High-dose vitamin D3 during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial

Martineau, Adrian R.; Timms, Philip; Bothamley, Graham; Hanifa, Yasmeen; Islam, Kamrul; Claxton, Alleyna; Packe, Geoffrey E.; Moore-Gillon, J; Darmalingam, M; Davidson, Robert N.; Milburn, Heather; Baker, Lucy; Barker, Richard D.; Woodward, Nicholas; Venton, Timothy R; Barnes, Korina E.; Mullett, Christopher J; Coussens, Anna K.; Rutterford, Clare; Mein, Charles A.; Davies, Geraint R.; Wilkinson, Robert J.; Nikolayevskyy, Vladyslav; Drobniewski, Francis; Eldridge, Sandra; Griffiths, Christopher J.

doi:10.1016/s0140-6736(10)61889-2

Cited by 508 publications

(483 citation statements)

References 28 publications

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“…122 VitD3 deficiency is a risk factor for development of TB disease, 123 although a randomised control trial failed to show a profound effect on TB treatment outcome. 124 Further trials are required to accurately define the value of vitD3 as TB HDT. Vitamin A (vitA) possesses host immunomodulatory potential and in vitro anti-mycobacterial capabilities, 125 deficiency strongly predicts the risk of incident TB amongst TB household contacts (HHC) and supplementation (with zinc) improves TB treatment outcomes.…”

Section: Vitaminsmentioning

confidence: 99%

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tiberi

Plessis

Walzl

et al. 2018

The Lancet Infectious Diseases

289

275

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Tuberculosis (TB) remains the top killer from an infectious globally causing an estimated 1.674.000 million deaths worldwide. In 2016, WHO estimates 600.000 cases of rifampicin-resistant TB of which 490.000 had multidrug-resistant (MDR) and less than half of them survive after receiving currently recommended WHO treatment regimens, illustrating weaknesses in current treatment approaches. We review progress and advances in the development of new and repurposed TB drugs, treatment trials and host-directed therapies. Updates are provided on phase 3 trials of the new compounds bedaquiline, delamanid, pretomanid; phase 2 trials of sutezolid, SQ-109, LCB01-0371, PBTZ-169; and five new drugs in phase 1 development. Approved or repurposed drugs undergoing further testing are rifampicin, rifapentine, clofazimine, and linezolid. Update on ongoing clinical trials, which aim to shorten TB treatment and improve treatment outcome is given. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR-TB, and five antimicrobial drug candidates are in phase 1 (Q203, TBI-166, OPC-167832, GSK 070, TBA-7371) and 5 in pre-clinical studies. Specific issues of safety and toxicity; drug-drug interactions; Therapeutic Drug Monitoring are reviewed. A wide range of candidate host-directed therapies (HDTs) and immune-based treatments are being investigated to accelerate the eradication of M.tb infection and for use as adjunctive therapy in shortening duration of treatment, preventing permanent lung injury and improving treatment outcomes of MDR-TB. Ongoing clinical trials of HDTs for TB treatment, the current HDT development pipeline and translational research efforts for advancing further HDT options are presented. Ongoing clinical trials of HDTs for TB treatment, the current HDT development pipeline and translational research efforts for advancing further HDT options are presented.5

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Section: Vitaminsmentioning

confidence: 99%

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tiberi

Plessis

Walzl

et al. 2018

The Lancet Infectious Diseases

289

275

View full text Add to dashboard Cite

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“…Individuals with VDR minor genotypes are more sensitive to vitamin D administration and exhibit low calcium absorption [31,32]. Moreover, VDR minor alleles have been reported to alter VDR function or expression [33,34].…”

Section: Gene Analysismentioning

confidence: 99%

Association of vitamin D-related gene polymorphisms with manifestation of vitamin D deficiency in children

et al. 2012

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“…However, vitamin D seems to have limited benefit for treating those with TB (Davies, 2010). Vitamin D treatment for those with TB seems to be beneficial only for those with the homozygous recessive tt genotype of the TaqI vitamin D receptor (Martineau et al, 2011).…”

Section: Cardiovascular Diseasementioning

confidence: 99%

An estimate of the global reduction in mortality rates through doubling vitamin D levels

Grant

2011

Eur J Clin Nutr

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Background/Objectives: The goal of this work is to estimate the reduction in mortality rates for six geopolitical regions of the world under the assumption that serum 25-hydroxyvitamin D (25(OH)D) levels increase from 54 to 110 nmol/l. Subjects/Methods: This study is based on interpretation of the journal literature relating to the effects of solar ultraviolet-B (UVB) and vitamin D in reducing the risk of disease and estimates of the serum 25(OH)D level-disease risk relations for cancer, cardiovascular disease (CVD) and respiratory infections. The vitamin D-sensitive diseases that account for more than half of global mortality rates are CVD, cancer, respiratory infections, respiratory diseases, tuberculosis and diabetes mellitus. Additional vitamin D-sensitive diseases and conditions that account for 2 to 3% of global mortality rates are Alzheimer's disease, falls, meningitis, Parkinson's disease, maternal sepsis, maternal hypertension (pre-eclampsia) and multiple sclerosis. Increasing serum 25(OH)D levels from 54 to 110 nmol/l would reduce the vitamin D-sensitive disease mortality rate by an estimated 20%. Results: The reduction in all-cause mortality rates range from 7.6% for African females to 17.3% for European females. Reductions for males average 0.6% lower than for females. The estimated increase in life expectancy is 2 years for all six regions. Conclusions: Increasing serum 25(OH)D levels is the most cost-effective way to reduce global mortality rates, as the cost of vitamin D is very low and there are few adverse effects from oral intake and/or frequent moderate UVB irradiance with sufficient body surface area exposed.

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High-dose vitamin D3 during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial

Abstract: Background-Vitamin D was used to treat tuberculosis in the pre-antibiotic era, and its metabolites induce antimycobacterial immunity in vitro. Clinical trials investigating the effect of adjunctive vitamin D on sputum culture conversion are lacking.

Cited by 508 publications

References 28 publications

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Association of vitamin D-related gene polymorphisms with manifestation of vitamin D deficiency in children

An estimate of the global reduction in mortality rates through doubling vitamin D levels

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