|Year : 2010 | Volume
| Issue : 2 | Page : 45-48
|Status of zinc in pulmonary tuberculosis
Waseem Qureshi1, G Hassan2, SM Kadri3, MS Aatif2, GQ Khan2, Manzoor Ahmad2, Manish Kak2
1 Medical Superintendent, SMHS Hospital, Srinagar, Kashmir, India
2 Department of Medicine, Government Medical College, Srinagar, Kashmir, India
3 Regional Institute of Health and Family Welfare (RIHFW), Directorate of Health Services, Srinagar, Kashmir, India
Click here for correspondence address and email
|Date of Web Publication||1-Mar-2011|
| Abstract|| |
This prospective study including 50 patients of pulmonary tuberculosis (TB) and 30 subjects as the control group was conducted to study the status of zinc as a micronutrient in pulmonary TB. There was a statistically significant fall in serum zinc levels with advanced age and disease and the levels improved after institution of antitubercular therapy. We conclude that estimation of serum zinc levels is an important tool in the diagnosis, monitoring of response to treatment in pulmonary TB, and booster of the immunological mechanisms if instituted in the therapy.
Keywords: Antitubercular therapy, pulmonary tuberculosis, zinc
|How to cite this article:|
Qureshi W, Hassan G, Kadri S M, Aatif M S, Khan G Q, Ahmad M, Kak M. Status of zinc in pulmonary tuberculosis. Ann Trop Med Public Health 2010;3:45-8
|How to cite this URL:|
Qureshi W, Hassan G, Kadri S M, Aatif M S, Khan G Q, Ahmad M, Kak M. Status of zinc in pulmonary tuberculosis. Ann Trop Med Public Health [serial online] 2010 [cited 2020 Feb 19];3:45-8. Available from: http://www.atmph.org/text.asp?2010/3/2/45/77179
| Introduction|| |
Tuberculosis (TB) is as old as the mankind. World Health Organization (WHO) in 1993 declared it as a global emergency with respect to the reemerging menace of TB. Nearly one-third of the world's population is infected by Mycobacterium tuberculosis, the causative organism of TB. ,,,
The American Thoracic Society has estimated that the current TB morbidity and mortality ranges from a prevalence of 10-30 million cases of active disease to an incidence of 3.7-10 million new cases and 1-2 million deaths annually. , The Centre of Disease control (CDC) predicts that TB will claim 30 million lives in the current decade.  It is again estimated that between 2002 and 2020, approximately 1000 million people will be newly infected, over 150 million will get sick and 36 million will die of TB if proper control measures are not instituted.  In India, around 4.8 million people are suffering from TB infection, of whom 2.2 million are smear positive; annual risk of infection is 1-2% and case fatality rate is 24%. 
Malnutrition is frequently observed in patients with pulmonary TB, but their nutritional status, especially of micronutrients, is still poorly documented.  Among the micronutrients, zinc is essential for human growth, development and immune function, and deficiency of this micronutrient impairs overall immune function and resistance to infection.  Several studies have demonstrated that the serum levels of zinc decrease significantly during active TB and increase following recovery after institution of antitubercular therapy (ATT) and improvement of nutritional status. ,,,,,, In fact, vitamin A and zinc supplementation improves the effect of TB medication after 2 months of ATT and results in earlier sputum smear conversion. Estimation of serum zinc levels during the course of TB could be used as a valuable tool for the clinicians to assess response to therapy or effectiveness of the ongoing ATT. , Even zinc has been documented to increase the PPD induration size in children, irrespective of nutritional status. 
The objective of the present study was to assess the status of serum zinc levels in patients of pulmonary TB in Kashmir valley of India.
| Material and Methods|| |
The study included 50 patients of pulmonary TB and 30 subjects of age- and sex-matched healthy people as the control group and was conducted in the department of Government Medical College, Srinagar, Kashmir, India. The patients of pulmonary TB were diagnosed on the basis of history, clinical examination, chest radiography, sputum examination, Montoux test and related laboratory parameters.
Since serum zinc levels are affected by many physiological and pathological states and drugs, subjects with these states were excluded. The exclusion criteria included the following:
Parameters like age, sex, body weight, height, body mass index in addition to nutrition details, were recorded in the proforma of every subject of study. Patients were placed in three stages on the basis of chest radiography according to the guidelines of National Tuberculosis Association of USA , as follows.
- pregnant women,
- women on oral contraceptives,
- patients with
- chronic liver disease,
- nontuberculous pulmonary infections,
- extrapulmonary TB,
- indolent ulcers,
- chronic renal failure,
- myocardial infarction,
- metastatic carcinoma,
- nephrotic syndrome,
- malabsorption syndrome,
- cystic fibrosis and
- patients taking zinc as medication.
Stage 1 (minimal)
Lesions which are of slight to moderate density but do not contain demonstrable cavitation. They may involve a small part of one or both lungs, but the total extent, regardless of distribution, should not exceed the volume of lung on one side which is present above the second chondrosternal junction and spine of the 4 th or the body of 5 th thoracic vertebra.
Stage 2 (moderately advanced)
Lesions may be present in one or both lungs, but the total extent should not exceed the following limits: disseminated lesions of slight to moderate density which may extend throughout the total volume of one lung or equivalent in both the lungs; dense and confluent lesions which are limited in extent to one-third the volume of one lung; total diameter of cavitation, if present, must be less than 4 cm.
Stage 3 (far advanced)
Lesions more extensive than "moderately advanced" - The serum zinc levels of the selected patients were estimated before, during and after the completion of ATT. Blood samples from the cases and controls were collected in fasting state via venipuncture to determine total white blood cell count, hematocrit, erythrocyte sedimentation rate (ESR), and various other biochemical parameters. All biochemical tests were carried out on the same day, in accordance with the study of Karyadi et al.
The samples for serum zinc estimation were collected in zinc free plastic syringes and the blood was allowed to clot in acid cleaned glass test tubes and stored at 16°C until collection was completed. The estimation of zinc level was done using atomic absorption spectrophotometery method and the readings were recorded in proforma.
The data were analyzed by using paired students "t" test (95% confidence limits) and chi-square tests, where appropriate. P value of less than 0.05 was considered significant.
| Results|| |
Of the 50 cases of pulmonary TB, 23 (46%) cases were in the age group of 30-39 years, 12 (24%) cases in the age group of 40-49 years, 8 (16%) cases were of 50-65 years and 7 (14%) were of 20-29 years. The mean age was 38.4 ± 15.38 (mean ± SD) years. Among the controls, the age ranged from 20 to 55 years with mean of 36 ± 4.2 years. Twenty-one (42%) patients of pulmonary TB and 13 (43.3%) controls were females with age ranging from 23 to 51 years (mean 31 ± 2.3).The serum zinc levels revealed an inverse relationship with age in both the groups, i.e., the levels on average were observed lower with the advancement in age [Table 1]. Such a discrepancy in either of the groups was statistically highly significant. Moreover, when the groups were compared to each other, the pulmonary TB group revealed a significant fall in the zinc levels in contrast to the control group. Overall, the pulmonary TB group prior to therapy showed a significant fall (P value <0.05) in average serum zinc levels in contrast to the control group. In the study group of pulmonary TB, there was progressive fall in the serum zinc level with maximum decrease in the stage 3, which was statistically highly significant. After second month of institution of the ATT and within 2 months after completion of treatment of TB, there was again a significant increase in the serum zinc levels [Table 2]. However, no statistical significance was observed with the serum zinc levels and the sex, body weight and body mass index in either cases or controls.
|Table 1: Serum zinc levels in cases and controls before institution of antitubercular therapy in the study group, as per the age distribution|
Click here to view
|Table 2: Serum zinc levels in relation to stage of pulmonary tuberculosis prior to, during and after the antitubercular therapy|
Click here to view
| Discussion|| |
The study demonstrated diminished serum zinc levels in advanced age and progressed pulmonary TB. Although the literature regarding this is sparse, similar results have been documented in previous studies. ,,,,,,, In India, Ray  and co-workers studied the plasma zinc status of 50 children with TB and compared the observations with 10 healthy and 10 malnourished children without TB at 0, 1, 2, 3 and 6 months of the ATT. The children with TB had significantly lower plasma zinc level than those without the disease, irrespective of the nutritional status. Our results are in agreement with another study from India by Taneja  who found significantly low zinc levels in cases of pulmonary TB. Similarly, Karyadi and the co-authors from Indonesia studied the nutritional status of patients with active pulmonary TB and compared the values with those of healthy controls. The authors found poor nutritional status and significantly low serum zinc levels in TB patients compared to controls. Contrary to previous studies and the present one, Ciftci et al. from Turkey, after studying 22 pulmonary TB patients and 18 healthy subjects, found an increase in the levels of zinc and decrease in Cu/Zn ration. However, the mechanism of this increase in zinc levels was not explained. The possible mechanisms for the lowered zinc levels in cases of pulmonary TB include redistribution of zinc from plasma to other tissues,  reduction of hepatic production of zinc carrier protein X 2 macroglobulin and a rise in the production of metallothionein, a protein that transports zinc to liver.  Rankovic and Drdevic  studied zinc levels in serum and pleural effusion in 104 patients and found higher zinc levels in effusion due to TB compared to that in the serum, and concluded that zinc concentration in the effusion and serum higher than 1.0 reliably indicates the presence of TB pleurisy signifying the diagnostic value of zinc in TB. Again Cuevas  and co-workers in UK studied the effect of zinc on the tuberculin response of 98 children exposed to adults with smear positive TB. They found higher proportion of children as PPD positive in the zinc supplemented group (57.1%) than in placebo group (53.1%). It is postulated that zinc supplementation could work by correcting asymptomatic or marginal zinc deficiencies or as a nonspecific booster of immunity irrespective of zinc deficiency. Overall, the studies conclude that zinc supplementation improves the effect of TB medication after 2 months of ATT, results in earlier sputum smear conversion, and serves as a booster of immunologic process, , and estimation of the zinc levels could be used as a valuable laboratory tool to assess to therapy or the effectiveness of the ongoing ATT. , We suggest that in view of the poor nutritional status in patients of pulmonary TB, zinc supplementation be made a mandatory constituent of the treatment protocol.
| References|| |
|1.||World Health Organisation. Tuberculosis fact sheet. World Health Organisation Tuberculosis site (cited 2002 sept 15) Available from www.who.int/gtb/publications/factsheet/index.htm |
|2.||World Health Organisation. Treatment of Tuberculosis: Guidelines for National Programmes, Geneva; 2003. |
|3.||Amarpurkar D. Abdominal Tuberculosis in India. In: Das S, Goenka RK, Panda JK, editors. Medicine update Association of Physicians of India. 2003. p. 108-11. |
|4.||Sharma SK, Mohan A. Multidrug Resistant Tuberculosis: Current Trends. In: Das S, Goenka RK, Panda JK, editor. India: Medicine update Association of Physicians of India; 2003. p. 131-5. |
|5.||ATS Confrence on Tuberculosis Research. Future research in tuberculosis. Am Rev Respir Dis 1988;138:1327-9. |
|6.||Shakar PS. Epidemiology. Principles and Mangement of Tuberculosis. 3 rd ed. New Delhi: B.I. Churchill Livingstone; 2002. p. 17-27. |
|7.||Grange JM, Zumla A. The global emergency of tuberculosis: What is the cause? J R Soc Health 2002;122:78-81. |
|8.||Karyadi E,Schultink W, Nelwan RH, Gross R, Amin Z, Dolmans WM, et al. Poor Micronutrient Status of Active Pulmonar Tuberculosis patients in Indonesia. J Nutrition 2000;130:2953-8. |
|9.||Walker CF, Black RE. Zinc and the risk for infectious disease. Annu Rev Nutr 2004;24:255-75. |
|10.||Koyanagi A, Kullo D, Gresley L, Shenkin A, Cuevas LE. Relationships between serum concentrations of C -reactive protein and micronutrients in patients with tuberculosis. Ann Trop Med Parasitol 2004;98:391-400. |
|11.||Wiid T, Seaman T, Hoal EG, Benade AJ, Van Helden PD. Total antioxidant levels are low during active TB and rise with anti-tuberculosis therapy. IUBMB Life 2004;56:101-6. |
|12.||Karyadi E, West CE, Schultink W, Nelwan RH, Gross R, Amin Z, et al. 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 2002;75:720-7. |
|13.||Deveci F, Ilhan N. Plasma malondialdehyde and serum trace element concentrations in patients with active pulmonary tuberculosis. Biol Trace Elem Res 2003;95:29-38. |
|14.||Lin X, Ding L, Wang Y, Yang Y. Determination of trace elements in serum of tuberculosis patients. Wei Sheng Yan Jiu 2000;29:395-6. |
|15.||Milano A, Branzoni M, Canneva F, Profumo A, Riccardi G. The Mycobacterium tuberculosis Rv2358-furB operon is induced by zinc. Res Microbiol 2004;155:192-200. |
|16.||Ray M, Kumar L, Prasad R. Plasma zinc status in Indian childhood tuberculosis: Impact of antituberculosis therapy. Int J Tuberc Lung Dis 1998;2:719-25. |
|17.||Cuevas LE, Almeida LM, Mazunder P, Paixao AC, Silva AM, Maciel L, et al. Effect of zinc on the tuberculin response of children exposed to adults with smear-positive tuberculosis. Ann Trop Paediatr 2002;22:313-22. |
|18.||Clinical Features of Tuberculosis. In: Seaton A, Seaton D, Leitch AG, editors. Crofton and Douglas′s Respiratory Diseases. 4 th ed. London: Blackwell Scientific Publications; 1989. p. 395-422. |
|19.||Bchera D. Tuberculosis. In: Bchera D, editor. Text book of Pulmonary Medicine. 1 st ed. New Delhi: Jaypee Brothers; 1995. p. 233-86. |
|20.||Taneja DP. Obervations on serum zinc in patients of pulmonary tuberculosis. J Indian Med Assoc 1990;88:280-281 |
|21.||Ciftci TU, Ciftci B, Yis O, Guney Y, Bilgihan A, Ogretensoy M. Changes in serum selenium, copper, zinc levels and cu/zn ratio in patients with pulmonary tuberculosis during therapy. Biol Trace Elem Res 2003;95:65-71. |
|22.||Filteau SM, Tomkins AM. Micronutrients and tropical injections. Travs R Soc Trop Med Hyg 1994;88:1-3. |
|23.||Gabay C, Kushner I. Acute phase protein and other systemic responses to inflammation. N Engl J Med 1999;340:448-54. |
|24.||Rankovic B, Dordevic R. Diagnostic importance of zinc in the etiologic determination of pleural effusions. Vojnosanit Pregl 2002;59:385-92. |
Medical Superintendent, PO Box 1143, GPO, Srinagar 190001, Kashmir
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2]
| Article Access Statistics|
| Viewed||3328 |
| Printed||173 |
| Emailed||5 |
| PDF Downloaded||11 |
| Comments ||[Add] |