Classic Kaposi's sarcoma associated with human herpesvirus 8 infection in a 13-year-old male: a case report.

PURPOSE: Classic Kaposi's sarcoma (KS) is rare in children. Although its etiology is not fully understood, human herpesvirus 8 (HHV-8) is present in the angiogenic lesions. We report an HIV-negative, 13-year-old patient of Sicilian descent with HHV-8-associated classic KS to facilitate the diagnosis and treatment of this entity in children. EXPERIMENTAL DESIGN: DNA was extracted from the skin specimen of the patient and analyzed via PCR assay and Southern blot hybridization for HHV-8 DNA. The amplified HHV-8 DNA was cloned, sequenced, and compared with the prototype HHV-8-KS330/BAM. RESULTS: The patient presented with purpuric lesions on the distal lower extremities and the tip of his nose, associated with thrombocytopenia and leukopenia, suggesting an immune-mediated cytopenia. While on prednisone, he developed marked vascular proliferation in the groins. Biopsy of the skin lesions showed KS, and HHV-8 was detected in the tissues by PCR. Sequence analysis of the amplified DNA was homologous to the prototype HHV-8-KS330/BAM. His HHV-8 strain was the A subgroup, the type associated with Mediterranean classic KS. Stopping prednisone and treatment with IFN-alpha and IgG resulted in regression of the groin lesions. CONCLUSIONS: This report emphasizes the importance of recognizing classic KS in children and avoiding immunosuppressive therapies in indolent classic KS. The diagnostic and therapeutic strategies were effective and well tolerated.

Natural history of neonatal herpes simplex virus infections in the acyclovir era.

OBJECTIVE: During the 2 decades in which effective antiviral therapies have been available for neonatal herpes simplex virus (HSV) disease, changes have been documented not only in the outcomes of infected infants, but also in the natural history of the disease itself. Numerous studies previously have reported that early institution of antiviral therapy is beneficial to the outcome of the disease. The objective of this study was to provide an update of neonatal HSV disease to identify means by which future improvements in the management of HSV-infected neonates can be made. DESIGN/METHODS: Neonates enrolled in 2 studies of parenteral acyclovir for the treatment of neonatal HSV disease provided the data source. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted the studies between 1981 and 1997. A total of 186 patients are summarized, all of whom were treated with acyclovir. Demographic and clinical characteristics of these patients are reported. RESULTS: Comparisons between patients treated in the periods between 1981-1988 and 1989-1997 according to extent of disease revealed that the mean time between the onset of disease symptoms and initiation of therapy has not changed significantly from the early 1980s to the late 1990s. Of all patients evaluated, 40% had fetal scalp monitors during the delivery process. A significant minority of patients did not have skin vesicles at the time of their presentation and did not develop them during the acute HSV disease (39% of patients with disseminated disease; 32% of patients with central nervous system [CNS] disease; and 17% of patients with skin, eye, and/or mouth disease). Among patients with CNS disease, mortality was associated with prematurity. Among patients with disseminated HSV disease treated with acyclovir at 30 mg/kg/d, mortality was associated with aspartate transaminase elevations of >/=10 times the upper limit of normal at the time of initiation of acyclovir therapy. Mortality was also associated with lethargy at initiation of antiviral therapy for patients with disseminated disease. Patients' morbidity status was associated with the extent of disease (skin, eye, and/or mouth disease vs CNS vs disseminated). For those patients with CNS disease, morbidity was also associated with seizures at initiation of antiviral therapy. CONCLUSION: Data presented in the current comparison of neonatal HSV disease over the 2 periods (1981-1988 vs 1989-1997) demonstrate that no progress has been made in decreasing the interval between onset of HSV symptoms and initiation of antiviral therapy. Additional strides in the improvement of disease outcome may occur only if the interval between onset of symptoms and initiation of therapy is shortened. The means by which this will be accomplished lie in increased consideration of neonatal HSV infections in acutely ill infants. Specific data and recommendations to facilitate this goal are contained within.

Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections.

OBJECTIVE: The objective of this investigation was to establish the safety of high-dose (HD) acyclovir for the treatment of neonatal herpes simplex virus (HSV) disease. In addition, an estimate of therapeutic efficacy was sought, both with respect to mortality and to morbidity. Virologic efficacy of HD acyclovir was also assessed. PARTICIPANTS: Infants who were

Risk factors for sternal wound and other infections in pediatric cardiac surgery patients.

BACKGROUND: This study was undertaken to determine the incidence, pathogens and risk factors associated with development of sternal wound and other infections in children undergoing cardiac surgery. METHODS: Retrospective chart review was performed for all cardiac surgeries performed on children <18 years of age at Upstate Medical University at Syracuse between January, 1996, and June, 1998. For evaluation of risk factors for sternal wound infection, only patients undergoing sternotomy are included in the analysis: those with infection are compared with those without for preoperative, intraoperative and postoperative risk factors. RESULTS: Sternal wound infection developed in 10 of 202 (5%) children after median sternotomy. Superficial sternal wound infection developed in 6 (3%) children, and 4 (2%) had deep infection. Children with sternal wound infection had lower age, higher American Society of Anesthesiologist score, longer preoperative stay, longer period of ventilation and inotropic support, longer intensive care unit and total postoperative hospital stays and increased leukocyte band cell counts preoperatively and on Postoperative Day 1 than those without sternal infection. Causative agents for sternal wound infection were Staphylococcus aureus (6), Pseudomonas aeruginosa (1) and Haemophilus influenzae non-type b (1). In addition 32 bacterial infections occurred at nonsurgical sites after 28 procedures. Infections included pneumonia, urinary tract infection and bacteremia. Longer bypass time and longer operation time were two additional risk factors for nonwound infection. CONCLUSION: Infections continue to be a significant cause of morbidity in cardiac surgery patients. Knowledge of risk factors for infection could be useful in preventive and treatment strategies for these high-risk groups.

Enteroviral meningoencephalitis as a complication of X-linked hyper IgM syndrome.

We describe 5 children from 2 families with mutations in the CD40 ligand (CD40L) gene leading to absent expression of CD40L on activated CD4 cells. All subjects presented with interstitial pneumonia with low serum IgG and normal serum IgM. One child had normal and one child had elevated serum IgA. Four had confirmed Pneumocystis carinii pneumonia. In spite of intravenous immunoglobulin treatment yielding therapeutic serum immunoglobulin levels, 3 children had enteroviral encephalitis. When assessed by flow cytometry, the 3 surviving affected male children had absent CD40L expression on activated CD4(+) T cells. The affected children from both families were shown to have the same single nucleotide insertion (codon 131) resulting in frameshift and early termination within exon 4 (extracellular domain). This observation demonstrates that persistent enteroviral infection is not only observed in X-linked agammaglobulinemia but may also occur in patients with X-linked hyper IgM syndrome.

"McFlu". The Monroe County, New York, Medicare vaccine demonstration.

BACKGROUND: Monroe County (MC) NY was one of 9 original sites for the 1988-1992 Medicare Influenza Vaccine Demonstration, which led to Medicare coverage of annual influenza vaccination. The "McFlu" project involved collaboration among university, health department, and practice community. METHODS: Community-wide systems for promoting and/or documenting influenza vaccine delivery and for conducting laboratory-based influenza surveillance were established in MC and in neighboring Onondaga County (OC), which served as a comparison site without Medicare coverage of vaccination. Vaccination utilization and virologic surveillance data collected from physician practices, hospitals, and nursing homes were furnished to national demonstration evaluators. RESULTS: Influenza vaccination rates among persons > or = 65 years of age increased from 41% to 74% in MC compared to an increase from 46% to 57% in OC. The greatest increase occurred in physician offices utilizing an innovative vaccination promotion and tracking strategy. Community-wide influenza A/H3N2 and B outbreaks were documented in three successive demonstration years, affording investigators the opportunity to better define influenza impact and vaccine effectiveness among the Medicare population. CONCLUSION: The McFlu project exemplifies the potential for linking the academic and public health sectors to complement each others' strengths in planning, implementing and documenting a targeted program for improving community health. This model of medicine and public health collaboration should be applicable to attaining other well articulated goals for the health of the public.

Early language development in children exposed to or infected with human immunodeficiency virus.

OBJECTIVES: To compare language development in infants and young children with human immunodeficiency virus (HIV) infection to language development in children who had been exposed to HIV but were uninfected, and (among subjects with HIV infection) to compare language development with cognitive and neurologic status. DESIGN: Prospective evaluation of language development in infected and in exposed but uninfected infants and young children. SETTING: Pediatric Infectious Disease Clinic, State University of New York-Health Science Center at Syracuse. SUBJECTS: Nine infants and young children infected with HIV and 69 seropositive but uninfected infants and children, age 6 weeks to 45 months. RESULTS: Mean Early Language Milestone Scale, 2nd edition (ELM-2) Global Language scores were significantly lower for subjects with HIV infection, compared with uninfected subjects (89.3 vs 96.2, Mann-Whitney U test). The proportion of subjects scoring >2 SD below the mean on the ELM-2 on at least one occasion also was significantly greater for subjects with HIV infection, compared with uninfected subjects (4 of 9 infected subjects, but only 5 of 69 uninfected subjects; Fisher's exact test). Seven of the 9 subjects with HIV infection manifested deterioration of language function. Four manifested unremitting deterioration; only 1 of these 4 demonstrated unequivocal abnormality on neurologic examination. Three subjects with HIV infection and language deterioration showed improvement in language almost immediately after the initiation of antiretroviral drug treatment. Magnetic resonance imaging or computed tomography of the brain were performed in 6 of 7 infected subjects with language deterioration, and findings were normal in all 6. ELM-2 Global Language scaled scores showed good agreement with the Bayley Mental Developmental Index or the McCarthy Global Cognitive Index (r = 0. 70). Language deterioration, or improvement in language after initiation of drug therapy, coincided with or preceded changes in global cognitive function, at times by intervals of up to 12 months. CONCLUSIONS: Language deterioration occurs commonly in infants and young children with HIV infection, is seen frequently in the absence of abnormalities on neurologic examination or central nervous system imaging, and may precede evidence of deterioration in global cognitive ability. Periodic assessment of language development should be added to the developmental monitoring of infants and young children with HIV infection as a means of monitoring disease progression and the efficacy of drug treatment.

Influenza surveillance in community-dwelling elderly compared with children.

BACKGROUND: Acute respiratory illnesses (ARIs) are the leading cause of medical visits for community-dwelling patients of all ages, but virologic and clinical descriptions of these illnesses in older adults are infrequent. OBJECTIVES: To determine the feasibility of influenza surveillance in a population of community-dwelling elderly, to compare the patterns of influenza infection in elderly persons with that observed in young populations in which surveillance is usually conducted, and to describe the clinical presentation of influenza infection in elderly outpatients who seek medical attention for ARI. DESIGN: Prospective clinical and viral surveillance of ARIs among ambulatory patients during 3 consecutive winter seasons. SETTING: Nine internal medicine and 3 pediatric practices in Upstate New York in cooperation with the Medicare Influenza Vaccine Demonstration Project. PATIENTS: Elderly (n=808) and pediatric (n=2080) outpatients with ARI office visits. MEASUREMENTS: Frequency of influenza and other respiratory virus isolates and clinical profile of influenza among older adults and children with ARIs. RESULTS: Influenza virus was the viral agent recovered most often from specimens obtained from patients in both age groups with ARI symptoms, especially those with fever. Influenza accounted for 11% of ARIs in adults (87 isolates) and 20% in children (408 isolates). At the initial illness visit, influenza infection was equally common in elderly individuals with or without underlying cardiopulmonary conditions. Lower respiratory tract signs occurred in 13% of the adults and in 7% of the children with influenza documented by laboratory studies. Other respiratory viruses were recovered from specimens obtained from 20 adults and from 259 children. CONCLUSIONS: Viruses are important agents of ARIs in elderly outpatients. Children and older adults experience similar patterns of influenza infection and other epidemic respiratory pathogens, such as parainfluenza and respiratory syncytial viruses. Viral identification is feasible in older adults seen in physicians' offices and may contribute to improved measures of effects of influenza and other respiratory viruses on ARIs.

Acute manifestations and neurologic sequelae of Epstein-Barr virus encephalitis in children.

BACKGROUND: Complications of Epstein-Barr virus (EBV) infection are diverse and include a number of neurologic manifestations such as meningitis, meningoencephalitis, cerebellitis, cranial neuritis and others. In general encephalitis caused by EBV in pediatric patients has been considered a self-limited illness with few or no sequelae. METHODS: Charts were reviewed from all patients < 18 years of age admitted to or discharged from the State University of New York Health Science Center at Syracuse between 1982 and 1992 with a diagnosis of encephalitis or meningo-encephalitis. Eleven cases of EBV encephalitis diagnosed during a 10-year period were reviewed to characterize the clinical and laboratory findings in the acute setting and the extent of neurologic sequelae on follow-up. RESULTS: Acute neurologic manifestations were diverse and included combative behavior (55%), seizures (36%), headache (36%) and evidence of focal involvement (27%). Classic findings of infectious mononucleosis were noted infrequently; 18% each had pharyngitis, adenopathy, positive heterophile antibody tests or atypical lymphocytosis. Two patients (18%) had abnormal neuroimaging studies, one in the acute stage and the other at the time of follow-up. Seven patients (64%) had abnormal electroencephalograms (EEGs) in the acute setting; of these three had persistent abnormalities on follow-up. Forty percent developed persistent neurologic abnormalities including global impairment, perseverative autistic-like behavior and persistent left upper extremity paresis. CONCLUSIONS: Classic signs, symptoms and laboratory findings in infectious mononucleosis may be absent in Epstein-Barr virus encephalitis. Neurologic sequelae occur in a substantial number of patients.

Immunoblot analysis of anti-Ureaplasma urealyticum antibody in pregnant women and newborn infants.

The purpose of the present study was to determine the frequency in which antibody reactive to Ureaplasma urealyticum could be detected in a population of pregnant women and newborn infants. Serum samples from a prospective cohort of 80 healthy, U. urealyticum culture-positive and culture-negative pregnant women and a retrospective cohort of 522 infants born at between 25 and 42 weeks of gestation were studied by immunoblot analysis. Cultures of specimens from the lower genital tract were positive for U. urealyticum for 83% of the pregnant women, and serum immunoglobulin G (IgG) antibody which reacted to U. urealyticum was detectable in 93% of the pregnant women. Samples from five women (8%) had increases in the number of anti-U. urealyticum IgG bands over the course of the pregnancy. Samples from four of these five women had corresponding increases in the number of antibody bands present in IgA immunoblots. Six of the 522 samples from newborns or cord blood (1.1%) were positive for anti-U. urealyticum IgA; 5 of these 6 samples were also positive for IgM. The six anti-U. urealyticum IgA-positive infants were distributed as follows; 3 of 67 (4.5%) infants were delivered at 25 to 30 weeks of gestation, 3 of 176 (1.7%) infants were delivered at 31 to 34 weeks of gestation, and 0 of 279 infants were delivered at > or = 35 weeks of gestation. An antibody response to U. urealyticum can be detected in pregnant women and preterm infants and may serve as a marker of infection.

Failure to identify human immunodeficiency virus-seropositive newborns: epidemiology and enrollment patterns in a predominantly white, nonurban setting.

OBJECTIVE: To describe the epidemiology of newborn seroprevalence for human immunodeficiency virus (HIV) in a predominantly white, nonurban population, and to determine the factors associated with enrollment at a regional pediatric acquired immunodeficiency syndrome (AIDS) center serving that population. DESIGN: Retrospective case series of children enrolled at a regional pediatric AIDS center during a 6-year period and comparison with universal blind newborn screening data collected by the state of New York during the same time interval. SETTING: The Pediatric AIDS Center at State University of New York-Health Science Center at Syracuse, which serves as the only source of HIV-related pediatric care for children in a 16-country region of upstate New York totaling 1.8 million population. RESULTS: One hundred thirty-nine HIV-seropositive infants were born in the region during the 6-year study period; complete blind screening data were available for 138. Sixty-five (47%) of these infants were white. Thirty-nine (28%) of 138 had been enrolled at the Pediatric AIDS Center within the first 90 days of life. An additional 22 (16%) were enrolled at older than 90 days of life. The remaining 77 (56%) have never been seen at the center and are presumed to be unidentified. County enrollment rates varied from 0% to 100% and correlated with percent nonwhite births (r = .58; 95% confidence interval, 0.04-0.86). Children in outlying counties were at greater risk for nonenrollment than children from Onondaga County (site of the Pediatric AIDS Center) (adjusted relative risk, 1.38; 95% confidence interval, 1.05-1.85). White infants residing outside of Onondaga County were at the greatest risk of nonenrollment; of 50 seropositive white infants residing outside of Onondaga County, only 7 (14%) were enrolled at the center within the first 90 days of life. CONCLUSIONS: Local demographic factors can skew the racial distribution of HIV-seropositive infants dramatically compared with the national experience. White race and residence in counties away from the medical center each constituted risk factors for nonenrollment at the Pediatric AIDS Center. The epidemiology of HIV in this predominantly white, rural population, coupled with physician practices, probably contributed to low identification and enrollment rates. As the AIDS epidemic spreads into similar populations elsewhere, HIV infection in pregnant women or newborn infants is likely to become progressively harder to detect, unless universal screening is adopted.

Respiratory syncytial virus and influenza A infections in the hospitalized elderly.

Respiratory syncytial virus (RSV) infections in the institutionalized elderly have been described; however, there is little information on the impact of RSV infection on community-dwelling elderly. The purpose of this study was to determine the relative numbers of hospitalizations associated with RSV infection and compare the clinical manifestations with influenza A infection. Between November and April during 1989-1992, persons > or = 65 years old hospitalized with acute cardiopulmonary conditions or influenza-like illnesses were evaluated. Evaluation included viral culture, RSV antigen detection, and serologic analysis; 159 (10%) of 1580 had RSV infection and 221 (11%) of 2091 had influenza A. RSV and influenza A cases occurred simultaneously throughout the 3 years. Clinical manifestations were similar; however, patients with RSV infection were more likely to receive therapy for bronchospasm. Death rates were 10% and 6% for RSV infection and influenza A, respectively. RSV infection is the cause of serious disease in community-dwelling older persons.

Communitywide laboratory-based influenza surveillance focused on older persons, 1989-1992.

We collected surveillance data as part of the Medicare Influenza Vaccine Demonstration to describe communitywide epidemiology of influenza, focusing on the elderly. Laboratory-based surveillance was established in medical practices, hospitals, and nursing homes in a two-county demonstration in upstate New York. Time course and intensity of epidemic influenza were compared between counties, between influenza A and B epidemics, and among several levels of surveillance involving elderly persons as well as children during the years 1989-1992. The counties experienced parallel epidemics during each of the three demonstration years. Influenza A/H3N2, predominant in 1989-1990 and 1991-1992, was equally intense among young and old, accounted for 11%-28% of acute cardiopulmonary hospitalizations of older persons, and caused focal outbreaks in 30%-40% of nursing homes in the respective epidemics. Influenza B, predominant in 1990-1991, showed modest impact among the elderly as compared with children. Influenza A/H1N1 occurred among children each year but was virtually absent among the elderly. Systematic surveillance during the "influenza season" consistently confirms widespread infection among older patients, both in the community and in institutions. However, much febrile respiratory illness in this age group during periods of epidemic influenza is culture-negative for influenza virus and thus may be caused by other respiratory pathogens.

Diagnosis and management of Baylisascaris procyonis infection in an infant with nonfatal meningoencephalitis.

Baylisacaris procyonis, the common raccoon ascarid, is known to cause life-threatening visceral, neural, and ocular larva migrans in mammals and birds. Two human fatalities have been previously described; however, little is known about the spectrum of human disease caused by B. procyonis. In this report, the case of a 13-month-old child who had nonfatal meningoencephalitis secondary to B. procyonis infection is presented. The suspected diagnosis was confirmed with use of newly developed enzyme immunoassay and immunoblot techniques. The diagnosis, management, and prevention of B. procyonis infection in humans is discussed. Clinical, serological, and epidemiological evaluations established B. procyonis as the etiologic agent. The child survived his infection but continued to have severe neurological sequelae. The potential for human contact and infection with B. procyonis is great. There is no effective therapy; therefore, prevention is paramount.

Pharyngitis associated with herpes simplex virus in college students.

During a 16-month period patients who presented to the Syracuse University Health Center with upper respiratory complaints had throat swabs obtained for viral, streptococcal and Mycoplasma pneumoniae cultures. Thirty-five of 613 patients (5.7%) had herpes simplex virus (HSV) isolated. All but 2 of the HSV isolates were found to be type 1 by immunofluorescent staining. Two HSV-positive patients also grew Group A Streptococcus, one grew M. pneumoniae and three had serum heterophile antibody tests that were positive. On physical examination 25 of the 35 HSV-positive patients had pharyngeal erythema and 14 had pharyngeal exudate. Twelve of these patients had vesicular lesions of the lips, throat or gums associated with their other symptoms. For 29 of the 35 HSV-positive students the primary diagnosis assigned was pharyngitis, for 2 the diagnosis was stomatitis and the remainder were assigned a primary diagnosis of upper respiratory infection, pneumonia, bronchitis or dental infection. Thirty-two of the 35 HSV-positive patients were treated with oral antibiotics and 7 were treated with oral or topical acyclovir. During the same 16-month period 89 (6.9%) of 1297 students presenting with sore throat were culture-positive for influenza A or B, 30 (2.3%) of 1283 were culture-positive for M. pneumoniae and 169 (2.8%) of the 6016 cultured for Group A Streptococcus were positive. Serum was tested for heterophile antibody in 2438 students, and 257 (10.5%) were positive. Herpes simplex virus is associated with pharyngeal symptoms in college students, and herpes simplex pharyngitis cannot easily be distinguished clinically from other causes of acute pharyngitis in this age group.

Rhinovirus infection associated with serious illness among pediatric patients.

Rhinovirus is an important cause of respiratory infection among all age groups, but it is primarily thought of as being responsible for upper respiratory tract infection. Rhinovirus was isolated from the respiratory tract of 48 pediatric patients who were hospitalized (40) or seen in a pediatric emergency room (8) during the period of July, 1985, through December, 1988. Twenty-eight (58%) of the patients presented during the spring and early summer. Forty-one (86%) of the 48 patients were less than 12 months of age. All except four of the patients had viral cultures performed because of respiratory symptoms. Bronchiolitis was the single most frequent clinical diagnosis and was noted in equal proportion among children less than 3 months and 3 to 12 months of age. Nine patients were assigned a diagnosis of suspected sepsis. Rhinovirus infection was a complication of underlying illness for 17 (44%) of the 40 hospitalized patients, and those patients tended to be older than the otherwise healthy hospitalized infants with rhinovirus. Twenty-six patients (54%) were treated with antibacterial agents, although only one patient was documented to have a concomitant bacterial infection (Chlamydia trachomatis). Overall rhinovirus isolation during the study period represented 0.7% of all specimens submitted for viral isolation compared with 8.2% for respiratory syncytial virus. Rhinovirus infection leads to hospitalization less frequently than does respiratory syncytial virus infection, but the severity of illness and clinical presentation in young infants are similar.

Can early bacterial complications of aspiration with respiratory failure be predicted?

We studied the early infectious complications of all children admitted for intensive care over a six-year period who were at high risk of having severe aspiration of gastric or pharyngeal secretions. Patients were only analyzed if they required mechanical ventilation for acute respiratory failure, had a blood culture obtained in the first 48 hours, and survived at least 24 hours. Infections were identified by positive blood cultures. Possible infections were defined as fever (over 38.5 degrees C), abnormal leukocyte count (greater than 10,000 or less than 5000), and a potential pathogen in tracheal secretions. Patients' diagnoses included near-drowning (13), aspirated foreign body (5), observed aspiration of gastric contents in a hospitalized patient (2), and hydrocarbon aspiration (1). Of 21 high-risk patients, five (23.8%) had infections and two (9.5%) had possible infections in the first 48 hours. In contrast, no late infections were seen. Infected patients tended to be older (P less than 0.05). No diagnostic features in the first two days of hospitalization reliably identified those who would develop early infections (P greater than 0.05). Since early life-threatening infection is common and cannot be reliably predicted by clinical signs, we recommend aggressive bacteriologic surveillance and the administration of IV antibiotics on admission to all patients in respiratory failure requiring mechanical ventilation after presumed aspiration of gastric or pharyngeal secretions.