There has been much controversy regarding the Covid-19 diagnostic test kit produced by Gonoshayasta (GK) Kendra in Bangladesh.
It is imperative that any confusion is resolved without further ado as any confusion regarding the quality of the test as well as any flawed test that mistakenly suggests people have the infection or are immune when they are not could be extremely dangerous for the individual, health care professionals, the wider community, and our fight against this devastating pandemic.
In March this year, the UK government purchased 3.5 million antibody tests. But after trial, they found that the test kits were inaccurate and unreliable, and the they cancelled the order and tried to get back the money spent in purchasing those test kits.
This was exactly the experience of the government of Spain who had discovered that, though the Chinese manufacturing company was claiming 90% accuracy, in fact, the Spanish government detected that the sensitivity was 30% when they compared the test with RT-PCR test being used as the gold standard.
The UK Department of Health and Social Care stated in early April that no country has a valid antibody test in use. However, Abbott, the company that manufactures pharmaceuticals, diagnostic, and medical devices, announced on April 28 the immediate availability of its lab-based antibody test for Covid-19 in Europe after it was granted a CE Mark -- a certification mark indicating conformity with health, safety, and environmental protection standards for products sold in the European Union.
The company had already secured permission from the American FDA. According to Abbott, it has demonstrated specificity and sensitivity of greater than 99%. The test adds to Abbott's existing tests in the US and the UK that are already being used on its m2000 molecular laboratory system.
I explained in an article published in the Dhaka Tribune last week that the basic structure of SARS-CoV-2 virus comprises of: (a) a spherical or circular envelope/wall made of matrix-protein that contains: (b) a single-stranded RNA, the virus, and a nucleoprotein.
The envelope bears: (c) club-shaped glycoprotein projections, the “spike glycoprotein,” so from inside out: ( i) the RNA virus and N-protein, (ii) the envelope and (iii) spike glycoprotein that are the antigen or antibody basis for any Covid-19 test.
Diagnostic tests for a virus like SARS-CoV-2 are largely based on four different techniques, some utilizing virus material and antibody produced in the human against the virus:
1. RT-PCR: Reverse Transcription Polymerase Chain Reaction.
2. LAMP: Loop-Mediated Isothermal Amplification -- a simple, but less developed testing method.
3. Lateral Flow: Hand-held single-use assays providing results for an individual patient in as short as 15 minutes.
4. Enzyme-Linked Immunosorbent Assay: Quick and technically simple assays that are easily read and offer relatively high throughput.
The researchers and clinicians with a background in deoxyribonucleic acid (DNA) amplification and antibody and antigen assays are well aware of these techniques but not the broader community.
RT-PCR Test: PCR is a very common widely-used scientific technique to detect genetic information. RT-PCR is a special version used when RNA is being detected and it is now being used as a frontline test to detect the Covid-19 virus SARS-CoV-2, directly testing the presence of the virus RNA by capturing and amplifying regions of the virus’ genetic material, usually the Spike protein, N-protein or envelope and may be performed fairly quickly, is highly sensitive and fairly reliable if performed on a sample from an infected part of the body whilst an active infection is occurring and is capable of producing results in three to four hours but longer if the samples are being sent to external laboratories.
A positive PCR result means that the person the sample was taken from is currently infected by the virus and a negative PCR result could mean that the person is not currently infected by this virus, ie the virus is not present at the site the sample was taken from, the sample taken was of poor quality, or that it is too early or too late in the infection to detect the replicating virus.
This is why negative test results require new patient samples to be taken a few days later to reduce the chance of incorrectly missing an infected person. The RT-PCR test cannot detect if a person has had the virus and then cleared it after the end of the Covid-19 disease, ie whether a person had the disease, as it only detects when the active virus is present. RT-PCR is accepted by scientists and medical staff as a robust and well-documented technique.
LAMP -- Loop-mediated Isothermal Amplification -- is a similar process to RT-PCR, but instead of using a series of temperature changes to produce copies of the viral DNA, LAMP is conducted at a constant temperature and as such may be completed far quickly than RT-PCR tests, producing results in two to three hours.
The technology is newer and still being assessed in clinical settings. Only Singapore has claimed success.
Antibody tests for Covid-19 diagnosis fall into two groups: Antibody tests for diagnosis performed in laboratory on specialist equipment and point of care antibody tests using a “lateral flow” mechanism.
Lateral flow antibody tests require no specialist equipment and can be done anywhere, producing results in between 10 to 20 minutes. To date, no such test has been validated and experts have urged people against purchasing unvalidated antibody (lateral flow) tests.
Newspapers in Bangladesh and Al-Jazeera reported that the GK scientist seems to have found a testing formula for SARS in 2003 while working in Singapore, apparently the patent later bought by the Chinese government. He had joined Gonoshasthya-RNA Biotech two years ago.
GK said in March that they have a test, antibody based, but need raw material. Initially, they appear to use the Chinese ingredient which was unacceptable in European countries and the US. They sought permission to get it from the UK and the honourable prime minister of Bangladesh kindly allowed the importation of the reagents from the UK. But then, confusion started.
After receiving the material and producing the test kit, GK did not provide any scientific evidence showing that the test kit works and has an acceptable specificity and sensitivity, the very basic information required for any scientific test used for screening, diagnosis, and monitoring purposes.
It is now clear that they had not carried out any sort of trial to support its use and it is only now that the trial is being conducted in collaboration with the Bangabandhu Sheikh Mujib Medical University (BSMMU).
Confusion solidified further when the DG, DGDA stated that though the initial proposal was to produce antibody test kits, GK has now shown that the test kit was for detecting viral antigen.
This would cast a huge shadow on the credibility of the test and this confusion must be alleviated as credibility of the diagnostic test is very much dependent on the test material, whether it is an antigen or an antibody related to the virus.
Dr Raqibul Mohammad Anwar is a Colonel, Royal Army Medical Corps, UK Armed Forces, and Specialist Surgeon & Global Health Policy and Planning Expert.
