Enhancing the diagnostic scope of the PathoDetect^TM MTB RIF & INH assay: A call for inclusive evaluation

Sir,

We acknowledge the valuable work done by Choudhary et al¹ in their article on validation of the PathoDetect^™ MTB RIF and INH Assay for detecting Mycobacterium tuberculosis (MTB) and drug resistance to rifampicin (RIF) and isoniazid (INH) published in the May 2025 issue of the Indian Journal of Medical Research. The authors have evaluated an indigenous molecular diagnostic test on the XL/Q platform that can detect MTB as well as resistance to two key first-line drugs – RIF and INH – simultaneously.

Traditional methods for diagnosing tuberculosis (TB), like smear microscopy and culture, have certain drawbacks. These include being time-consuming, having a high chance of contamination, or lacking sensitivity. WHO-approved molecular tests such as Truenat^® and Xpert^® are faster but have limited capacity for processing multiple samples daily. In comparison, PathoDetect^TM can process up to 32 samples at once, gives quicker results, and can detect INH resistance – a feature not commonly found in many other tests.

However, we would like to highlight a few limitations of this study.

1. Exclusion of extra-pulmonary TB (EPTB): The study focuses only on pulmonary TB, excluding EPTB, which accounts for a large number of TB cases, especially in high-burden areas. In contrast EPTB samples are more complex and usually have a lower bacterial load. A study by Ruiz et al² from Spain which used the Abbott RealTime MTB RIF/INH assay showed high accuracy (98-100%) for both pulmonary and extra-pulmonary TB, suggesting the need to include EPTB in future studies².

2. No analysis of human immunodeficiency virus (HIV) co-infection: Although immunosuppressed individuals were excluded, the study did not examine the test’s performance in HIV-positive patients. Since TB often behaves differently in people with HIV and may show low bacterial counts, this can affect test accuracy. Also, TB infection can worsen HIV progression, making it important to evaluate diagnostic tools in such cases³.

3. Use of only one sputum sample: The study used just one sputum sample per patient. Previous research, such as that by Islam et al⁴, has shown that second or early morning sputum samples can improve detection rates. Using more than one sample could increase the reliability of results⁴.

4. Cross-sectional study design: The study design gives results at only one point in time. Long-term studies could provide more useful information about how well the test works during treatment or disease progression⁵.

In conclusion, while the PathoDetect^TM assay is promising and shows great potential for routine diagnosis of pulmonary TB and drug resistance, further improvements are necessary. Expanding its evaluation to include EPTB, HIV-positive individuals, repeated sputum sampling, and longitudinal monitoring would significantly enhance its diagnostic accuracy and clinical relevance. Such enhancements would make it a more comprehensive and widely applicable tool in global TB control efforts.