Tuberculosis (TB) remains one of the most significant global public health challenges, claiming millions of lives annually despite advancements in diagnostic methods, treatment regimens, and preventive strategies [1]. Mortality due to TB remains unacceptably high, with over 1.6 million deaths globally in the year 2022[2]. This underscores the enduring challenge posed by TB in achieving the United Nations Sustainable Development Goals (SDGs) and the WHO’s End TB Strategy.

India bears the highest burden of TB cases worldwide, accounting for nearly a quarter of the global TB burden[2]. In 2022, the National TB Elimination Program (NTEP) in India recorded a historic high of 24.2 lakh notified TB cases, with a case notification rate of approximately 172 cases per lakh population. Furthermore, the rise in drug-resistant forms of TB, such as multi-drug-resistant (MDR) and extensively drug-resistant (XDR) TB, has added complexity to the management of the disease. Several critical challenges hinder TB management, demanding innovative and integrative strategies[3,4]. Over the past decade, the global burden of TB has remained substantial, with a resurgence in incidence in recent years. This rise is attributed to factors such as: Limited access to diagnostic facilities and delayed identification of cases, especially in resource-limited settings, allow TB to spread unchecked.

India, which shoulders the world's highest TB burden, exemplifies this challenge. Despite achieving record-high case notifications in recent years, gaps in early detection, treatment adherence, and preventive measures persist, perpetuating the disease cycle. The emergence of drug-resistant TB strains has exacerbated the global TB crisis. Multi-drug-resistant TB (MDR-TB), defined as resistance to isoniazid and rifampicin, and extensively drug-resistant TB (XDR-TB), which includes resistance to additional classes of TB drugs, represent formidable challenges to TB control[5]. The prevalence of these forms of TB is driven by: Poor adherence to treatment regimens and suboptimal healthcare infrastructure often lead to drug resistance. Individuals with drug-resistant TB can transmit these strains directly, further complicating control efforts[6]. Treating drug-resistant TB requires prolonged, expensive, and often toxic regimens, with limited success rates. This not only increases the healthcare burden but also exacerbates patient morbidity and mortality [7].

A single centre, hospital-based, 1:1, comparative, cross-sectional observational study conducted to evaluate Vitamin D levels in newly diagnosed tuberculosis (TB) patients in Central India. Participants were enrolled from outpatient and inpatient departments of Respiratory Medicine, based on the inclusion and exclusion criteria. The study was conducted in the Department of Respiratory Medicine at Amaltas Institute of Medical Sciences, Dewas, Madhya Pradesh, a tertiary care teaching hospital catering to a population representative of Central India.

Inclusion Criteria:

1. Patients aged 18 years or older.
2. Diagnosed cases of active pulmonary or extrapulmonary tuberculosis.
3. Patients willing to participate and provide written informed consent.

Exclusion Criteria:

1. Patients with comorbid conditions such as HIV infection, diabetes mellitus, cancer, or those on corticosteroids or chemotherapeutic drugs within 30 days.
2. Patients who had undergone anti-tubercular therapy (ATT) within the past two years.
3. Pregnant or lactating women.

Group A: The study group included patients diagnosed with active pulmonary tuberculosis, confirmed through clinical evaluation, radiological findings, and microbiological testing (sputum smear microscopy or GeneXpert).

Group B: Healthy Controls- Confirmed sputum negative participants without any symptoms suggestive of active PTB. The controls were matched for age and gender of the participants.

The distribution of tuberculosis types among the TB patients. It was observed that the majority of patients, 81.82%, had pulmonary tuberculosis, while 18.18% of the cases had extrapulmonary tuberculosis.

The pattern of extrapulmonary tuberculosis among the affected participants. Pleural tuberculosis and abdominal tuberculosis were the most common types, each accounting for 28.57% of the extrapulmonary cases. Lymph node tuberculosis and lumbar spine tuberculosis were observed in 21.43% of the cases each.

The prevalence of Vitamin D deficiency among TB cases and healthy controls. A significantly higher proportion of TB patients (85.7%) had Vitamin D deficiency compared to healthy controls (61%). This difference was statistically significant with a chi-square value of 11.9996 and a p-value of 0.001.

The risk of Vitamin D deficiency among TB cases compared to healthy controls. The odds of having Vitamin D deficiency were 3.83 times higher in TB patients than in healthy individuals. This association was statistically significant with a p-value of 0.001 and the 95% confidence interval ranged from 1.746 to 8.402.

This study addresses an important gap in the existing knowledge regarding the role of Vitamin D in tuberculosis. Vitamin D plays a critical role in immune regulation and host defence against Mycobacterium tuberculosis. Identifying a high prevalence of Vitamin D deficiency among TB patients highlights a modifiable risk factor that could influence disease progression and outcomes[8]. Comparing TB cases with healthy controls was crucial to clearly establish whether the deficiency was specifically associated with TB rather than being common in the general population. The findings from this study have significant clinical implications, suggesting that routine screening and correction of Vitamin D deficiency could be considered as a supportive strategy in TB management[9].

By highlighting the association between Vitamin D deficiency and active TB, the present study sets the stage for future research focusing on interventional trials assessing the role of Vitamin D supplementation as an adjunct to standard anti-tubercular therapy[10]. It also opens avenues for exploring Vitamin D-based preventive strategies in high-risk groups.

Workineh et al. (2017) in Gondar, Ethiopia also demonstrated a significant association between vitamin D deficiency and TB. Their study reported an adjusted odds ratio of 1.93 (95% CI: 1.06–2.86) for vitamin D deficiency in TB patients, and a higher odds ratio of 2.13 (95% CI: 1.02–3.28) for severe deficiency in those with low BMI[11].

Zafar et al. (2024), in their case-control study from Jhansi, Central India, found a statistically significant difference in vitamin D deficiency prevalence between TB patients (62.5%) and healthy household contacts (15%), with a chi-square value of 173.97 and p-value of 0.001. This difference implies a strong association, though odds ratios were not reported[12].

The primary outcome measured was the serum Vitamin D level, while secondary objectives included determining the prevalence and severity of Vitamin D deficiency and estimating the risk of deficiency among TB cases. A total of 154 participants were enrolled, comprising 77 TB patients and 77 age- and gender-matched healthy controls.

The findings of the study revealed that Vitamin D deficiency was significantly more prevalent among TB patients (85.7%) compared to healthy controls (61%), with a statistically significant p-value of 0.001. Furthermore, the severity of Vitamin D deficiency was greater among TB cases, with fewer individuals achieving desirable Vitamin D levels compared to controls, and this difference was also statistically significant (p < 0.001).

1. World Health Organization. Global Tuberculosis Report. 2024. Web. http://www.who.int/tb/publications/global_report/en/index.html.
2. "2.2 TB Mortality." World Health Organization, 2024. Web. Accessed 19 Nov. 2024. https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2024/tb-disease-burden/1-2-tb-mortality.
3. Dean, A. S., Tosas Auguet, O., Glaziou, P., Zignol, M., Ismail, N., Kasaeva, T., et al. "25 Years of Surveillance of Drug-Resistant Tuberculosis: Achievements, Challenges, and Way Forward." The Lancet Infectious Diseases, vol. 22, no. 7, 2022, pp. e191–e196.
4. "1.3 Drug-Resistant TB." World Health Organization. Web. Accessed 19 Nov. 2024. https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2024/tb-disease-burden/1-3-drug-resistant-tb.
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9. Wang, C-Y., Hu, Y-L., Wang, Y-H., Chen, C-H., Lai, C-C., et al. "Association between Vitamin D and Latent Tuberculosis Infection in the United States: NHANES, 2011–2012." PLOS ONE, vol. 12, 2019.
10. Kearns, M. D., and Tangpricha, V. "The Role of Vitamin D in Tuberculosis." Journal of Clinical and Translational Endocrinology, vol. 1, no. 4, 2014, pp. 167–169.
11. Workineh, M., Mathewos, B., Moges, B., Gize, A., Getie, S., Stendahl, O., et al. "Vitamin D Deficiency among Newly Diagnosed Tuberculosis Patients and Their Household Contacts: A Comparative Cross-Sectional Study." Archives of Public Health, vol. 75, no. 1, 2017, pp. 1–7.
12. Zafar, S., Siddiqui, Z., Agrawal, N., Madhurmay, and Singh, M. "A Comparative Analysis of Vitamin D Status among Tuberculosis Patients and Healthy Household Contacts: A Case–Control Study from Central India." Apollo Medicine, vol. 21, no. 4, 2024, pp. 308–313.