Value of urine-based lipoarabinomannan (LAM) antigen tests for diagnosing tuberculosis in children: systematic review and meta-analysis

Seid, Getachew; Alemu, Ayinalem; Tsedalu, Tsegaye; Dagne, Biniyam

doi:10.1016/j.ijregi.2022.06.004

Cited by 18 publications

(14 citation statements)

References 31 publications

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“…Patients were recruited from different levels of healthcare facilities, with tertiary referral centers more likely to have children with advanced disease and higher mycobacterial burdens [ 36 ]. The trend for a higher NPA yield in CLHIV compared to HIV-negative children suggested in our review has been noted in other diagnostic specimens [ 37 – 39 ] and could be related to the greater risk of TB and more advanced disease. In contrast, the trend for a greater NPA yield in younger children is surprising since they often have paucibacillary disease, although other factors may contribute to these findings.…”

Section: Discussionsupporting

confidence: 72%

The diagnostic yield of nasopharyngeal aspirate for pediatric pulmonary tuberculosis: a systematic review and meta-analysis

Khambati,

Song,

MacLean

et al. 2023

BMC Global Public Health

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Background Tuberculosis (TB) is a leading cause of death in children, but many cases are never diagnosed. Microbiological diagnosis of pulmonary TB is challenging in young children who cannot spontaneously expectorate sputum. Nasopharyngeal aspirates (NPA) may be more easily collected than gastric aspirate and induced sputum and can be obtained on demand, unlike stool. However, further information on its diagnostic yield is needed. Methods We systematically reviewed and meta-analyzed the diagnostic yield of one NPA for testing by either culture or nucleic acid amplification testing (NAAT) to detect Mycobacterium tuberculosis from children. We searched three bibliographic databases and two trial registers up to 24th November 2022. Studies that reported the proportion of children diagnosed by NPA compared to a microbiological reference standard (MRS) were eligible. Culture and/or WHO-endorsed NAAT on at least one respiratory specimen served as the MRS. We also estimated the incremental yield of two NPA samples compared to one and summarized operational aspects of NPA collection and processing. Univariate random-effect meta-analyses were performed to calculate pooled diagnostic yield estimates. Results From 1483 citations, 54 were selected for full-text review, and nine were included. Based on six studies including 256 children with microbiologically confirmed TB, the diagnostic yield of NAAT on one NPA ranged from 31 to 60% (summary estimate 44%, 95% CI 36–51%). From seven studies including 242 children with confirmed TB, the diagnostic yield of culture was 17–88% (summary estimate 58%, 95% CI 42–73%). Testing a second NPA increased the yield by 8–19% for NAAT and 4–35% for culture. NPA collection procedures varied between studies, although most children had NPA successfully obtained (96–100%), with a low rate of indeterminate results (< 5%). Data on NPA acceptability and specifically for children under 5 years were limited. Conclusions NPA is a suitable and feasible specimen for diagnosing pediatric TB. The high rates of successful collection across different levels of healthcare improve access to microbiological testing, supporting its inclusion in diagnostic algorithms for TB, especially if sampling is repeated. Future research into the acceptability of NPA and how to standardize collection to optimize diagnostic yield is needed.

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Section: Discussionsupporting

confidence: 72%

The diagnostic yield of nasopharyngeal aspirate for pediatric pulmonary tuberculosis: a systematic review and meta-analysis

Khambati,

Song,

MacLean

et al. 2023

BMC Global Public Health

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“…However, its sensitivity is limited to a moderate range (40-60%) and is primarily applicable to HIV-infected patients with low CD4 + T-cell counts. [15] Consequently, there is an urgent need to enhance the sensitivity of LAM testing specifically in HIV-negative TB patients. [16,17] Research has demonstrated that leveraging the latest generation of anti-LAM monoclonal antibodies and high-throughput laboratory immunoassay platforms can significantly improve the sensitivity and specificity of urine LAM testing.…”

Section: The Authors Have No Conflicts Of Interest To Disclosementioning

confidence: 99%

Breakthrough of chemiluminescence-based LAM urine test beyond HIV-positive individuals: Clinical diagnostic value of pulmonary tuberculosis in the general population

Zhang,

Chen,

Wei

et al. 2023

Medicine

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To investigate the diagnostic value of a novel high-sensitivity urine lipoarabinomannan (LAM) test (chemiluminescence-based) for active tuberculosis in the general population. A retrospective study was conducted on 250 clinical suspected tuberculosis patients who were HIV-negative and visited the Fourth People’s Hospital of Foshan from January 2022 to December 2022. Among them, there were 135 cases of pulmonary tuberculosis, 34 cases of extrapulmonary tuberculosis, and 81 cases of non-tuberculosis. Urine samples were collected for LAM antigen detection before treatment, and laboratory data of sputum smear acid-fast staining (smear method), sputum culture, and GeneXpert method were collected. Using clinical diagnosis as the reference standard, the diagnostic efficacy of 4 methods for detecting active tuberculosis was evaluated. For the 135 cases of pulmonary tuberculosis, the sensitivity of sputum smears, sputm culture, sputm GeneXpert method, and urine LAM were 29.6% (40/135), 45.9% (62/135), 59.3% (80/135), and 51.9% (70/135), respectively. The combination of LAM + GeneXpert and LAM + culture had the highest sensitivity for detecting active pulmonary tuberculosis, which were 71.0% and 78.2%, respectively. For the detection of sputum culture-negative pulmonary tuberculosis, the positive rates of smear, GeneXpert, and LAM were 0.0% (0/73), 53.4% (39/73), and 52.1% (38/73), respectively. LAM + smear and LAM + Genexpert could detect 52.1% and 68.5% of sputum culture-negative patients, respectively. The high-sensitivity urine LAM test holds promise for tuberculosis diagnosis in the general population. It demonstrates high-sensitivity, enabling the detection of sputum culture-negative pulmonary tuberculosis patients. Furthermore, when combined with existing methods, it can enhance the overall detection rate.

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“…In the 11 hematogenous disseminated TB patients in this study, the CLIA-LAM assay demonstrated high sensitivity (81.8%), providing promising results for future research. It is yet to be determined whether this CLIA-LAM assay can also be used to diagnose extrapulmonary TB (EPTB), pediatric patients [ 27 , 28 ], and ICU patients, and further investigation is required to address these questions.…”

Section: Discussionmentioning

confidence: 99%

Improving the diagnosis of active tuberculosis: a novel approach using magnetic particle-based chemiluminescence LAM assay

Li,

Ru,

Wei

et al. 2024

BMC Pulm Med

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Objectives Tuberculosis (TB) is a significant global health concern, given its high rates of morbidity and mortality. The diagnosis using urine lipoarabinomannan (LAM) primarily benefits HIV co-infected TB patients with low CD4 counts. The focus of this study was to develop an ultra-sensitive LAM assay intended for diagnosing tuberculosis across a wider spectrum of TB patients. Design & Methods To heighten the sensitivity of the LAM assay, we employed high-affinity rabbit monoclonal antibodies and selected a highly sensitive chemiluminescence LAM assay (CLIA-LAM) for development. The clinical diagnostic criteria for active TB (ATB) were used as a control. A two-step sample collection process was implemented, with the cutoff determined initially through a ROC curve. Subsequently, additional clinical samples were utilized for the validation of the assay. Results In the assay validation phase, a total of 87 confirmed active TB patients, 19 latent TB infection (LTBI) patients, and 104 healthy control samples were included. Applying a cutoff of 1.043 (pg/mL), the CLIA-LAM assay demonstrated a sensitivity of 55.2% [95%CI (44.13%~65.85%)], and a specificity of 100% [95%CI (96.52%~100.00%)], validated against clinical diagnostic results using the Mann-Whitney U test. Among 11 hematogenous disseminated TB patients, the positive rate was 81.8%. Importantly, the CLIA-LAM assay consistently yielded negative results in the 19 LTBI patients. Conclusion Overall, the combination of high-affinity antibodies and the CLIA method significantly improved the sensitivity and specificity of the LAM assay. It can be used for the diagnosis of active TB, particularly hematogenous disseminated TB.

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Value of urine-based lipoarabinomannan (LAM) antigen tests for diagnosing tuberculosis in children: systematic review and meta-analysis

Cited by 18 publications

References 31 publications

The diagnostic yield of nasopharyngeal aspirate for pediatric pulmonary tuberculosis: a systematic review and meta-analysis

The diagnostic yield of nasopharyngeal aspirate for pediatric pulmonary tuberculosis: a systematic review and meta-analysis

Breakthrough of chemiluminescence-based LAM urine test beyond HIV-positive individuals: Clinical diagnostic value of pulmonary tuberculosis in the general population

Improving the diagnosis of active tuberculosis: a novel approach using magnetic particle-based chemiluminescence LAM assay

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