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Delivery of oral doses of vitamin A to prevent vitamin-A deficiency and nutritional blindness

Keith P. West, Jr., and Alfred Sommer

Administration of large doses of vitamin A to young children land often to lactating, non-pregnant mothers as well) is a commonly practiced intervention against nutritional blindness, and may emerge as a major strategy to reduce childhood mortality where vitamin-A deficiency is endemic. On the basis of available evidence from nearly two decades of experience, large-dose vitamin-A distribution can generally be regarded as a safe and potentially effective intervention to prevent xerophthalmia. While this approach is conceptually simple, the adequacy and efficiency of programmes pose major challenges and determine their success in preventing nutritional blindness.

A 200,000 IU dose of vitamin A with 40 IU vitamin E in an oil solution for oral administration given every six months is used in most prevention programmes. This is preferred to water-miscible preparations for reasons of safety and practicality of delivery. A gelatine capsule, provided to governments by UNICEF, is the most widely used form of dose except in India, where a domestically produced oil concentrate is used.

The protection afforded by six-monthly dosing seems very adequate as measured by clinical signs of the deficiency. Controlled field and other clinical studies indicate that a single dose gives effective protection of 90% or better (its prophylactic efficacy) against developing mild xerophthalmia for at least 4 to 6 months. Data from a case-control study in India suggest this degree of efficacy extends to severe, potentially blinding xerophthalmia as well. However, the protective period is likely to vary with the frequency and severity of precipitating and contributory factors such as infection and protein-energy malnutrition. Efficacy establishes the upper limit of of effectiveness when large-dose vitamin-A delivery is implemented through a routine programme.

The presence of certain infections reduces absorption and retention of vitamin A, such that while 40%50% of a large dose is retained in healthy children, only 20%-30% may be stored and utilized in those with respiratory or gastrointestinal infections. But treatment for xerophthalmia using standard oral doses of vitamin A appears effective even in the presence of such infections. Absorption and retention of vitamin A appear to be inversly related to the dosage; thus, a 200,000 IU dose is proportionally less well absorbed and retained than a physiologic amount (e.g., 3,000 IU) of vitamin A.

Theoretical estimates of the sufficiency of hepatic stores conferred by a 200,000 IU dose range from 60 to 240 days; however, the observed protective period against low serum-vitamin-A levels in children who are "at risk" of vitamin-A deficiency may last little more than 56 days. This may in part be explained by degrees of inaccuracy of serum-vitamin-A levels in representing true vitamin-A status. The short-term effect of a large vitamin-A dose may be greatest when regular dietary intake is most restricted, but routine intake of as little as 15-30 grams of dark green leafy vegetables per day may extend to several months the protective period afforded by a single large dose of vitamin A.

Three basic systems are employed to distribute vitamin A to the "at-risk" community: medical, targeted, and universal. Medical distribution (essentially, treating those presenting with deficiency signs or infection in endemic areas) is usually incorporated into the other two systems and has not been independently evaluated. Targeted distribution focuses on specific high-risk groups, defined usually by age and/or location. One targeted system that has been evaluated, in Haiti, showed a ninefold reduction in corneal xerophthalmia three years after initiation of the programme. Other environmental improvements may have contributed to this reduction in disease as well. Targeted delivery can be expected to reach only 10%-15% of the "at-risk" population at existing levels of utilization of the health services. A routine dosing schedule is also difficult to achieve. While effectiveness may be less than that expected from a high-coverage universal distribution, higher target-group specificity and efficiency could make targeted delivery a more attractive option. Before making full use of the present health-care system for targeted delivery, the opportunity costs associated with conducting universal distribution should be explored.

The effectiveness of universal distribution in preventing mild xerophthalmia is, in part, directly related to coverage. A 75%80% reduction in prevalence among one- to four-year-olds has been repeatedly associated with universal distribution that achieves at least 65% coverage. For example, in the Philippines, reduction in xerophthalmia of nearly 70% was directly attributable to capsule distribution. Conversely, no measurable impact on xerophthalmia has been observed when coverage has been less than 25%. In the Philippines, an 80% associated reduction in xerophthalmia could be linked to a 70% reduction in disease directly attributable to capsule distribution. Above 85% coverage, the effectiveness of universal delivery in preventing the less prevalent but more severe corneal xerophthalmia may be high as 90%.

Vitamin-A distribution-programme infrastructure tend to be similar, administered by the ministry of health and implemented through local health centres. Originally designed to be single-purpose, vitamin-A delivery is being increasingly built into health services, with nutrition-education components.

Programme efficiency needs to be sustained at practically every level. Problems arise in ensuring the uninterrupted supply of vitamin-A doses, in supervision, training, and retraining of personnel, and in administration (e.g. record-keeping). Maintaining acceptable coverage at each distribution cycle represents a formidable challenge to almost every vitamin-A distribution programme. Declining target group coverage is likely to be the single most important cause of ineffective xerophthalmia prevention.

Information on programme costs and effects is still scarce. Development of a standard budget schedule has been recommended by WHO. Suitable indicators of cost-effectiveness include the cost per dose recipient and cost per target-group recipient. On the basis of the sparse data available, the current cost per six-monthly dose recipient may be about US$0.44 per year in a universal-delivery system, and between US$0.22 and US$0.33 per capsule distributed in a targeted system.

Biological cost-effectiveness indicators include the cost per percent change in the prevalence or incidence of xerophthalmia, and possibly in mortality rates. Such information requires concurrent data on programme costs and effects, which are rare as yet. Preliminary benefit-cost analysis shows that the benefits of preventing xerophthalmia calculated in monetary terms can far outweigh programme costs, thus supporting the continued use of periodic vitamin-A distribution campaigns. Given the emerging evidence that vitamin-A supplementation may reduce mortality among children with even mild vitamin-A deficiency, the benefits from improving vitamin-A nutrition in a population may be even greater than those so far assessed.

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