Combining urine lipoarabinomannan with antibody detection as a simple non-sputum-based screening method for HIV-associated tuberculosis

Hiba Younis, Isabell Kerschbaumer, Jee Young Moon, Ryung S. Kim, Caroline J. Blanc, Tingting Chen, Robin Wood, Steven Lawn, Jacqueline M. Achkar

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Simple methods for the accurate triaging and screening of HIV-associated tuberculosis (TB) are urgently needed. We hypothesized that combining serum antibody with urine lipoarabinomannan (U-LAM) detection can improve the detection of HIV-associated TB. METHODS: We performed a case-control study with sampling from a prospective study of South African HIV-infected subjects who were screened for TB prior to initiating antiretroviral therapy. Sera from all available TB cases (n = 74) and randomly selected non-TB controls (n = 30), all tested for U-LAM, sputum microscopy, GeneXpert, and cultures, were evaluated for antibodies to LAM and arabinomannan (AM). Diagnostic logistic regression models for TB were developed based on the primary test results and the additive effect of antibodies with leave-one-out cross-validation. RESULTS: Antibody responses to LAM and AM correlated strongly (p<0.0001), and IgG and IgM reactivities were significantly higher in TB than non-TB patients (p<0.0001). At 80% specificity, the target specificity for a non-sputum-based simple triage/screening test determined by major TB stakeholders, combining U-LAM with IgG detection significantly increased the sensitivity for HIV-associated TB to 92% compared to 30% for U-LAM alone (p<0.001). Sputum microscopy combined with IgG detection increased sensitivity to 88% compared to 31% for microscopy alone, and Xpert with IgG increased sensitivity to 96% and 99% compared to 57% for testing one, and 70% for testing two sputa with Xpert alone, respectively. CONCLUSION: Combining U-LAM with serum antibody detection could provide a simple low-cost method that meets the requirements for a non-sputum-based test for the screening of HIV-associated TB.

Original languageEnglish (US)
Pages (from-to)e0218606
JournalPloS one
Volume14
Issue number6
DOIs
StatePublished - Jan 1 2019

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antibody detection
tuberculosis
Screening
Tuberculosis
urine
HIV
Urine
screening
Antibodies
Immunoglobulin G
Microscopic examination
Sputum
Microscopy
microscopy
antibodies
methodology
Logistic Models
Serum
Testing
first aid

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Combining urine lipoarabinomannan with antibody detection as a simple non-sputum-based screening method for HIV-associated tuberculosis. / Younis, Hiba; Kerschbaumer, Isabell; Moon, Jee Young; Kim, Ryung S.; Blanc, Caroline J.; Chen, Tingting; Wood, Robin; Lawn, Steven; Achkar, Jacqueline M.

In: PloS one, Vol. 14, No. 6, 01.01.2019, p. e0218606.

Research output: Contribution to journalArticle

Younis, Hiba ; Kerschbaumer, Isabell ; Moon, Jee Young ; Kim, Ryung S. ; Blanc, Caroline J. ; Chen, Tingting ; Wood, Robin ; Lawn, Steven ; Achkar, Jacqueline M. / Combining urine lipoarabinomannan with antibody detection as a simple non-sputum-based screening method for HIV-associated tuberculosis. In: PloS one. 2019 ; Vol. 14, No. 6. pp. e0218606.
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abstract = "BACKGROUND: Simple methods for the accurate triaging and screening of HIV-associated tuberculosis (TB) are urgently needed. We hypothesized that combining serum antibody with urine lipoarabinomannan (U-LAM) detection can improve the detection of HIV-associated TB. METHODS: We performed a case-control study with sampling from a prospective study of South African HIV-infected subjects who were screened for TB prior to initiating antiretroviral therapy. Sera from all available TB cases (n = 74) and randomly selected non-TB controls (n = 30), all tested for U-LAM, sputum microscopy, GeneXpert, and cultures, were evaluated for antibodies to LAM and arabinomannan (AM). Diagnostic logistic regression models for TB were developed based on the primary test results and the additive effect of antibodies with leave-one-out cross-validation. RESULTS: Antibody responses to LAM and AM correlated strongly (p<0.0001), and IgG and IgM reactivities were significantly higher in TB than non-TB patients (p<0.0001). At 80{\%} specificity, the target specificity for a non-sputum-based simple triage/screening test determined by major TB stakeholders, combining U-LAM with IgG detection significantly increased the sensitivity for HIV-associated TB to 92{\%} compared to 30{\%} for U-LAM alone (p<0.001). Sputum microscopy combined with IgG detection increased sensitivity to 88{\%} compared to 31{\%} for microscopy alone, and Xpert with IgG increased sensitivity to 96{\%} and 99{\%} compared to 57{\%} for testing one, and 70{\%} for testing two sputa with Xpert alone, respectively. CONCLUSION: Combining U-LAM with serum antibody detection could provide a simple low-cost method that meets the requirements for a non-sputum-based test for the screening of HIV-associated TB.",
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T1 - Combining urine lipoarabinomannan with antibody detection as a simple non-sputum-based screening method for HIV-associated tuberculosis

AU - Younis, Hiba

AU - Kerschbaumer, Isabell

AU - Moon, Jee Young

AU - Kim, Ryung S.

AU - Blanc, Caroline J.

AU - Chen, Tingting

AU - Wood, Robin

AU - Lawn, Steven

AU - Achkar, Jacqueline M.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - BACKGROUND: Simple methods for the accurate triaging and screening of HIV-associated tuberculosis (TB) are urgently needed. We hypothesized that combining serum antibody with urine lipoarabinomannan (U-LAM) detection can improve the detection of HIV-associated TB. METHODS: We performed a case-control study with sampling from a prospective study of South African HIV-infected subjects who were screened for TB prior to initiating antiretroviral therapy. Sera from all available TB cases (n = 74) and randomly selected non-TB controls (n = 30), all tested for U-LAM, sputum microscopy, GeneXpert, and cultures, were evaluated for antibodies to LAM and arabinomannan (AM). Diagnostic logistic regression models for TB were developed based on the primary test results and the additive effect of antibodies with leave-one-out cross-validation. RESULTS: Antibody responses to LAM and AM correlated strongly (p<0.0001), and IgG and IgM reactivities were significantly higher in TB than non-TB patients (p<0.0001). At 80% specificity, the target specificity for a non-sputum-based simple triage/screening test determined by major TB stakeholders, combining U-LAM with IgG detection significantly increased the sensitivity for HIV-associated TB to 92% compared to 30% for U-LAM alone (p<0.001). Sputum microscopy combined with IgG detection increased sensitivity to 88% compared to 31% for microscopy alone, and Xpert with IgG increased sensitivity to 96% and 99% compared to 57% for testing one, and 70% for testing two sputa with Xpert alone, respectively. CONCLUSION: Combining U-LAM with serum antibody detection could provide a simple low-cost method that meets the requirements for a non-sputum-based test for the screening of HIV-associated TB.

AB - BACKGROUND: Simple methods for the accurate triaging and screening of HIV-associated tuberculosis (TB) are urgently needed. We hypothesized that combining serum antibody with urine lipoarabinomannan (U-LAM) detection can improve the detection of HIV-associated TB. METHODS: We performed a case-control study with sampling from a prospective study of South African HIV-infected subjects who were screened for TB prior to initiating antiretroviral therapy. Sera from all available TB cases (n = 74) and randomly selected non-TB controls (n = 30), all tested for U-LAM, sputum microscopy, GeneXpert, and cultures, were evaluated for antibodies to LAM and arabinomannan (AM). Diagnostic logistic regression models for TB were developed based on the primary test results and the additive effect of antibodies with leave-one-out cross-validation. RESULTS: Antibody responses to LAM and AM correlated strongly (p<0.0001), and IgG and IgM reactivities were significantly higher in TB than non-TB patients (p<0.0001). At 80% specificity, the target specificity for a non-sputum-based simple triage/screening test determined by major TB stakeholders, combining U-LAM with IgG detection significantly increased the sensitivity for HIV-associated TB to 92% compared to 30% for U-LAM alone (p<0.001). Sputum microscopy combined with IgG detection increased sensitivity to 88% compared to 31% for microscopy alone, and Xpert with IgG increased sensitivity to 96% and 99% compared to 57% for testing one, and 70% for testing two sputa with Xpert alone, respectively. CONCLUSION: Combining U-LAM with serum antibody detection could provide a simple low-cost method that meets the requirements for a non-sputum-based test for the screening of HIV-associated TB.

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