Abstract
Vitamin D plays an increasingly recognized role in the innate and adaptive immune response to infection. Based on demonstrated roles in up-regulating innate immunity, decreasing inflammation, and reducing the severity of disease in illnesses such as tuberculosis and influenza, we hypothesized that poor vitamin D status would be associated with severe malaria. We measured 25-hydroxyvitamin D [25(OH)D] by immunoassay in a sample of Ugandan children aged 18 months –12 years with severe malaria (cerebral malaria or severe malarial anemia, n = 40) and in healthy community children (n = 20). Ninety-five percent of children with severe malaria (n = 38) and 80% of control children (n = 16) were vitamin D-insufficient [plasma 25(OH)D <30 ng/mL]. Mean plasma 25(OH)D levels were significantly lower in children with severe malaria than in community children (21.2 vs. 25.3 ng/mL, p = 0.03). Logistic regression revealed that for every 1 ng/mL increase in plasma 25(OH)D, the odds of having severe malaria declined by 9% [OR = 0.91 (95% CI: 0.84, 1.0)]. These preliminary results suggest that vitamin D insufficiency may play a role in the development of severe malaria. Further prospective studies in larger cohorts are indicated to confirm the relationship of vitamin D levels to severity of malaria infection and to investigate causality.
Highlights
In addition to its established role in maintaining calcium homeostasis and optimal bone health, vitamin D plays an important immune-modulating role as a key PLOS ONE | DOI:10.1371/journal.pone.0113185 December 3, 2014Vitamin D and Severe Malaria player in innate and adaptive immunity [1]
Activation of toll-like receptor 2/1 (TLR 2/1) in human macrophages by mycobacterial surface lipoprotein up-regulates expression of the vitamin D receptor (VDR) and 1a-hydroxylase, the enzyme required to convert 25-hydroxy vitamin D [25(OH)D] to its active form, 1,25-dihydroxy vitamin D [1,25(OH)2D]. 1,25(OH)2D binds to the VDR, increasing transcription of anti-microbial peptides (AMP), including cathelicidin, which results in improved response to anti-tuberculous therapy in individuals treated with vitamin D [5]
Community children and children with severe malaria were similar with regard to age, sex, height-for-age z-score, and indicators of socioeconomic status and food security (Table 1)
Summary
In addition to its established role in maintaining calcium homeostasis and optimal bone health, vitamin D plays an important immune-modulating role as a key PLOS ONE | DOI:10.1371/journal.pone.0113185. Vitamin D and Severe Malaria player in innate and adaptive immunity [1]. Poor vitamin D status can worsen infectious illness, as is perhaps best exemplified by its relationship with M. tuberculosis. Work by Liu et al [4] demonstrated that this benefit of vitamin D in tuberculosis is exerted via strengthening of the innate immune response to infection. 1,25(OH)2D binds to the VDR, increasing transcription of anti-microbial peptides (AMP), including cathelicidin, which results in improved response to anti-tuberculous therapy in individuals treated with vitamin D [5] Activation of toll-like receptor 2/1 (TLR 2/1) in human macrophages by mycobacterial surface lipoprotein up-regulates expression of the vitamin D receptor (VDR) and 1a-hydroxylase, the enzyme required to convert 25-hydroxy vitamin D [25(OH)D] to its active form, 1,25-dihydroxy vitamin D [1,25(OH)2D]. 1,25(OH)2D binds to the VDR, increasing transcription of anti-microbial peptides (AMP), including cathelicidin, which results in improved response to anti-tuberculous therapy in individuals treated with vitamin D [5]
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