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of clinical trials involving children in developing countries (Beaton et al., 1993). This chapter will review the potential importance of vitamin A to immune function in adult men and women.

Clinical Manifestations of Vitamin A Deficiency

The most commonly recognized clinical manifestations of vitamin A deficiency involve the eye, and a complete description of the clinical staging is described in Sommer (1982). The occurrence of ocular signs and symptoms of mild and advanced vitamin A deficiency have relevance to immune status as their presence signals a high risk of vitamin A-related immune abnormalities in the individual. Night blindness is one of the earliest symptoms of mild vitamin A deficiency. Typically the vision is normal during the day, but the ability to distinguish objects under less well-illuminated conditions—at dusk or during the night—is impaired. Vitamin A is involved in the generation of rhodopsin, the visual pigment in rod photoreceptors, which allows the retina to detect light in dark-adapted conditions. Other conditions besides vitamin A deficiency can cause night blindness, including advanced glaucoma, pupillary abnormalities involving a small pupil, retinitis pigmentosa, and certain rare retinal disorders involving rod function of the retina. Mild vitamin A deficiency is also characterized by keratinizing, squamous metaplasia of the conjunctiva. A well-defined, raised area of conjunctival metaplasia can sometimes be recognized, typically on the temporal and/or nasal bulbar conjunctiva, and this lesion, known as a Bitot's spot, is considered pathognomonic for vitamin A deficiency.

Advanced vitamin A deficiency is characterized by corneal xerosis, in which the clear, shiny corneal epithelium is replaced by areas of keratinized epithelium, giving the cornea a dull, grayish-white appearance. Cornea ulcers may occur in advanced vitamin A deficiency, and typically these ulcers are small, round or oval, full-thickness ulcers that may allow the aqueous humor to drain from the anterior chamber of the eye. The most advanced eye lesion of vitamin A deficiency is keratomalacia, a condition in which the cornea undergoes widespread ulceration and necrosis, with or without concomitant bacterial or fungal superinfection. Usually under these circumstances, the affected individual will become blind in the affected eye(s) and is at greatly increased risk of immunodeficiency and death.

Epidemiology of Vitamin A Deficiency

Vitamin A deficiency is one of the most common micronutrient deficiencies in the world, affecting an estimated 125 million individuals (Sommer and West, 1996). The groups at highest risk for the development of vitamin A deficiency are infants, preschool children, pregnant women, and lactating women. Vitamin A deficiency is the most common in developing countries, affecting areas of the



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