New York Times
POSTED: 1:30 a.m. HST, Jan 31, 2013
Two studies of malnourished children offer the first new scientific findings in a decade about the causes and treatment of severe malnutrition, which afflicts more than 20 million children around the world and contributes to the deaths of more than 1 million a year. Merely giving children a cheap antibiotic along with the usual nutritional treatment could save tens of thousands of lives a year, researchers found.
The studies, in Malawi, led by scientists from Washington University in St. Louis, reveal that severe malnutrition often involves more than a lack of food, and that feeding alone may not cure it.
The antibiotic study found that a week of the medicine raised survival and recovery rates whengiven at the start of a longer course of a tasty "therapeutic food" made from peanut butter fortified with milk powder, oil, sugar and micronutrients. Malnourished children are prone to infections, and the drugs — either amoxicillin or cefdinir — were so helpful that researchers said medical practice should change immediately to include an antibiotic in the routine treatment of severe malnutrition.
"This is ready for prime time," said Dr. Indi Trehan, the first author of the study, which was published Wednesday in The New England Journal of Medicine. The senior author is Dr. Mark J. Manary, an expert on malnutrition and one of the pioneers in using the fortified peanut butter, which researchers say has saved countless lives.
Because of the results, the World Health Organization expects to recommend broader use of antibiotics innew guidelines on treating malnutrition that are to be issued next month, said Zita Weise Prinzo, a technical officer in the organization's nutrition department.
The second study shows, for the first time, that an imbalance in bacterial populations in the gut may contribute to a severe form of malnutrition called kwashiorkor.
And it found that the fortified peanut butter could help restore the proper balance. But the senior author of the study, Dr. Jeffrey I. Gordon, said that for the improvement to last, it may be necessary to continue the feeding for longer than the few months that is now customary. Eventually, he said, it may also be possible to help children with kwashiorkorby giving them the bacteria they lack, but such treatments have not been developed. The study was published Wednesday in the journal Science.
A researcher not involved in the study, Dr. David Relman, of Stanford University, who wrote a commentary in Science, called the findings remarkable, and said they provided hope that an improved understanding of the gut microbiome could lead to better treatments for malnutrition.
Both studies grew out of a troubling observation. Although use of the enriched peanut butter — known as ready to use therapeutic food — was a huge advance during the last decade, some malnourished children died despite receiving it, or did not grow or gain weight as well as expected. Researchers have long suspected that factors beyond lack of food were involved, like infections or gut problems that interfered with nutrient absorption.
Health authorities already recommend that children sick enough to be hospitalized for malnutrition be given antibiotics routinely, and some doctors have advocated even wider use in malnourished children outside the hospital. But until now, the practice had not been tested in a controlled, rigorous way.
The experiment by Trehan and his colleagues involved 2,767 children, 6 months to 5 years old, who had a condition called severe acute malnutrition but were well enough to be treated as outpatients. All were given the enriched peanut butter and were assigned at random to receive an antibiotic or a placebo for one week.
The researchers tracked rates of recovery and of death, with recovery defined in terms of growth, weight gain and the disappearance of symptoms like swelling, which occur in some of the worst cases.
In the placebo group, 7.4 percent of the children died, compared with only 4.1 percent taking cefdinir and 4.8 percent taking amoxicillin. The figures mean that for every 100 children treated, two to three lives could be saved; treating 1 million could save more than 20,000.
Antibiotics also helped the children recover from malnutrition. Of those taking placebos, 85.1 percent recovered, compared with 88.7 percent taking amoxicillin and 90.9 percent taking cefdinir. In the children who recovered, the ones taking antibiotics had a higher rate of weight gain.
The researchers were surprised to find that the drugs helped so much and are not sure how to explain it, Trehan said. But malnutrition and infection can become a vicious cycle, with damage to the intestine disrupting the ability to absorb food and also allowing bacteria to leak into the bloodstream and cause severe illness.
"By a week or two of treatment you see these kids gaining incredible amounts of weight," Trehan said, adding that the week of antibiotics seemed to make a big difference. Although there is concern that overuse of antibiotics can produce drug-resistant strains of bacteria, he said that weeklong treatment in these cases was unlikely to cause that problem.
The second study focused on children with kwashiorkor, which the researchers called "enigmatic" and "virulent." These children often have bulging, distended bellies and spindly arms and legs, but with swelling under the skin.
They suffer from liver disease, rashes and skin ulcers, and have poor appetites. Not all malnourished children develop kwashiorkor, and researchers do not know why some do. The disease can lead to lowered IQ and lifelong impairment.
Although insufficient protein and calories have been blamed, studies have not been able to pinpoint the exact causes.
"Could it be human genetic variations?" Gordon asked. "Environmental factors? Malnutrition interacting with impaired immunity? Diarrhea? All these infections? What the heck is going on? That was in a sense part of the birthplace for our study."
The researchers were interested in the makeup of the trillions of bacteria that inhabit the gut — the so-called microbiome — and that aid in metabolism, and make some needed vitamins and amino acids. The team studied twins in their first three years of life, including pairs in which one had kwashiorkor and the other did not.
Fecal samples revealed that the children with kwashiorkor had a different, less diverse microbiome than the healthy children. The bacterial mix in their gut became healthier when they were fed the enriched peanut butter — but reverted when the supplement was stopped and the children went back to their usual starchy diets.
When gut bacteria from the children with kwashiorkor were transplanted into the guts of germ-free mice, the animals lost weight if they were fed a typical starchy Malawian diet, and their metabolism became abnormal. They improved if given the enriched peanut butter — but, like the children, reverted when it was taken away.
All the children were treated with the enriched peanut butter, and all improved.