Improved Alere Determine Lipoarabinomannan Antigen Detection Test for the Diagnosis of Human and Bovine Tuberculosis by Manipulating Urine and Milk

García, Juan Ignacio García; Kelley, Holden V.; Meléndez, Johanna; León, Rosa Alejandra Alvarez de; Castillo, Antonio del; Sidiki, Sabeen; Yusoof, Kizil A.; Nunes, Elizabete; Téllez, Cesar López; Mejía-Villatoro, Carlos; Ikeda, Janet; García‐Basteiro, Alberto L.; Wang, Shuhua; Torrelles, Jordi B.

doi:10.1038/s41598-019-54537-9

Cited by 19 publications

(19 citation statements)

References 23 publications

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“…Contrary to our study in the laboratory setting, where α-mannosidase treatment of LAM spiked human urine significantly increased the efficiency of the LAM-test [14], we did not find any sensitivity and specificity differences comparing the LAM-test results in α-mannosidase treated vs. untreated urine using our composite gold referenced standard. This could be explained by several factors, including the viability and storage conditions of the α-mannosidase enzyme being used in the IAUs, as well as the use of a twofold diluted urine in sodium bicarbonate when performing the LAM-test in the α-mannosidase treated urine.…”

Section: D-contrasting

confidence: 99%

“…Our published laboratory data indicate that α-mannosidase treatment of LAM-spiked human urine using purified LAM from different M. tuberculosis strains, can increase tenfold the detection of LAM molecules in urine by the LAM-test [14]. Our field validation analysis of the LAM-test performed in α-mannosidase treated vs. untreated urine was run in two different clinical settings.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, this is the first reported diagnostic accuracy analysis of the urine LAM-test performed in Central America in PLWH. It is also the first time that an innovative procedure using α-mannosidase pre-treatment of urine was implemented in clinical settings to evaluate its diagnosis accuracy [ 14 ]. Importantly, a positive LAM-test result confirmed mortality prediction in our PLWH cohort with TB clinical symptoms as previously reported [ 23 – 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…Herein, we focused on the LAM-test to address its efficacy in detecting M. tuberculosis in a cohort of PLWH with TB symptoms in Guatemala. We also determined if a 30 min α-mannosidase pre-treatment of urine using an enzyme that removes the mannose caps of LAM could improve the sensitivity of the LAM-test as we have shown in the laboratory settings [14], and further correlated LAM-test results with TB incidence, mortality rates, and risk factors in our cohort of PLWH.…”

Section: Introductionmentioning

confidence: 99%

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Accuracy of the tuberculosis point-of-care Alere determine lipoarabinomannan antigen diagnostic test using α-mannosidase treated and untreated urine in a cohort of people living with HIV in Guatemala

et al. 2020

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Background Improved point-of-care diagnostic tests for tuberculosis (TB) in severe immune suppressed people living with HIV (PLWH) are needed to decrease morbidity and mortality outcomes. The aim of the study is to evaluate the performance of the lipoarabinomannan antigen test (LAM-test) with and without α-mannosidase pre-treated urine in a cohort of PLWH in primary care clinics in Guatemala. We further determined TB incidence, and mortality rates and its risk factors in PLWH with TB symptoms. Methods Prospective longitudinal study of PLWH with TB symptoms. Urine samples were collected at 2 HIV sites to test the sensitivity of the LAM-test in urine with and without α-mannosidase pre-treatment. A composite reference standard of either a positive Mycobacterium tuberculosis complex culture and/or GeneXpert® MTB/RIF (Xpert, Cepheid, Sunnyvale, CA, USA) results was used in the LAM-test diagnostic accuracy studies. Cox proportional hazards regression was used to study mortality predictors. Results The overall sensitivity of the LAM-test was of 56.1% with 95% CI of (43.3–68.3). There were no differences in the LAM-test sensitivity neither by hospital nor by CD4 T cell values. LAM-test sensitivity in PLWH with < 200 CD4 T cells/µl was of 62.2% (95% CI 46.5–76.2). There were no significant differences in sensitivity when comparing LAM-test results obtained from untreated vs. α-mannosidase treated urine [55.2% (95% CI 42.6–67.4) vs. 56.9% (95% CI 44–69.2), respectively]. TB incidence in our cohort was of 21.4/100 person years (PYs) (95% CI 16.6–27.6), and mortality rate was of 11.1/100 PYs (95% CI 8.2–15.0). Importantly, PLWH with a positive LAM-test result had an adjusted hazard ratio (aHR) of death of 1.98 (1.0–3.8) with a significant p value of 0.044 when compared to PLWH with a negative LAM-test result. Conclusions In this study, α-mannosidase treatment of urine did not significantly increase the LAM-test performance, however; this needs to be further evaluated in a large-scale study due to our study limitations. Importantly, high rates of TB incidence and mortality were found, and a positive LAM-test result predicted mortality in PLWH with TB clinical symptoms.

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Section: D-contrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Accuracy of the tuberculosis point-of-care Alere determine lipoarabinomannan antigen diagnostic test using α-mannosidase treated and untreated urine in a cohort of people living with HIV in Guatemala

et al. 2020

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“…Under our experimental conditions and following manufacturer's guidelines, the LAM-test is not considered valid for accurate diagnosis of BTB in cattle using milk or urine samples. The use of the LAM-test for BTB diagnosis in urine and milk samples will need further evaluation, as a recent report indicate that enzymatic treatments of LAM-spiked urine and milk could increase the efficiency of the LAM-test in detecting LAM in these samples 28 . This is an active research in our laboratories.…”

Section: Type Of Testmentioning

confidence: 99%

Accuracy of Two Point-of-Care Tests for Rapid Diagnosis of Bovine Tuberculosis at Animal Level using Non-Invasive Specimens

Kelley

Waibel²,

Sidiki

et al. 2020

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Bovine tuberculosis (BTB) testing in cattle requires a significant investment of time, equipment, and labor. Novel, rapid, cheaper and accurate methods are needed. The Alere Determine TB lipoarabinomannan antigen (LAM-test) is a World Health Organization-endorsed point-of-care urine test designed to detect active TB disease in humans. The Lionex Animal TB Rapid Test (Lionex-test) is a novel animal specific TB diagnostic blood test. An animal level analysis was performed using urine (n = 141) and milk (n = 63) samples from depopulated BTB-suspected cattle to test the accuracy of the LAM-test when compared to results of positive TB detection by any routine BTB tests (BOVIGAM, necropsy, histology, culture, PCR) that are regularly performed by the United States Department of Agriculture (USDA). The agreement between the urine LAM-test and USDA standard tests were poor at varying testing time points. The same milk samples did not elicit statistically significant agreement with the Lionex-test, although positive trends were present. Hence, we cannot recommend the LAM-test as a valid BTB diagnostic test in cattle using either urine or milk. The Lionex-test's production of positive trends using milk samples suggests larger sample sizes may validate the Lionex-test in accurately diagnosing BTB in cattle using milk samples, potentially providing a quick and reliable field test for BTB.Bovine tuberculosis (BTB) is a zoonotic disease caused by the bacterium Mycobacterium bovis 1,2 . The Cooperative State-Federal TB Eradication Program, including the United States Department of Agriculture (USDA), state animal health agencies, and US livestock producers, have nearly eliminated M. bovis infection from cattle in the US 3,4 . Although inspectors test more than one million animals a year for BTB and have taken steps to eradicate this disease, M. bovis is still present 5 . Globally, M. bovis is typically spread from cattle to cattle but in the US, wildlife (e.g. white tail deer, elk, bison, badgers, etc.) more frequently infect cattle, particularly in Michigan, which is the focus of this study 5,6 . Thus, domestic cattle and wildlife pose a potential threat to human health 5,6 . Indeed, BTB is typically transmitted from cattle to humans primarily through consumption of unpasteurized dairy products or occasionally contaminated meats 2,7,8 . Current diagnostic testing and eradication protocols along with pasteurization have caused the prevalence of BTB to drop significantly in the US as well as in other developed countries 9,10 .In 2016, the World Health Organization (WHO) estimated 147,000 cases of zoonotic TB with 12,500 deaths 11 . Globally, however, the median proportion of M. bovis cases of the total TB cases reported in humans ranges from 15.4 to 26.1% in African countries like Ethiopia, Nigeria, and Tanzania 1 .Diagnosis of BTB is difficult since animals with disease often do not show signs until the infection has reached an advanced stage 8,9 . In some countries, delay in BTB diagnosis may increase transmission rates from an...

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New Developments and Insights in the Improvement of Mycobacterium tuberculosis Vaccines and Diagnostics Within the End TB Strategy

et al. 2021

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Purpose of review The alignment of sustainable development goals (SDGs) with the End Tuberculosis (TB) strategy provides an integrated roadmap to implement key approaches towards TB elimination. This review summarizes current social challenges for TB control, and yet, recent developments in TB diagnosis and vaccines in the context of the End TB strategy and SDGs to transform global health. Recent findings Advances in non-sputum based TB biomarkers and whole genome sequencing technologies could revolutionize TB diagnostics. Moreover, synergistic novel technologies such as mRNA vaccination, nanovaccines and promising TB vaccine models are key promising developments for TB prevention and control. Summary The End TB strategy depends on novel developments in point-of-care TB diagnostics and effective vaccines. However, despite outstanding technological developments in these fields, TB elimination will be unlikely achieved if TB social determinants are not fully addressed. Indeed, the End TB strategy and SDGs emphasize the importance of implementing sustainable universal health coverage and social protection.

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Improved Alere Determine Lipoarabinomannan Antigen Detection Test for the Diagnosis of Human and Bovine Tuberculosis by Manipulating Urine and Milk

Cited by 19 publications

References 23 publications

Accuracy of the tuberculosis point-of-care Alere determine lipoarabinomannan antigen diagnostic test using α-mannosidase treated and untreated urine in a cohort of people living with HIV in Guatemala

Accuracy of the tuberculosis point-of-care Alere determine lipoarabinomannan antigen diagnostic test using α-mannosidase treated and untreated urine in a cohort of people living with HIV in Guatemala

Accuracy of Two Point-of-Care Tests for Rapid Diagnosis of Bovine Tuberculosis at Animal Level using Non-Invasive Specimens

New Developments and Insights in the Improvement of Mycobacterium tuberculosis Vaccines and Diagnostics Within the End TB Strategy

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