Skip to main content

Advertisement

SpringerLink
Log in

Association of Serum Levels of Iron, Copper, and Zinc, and Inflammatory Markers with Bacteriological Sputum Conversion During Tuberculosis Treatment

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Iron, copper, and zinc are key micronutrients that play an important role in the immune response to Mycobacterium tuberculosis. The present study aimed to evaluate the association between serum levels of those micronutrients, inflammatory markers, and the smear and culture conversion of M. tuberculosis during 60 days of tuberculosis treatment. Seventy-five male patients with pulmonary tuberculosis (mean age, 40.0 ± 10.7 years) were evaluated at baseline and again at 30 and 60 days of tuberculosis treatment. Serum levels of iron, copper, zinc, albumin, globulin, C-reactive protein, and hemoglobin, and smear and cultures for M. tuberculosis in sputum samples were analyzed. Compared to healthy subjects, at baseline, patients with PTB had lower serum iron levels, higher copper levels and copper/zinc ratio, and similar zinc levels. During the tuberculosis treatment, no significant changes in the serum levels of iron, zinc, and copper/zinc were observed. Lower serum copper levels were associated with bacteriological conversion in tuberculosis treatment (tuberculosis-negative) at 30 days but not at 60 days (tuberculosis-positive). C-reactive protein levels and the C-reactive protein/albumin ratio were lower in tuberculosis-negative patients than in tuberculosis-positive patients at 30 and 60 days after treatment. Albumin and hemoglobin levels and the albumin/globulin ratio in patients with pulmonary tuberculosis increased during the study period, regardless of the bacteriological results. High serum globulin levels did not change among pulmonary tuberculosis patients during the study. Serum copper levels and the C-reactive protein/albumin ratio may be important parameters to evaluate the persistence of non-conversion after 60 days of tuberculosis treatment, and they may serve as predictors for relapse after successful treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. World Health Organization (WHO) (2013) Global tuberculosis control: WHO report 2013. WHO/HTM/TB/2013.11

  2. Raviglione M (2006) XDR-TB: Entering the post-antibiotic era? Int J Tuberc Lung Dis 10:1185–1187

    PubMed  Google Scholar 

  3. Hernández-Garduño E, Pérez-Guzmán C (2007) Appetite and tuberculosis: is the lack of appetite an unidentified risk factor for tuberculosis? Med Hypotheses 69:869–872

    Article  PubMed  Google Scholar 

  4. Schaible UE, Kaufmann SHE (2007) Malnutrition and infection: complex mechanisms and global impacts. PLoS Med. doi:10.1371/journal.pmed.0040115

    PubMed Central  PubMed  Google Scholar 

  5. Pakasi TA, Karyadi E, Suratih NMD, Salean M, Darmawidjaja N, Bor H, van der Velden K, Dolmans WMV, van der Meer JWM (2010) Zinc and vitamin A supplementation fails to reduce sputum conversion time in severely malnourished pulmonary tuberculosis patients in Indonesia. Nutr J. doi:10.1186/1475-2891-9-41

    PubMed Central  PubMed  Google Scholar 

  6. Rowland JL, Niederweis M (2012) Resistance mechanisms of Mycobacterium tuberculosis against phagosomal copper overload. Tuberculosis 92:202–210. doi:10.1016/j.tube.2011.12.006

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Johnson EE, Wessling-Resnick M (2012) Iron metabolism and the innate immune response to infection. Microbes Infect 14:207–216

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Neyrolles O, Mintz E, Catty P (2013) Zinc and copper toxicity in host defense against pathogens: Mycobacterium tuberculosis as a model example of an emerging paradigm. Front Cell Infect Microbiol 3:89. doi:10.3389/fcimb.2013.00089

    PubMed Central  PubMed  Google Scholar 

  9. Wells RM, Jones CM, Xi Z, Speer A, Danilchanka O, Doornbos KS, Sun P, Wu F, Tian C, Niederweis M (2013) Discovery of a siderophore export system essential for virulence of Mycobacterium tuberculosis. PLoS Pathog 9(1):e1003120. doi:10.1371/journal.ppat.1003120

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Drakesmith H, Prentice AM (2012) Hepcidin and the iron–infection axis. Science 338(6108):768–772. doi:10.1126/science.1224577

    Article  CAS  PubMed  Google Scholar 

  11. Niculescu T, Dumitru R, Burnea D (1981) Changes of copper, iron, and zinc in the serum of patients with silicosis, silicotuberculosis, and active lung tuberculosis. Environ Res 25:260–268

    Article  CAS  PubMed  Google Scholar 

  12. Onwubalili JK (1988) Malnutrition among tuberculosis patients in Harrow, England. Eur J Clin Nutr 42:363–366

    CAS  PubMed  Google Scholar 

  13. Karyadi E, Schultink W, Nelwan RH, Gross R, Amin Z, Dolmans WM, van der Meer JW, Hautvast JG, West CE (2000) Poor micronutrient status of active pulmonary tuberculosis patients in Indonesia. J Nutr 130:2953–2958

    CAS  PubMed  Google Scholar 

  14. Ciftci TU, Ciftci B, Yis Ö, Guney Y, Bilgihan A, Ogretensoy M (2003) Changes in serum selenium, copper, zinc levels and Cu/Zn ratio in patients with pulmonary tuberculosis during therapy. Biol Trace Elem Res 95:65–71

    Article  CAS  PubMed  Google Scholar 

  15. Deveci F, Ilhan N (2003) Plasma malondialdehyde and serum trace element concentrations in patients with active pulmonary tuberculosis. Biol Trace Elem Res 95:29–38

    Article  CAS  PubMed  Google Scholar 

  16. Koyanagi A, Kuffó D, Gresely L, Shenkin A, Cuevas LE (2004) Relationships between serum concentrations of C-reactive protein and micronutrients in patients with tuberculosis. Ann Trop Med Parasitol 98:391–399

    Article  CAS  PubMed  Google Scholar 

  17. Kassu A, Yabutani T, Mahmud ZH, Mohammad A, Nguyen N, Huong BT, Hailemariam G, Diro E, Ayele B, Wondmikun Y, Motonaka J, Ota F (2006) Alterations in serum levels of trace elements in tuberculosis and HIV infections. Eur J Clin Nutr 60:580–586

    Article  CAS  PubMed  Google Scholar 

  18. Cernat RI, Mihaescu T, Vornicu M, Vione D, Olariu RI, Arsene C (2011) Serum trace metal and ceruloplasmin variability in individuals treated for pulmonary tuberculosis. Int J Tuberc Lung Dis 15:1239–1245

    Article  CAS  PubMed  Google Scholar 

  19. Wang GQ (2011) Lin MY (2011) Serum trace element levels in tuberculous pleurisy. Biol Trace Elem Res 141:86–90. doi:10.1007/s12011-010-8722-1

    Article  CAS  PubMed  Google Scholar 

  20. Nagu TJ, Spiegelman D, Hertzmark E, Aboud S, Makani J, Matee MI, Fawzi W, Mugusi F (2014) Anemia at the initiation of tuberculosis therapy is associated with delayed sputum conversion among pulmonary tuberculosis patients in Dar-es-Salaam, Tanzania. PLoS ONE 18(3):e91229. doi:10.1371/journal.pone.0091229, 9

    Article  Google Scholar 

  21. Isanaka S, Aboud S, Mugusi F, Bosch RJ, Willett WC, Spiegelman D, Duggan C, Fawzi WW (2012) Iron status predicts treatment failure and mortality in tuberculosis patients: a prospective cohort study from Dar es Salaam, Tanzania. PLoS ONE 7(5):e37350. doi:10.1371/journal.pone.0037350

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Pakasi TA, Karyadi E, Suratih NM, Salean M, Darmawidjaja N, Bor H, van der Velden K, Dolmans WM, van der Meer JW (2010) Zinc and vitamin A supplementation fails to reduce sputum conversion time in severely malnourished pulmonary tuberculosis patients in Indonesia. Nutr J 28;9:41. doi: 10.1186/1475-2891-9-41

  23. Wobrauschek P (2007) Total reflection X-ray fluorescence analysis—a review. X-Ray Spectrom 36:289–300

    Article  CAS  Google Scholar 

  24. Gibson RS (2005) Principles of nutritional assessment, 2nd edn. Oxford University Press, New York, pp 245–293

    Google Scholar 

  25. World Health Organization (WHO) (1995) Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee.WHO Technical Report Series 854. World Health Organization, Geneva

    Google Scholar 

  26. Brasil. Ministério da Saúde (2005) Guia de Vigilância Epidemiológica. Ministério da Saúde: Secretaria de Vigilância Epidemiológica, Brasília

    Google Scholar 

  27. Mayfield DG, McLead G, Hall P (1974) The CAGE questionnaire validation of a new alcoholism screening instrument. Am J Psychiatry 131:1121–1123

    CAS  PubMed  Google Scholar 

  28. Bogden JD, Kemp FW, Han S, Li W, Bruening K, Denny T, Oleske JM, Lioyd J, Baker H, Perez G, Kloser P, Skurnick J, Louria DB (2000) Status of selected nutrients and progression of human immunodeficiency virus type 1 infection. Am J Clin Nutr 72:809–815

    CAS  PubMed  Google Scholar 

  29. Mohan G, Kulshreshtha S, Sharma P (2006) Zinc and copper in Indian patients of tuberculosis: impact on antitubercular therapy. Biol Trace Elem Res 111:63–69

    Article  PubMed  Google Scholar 

  30. Wolschendorf F, Ackart D, Shrestha TB, Hascall-Dove L, Nolan S, Lamichhane G, Wang Y, Bossmann SH, Basaraba RJ, Niederweis M (2011) Copper resistance is essential for virulence of Mycobacterium tuberculosis. PNAS 108:1621–1626

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. World Health Organization (WHO) (2009) Treatment of tuberculosis: guidelines. Fourth edition. WHO/HTM/TB/2009.420

  32. Gengenbacher M, Kaufmann SHE (2012) Mycobacterium tuberculosis: success through dormancy. FEMS Microbiol 36(3):514–532. doi:10.1111/j.1574-6976.2012.00331.x

    Article  CAS  Google Scholar 

  33. Connolly LE, Edelstein PH, Ramakrishnan L (2007) Why is long-term therapy required to cure tuberculosis? PLoS Med 4(3):e120. doi:10.1371/journal.pmed.0040120

    Article  PubMed Central  PubMed  Google Scholar 

  34. Taha DA, Thanoon IAJ (2010) Antioxidant status, C-reactive protein and iron status in patients with pulmonary tuberculosis. SQU Med J 10:361–369

    Google Scholar 

  35. Lounis N, Truffot-Pernot C, Grosset J, Gordeuk VR, Boelaert JR (2001) Iron and Mycobacterium tuberculosis infection. J Clin Virol 20:123–126

    Article  CAS  PubMed  Google Scholar 

  36. Wiid I, Seaman T, Hoal EG, Benade AJ, Van Helden PD (2004) Total antioxidant levels are low during active TB and rise with anti-tuberculosis therapy. IUBMB Life 56:101–106

    Article  CAS  PubMed  Google Scholar 

  37. Ghulam H, Kadri SM, Manzoor A, Waseem Q, Aatif MS, Khan GQ, Manish K (2009) Status of zinc in pulmonary tuberculosis. J Infect Dev Ctries 3:365–368

    CAS  PubMed  Google Scholar 

  38. Drain PK, Mayeza L, Bartman P, Hurtado R, Moodley P, Varghese S, Maartens G, Alvarez GG, Wilson D (2014) Diagnostic accuracy and clinical role of rapid C-reactive protein testing in HIV-infected individuals with presumed tuberculosis in South Africa. Int J Tuberc Lung Dis 18(1):20–26

    Article  CAS  PubMed  Google Scholar 

  39. Muller BL, Ramalho DM, dos Santos PF, Mesquita ED, Kritski AL, Oliveira MM (2013) Inflammatory and immunogenetic markers in correlation with pulmonary tuberculosis. J Bras Pneumol 39(6):719–727. doi:10.1590/S1806-37132013000600011

    Article  PubMed  Google Scholar 

  40. Ali W, Ahmad I, Srivastava VK, Prasad R, Kushwaha RA, Saleem M (2014) Serum zinc levels and its association with vitamin A levels among tuberculosis patients. J Nat Sci Biol Med 5(1):130–134. doi:10.4103/0976-9668.127310

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Richter C, Perenboom R, Mtoni I, Kitinya J, Chande H, Swai AB, Kazema RR, Chuwa LM (1994) Clinical features of HIV-seropositive and HIV-seronegative patients with tuberculous pleural effusion in Dar es Salaam, Tanzania. Chest 106(5):1471–1475

    Article  CAS  PubMed  Google Scholar 

  42. Nassau E, Parsons ER, Johnson GD (1976) The detection of antibodies to Mycobacterium tuberculosis by microplate enzyme-linked immunosorbent assay (ELISA). Tuberculosis 57(1):67–70

    Article  CAS  Google Scholar 

  43. Oliveira HM, Brito RC, Kritski AL, Ruffino-Netto A (2009) Epidemiological profile of hospitalized patients with TB at a referral hospital in the city of Rio de Janeiro, Brazil. J Bras Pneumol 35(8):780–787

    Article  PubMed  Google Scholar 

  44. Singla R, Srinath D, Gupta S, Visalakshi P, Khalid UK, Singla N, Gupta UA, Behera D (2009) Risk factors for new pulmonary tuberculosis patients failing treatment under the Revised National Tuberculosis Control Programme, India. Int J Tuberc Lung Dis 13:521–526

    CAS  PubMed  Google Scholar 

  45. Thorson A, Long NH, Larsson LO (2007) Chest X-ray findings in relation to gender and symptoms: a study of patients with smear positive tuberculosis in Vietnam. Scand J Infect Dis 39:33–37

    Article  PubMed  Google Scholar 

  46. Piva SG, Costa Mda C, Barreto FR, Pereira SM (2013) Prevalence of nutritional deficiency in patients with pulmonary tuberculosis. J Bras Pneumol 39(4):476–483

    Article  PubMed  Google Scholar 

  47. Harries AD, Nkhoma WA, Thompson PJ, Nyangulu DS, Wirima JJ (1988) Nutritional status in Malawian patients with pulmonary tuberculosis and response to chemotherapy. Eur J Clin Nutr 42:445–450

    CAS  PubMed  Google Scholar 

  48. Ramakrishnan K, Shenbagarathai K, Kavitha A, Uma R, Balasubramaniam P, Thirumalaikolundusubramanian R (2008) Serum zinc and albumin levels in pulmonary tuberculosis patients with and without HIV. Jpn J 61:202–204

    CAS  Google Scholar 

  49. Belo MTCT, Luiz RR, Hanson C, Selig L, Teixeira EG, Chalfoun T, Trajman A (2010) Tuberculosis and gender in a priority city in the State of Rio de Janeiro, Brazil. J Bras Pneumol 36:621–625

    Article  PubMed  Google Scholar 

  50. Wallis RS, Wang C, Doherty TM, Onyebujoh P, Vahedi M, Laang H, Olesen O, Parida S, Zumla A (2010) Biomarkers for tuberculosis disease activity, cure and relapse. Lancet Infect Dis 10:68–69

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Council of Technological and Scientific Development/Science and Technology Ministry (Process: 573548/2008-0 and Process: 478033/2009-5), and the State Foundation for Research Support of the State of Rio de Janeiro (Process: E: 26/110974/2011).

Author information

Authors and Affiliations

  1. Montreal Chest Institute, McGill University, Montreal, Quebec, Canada

    Milena Lima de Moraes

  2. Tuberculosis Research Centre, Academic Tuberculosis Program, School of Medicine, Federal University of Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco 255, Centro de Pesquisa em Tuberculose 4 andar, Ilha do Fundão. CEP 21941-913, Rio de Janeiro, RJ, Brazil

    Milena Lima de Moraes, Daniela Maria de Paula Ramalho, Karina Neves Delogo, Pryscila Fernandes Campino Miranda, Afrânio Lineu Kritski & Martha Maria de Oliveira

  3. Ary Parreiras Institute—Rio de Janeiro State Secretary of Health, Rio de Janeiro, Brazil

    Eliene Denites Duarte Mesquita

  4. Santa Maria Hospital—Rio de Janeiro State Secretary of Health, Rio de Janeiro, Brazil

    Hedi Marinho de Melo Guedes de Oliveira

  5. School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil

    Antônio Ruffino Netto

  6. Institute of Physics, Rio de Janeiro State University, Rio de Janeiro, Brazil

    Marcelino José dos Anjos

Authors
  1. Milena Lima de Moraes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniela Maria de Paula Ramalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karina Neves Delogo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pryscila Fernandes Campino Miranda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eliene Denites Duarte Mesquita
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hedi Marinho de Melo Guedes de Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Antônio Ruffino Netto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marcelino José dos Anjos
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Afrânio Lineu Kritski
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Martha Maria de Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Milena Lima de Moraes.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Moraes, M.L., Ramalho, D.M.P., Delogo, K.N. et al. Association of Serum Levels of Iron, Copper, and Zinc, and Inflammatory Markers with Bacteriological Sputum Conversion During Tuberculosis Treatment. Biol Trace Elem Res 160, 176–184 (2014). https://doi.org/10.1007/s12011-014-0046-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-014-0046-0

Keywords

Search

Navigation