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Vitamin D deficiency has in the past been implicated in the pathogenesis of tuberculosis (TB), although most research has not found a significant association between the two.
The researchers in the current study conducted a mega-analysis to explore the association between vitamin D status and TB in children, searching three databases — Web of Science, Ovid Medline and EMBASE — for English-language studies discussing vitamin D status and TB in children before January 22, 2018.
Vitamin D deficiency and TB: Which causes which?
They eventually included 10 studies from 585 initially identified ones, and reported that based on the random effects model used to perform the meta-analysis, TB was indeed significantly associated with vitamin D deficiency in children.
Vitamin D levels were found to be markedly lower in TB patients than in the healthy controls, and the vitamin D deficiency was said to possibly "contribute to TB in children through multiple pathways".
Mounting evidence points to vitamin D deficiency's negative impact on immunity, which could lead to M tuberculosis infection by "increasing chemokine production, activating dendritic cells, and altering T cell activation".
In addition, the study stated that the risk of developing TB in vitamin D-deficient children was even higher in developing countries, and that the risk of developing vitamin D deficiency was prevalent in children with active TB and latent TB infection.
However, it also said that results of studies focusing on the link between TB and vitamin D deficiency in children had been inconsistent, something that could be explained by inter-individual differences caused by vitamin D receptor (VDR) polymorphisms.
While vitamin D deficiency was said to be a contributing factor to TB in children, the researchers said active TB also increased the risk of vitamin D deficiency in children.
The lower level of vitamin D in children with active TB could be attributed to poor nutrition or VDR polymorphisms, while TB was said to increase the risk of vitamin D deficiency through malnutrition, limited vitamin D absorption and sun exposure, immune dysregulation, and VDR polymorphisms.
There are also other factors that may interact with TB via pathogenetic pathways, resulting in vitamin D deficiency in children.
For instance, the immune dysregulation resulting from HIV infection and malnutrition made study subjects more vulnerable to both active TB and latent TB infection, with HIV status highlighted as a "significant predictor of TB".
Still, vitamin D deficiency remains a significant feature in children with TB, be it a result of developing TB, or a factor in the development of TB.
This information may warrant the use of vitamin D supplementation to treat and / or prevent TB in children.
Limitations and conclusions
The researchers said their meta-analysis may have been limited by the inclusion of only English-language studies, which may have resulted in publication bias.
The overall small sample sizes of the studies analysed also meant the results of the meta-analysis "should be interpreted with caution".
They added that many factors apart from TB could affect vitamin D level, and even the measurement of 25(OH)D "may not directly reflect vitamin D status".
In conclusion, they wrote: "Our pooled analyses provide strong evidence that vitamin D levels are significantly lower in children with TB or latent TB infection than in controls.
"TB may contribute to vitamin D deficiency in children, and thus, may be associated with TB in children. This knowledge may support the design and evaluation of randomised case–control clinical trials on the role of vitamin D supplementation in preventing TB in children."
"The association between vitamin D status and tuberculosis in children: A meta-analysis"
Authors: Xiaoyun Gou, et al.