Utility of urine lipoarabinomannan (LAM) in diagnosing tuberculosis and predicting mortality with and without HIV: prospective TB cohort from the Thailand Big City TB Research Network

Suwanpimolkul, Gompol; Kawkitinarong, Kamon; Manosuthi, Weerawat; Sophonphan, Jiratchaya; Gatechompol, Sivaporn; Ohata, Pirapon June; Ubolyam, Sasiwimol; Iampornsin, Thatri; Katerattanakul, Pairaj; Avihingsanon, Anchalee; Ruxrungtham, Kiat

doi:10.1016/j.ijid.2017.04.017

Cited by 44 publications

(32 citation statements)

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“…AlereLAM is not recommended for diagnosis of TB in people living with HIV with CD4 greater than 200 cells/μL due to a suboptimal sensitivity of 16% in this population ( 6 , 7 ). Performance in HIV-negative patients is very poor, with reported estimated sensitivities ranging from 4% to 31% ( 11 – 15 ).…”

Section: Introductionmentioning

confidence: 99%

Diagnostic accuracy of 3 urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients

Broger¹,

Nicol²,

Sigal³

et al. 2020

Journal of Clinical Investigation

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BACKGROUND Inadequate tuberculosis (TB) diagnostics are a major hurdle in the reduction of disease burden, and accurate point-of-care tests (POCTs) are urgently needed. We assessed the diagnostic accuracy of Fujifilm SILVAMP TB lipoarabinomannan (FujiLAM) POCT for TB diagnosis in HIV-negative outpatients and compared it with Alere Determine TB LAM Ag (AlereLAM) POCT and a laboratory-based ultrasensitive electrochemiluminescence LAM research assay (EclLAM). METHODS In this multicenter diagnostic test accuracy study, we recruited HIV-negative adults with symptoms suggestive of pulmonary TB presenting to outpatient health care centers in Peru and South Africa. Urine samples were tested using FujiLAM, AlereLAM, and EclLAM, and the diagnostic accuracy was assessed against a microbiological reference standard (MRS) and a composite reference standard. RESULTS Three hundred seventy-two HIV-negative participants were included and the prevalence of microbiologically confirmed TB was 30%. Compared with the MRS, the sensitivities of AlereLAM, FujiLAM, and EclLAM were 10.8% (95% confidence interval [CI] 6.3%–18.0%), 53.2% (95% CI 43.9%–62.1%), and 66.7% (95% CI 57.5%–74.7%), respectively. The specificities of AlereLAM, FujiLAM, and EclLAM were 92.3% (95% CI 88.5%–95.0%), 98.9% (95% CI 96.7%–99.6%), and 98.1% (95% CI 95.6%–99.2%), respectively. Positive likelihood ratios of AlereLAM, FujiLAM, and EclLAM were 1.4, 46.2, and 34.8, respectively, and positive predictive values were 37.5%, 95.2%, and 93.7%, respectively. CONCLUSION Compared with AlereLAM, FujiLAM detected 5 times more patients with TB in HIV-negative participants, had a high positive predictive value, and has the potential to improve rapid diagnosis of TB at the point-of-care. EclLAM demonstrated that additional sensitivity gains are possible, which highlights LAM’s potential as a biomarker. Additional research is required to assess FujiLAM’s performance in prospective cohorts, its cost-effectiveness, and its impact in real-world clinical settings. FUNDING Global Health Innovative Technology Fund, the UK Department for International Development, the Dutch Ministry of Foreign Affairs, the Bill and Melinda Gates Foundation, the Australian Department of Foreign Affairs and Trade, the German Federal Ministry of Education and Research through Kreditanstalt für Wiederaufbau, and the NIH and National Institute of Allergy and Infectious Diseases.

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Section: Introductionmentioning

confidence: 99%

Diagnostic accuracy of 3 urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients

Broger¹,

Nicol²,

Sigal³

et al. 2020

Journal of Clinical Investigation

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“…Validated tests for urine antigen in infectious diseases include those for schistosomiasis [ 35 ], tuberculosis [ 36 ], Legionella pneumophila and Streptococcus pneumoniae [ 37 ], among others. Here, we captured L .…”

Section: Discussionmentioning

confidence: 99%

Isolation and characterisation of Leishmania donovani protein antigens from urine of visceral leishmaniasis patients

et al. 2020

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Diagnosis of visceral leishmaniasis (VL) relies on invasive and risky aspirate procedures, and confirmation of cure after treatment is unreliable. Detection of Leishmania donovani antigens in urine has the potential to provide both a non-invasive diagnostic and a test of cure. We searched for L . donovani antigens in urine of VL patients from India and Sudan to contribute to the development of urine antigen capture immunoassays. VL urine samples were incubated with immobilised anti- L . donovani polyclonal antibodies and captured material was eluted. Sudanese eluted material and concentrated VL urine were analysed by western blot. Immunocaptured and immunoreactive material from Indian and Sudanese urine was submitted to mass spectrometry for protein identification. We identified six L . donovani proteins from VL urine. Named proteins were 40S ribosomal protein S9, kinases, and others were hypothetical. Thirty-three epitope regions were predicted with high specificity in the 6 proteins. Of these, 20 were highly specific to Leishmania spp. and are highly suitable for raising antibodies for the subsequent development of an antigen capture assay. We present all the identified proteins and analysed epitope regions in full so that they may contribute to the development of non-invasive immunoassays for this deadly disease.

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“…Clinical screening performs poorly in PLHIV and may miss up to 25% of all laboratory-confirmed tuberculosis cases and up to 70% among HIV-infected pregnant women [ 9 ▪▪ ]. Molecular and lateral flow diagnostics with greater sensitivity are showing promise for improving the situation [ 10 , 11 ▪▪ , 12 , 13 ▪▪ , 14 ].…”

Section: Co-infections In Hivmentioning

confidence: 99%

When do co-infections matter?

McArdle¹,

Turkova

Cunnington

2018

Current Opinion in Infectious Diseases

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Purpose of reviewAdvances in diagnostic methods mean that co-infections are increasingly being detected in clinical practice, yet their significance is not always obvious. In parallel, basic science studies are increasingly investigating interactions between pathogens to try to explain real-life observations and elucidate biological mechanisms.Recent findingsCo-infections may be insignificant, detrimental, or even beneficial, and these outcomes can occur through multiple levels of interactions which include modulation of the host response, altering the performance of diagnostic tests, and drug–drug interactions during treatment. The harmful effects of chronic co-infections such as tuberculosis or Hepatitis B and C in association with HIV are well established, and recent studies have focussed on strategies to mitigate these effects. However, consequences of many acute co-infections are much less certain, and recent conflicting findings simply highlight many of the challenges of studying naturally acquired infections in humans.SummaryTackling these challenges, using animal models, or careful prospective studies in humans may prove to be worthwhile. There are already tantalizing examples where identification and treatment of relevant co-infections seems to hold promise for improved health outcomes.

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Utility of urine lipoarabinomannan (LAM) in diagnosing tuberculosis and predicting mortality with and without HIV: prospective TB cohort from the Thailand Big City TB Research Network

Abstract: This promising diagnostic tool could increase the yield of TB diagnosis and may predict the mortality rate of TB infection, particularly in TB/HIV co-infected patients.

Cited by 44 publications

References 20 publications

Diagnostic accuracy of 3 urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients

Diagnostic accuracy of 3 urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients

Isolation and characterisation of Leishmania donovani protein antigens from urine of visceral leishmaniasis patients

When do co-infections matter?

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