JOURNAL OF CLINICAL MICROBIOLOGY, Oct. 2010, p. 3803–3805 Vol. 48, No. 10 0095-1137/10/$12.00 doi:10.1128/JCM.00825-10 Copyright ? 2010, American Society for Microbiology. All Rights Reserved.
Complex Febrile Seizures Followed by Complete Recovery in an Infant
with High-Titer 2009 Pandemic In，uenza A (H1N1) Virus Infection
11,21,32Mandy F. O’Leary,James D. Chappell,Charles W. Stratton,Robert M. Cronin, 21,3Mary B. Taylor,and Yi-Wei Tang*
123Departments of Pathology,Pediatrics,and Medicine,Vanderbilt University School of Medicine, Nashville, Tennessee 37232
Received 25 April 2010/Returned for modi！cation 13 June 2010/Accepted 5 August 2010
We describe a 2009 H1N1 virus infection with a high viral load in a previously healthy infant who presented
with complex febrile seizures and improved on oseltamivir without neurologic sequelae. Febrile seizures may
be a complication in young children experiencing infection with high viral loads of 2009 H1N1 in;uenza virus.
12 h for the chest X-ray ！ndings. Temperatures up to 104?F CASE REPORT rectally were recorded overnight in the absence of overt sei- In March of 2010, a previously healthy 8-month-old male zure activity. The following morning, the venous blood gas presented to the emergency room (ER) with 2 days of upper values normalized, and the patient was extubated and weaned respiratory symptoms, including cough, congestion, fever to from Osupplementation. Ceftriaxone therapy was changed to 2 102.5?F, and seizure activity. Three seizures occurred prior to an oral cephalosporin. Bacterial cultures of urine, blood, and presentation to the ER, each episode lasting up to 2 h. These CSF were all negative. The patient was treated with 24 mg events were accompanied by perioral cyanosis and emesis. The oseltamivir every 12 h for 5 days, and family members received family history was signi！cant for complex febrile seizures in the oseltamivir for in，uenza prophylaxis. On day 3 of admission, patient’s mother and sister, who had no history of epilepsy. the patient continued to improve, with good oral intake and Upon arrival in the ER, the patient continued to have seizure- without further seizure activity, and was discharged home the like activity described as ―glassy-looking eyes‖ and limpness following day with diazepam for future possible complex fe- with concurrent myoclonal jerking of the head. His vital signs brile seizures. at presentation were as follows: rectal temperature, 103.3?F; Viral culture using rhesus monkey kidney cells, direct ，uo- heart rate, 132 beats per minute; respiratory rate, 40 breaths rescent antibody (DFA) assay (Light Diagnostics Respiratory per minute. His level of consciousness was 9 on the Glasgow Virus Panel I DFA; Millipore, Billerica, MA), rapid immuno- coma scale. His venous blood gas pH was 6.9, with a partial O 2 diagnostic assay (BinaxNow In，uenza A&B; Inverness Medi- pressure (pO) of 77 mm Hg. Due to decreased breath sounds 2 cal Professional Diagnostics, Princeton, NJ), and a multiplex bilaterally, increased work of breathing, and diminished neu- PCR respiratory virus panel (ResPlex II, Qiagen, Valencia, rologic status, the patient was placed on mechanical ventilation CA) was performed on an NPS specimen. Each was positive and admitted to the intensive care unit (ICU). The results of for in，uenza A virus, which was subtyped as 2009 H1N1 using noncontrasted computed tomography (CT) of the head, elec- the proFlu-ST multiplex real-time PCR assay (Prodesse, Mad- troencephalogram (EEG), complete blood count (CBC), and a ison, WI). No in，uenza virus was detected by reverse trans- basic metabolic panel, including aspartate transaminase (AST) criptase PCR (RT-PCR) in a CSF specimen collected at the and alanine aminotransferase (ALT), were within normal lim- time of admission. its, with the exception of a blood glucose level of 185 mg/dl. In，uenza A virus titers in the NPS specimen were deter- Urine, cerebrospinal ，uid (CSF), blood, and respiratory spec- mined by both quantitative RT-PCR and culture. For viral load imens were collected for detection of potential pathogens. A determination by RT-PCR, a quanti！cation standard curve was nasopharyngeal swab (NPS) specimen revealed a positive PCR achieved using four standards ranging from 1 to 1,000 50% result for in，uenza A virus, which was further subtyped as 2009
H1N1. CSF studies were remarkable for pleocytosis, with 46 tissue culture infective doses (TCID) (OptiQuant 2009 50H1N1 quanti！cation panel; AcroMetrix, Benicia, CA). Serial total cells in the chamber and a lymphocyte predominance and
10-fold dilutions of the original NPS specimen were tested in CSF glucose of 126 mg/dl; no red cells were observed. CSF
triplicate, and viral loads were extrapolated from the standard protein was within normal limits at 30 mg/dl. A chest X-ray revealed a vague opacity suggestive of atelectasis, contusion, or curve based on the average threshold cycle (C) values ob- T6 in！ltrate in the central left lung. tained. The calculated load was 1.3 10TCIDper ml of 50 The patient was started simultaneously on 24 mg oseltamivir sample. For quantitative viral culture, serial 10-fold dilutions every 12 h for the positive NPS and 500 mg ceftriaxone every of the NPS specimen in viral transport medium were prepared and inoculated into quintuplicate RMIX Too shell vials (Diagnostic Hybrids Inc., Athens, OH), followed by immuno- * Corresponding author. Mailing address: Molecular Infectious Dis- ，uorescence staining at 48 h of incubation using a ，uorescein ease Laboratory, Vanderbilt University Hospital, 4605 TVC, Nashville, isothiocyanate (FITC)-conjugated in，uenza A-speci！c mono- TN 37232-5310. Phone: (615) 322-0126. Fax: (615) 343-8420. E-mail: clonal antibody (Millipore, Billerica, MA). Viral titers were firstname.lastname@example.org. determined by enumeration of ，orescent cells, and the infec- Published ahead of print on 11 August 2010.
3804 CASE REPORTS J. CLIN. MICROBIOL.
FIG. 1. (A) Direct immuno，uorescence staining of 2009 H1N1 in，uenza A virus-infected cells in a nasopharyngeal swab specimen. (B, C, and D) An average of 43.7% of cells were positive for in，uenza A antigen. Pleomorphic staining patterns were recognized.
6It has been postulated that younger age may predispose to a tious titer was 6.5 10，uorescent focus units per ml. The
higher propensity for more serious neurological sequelae, and viral burden was further characterized by assessing the propor-
long-term neurological damage may result from hypercytoki- tion of in，uenza virus-positive cells in the DFA assay. An
average of 43.7% of respiratory cells collected in the NP spec- nemia and immune system dysregulation due to infection (1, 3,
4, 24). Perhaps increased in，uenza A virus loads borne by imen were positive for in，uenza virus antigen among 214 cells
younger individuals provoke especially exuberant or aberrant examined across 10 ！elds viewed at 20 (Fig. 1).
immune responses that lead to CNS injury. The neurologic
dysfunction may be transient, however, as observed for our
patient and other pediatric subjects who experienced 2009 In，uenza A virus is known to be an important cause of H1N1-associated neurologic disease (2). We suggest that the complex febrile seizures in the pediatric population. There are, seizures suffered by our patient were associated with the high however, limited laboratory and clinical data characterizing viral load, probably through indirect immunologic mecha- neurologic complications such as seizures associated with pan- nisms, though direct viral damage to the CNS cannot be ex- demic 2009 H1N1 in，uenza virus infection of infants (6, 9–11, cluded. Further studies are necessary to fully elucidate the 13, 18, 23). Available literature addressing the neurologic com- relationship of viral loads and various neurologic complica- plications of in，uenza A virus infection emphasizes serious tions of H1N1 virus infection. Moreover, we agree with previ- neurological sequelae such as acute encephalopathy with bi-