ABSTRACT
Vitamin A deficiency (VAD) is a serious and widespread public health problem in the Philippines. Initiated in 1993, the Philippines National Vitamin A Supplementation Program (NVASP) is one of the oldest, most mature and comprehensive of its kind. This paper presents a cost-effectiveness and efficiency analysis of the NVASP and of a hypothetical program of vitamin A fortification of wheat flour that was conducted to inform policymakers as to how to modify the program. Employing a proxy effectiveness indicator of VAD--the intake of < 70% of the recommended daily allowance of vitamin A--in a series of simulations using individual child consumption data, the analysis finds that fortification is more efficient in reducing inadequate vitamin A intake (IVAI) compared to the NVASP. Due to the nature of food consumption patterns, however, fortification alone, is not enough. At what is regarded as the maximum politically acceptable fortification level, there will still be 2.2 million (29%) Filipino children aged 12-59 months who will have IVAI. An investigation of the cost and efficiency of geographically targeted supplementation programs reveals that maintaining a universal supplementation program in urban areas and, in rural areas, introducing a targeted program to only the poorest municipalities (where the prevalence of VAD is the highest) will provide a more acceptable public health policy response than fortification alone. Such a policy will reduce incremental direct Government expenditures on vitamin A programs by nearly 20% and will reduce the number of children with IVAI to 900,000 (12%) Filipino children. The paper describes the fortification and supplementation programs, and how their costs were estimated. Lessons for program designers and policymakers in other countries in which vitamin A deficiency constitutes a public health problem are also discussed.
Subject(s)
Health Care Costs , Health Planning , National Health Programs/economics , Vitamin A Deficiency/prevention & control , Child, Preschool , Cost-Benefit Analysis , Dietary Supplements/economics , Flour , Food, Fortified/economics , Health Expenditures , Humans , Infant , Marketing of Health Services/economics , Models, Econometric , National Health Programs/organization & administration , Philippines/epidemiology , Vitamin A Deficiency/epidemiologyABSTRACT
This paper compares the functional properties of ion channels formed in planar lipid membranes by the wild and mutant Staphylococcus aureus alpha-toxin. It was shown that replacement of the amino acid Gly at position 130 by Cys in the primary structure of the toxin decreases the single-channel conductance with a concomitant decrease in the pH at which the channel becomes unable to discriminate between Cl- and K+ ions. The mutation also induced an increase in the asymmetry in the current-voltage relationship of the channel. The results of our experiments suggest that the trans-mouth of the channel is responsible for all the observed changes in channel properties. It was assumed that this entrance is built by the glycine-rich hinge portion of the toxin and is situated close to the surface of monolayer facing the trans-compartment.
Subject(s)
Bacterial Toxins/chemistry , Hemolysin Proteins/chemistry , Ion Channels/metabolism , Lipid Bilayers/metabolism , Staphylococcus aureus/chemistry , Bacterial Toxins/genetics , Bacterial Toxins/metabolism , Electric Conductivity , Electrophysiology , Glucose/metabolism , Hemolysin Proteins/genetics , Hemolysin Proteins/metabolism , Hydrogen-Ion Concentration , Membrane Potentials , Mutation , Particle Size , Phosphatidylcholines/metabolism , Phospholipids/metabolism , Polyethylene Glycols/metabolism , Sucrose/metabolismABSTRACT
Replacement of an amino acid residue at position 130 -Gly by Cys- in the primary structure of Staphylococcus aureus alpha-toxin decreases the single-channel conductance induced by the toxin in planar lipid bilayers. Concomitantly, the pH value at which the channel becomes unable to discriminate between Cl- and K+ ions is also decreased. By contrast, the pH dependence of the efficiency of the mutant toxin to form ion channels in lipid bilayers was unchanged (maximum efficiency at pH 5.5-6.0). The asymmetry and nonlinearity of the current-voltage characteristics of the channel were increased by the point mutation but the diameter of the water pore induced by the mutant toxin, evaluated in lipid bilayers and in erythrocyte membranes, was found to be indistinguishable from that formed by wild-type toxin and equal to 2.4-2.6 nm. Alterations at the "trans mouth" were found to be responsible for all observed changes of the channel properties. This mouth is situated close to the surface of the second leaflet of a bilayer lipid membrane. The data obtained allows us to propose that the region around residue 130 in fact determines the main features of the ST-channel and takes part in the formation of the trans entrance of the channel.
