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Alterations in serum levels of trace elements in tuberculosis and HIV infections

Abstract

Objective:

To evaluate serum concentrations of trace elements in tuberculosis (TB) patients with or with out human immunodeficiency virus (HIV) coinfection before and after anti-TB chemotherapy.

Subjects:

A total of 155 TB patients, 74 of which were coinfected with HIV, and 31 healthy controls from Gondar, Ethiopia.

Methods:

Serum levels of copper, zinc, selenium and iron were determined using an inductively coupled plasma mass spectrometer from all subjects at baseline and from 44 TB patients (22 with HIV coinfection) at the end of an intensive phase of anti-TB chemotherapy.

Results:

Compared with the control group, the concentrations of iron, zinc and selenium were significantly lower (P<0.05) while that of copper and copper/zinc ratio was significantly higher (P<0.05) in the serum of TB patients. TB patients with HIV coinfection had significantly lower serum zinc and selenium concentrations and significantly higher copper/zinc ratio compared to that in TB patients without HIV coinfection (P<0.05). The serum concentration of zinc had significantly increased at the end of intensive phase of anti-TB chemotherapy in patients without HIV coinfection (P<0.05). An increase in serum selenium level was observed in TB patients with or without HIV coinfection after therapy. On the contrary, serum copper concentration and copper/zinc ratio declined significantly after anti-TB chemotherapy irrespective of HIV serostatus (P<0.05).

Conclusions:

The results indicate that TB patients have altered profile of trace elements in their sera. This warrants the need for further investigations so that strategies for trace elements supplementation can be planned in addition to their potential as diagnostic parameters in monitoring responses to anti-TB chemotherapy.

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References

  • Ahmad P, Garg R, Salahuddin A (1985). Serum zinc and copper in tuberculosis. Indian J Pediatr 22, 786–788.

    CAS  Google Scholar 

  • Beck FW, Prasad AS, Kaplan J, Fitzgerald JT, Brewer GJ (1997). Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans. Am J Physiol 272, E1002–E1007.

    CAS  PubMed  Google Scholar 

  • Beck KW, Schramel P, Hedl A, Jaeger H, Kaboth W (1990). Serum trace element levels in HIV-infected subjects. Biol Trace Elem Res 25, 89–96.

    Article  CAS  Google Scholar 

  • Beisel W (1976). Trace elements in infectious processes. Med Clin North Am 60, 831–849.

    Article  CAS  Google Scholar 

  • Bogden J, Lintz D, Joselow M, Charles J, Salaki J (1977). Effect of pulmonary tuberculosis on blood concentrations of copper and zinc. Am J Clin Pathol 67, 251–256.

    Article  CAS  Google Scholar 

  • Bogden JD, Kemp FW, Han S, Li W, Bruening K, Denny T et al. (2000). Status of selected nutrients and progression of human immunodeficiency virus type 1 infection. Am J Clin Nutr 72, 809–815.

    Article  CAS  Google Scholar 

  • Burbano X, Miguez-Burbano MJ, McCollister K, Zhang G, Rodriguez A, Ruiz P et al. (2002). Impact of selenium chemopreventive clinical trial on hospital admissions of HIV infected participants. HIV Clin Trials 3, 483–491.

    Article  Google Scholar 

  • Castaldo A, Tarallo L, Palomba E, Albano F, Russo S, Zuin G et al. (1996). Iron deficiency and intestinal malabsorption in HIV disease. J Pediatr Gastroenterol Nutr 22, 359–363.

    Article  CAS  Google Scholar 

  • Ciftci TU, Ciftci B, Yis O, 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  Google Scholar 

  • Corbett EL, Watt CJ, Walker N, Maher D, Williams BG, Raviglione MC et al. (2003). The growing burden of tuberculosis. Global trends and interactions with the HIV epidemic. Arc Intern Med 163, 1009–1021.

    Article  Google Scholar 

  • Cousins RJ, Leinart AS (1988). Tissue-specific regulation of zinc metabolism and metallothionein genes by interleukin 1. FASEB J 2, 1890–2884.

    Article  Google Scholar 

  • Dallman PR (1987). Iron deficiency and the immune response. Am J Clin Nutr 46, 329–334.

    Article  CAS  Google Scholar 

  • Dobmeyer TS, Findhammer S, Dobmeyer JM, Klein SA, Raffel B, Hoelzer D et al. (1997). Ex vivo induction of apoptosis in lymphocytes is mediated by oxidative stress: role for lymphocyte loss in HIV infection. Free Radic Biol Med 22, 775–785.

    Article  CAS  Google Scholar 

  • Dworkin BM (1994). Selenium deficiency in HIV infection and the acquired immunodeficiency syndrome (AIDS). Chem Biol Interact 91, 181–186.

    Article  CAS  Google Scholar 

  • Failla ML (2003). Trace elements and host defense: recent advances and continuing challenges. J Nutr 133, 1443S–1447S.

    Article  CAS  Google Scholar 

  • Falchuk KH (1998). Disturbances in trace elements. In: Fauci AC, Braunwald E, Isselbacher KJ, Wilson JD, Martin JB, Kasper DL, Hauser SL, Longo DL (eds). Harrison's Principles of Internal Medicine. McGraw-Hill: New York. pp 489–492.

    Google Scholar 

  • Gabay C, Kushner I (1999). Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340, 448–454.

    Article  CAS  Google Scholar 

  • Graham NM, Sorensen D, Odaka N, Brookmeyer R, Chan D, Willett WC et al. (1991). Relationship of serum copper and zinc levels to HIV-1 seropositivity and progression to AIDS. J Acquir Immune Defic Syndr 4, 976–980.

    CAS  PubMed  Google Scholar 

  • Hamed SA, Abdellah MM, El-Melegy N (2004). Blood levels of trace elements, electrolytes, and oxidative stress/antioxidant systems in epileptic patients. J Pharmacol Sci 96, 465–473.

    Article  CAS  Google Scholar 

  • Hasegawa T, Inagaki K, Haraguchi H (2001). Multielement correlation analysis of major to trace elements in human blood serum for medical diagnosis as studied by ICP-AES and ICP-MS. Anal Sci 17 (Suppl), i979–i982.

    Google Scholar 

  • Hua-Dong LU, Zhi-Qiang W, Yu-Rong P, Tian-Shu Z, Xi-Zhu X, Tian-Wang K (1999). Comparison of serum Zn, Cu and Se contents between healthy people and patients in high, middle and low incidence areas of gastric cancer of Fujian Province. World J Gastroenterol 5, 84–86.

    Article  Google Scholar 

  • Jurado RI (1997). Iron, infection, and anaemia of inflammation. Clin Infect Dis 25, 888–895.

    Article  CAS  Google Scholar 

  • Kaminskaia GO, Abdullaev RIU (2002). Iron metabolism with different variants of pulmonary tuberculosis. Probl Tuberk 12, 49–51.

    Google Scholar 

  • Karakas Z, Demirel N, Tarakcioglu M, Mete N (2001). Serum zinc and copper levels in Southeastern Turkish children with giardiasis or amebiasis. Biol Trace Elem Res 84, 11–18.

    Article  CAS  Google Scholar 

  • Karyadi E, Schultink W, Nelwan RHH, Gross R, Amin Z, Dolmans WMV et al. (2000). Poor micronutrient status of active pulmonary tuberculosis patients in Indonesia. J Nutr 130, 2953–2958.

    Article  CAS  Google Scholar 

  • Karyadi E, West CE, Schultink W, Nelwan RH, Gross R, Amin Z et al. (2002). A double-blind, placebo-controlled study of vitamin A and zinc supplementation in persons with tuberculosis in Indonesia: effects on clinical response and nutritional status. Am J Clin Nutr 75, 720–727.

    Article  CAS  Google Scholar 

  • Kassu A, Mohammad A, Fujimaki Y, Moges F, Elias D, Mekonnen F et al. (2004). Serum IgE levels of tuberculosis patients in a tropical setup with high prevalence of HIV and intestinal parasitoses. Clin Exp Immunol 138, 122–127.

    Article  CAS  Google Scholar 

  • Koyanagi A, Kuffo 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  Google Scholar 

  • Kuo HW, Chen SF, Wu CC, Chen DR, Lee JH (2002). Serum and tissue trace elements in patients with breast cancer in Taiwan. Biol Trace Elem Res 89, 1–12.

    Article  CAS  Google Scholar 

  • Lawn SD, Obeng J, Acheampong JW, Grif.n GE (2000). Resolution of the acute-phase response in West African patients receiving treatment for pulmonary tuberculosis. Int J Tuberc Lung Dis 4, 340–344.

    CAS  PubMed  Google Scholar 

  • Lettow van M, Harries AD, Kumwenda JJ, Zijlstra EE, Clark TD, Taha TE et al. (2004). Micronutrient malnutrition and wasting in adults with pulmonary tuberculosis with and without HIV co-infection in Malawi. BMC Infect Dis 4, 61–68.

    Article  Google Scholar 

  • Mayordomo L, Marenco J, Gomez-Mateos J, Rejon E (2002). Pulmonary miliary tuberculosis in a patient with anti-TNF-alpha treatment. Scand J Rheumatol 31, 44–45.

    Article  Google Scholar 

  • McKenzie RC, Rafferty TS, Beckett GJ (1998). Selenium: an essential element for immune function. Immunol Today 19, 342–345.

    Article  CAS  Google Scholar 

  • Meram I, Sirmatel F, Ahi S, Tarakcioglu M (2004). Plasma copper and zinc levels in chronic viral hepatitis. Saudi Med J 25, 1066–1069.

    PubMed  Google Scholar 

  • Ministry of Health (2002a). AIDS in Ethiopia, 4th edn. Disease Prevention and Control Department, Ministry of Health: Addis Ababa, Ethiopia.

  • Ministry of Health (2002b). Manual: Tuberculosis and Leprosy Prevention and Control Programme, 2nd edn. Disease Prevention and Control Department, Ministry of Health: Addis Ababa, Ethiopia.

  • Monteiro JP, Cunha DF, da Cunha SF, dos Santos VM, Silva-Vergara ML, Correia D et al. (2000). Iron status, malnutrition and acute phase response in HIV-positive patients. Rev Soc Bras Med Trop 33, 175–180.

    Article  CAS  Google Scholar 

  • Moreno T, Artacho R, Navarro M, Perez A, Ruiz-Lopez MD (1998). Serum copper concentration in HIV-infection patients and relationships with other biochemical indices. Sci Total Environ 217, 21–26.

    Article  CAS  Google Scholar 

  • Newport MJ, Huxley CM, Huston S, Hawrylowicz CM, Oostra BA, Williamson R et al. (1996). A mutation in the interferongamma-receptor gene and susceptibility to mycobacterial infection. N Engl J Med 335, 1941–1949.

    Article  CAS  Google Scholar 

  • Niyongabo T, Henzel D, Idi M, Nimubona S, Gikoro E, Melchior JC et al. (1999a). Tuberculosis, human immunodeficiency virus infection, and malnutrition in Burundi. Nutrition 15, 289–293.

    Article  CAS  Google Scholar 

  • Niyongabo T, Henzel D, Ndayishimyie JM, Melchior JC, Ndayiragije A, Ndihokubwayo JB et al. (1999b). Nutritional status of adult inpatients in Bujumbura, Burundi (impact of HIV infection). Eur J Clin Nutr 53, 579–582.

    Article  CAS  Google Scholar 

  • Pace GW, Leaf CD (1995). The role of oxidative stress in HIV disease. Free Radic Biol Med 19, 523–528.

    Article  CAS  Google Scholar 

  • Pant K, Biswas S, Chawla R, Shah A, Singh M (1987). Zinc in active tuberculosis. Indian J Chest Dis Allied Sci 29, 144–149.

    CAS  PubMed  Google Scholar 

  • Rayman MP (2000). The importance of selenium to human health. Lancet 356, 233–241.

    Article  CAS  Google Scholar 

  • Rosas R, Poo JL, Montemayor A, Isoard F, Majluf A, Labardini J (1995). Utility of the copper/zinc ratio in patients with lymphoma or acute or chronic leukemias. Rev Invest Clin 47, 447–452.

    CAS  PubMed  Google Scholar 

  • Roy M, Kiremidjian-Schumacher L, Wishe HI (1994). Supplementation with selenium and human immune cell functions. Biol Trace Elem Res 41, 103–114.

    Article  CAS  Google Scholar 

  • Sappey C, Legrand-Poels S, Best-Belpomme M, Favier A, Rentier B, Piette J (1994). Stimulation of glutathione peroxidase activity decreases HIV type 1 activation after oxidative stress. AIDS Res Hum Retroviruses 10, 1451–1461.

    Article  CAS  Google Scholar 

  • Sauberlich H, Page JB (1997). High risk of HIV-related mortality is associated with selenium deficiency. J Acquir Immune Defic Syndr Hum Retrovirol 15, 370–374.

    Article  Google Scholar 

  • Sauberlich HE (1999). Laboratory Tests for the Assessment of Nutritional Status, 2nd edn. CRC press: Boca Raton.

    Google Scholar 

  • Schreck R, Rieber P, Baeuerie PA (1991). Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. EMBO J 10, 2247–2258.

    Article  CAS  Google Scholar 

  • Scrimshaw NS (1975). Nutrition and infection. Prog Food Nutr Sci 1, 393–420.

    CAS  PubMed  Google Scholar 

  • Scrimshaw NS, Taylor C, Gordon JE (1968). Interactions of Nutrition and Infection. World Health Organization: Geneva.

    Google Scholar 

  • Shah S, Whalen C, Kotler DP, Mayanja H, Namale A, Melikian G et al. (2001). Severity of human immunodeficiency virus infection is associated with decreased phase angle, fat mass and body cell mass in adults with pulmonary tuberculosis infection in Uganda. J Nutr 131, 2843–2847.

    Article  CAS  Google Scholar 

  • Shears P (1991). Epidemiology and infection in famine and disasters. Epidemiol Infect 107, 241–251.

    Article  CAS  Google Scholar 

  • Shenkin A (1995). Trace elements and inflammatory response: im-plications for nutritional support. Nutrition 11 (Suppl 1), 100–105.

    CAS  Google Scholar 

  • Shor-Posner G, Miguez M, Pineda L, Rodriguez A, Ruiz P, Castillo G et al. (2002). Impact of selenium status on the pathogenesis of mycobacterial disease in HIV-1 infected drug users during the era of highly active antiretroviral therapy. J Acquir Immune Defic Syndr 29, 169–173.

    Article  CAS  Google Scholar 

  • Tomkins A (2003). Assessing micronutrient status in the presence of inflammation. J Nutr 133, 1649S–1655S.

    Article  CAS  Google Scholar 

  • UNAIDS/WHO (2003). Reports on the Global AIDS epidemic. UNAIDS/WHO: Geneva, Switzerland.

  • WHO (1995). Physical status: the use and interpretation of anthropometry. Report of WHO Expert Committee. World Health Organ Tech Rep Ser 854, 1–452.

  • WHO (2003). World Health Organization, Global Tuberculosis Control: surveillance, planning, financing. WHO Report 2003, Geneva, Switzerland, WHO/CDS/TB/2003.316.

  • Yu KJ (1989). Determination and analysis of some serum trace elements of active pulmonary tuberculosis. Zhonghua Jie He He Hu Xi Za Zhi 12, 10–11.

    CAS  PubMed  Google Scholar 

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Acknowledgements

The study was financially supported by a Grant in Aid (No. 14657017) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and also partly by the University of Gondar, Ethiopia and the Sasakawa Scientific Research Grant from the Japan Science Society (No. 17–241). We thank the study participants, and staff of TB clinic and laboratory of University of Gondar Hospital without whom this study could not have been completed.

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Correspondence to F Ota.

Additional information

Guarantor: A Kassu.

Contributors: AK was responsible for the design of research and sampling, preparation of research protocol, collection of data, analyses of data, interpretation and manuscript writing. TY was involved in preparation of research protocol, in ICP-MS analyses, interpretation of results and manuscript writing. ZHM, AM, NN and BTMH were involved in preparation of research protocol, in analyses of data and manuscript writing. GH was involved in preparation of research protocol, in collection of clinical samples, in laboratory investigations and manuscript writing. ED and BA were involved in design of research, recruiting patients and controls, in clinical examination, data analyses and manuscript writing. YW was involved in preparation of research protocol, in collection of clinical samples, interpretation of results and writing of the manuscript. JM was involved in preparation of research protocol, interpretation of results and writing of the manuscript. FO was involved in design of the research, in consultation and guidance during data collection and analyses, and in writing of the manuscript.

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Kassu, A., Yabutani, T., Mahmud, Z. et al. Alterations in serum levels of trace elements in tuberculosis and HIV infections. Eur J Clin Nutr 60, 580–586 (2006). https://doi.org/10.1038/sj.ejcn.1602352

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  • DOI: https://doi.org/10.1038/sj.ejcn.1602352

Keywords

  • tuberculosis
  • HIV
  • trace elements
  • ICP-MS
  • Gondar
  • Ethiopia

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