Atypical hand, foot, and mouth disease associated with coxsackievirus A6 infection, Edinburgh, United Kingdom, January to February 2014.

In January to February 2014, 16 hand, foot and mouth disease (HFMD) cases were identified in Edinburgh, United Kingdom. All presented with atypical features, with most (n=13) resembling eczema herpeticum or chickenpox. Coxsackievirus A6 (CV-A6) was identified in all the typed cases (n=11). As atypical forms of HFMD associated with CV-A6 are likely to emerge throughout Europe, clinicians should be alert to unusual clinical presentations of HFMD and virologists aware of effective diagnostic testing and enterovirus typing methods.

Disease burden of the most commonly detected respiratory viruses in hospitalized patients calculated using the disability adjusted life year (DALY) model.

BACKGROUND: The most common acute infections occur in the respiratory tract. Recent discoveries of several novel viruses have markedly increased the repertoire of agents understood to cause presentations of acute respiratory disease. OBJECTIVES: Further understanding is needed of the relative importance of newly discovered pathogens in the clinical setting to provide clinicians with an indication of appropriate diagnostic and therapeutic targets. To address this, quantification of the disease burden of respiratory viruses in hospitalized patients was undertaken. STUDY DESIGN: Disease burden caused by respiratory viruses in hospitalized patients was quantified using the World Health Organization endorsed DALY model. Diagnostic testing results from samples collected over three years for adenovirus (AdV), influenzas A and B, parainfluenza viruses 1, 2 and 3 (PIV-1, -2 and -3), respiratory syncytial virus (HRSV), and previously published retrospective screening for human metapneumovirus, rhinoviruses, and four respiratory coronaviruses were applied to the DALY model. Disability weights were calculated per 1000 hospitalized patients in age banded groups. RESULTS: Strikingly different disease burden profiles were observed in children and adults. Adenoviruses were among the leading cause of respiratory presentations in children but not adults. HRSV and influenza A were consistently one of the greatest causes of disease regardless of sampled population. Rhinoviruses and PIV-3 were significant pathogens in all groups except those aged 16-64 years. In immunocompromised patients rhinoviruses were the leading viral cause of disease. CONCLUSIONS: These analyses provide a framework which can be used to identify where finite resources should be directed in respiratory therapeutics and vaccine development.

Epidemiology and clinical presentations of the four human coronaviruses 229E, HKU1, NL63, and OC43 detected over 3 years using a novel multiplex real-time PCR method.

Four human coronaviruses (HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43) are associated with a range of respiratory outcomes, including bronchiolitis and pneumonia. Their epidemiologies and clinical characteristics are poorly described and are often reliant on case reports. To address these problems, we conducted a large-scale comprehensive screening for all four coronaviruses by analysis of 11,661 diagnostic respiratory samples collected in Edinburgh, United Kingdom, over 3 years between July 2006 and June 2009 using a novel four-way multiplex real-time reverse transcription-PCR (RT-PCR) assay. Coronaviruses were detected in 0.3 to 0.85% of samples in all age groups. Generally, coronaviruses displayed marked winter seasonality between the months of December and April and were not detected in summer months, which is comparable to the pattern seen with influenza viruses. HCoV-229E was the exception; detection was confined to the winter of 2008 and was sporadic in the following year. There were additional longer-term differences in detection frequencies between seasons, with HCoV-OC43 predominant in the first and third seasons and HCoV-HKU1 dominating in the second (see Results for definitions of seasons). A total of 11 to 41% of coronaviruses detected were in samples testing positive for other respiratory viruses, although clinical presentations of coronavirus monoinfections were comparable to those of viruses which have an established role in respiratory disease, such as respiratory syncytial virus, influenza virus, and parainfluenza viruses. The novel multiplex assay for real-time pan-coronavirus detection enhances respiratory virus diagnosis, overcomes potential diagnostic problems arising through seasonal variation in coronavirus frequency, and provides novel insights into the epidemiology and clinical implications of coronaviruses.

Screening respiratory samples for detection of human rhinoviruses (HRVs) and enteroviruses: comprehensive VP4-VP2 typing reveals high incidence and genetic diversity of HRV species C.

Rhinovirus infections are the most common cause of viral illness in humans, and there is increasing evidence of their etiological role in severe acute respiratory tract infections (ARTIs). Human rhinoviruses (HRVs) are classified into two species, species A and B, which contain over 100 serotypes, and a recently discovered genetically heterogeneous third species (HRV species C). To investigate their diversity and population turnover, screening for the detection and the genetic characterization of HRV variants in diagnostic respiratory samples was performed by using nested primers for the efficient amplification of the VP4-VP2 region of HRV (and enterovirus) species and serotype identification. HRV species A, B, and C variants were detected in 14%, 1.8%, and 6.8%, respectively, of 456 diagnostic respiratory samples from 345 subjects (6 samples also contained enteroviruses), predominantly among children under age 10 years. HRV species A and B variants were remarkably heterogeneous, with 22 and 6 different serotypes, respectively, detected among 73 positive samples. Similarly, by using a pairwise distance threshold of 0.1, species C variants occurring worldwide were provisionally assigned to 47 different types, of which 15 were present among samples from Edinburgh, United Kingdom. There was a rapid turnover of variants, with only 5 of 43 serotypes detected during both sampling periods. By using divergence thresholds and phylogenetic analysis, several species A and C variants could provisionally be assigned to new types. An initial investigation of the clinical differences between rhinovirus species found HRV species C to be nearly twice as frequently associated with ARTIs than other rhinovirus species, which matches the frequencies of detection of respiratory syncytial virus. The study demonstrates the extraordinary genetic diversity of HRVs, their rapid population turnover, and their extensive involvement in childhood respiratory disease.

System to monitor a portion of the total testing process in medical clinics and laboratories: evaluation of a split-specimen design.

To evaluate a split-specimen design to identify problems in the testing process in hospital and physician office laboratories, we examined the testing for serum total cholesterol (n = 646) and potassium (n = 732) at 11 medical clinics evaluating 30-199 patients (mean, 125). Clinic personnel collected three tubes of blood from each patient. One specimen was processed routinely, the second was sent to a referral laboratory (RL), and the third specimen was sent to a holding facility for storage. The corresponding stored sample was retrieved and divided into three audit samples randomly and when result difference for the first two specimens exceeded critical values; one audit sample was sent to the original participant, the second to the RL, and the third to a referee laboratory. When three criteria were used, the result discrepancy rates were 2.5-8.7% for potassium and 1.5-4.6% for cholesterol. The split-specimen design could be implemented and evaluated as a monitoring system for a portion of the testing process.

Accuracy of reporting nosocomial infections in intensive-care-unit patients to the National Nosocomial Infections Surveillance System: a pilot study.

OBJECTIVE: To assess the accuracy of nosocomial infections data reported on patients in the intensive-care unit by nine hospitals participating in the National Nosocomial Infections Surveillance (NNIS) System. DESIGN: A pilot study was done in two phases to review the charts of selected intensive-care-unit patients who had nosocomial infections reported to the NNIS System. The charts of selected high- and low-risk patients in the same cohort who had no infections reported to the NNIS System also were included. In phase I, trained data collectors reviewed a sample of charts for nosocomial infections. Retrospectively detected infections that matched with previously reported infections were deemed to be true infections. In phase II, two Centers for Disease Control and Prevention (CDC) epidemiologists reexamined a sample of charts for which a discrepancy existed. Each sampled infection either was confirmed or disallowed by the epidemiologists. Confirmed infections also were deemed to be true infections. True infections from both phases were used to estimate the accuracy of reported NNIS data by calculating the predictive value positive, sensitivity, and specificity at each major infection site and the "other sites." RESULTS: The data collectors examined a total of 1,136 patients' charts in phase I. Among these charts were 611 infections that the study hospitals had reported to the CDC. The data collectors retrospectively matched 474 (78%) of the prospectively identified infections, but also detected 790 infections that were not reported prospectively. Phase II focused on the discrepant infections: the 137 infections that were identified prospectively and reported but not detected retrospectively, and the 790 infections that were detected retrospectively but not reported previously. The CDC epidemiologists examined a sample of 113 of the discrepant reported infections and 369 of the discrepant detected infections, and estimated that 37% of all discrepant reported infections and 43% of all discrepant detected infections were true infections. The predictive value positive for reported bloodstream infections, pneumonia, surgical-site infection, urinary tract infection, and other sites was 87%, 89%, 72%, 92%, and 80%, respectively; the sensitivity was 85%, 68%, 67%, 59%, and 30%, respectively; and the specificity was 98.3%, 97.8%, 97.7%, 98.7%, and 98.6%, respectively. CONCLUSIONS: When the NNIS hospitals in the study reported a nosocomial infection, the infection most likely was a true infection, and they infrequently reported conditions that were not infections. The hospitals also identified and reported most of the nosocomial infections that occurred in the patients they monitored, but accuracy varied by infection site. Primary bloodstream infection was the most accurately identified and reported site. Measures that will be taken to improve the quality of the infection data reported to the NNIS System include reviewing the criteria for definitions of infections and other data fields, enhancing communication between the CDC and NNIS hospitals, and improving the training of surveillance personnel in NNIS hospitals.

A system to monitor a portion of the total testing process in medical clinics and laboratories: feasibility of a split-specimen design.

OBJECTIVE: The purpose of this study was to assess the feasibility of using a prototype split-specimen design to assess integrity of a portion of the total testing process in medical clinics and laboratories. DESIGN: Two or three tubes of venous blood were collected from 177 patients for analysis of one of three analytes (serum potassium, serum total cholesterol, and whole-blood hemoglobin). Patients were seen at one of the nine clinics participating in this study. In all cases, one tube of blood from each patient was sent to a commercial referral laboratory, and the other tube(s) forwarded to the laboratory that routinely tested specimens for the clinic (participating laboratory) for analysis. Each participating laboratory removed a preanalysis and sometimes a post-analysis aliquot from each specimen and forwarded these to the referral laboratory for analysis. SETTING: The study was conducted in six physician office laboratories (three serving 1 to 4 [mean, 2.7] internists and three serving 3 to 24 [mean, 12] family physicians) and three hospital laboratories (serving hospitals with 100 to more than 700 beds). PATIENTS: Study patients were voluntary participants and provided informed consent. Patient age ranged from 18 to 80 years, and for all the laboratory test was specifically ordered for clinical reasons. Patients who were unable or unwilling to provide informed consent, those for whom testing would require that they provide more than 100 mL of blood, those whose blood was being collected by fingerstick, and those with results that were part of a laboratory test profile were excluded. MAIN OUTCOME MEASURES: Two main outcome measures were assessed: (1) percent differences between split-specimen results exceeding the maximum allowable imprecision level, which was based on published biological variation data (defined as one-half of the intraindividual percent coefficient of variation), for each analyte (result discrepancies); and (2) all "problems" (defined as departures from standard operating procedures) that could be documented by retrospective review of all relevant medical and laboratory records. RESULTS: The rate of result discrepancies was 1 in 20 (5%) for patients in whom hemoglobin was analyzed, 12 in 57 (21%) for patients in whom potassium was analyzed, and 1 in 60 (2%) for patients in whom total cholesterol was analyzed. Results of samples obtained during the aliquoting and storage phases of the total testing process were subject to study-induced problems and were generally not useful in tracing problems to specific stages of the testing process. A total of 28 problems (involving 26 patients) were documented, but only 6 problems were due to routine testing processes. CONCLUSIONS: The feasibility and limitations of a split-specimen design to detect result discrepancies were demonstrated. Most documented problems (22 of 28, or 79%) were study induced. To assess integrity of the total testing process, such problems need to be avoided.