The clinical utility of the urine-based lateral flow lipoarabinomannan assay in HIV-infected adults in Myanmar

An observational study

Swe Swe Thit, Ne Myo Aung, Zaw Win Htet, Mark A. Boyd, Htin Aung Saw, Nicholas M. Anstey, Tint Tint Kyi, David A. Cooper, Mar Mar Kyi, Josh Hanson

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    Abstract

    Background: The use of the point-of-care lateral flow lipoarabinomannan (LF-LAM) test may expedite tuberculosis (TB) diagnosis in HIV-positive patients. However, the test's clinical utility is poorly defined outside sub-Saharan Africa.

    Methods: The study enrolled consecutive HIV-positive adults at a tertiary referral hospital in Yangon, Myanmar. On enrolment, patients had a LF-LAM test performed according to the manufacturer's instructions. Clinicians managing the patients were unaware of the LF-LAM result, which was correlated with the patient's clinical course over the ensuing 6 months.

    Results: The study enrolled 54 inpatients and 463 outpatients between July 1 and December 31, 2015. On enrolment, the patients' median (interquartile range) CD4 T-cell count was 270 (128-443) cells/mm3. The baseline LF-LAM test was positive in 201/517 (39%). TB was confirmed microbiologically during follow-up in 54/517 (10%), with rifampicin resistance present in 8/54 (15%). In the study's resource-limited setting, extrapulmonary testing for TB was not possible, but after 6 months, 97/201 (48%) with a positive LF-LAM test on enrolment had neither died, required hospitalisation, received a TB diagnosis or received empirical anti-TB therapy, suggesting a high rate of false-positive results. Of the 97 false-positive tests, 89 (92%) were grade 1 positive, suggesting poor test specificity using this cut-off. Only 21/517 (4%) patients were inpatients with TB symptoms and a CD4 T-cell count of < 100 cells/mm3. Five (24%) of these 21 died, three of whom had a positive LF-LAM test on enrolment. However, all three received anti-TB therapy before death - two after diagnosis with Xpert MTB/RIF testing, while the other received empirical treatment. It is unlikely that knowledge of the baseline LF-LAM result would have averted any of the study's other 11 deaths; eight had a negative test, and of the three patients with a positive test, two received anti-TB therapy before death, while one died from laboratory-confirmed cryptococcal meningitis. The test was no better than a simple, clinical history excluding TB during follow-up (negative predictive value (95% confidence interval): 94% (91-97) vs. 94% (91-96)).

    Conclusions: The LF-LAM test had limited clinical utility in the management of HIV-positive patients in this Asian referral hospital setting.

    Original languageEnglish
    Article number145
    Pages (from-to)1-11
    Number of pages11
    JournalBMC Medicine
    Volume15
    Issue number1
    DOIs
    Publication statusPublished - 4 Aug 2017

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    Myanmar
    Observational Studies
    Tuberculosis
    HIV
    Urine
    CD4 Lymphocyte Count
    Inpatients
    Point-of-Care Systems
    Cryptococcal Meningitis
    T-Lymphocytes
    lipoarabinomannan
    Africa South of the Sahara
    Therapeutics
    Rifampin
    Tertiary Care Centers
    Hospitalization
    Outpatients
    Referral and Consultation
    Confidence Intervals

    Cite this

    Thit, Swe Swe ; Aung, Ne Myo ; Htet, Zaw Win ; Boyd, Mark A. ; Saw, Htin Aung ; Anstey, Nicholas M. ; Kyi, Tint Tint ; Cooper, David A. ; Kyi, Mar Mar ; Hanson, Josh. / The clinical utility of the urine-based lateral flow lipoarabinomannan assay in HIV-infected adults in Myanmar : An observational study. In: BMC Medicine. 2017 ; Vol. 15, No. 1. pp. 1-11.
    @article{53fcb1b34b8f4e7585c5977e02c7b380,
    title = "The clinical utility of the urine-based lateral flow lipoarabinomannan assay in HIV-infected adults in Myanmar: An observational study",
    abstract = "Background: The use of the point-of-care lateral flow lipoarabinomannan (LF-LAM) test may expedite tuberculosis (TB) diagnosis in HIV-positive patients. However, the test's clinical utility is poorly defined outside sub-Saharan Africa. Methods: The study enrolled consecutive HIV-positive adults at a tertiary referral hospital in Yangon, Myanmar. On enrolment, patients had a LF-LAM test performed according to the manufacturer's instructions. Clinicians managing the patients were unaware of the LF-LAM result, which was correlated with the patient's clinical course over the ensuing 6 months. Results: The study enrolled 54 inpatients and 463 outpatients between July 1 and December 31, 2015. On enrolment, the patients' median (interquartile range) CD4 T-cell count was 270 (128-443) cells/mm3. The baseline LF-LAM test was positive in 201/517 (39{\%}). TB was confirmed microbiologically during follow-up in 54/517 (10{\%}), with rifampicin resistance present in 8/54 (15{\%}). In the study's resource-limited setting, extrapulmonary testing for TB was not possible, but after 6 months, 97/201 (48{\%}) with a positive LF-LAM test on enrolment had neither died, required hospitalisation, received a TB diagnosis or received empirical anti-TB therapy, suggesting a high rate of false-positive results. Of the 97 false-positive tests, 89 (92{\%}) were grade 1 positive, suggesting poor test specificity using this cut-off. Only 21/517 (4{\%}) patients were inpatients with TB symptoms and a CD4 T-cell count of < 100 cells/mm3. Five (24{\%}) of these 21 died, three of whom had a positive LF-LAM test on enrolment. However, all three received anti-TB therapy before death - two after diagnosis with Xpert MTB/RIF testing, while the other received empirical treatment. It is unlikely that knowledge of the baseline LF-LAM result would have averted any of the study's other 11 deaths; eight had a negative test, and of the three patients with a positive test, two received anti-TB therapy before death, while one died from laboratory-confirmed cryptococcal meningitis. The test was no better than a simple, clinical history excluding TB during follow-up (negative predictive value (95{\%} confidence interval): 94{\%} (91-97) vs. 94{\%} (91-96)). Conclusions: The LF-LAM test had limited clinical utility in the management of HIV-positive patients in this Asian referral hospital setting.",
    keywords = "Clinical management, Diagnostic test, Human immunodeficiency virus, Lipoarabinomannan, Myanmar, Tuberculosis",
    author = "Thit, {Swe Swe} and Aung, {Ne Myo} and Htet, {Zaw Win} and Boyd, {Mark A.} and Saw, {Htin Aung} and Anstey, {Nicholas M.} and Kyi, {Tint Tint} and Cooper, {David A.} and Kyi, {Mar Mar} and Josh Hanson",
    year = "2017",
    month = "8",
    day = "4",
    doi = "10.1186/s12916-017-0888-3",
    language = "English",
    volume = "15",
    pages = "1--11",
    journal = "BMC Medicine",
    issn = "1741-7015",
    publisher = "BioMed Central",
    number = "1",

    }

    Thit, SS, Aung, NM, Htet, ZW, Boyd, MA, Saw, HA, Anstey, NM, Kyi, TT, Cooper, DA, Kyi, MM & Hanson, J 2017, 'The clinical utility of the urine-based lateral flow lipoarabinomannan assay in HIV-infected adults in Myanmar: An observational study', BMC Medicine, vol. 15, no. 1, 145, pp. 1-11. https://doi.org/10.1186/s12916-017-0888-3

    The clinical utility of the urine-based lateral flow lipoarabinomannan assay in HIV-infected adults in Myanmar : An observational study. / Thit, Swe Swe; Aung, Ne Myo; Htet, Zaw Win; Boyd, Mark A.; Saw, Htin Aung; Anstey, Nicholas M.; Kyi, Tint Tint; Cooper, David A.; Kyi, Mar Mar; Hanson, Josh.

    In: BMC Medicine, Vol. 15, No. 1, 145, 04.08.2017, p. 1-11.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - The clinical utility of the urine-based lateral flow lipoarabinomannan assay in HIV-infected adults in Myanmar

    T2 - An observational study

    AU - Thit, Swe Swe

    AU - Aung, Ne Myo

    AU - Htet, Zaw Win

    AU - Boyd, Mark A.

    AU - Saw, Htin Aung

    AU - Anstey, Nicholas M.

    AU - Kyi, Tint Tint

    AU - Cooper, David A.

    AU - Kyi, Mar Mar

    AU - Hanson, Josh

    PY - 2017/8/4

    Y1 - 2017/8/4

    N2 - Background: The use of the point-of-care lateral flow lipoarabinomannan (LF-LAM) test may expedite tuberculosis (TB) diagnosis in HIV-positive patients. However, the test's clinical utility is poorly defined outside sub-Saharan Africa. Methods: The study enrolled consecutive HIV-positive adults at a tertiary referral hospital in Yangon, Myanmar. On enrolment, patients had a LF-LAM test performed according to the manufacturer's instructions. Clinicians managing the patients were unaware of the LF-LAM result, which was correlated with the patient's clinical course over the ensuing 6 months. Results: The study enrolled 54 inpatients and 463 outpatients between July 1 and December 31, 2015. On enrolment, the patients' median (interquartile range) CD4 T-cell count was 270 (128-443) cells/mm3. The baseline LF-LAM test was positive in 201/517 (39%). TB was confirmed microbiologically during follow-up in 54/517 (10%), with rifampicin resistance present in 8/54 (15%). In the study's resource-limited setting, extrapulmonary testing for TB was not possible, but after 6 months, 97/201 (48%) with a positive LF-LAM test on enrolment had neither died, required hospitalisation, received a TB diagnosis or received empirical anti-TB therapy, suggesting a high rate of false-positive results. Of the 97 false-positive tests, 89 (92%) were grade 1 positive, suggesting poor test specificity using this cut-off. Only 21/517 (4%) patients were inpatients with TB symptoms and a CD4 T-cell count of < 100 cells/mm3. Five (24%) of these 21 died, three of whom had a positive LF-LAM test on enrolment. However, all three received anti-TB therapy before death - two after diagnosis with Xpert MTB/RIF testing, while the other received empirical treatment. It is unlikely that knowledge of the baseline LF-LAM result would have averted any of the study's other 11 deaths; eight had a negative test, and of the three patients with a positive test, two received anti-TB therapy before death, while one died from laboratory-confirmed cryptococcal meningitis. The test was no better than a simple, clinical history excluding TB during follow-up (negative predictive value (95% confidence interval): 94% (91-97) vs. 94% (91-96)). Conclusions: The LF-LAM test had limited clinical utility in the management of HIV-positive patients in this Asian referral hospital setting.

    AB - Background: The use of the point-of-care lateral flow lipoarabinomannan (LF-LAM) test may expedite tuberculosis (TB) diagnosis in HIV-positive patients. However, the test's clinical utility is poorly defined outside sub-Saharan Africa. Methods: The study enrolled consecutive HIV-positive adults at a tertiary referral hospital in Yangon, Myanmar. On enrolment, patients had a LF-LAM test performed according to the manufacturer's instructions. Clinicians managing the patients were unaware of the LF-LAM result, which was correlated with the patient's clinical course over the ensuing 6 months. Results: The study enrolled 54 inpatients and 463 outpatients between July 1 and December 31, 2015. On enrolment, the patients' median (interquartile range) CD4 T-cell count was 270 (128-443) cells/mm3. The baseline LF-LAM test was positive in 201/517 (39%). TB was confirmed microbiologically during follow-up in 54/517 (10%), with rifampicin resistance present in 8/54 (15%). In the study's resource-limited setting, extrapulmonary testing for TB was not possible, but after 6 months, 97/201 (48%) with a positive LF-LAM test on enrolment had neither died, required hospitalisation, received a TB diagnosis or received empirical anti-TB therapy, suggesting a high rate of false-positive results. Of the 97 false-positive tests, 89 (92%) were grade 1 positive, suggesting poor test specificity using this cut-off. Only 21/517 (4%) patients were inpatients with TB symptoms and a CD4 T-cell count of < 100 cells/mm3. Five (24%) of these 21 died, three of whom had a positive LF-LAM test on enrolment. However, all three received anti-TB therapy before death - two after diagnosis with Xpert MTB/RIF testing, while the other received empirical treatment. It is unlikely that knowledge of the baseline LF-LAM result would have averted any of the study's other 11 deaths; eight had a negative test, and of the three patients with a positive test, two received anti-TB therapy before death, while one died from laboratory-confirmed cryptococcal meningitis. The test was no better than a simple, clinical history excluding TB during follow-up (negative predictive value (95% confidence interval): 94% (91-97) vs. 94% (91-96)). Conclusions: The LF-LAM test had limited clinical utility in the management of HIV-positive patients in this Asian referral hospital setting.

    KW - Clinical management

    KW - Diagnostic test

    KW - Human immunodeficiency virus

    KW - Lipoarabinomannan

    KW - Myanmar

    KW - Tuberculosis

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    U2 - 10.1186/s12916-017-0888-3

    DO - 10.1186/s12916-017-0888-3

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    VL - 15

    SP - 1

    EP - 11

    JO - BMC Medicine

    JF - BMC Medicine

    SN - 1741-7015

    IS - 1

    M1 - 145

    ER -