Enterovirus Polymerase Chain Reaction Research Articles

Outbreak of Neurologic Enterovirus Type 71 Disease: A Diagnostic Challenge

Similar to poliovirus, enterovirus type 71 (EV71) causes severe disease, including aseptic meningitis, encephalitis, acute flaccid paralysis, and acute cardiopulmonary dysfunction. Large epidemics of EV71 infection have been reported worldwide. After recognition of a cluster of cases of EV71 disease, we reviewed records of patients with EV71 disease who required hospitalization at The Children's Hospital in Denver, Colorado, from 2003 through 2005. The presence of enterovirus was detected by reverse-transcriptase polymerase chain reaction (PCR) and/or viral culture of specimens from multiple sources, and the virus was typed as EV71 using genetic sequencing. Eight cases of EV71 disease were identified in both 2003 and 2005. Fifty-six percent of patients with EV71 disease were < or = 6 months of age (range, 4 weeks to 9 years). All 16 patients had EV71 central nervous system infection. Enterovirus PCR (EV-PCR) of cerebrospinal fluid specimens yielded positive results for only 5 (31.2%) of the 16 patients; all of these patients were < 4 months of age and had less severe disease. However, EV-PCR of upper respiratory tract specimens yielded positive results for 8 (100%) of 8 patients, and EV-PCR of lower gastrointestinal tract specimens yielded positive results for 7 (87.5%) of 8 patients. An outbreak of neurologic EV71 disease occurred in Denver, Colorado, during 2003 and 2005. Likely, EV71 disease remains unrecognized in other parts of the United States, because EV-PCR of cerebrospinal fluid frequently yields negative results. EV-PCR of specimens from the respiratory and gastrointestinal tracts had higher diagnostic yields than did EV-PCR of cerebrospinal fluid. EV71 infection should be considered in young children presenting with aseptic meningitis, encephalitis, acute flaccid paralysis, or acute cardiopulmonary collapse. EV71 infection may be an underrecognized emerging disease in the United States.

Routine Cerebrospinal Fluid Enterovirus Polymerase Chain Reaction Testing Reduces Hospitalization and Antibiotic Use for Infants 90 Days of Age or Younger

The goal was to evaluate the impact of cerebrospinal fluid enterovirus polymerase chain reaction testing on the length of hospitalization and the duration of antibiotic use for infants < or = 90 days of age with suspected aseptic meningitis. This retrospective cohort study was conducted at an urban, tertiary-care children's hospital. Data were collected for 478 patients < or = 90 days of age for whom cerebrospinal fluid enterovirus polymerase chain reaction testing was performed during the enteroviral seasons of 2000 to 2006. The length of hospitalization and the duration of antibiotic use were assessed. Cerebrospinal fluid enterovirus polymerase chain reaction test results were positive for 154 patients (34.8%). The mean length of stay was 3.65 days. The median polymerase chain reaction turnaround time was 23 hours. In multivariate analysis, having a positive cerebrospinal fluid enterovirus polymerase chain reaction result was associated with a 1.54-day decrease in the length of stay and a 33.7% shorter duration of antibiotic use. When patients were stratified according to the presence or absence of pleocytosis, both groups demonstrated significant reductions in the length of stay with positive cerebrospinal fluid enterovirus polymerase chain reaction results (1.32 and 1.38 days, respectively). Furthermore, increasing the polymerase chain reaction turnaround time by 24 hours increased the length of stay by 13.6% for patients with positive cerebrospinal fluid enterovirus polymerase chain reaction results. Having positive cerebrospinal fluid enterovirus polymerase chain reaction results decreases the length of hospitalization and the duration of antibiotic use for young infants. These results support the routine use of this test during periods of peak enterovirus prevalence.

Aseptic Meningitis in Children: Analysis of 506 Cases

BackgroundNon-polio human enteroviruses are the leading cause of aseptic meningitis in children. The role of enterovirus PCR for diagnosis and management of aseptic meningitis has not been fully explored.Methodology/Principal FindingsA retrospective study was conducted to determine the epidemiological, clinical, and laboratory characteristics of aseptic meningitis and to evaluate the role of enterovirus PCR for the diagnosis and management of this clinical entity. The medical records of children who had as discharge diagnosis aseptic or viral meningitis were reviewed. A total of 506 children, median age 5 years, were identified. The annual incidence rate was estimated to be 17/100,000 children less than 14 years of age. Most of the cases occurred during summer (38%) and autumn (24%). The dominant clinical symptoms were fever (98%), headache (94%) and vomiting (67%). Neck stiffness was noted in 60%, and irritation in 46% of the patients. The median number of CSF cell count was 201/mm3 with polymorphonuclear predominance (>50%) in 58.3% of the cases. Enterovirus RNA was detected in CSF in 47 of 96 (48.9%) children tested. Children with positive enterovirus PCR had shorter hospitalization stay as compared to children who had negative PCR or to children who were not tested (P = 0.01). There were no serious complications or deaths.ConclusionsEnteroviruses accounted for approximately one half of cases of aseptic meningitis. PCR may reduce the length of hospitalization and plays important role in the diagnosis and management of children with aseptic meningitis.

Probable Intrafamilial Transmission of Coxsackievirus B3 With Vertical Transmission, Severe Early-Onset Neonatal Hepatitis, and Prolonged Viral RNA Shedding

Here we report a familial cluster of 3 cases of coxsackievirus B3 infection: a recent history of illness in a woman's 3-year-old son with a coxsackievirus B3-positive stool culture indicated that he probably infected his mother at home during her last week of pregnancy. Consequently, she delivered an infected neonate who developed severe hepatitis, disseminated intravascular coagulation, and bilateral intracranial hemorrhage. The neonate remained well for the first 2 days of life. On the third day, he developed fever (39 degrees C) and poor peripheral circulation. On the fourth day, he developed petechiae and bruises over his chest wall and extremities, and prolonged bleeding was observed over venipuncture sites. Investigations revealed severe thrombocytopenia (platelets: 41 x 10(9)/L) and a markedly deranged coagulation profile (prothrombin time: 19 seconds [reference: < 10 seconds]; activated partial thromboplastin time: > 120 seconds [reference: 24.2-37.0 seconds], serum D-dimers: 6722 ng/mL [reference: < 500 ng/mL]), suggestive of disseminated intravascular coagulopathy. Clinical examination revealed yellow sclera, hepatomegaly (5 cm), and splenomegaly (2 cm), consistent with hepatitis. Serial chest radiographs showed bilateral pleural effusions, and an ultrasound of the abdomen demonstrated ascites. An echocardiogram showed normal cardiac structure and good contractility of both ventricles. However, a cranial ultrasound revealed bilateral grade 2 intraventricular hemorrhages. Serum C-reactive protein increased to 33.9 mg/L. Liver-function tests were also markedly deranged at this time, with maximum values for serum alanine transferase, bilirubin, alkaline phosphatase, and ammonia concentration of 1354 IU/L, 258 micromol/L, 189 IU/L, and 147 micromol/L, respectively. Serum glucose levels were normal. Over the next 3 days, his fever subsided, and his liver function and clotting profile normalized by day 13 after onset of illness. A stool sample from the older brother, collected 14 days after his onset of illness at home, was positive for coxsackievirus B3 by both virus culture and enterovirus reverse-transcription polymerase chain reaction. He had neutralizing coxsackievirus B3 antibody titers of 1:2560 and 1:1280 on days 14 and 28 after his onset of illness, respectively. No virus was cultured from the mother's stool sample, collected 5 days after her onset of illness, but the enterovirus polymerase chain reaction was positive and maternal sera neutralized the coxsackievirus B3 isolated from the neonate. The maternal sera also showed a more than fourfold rise in antibody titer from 1:80 to 1:640 on days 5 and 16 after her onset of illness, respectively. Neonatal antibody titers also showed a more than fourfold rise from < 1:80 to 1:2560 on days 1 and 21 after his onset of illness, respectively. This demonstrates that both the mother and the neonate had had recent coxsackievirus B3 infections. Serially collected neonatal throat swab and stool samples were culture negative for enterovirus by 4 and 8 days after his onset of illness, respectively. However, enterovirus RNA remained detectable by reverse-transcription polymerase chain reaction in these samples for considerably longer, only becoming undetectable by 16, 23, and 41 days after his onset of illness. We show that even mild household infections may have potentially serious consequences for pregnant women and their infants.

Diagnosis of Myocarditis

Determining the etiology of cardiac dysfunction in patients with heart failure influences management and prognosis.1 Myocarditis, diagnosed by the current histopathological Dallas criteria, accounts for &10% of patients with new-onset cardiac dysfunction submitted to endomyocardial biopsy.1,2 Despite complete evaluation including history, physical examination, blood work, echocardiography, coronary angiography, and endomyocardial biopsy, &50% of patients with dilated cardiomyopathy have no etiology identified.1 Recent data suggest that patients in the “idiopathic” category may be suffering from myocardial inflammation due to persistent viral replication or autoimmune activation after a viral infection. These studies raise the question of whether the current histopathological criteria for myocardial inflammation (the Dallas criteria) are sensitive enough to identify the population with viral or autoimmune-related heart compromise. The Dallas criteria were proposed in 1986 and provided a histopathological categorization by which the diagnosis of myocarditis could be established. Dallas criteria myocarditis requires an inflammatory infiltrate and associated myocyte necrosis or damage not characteristic of an ischemic event. Borderline myocarditis requires a less intense inflammatory infiltrate and no light microscopic evidence of myocyte destruction.3 These criteria have been used exclusively by American investigators over the last 2 decades. Sampling error, variation in expert interpretation, variance with other markers of viral infection and immune activation in the heart, and variance with treatment outcomes all suggest that the Dallas criteria are no longer adequate. Chow et al and Hauck et al4,5 demonstrated by biopsying postmortem hearts of patients who had died with myocarditis that, from a single endomyocardial biopsy, histological myocarditis could be demonstrated in only 25% of samples. With >5 biopsies, Dallas criteria myocarditis could be diagnosed in approximately two thirds of subjects. A recent MRI study used focal imaging abnormalities to guide heart biopsy investigation of possible myocarditis. The authors showed that the earliest myocardial …

Clinical and diagnostic findings of an echovirus meningitis outbreak in the north west of England

Introduction: An outbreak of echovirus meningitis occurred in the north west of England in 2001. This paper reviewed the clinical features and the role of different diagnostic methods. Methods: This...

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

High Prevalence of Cardiotropic Viruses in Myocardial Tissue from Explanted Hearts of Heart Transplant Recipients and Heart Donors: A 3-Year Retrospective Study from a German Patients’ Pool

The prevalence of some cardiotropic viruses in virus-associated inflammatory cardiac disease remains controversial. The aim of this study was to examine myocardial tissue samples from explanted hearts of heart transplant recipients and heart donors for nucleic acids of myocardiotropic viruses and to observe the potential risk of viral-induced post-transplantation complications in recipients of cardiac allografts or heart valve homografts. Myocardial tissue samples were analyzed by polymerase chain reaction (PCR) for enteroviruses, adenoviruses, human cytomegalovirus (HCMV), parvovirus B19 (PVB19), and influenza viruses. The results were compared with serologic and histopathologic findings. PCR analysis of 449 myocardial tissue samples from explanted hearts indicated infection in 34 (47%) of 73 heart transplant recipients and 48 (60%) of 80 donors. The prevalence of virus infection in donors aged over 65 years was significantly higher than in heart transplant recipients (p = 0.005) or donors aged under 65 years (p = 0.02). The most frequently detected viruses were enteroviruses (group B coxsackievirus) and adenoviruses. HCMV and PVB19 were found less frequently. All samples were negative for influenza viruses. Although the serologic findings and PCR results for different viruses were discordant in 4% to 27% of cases, PCR and histopathologic findings were highly correlated (88%). The frequent detection of viral genome sequences in myocardial tissue of both heart transplant recipients and heart donors suggests a significant risk for graft-transmitted viral infection in cardiac and heart valve transplant recipients.

Quantitative PCR-Enhanced Immunoassay for Measurement of Enteroviral Immunoglobulin M Antibody and Diagnosis of Aseptic Meningitis

A PCR-enhanced immunoassay (PIA) to detect enterovirus (EV) immunoglobulin M (IgM) for diagnosis of recent EV infection was recently developed. This test was compared with another EV IgM capture technique, the solid-phase reverse immunosorbent test (SPRIST). Fourteen of 43 serum samples from aseptic meningitis patients were positive by PIA, whereas 10 were positive by SPRIST. One of 39 control serum samples was weakly positive by PIA. A single-serum-dilution real-time PCR-based PIA for EV IgM (quantitative PIA [QPIA]) was also developed and evaluated against PIA, SPRIST, an EV IgM radioimmunoassay (RIA), and clinical data. A mixture of 12 EVs was used as the antigen. Results from investigating four groups of serum samples were as follows. (i) The nine PIA-positive serum samples in group 1 were all positive by QPIA. (ii) Group 2 consisted of 59 serum samples from aseptic meningitis patients. Nineteen of 30 serum samples (63%) taken at hospital admission were positive by QPIA. Of these, 17 were positive in EV PCR. (iii) None of the 30 control serum samples in group 3 were positive by QPIA. (iv) For the 24 serum samples in group 4, of which 11 were positive and 13 were negative by RIA, the QPIA results were completely concordant. The sensitivity and specificity of QPIA for diagnosis of EV infection were 70 and 80%, respectively. QPIA provides a rational strategy for the detection of EV IgM, allows the use of viral antigens with minimal purification, and needs no virus-specific reagents apart from those in the PCR. QPIA is a generally applicable method for the detection of viral IgM in IgM capture assays.

Positive PCR for enterovirus in the cerebrospinal fluid of a child with acute disseminated encephalomyelitis

Positive PCR for enterovirus in the cerebrospinal fluid of a child with acute disseminated encephalomyelitis

Practice patterns and management of aseptic meningitis in a pediatric emergency department

Study objectives: Data describing the pediatric emergency department (ED) practice patterns and management in aseptic meningitis are limited. We evaluate use of diagnostic tests, antibiotic use, and ED disposition in an urban pediatric ED. Methods: This was a retrospective review of patients with an International Classification of Diseases, Ninth Revision discharge diagnosis of aseptic meningitis during January 1, 1996, and December 31, 2000, in an urban pediatric teaching hospital. Results: Sample size was 131 cases (56% male patients). More than 75% of patients presented during August to October. Seventy-two percent of patients presented complaining of 1 or more of the following symptoms; fever, stiff neck, headache, or vomiting, and average duration of symptoms before presentation was 48 hours. Classic examination findings of meningeal irritation were found in less than 16% of patients. Cranial computed tomography (CT) was ordered in 21% of suspected meningitis cases with normal level of consciousness, and no abnormalities were found. Median circulating WBC count was 10,800 cells/mL. Median cerebrospinal fluid WBC count was 345 cells/mL. The most common antibiotic administered was Ceftriaxone (63%). Rapid antigen tests were used in only 53% of children. Enteroviral polymerase chain reaction was used in only 53% of cases. Herpes virus polymerase chain reaction was ordered in 6 cases, and 1 length of stay was 3 days. Thirty-three percent of patients were admitted to the general medical floor, and 23.5% were sent home from the ED. Seventy-nine percent of patients were continued on Ceftriaxone as an inpatient until cerebrospinal fluid studies were completed. Ninety percent of patients were discharged without antibiotics. Conclusion: Aseptic meningitis has a benign presentation, and use of lumbar puncture may account for seasonal preponderance. Use of cranial CT is limited but appropriately so. Rapid adjunct diagnostic tests are ordered infrequently. New strategies to standardize ED care and reduce unnecessary laboratory tests are needed.

Neonatal coxsackie B virus infection-a treatable disease?

Ten neonates with coxsackie B viral infection presented over a 3-month period. Clinical features included meningoencephalitis, thrombocytopenia, disseminated intravascular coagulopathy, cardiomyopathy, and hepatitis. Eight infants had multiorgan disease, four with severe myocardial dysfunction, of whom two died. All of the infants with severe disease developed symptoms within 7 days of age. In infants presenting within 10 days of birth, in all cases there were symptoms compatible with maternal infection prior to delivery. Severity was associated with perinatal transmission. Enteroviral polymerase chain reaction of CSF, urine, stool or throat swab was positive in nine of the ten babies. Seven of the infants were treated with a 7-day course of the new anti-picornaviral drug pleconaril (5 mg/kg 3 times daily). These cases highlight the importance of not missing coxsackie B viral infection in the differential diagnosis of the septic neonate, especially as there is now a potential treatment.

Impact of rapid polymerase chain reaction results on management of pediatric patients with enteroviral meningitis.

Enterovirus (EV) infections can be rapidly detected by PCR. However, several studies suggest that results must be available early in the management of the patient to impact significantly on patient care. We evaluated this hypothesis directly during an outbreak of EV aseptic meningitis. From June through November, 1998, EV PCR was performed 5 days a week on cerebrospinal fluid specimens from pediatric patients evaluated for meningitis. We compared antibiotic use, length of stay and hospital charges in a group of patients with EV meningitis whose positive EV PCR results were available within 24 h of specimen collection, to a group of similar patients whose results were available >24 h after collection. Cerebrospinal fluid specimens were submitted for EV PCR from 113 patients with suspected EV meningitis, and 50 of 113 (44%) were positive. Of these 50 EV-PCR-positive patients, 17 of 50 (34%) had EV PCR results available in < or = 24 h and 33 of 50 (66%) had results available in >24 h. Patients with EV-positive results reported < or = 24 h after specimen collection had 20 h less of antibiotic use (P = 0.006) and $2,798 less in hospital charges (P = 0.001) than patients with positive results available in >24 h. Hospitalized patients who received positive results rapidly did not have significantly less antibiotic therapy or shorter length of stay, but hospital charges were reduced by $2,331 (P = 0.009). Rapid reporting of PCR results can have a significant impact on several outcome measures for patients with EV meningitis.

Rapid diagnosis of enterovirus infections by real-time PCR on the LightCycler using the TaqMan format

A 2 h single-tube, reverse-transcription(RT)-PCR/hybridization assay using the TaqMan format for rapid diagnostic screening of enterovirus (EV) infections was optimized for the real-time LightCycler (LC) technology. For low EV load clinical samples an additional 30 min reamplification step using a novel primer-mix/probe design resulted in a 100% concordance with AMPLICOR EV PCR Test and in-house RT-PCR. Combined with maximum specificity, the sensitivity of LC-PCR was 10- to 100-fold higher compared to AMPLICOR EV Test.

Risk of infection by reprocessed and resterilized virus-contaminated catheters; an in-vitro study.

In spite of increasing reuse of disposable catheters, there are few scientific data on potential viral transmission and infection after reuse. To determine the theoretical risk of virus transmission during reuse of catheters an in vitro study was performed using an RNA virus (echovirus-11) and a DNA virus (adenovirus-2). After deliberate contamination of the catheters, reprocessing and reuse of the cleaned and glutaraldehyde sterilized catheters was simulated. The presence of residual virus was determined by cell culture and by polymerase chain reaction (PCR). After the sterilization step, infectious enterovirus was detectable in one (10%) of the samples, whereas two (20%) contained detectable enterovirus RNA. After simulated reuse, enterovirus was cultured from one (10%) of the catheters, but no less than six (60%) of the samples were enterovirus PCR positive and one (10%) contained detectable adenovirus DNA. After sonification of the catheter tips no infectious virus could be detected, but enterovirus RNA was detected in two (20%) and adenovirus DNA in three (30%) of the samples. It has been clearly demonstrated in this in vitro study that, even after rigorous cleaning and sterilization, virus was still present in the catheter. Reuse of catheters, labelled for single-use only, is dangerous and should be prevented.

Coxsackie B virus infection in idiopathic dilated cardiomyopathy: clinical and pharmacological implications.

Idiopathic dilated cardiomyopathy (IDC) is a myocardial disease characterised by ventricular dilatation, impaired contractility, and the symptoms of congestive heart failure. Although the causes of IDC remain uncertain, much interest has been focused on the enteroviral infection in the myocardium in the pathogenesis of this disease. Enteroviral RNA has been demonstrated in the myocardium at all stages of IDC. Recent studies using sequence analysis of enteroviral polymerase chain reaction (PCR) products have shown that the viruses detected in hearts of patients with IDC are coxsackie B. In addition, active coxsackieviral RNA replication in the myocardium has been demonstrated by strand-specific detection of viral RNA. Viral antigen has also been found in hearts with IDC by immunohistochemical techniques. In tissue culture experiments and transgenic mice, it has been shown that restricted coxsackieviral RNA replication, and not infectious virus progeny, in the myocardium can impair cardiac contractile function and lead to dilated cardiomyopathy. Coxsackieviral RNA in the myocardium can be a marker of a poor clinical outcome after partial left ventriculectomy, and might influence prognosis after heart transplantation. Therefore, there is a therapeutic need to detect replicating coxsackieviral RNA in the myocardium, and a specific therapy for coxsackie B viruses is indicated in the management of patients with virus-positive IDC.

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

Cost analysis of enteroviral polymerase chain reaction in infants with fever and cerebrospinal fluid pleocytosis.

Infants with fever and cerebrospinal fluid (CSF) pleocytosis are routinely admitted to the hospital for parenteral antibiotic therapy for potential bacterial meningitis pending results of CSF culture. Published estimates suggest that 90% of all episodes of meningitis are caused by enterovirus. Enteroviral polymerase chain reaction (ePCR) has a sensitivity of 92% to 100% and a specificity of 97% to 100% in CSF. To compare a management strategy using ePCR with current practice to determine potential savings by allowing earlier discharge. Decision analysis comparing 2 strategies for the care of a retrospective cohort of infants with fever and CSF pleocytosis: standard practice vs ePCR testing of all CSF samples. Model assumptions include the following: (1) standard practice patients continue parenteral antibiotic therapy until CSF cultures are negative at 48 hours, (2) patients with positive ePCR results would be discharged after 24 hours, (3) patients with positive ePCR results have a negative CSF culture, and (4) costs are calculated from actual patient charges with a cost-to-charge ratio of 0.65. All infants aged 28 days to 12 months admitted to an urban teaching hospital with fever, CSF pleocytosis, and a negative CSF Gram stain from January 1996 through December 1997. Total cost of hospitalization. A total of 126 infants were identified. One hundred twelve (89%) were discharged with a diagnosis of aseptic meningitis; 72% of these cases occurred during the peak enterovirus season (June to October). Three of 3 patients with positive CSF cultures had bacterial growth within 24 hours of admission. Mean length of stay for patients with aseptic meningitis was 2.3 days (SD, +/-1.4 days). Total cost of hospital care for all 126 infants was $381,145. In our patient population, total patient costs would be reduced by the ePCR strategy if enterovirus accounts for more than 5. 9% of all meningitis cases. Varying the sensitivity of the ePCR assay from 100% to 90% changes the "break-even" prevalence from 5.8% to 6.5%. Total cost savings of 10%, 20%, and 30% would occur at an enteroviral meningitis prevalence of 36.3%, 66.7%, and 97.1%, respectively. Enteroviral PCR analysis of CSF for infants admitted to the hospital with meningitis can result in cost savings when the prevalence of enteroviral meningitis exceeds 5.9%. Limiting use of ePCR to the enterovirus season would increase cost savings. A prospective study is needed to validate these results. Arch Pediatr Adolesc Med. 2000;154:817-821

Enteric virus infections and diarrhea in healthy and human immunodeficiency virus-infected children.

Forty-three stool samples from 27 human immunodeficiency virus (HIV)-seropositive children and 38 samples from 38 HIV-negative children, collected during a 15-month period, were examined for enteric viruses. Diagnostic assays included enzyme immunoassays for rotavirus, adenovirus, and Norwalk virus; polyacrylamide gel electrophoresis for picobirnavirus and atypical rotavirus; and PCR for astrovirus and enterovirus. Specimens from HIV-positive children were more likely than those of HIV-negative children to have enterovirus (56 versus 21%; P < 0.0002) and astrovirus (12 versus 0%; P < 0.02), but not rotavirus (5 versus 8%; P > 0.5). No adenoviruses, picobirnaviruses, or Norwalk viruses were found. The rates of virus-associated diarrhea were similar among HIV-positive and HIV-negative children. Enteroviruses were excreted for up to 6 months in HIV-positive children; however, no evidence for prolonged excretion of poliovirus vaccine was observed. These results suggest that although infection with enterovirus and astrovirus may be frequent in HIV-infected children, enteric viruses are not associated with the diarrhea frequently suffered by these children.

Utility of Enterovirus PCR Testing of CSF

Infectious Diseases| August 01 2000 Utility of Enterovirus PCR Testing of CSF AAP Grand Rounds (2000) 4 (2): 10–11. https://doi.org/10.1542/gr.4-2-10 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Utility of Enterovirus PCR Testing of CSF. AAP Grand Rounds August 2000; 4 (2): 10–11. https://doi.org/10.1542/gr.4-2-10 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: cerebrospinal fluid, enterovirus, polymerase chain reaction Source: Ramers C, Billman G, Hartin M, et al. Impact of a diagnostic cerebrospinal fluid enterovirus polymerase chain reaction test on patient management. JAMA. 2000;283:2680–2685. Ramers et al retrospectively reviewed the records of patients for whom an enterovirus-specific (EV) PCR of the cerebrospinal fluid (CSF) was performed at the Children’s Hospital, San Diego during 1998 in patients with suspected aseptic meningitis. The median age of the 276 patients tested was 5.5 months (range 0 to 201 months). Of the patients tested, 49.6% (137) had a positive result. The test was available 6 days per week June-December, 3 days per week January–May. Eighty-nine patients were discharged before their PCR result was available. Median PCR result turnaround time was longer (48 hours) for patients discharged before results were available than for patients who received the results before discharge (32 hrs, P<.001). Of the 187 results... You do not currently have access to this content.