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Low-dose zinc effective against acute childhood diarrhea

New England Journal of Medicine
Reuters Health - 23/09/2020 - Doctors who use zinc to treat children for acute diarrhea can throttle back on the recommended dose and may, in the process, prevent the vomiting that can accompany the therapy, a new study of 4,500 youngsters in India and Tanzania has concluded.

The World Health Organization (WHO) recommends a dose of 20 mg/day for 10 to 14 days. The new results, published in The New England Journal of Medicine, show that 5 mg was nearly as effective.

Diarrhea lasted more than 5 days in 6.5% of the children who received 20 mg daily, 7.7% given 10 mg daily and 7.2% of the youngsters who received 5 mg daily.

The rates of vomiting within 30 of taking the zinc were 19.3%, 15.6% and 13.7% respectively.

"Lower doses of zinc are equally effective as higher doses but have an improved safety profile. That should induce policy makers to change the policy and implement the newer therapy," coauthor Dr. Christopher Duggan, director of the Center for Nutrition at Boston Children's Hospital told Reuters Health in a telephone interview.

The study, known as ZTDT, was funded by the Bill and Melinda Gates Foundation.

Roughly a half million children worldwide die from diarrhea each year. The 20 mg dose of zinc is 4 to 10 times the recommended daily allowance for infants and young children.

But the treatment, although recommended by the WHO for many years, has not been widely embraced in developing countries. Part of the problem may be the vomiting issue.

"If you think about it, you have a child who is sick anyway. To give them a treatment that makes them vomit in addition to being sick with diarrhea isn't really appealing," said Dr. Nancy Krebs, medical director for clinical nutrition at Children's Hospital Colorado, who was not involved in the study.

"I think this study is important in that it really will inform the question of dose," she told Reuters Health in a telephone interview. "The fact that a lower dose is equally effective is important to look at."

The team tested children ages 6 to 59 months who had been brought to an outpatient health facility. They either suffered from dysentery or typically were in their second day of diarrhea. Severely malnourished children were excluded, as were children with other serious illnesses.

The zinc was dissolved in water or breast milk. Blood samples were used to assess zinc levels.

The lower dose of zinc was also not inferior to the conventional dose when it came to the number of loose or watery stools the children produced. The mean number in the intention-to-treat analysis was 10.8 with 5 mg, 10.9 with 10 mg and 10.7 with 20 mg.

"Children in the 5-mg group had a 29% lower risk of vomiting within 30 minutes after zinc administration than children in the 20-mg group," said the team, led by Usha Dhingra of the Center for Public Health Kinetics in New Delhi. "Children in the 10-mg group had a 19% lower risk of vomiting within 30 minutes after zinc administration than children in the 20-mg group. Similar effects were seen for vomiting beyond 30 minutes after zinc administration."

The researchers did see a difference in the results for the two countries.

"Children in India appeared to benefit more from lower zinc doses with respect to vomiting than did children in Tanzania," they said. "In addition to differing with respect to their country of origin and possibly other, unmeasured factors, the cohorts of children from the two countries included in the trial differed with respect to age (Tanzanian children were younger), nutritional status (Indian children were less well nourished), and rotavirus vaccine coverage (high in Tanzania and very low in India). "

"Although we did not collect data on the underlying causes of diarrhea, it is possible that Indian children, because of the lack of a nationwide rotavirus immunization program, were more likely to have rotavirus as a cause of their symptoms," they speculated.

Dr. Duggan said the results are probably not relevant in developed countries, where youngsters are more likely to have higher zinc levels in their bodies to begin with.

"Have there been a ton of studies on this? No. But the suspicion is that the nutritional status of children in developed countries is probably so good they would not benefit," he said.

By Gene Emery

SOURCE: https://bit.ly/32HOwJh The New England Journal of Medicine, online September 23, 2020.

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