Widespread use of serological tests for tuberculosis: data from 22 high-burden countries

To the Editors:

There is great excitement over the introduction of new tuberculosis (TB) diagnostics [1]. Since 2007, several TB diagnostics and approaches have been endorsed by the World Health Organization (WHO) [2],with Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) being the most recent [3]. Amidst this excitement, there is growing concern surrounding the use of inappropriate and suboptimal TB diagnostics [4, 5].

Currently available commercial serological (antibody detection) tests for TB are inaccurate and highly inconsistent [6–8]. The International Standards for TB Care explicitly discourage their use [9]. Even so, serological tests are known to be widely used in countries such as India [2, 4, 5]. In addition to posing an economic burden on patients and healthcare systems, use of serological tests also entails potential harm to patients (e.g. unnecessary TB therapy because of false-positive results, or morbidity and mortality because of false-negative serology results).

After reviewing the evidence, including the findings of an updated meta-analysis [10], the WHO recently announced its first negative policy in TB, against the use of current TB serological tests [5, 11]. In the context of this new policy, we conducted a survey of 22 high-TB burden countries, in order to quantify the current market for serological tests and settings where they are used, and elicit perceptions about regulatory agencies.

We identified TB experts in each country and invited them to complete an electronic e-mailed survey. Although no specific selection criteria were used, we contacted a mix of public and private providers, including experts from national TB programmes. Completed surveys were obtained from at least two respondents in each of the 22 countries. When discrepant responses were noted, surveys were sent to additional experts. Thus, three or four experts were surveyed for some countries. As shown in table 1, respondents from 17 (77%) out of 22 countries reported that serological tests were on the market and being used.

In 13 out of the 17 countries where serological tests were used, both rapid test kits and ELISA-based assays were available, and all 17 countries had imported tests on the market. The most commonly available tests included MycoDot (Mossman Associates, Millford, MA, USA), ICT TB (ICT Diagnostics, Sydney, NSW, Australia), SD Rapid TB (SD Bio Standard Diagnostics, Gurgaon, India), Pathozyme Myco (Omega Diagnostics, Clackmannanshire, UK), TB IgG, IgM, IgA (J. Mitra & Co., Delhi, India), and Anda TB (Anda Biologicals, Strasbourg, France).

As shown in table 1, none of the 17 countries had any policies that recommended serological tests. Of these countries, 15 (88%) reported use in the private sector and eight (47%) in the public sector (all outside of the National Tuberculosis Control Programme). When asked to rank the most commonly used tests for active TB, respondents in all countries ranked microbiological techniques (sputum smears and cultures) as more frequently used than serological tests, but serological tests were generally ranked higher in the private sector than in the public sector.

Respondents from 11 (65%) out of 17 countries reported that serological tests were used as the basis for initiating therapy for active TB; those in India, Indonesia and South Africa reported that this happened “often” in the private sector. Respondents from 12 (71%) out of 17 countries perceived their regulatory agencies as being “weak”, and 11 acknowledged that such weakness may allow for the importation and/or use of serological tests. Interestingly, some respondents rated their regulatory agencies as “strong”, despite the fact that serological tests were available in these countries.

While most respondents were unable to provide much data on the volume or cost, the median cost to a patient for one test was estimated at US $12 (range $5–130). India reported the highest volume of testing, an estimated 1.5 million TB serological tests were performed, at an expenditure conservatively estimated at US $15 million per year. But serological testing was widespread in other countries as well, especially China, Indonesia, Pakistan, Vietnam and Uganda. Further work is necessary to collect more reliable estimates of test volumes and costs.

While the abuse of serological tests in India has received press coverage [4, 5, 12–15], the problem extends beyond India to most other high-burden countries. Regulation of TB diagnostics is weak in these countries, allowing for poorly performing tests to enter the market. Once on the market, financial gains by stakeholders (doctors, laboratories and diagnostic companies) keep such products profitable [4, 5, 14]. Our survey also confirms the previous observation [5, 14, 15] that companies in western countries (e.g. France, UK, USA, Germany and Australia) are exporting inaccurate and unreliable TB diagnostics to poor countries, while not approving the same tests for domestic use.

Misdiagnosis of TB is harmful both to individual patients and to public health; every missed TB diagnosis may result in additional TB transmission. Furthermore, when inaccurate and inappropriate tests are widely used, scale-up of validated diagnostics may be more difficult. While the recent WHO policy against serological TB testing provides important guidance at the global level, it will have no impact unless high-burden countries implement this policy, tighten regulations, and educate doctors, laboratories and consumers to prevent continued abuse of such diagnostics. Countries must also find ways to incentivise the private sector to substitute serological tests with validated WHO-endorsed products, such that the economic incentives of the private sector are more closely aligned with the health incentives of individual TB patients. Lastly, intensive biomarker research is urgently needed to develop accurate and reliable point-of-care serological tests that can replace the existing ineffective assays.

• ©ERS 2012