Infant Deaths Fall Sharply in Africa With Routine Antibiotics

Infant Deaths Fall Sharply in Africa With Routine Antibiotics

Two doses a year of an antibiotic can sharply cut death rates among infants in poor countries, perhaps by as much as 25 percent among the very young, researchers reported on Wednesday.

Their large study — of nearly 200,000 children in three African countries — raises the exciting possibility that deploying antibiotics as doctors do vaccines could rapidly reduce deaths among newborns and infants. Death rates in this age group have remained stubbornly high in poor countries even as deaths among all children under age 5 have dropped by half, thanks to vaccines against childhood diseases.

As a result of the study, the World Health Organization is considering whether to recommend routinely giving antibiotics to newborns.

“Our independent expert panel says this holds a lot of promise,” said Dr. Per Ashorn, a W.H.O. expert in maternal and child health. “But we will review it with very rigorous procedures.”

The agency will make a decision “as soon as possible, latest in 2019,” he added.

The Bill and Melinda Gates Foundation, which paid for the study, “is optimistic that this will be a new tool to help prevent childhood mortality,” said Dr. Rasa Izadnegahdar, deputy director of global health at the foundation. “It’s an exciting time.”

But wider use of antibiotics would raise some serious concerns. Would handing out tens of million of doses in poor countries speed the emergence of antibiotic-resistant bacteria? And could it be done without the drugs being stolen or misused?

The study’s authors — from top American, British and African medical schools, and the Atlanta-based Carter Center — argue that those risks are small and much outweighed by the greater good of saving children’s lives.

“At one time, people said you couldn’t give out H.I.V. drugs in Africa because it would create drug resistance,” said Dr. Thomas M. Lietman, an ophthalmologist at the University of California, San Francisco, and the study’s lead author. “That implied that we should just let Africans die so we could keep giving out the drugs in the U.S.”

About 35 million youngsters, Dr. Izadnegahdar said, live in the countries most likely to be targeted — those where a child now has a 1-in-10 chance of dying before age 5.

In the study — known as the Mordor trial and published in the New England Journal of Medicine — 190,238 children under age 5 in 1,500 villages in Malawi, Niger and Tanzania were given one dose of azithromycin or a placebo every six months for two years.

Overall, there were 14 percent fewer deaths among children getting the antibiotic; the reduction was strongest in Niger, where infant mortality is highest.

The protection appeared to be greatest for infants aged 1 month to 5 months; the antibiotic prevented one in four deaths in this group.

The researchers could not say definitively why it worked. Azithromycin, made by Pfizer and sold as Zithromax in the United States, kills many species of bacteria that cause pneumonia and diarrhea, which are major killers of newborns. It also kills malaria parasites.

The new trial grew out of a 2009 study of ways to prevent trachoma, a blinding eye disease, in 18,000 Ethiopian children. The group of children there who got one dose of azithromycin as part of their regimen suffered about half as many deaths as other children.

“That was groundbreaking, just quite amazing,” said Kelly Callahan, who runs the Carter Center’s trachoma program and helped oversee the Ethiopia study. “It was beyond saving sight — it was saving lives.”

Other small studies have shown similar benefits. A 2014 study of Gambian women given one antibiotic dose during labor showed that both they and their babies had fewer overall infections and less often harbored the bacteria responsible for lethal neonatal sepsis.

Some experts argued that distributing antibiotics could hasten the appearance of drug-resistant bacteria. The W.H.O.’s panel would look hard at that, Dr. Ashorn said, “because this would be broadening rather drastically the way we use antibiotics.”

Sabiha Essack, director of antimicrobial research at the University of KwaZulu-Natal in South Africa, said it was “unclear whether the benefits will outweigh the costs” and noted that the study did not look at the effects on the infants’ microbiomes, or bacterial makeup.

But other experts said they considered the risk relatively low, for several reasons.

The drugs would be given only to youngsters, only infrequently and probably only for a few years.

Dr. Charles Knirsch, vice president for clinical research at Pfizer, said his company had donated more than 700 million azithromycin doses to the International Trachoma Initiative, which gives them to people of all ages. No permanent resistance mutations have emerged in any bacteria.

Such mutations “are more of a concern in I.C.U.’s in New York City than in places like Niger, where’s there such low access to antibiotics,” he said.

Each year, when azithromycin is given out, some pneumococcal bacteria resistant to it appear, said Paul Emerson, the trachoma initiative’s director. But those strains fade out within weeks or months, he said.

Also, he noted, the resistance is only to macrolides, the drug class to which azithromycin belongs. Macrolides are not heavily used in Africa, where W.H.O. guidelines still recommend penicillins and even older sulfa drugs because they are cheap and effective.

Pharmaceutical supply chains in some poor countries are plagued by theft, and antibiotics are tempting targets because they cure sexually transmitted diseases and other ills. But less than 1 percent of Pfizer’s donations have been lost to theft or expiration, Dr. Emerson said.

For enhanced security, azithromycin is distributed in special purple packaging saying it is to be used only for trachoma. Also, he noted, pediatric doses are liquids, which adults do not normally take.

Dr. Emerson said his initiative would be happy to handle distribution if the W.H.O. approves routinely giving antibiotics to infants.

“How many times do you get an offer to help save tens of thousands of lives?” he said.

Although azithromycin is not approved by the Food and Drug Administration for children under 6 months old, the Centers for Disease Control and Prevention recommends it for infants of any age with whooping cough.

The trial’s gloomy nickname, Mordor, comes from J.R.R. Tolkien’s “Lord of the Rings” trilogy, in which it is the shadowy land of Mount Doom. The initials stand roughly for “Mortality Reduction Through Oral Azithromycin.” (In French, “Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance” — “Oral Macrolides to Reduce Deaths With an Eye on Resistance.”)

The acronym was coined before the initials were chosen, authors said, because the 2009 trial was done in Ethiopia’s Gondar region. In Tolkien’s trilogy, Gondor, the land of men, battles Mordor. (Some readers think Tolkien used Ethiopian place names, Dr. Izadnegahdar said; according to a biographer, he denied consciously doing so.)

“Some team members thought the name was creepy, but the study is about death,” Dr. Lietman said. “It took on a life of its own, and we never looked back.”

The study’s name, Dr. Izadnegahdar said, might be changed to Reach, for “Resilience Through Azithromycin for Children.”

This article was originally published in The New York Times.  Read the original article.

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