Immunological and Clinical Responses to Zinc in Children With Diarrhoea

Summary

Zinc deficiency has been found to be widespread among children in developing countries.Clinical and field studies have consistently observed an association between zinc deficiency and higher rates of infectious diseases, including skin infections, diarrhea, respiratory infections, malaria, and delayed wound healing. Based upon the impact of zinc deficiency on diarrheal disease alone, it is estimated correction of this deficiency could save 450,000 under-five deaths annually. What is the physiological explanation for this? Zinc has been identified to play critical roles in metallo-enzymes, poly-ribosomes, the cell membrane, and cellular function, leading to the understanding that it also plays a central role in cellular growth and in the function of the immune system. With zinc deficiency epithelial barriers are compromised and multiple components of the immune system malfunction. The obvious conclusion is that zinc deficiency results in diminished immunological competence that in turn leads to an increased risk for infectious diseases and greater severity of illnesses. Whether this is the case requires substantiation. A related, but more pragmatic question is the value added of zinc supplementation in addition to zinc treatment. The scale-up strategy being pursued in Bangladesh is to provide zinc for 10 days as a treatment at the time of a diarrhea episode. This is in accordance with recently revised WHO recommendations for the treatment of childhood diarrhea (WHO, in press). Can we conclude there is no or minimal value added to continuing zinc as a dietary supplement in zinc deficient children following an acute episode? If there is added benefit, can this be explained by improvement in zinc levels and/or immune function? The aims of this study include:1. In children six to twenty-four months of age with an acute episode of diarrhea attributable to enterotoxigenic E. coli (ETEC), to describe the innate and adaptive immune response to zinc and to relate changes in immune function or zinc status to the occurrence of repeat infectious illnesses over a 9 month period of observation. 2a. In children six to twenty-four months of age with an acute episode of diarrhea with enterotoxigenic E. coli (ETEC), and other non-ETEC diarrhea, to determine the value added of zinc supplementation following treatment in terms of the future occurrence of ACD, ARI, and impetigo and 2b. to assess the impact of zinc supplementation on health services utilization and household expenditures for ACD, ARI and impetigo.

Conditions

• Diarrhoea

Interventions

DRUG

Zinc

Sponsors & Collaborators

• Bill and Melinda Gates Foundation

  collaborator OTHER

• International Centre for Diarrhoeal Disease Research, Bangladesh

  lead OTHER

Principal Investigators

• Amit Saha, MBBS · International Centre for Diarrhoeal Disease Research, Bangladesh

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

6 Months

Max Age

24 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2004-11-30

Primary Completion

2006-08-31

Completion

2006-11-30

Countries

• Bangladesh

Study Locations