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Soluble membrane attack complex is diagnostic for intraventricular shunt infection in children
Theresa N. Ramos, Anastasia A. Arynchyna, Tessa E. Blackburn, Scott R. Barnum, James M. Johnston
Theresa N. Ramos, Anastasia A. Arynchyna, Tessa E. Blackburn, Scott R. Barnum, James M. Johnston
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Clinical Research and Public Health Immunology Infectious disease

Soluble membrane attack complex is diagnostic for intraventricular shunt infection in children

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Abstract

BACKGROUND. Children treated with cerebrospinal fluid (CSF) shunts to manage hydrocephalus frequently develop shunt failure and/or infections, conditions that present with overlapping symptoms. The potential life-threatening nature of shunt infections requires rapid diagnosis; however, traditional microbiology is time consuming, expensive, and potentially unreliable. We set out to identify a biomarker that would identify shunt infection.

METHODS. CSF was assayed for the soluble membrane attack complex (sMAC) by ELISA in patients with suspected shunt failure or infection. CSF was obtained at the time of initial surgical intervention. Statistical analysis was performed to assess the diagnostic potential of sMAC in pyogenic-infected versus noninfected patients.

RESULTS. Children with pyogenic shunt infection had significantly increased sMAC levels compared with noninfected patients (3,211 ± 1,111 ng/ml vs. 26 ± 3.8 ng/ml, P = 0.0001). In infected patients undergoing serial CSF draws, sMAC levels were prognostic for both positive and negative clinical outcomes. Children with delayed, broth-only growth of commensal organisms (P. acnes, S. epidermidis, etc.) had the lowest sMAC levels (7.96 ± 1.7 ng/ml), suggesting contamination rather than shunt infection.

CONCLUSION. Elevated CSF sMAC levels are both sensitive and specific for diagnosing pyogenic shunt infection and may serve as a useful prognostic biomarker during recovery from infection.

FUNDING. This work was supported in part by the Impact Fund of Children’s of Alabama.

Authors

Theresa N. Ramos, Anastasia A. Arynchyna, Tessa E. Blackburn, Scott R. Barnum, James M. Johnston

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Figure 4

Cerebrospinal fluid sMAC levels decline rapidly in children with pyogenic infections after antibiotic administration.

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Cerebrospinal fluid sMAC levels decline rapidly in children with pyogeni...
Serial CSF samples were obtained via the external ventricular drain and assayed for sMAC levels using the sC5-9 ELISA. The day 0 samples were obtained prior to administering antibiotics, while subsequent samples were collected after initiation of antibiotic treatment. In patients responsive to antibiotic and supportive therapy, the sMAC levels dropped to 50% of their initial level within 4–5 days and returned close to baseline levels within 2 weeks (dotted lines) (A–C). In patients unresponsive to antibiotic therapy, CSF sMAC levels frequently increased after day 0 and rarely returned to baseline (D and E). In patients with symptomatic shunt failure as diagnosed by MRI imaging, the sMAC levels were markedly lower than in pyogenic infection and varied widely over the course of monitoring (F–H).

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