• CHLAMYDIA TRACHOMATIS
• DIAGNOSIS
• LABORATORY METHODS
• CLINICAL TRIALS

While scanning De Baetselier and colleagues’ article evaluating an enzymatic Chlamydia trachomatis (CT) point-of-care assay (POC), I was struck by a feeling of déjà vu.1 They found the BioChekSwab Rapid Test performed poorly, missing all nine infections detected by PCR. This reminded me of a paper by Moi in 2007 reporting the very poor performance of a POC for CT, HandiLab-C.2 Reading further, I realised this was not coincidence. The two assays seemed to use the same technology.

BioChekSwab Rapid Test seems to be an updated HandiLab-C test that was widely available about 10 years ago. Sold in at least 17 countries, it had a CE mark with approval for POC professional use and over-the-counter sale (meaning self-test).^Web1 In 2006, workers at the National Chlamydia Screening Programme, concerned about use of the test in England (it was for sale in pharmacies and supermarkets), asked me to speak about chlamydia diagnostics at their annual meeting. My talk emphasised nucleic acid amplification tests (NAATs) for CT diagnosis and warned about using HandiLab-C because the technology was not new and there were no reproducible clinical data supporting its use despite the company’s claims.

Within a year, the Moi paper appeared stating that the HandiLab-C assay was not what it claimed. Subsequent trials confirmed that, finding sensitivity of only 12.5% and 19.4% in two clinics in the Philippines, and 12% in an STD clinic in the Netherlands.3 ,4

I was familiar with the HandiLab-C technology because in the 1980s Diversified Diagnostics Inc. (DDI) had a similar assay ‘MicroZyme the Easy Test’, claiming sensitivity of 96% and specificity of 97.9% for CT detection.^Web2 It was described as the only totally biochemical test system; easy to perform; only 10 min to get a result. The procedure was collect a swab, drop two reagents on it, wait 10 min and drop a third reagent onto it. A purple colour would develop if CT was present. The company had similar assays, under several names, for gonorrhoea, candida, salmonella and others. Assuming this assay detects an enzyme unique to each organism, the company would need specific substrates for each organism’s enzyme.

The HandiLab-C technology was quite similar. Described as enzyme detection technology, the test could also be performed on a swab placed in a self-contained device. The company had identical protocols ‘For All HandiLab Tests (Chlamydia, Gonorrhea, Strep-A, Yeast)’.^Web3

The BioChekSwab CT Rapid Test is almost identical.^Web4 It is part of a portfolio of assays described under ‘Testing with Unique Enzymatic Diagnostic Systems for Detection of Bacteria and Other Infectious Diseases’. The target is said to be CT's Peptidase 123CBV.1 A HandiLab-C technical alert announced discovery of CT’s Peptidase 123A and synthesis of a specific substrate in 2005.^Web5

Even an interested observer has difficulty following what is going on when companies with different names market tests with similar technology under different names. First, there was DDI and Microzyme, then Zonda and HandiLab-C. Vista Enterprises Inc. (VEI) then announced that BioVei Inc. had developed a chlamydia test and that it would be distributed by EnZtek.^Web6 The BioVei test was evaluated and found inadequate.5 But it was marketed by EnZtek as The BioChekSwab test and by ValiMedix as the SELFCheck Chlamydia assay.1 ^Web7 At this writing, the latter test is available for purchase on the internet.6 The instructions for the kit state it was manufactured by EnZtek.7

The manufacturers of these tests have many things in common. All were based in the San Francisco Bay area. DDI in Concord, Zonda (HandiLab-C) in Moraga, VEI and BioVei in Antioch, and EnZtek Diagnostics (BioChekSwab CT Rapid Test) in Rio Vista.

There is also considerable overlap of officers of the companies: Laurie Oleksiewicz has been a president of both Zonda and EnZtek.^{Web8 9} Robert Hird has been a president of DDI (and was its founder) and a chief technology officer of EnZtek.^Web10 They have both been officers of BioVei and VEI.^{Web11 12} Both names are on the patent for the self-contained device used in the assays.8

These companies had a common marketing strategy. It was not the typical approach of assessing test performance by multicentre trials, publishing results in peer-reviewed journals, and obtaining US Food and Drug Administration (FDA) clearance. Rather, they hired space at a major medical exposition (say MEDICA, among others), passed out materials describing their test, its performance and advantages. This gained exposure to the press, to some members of the STD community, and, most important, to potential distributors of their product. The press reports the information presented by the companies. The companies in turn issue press releases describing the favourable reception received at the expo and how much excitement their test had generated.

The STD community has been desperate for a good performing POC for CT. It would benefit patients and researchers. And some have become willing victims of this marketing strategy by providing a market for a poor performing test. The strategy seems most successful for HandiLab-C. Zonda made some press releases, but the volume increased considerably after CLX Investments Inc. (Temecula, California, USA) invested in Zonda, and then became the majority stockholder.^Web13 Frequent (at times daily) press releases were made: announcing the enthusiastic reception the test had received at a meeting; the distribution agreements made in a number of countries; corporate news; and notices related to the planned clinical trials to obtain FDA clearance (these were never reported).^Web14 These announcements were likely made with the a dual purpose of stimulating interest in both the test and the stock.

In their discussion, De Baetselier cite, “The sensitivity and specificity of the BioChekSwab test were previously determined by the manufacturer in a Hungarian Genitourinary Clinic. In that study with 197 women … CT prevalence by gold standard test was 27%, and the BioCheckSwab test was 98.2% sensitive (95% CI 90.1% to 100%) and 97.9% specific (95% CI 94.0% to 99.6%) (unpublished data, EnZtek Diagnostics, 2013)”.

But that protocol, and those exact numbers were published in an evaluation of an assay called Sumatest in Hungary in 2006.9 Sumatest was the name used for HandiLab-C in Hungary. I found those results difficult to accept. There was no information as to the performance or design of the ‘home brew’ PCR, and the age distribution of the CT infections was unprecedented (28% in women >40 years old).

There is a documented history of wrongdoing in support of enzyme detection technology. In 1993, Robert Hird (see above) was on probation for prior offenses related to the marketing of ineffective diagnostic kits when he was accused by the FDA of being behind a similar marketing scheme, which included altering study data to show a chlamydia test manufactured by DDI to be more effective than actual results demonstrated. He was convicted of 21 felony charges and sentenced to 5 years in jail in 1995.10 A Zonda press release discussing the reports of poor performance of their test made mention of an employee who had been debarred by the FDA.^Web15

What we have here is a relentless marketing scheme that has been going on for >25 years. There are three generations (roughly 1990, 2005 and 2015) of enzyme detection diagnostic tests for CT. I have found no series of peer-reviewed evaluations to support their use. There is no credible evidence that peptidase detection has any role in diagnosing chlamydial infection. This is a recurrent tale of a POC of no proven value being presented with exaggerated claims to a target audience rendered susceptible by their desire to use such a test. The test has a brief success, until published independent evaluations expose its poor performance. Then, with minor technical change, it will be marketed by successor companies under different names. This scenario could have been repeated in food sciences, environmental sanitation, MRSA and other areas where enzyme detection for diagnosis has been pushed by these same companies.

This is not a simple money-making scheme. It does harm! Think of the uninfected, asymptomatic young woman who admirably decides to self-test for CT. A false-negative result could lead to infecting a new partner, a serious, painful and expensive clinical episode, or even, infertility. This must stop! A strong CE mark would be a good start.

What have we learned from this repeated bad experience? As a community we are susceptible to this ‘creative’ marketing approach. Manufacturer’s performance claims in Europe are not scrutinised as they would be by the FDA in the USA. But, even though it may be slow, we have a self-policing mechanism. Independent studies and peer-reviewed literature ultimately expose unrealistic claims. Kudos to Moi and De Baetselier et al for sounding the alarm. Negative studies are worth publishing. STI did its job.

Do not blindly accept unsubstantiated claims of test manufacturers. Rely on the peer-reviewed literature. Be a sceptic.