High Rate of Febrile Seizures in Japanese Children With Occult Bacteremia.

OBJECTIVES: Fever of 39°C or higher and a white blood cell (WBC) count of 15,000/µL or greater are known predictors of occult bacteremia (OB). However, because of a decreasing prevalence of OB, WBC counts have become poor predictors of OB in populations of routinely immunized children. Thus, we aim to evaluate the clinical characteristics of OB in Japanese children and identify potential risk factors for OB. METHODS: We conducted an observational study of children aged 3 to 36 months old with positive blood cultures for Streptococcus pneumoniae or Haemophilus influenzae at an emergency department in a tertiary care children's hospital between April 2002 and December 2015. Patients with significant underlying diseases, a proven source of infection, or toxic appearance, were excluded. RESULTS: Positive blood cultures were recorded in 231 patients; of these, 110 were included in the study (S. pneumoniae, n = 102; H. influenzae, n = 8). Median age was 16 (3-34) months. Patients had a high median body temperature of 39.2 (interquartile range, 38.6-39.9) °C and median WBC of 21,120 (interquartile range, 16,408-24,242)/µL. A high rate of febrile seizures (58 patients, 53%) was observed, with complex febrile seizures accounting for 43% of the episodes. Frequency of febrile seizures was positively associated with age (P = 0.001). CONCLUSIONS: Our study revealed a high rate of children presenting with febrile seizures, especially complex seizures, among children with OB in Japan. A further study is necessary to evaluate the role of febrile seizures as a predictor for OB.

Febrile seizures with leukocytosis as a predictor for occult bacteremia.

BACKGROUND: Febrile children 3-36 months old, who had a body temperature >39°C and white blood cell (WBC) count >15 000/mm3 were known to be at risk for occult pneumococcal bacteremia (OPB) in the pre-pneumococcal conjugate vaccine (PCV) era. The positive predictive value of these criteria, however, decreased dramatically after the introduction of PCV, indicating a need for alternative criteria. A high rate of febrile seizures has been noted in children with OPB, suggesting that screening may still be practical in this population. We performed a retrospective analysis to evaluate factors that predict OPB in patients visiting the emergency department (ED) with febrile seizures. METHODS: Children 3-36 months old who visited the ED for febrile seizures and had blood cultures taken were included. Patients with underlying diseases were excluded from analysis. We performed statistical analyses comparing patient demographics according to the presence or absence of OPB. RESULTS: One thousand and eighty-two patients visited the ED with febrile seizure, and blood cultures were taken in 397, of whom 87% had received more than three doses of PCV. Of the nine patients with OPB, eight (89%) met the risk criteria. In contrast, only 12% (48/388) of those without OPB met the criteria. In this population, those who fulfilled the risk criteria were more likely to have OPB than those who did not (14.3% vs 0.3%; likelihood ratio, 7.17). CONCLUSIONS: High WBC count and fever may effectively predict OPB in pediatric patients with febrile seizure in the post-PCV era.

Children with first episode of fever with seizure: is lumbar puncture necessary?

Fever with seizure, a common presentation with which a child may present to the emergency is mainly due to febrile seizure, but it may also be due to meningitis. This study was done to find out the incidence of meningitis and to find out whether lumbar puncture is necessary in different age groups of children presenting with first episode of fever with seizure. A prospective study was conducted in the emergency department of Kanti Children's Hospital. Children who presented with first episode of fever and seizure in the age group of 6 months to 5 years were included. Meningitis was diagnosed on the basis of either cytological and biochemical criteria or if a bacterial pathogen was isolated. Of the 175 children included, 17% were diagnosed to have meningitis. Cerebrospinal fluid was positive for a bacterial pathogen in 4.5% of the cases. In the age group of 6 months to 12 months, 30% of the children had meningitis as compared to 20 % and 5% in other age groups of 12- 18 months and above 18 months respectively. All children with culture proven bacterial meningitis were in the age group of 6-12 months and had no evidence of meningeal irritation. Signs of meningeal irritation had high specificity in diagnosing meningitis. Organisms grown were Haemophilus influenza in three cases, Streptococcus pneumoniae in two cases and Staphylococcus aureus in three cases. In conclusion, incidence of meningitis was found to be high in children presenting with first episode of fever and seizure. Lumbar puncture to rule out meningitis should especially be considered in children in the younger age group even without evidence of meningeal irritation.

Methods of investigation and management of infections causing febrile seizures.

The management of febrile seizures is reviewed, with emphasis on methods of investigation and treatment of associated infections. Records of 100 consecutive febrile seizure patient-visits were examined retrospectively at an East Carolina University-affiliated hospital. Causes of fever and infection, viral and bacterial studies, antipyretic, antibiotic, and antiviral treatments, and indications for lumbar puncture were analyzed. Febrile seizures were first episodes in 64, simple in 76, and complex in 23 (prolonged, at 30-60 minutes, in 4). The mean age was 20 months. Viral studies in 26 patients were positive in 9 (35%). Bacterial cultures in 100 were positive in 5%, none from CSF. Antibiotics were prescribed in 65%, and antipyretics in 89%. Lumbar puncture was performed in 14 patients; 11 had complex seizures, and 3 simple. Of simple seizure patients, none was aged <12 months, and only 1 was aged <18 months at time of lumbar puncture. Clinical manifestations and complex seizures are the principal indications for lumbar puncture, and not patient age. Viral infection is the most common cause of fever, and bacterial infection is infrequent. Early viral diagnosis should lessen the emphasis on bacterial cultures, and lead to reduced use of empiric antibiotics.

Analysis of the results of routine lumbar puncture after a first febrile convulsion in Hofuf, Al-Hassa, Saudi Arabia.

Cerebrospinal fluid (CSF) was analysed to determine a lumbar puncture (LP) yield for meningitis in 95 children who presented with their first febrile convulsions between July 1993 and June 1994. There were 52 males and 43 females aged six months to six years with a mean age of 21.9 +/- 13.0 months at presentation. 87(91.6%) had simple febrile convulsions (SFC) while the remaining 8(8.4%) had complex febrile convulsions (CFC). The majority of the subjects presented with a sudden onset of convulsions that were preceded by a day or two history of fever, coryza, cough and respiratory distress while others had their convulsions preceded by fever and passage of bloody stools. The LP yield for meningitis in this series was 6.3%. The CSF analysis revealed six cases of meningitis comprising an eight month old infant with Haemophilus influenzae type B (HIB) meningitis, two partially treated pyogenic meningitis and three aseptic meningitis. All of them had presented with febrile convulsions without signs of meningeal irritation. Excluding aseptic meningitis from this series, a 3.1% LP yield for pyogenic meningitis is significant enough to recommend continued performance of LP in children with first febrile convulsions, especially if under the age of eighteen months.

The diagnosis of tuberculous meningitis using the polymerase chain reaction.

AIM: DNA amplification by the polymerase chain reaction (PCR) was evaluated as a means for rapid diagnosis of tuberculous meningitis (TBM). METHODS: A 240 bp region (nts 460-700) from the MPB 64 protein coding gene specific for Mycobacterium tuberculosis (TB) was selected for amplification. Nineteen clinical samples were studied. Six were obtained from patients with TBM diagnosed by culture (4/6) or by response to therapy (2/6). The remaining 13 samples were obtained from patients with febrile seizu es (8/13), aseptic meningitis (3/13) and septic meningitis (2/13), and these served as negative controls. RESULTS: We detected TB DNA in all the 6 CSF specimens obtained from patients with TBM. PCR alone was sufficient to detect TB DNA in 5 of these 6 samples. However, one sample was positive only when PCR was followed by oligonucleotide hybridisation. In the 2 patients whose CSF were obtained only after commencement of TB therapy, TB cultures were negative but positive on PCR nd oligoprobe labelling. The diagnosis of TBM was confirmed based on their remarkable response to therapy. Twelve of the thirteen negative controls were TB DNA negative. There was one false positive sample, which was thought to be due to TB DNA contamination. CONCLUSION: Taken together, our results indicate that DNA amplification using PCR, followed by oligonucleotide hybridisation offers a rapid (5 working days) means of diagnosis of TBM, provided care is taken to ensure that cross contamination of DNA samples is avoided.

Association of human herpesvirus 6 infection of the central nervous system with recurrence of febrile convulsions.

To determine the relationship of human herpesvirus-6 (HHV-6) infection to febrile convulsions, cerebrospinal fluid (CSF) from patients with a history of febrile convulsion were tested by polymerase chain reaction (PCR) amplification for HHV-6 DNA. HHV-6 DNA was detected in 9 of 10 samples from patients with exanthem subitum who showed neurologic symptoms. Also, 8 of 10 CSF samples from 8 patients who had three or more febrile convulsions and 1 of 7 CSF samples from patients who had a single febrile convulsion contained HHV-6 DNA. These data suggest that HHV-6 may invade the brain during the acute phase of exanthem subitum and that recurrence of febrile convulsions may be associated with reactivation of HHV-6.

Human herpesvirus 6 (HHV-6) infection in the central nervous system.

Human herpesvirus 6 (HHV 6) was isolated from patients with exanthema subitum (ES) with a high frequency, and it is now believed that this virus causes ES as a primary infection in childhood. HHV 6 infection is highly prevalent in early childhood and this virus may infect infants through the saliva mainly from mother to child. HHV 6 has a tropism to CD4+ cells and destroys cells in vitro. Although children recover from ES without any sequelae, neurological symptoms associated with exanthema subitum are often observed, and we could detect HHV 6 in the cerebrospinal fluid of ES patients. This result suggests that HHV 6 may invade the central nervous system and cause neurological symptoms.

Viral infections and recurrences of febrile convulsions.

To determine whether complicated febrile seizures occur more often in children with a proven viral infection, we performed viral examinations on 144 children with febrile convulsions, of whom 112 had simple and 32 had complicated seizures. A diagnosis of virus infection was verified in 46% of the former patients and 53% of the latter. Three adenoviruses, one parainfluenza virus type 2 and one type 3, one respiratory syncytial virus, one echovirus type 11, one herpes simplex virus type 2, and one influenza B virus were isolated from the cerebrospinal fluid. A simple febrile convulsion occurred in seven children with a positive cerebrospinal fluid viral isolation, and two had a complex febrile seizure. In a follow-up of 2 to 4 years (mean 3.3 years), 21 of the 107 children with simple seizures (19.6%) and 3 of the 32 children with complicated seizures (9.4%) had recurrent febrile seizures. The children with positive evidence for a viral infection, even with a virus isolated from the cerebrospinal fluid, had no more recurrences than those without any proven viral infection. We conclude that children with a proven viral infection have no worse prognosis than those without.

Occult bacteremia in children with simple febrile seizures.

The controversy surrounding the diagnostic workup for simple febrile seizures has centered around the lumbar puncture. This focus has obscured the potential importance of other tests. A retrospective study was performed to determine the frequency of occult bacteremia in simple febrile seizures. In a pediatric emergency department, we identified 115 cases of simple febrile seizures in children treated as outpatients. Blood cultures were performed in 93 (81%) of 115 patients; five (5.4%) were positive. Children were less likely to have blood cultures performed if they were older than 24 months or had a medical history of simple febrile seizures. However, neither age nor history of febrile seizures affected the risk of bacteremia. These data suggest that patients with simple febrile seizures are at approximately the same risk for bacteremia as children with fever alone. Patients with simple febrile seizures should be treated in the same manner as other patients of the same age with regard to the performance of blood cultures.

HLA antigens, epilepsy and cytomegalovirus infection.

Thirty-one epileptic patients, selected from among 900 children with previous febrile convulsions and subsequent epilepsy, were typed for HLA antigens. In 16 of the 31 patients CMV was isolated from the urine shortly after the appearance of spontaneous fits; in the remaining 15 patients the virus was never detected. All the examined children were typed for 14 HLA-A, 23 HLA-B, 7 HLA-C and 9 HLA-DR specificities, and compared with a group of healthy subjects. The HLA-A11 antigen was present in 25% of the children with chronic CMV infection and epilepsy, and absent in patients with epilepsy but without CMV infection (p less than 0.02). The possibility that the A11 antigen is a marker of the predisposing genes for CMV infection in children with epilepsy following FC is proposed.