Schools can be made safer from germs by: 1. Reinforcing students' personal health and hygiene practices such as hand washing, proper wound care, timely immunizations, nutritious diet, adequate sleep, reducing long-term stress, regular moderate exercise, and matching wardrobe to the weather; 2. Adherence to health department exclusion/inclusion policies for students who are infected, symptomatic, exposed to infection, or susceptible to infection; 3. Practicing sound environmental hygiene, with particular attention to surface disinfecting and food safety.

BACKGROUND: Enteroviruses (EV) cause a broad spectrum of human diseases, of which aseptic meningitis is among the most common and most clinically vexing. While the clinical symptoms of meningitis caused by bacteria, fungi and viruses are similar, the diagnosis, therapy and outcome of disease caused by these agents vary greatly. In order to appropriately manage meningitis patients, rapid and reliable diagnosis of EV meningitis impacts significantly on patient management. OBJECTIVE: To develop a direct and uninterrupted RNA amplification of enteroviruses using rTth DNA polymerase. STUDY DESIGN: Purified coxsackievirus B6 RNA of various concentrations was amplified by rTth DNA polymerase-mediated amplification to determine analytic sensitivity. The specificity of the EV amplification was examined with a panel of nucleic acids from 36 EV serotypes, 15 non-EV pathogens and 10 coded clinical specimens of cerebrospinal fluid (CSF). RESULTS: All EV serotypes tested were detected successfully by this method at a sensitivity of 1 TCID(50) with the exception of echoviruses 1, 5, 22 and 23. Echovirus 5 was detected at 10 TCID(50), and echovirus 1 was detected at 100 TCID(50). Echoviruses 22 and 23 were not detectable at 100 TCID(50). Cross-reactivity of EV RT-PCR assay with 15 known non-EV meningitis pathogens has not been observed. Results of 10 CSF tested with this system correlated well with tissue culture. CONCLUSIONS: We have developed an EV amplification assay which has several important advantages over previously reported methods. This assay employs rTth DNA polymerase which possesses both reverse transcriptase and DNA polymerase activities, simplifying RNA reverse transcription and DNA amplification to an uninterrupted reaction. Additionally, potential carryover contamination and enhanced amplification specificity is provided by substituting dUTP for dTTP and adding uracil N-glycosylase (UNG) in the amplification reaction. Finally, the detection of amplified product is via a colorimetric, microwell format permitting the use of readily available instrumentation.

OBJECTIVE: To determine whether there is association between infection with enteroviruses and beta-cell autoimmunity in children at elevated risk of developing type 1 diabetes. BACKGROUND: Recent prospective and case-control studies of children who are at high risk of developing type 1 diabetes have suggested that enterovirus (EV) infections are a risk factor for beta-cell autoimmunity and type 1 diabetes. METHODS: A nested matched case-control study of incident cases of beta-cell autoimmunity within two prospective cohorts of genetically high-risk children (cases=26, controls=39). EV infection was detected by PCR of serum, saliva and rectal swab samples. RESULTS: Prior to autoimmunity conversion (or the equivalent age in controls), 11.5% of cases and 17.9% of controls were positive for EV infection. EV was detected in 19.5% of cases and 25.6% of controls over the whole follow-up period. Conditional logistic regression gave no evidence that the frequency of EV infection was associated with beta-cell autoimmunity. There was a trend for the mean number of EV infections found in EV-positive cases (2.2/case) to be higher than in EV-positive controls (1.2/control, P=0.08). However, there were no multiple infections prior to conversion in either cases or controls. CONCLUSIONS: There is no evidence from this study that EV infection is a risk factor for development of beta-cell autoimmunity. Further study is needed to assess whether persistent or repeated EV infections occur frequently in individuals with beta-cell autoimmunity.

The picornaviruses are a diverse group of viral pathogens that together comprise the most common causes of infections of humans in the developed world. Within the picornavirus family are three well-known groups of human pathogens-the enteroviruses (including polioviruses, coxsackieviruses, and echoviruses), the rhinoviruses, and the hepatoviruses (including hepatitis A). Recently, the parechoviruses (formerly, echoviruses 22 and 23) have been classified as a fourth genus of human picornaviruses. This article will focus on the enteroviruses and rhinoviruses agents, for which substantial effort has been expended and recent successes reported towards the development of safe and effective antiviral therapy.

Enteroviruses usually cause self-limited disease that, although associated with high morbidity, is rarely fatal. In certain patient populations, however, the enteroviruses may cause potentially life-threatening infections. Pleconaril is a novel compound that integrates into the capsid of picornaviruses, including enteroviruses and rhinoviruses, preventing the virus from attaching to cellular receptors and uncoating to release RNA into the cell. Pleconaril was used on a compassionate-release basis to treat patients with potentially life-threatening enterovirus infections, and for 38 of these patients sufficient follow-up data were available for determining responses to therapy. Response was evaluated in 4 categories: clinical, virological, laboratory, and radiological. Most patients (28 [78%] of 36), including 12 of 16 with chronic enterovirus meningoencephalitis, were judged to have a clinical response temporally associated with pleconaril therapy. Similarly, nearly all patients whose virological responses (12 [92%] of 13), laboratory responses (14 [88%] of 16), and radiological responses (3 [60%] of 5) could be evaluated were judged to have responded favorably to a course of pleconaril treatment. Adverse effects were minimal and the drug was generally well-tolerated.

Enteroviruses account for 85 to 95% of all cases of aseptic meningitis, but the arboviruses and herpes simplex virus are also important etiologic agents. Mumps, lymphocytic choriomeningitis virus, herpes zoster, human herpesvirus type 6, and influenza viruses are rare causes of meningitis. The virology, pathogenesis, epidemiology, clinical manifestations, diagnostic studies, and established and potential antiviral therapies for viral meningitis are discussed. A differential diagnosis of the aseptic meningitis syndrome is provided.

Picornaviruses, including the rhinoviruses and enteroviruses, are common causes of infections in the developed world and the most common reason for prescribing antibiotics. These ubiquitous pathogens are increasingly being recognized in more serious illnesses, such as sinusitis, exacerbations of asthma, exacerbations of cystic fibrosis, myocarditis, meningitis, and severe neonatal sepsislike disease. Recent advances have improved our ability to diagnosis and treat these infections.

The picornaviruses are a diverse group of viral pathogens that together comprise the most common causes of infection of humans in the developed world. Within the picornavirus family are three well-known groups of human pathogens--the rhinoviruses, the enteroviruses (including polioviruses, coxsackieviruses and echoviruses) and the hepatoviruses (including hepatitis A virus). This article will focus on the rhinoviruses and enteroviruses, agents for which substantial effort has been expended, and recent successes reported, toward the development of safe and effective antiviral therapy.

Cerebrospinal fluid samples obtained 7 years apart from a patient with chronic meningoencephalitis and underlying agammaglobulinemia were examined to determine enteroviral genotypic variability. From each sample, amplicons spanning 496 nucleotides within the 5' nontranslated region were generated directly from the cerebrospinal fluid and analyzed. A consensus sequence derived from 3 clones of each amplicon revealed only 7 nucleotide changes over the 7-year period within the region studied. The observed 5' nontranslated region mutation rate in this patient ( approximately 0.2% per year) was significantly lower than mutation rates reported for the poliovirus genome.

BACKGROUND: Enteroviruses are common causes of aseptic meningitis and nonspecific febrile illnesses in young children. During the summer-fall months, enterovirus-infected children are frequently evaluated in emergency room settings to rule out bacterial sepsis and/or meningitis. OBJECTIVES: We sought to determine the clinical significance of enterovirus infections in children evaluated for serious febrile illnesses in pediatric emergency rooms during the summer-fall season. METHODS: Children admitted to emergency rooms at four university teaching hospitals during a single summer-fall season who required blood culture and/or lumbar puncture to rule out bacterial sepsis/meningitis were prospectively studied. An extensive questionnaire was administered, and specimens of cerebrospinal fluid, serum, urine and throat were tested for enteroviruses by viral culture and PCR. Patients were followed to determine the duration, management and outcome of their illnesses. RESULTS: Of 203 patients studied 173 had no apparent explanation for their illness (e.g. bacterial sepsis, bacterial urinary tract infection, etc.). Of those 173 patients 79 (46%) were infected with enteroviruses, including 33 of 47 (70%) patients with aseptic meningitis, 13 of 25 (52%) patients with nonspecific febrile episodes and 33 of 101 (33%) patients with fever and focal findings (P < 0.0001 for aseptic meningitis vs. fever and focal findings; P = 0.0001 for aseptic meningitis vs. combined nonspecific febrile episodes and fever/focal patients). Among 119 hospitalized patients 65 (55%) were enterovirus-infected. Children < or =90 days of age were more likely to be enterovirus-infected (66 of 122; 54%) than children older than 90 days (13 of 51; 25%)(P = 0.0001). Enterovirus-infected children were more likely to be hospitalized as a result of the current emergency room visit (65 of 79 vs. 54 of 94; P = 0.0005) and were more likely to have had an additional hospitalization for the same illness (10 of 79 vs. 1 of 94; P = 0.003). Enterovirus-infected patients also had a shorter period from illness onset to presentation. Enterovirus-infected children were indistinguishable from those without enterovirus infection in their symptoms at onset, signs at presentation and total duration of illness (>7 days in both groups). Enterovirus-infected children were almost all treated with antibiotics (78 of 79; 99%), with 74 of 79 (94%) receiving parenteral antibiotics for a mean of 3.6 days. CONCLUSIONS: During the summer-fall months, 39%(79 of 203) of children for whom blood cultures and/or lumbar punctures were performed for suspected bacterial infection had enterovirus infection identified as the only explanation for their illness. Of those patients with no alternative diagnosis, enterovirus infection was confirmed in 46%(79 of 179). The majority of those patients requiring hospitalization were infected with enteroviruses. The use of PCR increases the number of children for whom a specific etiology of illness can be determined and may in the future reduce the hospitalization and use of unnecessary antibiotics in patients with enterovirus infections.