(From the February 2016 issue of Research Now)
Kawasaki disease is a rare but serious condition in children that involves inflammation of the blood vessels, specifically the heart vessels that supply the heart tissue (coronary arteries). It is the most common cause of pediatric acquired heart disease in the developed world. However, diagnosis is difficult as there are many other common illnesses that can resemble KD and there is no confirmatory test for diagnosis.
Human adenoviruses, which are responsible for 7-8% of all pediatric respiratory illness, have clinical features that mimic KD. In addition, these adenoviruses can sometimes be detected incidentally in the nose or throat (nasopharynx) in children, which poses an additional challenge for clinicians.
A multidisciplinary team of clinicians and microbiologists at Nationwide Children’s Hospital recently published a study in The Journal of Pediatrics describing the clinical, laboratory, and adenovirus characteristics that may help clinicians tell the two conditions apart in pediatric patients. The study is a follow up to a prior study in the journal Clinical Infectious Diseases, in which detection of adenovirus was found in about 8% of Kawasaki disease patients.
“Adenovirus can look a lot like KD, but adenovirus requires just supportive care for an otherwise healthy child, while KD requires timely treatment before the tenth day of fever,” says Preeti Jaggi, MD, physician in the Section of Infectious Diseases at Nationwide Children’s and senior author of The Journal of Pediatrics study. “For this reason, distinguishing the two is very important.”
The team first found that adenovirus could be detected in about 8% of patients who truly had KD. One contributing factor to this relatively high rate of detection is that polymerase chain reaction (PCR), the most commonly used test for viral detection, is very sensitive. As a result, explains Eunkyung Song, MD, fellow in the Section of Infectious Diseases at Nationwide Children’s and first author of the study, PCR might detect adenovirus in a patient that truly has Kawasaki disease, possibly causing confusion to clinicians.
The primary motivation for this study was to examine clinical, laboratory and adenovirus characteristics that might help distinguish patients presenting with adenovirus versus those with Kawasaki disease.
Dr. Jaggi and her team, which also included Octavio Ramilo, MD, chief of Infectious Diseases and principal investigator in the Center for Vaccines and Immunity at The Research Institute at Nationwide Children’s, specifically aimed to clarify the clinical and laboratory characteristics of two groups of patients. The first group included those with adenovirus disease that did not have KD, or “rule out Kawasaki disease patients.” The second group consisted of those with Kawasaki disease and incidental detection of adenovirus, or adenovirus incidentally detected in the nasopharynx of a patient that truly has KD.
To see if certain features of the virus could help differentiate the two conditions, Dr. Jaggi and her team decided to take additional steps to look at characteristics of the adenovirus found in these children. The team then used a process to detect different types of adenoviruses and quantified the burden of the virus, since these two procedures could potentially be done in a clinical lab.
“Using PCR, we looked for the relative amount of virus in the nasopharynx,” says Amy Leber, PhD, director of clinical microbiology at Nationwide Children’s, who provided assistance for laboratory testing. “In addition, we utilized viral culture to confirm if there was a significant amount of virus present.”
Dr. Song completed a thorough clinical classification of patients and found that adenovirus patients typically had less than four clinical criteria for KD, but sometimes did have high inflammatory markers and prolonged fever.
The team also found that adenovirus patients tended to have a higher amount of virus in the nasopharynx, as well as species B or E of adenovirus identified more often than the other species of adenovirus (which range from A-G). KD patients, on the other hand, tended to have a lower viral burden of adenovirus in the nasopharynx and were more likely to have type C adenovirus. Type C is most frequently found incidentally in the nasopharynx.
“We are examining if blood PCR aids in distinguishing the two illnesses,” says Dr. Jaggi of her team’s future directions in this arena of research. “In addition, we are examining the host blood gene expression profiles in those with Kawasaki disease and in those with adenovirus disease to see if the host immune response can be utilized to differentiate the two conditions.”
Song E, Kajon AE, Wang H, Salamon D, Texter K, Ramilo O, Leber A, Jaggi P. Clinical and Virologic Characteristics May Aid Distinction of Acute Adenovirus Disease from Kawasaki Disease with Incidental Adenovirus Detection. The Journal of Pediatrics. 2015 Dec 15 [Epub ahead of print].
Jaggi P, Kajon AE, Mejias A, Ramilo O, Leber A. Human Adenovirus Infection in Kawasaki Disease: A Confounding Bystander? Clinical Infectious Diseases. 2013 Jan; 56(1):58-64. Epub 2012 Sep 25.