New WHO guidelines for serious infant infections draw on Brown-led research

The World Health Organization has revised its recommendations and guidelines for diagnosing and treating conditions like sepsis, meningitis, and pneumonia in newborns worldwide, informed by the findings of a team led by a Brown physician-scientist.

Anne CC Lee, MD, MPH, the Levinger Family Professor of Pediatrics and founding director of the Brown Global Alliance for Infant and Maternal Health Research, and her multinational team performed five systematic reviews of studies and clinical trials published in Pediatrics related to the management of infections among infants up to 59 days old. The researchers focused on how young infants are diagnosed and treated globally, both inside and outside hospital settings. According to WHO, serious bacterial infections are responsible for more than half a million of the estimated 3 million infant deaths each year.

Ultimately, four of the WHO recommendations are new while seven were updated. The Guidelines Development Group strongly recommended the use of the Integrated Management of Childhood Illness (IMCI) algorithm in non-hospital settings for the identification of infants with possible serious bacterial infection who require further evaluation or treatment. The guidelines also had new recommendations for antibiotic regimens for suspected meningitis, pneumonia, and staphylococcal pneumonia. 

“In countries where I work, like Bangladesh or Ethiopia, community health workers or nurses are the frontline providers who assess and manage the majority of newborn babies,” Lee says. The WHO developed IMCI to improve case management of common childhood illnesses by training  these providers to diagnose and treat infants using standard algorithms at the primary health care level, she adds. 

“In our systematic review, we found that the presence of one of seven infant clinical signs could identify most babies who needed to be further evaluated or treated for serious bacterial infections with antibiotics,” Lee says.

Measuring signs like body temperature, breathing rate, and the quality of infant feeding can help identify babies with possible infection early, and mean the difference between life and death. While physicians in hospitals can assess blood counts or analyze the presence of bacteria in an infant’s blood, many infants around the world can’t receive such laboratory testing.

“For families living in rural, low-income communities, it is very important that these algorithms are accurate. We can’t afford to miss a baby with an infection and delay a potentially lifesaving treatment,” Lee says. “However, we also don’t want to over-refer infants who do not actually have an infection, because it requires resources, and we do not want to overload the health system.”

The first set of reviews validated different combinations of physical signs that can predict infections in newborns, with the aim of optimizing and improving the accuracy of diagnoses. The next set focused on the treatment of infections like sepsis, pneumonia, and meningitis, and identifying the most effective antibiotics regimens. 

While the resulting recommendations aren’t necessarily “major” changes, Lee says, the review identified key evidence gaps on firstline empiric antibiotic treatment and highlighted a lack of clinical trial data, as well as increasing antimicrobial resistance. Clinical trials of new antibiotic regimens among newborns or infants were scarce due to limited funding or hesitancy to test new therapies on babies.

“Unfortunately, there are little new clinical trial data on the optimal antibiotic regimens in young infants and, in an era of antibiotic resistance, it’s challenging to make global recommendations when you have so few trials and evolving epidemiology and antibiotic resistance patterns in different world regions,” Lee says.

Lee’s team was co-led by Dr. Krysten North at Brigham and Women’s Hospital.   The authors of the systematic reviews included investigators at WHO, Sick Kids, University of Papua New Guinea, Harvard, Emory, Stanford, NYU, and Oregon Health & Science University.