IMMUNITY, INFECTION, AND ZINC

The vital role it plays in sustaining appropriate immunological function is closely related to these effects. According to research, zinc shortage inhibits cell regeneration, epithelial barrier functions, and linear growth (22). Immune function is also hampered by zinc deficiency, which results in diminished cell-mediated immune responses, decreased T-lymphocytes, aberrant T-helper and/or suppressor activities, impaired macrophage function, and decreased killer cells and antibody-dependent cytotoxicity (23,24). In children with acute diarrhoea, zinc supplementation raises complement levels in the blood (Qadri F. Personal communication, 2006). Zinc levels also influence the activity of polymorphs of monocytes, macrophages, and neutrophils, as well as the release of reactive free radicals from phagocytes (23). Immune function abnormalities occur even at low levels of zinc deficiency.

Improved absorption of water and electrolytes by the intestines (25-27), regeneration of gut epithelium (28-31), increased levels of enterocyte brush-border enzymes (32,33), and enhanced immunologic mechanisms for infection clearance are some of the possible mechanisms of zinc treatment’s effect on the duration and severity of diarrhoea. Zinc supplementation boosts immunity (34-36), which may promote the fast clearance of diarrhoeal germs from the colon.

Alterations in zinc levels also disrupt innate immunity, the body’s initial line of defense against infections. Normal serum zinc levels are required for normal natural killer cell numbers and function (37). These levels also influence how monocytes, macrophages, and neutrophils operate (23). Zinc is also essential for T-lymphocyte growth and activation. When zinc supplements are given to those who have low zinc levels, the number of T-cell lymphocytes circulating in the blood increases, and lymphocytes’ ability to fight infection improves.

MORBIDITY AND ZINC DEFICIENCY

Given the multiple physiologic activities that rely on appropriate zinc levels, notably immunology, it is not unexpected that zinc shortage is linked to a variety of infectious diseases, but the link between diarrhoea and zinc is particularly well-established. Diarrhoea causes zinc loss and zinc metabolism problems. Significant amounts of zinc are lost during acute diarrhoea: in children, daily zinc losses during diarrhoea can be as high as 160 g/kg per day (38).

How significant are minor zinc deficiencies? Clinical and field investigations have consistently found a link between zinc deficiency and morbidity from infectious illnesses, especially diarrhoea in infancy (39-41). A 50% increase in the risk and number of days with diarrhoea is associated with marginal zinc deficiency. However, zinc deficiency causes an increase in the prevalence of other infectious disorders such as skin infections, lung infections, malaria, and delayed wound healing (17). Children who are zinc deficient are three times more likely to get an acute respiratory infection.

ZINC SUPPLEMENTATION EFFECTS

The RDA for infants aged 0-6 months is 2.0 mg per day, and it is 3.0 mg per day for young children aged 7-36 months (42). However, the quantity of zinc required in young newborns to maintain a positive zinc balance in places where zinc shortage is common remains uncertain. The bulk of published outcomes of zinc treatment efficacy trials evaluated dosages of elemental zinc ranging from 10 mg (infants) to 20 mg (under-five children) per day, a level that is safe in these children. Doses of up to 70 mg twice a week have been administered with no adverse effects or clinically severe copper deficiency.

Over the last decade, several controlled zinc-therapy experiments have established zinc’s positive function in the prevention and treatment of diarrhoea (1-3,6-9,44,45). According to meta-analyses of these trials, children aged three months to five years who get zinc for the treatment of a diarrhoeal sickness (20 mg/day for 10 days) recover faster and have a 30% lower risk of having persistent diarrhoea. Over the next 3-6 months, there is a 30% reduction in the chance of a repeat episode and an estimated 50% reduction in non-injury mortality.

Zinc has also been shown to be useful as a daily supplement in the prevention of diarrhea. A community-based, double-blind, randomized experiment in India found that children who got daily zinc supplementation for six months had a 26% lower incidence and a 35% lower prevalence of diarrhoea (48). In a trial of zinc supplementation (10 mg/day) in growth-retarded Vietnamese children, the incidence of diarrhoea was reduced by 71%. (49). A similar research in Mexico discovered that zinc-supplemented (20 mg/day) children had a 36% decreased incidence of diarrhoeal episodes (50). Zinc supplementation has also been shown to lessen the incidence of chronic diarrhoea and the risk of dysentery in zinc-deficient children (51). According to a Guatemalan study, zinc supplementation reduces the occurrence of all forms of diarrhoea (52). Zinc supplementation increases growth in children with diarrhoea, according to research from Bangladesh.

The table summarizes numerous recently published studies that looked at the preventive effects of zinc, either as a therapy or as a daily supplement. According to the table, either technique appears to provide protection against future occurrences of acute diarrhoea, and the protection lasts for 3-6 months after treatment or discontinuation of supplements. The medication also reduces the chances of an acute bout of diarrhoea progressing to a prolonged (>7 days) or chronic (>14 days) episode.

ZINC SCALING UP AS A TREATMENT FOR CHILDHOOD DIARRHEA

The most difficult problem for health researchers, practitioners, and funding organizations is determining how to translate zinc’s demonstrated effectiveness as a medication into action that will help the lives of young children, particularly those living in chronic poverty and malnutrition. ICDDR, B started the Scaling Up Zinc for Young Children (SUZY) Project in 2003 with the goal of putting Bangladesh on the path of delivering zinc treatment to all under-five children with diarrhoea, regardless of gender, income, or geographic location. The SUZY Project has been organized around five key activities to achieve this goal: (a) registration, production, and distribution of zinc tablets; (b) promotion among healthcare providers and mass media campaign; (c) professional training and introduction of zinc treatment into public, private, and NGO delivery systems; (d) formative and operations research in support of scaling up; and (e) knowledge transfer from Project findings.

In terms of registration and production, the Project decided to pursue the WHO-recommended scaling up of a dispersible, 20-mg zinc sulphate tablet (today known as ‘Baby Zinc’ in Bangladesh). The tablet is placed in a spoon or small cup, and water is added to dissolve it into a pleasant, vanilla-flavored syrup that conceals the taste of zinc. The medication comes in a 10-tablet blister pack, and caregivers are asked to provide one pill every day for 10 days. At the time of debut, it was unknown if young Bangladeshi children would find the tablet formulation acceptable, or whether caregivers would be able to follow treatment instructions appropriately. This was studied in both rural and urban settings, and the results showed that the formulation was extremely acceptable and that treatment instructions were simple to follow. Ninety-eight percent of caregivers successfully prepared the syrup; more than 90% thought the taste was acceptable to their children, and the tablets were provided for an average of eight days (66). There were also concerns about the formulation’s potential negative effects. As previously stated, the formulation was shown to be related with a transitory increase in the risk of vomiting, but no adverse clinical implications (64). Formative studies were conducted with caregivers of children with active diarrhoea, licensed and unlicensed healthcare practitioners, medicine dealers, and medical representatives (drug salesmen). According to a recent baseline study done throughout Bangladesh, the private sector is involved in the majority (>90%) of consultations with healthcare professionals for a childhood diarrhoea episode (67). This poll also revealed the differences in care received, favoring higher-income households and those living in cities. As a result, the SUZY Project has developed a promotion strategy that prioritizes awareness-building in the commercial sector, as well as sensitization and training programs for the government (public) and non-governmental organizations (NGOs). The initial caretaker and provider interviews resulted in the creation of a frequently-asked databank. The Appendix contains some additional frequently requested questions and responses.