Neonatal adenoviral infection: a seventeen year experience and review of the literature.

OBJECTIVES: To describe the clinical manifestations and short-term outcomes of adenoviral infections in neonates and review all published cases to better determine impact and treatment outcomes. STUDY DESIGN: Retrospective cohort study of all neonates hospitalized at Children's Medical Center (CMC) and Parkland Memorial Hospital (PMH), Dallas, TX with laboratory-confirmed adenoviral infection from January 1,1995-December 31, 2012. Neonates were identified by review of the CMC Virology Laboratory's prospective database of all positive adenovirus tests performed in the inpatient and ambulatory settings, and at PMH, of a prospective neonatal database that included all neonatal intensive care unit admissions. Patients also were identified by discharge International Classification of Disease, 9th edition codes for adenoviral infection. The medical records were reviewed, and a review of the English literature was performed. RESULTS: During 17 years, 26 neonates had adenoviral infection (25, CMC; 1, PMH). The principle reasons for hospitalization were respiratory signs (88%) and temperature instability (65%). Five (19%) had disseminated disease and 4 (80%) of these infants died. Ribavirin or cidofovir treatment, as well as immune globulin intravenous, did not improve outcomes except in 1 neonate. Literature review (n = 72) combined with our data found that disseminated infection was associated with death (68% vs 21% with localized infection, P < .001). In addition, neonates <14 days of age were more likely to have disseminated disease (44% vs 12%, P = .004) and death (48% vs 8%; P < .001). CONCLUSION: Adenoviral infection in hospitalized neonates was associated with severe morbidity and mortality, especially when infection was disseminated and involved the respiratory tract. Development of new therapeutic strategies is needed.

Respiratory viruses identified in an urban children's hospital emergency department during the 2009 influenza A(H1N1) pandemic.

OBJECTIVES: Two surges in influenza-like illness (ILI) visits to Children's Medical Center Emergency Departments, Dallas and Legacy, occurred in late spring (wave 1) and late summer 2009 (wave 2). This study describes respiratory viruses identified during the first weeks of waves 1 and 2 of the 2009 influenza A(H1N1) pandemic (pH1N1) and compares patients infected with pH1N1 with those infected with other respiratory viruses during wave 1. METHODS: From April 27 to May 7 and August 23 to September 7, 2009, nasopharyngeal swab specimens from all patients with temperature 38.2°C or higher plus 2 or more symptoms of ILI were tested by rapid antigen, direct fluorescent antibody, or multiplex polymerase chain reaction assays. Patients with pH1N1 during wave 1 were classified as cases and 3 age- and sex-matched controls were randomly selected from patients with 1 respiratory virus other than pH1N1. Odds ratios (ORs) and associated 95% confidence intervals (95% CIs) of characteristics associated with patients with pH1N1 were estimated using conditional logistic regression models. RESULTS: During wave 1, single viruses identified in 1023 symptomatic children were confirmed pH1N1 (55, 5.4%), rhinovirus (505, 49.4%), parainfluenza 3 (199, 19.5%), and human metapneumovirus (169, 16.5%). By multivariable analysis, duration of fever (OR, 1.49; 95% CI, 1.02-2.20) and myalgia at presentation (OR, 3.09; 95% CI, 1.09-8.76) were independent predictors associated with pH1N1. During wave 2, 114 (59.7%) of single viruses were pH1N1. CONCLUSIONS: During the epidemic of ILI in Spring 2009, other respiratory viruses were identified more frequently than pH1N1 influenza in children with ILIs. Clinical presentation was similar for all respiratory viruses. Molecular diagnostic testing can define the prevalent viruses during community outbreaks and provide guidance to physicians making treatment decisions in emergency departments.

Use of blood polymerase chain reaction testing for diagnosis of herpes simplex virus infection.

The use of herpes simplex virus (HSV) polymerase chain reaction for diagnosis of HSV disease involving the central nervous system has not translated into widespread use for the detection of DNAemia. We report our 6-year experience using blood polymerase chain reaction testing for HSV infection in neonates and older children with HSV disease.

2009 influenza A in infants hospitalized at younger than 6 months.

OBJECTIVE: To describe the clinical characteristics and outcomes of infants hospitalized at <6 months of age with 2009 influenza A infection. STUDY DESIGN: Prospective laboratory surveillance and discharge International Classification of Disease, 9th edition codes for influenza infection were used to identify all infants hospitalized at <6 months of age with positive influenza A tests at Children's Medical Center Dallas from April 27, 2009 to March 23, 2010. Retrospective chart review then was performed. RESULTS: Seventy-three infants aged <6 months were hospitalized with laboratory-confirmed influenza A infection at a median age of 48 days (range, 3-179 days). The most common clinical characteristics were fever and respiratory signs, and 53% were given a bolus of intravenous fluid. Median length of hospitalization was 2 days (range, 1-162 days). Twenty (27%) infants developed influenza-related complications, including pneumonia (n = 3), hypoxia (n = 18), seizures (n = 2), need for intensive care (n = 8), or death (n = 2). Oseltamivir was administered to 60 (82%) infants and was well tolerated. CONCLUSIONS: The majority of infants hospitalized with 2009 influenza A had community-acquired infection that was associated with short hospital stays and favorable short-term outcomes. Complications including death occurred, emphasizing the need for preventive strategies.

A lean laboratory: operational simplicity and cost effectiveness of the Luminex xTAG™ respiratory viral panel.

During certain months of the year, viral respiratory infections lead to a dramatic increase in pediatric emergency room visits and hospital admissions. Rapid identification of the infectious organism results in timely treatment and reductions in hospital cost and length of stay. Before the introduction of molecular testing to the virology laboratory, diagnosis relied on the standard methods of immunofluorescence and culture. These tests can be labor-intensive and costly. Recent studies have demonstrated the higher sensitivity, faster turnaround, and broader diagnostic spectrum provided by multiplexed RT-PCR assays. Data comparing the laboratory cost and labor efficiency of the tests are lacking. To address this issue, we chose to implement the principles of operational workflow analysis using lean methodology to critically evaluate the potential advantages of a multiplexed RT-PCR assay both in terms of workflow and cost effectiveness. Our results indicated that the implementation of the Luminex xTAG Respiratory Viral Panel (RVP) resulted in a standardized workflow with decreased requirements in laboratory cost as well as improvement in efficiency. In summary, we demonstrate that, in our laboratory, the Luminex xTAG RVP is more operationally streamlined and cost-effective than standard viral direct fluorescent antibody and culture. Further studies are needed to highlight additional benefits of the test, including shortened hospital stay and improved patient outcome.

2009 pandemic influenza A (H1N1) virus infection in pediatric oncology and hematopoietic stem cell transplantation patients.

BACKGROUND: Pediatric oncology and hematopoietic stem cell transplantation (HSCT) patients are at high risk for influenza infection and its associated complications. Little is known about infection with novel 2009 influenza A (H1N1) in this population. PROCEDURE: Prospective laboratory surveillance identified all children with positive influenza test results from 4/27/09-12/5/09. 2009 H1N1 infection was confirmed by PCR subtyping; cases in which subtyping was not performed were considered probable. Medical records of all pediatric oncology and HSCT cases were reviewed. RESULTS: Thirty children with cancer or HSCT had laboratory-confirmed influenza A. Patients with ALL (18), CNS tumors (4), CML (1), Ewing sarcoma (1), Hodgkin lymphoma (1), LCH (1), severe aplastic anemia (1), and HSCT (3), had confirmed (5) and probable (25) H1N1 by rapid (22; 73%), DFA (4; 13%), or RVP (4; 13%) assays. Most frequent presenting signs and symptoms were fever (93%; median 38.6°C), cough (97%), and rhinorrhea (83%). Ten patients required hospitalization for a median of 5 days, most commonly for fever and neutropenia (8). Imaging demonstrated lower respiratory tract involvement in three patients. There were no concomitant bacteremias; one patient had rhinovirus co-infection. Three patients required ICU care; 1 developed ARDS, multi-organ failure, and died after 5 days. Chemotherapy was delayed in five patients. Oseltamivir was administered to 28 patients; 1 patient developed an oseltamivir-resistant strain and was treated with zanamivir. CONCLUSIONS: 2009 influenza A H1N1 infection in children with cancer and HSCT is mild in most patients, but can lead to serious complications.