Feasibility of using Determine TB-LAM to diagnose tuberculosis in HIV-positive patients in programmatic conditions: a multisite study

Rücker, Sekai Chenai Mathabire; Cossa, Loide; Harrison, R J; Mpunga, James; Lobo, Sheila Fagundes; Kimupelenge, Patrick Kisaka; Kol'Ampwe, Felix Mandar; Quiles, Isabel Amoros; Molfino, Lucas; Szumilin, Elisabeth; Telnov, Oleksandr; Ndlovu, Zibusiso; Huerga, Helena

doi:10.1080/16549716.2019.1672366

Cited by 22 publications

(23 citation statements)

References 24 publications

(25 reference statements)

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“…Notably, Nicol and colleagues reported a significant increase in specificity from 66% to 97% (together with a pronounced loss of sensitivity) of Determine-LAM when omitting Grade 1 (out of 4 grades) from “positive” results among children (20% HIV-positive, 25% malnourished) [ 21 ]. A multi-site study found high ease-of-use for Determine-LAM operators and very good inter-reader agreement [ 34 ]. However, some operators reported difficulties distinguishing “fainter than Grade 1” intensity bands [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Potential value of urine lateral-flow lipoarabinomannan (LAM) test for diagnosing tuberculosis among severely acute malnourished children

Schramm¹,

Nganaboy²,

Uwiragiye³

et al. 2021

PLoS ONE

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Background Tuberculosis (TB) is a serious co-morbidity among children with severe acute malnutrition (SAM) and TB diagnosis remains particularly challenging in the very young. We explored whether, in a low HIV-prevalence setting, the detection of mycobacterial lipoarabinomannan (LAM) antigen in urine may assist TB diagnosis in SAM children, a pediatric population currently not included in LAM-testing recommendations. To that end, we assessed LAM test-positivity among SAM children with and without signs or symptoms of TB. Methods A cross-sectional assessment (February 2016-August 2017) included children <5 years with SAM from an Intensive-Therapeutic-Feeding-Centre in Madaoua, Niger. Group 1: children with signs or symptoms suggestive of TB. Group 2: children without any sign or symptom of TB. Urine-specimens were subjected to DetermineTM TB-LAM lateral-flow-test (using a 4-grade intensity scale for positives). LAM-results were used for study purposes and not for patient management. Programmatic TB-diagnosis was primarily based on patients’ clinical symptoms and TB contact history with no systematic access to X-ray or microbiological reference testing. Results 102 (Group 1) and 100 children (Group 2) were included (median age 18 months, 59.4% male, 1.0% HIV-positive). In Group 1, 22 (21.6%) children were started on TB-treatment (probable TB) and none of the children in Group 2. LAM-positivity was 52.0% (53/102) and 37.0% (37/100) in Group 1 and 2, respectively. Low-intensity (Grade 1) LAM test-positivity was similarly high in both Groups (37.3% and 36.0%, respectively), while Grade 2 or 3-positives were mainly detected in Group 1 (Group 1: 14.7%, Group 2: 1.0%, p<0.001). When considering only Grades >1 as positive, LAM-testing detected 22.7% (95%CI: 7.8, 45.4) among probable TB cases, while 99% (95%CI: 94.6, 99.9) of unlikely TB cases (Group 2) tested negative. Conclusion These findings suggest the potential utility of LAM urine testing in HIV-negative children with SAM. Determine LAM-positivity with Grades >1 may identify HIV-negative SAM children that are eligible for rapid TB-treatment initiation, though low-intensity (Grade 1) LAM-positive results may not be helpful in this way. Further studies in this specific pediatric population are warranted, including evaluations of new generation LAM tests.

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Section: Discussionmentioning

confidence: 99%

Potential value of urine lateral-flow lipoarabinomannan (LAM) test for diagnosing tuberculosis among severely acute malnourished children

Schramm¹,

Nganaboy²,

Uwiragiye³

et al. 2021

PLoS ONE

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“…Although LAM positivity was low in patients not eligible for LAM as per the 2019 WHO guidance, considering that some of the patients with TB symptoms may not be identified as having presumptive TB and that CD4 count is currently not routinely done (or results may not be immediately available) in settings similar to this one, systematic LAM testing for all HIV patients in medical wards regardless of their symptoms or CD4 could simplify the use of LAM. This strategy would be practical and easily implementable [ 14 ] and would lead to rapid TB treatment.…”

Section: Discussionmentioning

confidence: 99%

“…We encourage proper LAM test performance, using the manufacturer-provided test scale and LAM grade reporting. In Malawi, hospital teams observed that at the end of the study, test scales were no longer being used and LAM positivity was based on the appearance of any indicator line, regardless of its intensity, a type of misinterpretation that has been observed in other contexts [ 14 ]. Future improved LAM tests such as FujiLAM are expected to be even more beneficial for this population [ 20–22 ], and further studies are needed to assess different LAM testing strategies (eg, systematic vs clinician-directed).…”

Section: Discussionmentioning

confidence: 99%

Urine Lipoarabinomannan Testing for All HIV Patients Hospitalized in Medical Wards Identifies a Large Proportion of Patients With Tuberculosis at Risk of Death

Huerga¹,

Rücker²,

Bastard³

et al. 2020

Open Forum Infectious Diseases

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Background Diagnosing tuberculosis (TB), the leading cause of death in people with HIV, remains a challenge in resource-limited countries. We assessed TB diagnosis using a strategy that included systematic urine lipoarabinomannan (LAM) testing for all HIV patients hospitalized in medical wards and 6-month mortality according to LAM results. Methods This prospective, observational study included adult HIV patients hospitalized in the medical wards of a public district hospital in Malawi regardless of their TB symptoms or CD4 count. Each patient had a clinical examination, and Alere Determine TB-LAM, sputum microscopy, sputum GeneXpert MTB/RIF (Xpert), chest x-ray, and CD4 count were systematically requested. Results Among 387 inpatients, 54% had a CD4 <200 cells/µL, 64% had presumptive TB, and 90% had ≥1 TB symptom recorded in their medical file. LAM results were available for 99.0% of patients, microscopy for 62.8%, and Xpert for 60.7%. In total, 26.1% (100/383) had LAM-positive results, 48% (48/100) of which were grades 2–4. Any TB laboratory test result was positive in 30.8% (119/387). Among patients with no Xpert result, 28.5% (43/151) were LAM-positive. Cumulative 6-month mortality was 40.1% (151/377): 50.5% (49/97) in LAM-positives and 36.2% (100/276) in LAM-negatives (P = .013). In multivariable regression analyses, LAM-positive patients had a higher risk of mortality than LAM-negatives (adjusted odds ratio, 2.5; 95% CI, 1.1–5.8; P = .037). Conclusions In resource-limited hospital medical wards with high TB prevalence, a diagnostic strategy including systematic urine LAM testing for all HIV patients is an easily implementable strategy that identifies a large proportion of patients with TB at risk of death.

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“…1 , there is now an additional module for patients who report any TB symptom(s) during the symptom report. Symptomatic patients are tested using a lipoarabinomannan antigen of mycobacteria (LAM) test, which is a point-of-care urine test that requires approximately 25 min to administer [ 16 ]. LAM has been evaluated in multiple settings [ 16 – 20 ] and is recommended for patients with low CD4 counts [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

“…Symptomatic patients are tested using a lipoarabinomannan antigen of mycobacteria (LAM) test, which is a point-of-care urine test that requires approximately 25 min to administer [ 16 ]. LAM has been evaluated in multiple settings [ 16 – 20 ] and is recommended for patients with low CD4 counts [ 21 ]. Research in Kenya found that clinical signs plus LAM identified 84% of TB cases in a population of HIV-infected outpatients with CD4 counts below 200 cells/μl [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

Improved simplified clinical algorithm for identifying patients eligible for immediate initiation of antiretroviral therapy for HIV (SLATE II): protocol for a randomized evaluation

Rosen

Maskew

Brennan

et al. 2018

Trials

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BackgroundThe World Health Organization recommends rapid (≤ 7 days) or same-day initiation of antiretroviral treatment (ART) for HIV-positive patients. South Africa adopted this recommendation in 2017, but multiple clinic visits, long waiting times, and delays for laboratory tests remain common. Streamlined approaches to same-day initiation that allow the majority of patients to start ART immediately, while ensuring that patients who do require additional services receive them, are needed to achieve national and international treatment program goals.Methods/DesignThe SLATE II (Simplified Algorithm for Treatment Eligibility) study is an individually randomized evaluation of a clinical algorithm to reliably determine a patient’s eligibility for immediate ART initiation without waiting for laboratory results or additional clinic visits. It differs from the earlier SLATE I study in management of patients with symptoms of tuberculosis (under SLATE II these patients may be started on ART immediately) and other criteria for immediate initiation. SLATE II will randomize (1:1) 600 adult, HIV-positive patients who present for HIV testing or care and are not yet on ART in South Africa. Patients randomized to the standard arm will receive standard-of-care ART initiation from clinic staff. Patients randomized to the intervention arm will be administered a symptom report, medical history, brief physical exam, and readiness assessment. Symptomatic patients will also have a tuberculosis (TB) module with lipoarabinomannan antigen of mycobacteria test. Patients who have satisfactory results for all four components will be dispensed antiretrovirals (ARVs) immediately, at the same clinic visit. Patients who have any negative results will be referred for further investigation, care, counseling, tests, or other services prior to being dispensed ARVs. Follow-up will be by passive medical record review. The primary outcomes will be ART initiation in ≤ 7 days and retention in care 8 months after study enrollment.DiscussionSLATE II improves upon the SLATE I study by reducing the number of reasons for delaying ART initiation and allowing more patients with TB symptoms to start ART on the day of diagnosis. If successful, SLATE II will provide a simple and streamlined approach that can readily be adopted in other settings without investment in additional technology.Trial registrationClinicalTrials.gov, NCT03315013. Registered on 19 October 2017.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2928-5) contains supplementary material, which is available to authorized users.

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Feasibility of using Determine TB-LAM to diagnose tuberculosis in HIV-positive patients in programmatic conditions: a multisite study

Cited by 22 publications

References 24 publications

Potential value of urine lateral-flow lipoarabinomannan (LAM) test for diagnosing tuberculosis among severely acute malnourished children

Potential value of urine lateral-flow lipoarabinomannan (LAM) test for diagnosing tuberculosis among severely acute malnourished children

Urine Lipoarabinomannan Testing for All HIV Patients Hospitalized in Medical Wards Identifies a Large Proportion of Patients With Tuberculosis at Risk of Death

Improved simplified clinical algorithm for identifying patients eligible for immediate initiation of antiretroviral therapy for HIV (SLATE II): protocol for a randomized evaluation

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