April 2000
SAN DIEGO - Despite recent reports of an association between Chlamydia pneumoniae infection and Kawasaki syndrome (KS), a study conducted here found no relationship.
C. pneumoniae was believed to be a possible trigger for KS because of its link to endocarditis and myocarditis in children, and an increased risk of atherosclerosis and heart attack in adults.
KS is an acute febrile illness of infants and young children that affects the cardiovascular system and is the primary cause of acquired coronary artery disease in children. Researchers found no associated risk with current or past C. pneumoniae infection and concluded C. pneumoniae is not the etiologic agent responsible for Kawasaki syndrome.
However, an infectious etiology is still one of the leading hypotheses, according to Stephanie Schrag, PhD, Centers for Disease Control and Prevention (CDC), epidemic intelligence service. "Findings are consistent with a respiratory portal of entry of a pathogen," said Schrag. "There is a general feeling that maybe there is not one specific pathogen that is the immediate cause. There may be different sets of circumstances acting as a trigger and the syndrome is probably not the acute manifestation of an infection, but may occur sometime after an exposure."
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---Genetic predisposition for KS, coupled with exposure to an infectious agent, are essential elements in the pathogenesis of Kawasaki syndrome, according to the study researchers.
"It's always difficult with a negative result to really nail something down," said Schrag. "We did not find an association in this cluster, but you can't rule something out 100%. [The study] suggests researchers at this point shouldn't put a lot of energy into that hypothesis, which is what was starting to happen.
"There was a lot of interest in C. pneumoniae that was diverting focus from other potential causes. Our study is a piece of evidence that can be used to say that researchers should again look at the broad range of hypotheses."
The CDC investigated the possible outbreak when health officials feared the number of KS cases was above the typical seasonal increases during the months of February and March. The number of cases, however, was ultimately similar to those in previous years. Cases occurred during the height of the respiratory disease season.
Thirteen patients ranging from 1.1 to 8.6 years met study requirements. Requirements were fever for five or more days with four out of five other clinical indicators and occurring between Feb. 1 and March 31, 1999. Specimens and information about recent respiratory illness and antibiotic use were taken from all 13 patients, as well as 40 of their household members (median range 30 years old) and 45 controls. Ten of the 13 study patients lived with siblings who were younger than 10 years old. An average of three family members per patient were enrolled in the study.
Researchers performed culture and C. pneumoniae-specific polymerase chain reaction (PCR) on peripheral blood mononuclear cell specimens and pharyngeal specimens, and performed C. pneumoniae-specific serologic testing to determine if patients with KS were more likely to have been recently exposed to C. pneumoniae than controls.
All PCR and culture specimens, except for the specimen of a mother of a case patient, tested negative. Serologic analysis revealed no evidence of current infection. Family members and outpatient controls tested negative for evidence of current infection based on single titers. Urine cultures from Kawasaki patients failed to detect Chlamydia sp., contrasting findings of an earlier study.
According to the study, case patients were no more likely than control subjects to have had a respiratory illness in the previous two months. Almost 85% of the study patients had a respiratory illness, ranging from a runny nose to pneumonia, one month prior to the study. Seven of the 13 case patients took antibiotics two months prior to admission to the hospital for KS, however, not many of the antibiotics had activity against C. pneumoniae.
For more information:
- Schrag S, Besser R, Olson C, et. al. Lack of association between Kawasaki syndrome and Chlamydia pneumoniae infection: an investigation of a Kawasaki syndrome cluster in San Diego County. Pediatr Infect Dis J. 2000;19(1):17-22.
- Photo caption: Genetic predisposition for KS, coupled with exposure to an infectious agent, are essential
- elements in the pathogenesis of Kawasaki syndrome, according to the study researchers.
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