Catie Oldenburg, ScD, MPH, an associate professor at UC San Francisco’s Proctor Foundation, has long been interested in reducing morbidity and mortality related to infectious diseases in sub-Saharan Africa. Oldenburg, who focuses on antibiotic-based interventions for child mortality, trachoma and malnutrition, has received a $2.1 million grant from the National Institute of Child Health and Human Development to study the use of azithromycin as an adjunct to nutritional care in children with severe acute malnutrition.
“Severe acute malnutrition carries a high risk of mortality, about nine times that of a child who’s getting enough to eat,” Oldenburg said. “We know from past studies that azithromycin reduces all-cause mortality in children in Malawi, Tanzania and Niger, regardless of their nutritional status. So I was interested in seeing if it had similar effects in those with malnutrition.”
Children in Africa’s Sahel region face a number of threats to their survival, not the least of which are political instability, disease and food insecurity. Treating severe acute malnutrition is more complicated than it might appear, however; clinics are typically crowded and underfunded, family caregivers are often overwhelmed, and malnutrition makes the body more susceptible to infections. Strategies for addressing this complex of problems have traditionally included a course of amoxicillin along with therapeutic foods.
But over time, so much amoxicillin has been dispensed in the Sahel that many bacterial species have developed resistance. Moreover, because antibiotics in general can decrease the diversity of the gut biome, prescribing them may be risky in pediatric malnutrition patients, who are more likely to recover if their biomes are more diverse.
“Clinical trials of amoxicillin for severe acute malnutrition have had conflicting results,” Oldenburg noted. “One, in Malawi, found that it helped children recover and lowered their risk of dying. But another study in Niger showed no difference versus placebo. So the question is: Do these kids actually need an antibiotic, and if so, is amoxicillin the right one?”
Oldenburg thinks that azithromycin may provide a better answer, partly because it can be given in one dose, rather than the twice-a-day, weeklong dosing required with amoxicillin. Ideally, this will ease the burden on harried caregivers, who may be going hungry themselves, and decrease the risk of bacterial resistance associated with partial dosing.
“In a pilot study we did in Burkina Faso in 2020, we compared azithromycin to amoxicillin and found that the latter was more associated with diarrhea and other problems,” Oldenburg said. “That study didn’t include a placebo arm, but the full-scale trial we’re starting now will have one. The pilot study showed that kids who recovered from severe acute malnutrition had much more diverse gut microbiomes at enrollment than children who didn’t recover. So if the new study shows that kids aren’t benefiting from either antibiotic, we shouldn’t be giving them one, because we don’t want to affect the gut or select for bacterial resistance.”
Oldenburg said that severe acute malnutrition often has low recovery rates, in any case. In her eight-week pilot study, only about 40 percent of children recovered, and of those many later relapsed.
“Anything we can do to improve the situation will be helpful,” she said. “We just want to be sure we’re doing the right thing.”