Using Stable Isotope Techniques to Monitor and Assess the Vitamin A Status of Children Susceptible to Infection
Condition: Vitamin A Deficiency
MeSH terms: Night Blindness; Vitamin A Deficiency
Study type: Interventional

Summary: 
      The combination of infectious diseases and malnutrition is the most prevalent, preventable
      public health problem in the world, responsible for millions of deaths annually, particularly
      in infants and children. Approximately 13 million children die each year in developing
      countries from infectious diseases, with the majority of these deaths related to
      malnutrition. The relationship between infections and malnutrition is synergistic, each
      further compromising the outcome of the other. Malnutrition compromises natural immunity
      leading to increased susceptibility to infections, more frequent and prolonged disease
      episodes, and increased severity of disease. Likewise, infections can aggravate or
      precipitate malnutrition through decreased appetite and food intake, nutrient malabsorption,
      nutrient loss or increased metabolic needs. Another issue is that infections (as well as
      overweight and obesity status) affect nutritional biomarkers making it difficult to assess
      the real magnitude of some nutritional problems. This is the case of vitamin A. Vitamin A
      deficiency is defined to be of severe public health importance if 20% or more of a defined
      population has a serum retinol concentration of less than 0.7 µmol/L. However, circulating
      concentrations of serum retinol are reduced by infections and in such situations serum
      retinol concentration is not a good indicator of vitamin A status. Serum acute-phase proteins
      can indicate the severity and duration of an infection. Correcting vitamin A deficiency is
      addressed in Ethiopia through vitamin A supplementation of children, dietary diversity and
      using bio-fortified foods. However, assessing vitamin A status, and the effectiveness of
      government interventions, is challenging in settings where infectious diseases are endemic,
      as in most area of the country. Evaluation of vitamin A status is relatively insensitive when
      based on changes in serum retinol concentrations, which are homeostatically controlled and
      negatively affected by subclinical infections. Liver stores of vitamin A, the best indicator
      of vitamin A status, cannot be routinely evaluated. The isotope dilution technique is the
      preferred method for determining vitamin A status and assessing the efficacy and
      effectiveness of intervention programs aimed at improving vitamin A status. It is the only
      indirect assessment method that provides a quantitative estimate of vitamin A status across
      the continuum of deficient to excessive stores.
    

Detailed description: 
      Vitamin A deficiency is the leading cause of preventable blindness in children and is
      associated with a higher risk of under five mortality. Approximately 250,000 to 500,000
      children in developing countries become blind each year owing to vitamin A deficiency, with
      the highest prevalence in South Asia and Africa. In Africa, many countries have implemented
      vitamin A interventions of mega-dose supplementation for children under 5 years, sometimes in
      combination with food fortification programs.

      Vitamin A deficiency is a major nutritional concern; with more than 37.7% of under five
      children being vitamin A deficient by serum retinol and 50.7% had been sick in the previous
      15 days in Ethiopia. Vitamin A deficiency is addressed in the country through vitamin A
      supplementation every six months for 6-59 months of children and during the first 45 days of
      delivery for lactating mothers. There are also other vitamin A intervention programs like
      bio-fortification of orange flesh sweet potato (OFSP) in pocket areas. Unfortunately,
      assessing vitamin A status, and the effectiveness of government interventions, is challenging
      in settings where infectious diseases are endemic, as in most African countries including
      Ethiopia. This is because serum retinol concentration decreases during infection due to the
      acute phase response.

      The overall national prevalence of any helminthes infection in Ethiopia was 29.8% with
      variable degree of prevalence among regions, where by southern nation nationality people
      (SNNP) (51%) and Gambella (51%) have the highest prevalence. A survey in 13 foods for
      education program-supported schools in the SNNP region indicated that prevalence of soil
      transmitted helminthiasis infections are 44.4%. The proportion of school children infected
      with any parasite species was 55.4%. A. lumbricoides was the most prevalent species 32.1%,
      followed by hookworm 21.7%.

      Forty seven subjects (26 male and 21 female) met the survey definition of smear positive
      tuberculosis (TB) cases, with a prevalence of 108/100,000 (72-138). From smear positive TB
      cases, 37(78.7%) were new cases, 2(4.3%) were on treatment, and 8(17%) were previously
      treated in the last five years. Malaria prevalence is 4.5% in the malaria endemic area.

      Evaluation of Vitamin A status is relatively insensitive when based on changes in serum
      retinol, which is homeostatically controlled and negatively affected by subclinical
      infections. Liver stores of vitamin A are the best indicator of vitamin A status, but cannot
      be routinely evaluated. The isotope dilution technique is the preferred method for
      determining vitamin A status and assessing the efficiency and effectiveness of intervention
      programs. It is the only indirect assessment method that provides a quantitative estimate of
      vitamin A status across the continuum from deficient to excessive vitamin A.

      Hence, this project will assess the vitamin A and inflammatory status of 3-5 year old
      children 4-5 months after their semi-annual mega-dose vitamin A supplementation. The results
      will indicate the proportions of sampled children with low, normal or high vitamin A status,
      how inflammation (from obesity or recent infection or injury) affects assessment of vitamin A
      status using different vitamin A assessment methods, and how status differs by country, in
      possible association with food fortification practices.

      Gap /Problem /Needs Analysis

      The combination of infectious diseases and malnutrition is the most prevalent, preventable
      public health problem in the world, responsible for millions of deaths annually, particularly
      in infants and children. Approximately 13 million children die each year in developing
      countries from infectious diseases, with the majority of these deaths related to
      malnutrition. The relationship between infections and malnutrition is synergistic, each
      further compromising the outcome of the other. Malnutrition compromises natural immunity
      leading to increased susceptibility to infections, more frequent and prolonged disease
      episodes, and increased severity of disease. Likewise, infections can aggravate or
      precipitate malnutrition through decreased appetite and food intake, nutrient mal-absorption,
      nutrient loss or increased metabolic needs. Severe malnutrition often masks symptoms and
      signs of infectious diseases making prompt clinical diagnosis and treatment very difficult.
      Another issue is that infections (as well as overweight and obesity status) affect
      nutritional biomarkers making it difficult to assess the real magnitude of some nutritional
      problems. This is the case of vitamin A. Vitamin A deficiency is defined to be of severe
      public health importance if 20% or more of a defined population has a serum retinol
      concentration of less than 0.7 µmol/L. However, circulating concentrations of serum retinol
      are reduced by infections and in such situations serum retinol concentration is not a good
      indicator of vitamin A status. Infections are accompanied by an acute phase response, and
      serum acute-phase proteins can indicate the severity and duration of an infection.
      Acute-phase proteins, such as C-reactive protein (CRP), increase within the first 6h of
      infection, and reach their maximum concentrations within 24-48h. However,
      α1-acid-glycoprotein (AGP) rises more slowly, with maximum concentrations 2-5 days after
      infection. Vitamin A deficiency is a major nutritional concern in poor societies affecting
      190 million children globally.

      Vitamin A is an essential nutrient needed for the visual system, and maintenance of cell
      function for growth, epithelial integrity, red blood cell production, immunity and
      reproduction. All infants are born with low stores and depend on vitamin A from breast milk
      to initially accumulate and maintain adequate stores. Infants of vitamin A depleted women are
      at greater risk of becoming vitamin A deficient early in life, especially if they are not
      breast fed. Correcting vitamin A deficiency is addressed by some African countries through
      vitamin A supplementation of children and food fortification programs. However, assessing
      vitamin A status, and the effectiveness of government interventions, is challenging in
      settings where infectious diseases are endemic, as in most African countries. Evaluation of
      vitamin A status is relatively insensitive when based on changes in serum retinol
      concentrations, which are homeostatically controlled and negatively affected by subclinical
      infections. Liver stores of vitamin A, the best indicator of vitamin A status, cannot be
      routinely evaluated. The isotope dilution technique is the preferred method for determining
      vitamin A status and assessing the efficacy and effectiveness of intervention programs aimed
      at improving vitamin A status. It is the only indirect assessment method that provides a
      quantitative estimate of vitamin A status across the continuum of deficient to excessive
      stores. Thus, this technique can be used for assessing vitamin A status in populations at
      risk of excessive status due to exposure to too much vitamin A through combined
      supplementation and consumption of fortified foods and/or preformed vitamin A-rich foods. The
      aim of this project is to use nuclear techniques to evaluate vitamin A nutritional status of
      young children during semi-annual administration of vitamin A supplements, and to assess how
      this relates to infection status.

      The International Atomic Energy Agency (IAEA) has provided significant support on use of
      stable isotopes in assessing body composition and breast milk to Member States in Africa, it
      is now establishing the stable isotope technique to assess vitamin A body stores in Cameroon
      and Zambia (and additional implementation is possible in other country) for use throughout
      the region. These inputs will be used in this project to provide key information to
      stakeholders on how vitamin A intervention programs affect vitamin A status in children and
      how infections affect vitamin A status or validity of stable isotope techniques.

      Role of nuclear technology The nuclear techniques used will be the deuterated- and 13
      Carbon-retinol body pool measurements to assess vitamin A status. These nuclear methods are
      useful across the continuum of nutritional status from deficient to adequate to excess, in
      contrast with the more common measurement of serum retinol concentrations. In addition, the
      presence of infection/inflammation is less likely to interfere with interpretation of the
      nuclear method than that of the serum retinol method, but this will be investigated in this
      series of studies. This method is already being established in 2-3 countries and the serum
      retinol method is established in approximately 8 countries. Further use of the deuterated
      retinol body pool size nuclear method will contribute to capacity building in Africa, where
      vitamin A supplementation of children and widespread fortification are routine. The
      combination of multiple vitamin A interventions requires continuous monitoring. The IAEA is
      expected to provide technical and logistical support for the use of isotope dilution methods
      and facilitate Fellowships, Training, Scientific Visits, Expert Missions and Supplies.
    

Intervention name(s): Mega-dose of vitamin A supplement
Intervention type(s): Dietary Supplement
Intervention description(s): vitamin A supplementation normally given every six months for under five children in Ethiopia. In addition, there is also dietary intervention like orange flash sweet potato and promotion of other vitamin A rich foods to tackle vitamin A deficiency in Ethiopia.
Intervention MeSH terms: Vitamin A
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science