.. Malaria Morbidity in Young Children Vitamin A is often deficient in individuals living in malaria endemic areas, is essential for normal immune function, and several studies show it could play a part in potentiating resistance to malaria. Studies have shown that vitamin A deficient rats and mice are more susceptible to malaria than normal animals, and this susceptibility is readily reversed by vitamin A supplementation. Also, a genetic locus, which includes cellular retinol-binding protein, influences malaria mortality and parasitemia in mice. In vitro, addition of free retinol to P.falciparum cultures reduced parasite replication in one study but not in another (Shankar A H, et al 1999). In humans there has been evidence for the role of protective vitamin A but it has not been proven.
Although cross sectional studies with children and adults have shown that low plasma vitamin A concentrations are associated with increased blood parasite counts. However increased parasite counts can trigger an acute phase response, which transiently depresses the circulating vitamin A concentration. The number of episodes of falciparum malaria among children in Papua New Guinea was 30% lower in children that received vitamin A supplementation than in those who received a placebo. At a cost of US $0.03 per supplement and US $0.25 per delivery, vitamin A ranks at supplementation ranks among the more cost effective non-pharmacological interventions for malaria. The mechanism by which vitamin A affects morbidity due to P.
falciparum remain unknown. Also the beneficial effects of vitamin A are less evident in children younger than 1 year (Shankar A H, et al 1999). Nutrient status influences immune function and resistance to disease. It is also thought that other nutrients such as zinc and thiamine may also reduce malaria morbidity. Cost, safety, and potential efficiency of targeted nutritional supplementation suggest that a rational approach to development of such interventions for malaria would be useful. These could be integrated with other controls such as treated bednets, chemoprophylaxis, future detection and rapid detection and treatment. Vitamin A supplementation may be an effective, inexpensive, and programmatically way of controlling P.
falciparum malaria. Fortification Vitamin A deficiency is a serious public health problem in Guatemala, affecting an estimated 22% of all children under five (Phillips, M, et al, 1996). There is considerable international evidence that rectifying vitamin A deficiencies offers important health benefits and at relatively low cost, making such programs highly cost effective. Though in the case of Guatemala some approaches may be more efficient than others (Phillips, M, et al, 1996). There are three main strategies for combating vitamin A deficiency world-wide.
These strategies are food fortification, capsule distribution and diet modification. Guatemala has examples of each of these three strategies in operation. The sugar fortification programme, initiated in 1987-88, established by law that all sugar that is processed and marketed for direct household consumption in the country should contain 15 mg of vitamin A per gram of sugar. A level originally designed to meet 100% of the vitamin A requirements given average sugar consumption per day for young children. This national fortification program has been complemented by geographically targeted interventions in areas where localised deficiencies where detected.
These include the distributing vitamin A capsules and promoting the production and consumption of vitamin A rich foods in areas which had high prevalence of vitamin A deficiency (Phillips, M, et al, 1996). In contrast to the capsule and food production/education programs, fortification reaches individuals regardless of their need for vitamin A and unlike the capsule program is not specifically targeted at women and children. The low cost of distributing the fortificant through sugar compensates for the fact that quite a substantial amount of the vitamin A reaches consumers who do not need it. The only time when fortification looked lees attractive was in the 1989 program, when very low fortificant levels where detected in sugar samples despite adequate amounts of vitamin A being imported. The cost effectiveness of the capsule and food production/education programs has been high as the areas where they are implemented are often dispersed rural areas meaning transportation costs are high.
Although the capsule method seems to be more effective when considering high risk groups (Phillips, M, et al, 1996). Also a suitable vehicle for fortification must be considered if it is to be implemented. The food should be one which is consumed in a fairly homogeneous fashion by the targeted group, one which it is technically and economically feasible to fortify and one which will be culturally acceptable after fortification. With a very small budget it would probably be more worthwhile to invest in a focussed capsule distribution or perhaps a food production/education program in a high deficiency area rather than in fortification, whose effects would be highly diluted. Where universal coverage is not possible, it may be necessary to assess the relative efficiency of targeting interventions at different geographical areas (West, K, P, et al 1984). Vitamin C (Ascorbic Acid) Vitamin C is responsible for a number of benefits; it promotes healthy capillaries, gums, teeth, aids iron absorption, treats anaemia, especially for iron-deficiency anaemia, increases iron absorption from intestines, contributes to haemoglobin and red-blood-cell production in bone marrow, blocks production of nitrosamines.
Pregnancy requires vitamin-C supplements because of demands made by bone development, teeth and connective-tissue formation of fetus. Breast-feeding requires vitamin-C supplementation to support rapid growth of child. Anaemia as we know is a major public health problem. As in many developing countries, the most vulnerable population groups are pregnant and lactating women and pre-school and school-age children. School-age children are highly vulnerable to iron deficiency because there iron requirements for growth often exceed the dietary iron supply.
Several strategies have been proposed to overcome this problem including the use of iron supplements. This approach is effective but its usefulness is often limited by low compliance. Food fortification with iron is generally considered the most effective way to increase iron intake and can be achieved by fortifying a dietary staple such as cereal flour or by fortifying widely consumed foodstuffs such as sugar and salt. This strategy supplies everyone in the population with iron supplements including people who do not need it like adult men and postmenopausal women. The preferred approach to target children would be to fortify a speciality food for that age group. One possibility would be to fortify a chocolate-flavoured milk drink with iron as was done in a recent study (Davidson, L, et al 1998). These chocolate drinks as well as milk contain inhibitors of iron absorption. A way around this is to add vitamin C (ascorbic acid) as is done in industrially produced foods. The study showed the effect of added ascorbic acid on iron absorption from the chocolate flavoured drink was clear. The geometric mean iron absorption increased from 5.4% to 7.7% when the ascorbic acid content was doubled, from 25 to 50 mg.
The enhancing effect of ascorbic acid on iron absorption is believed to be due to its ability to reduce ferric iron to ferrous iron, which binds less strongly with polyphenols and phytic acid (found in the test meal) to form insoluble complexes (Fairweather-Tait, S, and Hurrel, R F, 1996). Iron Erythrocytic malaria parasites live in the blood which is rich in haemoglobin, a ready source of nutrients, but also a potential source of toxic forms of iron. In acquiring nutrients the parasites take up large quantities of haemoglobin. In this process, globin is hydrolysed to free amino acids and haem is converted to haemozoin. Globin hydrolysis is presumed to provide the bulk of amino acids for parasite protein synthesis, and haem processing is thought to both detoxify haem molecules and provide necessary parasite iron. The processes of haemoglobin catabolism and iron utilisation are targets for a number of compounds with antimalarial activity. Erythrocytic parasites require iron for the synthesis of iron containing proteins such as ribonucleotide reductase, superoxide dismutase and cytochromes and for de novo haem biosynthesis.
The source of free iron for malaria parasites is not known. Three possible sources are serum iron, free erythrocytic iron and haemoglobin. There are some reports of iron uptake from serum by parasitised erythrocytes, supporting a serum source for parasite iron. This backs-up the observations that iron deficient individuals are partially protected against malaria infection. Although studies showing a lack of transferin receptors on parasitised erythrocytes, argues against a serum source for parasite iron (Peto, T E A, Thompson, J L, 1986). Observations show that cell-impermeant, serum depleting, iron chelators have no antimalarial activity in culture.
A report showed that the antimalarial effects of iron chelators in mice are independent of host iron status and a study showed that the course of malaria in children is unaffected by iron supplementation (Peto, T E A, Thompson, J L, 1986). Arguing against free erythrocytic iron as the source of parasite iron are observations that iron chelators inserted into the erythrocyte cytoplasm are non toxic to cultured parasites. Considering this, the large amount of haemoglobin that is degraded by erythrocytic parasites, and the observation that small amounts of iron are released from haem after incubation at the pH of the food vacuole, it is logical that haemoglobin is the principal source of parasite iron (Rosenthal P J and Meshnick, S R, 1996). Although this has never been tested. The best studied antimalarial iron chelator is deferoxamine (desferrioxamine B, DFO). Its antimalarial activity has been demonstrated in vitro, in animals and patients with both moderate and severe P.
falciparum infections. The entry of DFO into the parasite is essential for antimalarial activity. DFO treatment of patients with cerebral malaria had a much greater effect on coma recovery time than on parasite clearance time, suggesting that iron chelation may have an effect on the disease process beyond its anti parasitic effect (Rosenthal, P J, 1996). This suggests that it may be possible that iron deposition in tissue may be partially responsible for severe malaria. Indeed, haemozoin deposition in the brain was significantly higher in mice with cerebral malaria like illness than in mice with ordinary malaria. Although DFO has shown promising activity, it is unlikely to be of practical use as it is expensive and must be administrated by continuous infusion. A number of other iron chelators have shown antimalarial activity in vitro and in vivo.
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