Value of Urine Lipoarabinomannan Grade and Second Test for Optimizing Clinic-Based Screening for HIV-Associated Pulmonary Tuberculosis

Abstract

Background We assessed the role of urine LAM (lipoarabinomannan) grade and a second LAM test for HIV-associated pulmonary tuberculosis (TB) screening in outpatient clinics in South Africa. Methods We enrolled newly-diagnosed HIV-infected adults (≥18 years) at 4 clinics, excluding those on TB therapy. Participants provided sputum for AFB microscopy and culture. Nurses conducted two rapid urine LAM tests at the point-of-care, and graded positive results from low (“faint”) to high (5+). Culture-confirmed pulmonary TB was the gold standard. We used area under receiver operating curves (AUROC) to compare screening strategies. Results Among 320 HIV-infected adults, median CD4 was 248/mm3 (IQR 107–379/mm3); 54 (17%) were TB culture-positive. 52 (16%) of all participants were LAM-positive by either test; correlation between LAM tests was high. Among 10 “faint” positive results, 2 (20%) had culture-positive TB. Using ≥1+ LAM grade as positive, one LAM test had sensitivity of 41% (95% CI 28–55%) and specificity of 92% (95% CI 88–95%). A 2 LAM test strategy had a sensitivity of 43% (95% CI 29–57%). One LAM test ≥1+ grade (AUROC=0.66; 95% CI 0.60–0.73) was significantly better than sputum AFB alone. The optimal strategy was sequentially performing one LAM test followed by sputum AFB if LAM grade <1+ (AUROC=0.70; 95% CI 0.63–0.77), which had sensitivity of 48% (95% CI 34–62%) and specificity of 91% (95% CI 87–94%). Conclusions In this clinic-based study, “faint” line was a false-positive, second urine LAM test added no value, and an optimal screening strategy was one LAM test followed by sputum AFB microscopy for urine LAM-negative people.

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

“…This is similar to findings by Peter et al where LAM test specificity increased from 78 % to 94 % when the composite reference standard was used instead of a microbiological reference standard [ 18 ]. Another key factor for test specificity is the positivity threshold for the LAM test as shown in previous studies [ 13 , 16 , 18 ]. There is consensus of using grade 2 cut-point as positivity threshold and in 2014 the LAM test manufacturers changed the reference scale card omitting the band corresponding to grade 1.…”

“…We found that an additional sample did not increase overall performance of the LAM test and agreement between results for a spot and morning sample was high. A recent study explored a two-test strategy performed on the same sample and did not show any added diagnostic value of the second test [ 13 ].…”

Test characteristics and potential impact of the urine LAM lateral flow assay in HIV-infected outpatients under investigation for TB and able to self-expectorate sputum for diagnostic testing

“…Published data, albeit limited, indicate that LAM sensitivity is increased with higher circulating LAM levels, occurring with higher mycobacterial disease burden, extrapulmonary TB, lower CD4 cell count and WHO clinical stage 3 and 4 in out- and in-patient settings [ 11 , 27 – 34 ]. Moreover, LAM and sputum smear microscopy identified non-overlapping sub-groups of culture-positive TB, thereby offering additive diagnostic value [ 11 – 14 , 16 , 35 ]. By contrast, we found no incremental benefit of LAM.…”

Rapid urine lipoarabinomannan assay as a clinic-based screening test for active tuberculosis at HIV diagnosis

“…In two clinic-based studies, we demonstrated that the rapid urine LAM assay had poor overall diagnostic sensitivity (28-41%) to be used as a stand-alone TB screening test at HIV diagnosis [13, 14]. With similar results from another outpatient screening study [15, 16], the WHO recently recommended against using the urine LAM assay as a TB screening test.…”

“…With similar results from another outpatient screening study [15, 16], the WHO recently recommended against using the urine LAM assay as a TB screening test. [17] However, since the rapid LAM assay can be easily performed by nurses in a clinic [13, 14], we sought to determine if urine LAM testing might augment symptom-based TB screening at HIV diagnosis in a high TB-endemic region of South Africa.…”