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.

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.

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.

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.

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.

Knowledge and awareness of congenital cytomegalovirus among women.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is a leading cause of disabilities in children, yet the general public appears to have little awareness of CMV. METHODS: Women were surveyed about newborn infections at 7 different geographic locations. RESULTS: Of the 643 women surveyed, 142 (22%) had heard of congenital CMV. Awareness increased with increasing levels of education (P<.0001). Women who had worked as a healthcare professional had a higher prevalence of awareness of CMV than had other women (56% versus 16%, P <.0001). Women who were aware of CMV were most likely to have heard about it from a healthcare provider (54%), but most could not correctly identify modes of CMV transmission or prevention. Among common causes of birth defects and childhood illnesses, women's awareness of CMV ranked last. CONCLUSION: Despite its large public health burden, few women had heard of congenital CMV, and even fewer were aware of prevention strategies.

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.

Intravenous Cidofovir therapy for disseminated adenovirus in a pediatric liver transplant recipient.

BACKGROUND: No definitive antiviral therapy exists for adenovirus (ADV) in immunosuppressed hosts. Cidofovir (CDV), a broad spectrum anti-DNA viral agent, has previously been shown to be of therapeutic benefit in life-threatening adenoviral disease in bone marrow stem-cell recipients. METHODS: A 71/2-month-old girl with a history of biliary atresia developed fevers, hematochezia, tachypnea, and laboratory evidence of hepatitis and pancreatitis 12 days after liver transplantation. A stool culture, oropharyngeal culture, blood viral culture, and blood polymerase chain reaction (PCR) confirmed ADV. Cidofovir 1 mg/kg intravenously three times per week was initiated. The patient received intravenous hydration and probenecid with the infusions to reduce the nephrotoxicity of CDV. Immunosuppression was reduced to achieve tacrolimus trough levels of approximately 8 ng/mL and prednisone at 0.1 mg/kg per day. Complete blood cell count, urinalysis, and viral studies were obtained weekly. RESULTS: Detection of ADV DNA by PCR made a transition from positive to negative during CDV therapy. Blood viral cultures became negative after two CDV doses. Alanine aminotransferase normalized by 5 weeks of therapy. CDV was discontinued after 7 weeks secondary to transient acidosis and proteinuria. The patient never developed azotemia, neutropenia, or ocular abnormalities. CONCLUSIONS: CDV was associated with improved clinical status, viral clearance, and minimal transient side effects in a pediatric liver transplant recipient with disseminated adenoviral disease. The current report documents clearance of disseminated ADV infection in a liver transplant recipient receiving CDV infusions.

Laboratory diagnosis of influenza: recent advances.

The rapid and accurate diagnosis of influenza virus infection now is available to clinicians practicing in both outpatient and inpatient settings. Newly licensed reagents are reliable and "user friendly" and may impact care by providing an immediate diagnosis that allows appropriate antiviral therapy to be given and encourages judicious use of antibiotics. The diagnosis of influenza by viral culture also has become more mainstream, allowing health professionals to confirm diagnoses in individual patients, as well as to track the pattern of each "flu season" in the community.

Severe acute respiratory syndrome (SARS): a review of the history, epidemiology, prevention, and concerns for the future.

During the first part of 2003, the world experienced the first epidemic of the 21st century with the emergence of a new and readily transmissible disease. The disease, severe acute respiratory syndrome (SARS), spread quickly and caused numerous deaths, as well as public panic. This article provides a brief review of the initial history of the epidemiology, as well as of the clinical definition, occurrence in the pediatric population, etiology, prevention, drug studies, and considerations for the future.

Gardnerella vaginalis bacteremia in a premature neonate.

Gardnerella vaginalis is a normal component of the human vaginal flora and commonly associated with bacterial vaginosis. Invasive infection in obstetrical patients due to G. vaginalis has also been reported. In the pediatric age range, infection due to G. vaginalis is extremely rare and limited to neonates. We describe a 23-week premature infant with G. vaginalis bacteremia and review the characteristics of neonatal G. vaginalis infection reported in the literature. Antibiotic susceptibility testing of G. vaginalis isolates has shown that penicillin, ampicillin, erthromycin, clindamycin, and vancomycin are effective in vitro.

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.