Oral administration of vitamin D and importance in prevention of cerebral malaria

Abstract

Cerebral malaria (CM) is a serious and fatal malaria-associated syndrome caused by the development of an overwhelming proinflammatory response. Vitamin D (Vit.D; cholecalciferol) has regulatory functions associated with both innate and adaptive immune responses. Prevention is better than cure, in this experiment, we evaluated prophylactic oral Vit.D as a means of preventing CM presentation before infection of C57BL/6 mice with Plasmodium berghei ANKA (PbA) by modulating the host proinflammatory response. Mice that were supplemented with oral Vit.D has reduce death rate and ameliorated the integrity of the blood brain barrier. Prophylactic oral vitamin D relieved the symptoms of brain malaria and avoided death, gained valuable time for the diagnosis and treatment post infection. The robust Th1 response was attenuated in the Vit.D + PbA group. Furthermore, T-cell trafficking to the brain was diminished before PbA infection using Vit.D. The results suggest that Vit.D supplementation mediates the development of an anti-inflammatory environment that improves CM severity. In summary, the use of Vit.D as a nutritional supplement in malaria-endemic regions may help reduce the severity and mortality of CM.

Vitamin D in malaria: more hypotheses than clues

“…2). Th1 excessive response, Th2 response mitigation and Treg cells dysfunction represent mechanisms involved in the onset and development of malaria [8, 9], and these effects can be limited by the action of 1,25(OH)2D on the immune response. Further, the hormone inhibits the synthesis of some pro-inflammatory cytokines such as IFN-γ and TNF-α, which are involved in the development of cerebral malaria (CM), an often fatal multifactoral pathogenesis syndrome [60].

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“…Finding new prevention and therapy tools is a matter of urgency. Studies on animal models and humans have hypothesised some mechanisms by which the hormone can influence malaria pathogenesis, and the role of Vitamin D analogues supplementation in preventing and treating this disease has been suggested [9].…”

“…Finding new prevention and therapy tools is a matter of urgency. Studies on animal models and humans have hypothesised some mechanisms by which the hormone can influence malaria pathogenesis, and the role of Vitamin D analogues supplementation in preventing and treating this disease has been suggested [9]. The purpose of this paper is to highlight the mechanisms by which Vitamin D can influence the pathogenesis of malaria and provide a critical review of the studies evaluating the association of Vitamin D and malaria, in order to determine whether and how supplementation can be useful in preventing and treating patients affected by this disease.…”

Elimination of Hepatic Rodent Plasmodium Parasites by Amino Acid Supplementation

“…Nutritional supplementation has long been suggested as a possible strategy to impact the outcome of several pathogenic infections (Read et al, 2019;Jimenez-Sousa et al, 2018;Rautiainen et al, 2016;Steinbrenner et al, 2015;Stephensen, 2001;Gois et al, 2017;Somerville et al, 2016). Recently, dietary alterations have been shown to significantly alter the capacity of Plasmodium, the malaria parasite, to replicate in the blood of its mammalian host, altering the clinical outcome of infection (Shankar, 2000, Clinton Health Access Initiative, 2016, Caulfield et al, 2004, (MSF), 2013, Nyariki et al, 2019Qin et al, 2019;Wu et al, 2018;Castberg et al, 2018;Goheen et al, 2017;Awasthi et al, 2017;Alkaitis and Ackerman, 2016;Meadows et al, 2015;Kirk and Saliba, 2007;Mancio-Silva et al, 2017;Counihan et al, 2017). Less is known about the impact of dietary alterations on the capacity of this parasite to complete the initial stage of its mammalian infection in the liver, and on how targeted modifications of nutritional availability can be employed as infection control tools (Vreden et al, 1995;Zuzarte-Luis et al, 2017;Goma et al, 1996;Ferrer et al, 2016).…”

“…That is also the case for malaria, for which it is well established that host deficiencies in several micronutrients (e.g., vitamin A and zinc) can exacerbate malaria, and that modulating parasite access to other nutrients, such as glucose, vitamin B5, and choline, can have a significant impact on parasite growth and, consequently, on disease (Kirk and Saliba, 2007;Mancio-Silva et al, 2017;Counihan et al, 2017;Shankar, 2000;Caulfield et al, 2004). Dietary supplementations employing various nutrients, such as Coenzyme Q10, Vitamin C, Vitamin D,iron,Arg,tetrahydrobiopterin (BH4), or folate, among others, have been shown to directly impact Plasmodium erythrocytic stages (Nyariki et al, 2019;Qin et al, 2019;Wu et al, 2018;Castberg et al, 2018;Goheen et al, 2017;Awasthi et al, 2017;Alkaitis and Ackerman, 2016;Meadows et al, 2015). Interestingly, cysteamine has been shown to potentiate the activity of anti-malarial drugs, like artemisinins (Moradin et al, 2016), opening a potential new pathway to using nutrient supplementation to improve malaria treatment.…”