乌鸦传媒

Community-wide distribution of azithromycin to both infants and children in Niger was effective in preventing deaths, but communities where only infants received the drug had no decrease in mortality, according to the AVENIR randomized trial.

Twice-yearly mass distribution of the antibiotic to infants and children ages 1 to 59 months reduced mortality by 14% (95% CI 7-22, P<0.001) across that age span, including a 17% reduction for 1- to 11-month-olds and 13% for 12- to 59-month-olds versus placebo.

However, azithromycin distributed only to infants ages 1 to 11 months didn't significantly protect them or older children, reported Thomas Lietman, MD, of the University of California San Francisco, and colleagues in the .

"The modest -- and not statistically significant -- effect of treating 1- to 11-month-olds alone was not in itself surprising," Lietman told 乌鸦传媒. "We were surprised at how treating [older children] had such a dramatic effect on mortality on the younger 1- to 11-month-olds."

The findings counter World Health Organization restricting mass distribution of the drug to infants ages 1 to 11 months in areas of sub-Saharan Africa where child mortality is high.

Azithromycin distributions limited to 1-11 month olds have not been previously studied, but that group benefited the most in the , in which twice-yearly community-wide distribution of azithromycin in sub-Saharan Africa to children ages 1 to 59 months reduced all-cause mortality in infants ages 1 to 11 months of age by 25% and by 13.5% in children up to 59 months of age.

Although the exact mechanism of how community distribution of azithromycin reduces mortality is unknown, azithromycin contains spread of Chlamydia trachomatis, offers short term protection against malaria, and is effective against enteric and lower respiratory tract infections. These infections are all major causes of mortality in sub-Saharan Africa.

Lietman and colleagues hypothesized that mass azithromycin might reduce community load of pathogens, rather than just treating individual infections. "We were surprised at how strongly this came out in the results," he said.

"These results challenge most of the current recommendations for mass distribution of azithromycin except for one -- the specter of increased antimicrobial resistance," Kathryn Maitland, MD, PhD, of Imperial College in London, and A. Sarah Walker, PhD, of University College London, wrote in .

Antimicrobial resistance data from AVENIR have not yet been released, the editorialists pointed out. In the MORDOR trial, determinants of resistance in communities receiving azithromycin were about than those in placebo communities, they noted, although a continuation study provided some reassurance of continued efficacy at 3 years.

The analysis included data from 1,229 rural communities randomized to twice-yearly distributions of azithromycin over the course of 2 years to children ages 1 to 59 months, 751 communities randomized to give the antibiotic to infants ages 1 to 11 months and placebo to those 12-59 months, and 929 communities to placebo for both age groups.

Among 382,582 children ages 1 month to 59 months participating in the study, 5,503 deaths occurred. Infants ages 1 to 11 months had a mortality rate of 22.3 per 1,000 person-years in communities where they received azithromycin compared with 23.9 per 1,000 person-years where they received placebo. Overall for children ages 1 to 59 months, mortality rates were 11.9 per 1,000 person-years when treated with azithromycin versus 13.9 per 1,000 person-years with placebo.

One serious adverse event occurred in the child azithromycin group, one in the infant azithromycin group, and three in the placebo group. No adverse events were attributed to azithromycin.

The authors acknowledged several limitations to the study. Overall mortality was lower than expected and was monitored for only 2 years, limiting conclusions on longer-term effectiveness of azithromycin. Also, the trial was limited to two regions in Niger, and results may not be generalizable to other geographic areas.

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