Zinc supplementation to improve treatment outcomes among children diagnosed with respiratory infections
Biological, behavioural and contextual rationale
Zinc is an essential trace element required for maintaining intestinal cells, bone growth, and immune function. Children who are living in low-income settings are often undernourished and zinc deficient (1,2). Severe zinc deficiency has been associated with stunting of growth, impaired immunity, skin disorders, learning disabilities and anorexia (3,4). Deficiencies may arise from the insufficient intake of foods containing zinc or insufficient absorption. Most foods high in zinc are of animal origin, such as meats, fish and dairy products. These foods may be more difficult to access for low-income populations. Dietary fibre and compounds called phytates, which are often found in foods such as cereals, nuts and legumes, bind to zinc and result in poor absorption (5,6). Frequent diarrhoea, that is also associated with chronic undernutrition, may further deplete body stores of zinc (7,8).
Zinc deficient children are at increased risk of restricted growth and developing diarrhoeal diseases, as well as respiratory tract infections such as acute lower respiratory tract infections (9–11). Diarrhoeal disorders and acute lower respiratory tract infections, especially pneumonia are the two most common causes of infant and child death in low-income countries (12). Undernutrition is considered the underlying cause of approximately half of these fatal acute lower respiratory tract infections (11). Pneumonia alone kills more children each year than AIDS, malaria or measles combined, with over two million deaths per year (13). Some research studies have suggested that zinc supplementation may reduce the number of episodes and severity of bronchiolitis and pneumonia cases (9,14–19) in children. Zinc supplementation in combination with oral rehydration solution has already formed the basis of the WHO/UNICEF recommendation for use in the management of children with diarrhoea (20).
Zinc is thought to help decrease susceptibility to acute lower respiratory tract infections by regulating various immune functions, including protecting the health and integrity of the respiratory cells during lung inflammation or injury (21). Studies of zinc supplementation for the treatment or improved management of acute lower respiratory tract infections, including pneumonia have had mixed results (14,22–27). A recent review and meta-analysis of existing studies, for example found that the beneficial effects of zinc supplementation have been most clearly demonstrated in south Asia, when children were given at least 70 milligrams of zinc per week (19). This review was not able to determine, however, whether zinc supplementation would be less effective if lower doses were given or if supplementation would have less of an impact on acute lower respiratory tract infection rates in other geographical regions. In resource-limited settings, it has also been difficult to determine zinc deficiency and as such, it can be difficult to effectively target populations most at risk (10,28,29). Another systematic review has demonstrated that zinc supplementation was significantly associated with reducing rates of pneumonia, and recommended supplementing zinc intake in deficient populations (18).
A range of supplementation doses have also been assessed, from 15 mg to 140 mg per week, with the upper range exceeding the recommended daily intake (RDI) for children of 2 mg per day for children less than one year of age and up to 7 mg per day for children between 1 to 3 years (30). It is important to better understand optimal supplementation doses, especially because high dosages of zinc and long-term supplementation have been shown to be associated with the inhibition of absorption of other nutrients such as copper and iron (14,23,31,32) as well as poorer survival rates for children with HIV (33). Dietary impacts on micronutrient absorption should also be considered, as it has been suggested that the bioavailability of zinc is greater in more refined urban diets (27,34). In addition, supplementation is not the only route to decrease nutrient deficiencies that may make children more susceptible to infection. Decreasing the consumption of absorption-inhibiting foods, dietary diversification and food fortification should also be investigated as possible alternatives (26).
A number of authors have confirmed that routine zinc supplementation for more than three months does have a positive effect on reducing the duration of acute lower respiratory tract infections among children in developing countries (11,19,35,36). These effects observed could translate into major absolute reductions in childhood morbidity and mortality rates given the numbers of children who die from acute lower respiratory tract infections every year (9). It remains important to better understand how zinc may also work in conjunction with antibiotics in the treatment of children with severe acute lower respiratory tract infections and to reduce the number of child deaths due to pneumonia.
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