Positive Enterovirus Polymerase Chain Reaction Research Articles

Impact of decreasing cerebrospinal fluid enterovirus PCR turnaround time on costs and management of children with suspected enterovirus meningitis.

To estimate the impact of implementing in-hospital enterovirus (EV) polymerase chain reaction (PCR) testing of cerebrospinal fluid (CSF) with same-day turn-around-time (TAT) on length-of-stay (LOS), antibiotic use and on cost per patient with suspected EV meningitis, compared with testing at an outside reference laboratory. A model-based analysis using a retrospective cohort of all hospitalized children with CSF EV PCR testing done between November 2013 and 2017. The primary outcome measured was the potential date of discharge if the EV PCR result had been available on the same day. Patients with positive EV PCR were considered for potential earlier discharge once clinically stable with no reason for hospitalization other than intravenous antibiotics. Descriptive statistics and cost-sensitivity analyses were performed. CSF EV PCR testing was done on 153 patients, of which 44 (29%) had a positive result. Median test TAT was 5.3 days (IQR 3.9–7.6). Median hospital LOS was 5 days (IQR 3–12). Most (86%) patients received intravenous antibiotics with mean duration of 5.72 ± 6.51 days. No patients with positive EV PCR had a serious bacterial infection. We found that same-day test TAT would reduce LOS and duration of intravenous antibiotics by 0.50 days (95%CI 0.33–0.68) and 0.67 days (95%CI 0.42–0.91), respectively. Same-day test TAT was associated with a cost reduction of 342.83CAD (95%CI 178.14–517.00) per patient with suspected EV meningitis. Compared with sending specimens to a reference laboratory, performing CSF EV PCR in-hospital with same-day TAT was associated with decreased LOS, antibiotic therapy, and cost per patient.

Risk Classification for Enteroviral Infection in Children With Meningitis and Negative Gram Stain.

Enterovirus is the most common cause of aseptic meningitis in children. This study aimed at identifying baseline variables associated with a positive cerebrospinal fluid (CSF) Enterovirus polymerase chain reaction (PCR) to aid clinicians in targeting patients who could be tested and treated as outpatients. We performed a retrospective review of children (2 months to 17 years old) admitted to the Children's Memorial Hermann Hospital in Houston, TX, between January 2005 and December 2010 with symptoms of meningitis, CSF white cell count of greater than 5 cells/mm, and a negative CSF Gram stain, who had a CSF Enterovirus PCR. One hundred thirty-seven children were reviewed; median age was 4.7 (0.1-17.1) years, and 79 (58%) were male. Fifty patients (37%) had positive CSF Enterovirus PCR. Only 13 (15%) of the Enterovirus PCR-negative patients had an identifiable etiology. All patients were hospitalized. The mean hospital stay for patients with Enterovirus was 2.9 days; 88% received empiric antibiotics. Rates of antibiotic administration were not different between PCR-positive and PCR-negative groups (P > 0.05). All patients with Enterovirus had a favorable clinical outcome.A predictive model was created using 3 baseline variables independently associated with a positive Enterovirus PCR (P < 0.05): May to November presentation, CSF protein of less than 100 mg/dL, and absence of focal neurologic signs. The model classified patients into 2 risk categories for a positive Enterovirus PCR (low risk, 0% [0/17 patients]; high risk, 42% [50/120 patients]; P < 0.001). Our predictive model can be used to identify children for whom Enterovirus PCR testing is warranted. Such testing could avoid unnecessary hospitalization and antibiotic administration.

Impact of Enteroviral Polymerase Chain Reaction Testing on Length of Stay for Infants 60 Days Old or Younger

To determine the impact of a cerebrospinal fluid enterovirus polymerase chain reaction (PCR) test performance on hospital length of stay (LOS) in a large multicenter cohort of infants undergoing evaluation for central nervous system infection. We performed a planned secondary analysis of a retrospective cohort of hospitalized infants ≤60 days of age who had a cerebrospinal fluid culture obtained at 1 of 18 participating centers (2005-2013). After adjustment for patient age and study year as well as clustering by hospital center, we compared LOS for infants who had an enterovirus PCR test performed vs not performed and among those tested, for infants with a positive vs negative test result. Of 19 953 hospitalized infants, 4444 (22.3%) had an enterovirus PCR test performed and 945 (21.3% of tested infants) had positive test results. Hospital LOS was similar for infants who had an enterovirus PCR test performed compared with infants who did not (incident rate ratio 0.98 hours; 95% CI 0.89-1.06). However, infants PCR positive for enterovirus had a 38% shorter LOS than infants PCR negative for enterovirus (incident rate ratio 0.62 hours; 95% CI 0.57-0.68). No infant with a positive enterovirus PCR test had bacterial meningitis (0%; 95% CI 0-0.4). Although enterovirus PCR testing was not associated with a reduction in LOS, infants with a positive enterovirus PCR test had a one-third shorter LOS compared with infants with a negative enterovirus PCR test. Focused enterovirus PCR test use could increase the impact on LOS for infants undergoing cerebrospinal fluid evaluation.

PO-0256 Enterovirus Meningitis: A Case Series Review

<h3>Background and aims</h3> Meningitis due to Enterovirus infection is usually mild and self-limiting, particularly affecting young infants. We found that we were increasingly diagnosing the condition and undertook a retrospective review, exploring case characteristics and whether increasing use of virology detection reduced antibiotic course length, having previously rarely employed these techniques. <h3>Methods</h3> All cases identified as being diagnosed with meningitis with a positive enterovirus polymerase chain reaction (PCR) result between January 2012 and December 2012, below 16 years of age, were retrospectively reviewed. <h3>Results</h3> Nine cases of enterovirus meningitis were identified in the time period. Seven were infants aged 3 months or less, with two patients aged 11 and 15 years respectively. There were five females and four males. The infants presented with fever, lethargy or irritability. The older children presented with fever and headache. Following full infection screens, all of the infants were treated with intravenous antibiotics. One patient had raised inflammatory markers and one patient had a significant cerebrospinal fluid (CSF) pleocytosis, the majority had a normal or minimally raised CSF white cell count. Eight patients had positive CSF Enterovirus PCR results and one patient had a Coxsackievirus positive serum PCR (having not undergone lumbar puncture). In three patients a prolonged course of antibiotics was discontinued following the PCR result. One patient had episodes of tachycardia with subsequent diagnosis of supraventricular tachycardia requiring treatment. <h3>Conclusion</h3> Positive enterovirus PCR results appear to have reduced antibiotic course length, limiting unnecessary antibiotic administration, and we advocate increasing use of this investigation.

PO-0203 Pcr Analysis For Neurotropic Viruses In Suspected Meningitis Is A Cost-effective Intervention: A Retrospective Observational Study

<h3>Background</h3> In suspected meningitis, cerebrospinal fluid (CSF) examination for presence of white blood cells (WBCs), red blood cells (RBCs), and protein and glucose concentrations is routine. These CSF variables may help in suspicion of bacterial meningitis, but using polymerase chain reaction (PCR) will help in accurate diagnosis and management. Aseptic meningitis due to enterovirus is self-limiting. Therefore, a positive enterovirus PCR may save costs related to prolonged antibiotic treatment. <h3>Methods</h3> A retrospective observational study of one hundred and fifty two patients admitted with suspected meningitis between 1st January 2011 and 31st December 2013 was conducted using an inpatient electronic database. A validated proforma was used to collect data. The outcomes with a positive lumbar puncture with or without PCR analysis were compared. <h3>Results</h3> Forty seven patients (31%) had lumbar puncture performed between 1st January 2011 and 30th June 2012. Out of which, seven patients (23%) had an abnormal cell count but enterovirus PCR was not requested. They required intravenous antibiotics for at least seven days. One hundred and five patients (69%) had lumbar puncture performed between 1st July 2012 and 31st December 2013. Out of which, twenty nine patients (26%) had abnormal cell counts. Nineteen CSF samples (65%) were analysed for enterovirus PCR. Eleven (57%) were enterovirus positive and therefore, antibiotics were discontinued within 48–72 h. Nine patients did not have enterovirus PCR analysed and therefore required antibiotics for at least seven days. A cost-analysis will be provided. <h3>Conclusion</h3> In suspected meningitis, CSF for viral PCR is a cost-effective adjunct.

Dermatological Spectrum of Hand, Foot and Mouth Disease from Classical to Generalized Exanthema

Hand, foot and mouth disease (HFMD) is classically defined as a childhood fever accompanied by a rash with vesicles or erosions of the oral mucosa, hands, feet and sometimes the buttocks. Severe neurological complications are associated with enterovirus 71 outbreaks in Asia. Recently, it has been suggested that HFMD is related to coxsackie virus A6 (CV-A6) when there is an atypical rash. The objective of the study is to determine the dermatological pattern of HFMD and to identify the virus serotypes associated with a specific dermatological pattern. A prospective, cross-sectional study was conducted in 7 pediatric dermatology units in France from March 2010 to February 2012. All children with clinically suspected diagnosis of HFMD were included. Clinical data were collected and swabs from the nasopharynx and vesicles were taken for reverse transcription polymerase chain reaction and genotyping. Only children with confirmed HFMD--defined by clinical diagnosis of HFMD and positive enterovirus polymerase chain reaction results--were included for analysis. One hundred and four children consulted for suspected HFMD, including 89 (mean age: 25.7 months; sex ratio M/F 1.54) with confirmed HFMD. Seventy-eight (87.6%) had skin lesions on sites other than hand, feet and mouth. Thirty-seven (41.5%) had 5 or more anatomical sites involved (hand, feet and mouth, buttocks, legs, arms and trunk) considered as widespread exanthema. Widespread vesicular exanthema was observed with both CV-A6 and CV-A16. Peri-oral rash was associated with CV-A6 (P < 0.001). HFMD has a clinical spectrum ranging from classical to generalized vesicular exanthema. Generalized and atypical exanthema were observed with both CV-A6 and CV-A16 infections. CV-A6 is associated with peri-oral rash.

Utility of polymerase chain reaction(PCR) according to sampling time in CSF and stool specimens from patient with aseptic meningitis

Purpose:Enteroviruses are the most common cause of aseptic meningitis in patients of all ages. A definite diagnosis of enteroviral meningitis can be established by detection of virus directly in CSF specimens. But this is time-consuming and lacks sensitivity, so polymerase chain reaction(PCR) detecting of viral RNA in patient specimens such as CSF, stool has been demonstrated. But little is known about the influence of sampling time on the results of CSF PCR and stool PCR. We investigated diagnostic utility of PCR of CSF and stool according to sampling time after the onset of symptoms. Methods:PCR results were analyzed according to sampling time for 42 patients diagnosed aseptic meningits in our hospital from 11th January to 30th August, 2005. Results:The diagnostic yield of the test was higher of CSF specimens obtained ≦2 days after clinical onset(positive PCR results 9/18, 50 percent), compared with CSF collected >2 days after onset(positive PCR results 1/24, 4.2 percent)(P=0.001). Instead, positive PCR results of fecal specimens maintained highly(average 90.5 percent), 10 cases had also positive PCR results even 5-6 days after onset. 10 cases of CSF specimens had positive enterovirus PCR results containing coxsackievirus B5 (n=6), coxsackievirus B3(n=3). 38 cases of stool specimens had positive enterovirus PCR results containing echovirus 18(n=7), echovirus 9(n=3), coxsackievirus B5(n=8), coxsackievirus B3(n=3). 6 cases(coxackie B5) had positive CSF PCR and stool PCR, both. Conclusion:Stool PCR was clinically sensitive for detecting enterovirus during enteroviral meningits and could give a presumptive diagnosis throughout the disease course. A definite diagnosis was obtained by CSF PCR, but its utility was clearly lower for samples obtained >2 days after clinical onset. Therefore, it is recommended that, in addition to performance of CSF PCR, fecal samples obtained from patients with suspected enteroviral meningitis should be tested by PCR, especially when the duration of symptoms is >2 days

Cerebrospinal fluid protein concentration in pediatric patients: defining clinically relevant reference values.

To define clinically relevant reference ("normal") values for cerebrospinal fluid (CSF) protein concentrations in pediatric patients who were evaluated for meningitis by traditional criteria and by enterovirus-polymerase chain reaction (EV-PCR). A cohort of 906 consecutive pediatric patients to receive CSF analysis at St Louis Children's Hospital, St Louis, Mo, from June 1, 1998, to December 31,1998, was studied for clinical and laboratory data. Age-dependent CSF protein concentrations were then derived from a reference group of 225 patients in whom meningitis and other neurologic diseases were excluded by traditional clinical or laboratory criteria (excluding EV-PCR). Available CSF samples from 132 patients of the reference group were subsequently tested for EV-PCR. In the reference group, the CSF protein concentration was highest and most variable in neonates, with a maximum of approximately 1.0 g/L. Cerebrospinal fluid protein concentration decreased rapidly to a nadir by 6 months and remained low throughout childhood, rarely exceeding 0.3 g/L and, finally, increasing in adolescence toward adult values. Enterovirus- polymerase chain reaction was positive in CSF of 11% of the reference group, with EV-PCR-positive patients having significantly higher CSF protein concentrations than EV-PCR-negative patients aged between 4 months and 14 years. Reference values for CSF protein exhibit a characteristic age dependence in pediatric patients. Continued standard use of adult reference values in the pediatric population is inappropriate. The unexpected finding of a positive EV-PCR in patients not diagnosed with meningitis by traditional criteria further emphasizes the importance of selecting the most clinically relevant reference group for age and other variables when defining normal laboratory values. Arch Pediatr Adolesc Med. 2000;154:827-831