Saliva Outperforms Blood in Testing for Recurrent Respiratory Infections in Children

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Pneumococcal pneumonia, illustration
Credit: KATERYNA KON/SCIENCE PHOTO LIBRARY/ Getty Images

Researchers at the Radboudumc Amalia Children’s Hospital and UMC Utrecht Wilhelmina Children’s Hospital, in the Netherlands, report they have developed a saliva test to indicate the severity of recurrent respiratory infections in children that outperforms the standard blood test. Reporting in the European Respiratory Journal, the investigators noted that if the saliva of children contains too few broadly protection antibodies, they are at higher risk of suffering from recurrent pneumonia episodes.

“We found no relationship between antibodies in the blood and disease burden,” said Mischa H. Koenen, an MD, PhD student at UMC Utrecht Center for Translational Immunology. “But in saliva, we observed broadly protective antibodies that work against a variety of pathogens. Children with lower levels of these antibodies had more severe infections. These antibodies in saliva are indeed a good indicator of disease burden.”

The investigators noted that roughly 10% to 15% of all children experience recurrent bouts of respiratory infections and, when they arrive in the hospital setting, they are routinely subjected to a blood draw to search for antibody deficiencies. Unfortunately, according to Lilly Verhagen, MD, PhD, Radboud UMC pediatric infectious disease specialist/immunologist and senior author of the study, these blood test rarely yield useful information.

“This is challenging for pediatricians because we really want to help the children. Therefore, we investigated whether we could find out more about the severity of the disease in another way. That would be very valuable in determining which children need more care and when it makes sense to give antibiotics,” she said.

For their study, the researchers enrolled 10 children with recurrent infections and found that a set of broadly protective antibodies are present in everyone’s airways, but that higher level of these antibodies provided more protection against respiratory infections. The team also found high levels of these same antibodies in family and caregivers of the children, noting that these antibodies bind to pathogens so broadly that they found antibodies in pre-pandemic children’s saliva that could bind to the SARS-CoV-2 virus.

The reason these antibodies are found in the airways of children as opposed to their blood is logical, Verhagen noted. “You inhale various things all day, including many respiratory pathogens, and therefore need a broad spectrum of antibodies in your airways. It’s different in the blood: only few pathogens enter the bloodstream through the mucosa of the intestines or airways. When that happens, your body benefits more from a strong, targeted immune response.”

For their research, the team also examined the microbiome of study participants to better understand the balance between healthy and harmful bacteria present on their mucous membranes. Here, too, they discovered a population of a specific bacterium, called Haemophilus influenzae, on the nasopharyngeal mucosa was strongly associated with infection severity. Already linked with pneumonia episodes from previous studies, this bacterium colonizes healthy airways and causes more winter infections in children with it in abundance.

The saliva test should positively affect the precision of clinical care provided to children with respiratory infections. “This helps us assess the amount of care and medication children need and which antibiotic to use, as the current standard does not work optimally against Haemophilus influenzae,” Koenen said. “I expect the initial blood test to remain, but for follow-up appointments, a more child-friendly saliva and nasopharyngeal swab could be used as indicators of expected respiratory disease burden.”



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