Neurodevelopmental outcomes following ganciclovir therapy in symptomatic congenital cytomegalovirus infections involving the central nervous system.

BACKGROUND: Ganciclovir protects against hearing deterioration in infants with symptomatic congenital cytomegalovirus (CMV) disease involving the central nervous system (CNS). OBJECTIVES: To assess the neurodevelopmental impact of ganciclovir therapy in this population. STUDY DESIGN: 100 neonates were enrolled into a controlled Phase III study of symptomatic congenital CMV involving the CNS, and were randomized to either 6 weeks of intravenous ganciclovir or no treatment. Denver developmental tests were performed at 6 weeks, 6 months, and 12 months. For each age, developmental milestones that > or =90% of normal children would be expected to have achieved were identified. The numbers of milestones not met ("delays") were determined for each subject. The average number of delays per subject was compared for each treatment group. RESULTS: At 6 months, the average number of delays was 4.46 and 7.51, respectively, for ganciclovir recipients and "no treatment" subjects (p=0.02). At 12 months, the average number of delays was 10.06 and 17.14, respectively (p=0.007). In a multivariate regression model, the effect of ganciclovir therapy remained statistically significant at 12 months (p=0.007). CONCLUSIONS: Infants with symptomatic congenital CMV involving the CNS receiving intravenous ganciclovir therapy have fewer developmental delays at 6 and 12 months compared with untreated infants. Based on these data as well as the previously published data regarding ganciclovir treatment and hearing outcomes, 6 weeks of intravenous ganciclovir therapy can be considered in the management of babies with symptomatic congenital CMV disease involving the CNS. If treatment is initiated, it should be started within the first month of life and patients should be monitored closely for toxicity, especially neutropenia. Since existing data only address the treatment of symptomatic congenital CMV disease involving the CNS, these data cannot be extrapolated to neonates with other manifestations of CMV disease, including asymptomatic babies and symptomatic babies who do not have CNS involvement.

Cost-effectiveness analysis of herpes simplex virus testing and treatment strategies in febrile neonates.

OBJECTIVE: To determine the clinical effectiveness and cost-effectiveness of testing for and empirically treating herpes simplex virus (HSV) infection in neonates with fever aged from birth to 28 days. DESIGN: Cost-effectiveness analysis. SETTING: Decision model. PATIENTS: Neonates with fever with no other symptoms and neonates with fever with cerebrospinal fluid (CSF) pleocytosis. INTERVENTIONS: Four clinical strategies: (1) HSV testing and empirical treatment while awaiting test results; (2) HSV testing and treatment if test results were positive for HSV or the patient had symptoms of HSV; (3) treatment alone without testing; or (4) no HSV testing or treatment unless the patient exhibited symptoms. The 2 HSV testing methods used were CSF HSV polymerase chain reaction (PCR) and comprehensive evaluation with blood HSV PCR, CSF HSV PCR, and multiple viral cultures. MAIN OUTCOME MEASURES: Twelve-month survival and quality-adjusted life expectancy with a cost-effectiveness threshold of $100,000 per quality-adjusted life year (QALY) gained. RESULTS: Clinical strategy 1, when applied in febrile neonates with CSF pleocytosis, saved 17 lives per 10,000 neonates and was cost-effective using CSF HSV PCR testing ($55,652/QALY gained). The cost-effectiveness of applying clinical strategy 1 in all febrile neonates depended on the cost of the CSF HSV PCR, prevalence of disease, and parental preferences for neurodevelopmental outcomes. Clinical strategies using comprehensive HSV testing were not cost-effective in febrile neonates ($368,411/QALY gained) or febrile neonates with CSF pleocytosis ($110,190/QALY gained). CONCLUSIONS: Testing with CSF HSV PCR and empirically treating with acyclovir sodium saves lives and is cost-effective in febrile neonates with CSF pleocytosis. It is not a cost-effective use of health care resources in all febrile neonates.

The search for adenovirus 14 in children in Houston, Texas.

Adenovirus (Ad)14 has recently emerged in the United States causing outbreaks of severe respiratory disease. To determine if Ad14 circulated in Houston, Texas, during the same time as an outbreak in military recruits in nearby San Antonio, 215 pediatric adenovirus isolates were serotyped using microneutralization. None were Ad14; Ad1, Ad2, and Ad3 were the most common identified serotypes.

The prevalence of neonatal herpes simplex virus infection compared with serious bacterial illness in hospitalized neonates.

OBJECTIVE: To determine the prevalence of herpes simplex virus (HSV) relative to other viral infections and serious bacterial illnesses (SBIs) in hospitalized neonates admitted from a pediatric emergency department over a 5-year period. STUDY DESIGN: Retrospective prevalence study of laboratory-confirmed viral infections and culture-proven SBIs, with electronic databases and medical record review. RESULTS: A total 5817 neonates were included: 8.4% with viral infection, 4.6% with SBIs. Of 960 neonates with documented fever, 17.2% had viral infections (0.3% HSV infection) and 14.2% had SBIs (1.3% bacterial meningitis). Of 204 neonates with fever and cerebrospinal fluid (CSF) pleocytosis, 1.0% had HSV infection and 5.4% had bacterial meningitis. Of 124 neonates with fever and mononuclear CSF pleocytosis, 1.6% had HSV and 0.8% had bacterial meningitis. Of 187 neonates with hypothermia, 1.1% had HSV infection presenting as a sepsis-like syndrome. CONCLUSIONS: In febrile neonates admitted to the hospital from the emergency department, the prevalence of HSV infection was similar to that of bacterial meningitis, suggesting that HSV infection be considered in the differential diagnosis of neonatal fever, especially in the presence of mononuclear CSF pleocytosis. HSV infection should also be considered in neonates with hypothermia and a sepsis-like syndrome.

Clinical and laboratory features of neonatal herpes simplex virus infection: a case-control study.

BACKGROUND: Neonatal herpes simplex virus (HSV) infection can cause significant morbidity and mortality but can be difficult to identify, particularly in neonates without vesicular rash. OBJECTIVE: To determine the unique clinical and laboratory features of neonates with and without HSV infection admitted to Texas Children's Hospital during a 14-year period. METHODS: An historic case-control study of all hospitalized neonates with laboratory-confirmed HSV infection and a restricted sample (ratio 1:4) of HSV test-negative hospitalized neonates. Univariate and multivariate analyses were performed to identify clinical and laboratory factors associated with neonatal HSV infection. RESULTS: Forty cases and 160 comparison subjects were identified. The following factors were associated with neonatal HSV infection by univariate analysis: maternal primary HSV infection, maternal fever, vaginal delivery, prematurity, postnatal HSV contact, vesicular rash, hypothermia, lethargy, seizures, severe respiratory distress, hepatosplenomegaly, thrombocytopenia, elevated hepatic enzymes, and cerebrospinal fluid (CSF) pleocyosis and proteinosis. Factors not associated with neonatal HSV infection were fever, total peripheral white blood cell count, and red blood cells in the CSF. For neonates presenting without vesicular rash, maternal fever, respiratory distress requiring mechanical ventilation, and CSF pleocytosis were independently associated with HSV infection. CONCLUSIONS: Inclusion of the newly appreciated features of maternal fever, respiratory distress, and thrombocytopenia might improve the detection of neonatal HSV infection. Clinical and laboratory factors typically associated with neonatal HSV infection were confirmed to be maternal primary HSV infection, vaginal delivery, prematurity, neonatal seizures, vesicular rash, elevated hepatic enzymes, and CSF pleocytosis.

Rapid assays for the diagnosis of influenza A and B viruses in patients evaluated at a large tertiary care children's hospital during two consecutive winter seasons.

BACKGROUND: The rapid and accurate diagnosis of influenza facilitates antiviral therapy, judicious antibiotic usage, and cohorting patients to decrease nosocomial infection. OBJECTIVE: To determine the utility of rapid influenza tests in a children's hospital. STUDY DESIGN: Two in vitro rapid immunochromatographic assays that detect and distinguish influenza A and B viruses were compared to the reference standard of viral culture. RESULTS: In 9186 patients tested, overall sensitivity of the rapid assays for influenza A was 64.4% and specificity was 98.3%. Sensitivity and specificity were 28% and 99.9%, respectively, for influenza B. Overall sensitivity and specificity for Remel Xpect (2004/2005) were 47.7% and 98.7% for influenza A, and 20.3% and 99.8% for influenza B, respectively. Overall sensitivity and specificity of Binax NOW Flu A&B (2005/2006) were 78.3% and 98% for influenza A, and 35.9% and 99.9% for influenza B, respectively. The results for influenza B with both assays were significantly lower than previously reported and lower than stated in the manufacturer's package insert. CONCLUSIONS: In a contemporary clinical setting, rapid assays for influenza displayed significantly lower sensitivities, especially for influenza B, than prior reports. Differences in pre- and post-licensure performance demonstrate the importance of continuous evaluation of rapid diagnostic tests for influenza.

Genotype prevalence and risk factors for severe clinical adenovirus infection, United States 2004-2006.

BACKGROUND: Recently, epidemiological and clinical data have revealed important changes with regard to clinical adenovirus infection, including alterations in antigenic presentation, geographical distribution, and virulence of the virus. METHODS: In an effort to better understand the epidemiology of clinical adenovirus infection in the United States, we adopted a new molecular adenovirus typing technique to study clinical adenovirus isolates collected from 22 medical facilities over a 25-month period during 2004-2006. A hexon gene sequence typing method was used to characterize 2237 clinical adenovirus-positive specimens, comparing their sequences with those of the 51 currently recognized prototype human adenovirus strains. In a blinded comparison, this method performed well and was much faster than the classic serologic typing method. RESULTS: Among civilians, the most prevalent adenovirus types were types 3 (prevalence, 34.6%), 2 (24.3%), 1 (17.7%), and 5 (5.3%). Among military trainees, the most prevalent types were types 4 (prevalence, 92.8%), 3 (2.6%), and 21 (2.4%). CONCLUSIONS: For both populations, we observed a statistically significant increasing trend of adenovirus type 21 detection over time. Among adenovirus isolates recovered from specimens from civilians, 50% were associated with hospitalization, 19.6% with a chronic disease condition, 11% with a bone marrow or solid organ transplantation, 7.4% with intensive care unit stay, and 4.2% with a cancer diagnosis. Multivariable risk factor modeling for adenovirus disease severity found that age <7 years (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4-7.4), chronic disease (OR, 3.6; 95% CI, 2.6-5.1), recent transplantation (OR, 2.7; 95% CI, 1.3-5.2), and adenovirus type 5 (OR, 2.7; 95% CI, 1.5-4.7) or type 21 infection (OR, 7.6; 95% CI, 2.6-22.3) increased the risk of severe disease.

Performance of a rapid assay (Binax NOW) for detection of respiratory syncytial virus at a children's hospital over a 3-year period.

A rapid assay, Binax NOW RSV, was compared to viral culture for 14,756 pediatric respiratory specimens obtained from 2003 to 2006. There were 794 viral culture-confirmed respiratory syncytial virus infections. Sensitivity was 81%, and specificity was 93.2%. Sensitivity was greatest for neonates (91.1% versus 80.7% [P < 0.01]).

Medically attended pediatric influenza during the resurgence of the Victoria lineage of influenza B virus.

OBJECTIVES: During the 2002-2003 season, a new variant of influenza B co-circulated with influenza A viruses. This study examines the characteristics and outcomes of children with influenza A and B virus infection vs. other acute respiratory illnesses. METHODS: A retrospective chart review was performed on children with laboratory-confirmed influenza infection, and influenza negative acute respiratory illnesses that prompted a hospital visit. RESULTS: Children with influenza were more often previously healthy and presenting with upper respiratory symptoms, while influenza negative patients typically had underlying medical conditions, and lower respiratory tract disease. Children with influenza B were older, were more likely to be in school, and presented with myositis more frequently than those with influenza A. A third of children with influenza A, and 42% with influenza B required hospitalization. The highest hospitalization rates were in infants under one year. No healthy children, and only 15% of those with chronic medical problems, had received influenza vaccine. Vaccine efficacy was estimated to be 82.6%. CONCLUSIONS: Most children with influenza were previously healthy. Overall, a third of children with influenza required hospitalization. Influenza A and B were clinically indistinguishable, except for older age and higher incidence of myositis in patients with influenza B. Influenza vaccine coverage in both healthy and high-risk children was low.

Performance characteristics of a rapid immunochromatographic assay for detection of influenza virus in children during the 2003 to 2004 influenza season.

STUDY OBJECTIVE: We evaluate the performance of a rapid assay (Binax NOW) for the detection of influenza A virus in children. METHODS: The performance of an in vitro rapid immunochromatographic assay for detection of influenza A virus was compared to viral culture in 4,383 consecutive respiratory specimens received during the 2003 to 2004 season, which included an influenza A epidemic in October and November of 2003. RESULTS: The overall test sensitivity was 61.6% (95% confidence interval [CI] 60.3% to 63.2%) and specificity was 95.8% (95% CI 95.1% to 96.3%). In preplanned subset analyses, we found the test more sensitive in infants aged 90 days or younger (sensitivity 70.3%; specificity 96.6%) and less specific during the epidemic (sensitivity 61.7%; specificity 90.4%). CONCLUSION: This rapid assay was highly specific for detecting influenza A in children and thus appears useful for confirming this infection. Because of its limited sensitivity, however, a negative test cannot rule out influenza A.

Frequent detection of polyomaviruses in stool samples from hospitalized children.

BACKGROUND: Infection with BK virus (BKV) generally occurs early during life, but its mode of transmission has not been clearly defined. We tested the hypothesis that polyomavirus shedding in stool may be a source of BKV exposure.METHODS. Pediatric stool and rectal swab samples were tested for the presence of polyomavirus DNA by a polymerase chain reaction (PCR) assay that could detect a conserved region in the large T antigen gene of BKV, JC virus (JCV), and simian virus 40 (SV40). The specific viruses detected by this assay were confirmed by DNA sequence analysis of the PCR amplicons.Results. Of 120 samples collected from 99 patients, 54 (45.0%) were positive for polyomavirus DNA. Of the 99 patients, 46 (46.5%) had at least 1 positive sample, with 38 (38.4%) positive for BKV and 8 (8.1%) positive for SV40. JCV was not detected. There was no association between polyomavirus fecal shedding and age, sex, race/ethnicity, immune status, or symptoms of gastrointestinal disease in the children studied. The BKV strains detected displayed polymorphisms in the T antigen sequence.Conclusions. Polyomaviruses are frequently present in stool samples from hospitalized children. These findings suggest that fecal-oral transmission of BKV may play a role in the ubiquity of infection.

Investigation of the role of congenital cytomegalovirus infection in the etiology of enlarged vestibular aqueducts.

OBJECTIVE: To determine whether congenital cytomegalovirus (CMV) infection is an etiologic factor in the pathogenesis of enlarged vestibular aqueducts (EVA). DESIGN: Two different cohort studies. Subjects The study population comprised 19 subjects with a history of congenital CMV infection and sensorineural hearing loss (cohort 1); 39 subjects with nonsyndromic EVA and their unaffected mothers (cohort 2); and 16 control subjects with EVA associated with Pendred syndrome and bi-allelic mutations of the SLC26A4 gene and their unaffected mothers. RESULTS: In cohort 1, we detected EVA in 0 of 19 subjects with congenital CMV infection and sensorineural hearing loss. In cohort 2, anti-CMV serologic profiles were consistent with possible congenital CMV infection in 10 (26%) of 39 subjects with nonsyndromic EVA and 6 (38%) of 16 control subjects with Pendred syndrome (P = .52). These seroprevalence rates are similar to those expected in the general population (40%). CONCLUSION: In spite of their auditory phenotypic similarities, congenital CMV infection is not a significant factor in the etiology of EVA.

Neurologic complications associated with influenza A in children during the 2003-2004 influenza season in Houston, Texas.

OBJECTIVES: Our objectives were to (1) describe the clinical characteristics of and viruses isolated from patients who presented with neurologic symptoms associated with influenza A infection and were hospitalized at Texas Children's Hospital during October and November 2003 and (2) to raise awareness of the neurologic complications of influenza among US children. METHODS: We reviewed the medical and laboratory records of all children who were hospitalized with neurologic symptoms and who also had evidence of influenza virus infection by rapid antigen testing or viral isolation. RESULTS: Eight children aged 5 months to 9 years with neurologic complications associated with influenza A were identified. None of the children had received the influenza vaccine. Four presented with seizures, 3 with mental status changes, and 1 with mutism. All but 1 of the patients had influenza A viral antigen detected in nasal wash samples. Influenza A virus was isolated in culture from nasal wash specimens obtained from 6 of the patients; influenza A virus was also isolated from the cerebrospinal fluid of 1 of these patients. None of the patients had serum metabolic abnormalities or other cerebrospinal fluid abnormalities. Three of the patients had brain imaging abnormalities. Five of the patients were treated with antivirals. All 8 of the patients survived, 6 with complete recovery and 2 with sequelae (1 mild and 1 severe). CONCLUSIONS: Neurologic symptoms and sequelae were associated with influenza A virus infection in children during the 2003-2004 influenza season in Houston, Texas. Influenza should be considered in the differential diagnosis in patients with seizures and mental status changes, especially if they present with respiratory symptoms or during an influenza outbreak.

Comparison of a new lateral-flow chromatographic membrane immunoassay to viral culture for rapid detection and differentiation of influenza A and B viruses in respiratory specimens.

The performance of a new rapid lateral-flow chromatographic membrane immunoassay test kit for detection of influenza virus was evaluated and compared to that of viral culture in respiratory secretions collected from 400 adults and children seen at three large university hospitals during the recent 2003 influenza season. The rapid test provided results in 15 min, with excellent overall performance statistics (sensitivity, 94.4%; specificity, 100%; positive predictive value, 100%; negative predictive value, 97.5%). Both influenza A and B type viruses were reliably detected, with no significant difference in performance statistics noted by influenza virus type or by the center performing the test.