Tuberculosis (TB), caused by *Mycobacterium tuberculosis*, is a leading infectious disease that contributes to significant morbidity and mortality, particularly in developing countries^1,2. India bears a large share of the global TB burden, accounting for one-fifth of cases and nearly 0.4 million deaths annually³. The global rise in TB cases, which began during the COVID-19 pandemic, has slowed, with 10.8 million cases reported in 2023, primarily affecting South-East Asia, Africa, and the Western Pacific regions⁴.

This data indicates the need to strengthen strategies for infection control, identification and management of TB patients, in addition to effective chemotherapy to reduce TB related morbidity and mortality. Bacilli load falls drastically in the expelled sputum soon after initiating TB treatment, containing rifampicin and isoniazid^5,6. It cuts down the chain of transmission thus, reducing the further spread of tuberculosis^7-10. While most TB patients become smear or culture negative after two to three months of DOTS therapy, approximately 10% remain culture-positive after two months, continuing the chain of transmission. Delayed smear conversion is linked to poor treatment outcomes and relapse within two years, with risk factors including cavitary lesions, high AFB load, multi-drug resistant TB, older age, diabetes, and delayed treatment initiation. These factors contribute to the persistence of infectiousness and challenges in TB management^11-12.Many of the essential trace elements like copper, zinc, magnesium influence the function of the immune system¹³.Magnesium is extremely essential for life and is present as intracellular ion in all living cells and tissues¹⁴.

Magnesium, the fourth most abundant cation in the body, plays a crucial role in enzymatic reactions, with only 0.3% of total body magnesium found in serum, which serves as a practical marker for magnesium imbalance, first identified in 1808 by Sir Humphrey Davy and later linked to muscle contractions by J. Loeb in 1900¹⁵.Studies (Jain et al., Narang et al.) have shown decreased serum magnesium levels in pulmonary tuberculosis, which improve with treatment, and this study aims to correlate the severity of the disease with serum magnesium. Magnesium plays a critical role in immune response, including T-lymphocyte and macrophage function, antibody synthesis, and immune cell activities, influencing the course of tuberculosis¹⁶. Epidemiological data suggests that higher magnesium intake is linked to a lower incidence of respiratory issues, and magnesium sulfate has been shown to improve lung function and cause vasodilation, though studies on magnesium levels in pulmonary tuberculosis are inconclusive. Changes in serum magnesium levels, such as hypermagnesemia in conditions like uncontrolled diabetes and hypomagnesemia in diseases like malabsorption and alcoholism, can lead to symptoms such as tremors, gastrointestinal disturbances, and seizures, making detection important in pulmonary tuberculosis patients^17-19. Tuberculosis and malnutrition is well recognized to go hand in hand as one can lead to the other²⁰. TB is also associated with various socioeconomic factors and often occurs in populations suffering from poverty, poor housing and economic deprivation and these are also major factors predisposing to poor nutritional status and impaired immune function^21-23.

AIM

To study the estimation of serum magnesium level in newly diagnosed pulmonary tuberculosis and its correlation with the stage of pulmonary tuberculosis and compare with controls.

The study will be conducted on patients attending the Department of Pulmonary Medicine at Sardar Patel Medical College & PBM Hospital, Bikaner. It is designed as a hospital-based case-control prospective study and will be conducted from the approval of the plan of thesis until one year or until the sample size is achieved, whichever is earlier.

The inclusion criteria for the case group are patients with a history of cough for more than two weeks, fever, weight loss, night sweats, sputum positive for acid-fast bacilli (AFB), and chest X-ray showing features of pulmonary tuberculosis. Additionally, patients who provide written informed consent and are over 15 years of age will be included in the study. The control group will consist of individuals without a history of fever, cough, weight loss, or night sweats, with sputum negative for AFB and a normal chest X-ray, and who are not on magnesium supplementation.Exclusion criteria include patients with chronic obstructive pulmonary disease (COPD) or other causes of chronic airway obstruction such as bronchial asthma, cystic fibrosis, bronchiectasis, and bronchiolitis obliterans. Patients with conditions like HIV, diabetes mellitus, or malabsorption syndromes, as well as those with serious chronic illnesses such as chronic renal failure, congestive cardiac failure, and rheumatic heart disease, will also be excluded. Furthermore, patients on medications like loop diuretics, antibiotics (e.g., amphotericin, aminoglycosides, pentamidine, gentamicin, tobramycin), digitalis, cyclosporine, or cisplatin, as well as those with known causes of hypomagnesemia such as alcoholism, renal causes (acute tubular necrosis), chronic diarrhea, vomiting, Crohn’s disease, ulcerative colitis, and Whipple’s disease, will not be included. Additionally, patients with conditions causing hypermagnesemia, such as adrenocortical insufficiency, hypothyroidism, schizophrenia, infective hepatitis, and pneumonia, will be excluded. Finally, patients who refuse to provide consent for active participation in the study will also be excluded.

Table-1: Distribution of patients according to their age group

The study found that 38% of cases were in the 41-60 years age group, with the least at 4% in the <20 years age group, and the mean age was 51.78±18.06 years for cases and 50.98±15.25 years for controls, with no statistically significant difference (p>0.05).

Graph 1: Distribution of patients according to their occurrence of chief complaintsand  Anthropometric parameters

The study found that 88% of cases had cough with expectoration for ≥2 weeks, 70% had fever for ≥2 weeks, and significant differences were observed in weight (47.68 ± 5.71 in cases vs. 64.2 ± 8.91 in controls, p<0.05), but no significant difference in height (1.64 ± 0.46 in cases vs. 1.67 ± 0.57 in controls, p>0.05).

Table-2: Distribution of patients according to their BMI

The study revealed that 76% of cases had a BMI <18.5, with a mean BMI of 17.46 ± 2.01, significantly lower than controls, who had a mean BMI of 23.22 ± 1.71 (p<0.05).

Table-3: Distribution of patients according to their laterality in chest X Ray

The majority of cases (66%) had minimal disease on chest X-ray, with 28% having moderately advanced disease and 6% far advanced disease, while all controls had normal chest X-rays, with a statistically significant difference (p<0.05).

Table-4: Distribution of patients according to their Serum Mg2+

The majority of cases (68%) had decreased serum Mg2+, with a mean serum Mg2+ of 1.46 ± 0.26, significantly lower than controls (1.86 ± 0.17), with a statistically significant difference (p<0.05).

Table-5: Association between chest Xray& serum Mg2+

The mean serum Mg2+ was highest in minimal disease (1.59 ± 0.26) and lowest in far advanced disease (1.03 ± 0.25), with a statistically significant difference (p<0.005).

In our study, maximum 38% cases were in 41-60 years group whereas minimum 4.00% were in 0-20 years age group. In control group maximum 36% were in 41-60 years group whereas minimum 4.00% were in 0-20 and >80 years age group. Mean age of cases was observed 51.78±18.06 years whereas 50.98 ± 15.25 yr in controls. The difference in both groups was statistically insignificant. (p>0.05) Similarly  NguyenTrong Hung et al. (2023)²⁴ found that Average age (year) was 51.3 ± 17.1 with min = 19; and max = 89.

In our study,  88% had cough, 70% had fever, 40% had significant weight loss, 20% had haemoptysis, 20% had breathlessness, 18% had chest pain and 16% had other complaints. In controls all patients had no complaints. The difference in both groups was statistically significant. (p<0.05) Similarly Mir MohdMujtaba Ali Baquri et al. (2022)²⁵ found that The most common symptoms among cases are fever and cough, found in all cases.

In our study, mean of weight in cases 47.68 ± 5.71 had lower than control 64.2 ± 8.91. (p<0.05) and mean height in cases 1.64 ± 0.46 and 1.67 ± 0.57 in controls. (p>0.05)

In our study, maximum 76% cases had <18.5 BMI whereas minimum 2% were in 25.0 – 29.9 BMI. In control maximum 82% were in 18.5 – 24.9 BMI whereas minimum 18% were in 25.0 – 29.0 BMI. Mean BMI in cases 17.46 ± 2.01 had lower BMI than controls 23.22 ± 1.71. (p<0.05) 

The severity of PTB was determined by classification by National Tuberculosis and Respiratory Disease Association, America, after Postero-Anterior view Chest xray⁶.

In our study, majority 66% had minimal disease followed by moderately advanced disease in 28% whereas 6% had far advanced disease. In control group all cases had normal chest Xray. The difference in both groups was statistically significant. (p<0.05) Similarly Mir MohdMujtaba Ali Baquri et al. (2022)²⁵ found that Among 30 PTB cases, 15 are in Minimal disease group(50%), 8 are in moderately advanced group (26%) and 7 are in Far advanced disease group (24%).

In our study, majority 68% cases had decreased serum Mg2+ whereas 4% had serum Mg2+ in controls. Mean Serum Mg2+ in cases 1.46 ± 0.26 had lower serum Mg2+ than controls 1.86 ± 0.17. The difference in both groups was statistically significant. (p<0.05) Similarly Mir MohdMujtaba Ali Baquri et al. (2022)²⁵found that Serum Magnesium was decreased in 29 cases while in controls it was normal in all controls. The variation being statistically significant (P<0.05)

 Serum magnesium level was significantly lower in sputum positive PTB as compared to sputum negative PTB and controls (p-value <0.05) though not in hypomagnesemic range. In the present study, serum magnesium level were similar to study conducted by Jain MK et al.²⁶

In our study, In grade 1 majority mean serum Mg2+ was 1.59 ± 0.26, was higher than 1.24 ± 0.25 grade 2 whereas 1.03 ± 0.25 in grade 3. The difference was found to be statistically significant. (p<0.005) Similarly Mir MohdMujtaba Ali Baquri et al. (2022)²⁵ found that the mean Serum Magnesium is 1.68±0.11 in Minimal disease, 1.43±0.05 in Moderately advanced disease and 1.14±0.10 in Far advanced disease. The variation of serum Magnesium in different severity of the disease is statistically significant (P<0.05).The mean serum Magnesium decreases as the severity of disease increases.

Our study showed that the mean serum magnesium levels were significantly lower in cavitary type than the non-cavitary type i.e., minimal disease and moderately and far advanced diseases. Our results are consistent with the findings of Jain et al,94 where 40 cases of pulmonary tuberculosis studied and found that cases with cavitary lesions had a lower magnesium level than non-cavitary lesion. This could be explained as the amount of lung destruction increases from no cavity through small cavity to medium or large cavity, the serum magnesium value falls significantly.

The study observed that a significant inverse relationship was observed between the level of serum magnesium with extent of the disease. Thus, serum magnesium was found to, be a reasonable indicator of severity of pulmonary tuberculosis. There is also a need to consider magnesium supplementation in the diet of tuberculosis patients.

1. Tuberculosis: a global emergency. World Health Forum. 1993;14(4):438.
2. 2)World Health Organization (WHO).Global Tuberculosis Report 2012. Geneva: World Health Organization;2012. Available at: http://www.who.int/iris/bitstream/ 10665/75938/1/9789241564502_eng.pdf, [accessed on 9th October 2016]
3. Das B, Prasanna C, Thimmaraju KV, Sumeru S, Raju SM. Study of serum magnesium values in pulmonary tuberculosis patients. Jour Adv Res Med Sci. 2012;4(1):54-57.
4. Lobe J ; Am J Phjsio1; 3:383,1900,Cited in M.B.J.4,373,1973.
5. World Health Organization 2.2 TB Mortality. [(accessed on 20 November 2023)]. Availableonline:https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022/tb-disease-burden/2-2-tb-mortality.
6. Rouillon A, Perdrizet S, Parrot R. Transmission of tubercle bacilli: The effects of chemotherapy. Tubercle. 1976;57(4):275–99.
7. Jindani A, Dore´ CJ, Mitchison DA. Bactericidal and sterilizing activities of antituberculosis drugs during the first 14 days. Am J RespCrit Care Med. 2003;67(10):1348–54.
8. Fitzwater SP, Caviedes L, Gilman RH, Coronel J, LaChira D, Salazar C, et al. Prolonged infectiousness of tuberculosis patients in a directly observed therapy shortcourse program with standardized therapy. Clin Infect Dis. 2010;51(4):371-78.
9. Fortún J, Martín-Dávila P, Molina A, Navas E, Hermida JM, Cobo J, et al. Sputum conversion among patients with pulmonary tuberculosis: are there implications for removal of respiratory isolation? J AntimicrobChemother. 2007;59(4):794-98.
10. Long R, Bochar K, Chomyc S, Talbot J, Barrie J, Kunimoto D, et al. Relative versus absolute non-contagiousness of respiratory tuberculosis on treatment. Infect Control HospEpidemiol. 2003;24(11):831-38.
11. ChienJY, Chen YT, Shu CC, Lee JJ, Wang JY, Yu CJ, et al. Outcome correlation of smear-positivity for acid-fast bacilli at the fifth month of treatment in nonmultidrug-resistant TB. Chest. 2013;143(6):1725-32.
12. Tiwari S, Kumar A, Kapoor SK. Relationship between sputum smear grading and smear conversion rate and treatment outcome in the patients of pulmonary tuberculosis undergoing dots–a prospective cohort study. Indian J Tuberc. 2012;59(3):135–40.
13. Güler M, Unsal E, Dursun B, Aydln O, Capan N. Factors influencing sputum smear and culture conversion time among patients with new case pulmonary tuberculosis. Int J ClinPract. 2007;61(2):231–35.
14. Senkoro M, Mfinanga SG, Morkve O. Smear microscopy and culture conversion rates among smear positive pulmonary tuberculosis patients by HIV status in Dar es Salaam, Tanzania. BMC infectious diseases. 2010;10:210.
15. Magnesium (Mg) Chemical Element; Available from https://www.britannica.com/science/magnesium
16. Chandra RK, Puri S. Trace element modulation of immune responses and susceptibility to infection. In Trace elements in nutrition in children. New York: Vevey/Raven Press 1987.p.87-105.
17. Whang R. Magnesium deficiency: pathogenesis, prevalence and clinical implications. The American journal of medicine. 1987 Mar 20;82(3):24-9.
18. Randall et al.; Magnesium deficiency in man. Ann IUnt Med, 1959;26:317-333.
19. 19)Macallan DC. Malnutrition in tuberculosis. Diagnostic microbiology and infectious disease. 1999 Junn 30;34(2):153-7.
20. Cegielski JP, McMurray DN. The relationship between malnutrition and tuberculosis : evidence from studies in humans and experimental animals. The international journal of tuberculosis and lung disease.2004 Mar 1; 8 (3):286-98.
21. Leung CC, Yew WW, Tam CM, Chan CK, Chang KC, Law WS, Wong MY, Au KF. Socio-economic factors and tuberculosis: a district- based ecological analysis in HaongKong. The International Journal of Tuberculosis and Lung Disease. 2004 Aug1; 8(8): 958-64.
22. Das B, Prasanna C, Thimmaraju KV, Sumeru S, Raju SM. Study of serum magnesium values in pulmonary tuberculosis patients Jour Adv Res Med Sci. 2012;4(1):54-57.[ Google Scholar]
23. Irfan et al.,Sch.J.App.Med.Sci.,Mar 2017;5(3F):1131-1136[The inverse correlation of serum Magnesium level with the stage of Pulmonary Tuberculosis.]
24. Nguyen TH, Nguyen THN, Le Xuan H, Nguyen PT, Nguyen KC, Le Thi TN. Nutritional status and dietary intake before hospital admission of pulmonary tuberculosis patients. AIMS Public Health. 2023 May 23;10(2):443-455. doi: 10.3934/publichealth.2023031. PMID: 37304581; PMCID: PMC10251045
25. Mohamad et al: The case control study of serum magnesium level in pulmonary tuberculosis and its correlation with the stage of Pulmonary Tuberculosis; Jul- Dec 2022, volume 11, Issue 2.
26. K. JAIN, S.K. KHANIJO, R.D.CHANDE, G.C. JAIN AND B.N. BISARYA; September 1984. Journal of the Association of Physicians of India 32(8): 725-7 [ Serum magnesium in pulmonary tuberculosis]