August 15, 2014
It’s complicated. That was one conclusion of a randomized trial of amoxicillin for children with uncomplicated severe acute malnutrition (SAM) in Niger. The trial was conducted by Epicentre, the research affiliate of Doctors Without Borders (Medicins sans Frontieres; MSF) to test the World Health Organization (WHO) recommendation that all kids with SAM be given an antibiotic amoxicillin along with ready-to-use therapeutic food, whether or not they have specific signs of infection. These are children who, though vulnerable and with a serious condition, can be treated effectively at home, unlike those children with complicated SAM, whom the WHO recommends be treated as inpatients. Those with uncomplicated SAM must be given nutritional support, but does an antibiotic give them a meaningful edge?
If an inexpensive, relatively safe antibiotic could save lives (or have other worthwhile benefits), treating them with antibiotics would be worth it. But given that inexpensive to even a poor American is not the same as inexpensive in a poor community in Africa if not, they could be better used elsewhere. Additionally, not using antibiotics would mean much less drug pressure to select for drug-resistant bacteria (mainly among the millions of normal gut bacteria exposed to the antibiotic, in addition to any pathogens).
I was lucky enough to be present at the first public airing of the trial’s results at Epicentre s 2014 Scientific Day in June of this year. It was the opening of a session on antibiotic resistance and what research in this area if any Epicentre should pursue. This trial had been their toe in the water.
The scene: rural Niger, where malnutrition is prevalent among the population. MSF has a long-term presence here and the local population has access to care through them.
Over the course of a year, Epicentre researchers in Madarounfa, Niger, randomly assigned 1200 under 5-year-olds with uncomplicated SAM to 7 days of amoxicillin (the WHO recommendation) along with the food supplement, and 1200 to a placebo plus the same food supplement. There was no detectable difference in the proportion who recovered or the proportion who died (seven of the amoxicillin group and six of the placebo group). The placebo children did, however, have a slightly higher risk of being admitted for treatment as an inpatient during the episode.
It sounds like an easy call: no antibiotics. But it’s more complicated than that. SAM may seem like a very specific diagnosis, but malnutrition takes many forms. It doesn’t take a lot of imagination to realize that food conditions around the world vary widely, changing with the season and over longer time periods. And the burden of infection changes by the types of agent that are prevalent and by the infection rate.
For this population and at this time, not giving antibiotics to children when they first present with SAM was all right. Epicentre was able to do the study safely in part because of the safety net the clinic available to everyone in the community. Making that call more broadly? Difficult, if not impossible. This study provides the best evidence on the question to date, but one has to wonder if it will ever be possible to confidently put the question to rest.
