Parvovirus B19 Infection Associated with Silent Cerebral Infarcts: A Secondary Analysis of the Silent Cerebral Infarct Trial Cohort

Introduction:

Silent cerebral infarcts (SCI) are the major cause of neurological injury occurring in almost 40% of the population in children with sickle cell anemia (SCA); and are associated with a Full-Scale IQ decrease of approximately 5 points. Acute anemic events, defined as hemoglobin< 6.0 g/dl, is associated with an increase odds ratio (OR) of SCI (OR 2.72; 95% CI, 1.13-6.54; P = .025; Bernaudin et al. Blood. 2015 Mar 5; 125(10):1653-61). Infection with parvovirus B19 (B19V) causes a transient reticulocytopenia and an acute drop in hemoglobin levels in children with SCA. We tested the hypothesis that a history of B19V infection was associated with increased odds ratio of SCIs.

Methods:

In this retrospective cross-sectional study design, we performed a secondary analysis on the Silent Cerebral Infarct Multi-Center Clinical Trial (SIT Trial). Children with SCA between 5 and 15 years of age, with no history of overt strokes or seizures, were screened for SCIs with MRIs of the brain. Research personnel reviewed medical records to determine a history of B19V infection.  Based on prior evidence from the SIT Trial cohort demonstrating that lower hemoglobin levels divided into tertiles are associated with an increase odds of SCI (DeBaun et al. Blood. 2012 Apr 19;119(16):3684-90), three analyses were performed. We stratified by hemoglobin levels into tertiles (<7.6g/dL, ³7.6 and ²8.4 g/dL, and >8.4 g/dL), to determine an association between SCI status and history of B19V infection. Chi squared statistic was used as the measure of association. As a secondary analysis of the original SIT trial cohort, the level of strong significance associated with an increased odds ratio of SCI was determined to be <0.01, with values <0.05 considered moderate significance.

Results:

A total of 814 of the SIT Trial participants had their SCI status adjudicated (present or absent) and a recorded history of B19V status (yes or no). In the cohort, 30% had a SCI and 17% had a history of B19V infection. Prior B19V infection with baseline hemoglobin levels <7.6 g/dL were associated with increase OR of SCI (OR 2.20; 95% CI, 1.22 to 3.97; p=0.008). Prior B19V infection with a baseline hemoglobin levels in the middle (³7.6 to²8.4 g/dL) and upper tertiles (> 8.4 g/dl) were not associated with an increased OR of SCI (OR 0.88; 95% CI, 0.47 to 1.66; p=0.695; and ³8.5 g/dL OR 1.39; 95% CI, 0.72 to 2.69; p=0.328; respectively).

Conclusion:

Children with SCA, a history of B19V and a low baseline hemoglobin level <7.6 g/dL have an increased OR of SCIs. Future efforts in developing a vaccine for B19V may provide an opportunity for decreasing the incidence of SCIs in children with SCA.