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September, 11 2024
Expert Perspective
Tuberculosis (TB) remains a significant global health challenge. In 2022, about 1.3 million people died from TB, while an estimated 10.6 million people contracted the disease.1 TB disproportionately impacts people in low- and middle-income countries,2 where healthcare resources are limited. However, new tests offer hope for better disease control.
TB is a major health concern in the Middle East and North Africa (MENA),1 where research shows a high prevalence (42%) of latent TB infections.3 If not treated, latent tuberculosis infections can progress to active TB, contributing to the spread of the disease.
Migration and crowded living conditions often worsen the spread of TB in the MENA region. For instance, mass gatherings like the Hajj pilgrimage offer opportunities for TB transmission. A 2023 study found 0.7% of non-hospitalized and 2.9% of hospitalized pilgrims tested positive for TB, with significant cases from South Asia and Africa.4 The study highlights the need for better TB screening and awareness to avoid missed cases.
The COVID-19 pandemic disrupted prior gains in TB management, resulting in increased TB incidence rates between 2020 and 2021, versus declines of about 2% per year for most of the past two decades. COVID-19-related disruptions resulted in a staggering half million excess deaths from TB.1 Although there was a major global recovery in new TB diagnoses in 2022, TB remained a leading cause of death from an infectious disease, second only to COVID-19 in 2022. Additionally, global TB targets set for 2018-2022 at the first UN high-level meeting on TB were largely missed, and END TB Strategy targets were not met.1 These statistics indicate a dire situation in need of action.
Missed cases during the Hajj pilgrimage provide one example of the diagnostic gap in TB. In 2022, the World Health Organization (WHO) estimated that 3.1 million people fell ill with TB but weren’t diagnosed or reported.1 Without a diagnosis, patients not only go without treatment but are also more likely to spread the illness to others.
Recent years have seen significant advancements in TB testing, which are vital for effective disease management. The WHO updated its guidelines in 2024, recommending diagnostic tools for TB relevant to various testing scenarios, including moderate and low-complexity automated nucleic acid amplification tests (NAATs) for the detection of TB and drug resistance, antigen detection tests, and line probe assays.5 One of the critical updates is the inclusion of targeted next-generation sequencing tests for drug-resistant TB (DR-TB). These tests can identify resistance to a broad list of drugs, informing treatment recommendations.
The Xpert® MTB/RIF and Xpert MTB/RIF Ultra tests are recommended as initial diagnostic tests for TB and rifampin resistance detection.5 These molecular tests detect TB bacterial DNA and rifampicin resistance genes directly from sputum samples. Rifampicin is a critical first-line drug for TB treatment, and resistance to it can indicate multidrug-resistant TB (MDR-TB), which is more complex to treat.
The WHO recommendation of such tests for detection in sputum rather than smear microscopy/culture and phenotypic drug susceptibility testing provides guidance towards simple, accurate, and accessible options to meet testing needs, even in resource-limited environments.
Xpert MTB/XDR is the only test in the new WHO-designated class “Low complexity automated NAATs for the detection of resistance to isoniazid and second-line anti-TB agents.”5 This new class of diagnostics is intended for use as a reflex test in Tb-positive specimens, offering rapid drug susceptibility information. WHO notes that “Results are available in under 90 minutes, leading to faster time to results than the current standard of care, which includes LPAs and culture-based phenotypic DST.”5
While the Xpert tests were the first ever WHO-endorsed tests for TB and rifampin resistance detection,6 several other molecular tests from various manufacturers are now included as WHO-recommended tools in the fight against TB.5 Given the magnitude of the TB crisis, continued innovation, development, and mechanisms to broaden access are crucial.
Molecular diagnostics have revolutionized TB management. Traditional methods, such as smear microscopy and culture, can be time-consuming and less accurate than molecular tests. The impact of front-line tests such as Xpert MTB/RIF Ultra has been widely reported, providing fast, accurate, and accessible results in developed as well as resource-limited settings.7-10 Yet, less than half of the 7.5 million people newly diagnosed with TB in 2022 received a WHO-recommended rapid diagnostic test.1
Modern molecular tests are being designed for use in laboratory environments and decentralized settings where care is provided. Such flexibility increases adoption within communities, allowing more patients to be reached. Recent advancements in drug resistance detection by molecular tests allow healthcare facilities to follow recommended treatment algorithms, which specify testing to determine and initiate appropriate therapy. These transitions will help close the diagnostic gap, allowing TB to be diagnosed earlier, more accurately, and more broadly than with traditional methods.
Dr. Tedros Adhanom Ghebreyesus, Director-General of the WHO has observed that “If the pandemic has taught us anything, it’s that with solidarity, determination, innovation and the equitable use of tools, we can overcome severe health threats. Let’s apply those lessons to tuberculosis. It is time to put a stop to this long-time killer. Working together, we can end TB.” These words ring true as a vital call to action. With continued improvements in diagnostic testing, greater access to recommended molecular tools, and sustained commitment to close the diagnostic gap, the goal of TB elimination remains in sight.
1. Global Tuberculosis Report 2023 [Internet]. [cited 2024 Jul 2]. Available from: https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2023
2. Tuberculosis - Our World in Data [Internet]. [cited 2024 Jul 2]. Available from: https://ourworldindata.org/tuberculosis
3. Barry M. Prevalence of latent tuberculosis infection in the middle east and north africa: A systematic review. Pulm Med. 2021 Jan 28;2021:6680651.
4. Yezli S, Yassin Y, Mushi A, Maashi F, Abdelmalek NM, Awam AH, et al. Undiagnosed and missed active pulmonary tuberculosis during mass gatherings: a prospective cross-sectional study from the Hajj pilgrimage. Eur J Clin Microbiol Infect Dis. 2023 Jun;42(6):727–40.
5. WHO consolidated guidelines on tuberculosis: Module 3: Diagnosis – Rapid diagnostics for tuberculosis detection. Geneva: World Health Organization; 2024.
6. Automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: Xpert MTB/RIF system: policy statement [Internet]. [cited 2024 Jul 2]. Available from: https://www.who.int/publications/i/item/9789241501545
7. Opota O, Zakham F, Mazza-Stalder J, Nicod L, Greub G, Jaton K. Added Value of Xpert MTB/RIF Ultra for Diagnosis of Pulmonary Tuberculosis in a Low-Prevalence Setting. J Clin Microbiol. 2019 Feb;57(2).
8. Saavedra B, Mambuque E, Nguenha D, Gomes N, Munguambe S, García JI, et al. Performance of Xpert MTB/RIF Ultra for tuberculosis diagnosis in the context of passive and active case finding. Eur Respir J. 2021 Dec 23;58(6).
9. Zifodya JS, Kreniske JS, Schiller I, Kohli M, Dendukuri N, Schumacher SG, et al. Xpert Ultra versus Xpert MTB/RIF for pulmonary tuberculosis and rifampicin resistance in adults with presumptive pulmonary tuberculosis. Cochrane Database Syst Rev. 2021 Feb 22;2:CD009593.
10. Choi HW, Miele K, Dowdy D, Shah M. Cost-effectiveness of Xpert® MTB/RIF for diagnosing pulmonary tuberculosis in the United States. Int J Tuberc Lung Dis. 2013 Oct;17(10):1328–35.
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