Double Vision and Gait Ataxia in an Immunocompetent 9-Year-Old Girl With Intracranial Phaeohyphomycosis.

ABSTRACT: A 9-year-old girl presented with morning headaches associated with vomiting, gait ataxia, and facial and ocular motor nerve palsies. Her initial imaging was concerning for demyelinating disease. After extensive infectious and rheumatologic workup returned negative, she was treated twice with intravenous immunoglobulin and intravenous steroids with near-complete resolution each time. She returned, however, with worsening neurologic deficits and imaging revealing focal ischemic infarction in the brainstem as well as new-onset hydrocephalus. A multispecialty workup was initiated without conclusive diagnosis. A novel, noninvasive test for plasma cell-free DNA established a diagnosis of Cladophialophora bantiana that was confirmed and validated by a brain biopsy taken during a clinical decompensation. Treatment was initiated with systemic voriconazole and intraventricular amphotericin B.

Rapid research response to the 2009 A(H1N1)pdm09 influenza pandemic (Revised).

BACKGROUND: When novel influenza viruses cause human infections, it is critical to characterize the illnesses, viruses, and immune responses to infection in order to develop diagnostics, treatments, and vaccines. The objective of the study was to collect samples from patients with suspected or confirmed A(H1N1)pdm09 infections that could be made available to the scientific community. Respiratory secretions, sera and peripheral blood mononuclear cells (PBMCs) were collected sequentially (when possible) from patients presenting with suspected or previously confirmed A(H1N1)pdm09 infections. Clinical manifestations and illness outcomes were assessed. Respiratory secretions were tested for the presence of A(H1N1)pdm09 virus by means of isolation in tissue culture and real time RT-PCR. Sera were tested for the presence and level of HAI and neutralizing antibodies against the A(H1N1)pdm09 virus. FINDINGS AND CONCLUSIONS: Thirty patients with confirmed A(H1N1)pdm09 infection were enrolled at Baylor College of Medicine (BCM). Clinical manifestations of illness were consistent with typical influenza. Twenty-eight of 30 had virological confirmation of illness; all recovered fully. Most patients had serum antibody responses or high levels of antibody in convalescent samples. Virus-positive samples were sent to J. Craig Venter Institute for sequencing and sequences were deposited in GenBank. Large volumes of sera collected from 2 convalescent adults were used to standardize antibody assays; aliquots of these sera are available from the repository. Aliquots of serum, PBMCs and stool collected from BCM subjects and subjects enrolled at other study sites are available for use by the scientific community, upon request.

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.

Polymorphisms within human cytomegalovirus chemokine (UL146/UL147) and cytokine receptor genes (UL144) are not predictive of sequelae in congenitally infected children.

Human cytomegalovirus (HCMV) viral chemokine, UL146, and TNF alpha-like receptor UL144 genes show a high degree of hypervariability in clinical isolates. These proteins are predicted to be immune modulators and may contribute to the pathogenesis of HCMV infections. We analyzed the UL146 and UL144 genetic variation of 51 HCMV isolates from congenitally infected children and 13 isolates from children in childcare. There was no statistically significant correlation between UL146 and UL144 genotypes and HCMV disease and/or sequelae. However, there were some groups that had a relatively large proportion of asymptomatic outcomes. These included UL146 group 8 (7/8 asymptomatic) and UL146 group 10 (3/3 asymptomatic). UL144 group B had 11/15 (73%) asymptomatic. UL146 and UL144 genes remained stable in serial isolates from children in daycare for intervals up to three years. These results indicate that most UL146 and UL144 genotypes do not predict clinical sequelae following congenital HCMV infections.

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.

Prospective evaluation of the risk of serious bacterial infection in children who present to the emergency department with hyperpyrexia (temperature of 106 degrees F or higher).

BACKGROUND: Previous studies of children with temperatures > or = 106 degrees F (hyperpyrexia) disagree as to whether hyperpyrexia confers a high risk of serious bacterial infection. OBJECTIVES: The purpose of this study was to determine (1) the risk of serious bacterial infection in children with hyperpyrexia and (2) whether clinical presentation can identify hyperpyrexic patients at risk for serious bacterial infection. METHODS: Data were collected prospectively on all children <18 years of age presenting to a pediatric emergency department during a 2-year period with rectal temperatures of > or = 106 degrees F. History, physical examination, complete blood cell counts, blood cultures, and nasopharyngeal viral cultures were obtained on all of the patients. RESULTS: Of 130828 visits, 103 children had hyperpyrexia (1 per 1270 patient visits). Of the 103 subjects, 20 had serious bacterial infection, and 22 had laboratory-proven viral illness (including 1 subject with bacterial/viral coinfection). The presence of a chronic underlying illness was associated with an increased risk of serious bacterial infection. The presence of rhinorrhea or any viral symptom was associated with a decreased risk of serious bacterial infection, although diarrhea itself was associated with an increased risk of serious bacterial infection. Age, maximum temperature, and total white blood cell count were not predictive of either bacterial or viral illness. CONCLUSIONS: Children with hyperpyrexia are at equally high risk for serious bacterial infection and for viral illness. Bacterial and viral coinfection also occurs. No aspect of the clinical presentation reliably distinguishes between bacterial and viral illness. We recommend consideration of antibiotic treatment for all children presenting to the emergency department with hyperpyrexia without confirmed viral illness.

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.