Tuberculosis diagnostics: overcoming ancient challenges with modern solutions

Abstract

Rapid, sensitive, accurate and portable diagnostics are a mainstay of modern medicine. Tuberculosis is a disease that has been with us since time immemorial and, despite the fact that it can be treated and cured, it still remains the world's biggest infectious killer, taking the lives of millions annually. There have been important developments in the diagnostic devices for tuberculosis however, these are often prone to error, expensive, lack the necessary sensitivity or accuracy and, crucially, not sufficiently portable and thus not applicable in the remote, rural areas, where they are most needed. Modern solutions have been emerging in the past decade, seeking to overcome many of the inhibiting issues in this field by utilising recent advances in molecular biology, genetics and sequencing or even completely ‘reinventing the wheel’, by developing novel and unprecedented diagnostic techniques. In this mini review, the issues and challenges arising from the historical methods of diagnosing tuberculosis are discussed, followed by outlaying their particular lack of appropriateness for regions of the world where tuberculosis still remains endemic. Subsequently, more recent developments of new methods and technological advancements as ‘modern weapons’ in the battle to defeat this disease and associated challenges are reviewed, and finally an outlook is presented, highlighting the future of the modern solutions under development, which are envisioned to lay the platform for improvements in delivering timely intervention, reduce immense expense and burden on healthcare systems worldwide, while saving millions of lives and eventually, may enable the eradication of this ancient disease.

Improved Conventional and New Approaches in the Diagnosis of Tuberculosis

“…This is probably due to the detection limit of 10 3 copies to diagnose M. tuberculosis ( Jaroenram et al, 2020 ). In addition, problems occur to identify latent infections, as well as pediatric and immunocompromised HIV patients( MacGregor-Fairlie et al, 2020 ). Therefore, further efforts are needed to develop immunosensors that are effective in diagnosing TB.…”

Machine learning analysis of SERS fingerprinting for the rapid determination of Mycobacterium tuberculosis infection and drug resistance

“…After Mtb infection, infected individuals could be generally classified into two categories: latent tuberculosis infection (LTBI), also known as the asymptomatic clinical state with no transmission risk (≈ 90%), and active TB disease with clinical symptoms such as cough, fever and night sweats (≈10%), though the binary view has recently changed and Mtb infection is considered as a spectrum of disease states [5] , [11] . In certain circumstances, Mtb could establish an infection outside lungs, leading to the development of extrapulmonary TB (≈15% of infected cases) [12] . As for the treatment of tuberculosis, the core regimen requires a long-term antituberculosis therapy phase (6–9 months) through various combinations of four first-line drugs, that is, rifampicin, isoniazid, pyrazinamide and ethambutol [13] .…”

“…So far, multiple techniques have been developed for the fast and accurate identification of Mtb infections, which involve molecular methods, immunological assays, and direct culture and observations and so forth [12] . Common diagnostic tests include bacterial culture, smear microscopy, serological test and chest X-ray screening [14] .…”

“…Common diagnostic tests include bacterial culture, smear microscopy, serological test and chest X-ray screening [14] . However, these methods suffer either insufficient testing inaccuracy or long turnaround testing time, not even mentioning the inconvenient applications in remote and rural areas [12] . For example, diagnosis relying on the culture of Mycobacteria requires high-level and expensive technological facilities and the process might take up to 2 months, causing significant delay of active tuberculosis diagnosis [15] .…”

Tuberculosis Diagnostics, a journey from the past Experiences to the Future Directions, Review

“…Newer methods have been incorporated which could reduce the above-mentioned limitations as well as introducing cost-effective infrastructure requirements. Currently available diagnostic tests of mycobacterium tuberculosis(Fairlie, 2020)…”