• proportion with treatment failures
  

• the effect of zinc administration on the time taken to recover from possible serious bacterial infection
  
• the effect of zinc administration on plasma zinc and copper
  
• the effect of zinc administration on markers of inflammation
  

Infant mortality rate continues to be high in most developing countries despite advances in child health care. Infections are the most important cause of deaths in infants. There is increasing recognition that nutritional deficiencies including micronutrients are important determinants of infection and their outcomes. Zinc is a crucial micronutrient as it influences various immune mechanisms and modulates host resistance to several pathogens. Supplementation with zinc has been documented to provide protection against common childhood infections. It has also shown benefits as an adjunct therapy in infections like diarrhea and pneumonia in older children. Given the predisposition of young infants in developing countries to zinc deficiency and infections, addition of zinc to standard treatment of serious bacterial infections may lead to significant improvements in the outcomes. This is critical to demonstrate because nearly 80% of infant mortality occurs in first 2 months of life.

The infant mortality rates in India continue to be in excess of 60 per 1000 live births. Neonatal mortality contributes to over 64% of the infant deaths particularly in those who are born low birth weight. Most of the other deaths occur in the second and third months. Serious systemic infections like sepsis and pneumonia constitute 30-40% of the causes of mortality. Any health programme that aims at reducing infant mortality rate needs to address mortality in the first two months of life.

Almost 90% of all low birth weight (LBW) babies are born in developing countries, particularly in the Indian subcontinent. Nearly 70% of these are small for gestational age unlike in the developed world where the bulk of low birth weight babies are preterms. Zinc deficiency during fetal development is documented to cause intra-uterine growth retardation and also impaired postnatal immune functions making these babies more susceptible to severe infections. Studies have shown good correlation between cord blood zinc, maternal zinc concentration and birth weights.

The zinc content of the breast milk decreases rapidly after birth. In addition, the requirements are likely to be high as young infants in developing countries live in high microbial load environment and are exposed to recurrent infections. Further, malnourished infants need more zinc for catch up growth. All these predispose them to develop zinc deficiency and infections. In a population based study by our group last year, nearly 40% of young infants had low plasma zinc despite being breast-fed, probably a reflection of inadequate tissue stores (unpublished data).

Zinc influences many aspects of the immune system starting with its effects on the barrier and various components of innate and acquired immunity. There is sufficient data from animal and human studies of increased host susceptibility to infections with zinc deficiency. A vicious cycle of infection and zinc deficiency exists. Infection reduces the plasma zinc concentration, which reflects the severity of the infection and inflammation. This may be observed early during the illness. Organs such as the skin, thymus, bones and the epithelium also become depleted during this process. Severe bacterial illnesses also lead to zinc redistribution. It is plausible that this redistribution increases the infection severity.

There is limited data on therapeutic effect of zinc supplementation on severe infections in young infants less than 4 months of age. A short inexpensive course of zinc for patients with serious bacterial infections can become a simple but potent intervention to reduce young infant mortality and morbidity. While the effects of zinc deficiency and of supplementation are reasonably well documented eventually the benefits on clinical outcome alone can result in its application.