Skip to main content
  • Original article
  • Open access
  • Published:

Evaluation of lipoarabinomannan in the diagnosis of tuberculosis

Abstract

Background

The detection of lipoarabinomannan (LAM) antigens in body fluids has several potential advantages compared with the diagnostic methods used currently.

Aim

The aim of this study was to evaluate the possible role of the detection of LAM in the serum and the urine as a diagnostic aid in the diagnosis of different forms of tuberculosis (TB).

Patients and methods

This study included 62 newly confirmed tuberculosis cases classified into two groups: group A included patients with pulmonary TB (n=36), and was further divided into two groups: group A1 [the smear-positive pulmonary TB group (n=24)] and group A2 [the smearnegative pulmonary TB group (n=12)]; group B included the extrapulmonary TB group (n=26); and 10 apparently healthy individuals served as the control group. The LAM level was measured in the serum and the urine by an enzyme-linked immunosorbant assay.

Results

The mean level of quantitative serum LAM was higher in group A1 (0.55±0.20?ng/ml) compared with group A2 (0.44±0.30?ng/ml) or group B (0.41±0.27?ng/ml). The mean level of quantitative urine LAM was higher in group A1 (0.81±0.24?ng/ml) compared with group B (0.72±0.35?ng/ml) and group A2 (0.65±0.37?ng/ml; P<0.001). The quantitative urine LAM test correlated positively with the degree of bacillary burden (P<0.05). Quantitative serum LAM had a sensitivity of 88.7%, specificity 90%, accuracy 88.9%, positive predictive value 98.2%, and negative predictive value 56.3%. Quantitative urine LAM had a sensitivity of 85.5%, specificity 90%, accuracy 86.1%, positive predictive value 98.1%, and negative predictive value 50%. A combination of serum and urine LAM tests identified that 98.4% of the cases with a positive TB culture correlated with higher serum LAM levels. Advanced chest radiography involvement and TB culture correlated with higher urine LAM levels (P<0.05).

Conclusion

The LAM test is a valuable addition in the diagnosis of TB and its different forms. A combination of quantitative serum and urine LAM increased the sensitivity of the test. The quantitative urine LAM test offers additional clinical insight into the degree of TB disease severity and has more applicability.

References

  1. World Health Organization (WHO). Global tuberculosis report (WHO/ HTM/TB/ 2015. 22); 2015. Available at: http://www.who.int/tb/ publications/global_report/gtbr15_main_text.pdf?ua=1. [Accessed 2016 Jan 10].

  2. Dorman SE. New diagnostic tests for tuberculosis: bench, bedside, and beyond. Clin Infect Dis 2010; 50(Suppl 3):S173–S177.

    Article  Google Scholar 

  3. Minion J, Leung E, Talbot E, Dheda K, Pai M, Menzies D. Diagnosing tuberculosis with urine lipoarabinomannan: systematic review and metaanalysis. Eur Respir J 2011; 38:1398–1405.

    Article  CAS  Google Scholar 

  4. Hamasur B, Bruchfeld J, Haile M, Pawlowski A, Bjorvatn B, Källenius G, Svenson SB Rapid diagnosis of tuberculosis by detection of mycobacterial lipoarabinomannan in urine. J Microbiol Methods 2001; 45:41–52.

    Article  CAS  Google Scholar 

  5. Boehme C, Molokova E, Minja F, Geis S, Loscher T, Maboko L, et al. Detection of mycobacterial lipoarabinomannan with an antigen-capture ELISA in unprocessed urine of Tanzanian patients with suspected tuberculosis. Trans R Soc Trop Med Hyg 2005; 99:893–900.

    Article  CAS  Google Scholar 

  6. Daley P, Michael JS, Hmar P, Latha A, Chordia P, Mathai D, et al. Blinded evaluation of commercial urinary lipoarabinomannan for active tuberculosis: a pilot study. Int J Tuberc Lung Dis 2009; 13:989–995.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Lawn SD, Edwards DJ, Kranzer K, Vogt M, Bekker LG, Wood R. Urine lipoarabinomannan assay for tuberculosis screening before antiretroviral therapy diagnostic yield and association with immune reconstitution disease. AIDS 2009; 23:1875–1880.

    Article  Google Scholar 

  8. Mutetwa R, Boehme C, Dimairo M, Bandason T, Munyati SS, Mangwanya D, et al. Diagnostic accuracy of commercial urinary lipoarabinomannan detection in African tuberculosis suspects and patients. Int J Tuberc Lung Dis 2009; 13:1253–1259.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Reither K, Saathoff E, Jung J, Minja LT, Kroidl I, Saad E, et al. Low sensitivity of a urine LAM-ELISA in the diagnosis of pulmonary tuberculosis. BMC Infect Dis 2009; 9:141.

    Article  Google Scholar 

  10. Dheda K, Davids V, Lenders L, Roberts T, Meldau R, Ling D, et al. Clinical utility of a commercial LAM-ELISA assay for TB diagnosis in HIV-infected patients using urine and sputum samples. PLoS One 2010; 5:e 9848.

    Article  Google Scholar 

  11. Shah M, Martinson NA, Chaisson RE, Martin DJ, Variava E, Dorman SE. Quantitative analysis of urine based assay for detection of lipoarabinomannan in patients with tuberculosis. J Clin Microbiol 2010; 48:2972–2974.

    Article  Google Scholar 

  12. Lawn SD. Serological diagnostic assays for HIV-associated tuberculosis in sub-Saharan Africa? Clin Vaccine Immunol 2014; 21:787–790.

    Article  Google Scholar 

  13. Kerkhoff AD, Wood R, Vogt M, Lawn SD. Prognostic value of a quantitative analysis of lipoarabinomannan in urine from patients with HIV-associated tuberculosis. PLoS One 2014; 9:e103285.

    Article  Google Scholar 

  14. Shah M, Variava E, Holmes CB, Coppin A, Golub JE, McCallum J, et al. Diagnostic accuracy of a urine lipoarabinomannan test for tuberculosis in hospitalized patients in a high HIV prevalence setting. J Acquir Immune Defic Syndr 2009; 52:145–151.

    Article  Google Scholar 

  15. Peter J, Green C, Hoelscher M, Mwaba P, Zumla A, Dheda K. Urine for the diagnosis of tuberculosis: current approaches, clinical applicability, and new developments. Curr Opin Pulm Med 2010; 16:262–270.

    Article  Google Scholar 

  16. National Tuberculosis Program Egypt (NTP). Programmatic management guidelines; 2012. Available at: http://www.ntp.mohealth.gov.eg/. [Accessed 2015 Dec 14].

  17. Abd el-Atty HE, Mohamad Bakr R, El-Helbawy R, Fathyaddass H, Elkalashy MM. The value of serum lipoarabinomannan in the diagnosis of pulmonary tuberculosis. Menoufia Med J 2015; 27:733–739.

    Google Scholar 

  18. Agha MA, El-Helbawy RH, El-Helbawy NG, El-Sheak NM. Utility of quantitative analysis of urine lipoarabinomannan in the diagnosis of tuberculosis. Egypt J Chest DisTuberc 2013; 62:401–407.

    Article  Google Scholar 

  19. Diagnostic Standards and Classification of Tuberculosis in Adults and Children. This official statement of the American Thoracic Society and the Centers for Disease Control and Prevention was adopted by the ATS Board of Directors, July 1999. This statement was endorsed by the Council of the Infectious Disease Society of America, September 1999. Am J Respir Crit Care Med 2000; 161(Pt 1):1376–1395.

  20. Lawn SD. Point-of-care detection of lipoarabinomannan (LAM) in urine for diagnosis of HIV-associated tuberculosis: a state of the art review. BMC Infect Dis 2012; 12:103.

    Article  Google Scholar 

  21. Sada E, Aguilar D, Torres M, Herrera T. Detection of lipoarabinomannan as a diagnostic test for tuberculosis. J Clin Microbiol 1992; 30:2415–2418.

    Article  CAS  Google Scholar 

  22. Mukundan H, Kumar S, Price DN, Ray SM, Lee YJ, Min S, et al. Rapid detection of Mycobacterium tuberculosis biomarkers in a sandwich immunoassay format using a waveguide-based optical biosensor. Tuberculosis (Edinb) 2012; 92:407–416. vcnb, smbvn, kdnb, m.

    Article  CAS  Google Scholar 

  23. Tessema TA, Hamasur B, Bjun G, Svenson S, Bjorvatn B. Diagnostic evaluation of urinary lipoarabinomannan at an Ethiopian tuberculosis centre. Scand J Infect Dis 2001; 33:279–284.

    Article  CAS  Google Scholar 

  24. Lawn SD, Kerkhoff AD, Vogt M, Wood R. Diagnostic accuracy of a lowcost, urine antigen, point-of-care screening assay for HIV-associated pulmonary tuberculosis before antiretroviral therapy: a descriptive study. Lancet Infect Dis 2012; 12:201–209.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hany H. Moussa MD.

Additional information

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Youssef, A.A., Kamel, M.H., Eissa, H.A. et al. Evaluation of lipoarabinomannan in the diagnosis of tuberculosis. Egypt J Bronchol 10, 291–300 (2016). https://doi.org/10.4103/1687-8426.193639

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.4103/1687-8426.193639

Keywords