Extrapulmonary tuberculosis (EPTB) remains diagnostically challenging due to its paucibacillary nature and variable presentation. Xpert and culture are limited in EPTB diagnosis due to sampling challenges, low sensitivity, and long turnaround times. This study evaluated the performance of the MPT64 antigen detection test for diagnosing EPTB, particularly tuberculous lymphadenitis (TBLN) and tuberculous pleuritis (TBP), in a high-TB, low-HIV setting. Conducted at Gulab-Devi Hospital, Lahore, Pakistan, this study evaluated the MPT64 test’s performance against conventional diagnostic methods, including culture, histopathology, and the Xpert MTB/RIF assay. Lymph node biopsies were collected, and cell blocks were made from aspirated pleural fluid from patients clinically presumed to have EPTB. Of 338 patients, 318 (94%) were diagnosed with EPTB. For TBLN, MPT64 demonstrated higher sensitivity (84%) than Xpert (48%); for TBP, the sensitivity was 51% versus 7%, respectively. Among histopathology-confirmed TBLN cases, MPT64 outperformed both culture and Xpert (85% vs. 58% and 47%). Due to the low number of non-TB cases, specificity could not be reliably assessed. The MPT64 test shows promise as a rapid, sensitive diagnostic tool for EPTB, particularly TBLN, in routine settings. While sensitivity is notably superior to Xpert, further studies are needed to evaluate its specificity and broader diagnostic utility.
The diagnostic challenges of extrapulmonary tuberculosis (EPTB) are multifaceted and stem from a combination of biological, logistical, and infrastructural issues. Accurate diagnosis of EPTB requires specific tests to detect mycobacteria, but medical professionals face challenges due to diverse clinical manifestations, the paucibacillary nature of the disease, and the fact that its diagnosis typically requires invasive procedures to obtain tissue samples, which depend on skilled personnel and functional laboratory system resources that are often limited in low- and middle-income countries (LMICs) [1,2].
EPTB accounts for approximately 20–30% of all active tuberculosis (TB) cases globally, with this proportion rising to 50% among individuals co-infected with human immunodeficiency virus (HIV) infections [3,4,5]. Tuberculous lymphadenitis (TBLN) is the most common expression, comprising 35–50% of cases, while tuberculous pleuritis (TBP) is the second most predominant manifestation, which accounts for 10–16% [3,6,7]. Combined, these two forms represent about half (50%) of all EPTB presentations. Globally, 8–10 million people are infected with TB annually, with EPTB accounting for up to 17% of all TB cases reported in 2023 [8]. The majority (80%) of incident TB cases and mortalities occur in low- and middle-income countries. Pakistan is among the high-TB-burden countries; 428,600 TB cases were notified in 2023, with 18% (77,148) being EPTB [8,9].
Despite significant advances in the field of TB diagnosis over the last decade, including advancements in microscopy, culture, and molecular techniques, the diagnosis of EPTB remains a major challenge [10,11]. The clinical and histological diagnostic criteria utilized have low sensitivity and specificity, which might lead to missed or overdiagnosis [12]. The Xpert MTB/RIF assay (Xpert), a significant milestone in TB diagnostics, shows reduced efficacy for EPTB due to variability in specimen types, limited tissue availability, and the need for complex sample processing [13,14]. Isolation of Mycobacterium tuberculosis (MTB) from clinical samples by culture remains the “gold standard” due to its high specificity, ability to detect viable bacilli (10–100 bacilli/mL) from biological samples, and ability to identify species. However, low sensitivity and long turnaround times limit the use of culture in resource-limited settings [1,15]. Due to the absence of a low-cost, robust, rapid, and accurate diagnostic method, diagnosis of EPTB is often delayed or misdiagnosed, resulting in increased disease severity and mortality. Therefore, there is an urgent need for a better diagnostic test that is feasible and sustainable in resource-limited settings.MPT64 is one of the major culture filtrate proteins (24 kDa) encoded by the RD2 region genes, secreted by MTB complex species, and is a specific antigen that differentiates it from the Mycobacterium other than tuberculosis species. The diagnostic potential of an immunochemistry-based MPT64 antigen detection test (MPT64 test) has demonstrated greater sensitivity compared with conventional methods and the Xpert. Its sensitivity and specificity are also comparable with the nested polymerase chain reaction (nested-PCR) [15,16,17,18]. Results from earlier research indicate that MPT64 has a unique capacity for intracellular accumulation that enables the detection of smaller numbers of mycobacteria in the lesion, which is not achievable using other conventional methods for the diagnosis of TB [15,19].
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