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Diagnostic accuracy of the rapid urine lipoarabinomannan test for pulmonary tuberculosis among HIV-infected adults in Ghana-findings from the DETECT HIV-TB study.

Bjerrum S, Kenu E, Lartey M, Newman MJ, Addo KK, Andersen AB, Johansen IS - BMC Infect. Dis. (2015)

Bottom Line: A two-sample LAM test strategy did not improve test performance.LAM test sensitivity was highest in patients with poor prognosis and subsequent death and did not increase with a two-sample strategy.A rigorous sputum microscopy strategy had superior sensitivity, but the simplicity of the LAM test holds operational possibilities as a TB screening method among severely sick patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Odense University Hospital, Odense, Denmark. steph@medicinsk.dk.

ABSTRACT

Background: Rapid diagnostic tests are urgently needed to mitigate HIV-associated tuberculosis (TB) mortality. We evaluated diagnostic accuracy of the rapid urine lipoarabinomannan (LAM) test for pulmonary TB and assessed the effect of a two-sample strategy.

Methods: HIV-infected adults eligible for antiretroviral therapy were prospectively enrolled from Korle-Bu Teaching Hospital in Ghana and followed for minimum 6 months. We applied the LAM test on urine collected as a spot and early morning sample. Diagnostic accuracy was analysed for a microbiological TB reference standard based on sputum culture and Gene Xpert MTB/RIF results and for a composite reference standard including clinical follow-up data. Performance of sputum smear microscopy was included for comparison.

Results: Of 469 patients investigated for TB, the LAM test correctly identified 24/55 (44 %) of microbiologically confirmed TB cases. Sensitivity of the LAM test was positively associated with hospitalisation (67 %), Modified Early Warning Score > 4 (57 %) and subsequent death (71 %). LAM test specificity was 95 % increasing to 98 % for the composite reference standard. A two-sample LAM test strategy did not improve test performance. Using concentrated sputum for Ziehl-Neelsen and fluorescence microscopy in combination yielded a sensitivity of 31/55 (56 %) that increased to 35/55 (64 %) when the LAM test was added. Surprisingly, nontuberculous mycobacteria were cultured in 34/469 (7 %) and associated with a positive LAM test (p = 0.008).

Conclusions: LAM test sensitivity was highest in patients with poor prognosis and subsequent death and did not increase with a two-sample strategy. A rigorous sputum microscopy strategy had superior sensitivity, but the simplicity of the LAM test holds operational possibilities as a TB screening method among severely sick patients.

No MeSH data available.


Related in: MedlinePlus

Flowchart of study participants and analysis. *Of 29 participants excluded; three (3) were on antituberculous treatment; twenty one (21) had no sputum samples; and five (5) had no urine sample. The remaining 469 participants were eligible for analysis with at least 1 sputum and 1 urine sample available
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Fig1: Flowchart of study participants and analysis. *Of 29 participants excluded; three (3) were on antituberculous treatment; twenty one (21) had no sputum samples; and five (5) had no urine sample. The remaining 469 participants were eligible for analysis with at least 1 sputum and 1 urine sample available

Mentions: Descriptive analysis was used to characterize the study population and reported with interquartile range (IQR) and standard deviations (SD) as appropriate. Kappa statistics were used to determine inter-reader agreement between LAM test results and agreement between test results reported with the standard error (SE). Accuracy measures (sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV) and likelihood ratio (LR)) were calculated with 95 % Confidence Interval (CI). In our primary analysis, we used a microbiological reference standard comparing “Confirmed TB” vs. participants with no positive cultures or positive Xpert results. In the secondary analysis we used a composite reference standard for TB and combined “Confirmed TB” and “Possible TB” for calculation of sensitivities versus “Non TB” cases to calculate specificity. Figure 1 outlines the analysis of groups. For subgroup analysis we stratified participants by: enrolment site (hospitalised patients vs. outpatients); CD4 cell count (CD4 < 100 cells/mm3 vs. CD4 ≥ 100 cells/mm3); MEWS (MEWS > 4 vs. MEWS ≤ 4); and vital status at 2 months (dead vs. alive). Sensitivity and specificity was compared across strata using chi-square test or Fisher Exact test as appropriate. We determined diagnostic accuracy for LAM test in combinations with sputum smear microscopy and for the two-sample LAM test strategy. When assessing performance of a combination of tests, the result was considered positive if any of the tests were positive. The result was considered negative if both tests were negative. McNemar’s test was used to compare two different test sensitivities and specificities. The cumulative probabilities of death were estimated by means of the Kaplain-Meier method, compared according to LAM test results with the log-rank test. Statistical significance was defined as a two-sided p-value less than 0.05 and all analysis were conducted using STATA™ version 13.1 software.Fig. 1


Diagnostic accuracy of the rapid urine lipoarabinomannan test for pulmonary tuberculosis among HIV-infected adults in Ghana-findings from the DETECT HIV-TB study.

Bjerrum S, Kenu E, Lartey M, Newman MJ, Addo KK, Andersen AB, Johansen IS - BMC Infect. Dis. (2015)

Flowchart of study participants and analysis. *Of 29 participants excluded; three (3) were on antituberculous treatment; twenty one (21) had no sputum samples; and five (5) had no urine sample. The remaining 469 participants were eligible for analysis with at least 1 sputum and 1 urine sample available
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4591579&req=5

Fig1: Flowchart of study participants and analysis. *Of 29 participants excluded; three (3) were on antituberculous treatment; twenty one (21) had no sputum samples; and five (5) had no urine sample. The remaining 469 participants were eligible for analysis with at least 1 sputum and 1 urine sample available
Mentions: Descriptive analysis was used to characterize the study population and reported with interquartile range (IQR) and standard deviations (SD) as appropriate. Kappa statistics were used to determine inter-reader agreement between LAM test results and agreement between test results reported with the standard error (SE). Accuracy measures (sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV) and likelihood ratio (LR)) were calculated with 95 % Confidence Interval (CI). In our primary analysis, we used a microbiological reference standard comparing “Confirmed TB” vs. participants with no positive cultures or positive Xpert results. In the secondary analysis we used a composite reference standard for TB and combined “Confirmed TB” and “Possible TB” for calculation of sensitivities versus “Non TB” cases to calculate specificity. Figure 1 outlines the analysis of groups. For subgroup analysis we stratified participants by: enrolment site (hospitalised patients vs. outpatients); CD4 cell count (CD4 < 100 cells/mm3 vs. CD4 ≥ 100 cells/mm3); MEWS (MEWS > 4 vs. MEWS ≤ 4); and vital status at 2 months (dead vs. alive). Sensitivity and specificity was compared across strata using chi-square test or Fisher Exact test as appropriate. We determined diagnostic accuracy for LAM test in combinations with sputum smear microscopy and for the two-sample LAM test strategy. When assessing performance of a combination of tests, the result was considered positive if any of the tests were positive. The result was considered negative if both tests were negative. McNemar’s test was used to compare two different test sensitivities and specificities. The cumulative probabilities of death were estimated by means of the Kaplain-Meier method, compared according to LAM test results with the log-rank test. Statistical significance was defined as a two-sided p-value less than 0.05 and all analysis were conducted using STATA™ version 13.1 software.Fig. 1

Bottom Line: A two-sample LAM test strategy did not improve test performance.LAM test sensitivity was highest in patients with poor prognosis and subsequent death and did not increase with a two-sample strategy.A rigorous sputum microscopy strategy had superior sensitivity, but the simplicity of the LAM test holds operational possibilities as a TB screening method among severely sick patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Odense University Hospital, Odense, Denmark. steph@medicinsk.dk.

ABSTRACT

Background: Rapid diagnostic tests are urgently needed to mitigate HIV-associated tuberculosis (TB) mortality. We evaluated diagnostic accuracy of the rapid urine lipoarabinomannan (LAM) test for pulmonary TB and assessed the effect of a two-sample strategy.

Methods: HIV-infected adults eligible for antiretroviral therapy were prospectively enrolled from Korle-Bu Teaching Hospital in Ghana and followed for minimum 6 months. We applied the LAM test on urine collected as a spot and early morning sample. Diagnostic accuracy was analysed for a microbiological TB reference standard based on sputum culture and Gene Xpert MTB/RIF results and for a composite reference standard including clinical follow-up data. Performance of sputum smear microscopy was included for comparison.

Results: Of 469 patients investigated for TB, the LAM test correctly identified 24/55 (44 %) of microbiologically confirmed TB cases. Sensitivity of the LAM test was positively associated with hospitalisation (67 %), Modified Early Warning Score > 4 (57 %) and subsequent death (71 %). LAM test specificity was 95 % increasing to 98 % for the composite reference standard. A two-sample LAM test strategy did not improve test performance. Using concentrated sputum for Ziehl-Neelsen and fluorescence microscopy in combination yielded a sensitivity of 31/55 (56 %) that increased to 35/55 (64 %) when the LAM test was added. Surprisingly, nontuberculous mycobacteria were cultured in 34/469 (7 %) and associated with a positive LAM test (p = 0.008).

Conclusions: LAM test sensitivity was highest in patients with poor prognosis and subsequent death and did not increase with a two-sample strategy. A rigorous sputum microscopy strategy had superior sensitivity, but the simplicity of the LAM test holds operational possibilities as a TB screening method among severely sick patients.

No MeSH data available.


Related in: MedlinePlus