Comparing accuracy of lipoarabinomannan urine tests for diagnosis of pulmonary tuberculosis in children from four African countries: a cross-sectional study

Nkereuwem, Esin; Togun, Toyin; Gomez, Marie P; Székely, Rita; Macé, Aurélien; Jobe, Dawda; Schumacher, Samuel G; Kampmann, Beate; Denkinger, Claudia M.; Abok, Ishaya I.; Angyu, Joshua Tsoukan; Diakité, Aziz; Diarra, Bassirou; Ebonyi, Augustine O.; Egere, Uzochukwu; Jallow, Musa; Konate, B.; Lakda, Gonen Mato; Mahiga, Hellen; Ntinginya, Nyanda Elias; Olomi, Willyhelmina; Sabi, Issa; Saidy, Binta; Sanogo, Moumine; Sillah, Abdou K; Sylla, M

doi:10.1016/s1473-3099(20)30598-3

Cited by 29 publications

(50 citation statements)

References 19 publications

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“…Children have a high risk of developing disseminated forms of TB, and the hematogenous and lymphatic spread of M. tuberculosis is likely to result in high amounts of LAM in urine [ 2 , 9 ]. However, few studies have reported the performance of FujiLAM in children [ 27 , 28 ]. A multicentre study in four African countries reported a relatively high sensitivity of 67.5% in HIV-negative children [ 28 ], but a cohort study in South Africa reported a lower sensitivity of 38.8% [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, few studies have reported the performance of FujiLAM in children [ 27 , 28 ]. A multicentre study in four African countries reported a relatively high sensitivity of 67.5% in HIV-negative children [ 28 ], but a cohort study in South Africa reported a lower sensitivity of 38.8% [ 27 ]. The authors concluded that the differences in their results may have been due to the severity of the TB episodes, and that some of the studies included a high proportion of malnourished children [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…A multicentre study in four African countries reported a relatively high sensitivity of 67.5% in HIV-negative children [ 28 ], but a cohort study in South Africa reported a lower sensitivity of 38.8% [ 27 ]. The authors concluded that the differences in their results may have been due to the severity of the TB episodes, and that some of the studies included a high proportion of malnourished children [ 28 ]. It has been reported that LAM detection in urine is associated to the overall amount of M. tuberculosis in the body, as well as the severity of the disease [ 10 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

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Diagnostic Performance of the Fujifilm SILVAMP TB-LAM in Children with Presumptive Tuberculosis

Comella-del-Barrio

Molina-Moya

Gautier

et al. 2021

JCM

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Current diagnostics for tuberculosis (TB) only manage to confirm a small proportion of children with TB and require respiratory samples, which are difficult to obtain. There is a need for non-invasive biomarker-based tests as an alternative to sputum testing. Fujifilm SILVAMP TB lipoarabinomannan (FujiLAM), a lateral-flow test to detect lipoarabinomannan in urine, is a novel non-sputum-based point-of-care diagnostic reported to have increased sensitivity for the diagnosis of TB among human immunodeficiency virus (HIV)-infected adults. We evaluate the performance of FujiLAM in children with presumptive TB. Fifty-nine children attending a paediatric hospital in Haiti with compatible signs and symptoms of TB were examined using Xpert MTB/RIF, smear microscopy and X-rays, and classified according to the certainty of diagnosis into bacteriologically confirmed TB (n = 5), unconfirmed TB (bacteriologically negative, n = 50) and unlikely TB (n = 4). Healthy children (n = 20) were enrolled as controls. FujiLAM sensitivity and specificity were 60% and 95% among children with confirmed TB. FujiLAM’s high specificity and its characteristics as a point-of-care indicate the test has a good potential for the diagnosis of TB in children.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Diagnostic Performance of the Fujifilm SILVAMP TB-LAM in Children with Presumptive Tuberculosis

Comella-del-Barrio

Molina-Moya

Gautier

et al. 2021

JCM

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“…While Fuji-LAM and Determine had comparable specificity (87.8% and 83.8%), sensitivity was notably higher with Fuji-LAM (64.9% versus 30.7%) using reference standards Xpert Ultra or MTB culture. Interestingly, in this study, Fuji-LAM sensitivity was higher among HIV-negative than HIV-positive children [ 38 ]. Together with these recent reports, our findings emphasize the potential value of LAM-testing for diagnosing TB in HIV-negative, SAM children.…”

Section: Discussionmentioning

confidence: 93%

“…Importantly, the sensitivity of both FujiLAM and Determine were notably higher among malnourished children (62% vs 31% FujiLAM, 67% vs 46% Determine-LAM) [ 21 ]. A second study compared Determine and Fuji-LAM among children with presumptive TB (15% HIV-positive) in four African countries [ 38 ]. While Fuji-LAM and Determine had comparable specificity (87.8% and 83.8%), sensitivity was notably higher with Fuji-LAM (64.9% versus 30.7%) using reference standards Xpert Ultra or MTB culture.…”

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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Screening tests for active pulmonary tuberculosis in children

Vonasek

Ness

Takwoingi

et al. 2021

Cochrane Database of Systematic Reviews

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Background Globally, children under 15 years represent approximately 12% of new tuberculosis cases, but 16% of the estimated 1.4 million deaths. This higher share of mortality highlights the urgent need to develop strategies to improve case detection in this age group and identify children without tuberculosis disease who should be considered for tuberculosis preventive treatment. One such strategy is systematic screening for tuberculosis in high‐risk groups. Objectives To estimate the sensitivity and specificity of the presence of one or more tuberculosis symptoms, or symptom combinations; chest radiography (CXR); Xpert MTB/RIF; Xpert Ultra; and combinations of these as screening tests for detecting active pulmonary childhood tuberculosis in the following groups. – Tuberculosis contacts, including household contacts, school contacts, and other close contacts of a person with infectious tuberculosis. – Children living with HIV. – Children with pneumonia. – Other risk groups (e.g. children with a history of previous tuberculosis, malnourished children). – Children in the general population in high tuberculosis burden settings. Search methods We searched six databases, including the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, on 14 February 2020 without language restrictions and contacted researchers in the field. Selection criteria Cross‐sectional and cohort studies where at least 75% of children were aged under 15 years. Studies were eligible if conducted for screening rather than diagnosing tuberculosis. Reference standards were microbiological (MRS) and composite reference standard (CRS), which may incorporate symptoms and CXR. Data collection and analysis Two review authors independently extracted data and assessed study quality using QUADAS‐2. We consolidated symptom screens across included studies into groups that used similar combinations of symptoms as follows: one or more of cough, fever, or poor weight gain and one or more of cough, fever, or decreased playfulness. For combination of symptoms, a positive screen was the presence of one or more than one symptom. We used a bivariate model to estimate pooled sensitivity and specificity with 95% confidence intervals (CIs) and performed analyses separately by reference standard. We assessed certainty of evidence using GRADE. Main results Nineteen studies assessed the following screens: one symptom (15 studies, 10,097 participants); combinations of symptoms (12 studies, 29,889 participants); CXR (10 studies, 7146 participants); and Xpert MTB/RIF (2 studies, 787 participants). Several studies assessed more than one screening test. No studies assessed Xpert Ultra. For 16 studies (84%), risk of bias for the reference standard domain was unclear owing to concern about incorporation bias...

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Comparing accuracy of lipoarabinomannan urine tests for diagnosis of pulmonary tuberculosis in children from four African countries: a cross-sectional study

Cited by 29 publications

References 19 publications

Diagnostic Performance of the Fujifilm SILVAMP TB-LAM in Children with Presumptive Tuberculosis

Diagnostic Performance of the Fujifilm SILVAMP TB-LAM in Children with Presumptive Tuberculosis

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

Screening tests for active pulmonary tuberculosis in children

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