection is to isolate positive patients from healthy individuals. In order to achieve this, adequate testing is essential.
Testing for Covid-19 involves a technique called real-time reverse transcription-polymerase chain reaction (rRT-PCR). This technique requires a long time (five-six hours), money, skilled personnel, and advanced technology.
Many countries simply do not have the infrastructure to support the testing of the required number of samples. As of June 18, for every 1,000 people, the US has tested 71 people whereas India and Bangladesh have tested four and three people, respectively.
To navigate this challenge, rapid-testing (that can deliver results in minutes) should be used in addition to rRT-PCR. One such rapid and inexpensive test is the serology test (to detect the presence of antigen or antibody).
Over 100 kinds of serology tests have been developed and a number of these tests have been approved by the US Food and Drug Administration (FDA).
It is to be noted that researchers from Bangladesh’s Gonoshasthaya Kendra have also developed such a test, however, Bangabandhu Sheikh Mujib Medical University recently concluded that the kit is not effective in detecting coronavirus.
Should we opt for rapid and low-cost testing?
To properly answer that, it’s important to know about rRT-PCR and serology tests. The rRT-PCR can accurately detect the presence of specific genetic material in the virus. The serology test detects the presence of antigen (proteins given off by the virus) or antibody (proteins that the patient develops after being exposed to the virus) in the human body.
Thus there are two types of serology tests: Antigen test and antibody test.
In the case of Covid-19, it takes about five-seven days for the antibody to develop inside the patients and therefore detectable levels of antibody might be absent at the initial stage of infection.
Antibody tests are therefore not an optimal tool to diagnose active viral infections. On the other hand, antigen tests that detect the proteins of the virus may play a vital role in the detection of the virus/infected patients.
The first rapid antigen test was approved by the FDA on May 9, 2020. WHO has still not approved any of the rapid tests for diagnostic purposes but the efficiency and potential diagnostic applications of the test warrants attention.
The reliability of a diagnostic test depends on multiple factors of which the two most important ones are sensitivity and specificity. The sensitivity of a test denotes the ability to identify the true positive case, and the specificity is the ability to identify true negative cases.
This means that a highly sensitive test will give very few false-negative results and a highly specific test will give fewer false-positive results. These factors are considered before a test is approved for clinical diagnosis.
Not a single test provides a 100% accurate result, not even the advanced rRT-PCR technique. However, rRT-PCR is still considered as the gold-standard test as the error margin is much lower compared to any other tests.
Countries with access to a huge number of rRT-PCR kits are trying to manage the pandemic using that but for a resource-limited and overpopulated country like Bangladesh, it is difficult.
Currently, it takes about four-five days for the test results to come out after the sample has been collected. Therefore, to increase the number of testing immediately, concerted efforts should be put to use rRT-PCR as well as rapid antigen tests.
A few considerations need to be kept in mind for the effective use of both tests:
1. Before implementing any rapid test kit for diagnostic purposes, clinical and analytical validity should be checked to confirm that the kit has acceptable levels of sensitivity and specificity.
Bangladesh has many research institutes and universities with well-equipped laboratories that can be employed to quickly test and select the appropriate test kit from available local or international options.
2. With the use of appropriate rapid antigen tests along with rRT-PCR, the risk of infection can be significantly reduced as more people with symptoms can be tested. Also, high-risk professionals and high-risk regions can be given priority for testing.
It takes skilled personnel, a well-equipped lab, and an estimated Tk3,000 to run a single rRT-PCR test. In contrast, the rapid antigen test requires fewer workers and is low-cost. Upazila health complexes can cater as primary test centres for these types of rapid tests, whereas minimum BSL2+ lab is required for rRT-PCR of the SARS-COV-2 virus.
3. If the appropriate rapid antigen testing is available, then it can be used as the primary screening technique. Based on the results of the rapid antigen test and rRT-PCR, an integrated decision can be made using the following decision-making algorithm. If decisions are made immediately, then the same sample can be used for both tests, removing the need for another sample collection.
4. Positive results from primary screening can be considered as true positives and the patients should be isolated or hospitalized accordingly.
The impact of false positives is minimum, and shouldn’t affect the treatment decision. This is because most Covid-19 positive patients do not require hospitalization and the ones requiring hospitalization can be retested using rRT-PCR if required.
5. It is also to be noted that not all negatives are true negatives. This is the primary drawback of rapid antigen testing. Patients may not have detectable amounts of the virus in the body and therefore, may appear negative; rRT-PCR also gives negative results under this condition.
All negative results can be categorized into two groups. First, people with no symptoms and no underlying health conditions can be considered as negatives. Secondly, people with Covid-19 symptoms and underlying health conditions can be retested by using the rRT-PCR test.
The number of people tested can be considerably increased by combining both rapid antigen tests and rRT-PCR even with our finite resources. Albeit, rapid antigen tests are less efficient than rRT-PCRs but considering the terrifying reality of the pandemic combining both rapid antigen tests and PCR is the logical way forward.
Most countries haven’t adopted rapid antigen tests as a diagnostic tool as WHO is yet to approve it but there is no limitation on researching the effectiveness and making the appropriate selection of the test kit.
Most recently, on June 15, the Indian Council of Medical Research approved the first rapid antigen test kit in India.
Another great example to look up to is Vietnam. It’s a lower-middle-income and overpopulated country with only around 300 cases of Covid-19. Locally developed rapid tests and aggressive contact tracing has helped them set an astonishing example.
In conclusion, instead of depending only on the time consuming, expensive, and advanced technology, we can also focus on researching the potential of low-cost, accessible, and rapid antigen tests to combat this pandemic even with our limited resources.
Md Zohorul Islam, PhD, is Postdoctoral research fellow (Microbiology), Harvard University, USA, and associate professor, Chattogram Veterinary and Animal Sciences University, Bangladesh. Ayesha Sania, PhD, is Research scientist (Epidemiologist), Columbia University, USA. Dr Nusrat Homaira, PhD, is Senior Lecturer (Respiratory Epidemiologist), University of New South Wales, Australia. Najmul Haider, PhD, is Postdoctoral Researcher (epidemiologist), Royal Veterinary College, London, UK. Shara Khan, PhD, is affiliated with University of Alberta, Canada.