The dengue virus (DENV), a member of the Flaviviridae family, causes the most widespread mosquito-borne viral infection in humans around the world today. The pathophysiology of dengue virus in the body and the host's immune response are not completely understood. Major disease manifestations in the body include capillary leak syndrome (plasma leakage caused by endothelial cell dysfunction), thrombocytopenia (low platelet counts), leukopenia, and hemorrhagic tendencies. It is known that the major viral envelope (E) glycoprotein in the virus assists its binding to host cells, after which the virus enters the cell and viral replication occurs. Data suggest that monocytes are the primary target. Infected monocytes induce the production of interferon-a (IFN-a) and IFN-ß. E, precursor membrane protein (pre-M), and nonstructural protein 1 (NS1) are the major proteins on dengue virus that are targeted by antibodies as part of the host immune response. Studies show that DENV-specific CD4+ and CD8+ T lymphocytes attack infected cells and release IFN-?, tumour necrosis factor-a (TNF-a), and lymphotoxin. Primary infection induces lifelong immunity in the individual to that particular serotype but not to secondary infection by a different serotype.

Host nutritional status is a strong predictor of immunity; in fact, malnutrition is the most common cause of immunodeficiency worldwide, estimated to cause about 50 per cent of childhood deaths and a significant fraction of deaths from infectious diseases in developing countries. A properly functioning immune system requires an adequate supply of micronutrients (a substance needed only in small amounts for normal body function (e.g., vitamins or minerals) to both prevent damage of cells participating in the innate immune response and restore tissues damaged from the host defense against the infectious agents. Earlier studies have, contradictorily, found that malnourished children are less likely to develop dengue hemorrhagic fever compared with well-nourished children, but recent studies have not supported this finding.

Vitamin D
Vitamin D is known to play an essential role in the immune system and vitamin D deficiency has long been associated with autoimmune diseases as well as increased susceptibility to viral infections. Vitamin D has been shown to promote both innate and adaptive immunity through a number of mechanisms such as T-cell activation (immunity enhancer). Many additional cells of the immune system (including B cells, monocytes, and dendritic cells) also respond to the immunomodulatory effects of vitamin D through the vitamin D receptor (VDR) expressed on their cell surface. Vitamin D binding to the VDR, in turn, activates vitamin D-responsive genes in the body, many of which induce a number of pathogen-fighting mechanisms. Vitamin D supplementation also has some success in helping to treat other viral infections, such as influenza.

Zinc
Similar to vitamin D, zinc is also very important for immune function, and deficiency in zinc has been associated with decreased resistance to viral infection. Affecting a number of immune cells and functions, zinc specifically influences lymphocyte maturation, cytokine production, and generation of free radicals while maintaining normal macrophage and natural killer (NK) cell activity in the immune response it also plays a role in T-cell and neutrophil activity as well as B-cell development. Zinc supplementation has also been found to reduce mortality from diarrhea and pneumonia and has been shown to be beneficial in preventing respiratory infection.

Vitamin A
Vitamin A, one of the most commonly studied nutrients in relation to immunity, is known to be a central regulator of the immune system; vitamin A deficiency has been shown in many studies to impair both humoral and cell-mediated immunity as well as the integrity of epithelial tissues of the eyes, lungs, and gut, all of which lead to an increased susceptibility to pathogens and infectious diseases. Specifically, vitamin A affects the activity of macrophages and the number and activity of NK cells as well as lymphocyte functions, such as B-cell proliferation and T-cell activation. Vitamin A supplementation has been found to have a significant impact on preventing morbidity and mortality in a number of infectious diseases in developing countries. Studies show that vitamin A supplementation decreases disease severity and risk of death in malaria and reduces mortality in measles.

Iron
The need for iron for proper immune function stems from its role in promoting the growth and differentiation of various immune cells; specifically, iron deficiency has been found to decrease natural killer cell activity, lymphocyte bactericidal activity, and neutrophil phagocytic activity while influencing cytokine activity in every stage of the immune response to infection.

Chromium
Chromium (an essential trace mineral) has been known for its effects on the regulation of blood sugar by promoting the action of insulin, and recently, it has been discovered to affect the immune response by influencing T and B lymphocytes, antigen-presenting cells (such as macrophages), and cytokine production. Chromium supplementation is known to increase immune function in animals and possibly by reducing serum cortisol levels.

Vitamin E
Vitamin E, a fat-soluble vitamin that is essential for normal reproduction and an important antioxidant that neutralizes free radicals in the body, immune function has been found to be especially sensitive to changes in vitamin E status; even marginal vitamin E deficiency prevents the immune system from exhibiting a proper response to infection. Importantly, the antioxidant properties of vitamin E protect immune cell membranes from oxidative damage. Vitamin E supplementation has been reported to enhance both humoral- and cell-mediated immune responses and resistance to infection in a number of human studies. It has been shown to enhance immunity in elderly populations.

Considering the potential of micronutrient supplements to represent low-cost and simple adjuncts to improve treatment success in patients with dengue, it is surprising that the scope of research in this area has been rather limited.