Incremental Yield of Including Determine-TB LAM Assay in Diagnostic Algorithms for Hospitalized and Ambulatory HIV-Positive Patients in Kenya

Abstract

BackgroundDetermine-TB LAM assay is a urine point-of-care test useful for TB diagnosis in HIV-positive patients. We assessed the incremental diagnostic yield of adding LAM to algorithms based on clinical signs, sputum smear-microscopy, chest X-ray and Xpert MTB/RIF in HIV-positive patients with symptoms of pulmonary TB (PTB).MethodsProspective observational cohort of ambulatory (either severely ill or CD4<200cells/μl or with Body Mass Index<17Kg/m2) and hospitalized symptomatic HIV-positive adults in Kenya. Incremental diagnostic yield of adding LAM was the difference in the proportion of confirmed TB patients (positive Xpert or MTB culture) diagnosed by the algorithm with LAM compared to the algorithm without LAM. The multivariable mortality model was adjusted for age, sex, clinical severity, BMI, CD4, ART initiation, LAM result and TB confirmation.ResultsAmong 474 patients included, 44.1% were severely ill, 69.6% had CD4<200cells/μl, 59.9% had initiated ART, 23.2% could not produce sputum. LAM, smear-microscopy, Xpert and culture in sputum were positive in 39.0% (185/474), 21.6% (76/352), 29.1% (102/350) and 39.7% (92/232) of the patients tested, respectively. Of 156 patients with confirmed TB, 65.4% were LAM positive. Of those classified as non-TB, 84.0% were LAM negative. Adding LAM increased the diagnostic yield of the algorithms by 36.6%, from 47.4% (95%CI:39.4–55.6) to 84.0% (95%CI:77.3–89.4%), when using clinical signs and X-ray; by 19.9%, from 62.2% (95%CI:54.1–69.8) to 82.1% (95%CI:75.1–87.7), when using clinical signs and microscopy; and by 13.4%, from 74.4% (95%CI:66.8–81.0) to 87.8% (95%CI:81.6–92.5), when using clinical signs and Xpert. LAM positive patients had an increased risk of 2-months mortality (aOR:2.7; 95%CI:1.5–4.9).ConclusionLAM should be included in TB diagnostic algorithms in parallel to microscopy or Xpert request for HIV-positive patients either ambulatory (severely ill or CD4<200cells/μl) or hospitalized. LAM allows same day treatment initiation in patients at higher risk of death and in those not able to produce sputum.

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

“…In Malawi, the MOH had stopped supplying CD4 testing material and CD4 testing was no longer available outside of study contexts. Introducing clinical criteria for LAM eligibility when the CD4 count is not available may be an intermediate solution, although this strategy risks missing some patients who could benefit from the LAM test [21]. The need for CD4 criteria in patient populations with a high risk of TB, such as hospitalized or ambulatory patients with symptoms of TB in high burden settings may also need to be reviewed.…”

Cost-effectiveness of diagnostic algorithms including lateral-flow urine lipoarabinomannan for HIV-positive patients with symptoms of tuberculosis

“…This study uses data from a single-centred, prospective study conducted between October 2013 and August 2015 at the Homa Bay County Hospital (Kenya) [15]. The population of the prospective study consisted on adults (�15 years) with symptoms of TB hospitalized in the inpatient department or attending the out-patients TB clinic, who were either severely ill, or with a CD4 count below 200cells/μl or a body mass index (BMI) below 17Kg/m 2 , and who had not taken fluoroquinolones or anti-tuberculosis drugs in the month prior to the consultation.…”

“…Using the prospective study efficacy data results of Huerga et al [15], a decision-analysis tree was constructed to determine the cost effectiveness of each TB diagnostic algorithm. In total, 10 algorithms for TB diagnosis were compared (Fig 1).…”

“…The Nyanza region, where Homa Bay is located, is the area with the highest case load reported in the country [14]. In Homa Bay, the overall HIV prevalence among people aged years was estimated at 20.7% in 2017 [14,15], more than four times the national average in the country and 74% among TB patients [13][14][15]. TB and HIV care was provided in Homa Bay District Hospital by the Ministry of Health and Médecins Sans Frontières free of charge.…”

“…HIV testing was proposed to all patients with symptoms of TB. A previous prospective observational study conducted in the same site showed that LF-LAM increased the diagnostic yield in ambulatory and hospitalized, immunocompromised (CD4<200cell/μL) or seriously ill, HIV-positive patients with symptoms of TB [15]. Using data from this cohort study, we aimed to evaluate the cost-effectiveness of introducing urine LF-LAM assay in 10 different TB diagnostic algorithms for this population of HIV-positive patients.…”