Old wine in new bottles: vitamin D in the treatment and prevention of tuberculosis

Abstract

Tuberculosis (TB) is a major cause of mortality, responsible for 1 . 68 million deaths worldwide in 2009. The global prevalence of latent Mycobacterium tuberculosis infection is estimated to be 32 %, and this carries a 5-20% lifetime risk of reactivation disease. The emergence of drug-resistant organisms necessitates the development of new agents to enhance the response to antimicrobial therapy for active TB. Vitamin D was used to treat TB in the pre-antibiotic era, and its active metabolite, 1,25-dihydoxyvitamin D, has long been known to enhance the immune response to mycobacteria in vitro. Vitamin D deficiency is common in patients with active TB, and several clinical trials have evaluated the role of adjunctive vitamin D supplementation in its treatment. Results of these studies are conflicting, reflecting variation between studies in baseline vitamin D status of participants, dosing regimens and outcome measures. Vitamin D deficiency is also recognised to be highly prevalent among people with latent M. tuberculosis infection in both high-and low-burden settings, and there is a wealth of observational epidemiological evidence linking vitamin D deficiency with increased risk of reactivation disease. Randomised controlled trials of vitamin D supplementation for the prevention of active TB have yet to be performed, however. The conduct of such trials is a research priority, given the safety and low cost of vitamin D supplementation, and the potentially huge public health consequences of positive results. Tuberculosis: Vitamin D: Immunomodulation: Clinical trialsTuberculosis (TB) is a major public health problem. The global prevalence of latent Mycobacterium tuberculosis (MTB) infection has been estimated at 32% (1) , and this carries a 5-20% lifetime risk of reactivation disease in people who are not infected with HIV (2) ; reactivation rates higher than 10% per annum have been reported in HIVinfected people (3) . The WHO estimates that in 2009 there were 9 . 4 million incident cases of active TB, 14 million prevalent cases of TB, 1 . 3 million deaths from TB in HIV-uninfected people and 0 . 38 million deaths from TB in HIV-infected people (4) . The development of new agents to prevent acquisition or reactivation of latent MTB infection and to allow shortening of antimicrobial therapy regimens for active TB without loss of efficacy is a research priority. This paper reviews the growing body of evidence from studies conducted both in vitro and in vivo suggesting that vitamin D might have a role in the prevention and treatment of TB.

Prevalence of vitamin D deficiency in Indian women

“…[1][2][3][4][5][6][7] Recent researches had also linked vitamin D deficiency with the increased risk of developing tuberculosis, otitis media, upper respiratory tract infections and influenza and many other infections. [8][9][10][11][12] Its deficiency has also linked with the increased risk of developing hypertension, diabetes, obesity and high triglyceride level ultimately leading to increased risk of cardiovascular mortality. 13 Researchers have shown epidemiological association of vitamin D deficiency and type1 diabetes.…”

Tuberculosis

“…A key research priority is to establish randomised controlled trials of vitamin D supplementation to prevent acquisition or reactivation of LTBI. Although some question the need for such studies to be conducted on the grounds that data from observational studies are suggestive, and that the methodological challenges of conducting such trials are too great [ 120 ] , others maintain that these trials are necessary, fundable and feasible [ 121 ] . Equivalent trials have been conducted to establish the role of chemoprophylaxis for TB prevention [ 122 ] , and investigation of the role of vitamin D supplementation in this regard should be no less of a research priority, given its safety and low cost.…”

Tuberculosis Vaccine Development — Its History and Future Directions

“…These living conditions could impair the ability of the immune system to respond properly both to a vaccination and exposure to a pathogen. Other conditions, such as diabetes or vitamin D deficiency, can also impair the ability of the immune system to produce a robust response and indeed, both conditions have been associated with an increased risk for developing TB [35][36][37].…”