Heterotypic Infection and Spread of Rhinovirus A, B, and C among Childcare Attendees.

Background: Despite the frequency of human rhinovirus (HRV), data describing the molecular epidemiology of HRV in the community are limited. Childcare centers are optimal settings to characterize heterotypic HRV cocirculation. Methods: HRV specimens were prospectively obtained from a cohort of childcare attendees at enrollment and weekly during respiratory illness. The 5' noncoding region sequences were used to determine HRV species (A, B, C) and genotypes. Results: Among 225 children followed, sequence data were available for 92 HRV infections: HRV-A (n = 80; 59%) was most common, followed by HRV-C (n = 52, 39%), and HRV-B (n = 3, 2%). Forty-one genotypes were identified and cocirculation was common. Frequent spread between classrooms occurred with 2 HRV-A genotypes. Repeated detections within single illnesses were a combination of persistent (n = 7) and distinct (n = 7) genotypes. Prevalence of HRV among asymptomatic children was 41%. HRV-C was clinically similar to HRV-A and HRV-B. Conclusions: HRV epidemiology in childcare consists of heterotypic cocirculation of genotypes with periodic spread within and among classrooms. Based on our finding of multiple genotypes evident during the course of single illnesses, the use of sequence-based HRV type determination is critical in longitudinal studies of HRV epidemiology and transmission.

Reliability, Validity, and Responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) Scores in Influenza-Positive Patients.

OBJECTIVES: To assess the reliability, validity, and responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) scores for quantifying the presence and severity of influenza symptoms. METHODS: An observational prospective cohort study of adults (≥18 years) with influenza-like illness in the United States, the United Kingdom, Mexico, and South America was conducted. Participants completed the 37-item draft FLU-PRO daily for up to 14 days. Item-level and factor analyses were used to remove items and determine factor structure. Reliability of the final tool was estimated using Cronbach α and intraclass correlation coefficients (2-day reliability). Convergent and known-groups validity and responsiveness were assessed using global assessments of influenza severity and return to usual health. RESULTS: Of the 536 patients enrolled, 221 influenza-positive subjects comprised the analytical sample. The mean age of the patients was 40.7 years, 60.2% were women, and 59.7% were white. The final 32-item measure has six factors/domains (nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic), with a higher order factor representing symptom severity overall (comparative fit index = 0.92; root mean square error of approximation = 0.06). Cronbach α was high (total = 0.92; domain range = 0.71-0.87); test-retest reliability (intraclass correlation coefficient, day 1-day 2) was 0.83 for total scores and 0.57 to 0.79 for domains. Day 1 FLU-PRO domain and total scores were moderately to highly correlated (≥0.30) with Patient Global Rating of Flu Severity (except nose and throat). Consistent with known-groups validity, scores differentiated severity groups on the basis of global rating (total: F = 57.2, P < 0.001; domains: F = 8.9-67.5, P < 0.001). Subjects reporting return to usual health showed significantly greater (P < 0.05) FLU-PRO score improvement by day 7 than did those who did not, suggesting score responsiveness. CONCLUSIONS: Results suggest that FLU-PRO scores are reliable, valid, and responsive to change in influenza-positive adults.

Development of the Flu-PRO: a patient-reported outcome (PRO) instrument to evaluate symptoms of influenza.

BACKGROUND: To develop content validity of a comprehensive patient-reported outcome (PRO) measure following current best scientific methodology to standardize assessment of influenza (flu) symptoms in clinical research. METHODS: Stage I (Concept Elicitation): 1:1 telephone interviews with influenza-positive adults (≥18 years) in the US and Mexico within 7 days of diagnosis. Participants described symptom type, character, severity, and duration. Content analysis identified themes and developed the draft Flu-PRO instrument. Stage II (Cognitive Interviewing): The Flu-PRO was administered to a unique set of influenza-positive adults within 14 days of diagnosis; telephone interviews addressed completeness, respondent interpretation of items and ease of use. RESULTS: Samples: Stage I: N = 46 adults (16 US, 30 Mexico); mean (SD) age: 38 (19), 39 (14) years; % female: 56%, 73%; race: 69% White, 97% Mestizo. Stage II: N = 34 adults (12 US, 22 Mexico); age: 37 (14), 39 (11) years; % female: 50%, 50%; race: 58% White, 100% Mestizo. SYMPTOMS: Symptoms identified by >50%: coughing, weak or tired, throat symptoms, congestion, headache, weakness, sweating, chills, general discomfort, runny nose, chest (trouble breathing), difficulty sleeping, and body aches or pains. No new content was uncovered during Stage II; participants easily understood the instrument. CONCLUSIONS: Results show the 37-item Flu-PRO is a content valid measure of influenza symptoms in adults with a confirmed diagnosis of influenza. Research is underway to evaluate the suitability of the instrument for children and adolescents. This work can form the basis for future quantitative tests of reliability, validity, and responsiveness to evaluate the measurement properties of Flu-PRO for use in clinical trials and epidemiology studies.

Epidemiology of multiple respiratory viruses in childcare attendees.

BACKGROUND: The identification of multiple viruses during respiratory illness is increasing with advances in rapid molecular testing; however, the epidemiology of respiratory viral coinfections is not well known. METHODS: In total, 225 childcare attendees were prospectively followed for up to 2 years. Nasal swabs were collected at respiratory illness onset and every 7-10 days until illness resolution. Swabs were tested by polymerase chain reaction for 15 respiratory viruses and subtypes. RESULTS: At least 1 virus was detected in 382 (84%) of 455 new-onset illnesses with multiple viruses identified in 212 (46%). The proportion of subject swabs with multiple viruses detected changed as respiratory illnesses progressed from week to week, as did the prevalence of individual viruses. Children with multiple viruses detected at the time of illness onset had less frequent fever (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.35, 0.90), however, these children more often had illness symptoms lasting over 7 days (OR, 1.94; 95% CI, 1.20, 3.14). CONCLUSIONS: A high proportion of daycare attendees had multiple viruses detected during respiratory illnesses. Delay between onset of illness and viral detection varied by virus, indicating that some viruses may be underrepresented in studies of virus epidemiology that rely on only a single test at symptom onset.

Frequent and prolonged shedding of bocavirus in young children attending daycare.

BACKGROUND: Little is known about human bocavirus (HBoV) persistence and shedding and the association between HBoV detection and the onset and resolution of respiratory symptoms. METHODS: We performed HBoV testing on nasal swab samples from a prospective, longitudinal study of respiratory illness in 119 children who attended daycare. RESULTS: HBoV was detected in 70 children (59%) and in 106 (33%) of the 318 cases of illness. Another virus was detected in 76 (72%) of 106 HBoV-positive cases. Extended and intermittent shedding was observed, with consistent HBoV detection documented for up to 75 days. HBoV was detected in 20 (44%) of 45 asymptomatic enrollment samples, and HBoV prevalence and viral load did not differ significantly between children with and children without symptoms at enrollment. HBoV-positive illnesses were longer than HBoV-negative illnesses (odds ratio for duration of symptoms >7 days, 2.44; 95% confidence interval, 1.41-4.22), and illnesses with HBoV load 4 log(10) copies/mL required a visit to a health care provider more often than did HBoV-negative illnesses (odds ratio, 1.64; 95% confidence interval, 1.02-2.64). CONCLUSION: HBoV was more common in illnesses with greater severity. However, detection of HBoV was not associated with the presence of respiratory illness or with specific respiratory symptoms in this prospective study of infants and toddlers attending daycare centers.

Mupirocin resistance related to increasing mupirocin use in clinical isolates of methicillin-resistant Staphylococcus aureus in a pediatric population.

We investigated the proportion of methicillin-resistant Staphylococcus aureus (MRSA) isolates from pediatric patients demonstrating mupirocin resistance related to mupirocin use at our institution. No mupirocin resistance was found in 98% of isolates, whereas mupirocin prescriptions increased by 110%. Resistance rates remained low despite the increasing use of mupirocin.

Comparable Disease Severity by Influenza Virus Subtype in the Acute Respiratory Infection Consortium Natural History Study.

INTRODUCTION: Since the influenza A/H1N1 pandemic of 2009 to 2010, numerous studies have described the clinical course and outcome of the different subtypes of influenza (A/H1N1, A/H3N2, and B). A recent systematic literature review concluded that there were no appreciable differences in either clinical presentation or disease severity among these subtypes, but study parameters limit the applicability of these results to military populations. We sought to evaluate differences in disease severity among influenza subtypes in a cohort of healthy, primarily outpatient adult U.S. Department of Defense beneficiaries. MATERIALS AND METHODS: From 2009 to 2014, we enrolled otherwise healthy adults age 18 to 65 years with influenza-like illness in an observational cohort study based in 5 U.S. military medical centers. Serial nasopharyngeal swabs were collected for determination of etiology and viral shedding by polymerase chain reaction. The presence and severity of symptoms was assessed by interview and patient diary. RESULTS: Over a 5-year period, a total of 157 adults with laboratory-confirmed influenza and influenza subtype were enrolled. Of these, 69 (44%) were positive for influenza A(H1N1), 69 (44%) for influenza A(H3N2), and 19 (12%) for influenza B. About 61% were male, 64% were active duty military personnel, and 72% had received influenza vaccine in the past 8 months. Almost 10% were hospitalized with influenza. Seasonal influenza virus distribution among enrollees mirrored that of nationwide trends each year of study. Individuals with A/H1N1 had upper respiratory composite scores that were lower than those with A/H3N2. Multivariate models indicated that individuals with A(H1N1) and B had increased lower respiratory symptom scores when compared to influenza A(H3N2) (A[H1N1]: 1.51 [95% CI 0.47, 2.55]; B: 1.46 [95% CI 0.09, 2.83]), whereas no other differences in symptom severity scores among influenza A(H1N1), influenza A(H3N2), and influenza B infection were observed. Overall, influenza season (maximum in 2012-2013 season) and female sex of the participant were found to be associated with increased influenza symptom severity. CONCLUSIONS: Our study of influenza in a cohort of otherwise healthy, outpatient adult Department of Defense beneficiaries over 5 influenza seasons revealed few differences between influenza A(H1N1), influenza A(H3N2), and influenza B infection with respect to self-reported disease severity or clinical outcomes. This study highlights the importance of routine, active, and laboratory-based surveillance to monitor ongoing trends and severity of influenza in various populations to inform prevention measures.

Alternating antipyretics: antipyretic efficacy of acetaminophen versus acetaminophen alternated with ibuprofen in children.

Methods A prospective, randomized double-blind placebo control study comparing the efficacy of acetaminophen to acetaminophen alternated with ibuprofen in 38 healthy outpatient children 6 months to 6 years presenting to the outpatient clinic with fever >38 degrees C was conducted. Temperatures were recorded at 0, 3, 4, 5, and 6 hours. Side effect diaries and parental perception of efficacy were filled out hourly by parents.Results There were no significant differences in temperature between the 2 groups at times 0, 3, and 6 hours. The alternating group had significantly lower mean temperatures at both 4 hours (38.0 degrees C vs 37.4 degrees C; P = .05) and 5 hours (37.1 degrees C vs 37.9 degrees C; P = .0032). Parents did not perceive any difference in fever control between the groups.Conclusions An alternating regimen of acetaminophen with ibuprofen significantly decreased fever at 4 and 5 hours compared with acetaminophen alone. However, parents did not perceive a difference in efficacy.

Species-specific clinical characteristics of human coronavirus infection among otherwise healthy adolescents and adults.

Human coronavirus (HCoV) is a known cause of influenza-like illness (ILI). In a multisite, observational, longitudinal study of ILI among otherwise healthy adolescents and adults, 12% of subjects were PCR-positive for HCoV. The distribution of species was as follows: HCoV-OC43 (34%), HCoV-229E (28%), HCoV-NL63 (22%), and HCoV-HKU1 (16%). We did not observe species-specific differences in the clinical characteristics of HCoV infection, with the exception of HCoV-HKU1, for which the severity of gastrointestinal symptoms trended higher on the fourth day of illness.

Performance of the inFLUenza Patient-Reported Outcome (FLU-PRO) diary in patients with influenza-like illness (ILI).

BACKGROUND: The inFLUenza Patient Reported Outcome (FLU-PRO) measure is a daily diary assessing signs/symptoms of influenza across six body systems: Nose, Throat, Eyes, Chest/Respiratory, Gastrointestinal, Body/Systemic, developed and tested in adults with influenza. OBJECTIVES: This study tested the reliability, validity, and responsiveness of FLU-PRO scores in adults with influenza-like illness (ILI). METHODS: Data from the prospective, observational study used to develop and test the FLU-PRO in influenza virus positive patients were analyzed. Adults (≥18 years) presenting with influenza symptoms in outpatient settings in the US, UK, Mexico, and South America were enrolled, tested for influenza virus, and asked to complete the 37-item draft FLU-PRO daily for up to 14-days. Analyses were performed on data from patients testing negative. Reliability of the final, 32-item FLU-PRO was estimated using Cronbach's alpha (α; Day 1) and intraclass correlation coefficients (ICC; 2-day reproducibility). Convergent and known-groups validity were assessed using patient global assessments of influenza severity (PGA). Patient report of return to usual health was used to assess responsiveness (Day 1-7). RESULTS: The analytical sample included 220 ILI patients (mean age = 39.3, 64.1% female, 88.6% white). Sixty-one (28%) were hospitalized at some point in their illness. Internal consistency reliability (α) of FLU-PRO Total score was 0.90 and ranged from 0.72-0.86 for domain scores. Reproducibility (Day 1-2) was 0.64 for Total, ranging from 0.46-0.78 for domain scores. Day 1 FLU-PRO scores correlated (≥0.30) with the PGA (except Gastrointestinal) and were significantly different across PGA severity groups (Total: F = 81.7, p<0.001; subscales: F = 6.9-62.2; p<0.01). Mean score improvements Day 1-7 were significantly greater in patients reporting return to usual health compared with those who did not (p<0.05, Total and subscales, except Gastrointestinal and Eyes). CONCLUSIONS: Results suggest FLU-PRO scores are reliable, valid, and responsive in adults with influenza-like illness.

Type-specific clinical characteristics of adenovirus-associated influenza-like illness at five US military medical centers, 2009-2014.

BACKGROUND: Adenovirus is a recognized cause of influenza-like illness (ILI). The proportion of ILI attributable to adenovirus is not known. Moreover, knowledge gaps remain with respect to the epidemiologic, virologic, and clinical characteristics of adenovirus-associated ILI among otherwise healthy individuals. METHODS: An observational, longitudinal study of <65-year-old patients with febrile ILI at five medical centers was conducted from 2009 to 2014. Nasopharyngeal specimens obtained at enrollment were first tested by single-reaction PCR for adenovirus, then further evaluated by a multiplex PCR assay for other respiratory viral pathogens. Symptoms over a 28-day period were collected. RESULTS: We enrolled 1536 individuals, among whom 43 (2·8%) were positive for adenovirus. The median age of cases was 3·4 years (range: 4 months to 41 years). Three were hospitalized. Species and serotype information was available for 33 (76·7%) cases. Species C (n = 21) was the most common, followed by B3 (n = 9) and one each of E4a, D46, and A. Species C infections were more frequent in children (P < 0·01). Half of the cases were positive for at least one other respiratory viral pathogen. Symptoms were generally mild and most commonly included cough (90%), fatigue (79%), rhinorrhea (74%), loss of appetite (71%), and sore throat (64%). Children with non-C adenovirus infection were more likely to report sore throat (P = 0·05) and hoarseness (P = 0·06) than those with species C infection. CONCLUSIONS: Adenovirus is frequently detected with other respiratory viruses. Persons with non-C adenovirus infections reported more severe symptoms, suggesting there may be species-specific differences in virulence and/or host response to infection.

Vaccine-associated reduction in symptom severity among patients with influenza A/H3N2 disease.

BACKGROUND: The moderate level of protection conferred by influenza vaccines is well-known, but the vaccine's ability to attenuate symptom severity among vaccinated individuals (i.e., vaccine failures) has not been established. METHODS: We enrolled otherwise healthy adults who presented with influenza-like illness (ILI) at five US military hospitals between 2009 and 2014. Influenza was diagnosed and subtyped by PCR. Individual and composite severity scores were compared between those who had vs. had not received the seasonal influenza vaccine >14 days prior to enrollment. RESULTS: A total of 155 cases of influenza (A/H1N1, n=69; A/H3N2, n=66; A/untyped, n=3; B, n=17) were identified, of whom 111 (72%; A/H1N1, n=44; A/H3N2, n=52; A/untyped, n=3; B, n=12) had been vaccinated. Women were significantly less likely to be vaccinated than men (49% vs. 89%; p<0.01). In multivariate analysis, vaccinated individuals were significantly less likely to report a fever >101°F (OR 0.24; 95% CI [0.10, 0.62]) and more likely to report myalgias (OR 3.31; 95% CI [1.22, 8.97]) than vaccinated individuals. Among patients with A/H3N2 infection, upper respiratory and total symptom severity scores were significantly lower for vaccinated patients during the first 2 days of illness, and differences in total symptom severity persisted over 7 days (p<0.05 for all comparisons). Differences across additional symptom categories (lower respiratory and systemic) were also observed throughout 7 days of illness in bivariate analyses. Differences in symptom severity were not observed between vaccinated and unvaccinated participants with A/H1N1 infection. CONCLUSIONS: Among patients with A/H3N2 infection, receipt of seasonal influenza vaccine was associated with reduced symptom severity. Patient-centered discussion about the benefits of influenza vaccination should be expanded to include the possibility that the vaccine could attenuate symptoms.

Neuraminidase inhibitor therapy in a military population.

BACKGROUND: Although neuraminidase inhibitors (NI) are the mainstay of treatment for influenza infection, prescribing practice for these agents is not well described. Additionally, benefit is contested. OBJECTIVES: We examined provider prescriptions of NI during the 2009 pandemic and post-pandemic periods. We also evaluated the effectiveness of NI in reducing severity of influenza infection. STUDY DESIGN: Data on NI prescription and severity of influenza infection were compiled in healthy pediatric and adult beneficiaries enrolled in a prospective study of influenza like illness conducted at five military medical centers over five years. Subjects underwent nasal swabs to determine viral etiology of their infection. Demographic, medication and severity data were collected. Subjects with positive influenza were included. RESULTS: Two hundred sixty three subjects were influenza positive [38% [H1N1] pdm09, 38.4% H3N2, and 20.5% B); 23.9% were treated with NI. NI were initiated within 48h in 63% of treated subjects. Although NI use increased over the five years of the study, early use declined. Most measures for severity of illness were not significantly reduced with NI; adults treated within 48h had only a modest reduction in duration and severity of some of their symptoms. CONCLUSIONS: NI use in our population is increasing, but early use is not. NI use resulted in no reduction in complications of illness. Resolution of symptoms and reduction in severity of some symptoms were slightly better in adults who were treated early. These modest benefits do not support routine treatment with NI in otherwise healthy individuals with influenza.

Epidemiologic, clinical, and virologic characteristics of human rhinovirus infection among otherwise healthy children and adults: rhinovirus among adults and children.

BACKGROUND: human rhinovirus (HRV) is a major cause of influenza-like illness (ILI) in adults and children. Differences in disease severity by HRV species have been described among hospitalized patients with underlying illness. Less is known about the clinical and virologic characteristics of HRV infection among otherwise healthy populations, particularly adults. OBJECTIVES: to characterize molecular epidemiology of HRV and association between HRV species and clinical presentation and viral shedding. STUDY DESIGN: observational, prospective, facility-based study of ILI was conducted from February 2010 to April 2012. Collection of nasopharyngeal specimens, patient symptoms, and clinical information occurred on days 0, 3, 7, and 28. Patients recorded symptom severity daily for the first 7 days of illness in a symptom diary. HRV was identified by RT-PCR and genotyped for species determination. Cases who were co-infected with other viral respiratory pathogens were excluded from the analysis. We evaluated the associations between HRV species, clinical severity, and patterns of viral shedding. RESULTS: eighty-four HRV cases were identified and their isolates genotyped. Of these, 62 (74%) were >18 years. Fifty-four were HRV-A, 11HRV-B, and 19HRV-C. HRV-C infection was more common among children than adults (59% vs. 10%, P<0.001). Among adults, HRV-A was associated with higher severity of upper respiratory symptoms compared to HRV-B (P=0.02), but no such association was found in children. In addition, adults shed HRV-A significantly longer than HRV-C (P trend=0.01). CONCLUSIONS: among otherwise healthy adults with HRV infection, we observed species-specific differences in respiratory symptom severity and duration of viral shedding.

The efficacy of duct tape vs cryotherapy in the treatment of verruca vulgaris (the common wart).

OBJECTIVE: To determine if application of duct tape is as effective as cryotherapy in the treatment of common warts. DESIGN: A prospective, randomized controlled trial with 2 treatment arms for warts in children. SETTING: The general pediatric and adolescent clinics at a military medical center. PATIENTS: A total of 61 patients (age range, 3-22 years) were enrolled in the study from October 31, 2000, to July 25, 2001; 51 patients completed the study and were available for analysis. INTERVENTION: Patients were randomized using computer-generated codes to receive either cryotherapy (liquid nitrogen applied to each wart for 10 seconds every 2-3 weeks) for a maximum of 6 treatments or duct tape occlusion (applied directly to the wart) for a maximum of 2 months. Patients had their warts measured at baseline and with return visits. MAIN OUTCOME MEASURE: Complete resolution of the wart being studied. RESULTS: Of the 51 patients completing the study, 26 (51%) were treated with duct tape, and 25 (49%) were treated with cryotherapy. Twenty-two patients (85%) in the duct tape arm vs 15 patients (60%) enrolled in the cryotherapy arm had complete resolution of their warts (P =.05 by chi(2) analysis). The majority of warts that responded to either therapy did so within the first month of treatment. CONCLUSION: Duct tape occlusion therapy was significantly more effective than cryotherapy for treatment of the common wart.

The relationship of breastfeeding to antimicrobial exposure in the first year of life.

We assessed the relationship between breastfeeding and antimicrobial use in the first year of life in healthy infants by surveying a military population of healthy term infants with questionnaires obtained at the 6-month and 12-month well-baby visits. Breastfed (BF) babies spent 48% as much time receiving antimicrobials by 6 months of age and 47.4% by 12 months of age as compared to formula-fed peers. Breastfed babies also showed significant differences in use of second-line agents at both 6 months (BF=5.5%, Non-BF=19%) and 12 months (19% BF, nonBF=36.9%). These results suggest that breastfeeding decreases exposure of infants to antimicrobials throughout the first year of life and also decreases use of second-line antibiotics in the first year of life.

Tertiary contact vaccinia in a breastfeeding infant.

On May 4, 2003, a US Army soldier received primary smallpox vaccination and experienced a primary uptake reaction at the inoculation site on days 6 through 8. The vaccinee reported observing all of the standard precautions to avoid household spread. In mid May, his breastfeeding wife developed vesicles on both areolas. On May 29, their infant daughter developed a papule on her philtrum. Contact vaccinia was confirmed by positive polymerase chain reaction and culture for vaccinia of both the maternal and infant lesions. This is the first documented case of inadvertent contact vaccinia transmission from a mother to her infant through direct skin-to-skin and skin-to-mucous membrane contact while breastfeeding. The mechanism of transfer from the vaccinee to the spouse is uncertain. This report demonstrates that breastfeeding infants living in close contact with smallpox vaccinees are at potential risk for contact vaccinia, even if the vaccinee is not the breastfeeding mother, and highlights the need for special precautions to prevent secondary transfer to breastfeeding mothers.

Human Parechovirus and Other Enteric Viruses in Childcare Attendees in the Era of Rotavirus Vaccines.

OBJECTIVE: We studied the prevalence of enteric viruses, including rotavirus, enterovirus, norovirus, adenovirus, and human parechovirus (HPeV), in stool samples of childcare attendees. The prevalence of enteric viruses was described in children with and those without gastroenteritis. METHODS: Children aged 1-19 months were recruited from 2 childcare centers in Tacoma, Washington, from October 2008 through June 2009. Stool samples were obtained at enrollment and during diarrheal illnesses for enteric virus testing. A symptom diary was completed by parents. RESULTS: One hundred six children (mean age, 10 months) were followed for an average of 170 days. At enrollment, 78 asymptomatic children had stool samples available. Forty-eight illnesses with acute diarrhea (stool samples were available for 24 illnesses) occurred in 37 children. Rotavirus was not detected in samples from symptomatic or asymptomatic children. HPeV was present in 21% and adenovirus in 46% of symptomatic children. At least 1 virus was detected in 78% of samples from asymptomatic children, including HPeV in 27% and adenovirus in 55%. No differences were found in symptom prevalence between HPeV-positive and HPeV-negative diarrheal illnesses. Molecular analysis revealed a diversity of HPeV types. CONCLUSIONS: Our study highlights the high level of HPeV circulation in childcare. The lack of rotavirus detected in this study supports the impact of rotavirus vaccine and emphasizes the need for a greater focus on the epidemiology of non-rotavirus etiologies of gastroenteritis.

A prospective study of parainfluenza virus type 4 infections in children attending daycare.

Studies of parainfluenza virus type 4 (PIV-4) have been limited by difficulty in culturing. We prospectively studied a cohort of 225 young children attending daycare followed for 165 child-years, using polymerase chain reaction to detect 12 viruses, including PIV-4. PIV-4 was second only to PIV-3, occurring in 9 of 87 (10%) PIV+ illnesses. PIV-4 illnesses were not more severe and not associated with a specific clinical syndrome.