Cerebral malaria is a fatal syndrome associated with malaria, and is caused by the development of an overwhelming pro-inflammatory response.
As vitamin D has regulatory functions linked to both adaptive and innate immune responses, researchers at the China medical university conducted a study to evaluate the usefulness of prophylactic oral vitamin D in helping to prevent the presentation of cerebral malaria prior to infection.
Attenuation of inflammation
They divided six- to eight-week-old female mice equally into three groups: a control group uninfected by Plasmodium berghei ANKA (PbA, a protozoan parasite that induces malaria in certain rodents), a group infected with PbA, and an infected group supplemented with vitamin D.
The vitamin D had been dissolved in soybean oil prior to the experiment, and each of the mice in the supplemented group were orally administered 50μg/kg of vitamin D once a day for five days before being injected intraperitoneally with PbA packed red blood cells.
The mice in the control group received an equivalent amount of soybean oil without vitamin D.
All the infected mice typically developed cerebral malaria symptoms within five days post-infection, with the non-supplemented mice succumbing to infection by six to 11 days post-infection.
The infected mice that received oral vitamin D, on the other hand, were found to be "completely resistant" to cerebral malaria itself, and survived for up to 15 days post-infection.
At the same time, oral vitamin D supplementation was said to have suppressed cerebral malaria-related pro-inflammatory immune responses in the brain, reducing the serum levels of IFN-γ and TNF-α — pro-inflammatory cytokines that contribute to the pathogenesis of cerebral malaria — in the infected and supplemented mice.
Cerebral cellular impact
The researchers also reported that the mice that had been supplemented with vitamin D saw a lowered mortality rate, as well as ameliorated integrity of the blood-brain barrier.
In addition, prophylactic oral vitamin D supplementation was reported to have alleviated the symptoms of brain malaria and prevented death, which led to "valuable time for diagnosis and treatment post-infection".
The researchers also tested the response from Th1 cells in the infected mice that had received vitamin D, as Th1 cells typically generate pro-inflammatory responses against Plasmodium infections.
They subsequently reported that vitamin D supplementation "inhibited the expansion of Th1 cells and pro-inflammatory cytokine secretion" in the infected mice.
Furthermore, T-cell trafficking to the brain — a significant aspect of the pathology of diseases like cerebral malaria — was found to have been diminished in the supplemented mice even before PbA infection.
In conclusion, the researchers wrote: "Prophylactic oral administration of vitamin D prevented cerebral malaria in mice, suggesting that administration of oral vitamin D could potentially be used to prevent cerebral malaria symptoms in malaria-endemic regions, such as sub-Saharan Africa.
"Any prevention strategy for malaria needs to consider the importance of nutrition, especially in children who are the most vulnerable to malnutrition.
"Data presented in this report suggest that vitamin D supplementation in malaria-endemic regions is likely to have an impact in reducing the disease burden of malaria, in part by decreasing the rates of cerebral malaria-related mortality."
Source: International Immunopharmacology
https://doi.org/10.1016/j.intimp.2018.08.041
"Oral administration of vitamin D and importance in prevention of cerebral malaria"
Authors: Bo Wu, et al.