Vitamin A Xerophthalmia Vernacular Terms Matang Manok Mata Ajam Khwak Moan Gred Gradei Mager Aagh Korapothu Chicken Eyes Chicken Eyes Dusk Blindness Scaly as Fish Fish Scales Scaly Tagalog Indonesian Khmer Thai Bengali Singhalese Impact of VADD on Public Health • 250 million preschool-age children have subclinical vitamin A deficient •7.2 million pregnant women • 3 million have clinical xerophthalmia • 300, 000 are blind from xerophthalmia Impact of Vitamin A Intervention on Child Survival “Improvement of vitamin A status in young child populations… leads to a reduction in all-cause mortality rates of about 23%.” United Nations, 1993 “Improved vitamin A nutriture would be expected to prevent approximately 1.3-2.5 million deaths annually among children aged under 5 years.” Bulletin of WHO, 1992 BUT Mechanisms involved are poorly understood Functions • Vision (night, day, colour) • Epithelial cell integrity against infections • Immune response • Haemopoiesis • Skeletal growth • Fertility (male and female) • Embryogenesis Tests of Vitamin A Status Subclinical • Relative dose-response test • Serum retinol Decreased Status • Retinal rod function • Conjunctival impression cytology (CIC) Clinical • Night blindness • Conjunctival and corneal eye signs Factors that may Affect Plasma Vitamin A or Retinol Levels • Liver disease deacreases plasma retinal levels, probably as a result of a combination of decreased synthesis and secretion of RBP. • Stress decreases plasma retinol levels. • Protein-energy malnutrition decreases RBP production because of a limited supply of protein substrate. Consequently hepatic release of vitamin A is impaired resulting in decreased serum retinol levels. • Zinc deficiency decreases plasma retinol levels via its role in the synthesis of RBP. • Infections and parasitic infections lower plasma retinol levels. • Cystic fibrosis is associated with a defect in the transport of vitamin A from the hepatic stores to the periphery resulting in decreased levels of circulating retinol and RBP. • Low fat diets impair absorption of vitamin A, lowering plasma retinol concentrations. • Estrogens, either endogenous or those used in contraceptive agents, increase plasma retinol and RBP apparently as a result of incresed mobilization of Vitamin A from the liver. • Age, sex and race influence serum retinol levels, as indicated by the NHANES II survey results. For the test, a baseline blood sample is taken immediately before the administration of a small oral dose (450µg) of vitamin A (as retinyl acetate or retinol palmitate); followed by a second blood sample, five hours later. The RDR (%) is calculated as: Plasma retinol at 5 hr – Plasma retinol at 0hr X 100 RDR(%) = Plasma retinol at 5 hr Vitamin-A-replete subjects have RDR values ranging from 0% to 14%. Relative dose response values greater than 14% to 20% are indicative of marginal vitamin A status in humans, the cutoff value depending on the coefficient of variation for the analytical method used to measure serum Percentage of Children with Positive RDR Test Classified by Serum Retinol Levels Serum Retinol (µg/dL) % Number Tested <20 100 12 21 - 29 86 21 30 - 40 26 19 >40 3 39 Total tested 91 Treatment Schedule (orally) Immediately on diagnosis: <6 months 50, 000 IU 6 months-12 months 100, 000 IU > 12 months 200, 000 IU Next day Same age-specific dose At least two weeks later Same age-specific dose Xerophthalmia Classification XN Night Blindness X1A Conjunctival Xerosis X1B Bitot’s Spot with Conjunctival Xerosis X2 Corneal Xerosis X3A Corneal Xerosis with ulceration X3B Keratomalcia XF Xerophthalmic Fundus XS Corneal scars from Xerophthalmia WHO criteria of a public health problem of xerophthalmia • Night Blindness (XN) In > 1% • Bitots spot (X1B) In > 0.5% • Corneal Xerosis/Ulceration/ Keratomalacia (X2, X3A, X3B) In >0.01% • Corneal scar (XS) In > 0.05% • Plasma retinol of <0.35µmol/l (10 µg/dl) In > 5% Percent with Serum Vitamin A: n <10 µg/dL 10-19 µg/dL >20 µg/dL 252 8 37 55 Children with nightblindness or Bitot’s 325 spots 30 55 15 Children with corneal xerophthalmia 75 24 1 Normal Children 98 Serum vitamin A levels in a sample of Indonesian children with and without ocular lesions. Conversion factor SI units(µmol/L)= x 0.035