A study of vitamin D supplementation with directly observed treatment short course for Pulmonary Tuberculosis
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20172227Keywords:
Anti-tubercular treatment, Adverse drug event, Sputum conversion, TB scoreAbstract
Background: Tuberculosis remains one of major global health problems due to growing resistance in TB bacilli against anti-tubercular treatment (ATT). Vitamin D3 has been reported to have immunostimulatory effect. Aim was to study effect of Vitamin D3 on efficacy and safety of ATT / Directly Observed Treatment, short course regimen.
Methods: Prospective, randomized and interventional study of 90 days was carried out in 60 newly diagnosed sputum positive pulmonary tuberculosis patients on DOTS strategy. Study was conducted in Government Medical College, Amritsar, Punjab, India. 30 patients each were randomly divided into two groups, A and B, with group A - vitamin D3 and DOTS regimen and Group B - DOTS alone. Patients were evaluated on day 0, 30, 60 and 90 by TB score, sputum microscopy, laboratory investigations, and adverse drug events. At the end of 90 days, results were tabulated and data analyzed statistically applying relevant tests.
Results: Statistically non-significant improvement in symptoms, sputum conversion and decrease in mean TB scores was seen in Group A vs B at 90 days. Significant increase in mean Vitamin D levels was seen in Group A at end of study. Insignificant difference in safety profile was observed in group A which showed additional adverse events suspected to be due to Vitamin D. Equivocal hepatoprotective effect of Vitamin D was observed.
Conclusions: Vitamin D as adjuvant to ATT does not confer additional benefit to newly diagnosed pulmonary tuberculosis patients. Large multi-centric trials are required to find any benefit of Vitamin D supplementation with ATT.
References
Global Tuberculosis Report. Geneva: WHO Press, World Health Organization; 2016. [Accessed 2017 March 09]. Available from: http://www.who.int/tb/publications/global_report/gtbr2016_executive_summary.pdf?ua=1
Global Tuberculosis Report 2015. 20th Ed. Geneva: WHO Press, World Health Organization; 2015 [Accessed 2015 Nov 4]. 204 p. Available from: http://apps.who.int/iris/bitstream/10665/191102/1/9789241565059_eng.pdf?ua=1
TB India 2014 Revised National TB Control Programme Annual Status Report. Central TB division, Directorate General of Health Services, Ministry of Health and Family Welfare; 2014 [Accessed 2015 Nov 4]. Available from: http://tbcindia.nic.in/pdfs/TB%20INDIA%202014.pdf
TB India 2015 Revised National TB Control Programme Annual Status Report. Central TB division, Directorate General of Health Services, Ministry of Health and Family Welfare; 2015 [Accessed 2015 Nov 4]. 120 p. Available from: http://www.tbcindia.nic.in/WriteReadData/l892s/254998242TB%20India%202015.pdf
Use of high burden country lists for TB by WHO in the post-2015 era. WHO 2015. Available from: http://www.who.int/tb/publications/global_report/high_tb_burdencountrylists2016-2020.pdf)
TB Statistics for India – National and state statistics. http://www.tbfacts.org/tb-statistics-india/ (Accessed 07.03.2017)
Revised National Tuberculosis Control Programme (RNTCP): DOTS Strategy. Available at https://www.nhp.gov.in/revised-national-tuberculosis-control-programme_pg.
Status Report on Revised National Tuberculosis Control Program (RNTCP). Indian J Tuberc 2011;58(4):199-203.
Marwaha RK, Tandon N, Garg MK, Kanwar R, Narang A, Sastry A, et al. Vitamin D Status in Healthy Indians Aged 50 Years and Above. J Assoc Physicians India. 2011;59:706-9.
Goswami R, Mishra SK, Kochupillai N. Prevalence and potential significance of vitamin D deficiency in Asian Indians. Indian J Med Res. 2008;127:229-38.
Vieth R. What is the optimal vitamin D status for health? Prog Biophys Mol Biol. 2006;92:26-32.
Talat N, Perry S, Parsonnet J, Dawood G, Hussain R. Vitamin D deficiency and tuberculosis progression. Emerg Infect Dis. 2010;16(5):853-5.
Yuk JM, Shin DM, Lee HM, Yang CS, Jin HS, Kim KK, et al. Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin. Cell Host Microbe. 2009;6(3):231-43.
Salahuddin N, Ali F, Hasan Z, Rao N, Aqeel M, Mahmood F. Vitamin D accelerates clinical recovery from tuberculosis: results of the SUCCINCT Study [Supplementary Cholecalciferol in recovery from tuberculosis]. A randomized, placebo-controlled, clinical trial of vitamin D supplementation in patients with pulmonary tuberculosis’. BMC Infectious Diseases. 2013;13:22.
Wejse C, Gomes VF, Rabna P, Gustafson P, Aaby P, Lisse IM, et al. Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2009;179(9):843-50.
Wejse C, Gustafson P, Nielsen J, Gomes VF, Aaby P, Andersen PL et al: TB score: Signs and symptoms from tuberculosis patients in a low-resource setting have predictive value and may be used to assess clinical course. Scand J Infect Dis. 2008;40(2):111-20.
Daley P, Jagannathan V, John KR, Sarojini J, Latha A, Vieth R, et al. Adjunctive vitamin D for treatment of active tuberculosis in India: a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2015;15(5):528-34.
Ralph AP, Waramori G, Pontororing GJ, Kenangalem E, Wiguna A, Tjitra E, et al. L-arginine and Vitamin D Adjunctive Therapies in Pulmonary Tuberculosis: A Randomised, Double-Blind, Placebo-Controlled Trial. PLoS ONE. 2013;8(8):e70032.
Farazi A, Didgar F, Sarafraz A. The effect of vitamin D on clinical outcomes in tuberculosis. Egyptian Journal of Chest Diseases and Tuberculosis 2017. Available from: http://ac.els-cdn.com/S0422763816302333/1-s2.0-S0422763816302333-main.pdf?_tid=f6e674f6-04e7-11e7-9892-00000aacb35e&acdnat=1489078178_ceeadddd62b3f3f527c6293d089a5a94.
Martineau AR, Timms PM, Bothamley GH, Hanifa Y, Islam K, Claxton AP, et al. High-dose vitamin D3 during intensive phase treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet. 2011;377(9761):242-50.
Nursyam EW, Amin Z, Rumende CM. The effect of vitamin D as supplementary treatment in patients with moderately advanced pulmonary tuberculous lesion. Acta Medica Indones. 2006;38(1):3-5.
Coussens AK, Wilkinson RJ, Hanifa Y, Nikolayevskyy V, Elkington PT, Islam K, et al. Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment. Proc Natl Acad Sci. 2012;109(38):15449-54.
Hassanein EG, Mohamed EE, Baess AI, EL-Sayed ET, Yossef AM. The role of supplementary vitamin D in treatment course of pulmonary tuberculosis. Egypt J Chest Dis Tuberculosis. 2016;65:629-35.
Bhaumik S, Hazra N. Role of genetic variants of vitamin D immunomodulation genes in clinical response to treatment of tuberculosis. Indian J Med Res. 2015;141(6):840-1.
Talat N, Perry S, Parsonnet J, Dawood G, Hussai R. Vitamin D Deficiency and Tuberculosis Progression. Emerg Infect Dis. 2010 May;16(5):853-5.
Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al. Toll-like receptor triggering of a vitamin D–mediated human antimicrobial response. Science. 2006;311:1770-3.
