Vitamin A Deficiency in Developing Countries

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Vitamin A Deficiency in Developing Countries
HSERV 590/NUTR 600 20 April 2007
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Global Distribution of Vitamin A Deficiency
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Under-5-mortality distribution of countries with
vitamin A survey information
Schultink, 2002
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Functions

• Vision (night, day, colour)
• Epithelial cell integrity against infections
• Immune response
• Haemopoiesis
• Skeletal growth
• Fertility (male and female)
• Embryogenesis

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Malnutrition and child death
VAD ?
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Association between xerophthalmia and mortality
Sommer, Hussaini, Tarwotjo, 1983
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Impact of vitamin A supplementation on child
mortality
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Impact of vitamin A on measles mortality
Sommer, West, 1996
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Maternal HIV-1 infection andvitamin A status
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Vitamin A status and some major childhood
infections

• benefit is greatest on measles
• fewer attendances in clinics
• fewer admissions to hospital
• little effect on respiratory infections
• Shigella gut infection reduced
• malaria reduced
• reduced mortality in children with HIV

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Impact of supplementation on mortality related to
pregnancy up to 12 weeks post partum
West, Katz, Khatry et al, 1999
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Stages of deficiency
Increasing deficiency

• Subclinical
• reducing stores
• lowering serum level
• metaplasia
• Clinical
• xerophthalmia
• - non-blinding
• - blinding

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Tests for assessment of vitamin A status
Decreasing status

• Subclinical
• relative dose-response test
• serum retinol
• retinal rod function
• conjunctival impression cytology (CIC)
• Clinical
• night blindness
• conjunctival and corneal eye signs

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Increasing impairment of retinal rod function,
illustrating the subclinical-clinical divide
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Progressive changes in conjunctiva and cornea,
illustrating the subclinical-clinical divide
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AS06
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Biological indicators of subclinical vitamin A
deficiency in children 6-71 months of age
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Xerophthalmia classification by ocular signs

• Night blindness (XN)
• Conjunctival xerosis (X1A)
• Bitots spot (X1B)
• Corneal xerosis (X2)
• Corneal ulceration/keratomalacia (X3A)
• lt1/3 of corneal surface
• Corneal ulceration/keratomalacia (X3B)
• ?1/3 of corneal surface
• Corneal scar (XS)
• Xerophthalmic fundus (XF)

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WHO, 1982
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WHO criteria of a public health problemof VADD

• Night blindness (XN) gt 1
• Bitots spot (X1B) gt 0.5
• Corneal sclerosis/ (X2, X3A, X3B) gt 0.01
  ulceration/keratomalacia
• Corneal scar (XS) gt 0.05
• Retinol gt 5 lt0.35 mmol/l (10 mg/dl)

WHO, 1982
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Scheme for the classification of night blindness
by interview

• Does your child have any problem seeing in the
  daytime?
• Does your child have any problem seeing at
  nighttime?
• If yes, is this problem different from other
  children in your community?
• Note this question is particularly appropriate
  where VAD is not very prevalent
• Does your child have night blindness?
• Use local term that describes the symptom

WHO, 1996
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Conjunctival xerosis (X1A) and corneal xerosis
(X2)
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Bitots spot (X1B)
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Characteristics of vitamin A-responsive Bitots
spots (X1B)

• Subject usually a child less than 6 years of age
• With the maximum vitamin A dosage, response
  usually evident within one week
• Usually accompanied by generalised conjunctival
  xerosis and night blindness
• Males more commonly affected than females

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Characteristics of vitamin A- unresponsive
Bitots spots (X1B)

• Commonly occur in children over 6 years and in
  otherwise healthy adults
• Usually a small, single spot
• No accompanying evidence of VAD
• Largely responsible for the apparent increase of
  X1B prevalence with increasing age

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Conjunctival and corneal xerosis (X1A and X2)
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Keratomalacia (X3A, X3B)
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Keratomalacia
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Corneal scarring (XS)
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Why do children become vitamin A deficient?

• Mothers of poor children often have VAD and
  produce deficient breast milk
• Childrens diets provide too little vitamin A
• Children spend a large part of their
  childhoodbeing sick
• Provitamin A carotenoids in vegetables and
  fruitsare less readily bioavailable than
  previously thought
• Early weaning is often onto foods low in vitamin
  A
• Growth velocity, and therefore vitamin
  Arequirement, is higher during pre-school age
  than atany other time postnatally

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Humphrey, Katz et al, 2002
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Major food sources

• Dark green leafy vegetables
• Yellow fruits
• Carrots
• Palm oils
• Liver and liver oils

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Examples of common vegetable/fruit-carotenoid
sources
mg RE/100 g edible portion Red palm
oil 30000 Buriti palm (pulp)
3000 Carrots 2000 Dark green leafy
vegetables 685 Sweet potato, red and yellow
670 Mango golden 307 Apricot
250 Papaya 124 Tomato 100
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Examples of common animal vitamin A sources
mg retinol/100 g edible portion Fatty fish
liver oils Halibut 900,000 Shark 180,0
00 Cod 18,000 Herring and
mackerel 50 Dairy
produce Margarine - fortified
900 Butter 830 Cheese, fatty type
320 Eggs
140 Milk 40 Meats Liver of sheep
and ox 15,000 Beef, mutton, pork
0-4
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Hierarchy of carotenoid bioavailability
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Retinol Activity Equivalent (RAE)
1 mg RAE 1 RE of retinol 1 mg retinol 2
mg b-carotene in oil 12 mg b-carotene in mixed
foods
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Children being taught about foodstuffs rich in
vitamin A
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Food supply of vitamin A - from provitamin A
carotenoids and preformed vitamin A food sources
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Control of VADD

• Supplementation
• Fortification
• Diet diversification
• Infectious disease control
• Disaster relief
• Plant breeding

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A child receiving a vitamin A capsule
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Periodic oral supplementation, IVACG 2001

• Infants 0-5 months 50,000 IU
• With each of the three infant doses of DPT/Polio
• Young children 6-11 months 100,000 IU
• Every 4-6 months
• Children 12-59 months 200,000 IU
• Every 4-6 months
• Women 15-44 years 200,000 IU
• Within 6 weeks of delivery, two doses gt24
  hoursapart for a total of 400,000 IU

IVACG, 2001
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Coverage of vitamin A supplementation in children
6-59 months old, Nicaragua
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Prevalence of VADD (serum retinol lt 20mg/dl) in
children 6 - 59 months old, Nicaragua
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Treatment schedule (orally)
Immediately on diagnosis lt6 months 50,000
IU 6-12 months 100,000 IU gt12 months 200,000
IU Next day Same age-specific dose At least
two weeks later Same age-specific dose Women of
reproductive age 200,000 IU with
xerophthalmia with milder eye signs 10,000
IU/d or 25,000 IU/week for 4 weeks
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WHO, 1997
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Prevention 2 Food fortification
Scientific rationale Economic
viability Industrial capacity Community
acceptance Training Sustainability
Advocacy Monitoring Legislative support
Quality control

• Economic viability
• Community acceptance
• Sustainability
• Monitoring
• Quality control

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Vitamin A-fortified sugar
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Prevention 3 Dietary diversification
Advantages Ultimate solution Community
involvement Generating income Provides other
nutrients Components Production (home,
school) Consumption (by vulnerable
groups) Problems Long-term cooperation Difficult
in slums and desert areas
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Promotion of training and education
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Nepali women and children during a vitamin A
distribution campaign
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Recent insights into dietary control of VADD in
developing countries

• Mean daily provitamin A intake is only 470 mg
  RE/day and not 720 as earlier calculated
• Provitamin A activity 40 lower than previously
  stated
• Solely vegetarian diet probably not protective
• Recent research explains why VADD have persisted
  despite abundant provitamin A food supplies

West, McLaren, 2002
20 April 2007