Zinc Supplementation Reduced Cost and Duration of Acute Diarrhea in Children

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Diarrhea and Zinc Supplementation

Germana V. Gregorio, M.D.

Department of Pediatrics

University of the Philippines College of Medicine

Philippine General Hospital

Taft Avenue, Manila, Philippines

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http://www.vitasearch.com/CP/experts/GVGregorioAT09-28-07.htm

“Zinc Supplementation Reduced Cost and Duration of Acute Diarrhea in

Children,”

J Clin Epidemiol, 2007 Jun;60(6):560-6. Epub 2006 Dec 11. 45975 (10/2007)

Kirk Hamilton: Can you please share with us your educational

background and current position?

Germana V. Gregorio: I am a Doctor of Medicine with specialty

training in the field of pediatric gastroenterology. I am presently a

Clinical Associate Professor in the Department of Pediatrics, University

of the Philippines College of Medicine, Philippine General Hospital.

KH: What got you interested in studying the role of zinc and acute

diarrhea in children?

GVG: It is not clear why some episodes of diarrhea persist for a longer

duration in some patients as compared with others but host factors, such

as nutritional deficiencies, which may increase susceptibility to

enteric infections and delay mucosal recovery would be expected to

contribute to this effect. Two well-documented determinants of diarrheal

duration are low weight-for-age and decreased cell-mediated immunity.

Common to both of these factors are zinc deficiency, which is prevalent

in children in developing countries.

KH: What is the biochemistry of zinc that might lead to a resolution

in acute diarrhea?

GVG: Zinc is an essential trace element for humans, being a constituent

of over 200 metalloenzymes. Zinc participates in major metabolic

pathways involving tissue and protein synthesis and turnover,

carbohydrates and energy metabolism, gene expression, embryogenesis and

apoptosis. Zinc is thus essential for growth, sexual maturation and

immune function. Zinc supplementation has been shown to improve immune

function and to reduce the incidence and prevalence of diarrhea among

children in developing countries. Possible roles for zinc include

regulation of intestinal water and electrolyte transport, improvement in

the enzymatic function of the brush borders and enhancement of the

repair of the intestinal mucosa, leading to a decreased duration of

diarrhea.

KH: What were the dose, frequency and type of zinc used? What was

the elemental amount of zinc given daily? Was it given in a liquid or

tablet form? With meals or away from meals?

GVG: The zinc tablets were in the form of zinc sulfate. It contains 20

mg elemental zinc given once daily for 14 days. The zinc tablets were

dissolved in water or milk before administration or were taken as is by

older children. The tablets were taken 2 hours after food intake.

KH: Were zinc levels sub-optimal in these children with acute

diarrhea? If so, did those supplemented with zinc and who recovered,

have documented improvement in zinc levels?

GVG: The present study did not measure the zinc levels of the patients

before and after administration. However, previous studies have

documented an improvement in the zinc levels (and a shorter duration of

the diarrhea) after supplementation

KH: Can you tell us about your study and the basic results?

GVG: The study included children aged between 2 to 59 months with a

history of diarrhea <7 days duration and no dehydration. Patients were

randomized to either the zinc supplemented or no treatment group. The

clinical outcome of interest was duration of diarrhea. The following

data on resources used and clinical outcomes were obtained during

randomization and on follow-ups during the first and second weeks: (1)

direct medical costs (building space, drugs, diagnostics and

professional fees); (2) direct non-medical costs (out-of-pocket

expenditures); (3) indirect cost (salary lost for parents or

caregivers); (4) compliance with medications; and (5) date of cessation

of diarrhea. The mean duration of diarrhea was shorter and the mean

total cost of treatment was 5% cheaper in the zinc treated group than in

the no treatment group. After computing for the cost effectiveness

ratio, it was shown that zinc supplementation as compared to no

treatment is more cost effective in the treatment of acute childhood

diarrhea.

KH: Were there any side effects with the zinc therapy? How was the

patient compliance?

GVG: The study did not observe any patient with vomiting after intake of

zinc, which is the known side effect of the drug. In a trial done in

Nepal, it was shown that the relative risk of vomiting increases by 3 to

4 times if children are given 3 times the RDA (15 and 30 mg) for zinc.

In this study, non-compliance with intake of zinc was defined as < 80%

intake of the recommended dose. This was assessed by counting the number

of remaining zinc tablets during the follow-up visits of the patient and

by asking the caregivers if they had given the zinc tablets to someone

else apart from the study patient. In the study, no patient was

considered non-compliant.

KH: In your opinion, should all cases of childhood diarrhea (acute)

be treated with a zinc supplement? How do you determine what dose to

give and who gets treated with zinc?

GVG: It is clear in different studies and in a meta-analysis that zinc

supplementation causes a reduction in the duration of diarrhea. In June

2004, a joint statement made by the WHO and UNICEF advocated the use of

zinc as an adjunctive therapy in acute childhood diarrhea. The WHO

recommends giving 20 mg/day of elemental zinc for 10-14 days in children

with diarrhea but the dose is reduced to 10 mg/day in infants less than

6 months.

KH: What would the savings be in morbidity and mortality from zinc

therapy?

GVG: Based on the outcomes that were measured in the trial, it was not

possible to assess the savings in terms of morbidity and mortality from

zinc treatment in acute diarrhea. However, in another study, it was

shown that the mean incremental cost effectiveness ratio was reduced

from US$113 to US$73 per disability adjusted life years (DALY) averted

when zinc is given.

KH: Do you have any further comments that you would like to make on

this very practical treatment?

GVG: It is recommended that further studies on cost-effectiveness

analysis of zinc supplementation in acute diarrhea be done using a

different costing method to validate the results of this study. The cost

of the present study was derived from the cost figures of an urban,

government, tertiary hospital. The cost figures of private hospitals or

rural, government hospitals could be used. Likewise, the cost in this

study was done from the society’s perspective. It will be of interest to

do an evaluation from the perspective of the patient or a health

maintenance organization.

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