1. Cerebrospinal Fluid Findings in Infants with Pertussis
Tina T. Chu, MD, Jesse Groh, MD, Andrea T. Cruz, MD, MPH
Department of Pediatrics
Baylor College of Medicine
Houston, Texas

2. Abstract
Infants with pertussis often receive extensive medical and laboratory evaluation for fever or apnea caused by this infection. Cerebrospinal fluid (CSF) findings in infants have not been reported.
The objective of this 5-year retrospective review is to describe the CSF findings in infants < 12 months of age with polymerase chain reaction (PCR) confirmed pertussis in whom CSF was obtained.
39 (19.6%) of the 199 infants with positive pertussis PCR received a lumbar puncture (LP). Reasons for performing LP included apnea (62%), toxic appearance (38%), fever and age < 1 month (26%), and altered mentation (10%). 24 (62%) children had elevated CSF protein. No child had bacterial meningitis hypoglycorrhachia, bacteremia, or intracranial hemorrhage. Length of stay and duration of parenteral antibiotics were not significantly different in children with normal versus abnormal CSF parameters.
In conclusion, elevated age normalized CSF protein was a
common finding in infants with pertussis.

3. Background The greatest burden of pertussis disease occurs in infants
Over 2600 admissions annually
86% of hospitalizations: infants ≤ 3 months
95% of cases: requiring mechanical ventilation
Pertussis symptoms are often atypical or nonspecific (cyanosis, apnea) and prompt examination of the cerebrospinal fluid (CSF)
CSF profiles in infants with pertussis have not been previously described

4. Objective
To report the cerebrospinal fluid findings of infants with pertussis and parapertussis

5. Methods
Retrospective review of children 0-12 months of age seen at Texas Children’s Hospital (TCH) from January 1, 2005 to December 31, 2008 with PCR confirmed Bordetella pertussis infection in whom CSF was obtained
Molecular pathology database accessed to identify those patients in whom CSF was obtained and sent for routine studies (cell count/differential, protein, glucose, Gram stain, and culture)
Data abstracted from medical records:
Demographics
Symptoms
Laboratory and radiographic evaluation
Clinical course

6. Materials and Methods
Abnormal CSF parameters were determined by patient age
CSF pleocytosis defined as white blood count (WBC):
≥ 25 cells/μL in neonates ≤ 28 days
≥ 10 cells/μL in infants > 28 days
Elevated CSF protein defined as:
> 108 g/dL if < 8 days
> 90 g/dL if 8-30 days
> 77 g/dL if days
> 60 g/dL if days
> 40 g/dL if days
Statistical analyses performed using STATA 10 (Stata, Inc., College Station, TX). Frequencies calculated for categorical variables. Means/medians calculated for continuous variables. Student t-test used to compare continuous variables. Differences in proportions between groups calculated using chi-square or Fisher’s exact test and reported with 95% confidence intervals

7. Patient Demographics 39 with pertussis or parapertussis received LP
Mean patient age: 43 days (range days)
Patient demographics:
51% female
67% Hispanic
20% non-Hispanic black
13% non-Hispanic white
No children had underlying medical problems
Pertussis immunizations:
4 not up-to-date
33 (85%) had not had any due to age < 60 days
72% with ill contacts with pertussis-like illnesses

8. Results Most common symptoms:
cyanosis (62%)
apnea (46%)
fever (31%; median 101.3°F)
rhinorrhea (31%)
Mean symptom duration: 9.4 days (range: 2-28 days)
Indications for LP:
apnea (62%)
toxic appearance (38%)
fever and age < 29 days (26%)
prior to receipt of antibiotics for other infections (26%)
3 with presumed urinary tract infections (UTIs)
7 with pneumonias (5 lobar, 2 interstitial)

9. Breakdown of PCR-Confirmed Pertussis Patients
239 Children with Confirmed Pertussis or Parapertussis,
211 < 1 year
28 ≥ 1 year
172 no CSF
39 CSF obtained† †
15 CSF normal
24 CSF abnormal*
4 ↑WBC
24 ↑ protein
0 ↓glucose
† : 36 children had B. pertussis, 2 had B. parapertussis, and 1 child had both B. pertussis and B. parapertussis
*: four patients had > 1 abnormal cerebrospinal fluid (CSF) parameter

10. Results All pertussis infants with CSF obtained were admitted
Abnormal CSF findings: 24/39 (62%) — all with elevated protein
No hypoglycorrhachia, positive CSF gram stain/bacterial culture, or bacteremia
2 traumatic LPs (> 500 cells/mm3)
4 had CSF pleocytosis
1 with PCR-positive enterovirus of the CSF
1 nasal wash confirmed enterovirus
2 no etiology identified
7 had pneumonia (2 rhinovirus, 1 picornavirus)
1 had a UTI
No significant differences between CSF cell counts, glucose, or culture results or in microbiologically or virologically confirmed infections in children with normal vs. abnormal CSF protein

11. Results: Hospital Course
Characteristic
Normal CSF
Abnormal CSF
P-value
Documented apnea
20%
71%
0.003
Length of hospital stay
14.3 days
12.4 days
0.72
Length of ICU stay
18.7 days
14.6 days
0.57
Admission to ICU
67%
75%
0.84
Intubated
0.64
Parenteral antibiotics
93%
92%
0.85
Duration of parenteral antibiotics
3 days
3.8 days
0.49
Brain imaging 7%
29%
0.20

12. Discussion
Our finding of increased CSF protein is difficult to explain and was unlikely due to:
Concomitant pyogenic bacterial infections (No meningitis or bacteremia)
Only 1 UTI and 5 lobar pneumonias.
A minority of children with elevated CSF protein had concomitant viral infections
Hypoxic CNS injury from apnea or paroxysms: no evidence on those with CNS imaging
Hyperthermia: no documented temperatures >104°F
Seizures: no witnessed seizures
Traumatic LPs: only 2 of 24 children had CSF RBC/mm3 > 500
Evaluation and clinical management of a toxic-appearing infant should not be limited by a positive pertussis or parapertussis PCR, but it is useful for to be cognizant that abnormal CSF protein can be seen in association with these infections

13. Conclusions
The most common CSF abnormality in infants with pertussis who received a lumbar puncture was elevated CSF protein
While this finding was associated with apnea documented during hospitalization, abnormal CSF findings in this population were not associated with concomitant co-infections or prognosis

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15. Credits
Andrea T. Cruz—Faculty of Infectious Diseases and Pediatric Emergency Medicine, Baylor, Houston, Texas
Mark Ward—Director of Baylor Pediatric Residency Program, Baylor, Houston, Texas