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Objective: The increased incidence of multidrug-resistant organisms is associated with increased morbidity, mortality, hospital length of stay, and cost. Estimates show that up to 50% of antimicrobial use is inappropriate. This initiative focuses on inappropriate use of antibiotics in respiratory syncytial virus (RSV) infections. This virus is the most common cause of bronchiolitis during childhood., Methods: Baseline data from the 2011-2012 RSV season showed that 56.2% of our RSV-positive patients received antibiotics. To decrease inappropriate antibiotic use in RSV infections, we established an antimicrobial stewardship program (ASP). This process improvement initiative aimed to decrease exposure to antibiotics and days of antibiotic therapy per 1,000 patient days (DOT/1000PD) in hospitalized RSV-positive patients by 25%. Key drivers included building health-care knowledge, proactive interventions using prospective audit and feedback, emergency department engagement, and performance dashboards., Results: We included a total of 290 children in the final analysis. After full implementation of the ASP, there was a significant reduction of antibiotic exposure from 56.2% to 30.9% ( P < 0.001), an absolute reduction of 25% and a relative reduction of 45%. There was also a significant decrease in DOT/1000PD from 432.7 to 268.1 days ( P = 0.017). This change represents a reduction of 164.6 DOT/1000PD from baseline after full ASP implementation., Conclusion: Despite the lack of a unified hospitalist group in our institution, we were successful in reducing inappropriate antibiotic use by focusing on standardizing care among different private pediatricians in the community. A multifaceted strategy and well-designed quality improvement methodology led to a sustained reduction in antibiotic use.

Objective  SENTINEL1 characterized U.S. preterm infants 29 to 35 weeks' gestational age (wGA) < 12 months old hospitalized for laboratory-confirmed respiratory syncytial virus (RSV) disease and not receiving RSV immunoprophylaxis during the 2014 to 2015 RSV season. Study Design  This is a noninterventional, observational, cohort study. Results  A total of 702 infants were hospitalized with community-acquired RSV disease, of whom an estimated 42% were admitted to the intensive care unit (ICU) and 20% required invasive mechanical ventilation (IMV). Earlier gestational age and younger chronologic age were associated with an increased frequency of RSV-confirmed hospitalization (RSVH), ICU admission, and IMV. Among infants 29 to 32 wGA and < 3 months of age, 68% required ICU admission and 44% required IMV. One death occurred of an infant 29 wGA. Among the 212 infants enrolled for in-depth analysis of health care resource utilization, mean and median RSVH charges were $55,551 and $27,461, respectively, which varied by intensity of care required. Outpatient visits were common, with 63% and 62% of infants requiring visits before and within 1 month following the RSVH, respectively. Conclusion  Preterm infants 29 to 35 wGA are at high risk for severe RSV disease, which imposes a substantial health burden, particularly in the first months of life., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

This is the first clinical practice guideline from the American Academy of Pediatrics that specifically applies to patients who have experienced an apparent life-threatening event (ALTE). This clinical practice guideline has 3 objectives. First, it recommends the replacement of the term ALTE with a new term, brief resolved unexplained event (BRUE). Second, it provides an approach to patient evaluation that is based on the risk that the infant will have a repeat event or has a serious underlying disorder. Finally, it provides management recommendations, or key action statements, for lower-risk infants. The term BRUE is defined as an event occurring in an infant younger than 1 year when the observer reports a sudden, brief, and now resolved episode of ≥1 of the following: (1) cyanosis or pallor; (2) absent, decreased, or irregular breathing; (3) marked change in tone (hyper- or hypotonia); and (4) altered level of responsiveness. A BRUE is diagnosed only when there is no explanation for a qualifying event after conducting an appropriate history and physical examination. By using this definition and framework, infants younger than 1 year who present with a BRUE are categorized either as (1) a lower-risk patient on the basis of history and physical examination for whom evidence-based recommendations for evaluation and management are offered or (2) a higher-risk patient whose history and physical examination suggest the need for further investigation and treatment but for whom recommendations are not offered. This clinical practice guideline is intended to foster a patient- and family-centered approach to care, reduce unnecessary and costly medical interventions, improve patient outcomes, support implementation, and provide direction for future research. Each key action statement indicates a level of evidence, the benefit-harm relationship, and the strength of recommendation., (Copyright © 2016 by the American Academy of Pediatrics.)

Pro: Children with chronic cough present a diagnostic challenge. Protracted bacterial bronchitis (PBB) is a chronic, persistent bacterial infection of conducting airways defined by the presence of cough for longer than 4 weeks that resolves with antimicrobial therapy and without an alternative diagnosis. The diagnosis is made by the findings of increased bronchial secretions and edema of the lower airways on flexible bronchoscopy and positive cultures on bronchoalveolar lavage. It is speculated that an initial respiratory insult such as viral infection disrupts normal surface morphology and ciliary function, which leads to chronic self-perpetuating inflammation with the formation of bacterial biofilms, leading to PBB. PBB is often misdiagnosed as asthma, leading to inappropriate and excessive use of steroids. The importance of timely diagnosis should be emphasized due to the potential that PBB may be a precursor to chronic suppurative lung disease or bronchiectasis if left untreated; however, every patient should be adequately assessed to exclude other causes of chronic cough. Con: Clinical criteria for the diagnosis of PBB are nonspecific and may not distinguish it from other known causes of chronic cough, including viral infections. Benefits from antibiotic therapy (particularly prolonged therapy) have not been demonstrated. Respiratory conditions are the most common reason for antibiotic prescriptions during ambulatory visits in the United States, and many of these prescriptions are inappropriate and/or unnecessary. The proposed diagnostic criteria and recommendations for the treatment of PBB will lead to unnecessary overuse of antibiotics., (Copyright 2015, SLACK Incorporated.)

Outbreaks of vaccine-preventable diseases continue to occur in the United States, and they have been occurring at increasing rates over the past decade. Factors contributing to these outbreaks include importation from abroad, under-vaccination of segments of the population, and incomplete protection or waning immunity with certain vaccines. This article reviews recent outbreaks of measles, mumps, and pertussis in the United States to highlight the extent to which outbreaks of these vaccine-preventable diseases are still occurring and even increasing. Appreciating the magnitude of these illnesses may help the physician in educating families who are hesitant about vaccines., (Copyright 2015, SLACK Incorporated.)

Unlabelled: Virulent strains of Escherichia coli are responsible for most diarrheal infections, meningitis, septicemia, and urinary tract infections in children worldwide. Clinicians must learn to recognize, treat, and prevent these infections., Objectives: After completing this article, readers should be able to: 1. Describe the epidemiology of E coli infections. 2. Recognize the clinical features of E coli infections, including the O157: H7 strain. 3. Appropriately treat children with various types of E coli infections. 4. Understand ways to prevent E coli infections.

Background: Infection with respiratory syncytial virus (RSV) is common among young children insured through Medicaid in the United States. Complete and timely dosing with palivizumab is associated with lower risk of RSV-related hospitalizations, but up to 60% of infants who receive palivizumab in Medicaid population do not receive full prophylaxis. The purpose of this study was to evaluate the association of partial palivizumab prophylaxis with the risk of RSV hospitalization among high-risk Medicaid-insured infants., Methods: Claims data from 12 states during 6 RSV seasons (October 1st to April 30th in the first year of life in 2003-2009) were analyzed. Inclusion criteria were birth hospital discharge before October 1st, continuous insurance eligibility from birth through April 30th, ≥ one palivizumab administration from August 1st to end of season, and high-risk status (≤34 weeks gestational age or chronic lung disease of prematurity [CLDP] or hemodynamically significant congenital heart disease [CHD]). Fully prophylaxed infants received the first palivizumab dose by November 30th with no gaps >35 days up to the first RSV-related hospitalization or end of follow-up. All other infants were categorized as partially prophylaxed., Results: Of the 8,443 high-risk infants evaluated, 67% (5,615) received partial prophylaxis. Partially prophylaxed infants were more likely to have RSV-related hospitalization than fully prophylaxed infants (11.7% versus 7.9%, p< 0.001). RSV-related hospitalization rates ranged from 8.5% to 24.8% in premature, CHD, and CLDP infants with partial prophylaxis. After adjusting for potential confounders, logistic regression showed that partially prophylaxed infants had a 21% greater odds of hospitalization compared with fully prophylaxed infants (odds ratio 1.21, 95% confidence interval 1.09-1.34)., Conclusions: RSV-related hospitalization rates were significantly higher in high-risk Medicaid infants with partial palivizumab prophylaxis compared with fully prophylaxed infants. These findings suggest that reduced and/or delayed dosing is less effective.

Background: Influenza B viruses from 2 lineages cocirculate annually. Because the single B strain contained in trivalent vaccines may not match the major circulating strain, adding a second B virus could enhance protection. This study compared the safety and immunogenicity of an investigational quadrivalent Ann Arbor strain live attenuated influenza vaccine (Q/LAIV) with that of 2 trivalent vaccines (T/LAIV), each containing a B strain from a different lineage., Methods: This randomized, double-blind study was designed to demonstrate the immunologic noninferiority of Q/LAIV compared with T/LAIV in children 2-17 years of age by comparing postdose geometric mean titers of hemagglutination inhibition antibodies. Children were randomized 3:1:1 to receive Q/LAIV or 1 of 2 T/LAIV vaccines. Those subjects who were 9-17 years of age received 1 dose, and those 2-8 years of age received 2 doses 1 month apart. Serum immune responses were evaluated 1 month after dose 1 (dose 2 for influenza vaccine-naive subjects aged 2-8 years)., Results: Q/LAIV was noninferior to T/LAIV: upper bounds for all four 95% confidence intervals for the postdose geometric mean titer ratios (T/LAIV divided by Q/LAIV) were ≤1.5, the predefined noninferiority margin. The overall seroresponse rates (4-fold rise) were comparable between treatment groups. Safety events were comparable, except that fever was more common after dose 1 in Q/LAIV subjects (5.1%) than in T/LAIV subjects (3.1%) 2-8 years of age., Conclusions: The immunogenicity of Q/LAIV was noninferior to that of T/LAIV in children aged 2-17 years; safety was also comparable. Q/LAIV may broaden the protection against influenza B strains provided by current trivalent influenza vaccines.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in infants and young children, accounting for more than 100,000 hospitalizations per year in the USA. The majority of hospitalizations occur in infants less than 1 year of age. Worldwide, RSV is associated with an annual mortality rate of 160,000-600,000 deaths. Premature infants, and infants with congenital heart disease, neuromuscular disease, structural airway abnormalities and immunodeficiencies are at increased risk for severe RSV disease. Despite the magnitude of RSV disease, treatment remains primarily supportive. Trials of bronchodilators, corticosteroids and montelukast have not demonstrated conclusive clinical benefit. The antiviral drug ribavirin has demonstrated only marginal clinical benefit and is not routinely indicated in treatment of RSV disease. Palivizumab is beneficial in prophylaxis for infants at high-risk for severe RSV infection although optimal indications based on cost-effectiveness considerations have not been defined. Future directions in treatment and prevention of RSV infections likely include the second-generation monoclonal antibody motavizumab, more potent antiviral compounds and more unique anti-inflammatory agents. Vaccination against RSV is in development but not eminent.

Objective: This study aimed to review cases of Lemierre's and Lemierre's-like syndromes in paediatric patients, to examine a possible association with Epstein-Barr virus as a predisposing factor, and to assess the impact of this virus on the severity of illness., Methods: We performed a retrospective analysis of data from the in-patient database at Winthrop University Hospital, from January 2001 to October 2007. We reviewed clinical and laboratory findings as well as the outcome of infection in patients aged 21 years or less with a diagnosis of Lemierre's syndrome. An additional case of Lemierre's-like syndrome was also included. The illness severity and duration of in-patient management of those testing positive for heterophile antibody were then compared with the same parameters in patients who tested negative., Results: Of the five patients diagnosed with Lemierre's syndrome, two had concomitant acute infection with Epstein-Barr virus. Additionally, a 19-year-old adolescent was admitted during this period with acute infectious mononucleosis, Fusobacterium necrophorum sepsis, sinusitis, frontal lobe abscess and ophthalmic vein thrombosis. The clinical presentation of all patients included fever, sore throat, and ear or neck pain. The duration of symptoms ranged from two days to three weeks prior to admission. The patients with acute Epstein-Barr virus infection had been diagnosed with infectious mononucleosis prior to admission, and tested positive for heterophile antibody. These patients subsequently underwent more extensive in-patient treatment, including intensive care management and ventilator support. The patients who tested negative for heterophile antibody experienced a milder course of illness, with a shorter duration of in-patient management., Conclusion: Two patients diagnosed with Lemierre's syndrome, and a third with Fusobacterium necrophorum sepsis, had coexisting acute Epstein-Barr virus infection. Patients who tested positive for heterophile antibody experienced a more severe course of illness. These observations suggest a possible association between Epstein-Barr virus infection and the severity of concomitant Lemierre's syndrome.

Background: During the period of this study, the American Academy of Pediatrics (AAP) 2006 guidelines recommended respiratory syncytial virus (RSV) prophylaxis for infants 32 to 35 weeks gestation age (wGA) with two or more of five risk factors (RFs). New recommendations have recently been published in 2009. The cost implications of expanding this list of RFs to include other evidence-based RFs like passive smoke exposure (PSE), crowded living conditions (CLCs), and young chronological age (YCA) are unclear., Methods: We estimated the prevalence of RSV RFs in a US sample of infants 32 to 35 wGA referred for prophylaxis from nine specialty pharmacy providers during the 2007-2008 season. We estimated the percent eligible for RSV prophylaxis under various potential RF coverage policies. Using a budget impact model, we calculated the per-member-per-month (PMPM) cost for each policy in 2007 USD for a hypothetical one million member plan., Results: Infants 32 to 35 wGA represented 0.08% of the plan. Approximately 20.2% of these infants met at least two or more of five AAP RFs. Expanding this list to include one additional RF of PSE, CLC, or YCA increased the percent of infants potentially prophylaxed to 29.9%, 23.9%, and 47%, respectively. Adding all three RFs to the list (two or more of eight) increased the percent of infants potentially prophylaxed to 55.6%, and increased payer costs by 9 cents PMPM., Conclusion: Expanding the AAP RF criteria to include PSE, CLC, and YCA would identify more 32 to 35 wGA infants at high risk for severe RSV disease at an acceptable budget impact.

This chapter discusses various drugs for human influenza A (H5N1) and multidrug-resistant mycobacterium tuberculosis (MDR-TB). The H5N1 avian influenza does not presently meet the criteria of an antigenically shifted strain. It is presently an avian strain that has not undergone reassortment with a human strain and is not well adapted to humans. H5N1 isolates are resistant to the M2 inhibitors amantadine and rimantadine; these antivirals do not have a role for the treatment or prophylaxis against the strain. The neuraminidase inhibitors, oseltamivir and zanamivir, have in vitro activities against the human H5N1 isolates; however, recent data suggest that higher doses for longer periods may be required to be effective. Oseltamivir is an oral agent approved for prophylaxis and the treatment of influenza infections. Zanamivir is delivered topically to the respiratory tract with similar indications. The drugs discussed in the chapter for MDR-TB fall into three categories-quinolones, nitroimidazoles, and pyrroles. Drugs such as moxifloxacin are methoxyfluoroquinolones, which are already available and approved for the treatment of acute respiratory infections, such as community-acquired pneumonia, intra-abdominal infections, acute sinusitis, and skin infections. Gatifloxacin 5, is another methoxyfluoroquinolone that is in clinical development for tuberculosis treatment., (Copyright © 2006 Elsevier Inc. All rights reserved.)

SARS and avian influenza have many common features. They both arose in Asia and originated from animal viruses. They both have the potential to become pandemics because human beings lack antibodies to the animal-derived antigens present on the viral surface and rapid dissemination can occur from the relative ease and availability of high speed and far-reaching transportation methods. Pediatricians, in particular, should remain alert about the possibility of pandemic illnesses in their patients. Annual rates of influenza in children may be 1.5 to 3 times those in the adult population, and infection rates during a community epidemic may exceed 40% in preschool-aged children and 30% in school-aged children. Infected children also play a central role in disseminating influenza, as they are the major point of entry for the virus into the household, from which adults spread disease into the community. Of course, children younger than 24 months also are at high risk for complications from influenza. A 1999 Centers for Disease Control and Prevention projection of an influenza pandemic in the US paints a grim picture: 89,000 to 207,000 deaths, 314,000 to 734,000 hospitalizations, 18 million to 42 million outpatient visits, and 20 million to 47 million additional illnesses, at a cost to society of at least dollars 71.3 billion to dollars 166.5 billion. High-risk patients (15% of the population) would account for approximately 84% of all deaths. Although SARS has been kind to the pediatric population so far, there are no guarantees that future outbreaks would be as sparing. To aid readers in remaining up-to-date with SARS and avian influenza, some useful websites are listed in the Sidebar. Two masters of suspense, Alfred Hitchcock and Stephen King, may have been closer to the truth than they ever would have believed. Both birds and a super flu could bring about the end of civilization as we know it. But all is not lost--to paraphrase Thomas Jefferson, the price of health is eternal vigilance. Although we may not be able to prevent future pandemics, mankind has the ability to recognize new diseases and outbreaks as they occur, to study these infections and find ways to contain and treat them, and to implement the necessary measures to defeat them.

Purpose of Review: New emerging infections over the last few years demonstrate the potential for the introduction of epidemic illness through global migration. The increasing number of children adopted internationally (>20,000 in 2003, from the United States State Department) provides a unique situation for the spread of emerging infections through the combination of international travel by parents through areas where such infections may be contracted and the nature of the living conditions for many of the orphans being placed by this process., Recent Findings: The recent literature on three emerging infections--avian influenza, severe acute respiratory syndrome (SARS) and measles--describes clinical aspects of the illnesses and their epidemiology. For avian influenza aspects of the agrarian economy in southeast Asia enabled the virus to reach the human population. The potential for further adaptation to people could set the stage for a new pandemic. SARS evolved in rural China and spread worldwide in one season with an approximate 10% mortality. Attention to public-health measures led to control of this new illness. Most recently, outbreaks of measles in Chinese orphanages have been documented. These findings demonstrate the potential of such infections to be transmitted during the process of international adoption, and in the case of measles the realization of this potential in recent reported cases from Chinese orphanages brought to the United States on commercial airlines., Summary: Clinicians involved in international adoption and public-health officials assessing emerging infections need to work together in monitoring these issues.

Foodborne illnesses impose a substantial economic and quality-of-life burden on society by way of acute morbidity and chronic sequelae. We developed an economic model to evaluate the potential cost-effectiveness of a disinfection program that targets high-risk food preparation activities in household kitchens. For the United States, Canada, and the United Kingdom, we used published literature and expert opinion to estimate the cost of the program (excluding the educational component); the number of cases of Salmonella, Campylobacter, and Escherichia coli O157:H7 infections prevented; and the economic and quality-of-life outcomes. In our primary analysis, the model estimated that approximately 80,000 infections could be prevented annually in U.S. households, resulting in 138 million dollars in direct medical cost savings (e.g., physician office visits and hospitalizations avoided), 15,845 quality-adjusted life-years (QALYs) gained, 788 million dollars in program costs, and a favorable cost-effectiveness ratio of 41,021 dollars/QALY gained. Results were similar for households in Canada and the United Kingdom (21,950 dollars Can/QALY gained and 86,341 pounds sterling/QALY gained, respectively). When we evaluated implementing the program only in U.S. households with high-risk members (those less than 5 years of age, greater than 65 years of age, or immunocompromised), the cost-effectiveness ratio was more favorable (10,163 dollars/QALY gained). Results were similar for high-risk households in Canada and the United Kingdom (1,915 dollars Can/QALY gained and 28,158 pounds sterling/QALY gained, respectively). Implementing a targeted disinfection program in household kitchens in the United States, Canada, and the United Kingdom appears to be a cost-effective strategy, falling within the range generally considered to warrant adoption and diffusion (<100,000 dollars/QALY gained).

In this report we present four patients who were found to have both an eating disorder and the chronic fatigue syndrome (CFS). Two of the patients presented for evaluation of an eating disorder and also had CFS, while two of the patients presented for evaluation of CFS and also had an eating disorder. In all four patients the eating disorder preceded the CFS. We consider the question of whether the occurrence of these two disorders in the same patients is merely a coincidence; whether an eating disorder can act as a precipitant for CFS, perhaps through the exacerbation of an underlying vascular instability; and whether overlapping etiologies may predispose some adolescents to develop both disorders. We also discuss similarities (including diagnostic dilemmas, cultural influences, psychological correlates, demographic similarities, perceptual biases, and cardiovascular effects) encountered in the management of both of these disorders.

Respiratory syncytial virus (RSV) infection is the leading cause of lower respiratory tract infection in infants and young children. Premature infants and infants with underlying lung disease are at increased risk for severe RSV infection in the first 1 - 2 years of life. Monthly prophylaxis with palivizumab (Synagis) during RSV season has been proven safe and effective in this population and these effects have persisted over the 4 years since the drug was approved by the US FDA in 1998. Issues remain regarding the optimal candidates for palivizumab prophylaxis and whether additional groups of high-risk individuals, for example infants with congenital heart disease or cystic fibrosis, and immunocompromised hosts, might benefit from such preventive therapy. It is possible that palivizumab in combination with antiviral or anti-inflammatory agents might also prove to be beneficial in the treatment of RSV disease. Newer monoclonal antibodies to RSV in development may offer the potential for less frequent dosing, increased efficacy and a role in treatment of RSV disease, but pending further evaluation of such products palivizumab provides significant protection for high-risk infants against a major pathogen.

Objective: To assess the economic impact, from a societal perspective, of a multidimensional infection control education program (ICEP) in a preschool for children with Down syndrome., Methods: Krilov et al implemented a comprehensive ICEP in a specialized preschool setting and reported a significant decrease in medical resource utilization and days absent from school. Clinical and economic data from Krilov et al and other sources were incorporated into a health-state transition (Markov) decision analysis model that estimated annual expected costs for the baseline and intervention years. Procedure and diagnosis codes were assigned to all physician office visits, emergency department visits, hospitalizations, and laboratory and diagnostic tests. Cost estimates then were derived using 1999 national reimbursement schedules and other sources. Productivity losses for parents were estimated using national wage rates. The costs of the ICEP were compared with the reduction in the costs of illness (direct medical costs plus costs associated with lost parental working time). The outcomes measured were mean annual costs of illness per child, total annual ICEP costs, and net annual costs or savings., Results: With a comprehensive ICEP, the mean costs of illness in the baseline year was $1235 per child, of which 68% and 14% were for productivity losses and physician visits, respectively. In the intervention year, the mean costs of illness per child was $615, of which 71% and 20% were for productivity losses and physician visits, respectively. The cost of the preexisting infection control (IC) practices in place at the onset of the study (baseline year) was $716. The comprehensive ICEP cost (intervention year) was $75 627, 92% of which was spent to hire a cleaning service to decontaminate toys 3 times per week. When a secondary analysis was performed to reflect a less intensive ICEP in a nonspecialized preschool setting, the mean costs of illness in the baseline and intervention years were $962 and $614 per child, respectively, representing a total annual cost-of-illness savings of $13 224 for the 38 children who participated in the study by Krilov et al. The annual incremental cost of the less intensive ICEP was $2371; therefore, the estimated net annual savings of the less intensive ICEP in a nonspecialized preschool was $10 853., Conclusions: This study suggests that the reduction in the costs of illness could more than offset the cost of implementing a multidimensional ICEP in a preschool setting.

In this work we continue our study of the biochemical responses of respiratory epithelial cells to infection with human paramyxovirus pathogens. In our earlier studies, we detected elevated concentrations of the proinflammatory chemokines MIP-1alpha and IL-8 in upper and lower respiratory tract secretions from patients infected with respiratory syncytial virus (RSV). Here we demonstrate the same trend for individuals infected with parainfluenza virus (PIV), with elevated concentrations of MIP-1alpha and IL-8 (means of 309 +/- 51 and 2280 +/- 440 pg/ml/mg protein, respectively) detected in nasal wash samples from 17 patients with culture-positive PIV. Similar to our findings with RSV, cells of the HEp-2 epithelial line and primary cultures of human bronchial epithelial cells respond to PIV infection with production and release of both MIP-1alpha and IL-8. Addition of the glucocorticoid anti-inflammatory agent hydrocortisone (200-1000 ng/ml) attenuated the production of MIP-1alpha and IL-8 in PIV-infected cells while having minimal to no effect on the production of these mediators from cells infected with RSV. Neither virus infection resulted in a change in the total cellular concentration of glucocorticoid receptors, nor did hydrocortisone exert any differential effect on viral replication. As repression of chemokine production by epithelial cells is likely to result in diminished recruitment of proinflammatory leukocytes, these results may explain in part why glucocorticoid therapy reduces the symptoms associated with acute PIV infection, but have little to no effect in the overall outcome in the case of RSV.

Respiratory syncytial virus (RSV) infection, which primarily manifests as bronchiolitis or pneumonia, is the leading cause of lower respiratory tract infection in infants and young children. It is associated with more than 100,000 pediatric hospitalizations each year in the United States. Infants who were premature; have chronic lung disease, congenital heart disease, or immunodeficiency disorders; or have underlying metabolic or neuromuscular disorders are at increased risk for especially severe RSV disease. Treatment of children hospitalized with RSV disease is primarily supportive, with administration of supplemental oxygen and fluid replacement therapy. Bronchodilators may benefit at least a subset of such patients. Antiviral therapy with aerosolized ribavirin is available for high-risk, severely ill patients. Handwashing, cleaning of environmental surfaces, and cohorting in hospital settings may decrease RSV transmission. In children born premature and younger than 1 year of age, and in patients with bronchopulmonary dysplasia younger than 2 years of age, passive protection against severe RSV disease may be achieved through monthly injections of anti-RSV antibody (palivizumab) during winter months. No vaccine is available to provide active immunity against RSV, but live attenuated and subunit cloned surface protein vaccines are in development.

Objective: To compare the clinical and laboratory features of children with Kawasaki disease with those with acute adenoviral infection, which may mimic Kawasaki disease., Design: We retrospectively compared the medical records of children with Kawasaki disease and atypical Kawasaki disease with those of children with acute adenoviral infection. All children included were initially evaluated because their primary care physicians were concerned that they might have Kawasaki disease. The utility of a rapid direct fluorescent antigen test for adenovirus was evaluated. Thirty-six children with Kawasaki disease (23 with classic and 13 with atypical presentations) and 7 patients with acute adenoviral infection were studied., Setting: A tertiary care pediatric hospital., Results: Children with Kawasaki disease were more likely to have conjunctivitis (36 of 36 vs 4 of 7), strawberry) tongues (23 of 36 vs 1 of 7), perineal peeling (19 of 36 vs 0 of 7), and distal extremity changes (22 of 36 vs 0 of 7) than those with acute adenoviral infection. Children with acute adenoviral infection were more likely to have purulent conjunctivitis (3 of 7 vs 1 of 36) and exudative pharyngitis (3 of 7 vs 1 of 35). In addition to pyuria (13 of 26 vs 0 of 6), patients with Kawasaki disease had higher mean white blood cell counts (15.3 +/- 3.5 vs 11.5 +/- 6.0 x 10(9)/L), erythrocyte sedimentation rates (56 vs 42 mm/h), platelet counts (426 vs 259 x 10(9)/L), and levels of alanine aminotransferase (101 vs 18 U/L) than those with acute adenoviral infection. Children with Kawasaki disease had lower mean albumin levels (32 vs 36 g/L). A rapid antigen test for adenovirus had a specificity and sensitivity of 100% compared with viral culture., Conclusions: Kawasaki disease and acute adenoviral infection can present with many of the same clinical characteristics. A rapid direct fluorescent antigen assay for adenovirus may be a helpful adjunctive test for distinguishing acute adenoviral infection from Kawasaki disease.

This article is an overview of the epidemiology and spectrum of clinical disease attributed to influenza and respiratory syncytial virus in children. It separately discusses the pathogenesis of the two diseases and the host responses to the viruses to emphasize each infection's significance and need for a vaccine. Updates on current preventive measures and a preview of potential future vaccine developments are presented.

Respiratory syncytial virus (RSV), a major cause of morbidity in children, results in severe lower respiratory tract infections. With an in vitro infection system of isolated cord or adult peripheral blood mononuclear cells, addition of virus to cell cultures resulted in significant reductions in cell deaths, as measured by 2 independent assays: quantitation of cells with subdiploid levels of DNA and cells with DNA strand breaks. Decreased cell death was observed in lymphocytes and monocytes of cord and adult samples, with more dramatic effects evident in cells from cord blood. This may be linked to the increased virulence observed in infants with RSV infection. These data suggest that RSV may be equipped with some mechanism to prevent apoptosis, which is a major component of the host defense system used to eliminate virally infected cells.

Central nervous system infections in children and adolescents involve a wide spectrum of illnesses, ranging from acute self-limited diseases, such as enteroviral meningitis, to severe diffuse or focal infections (i.e., arboviral encephalitis) resulting in devastating neurologic sequelae. All the clinical manifestations of CNS infections occur to some degree secondary to toxic mediators such as cytokines. These factors are neurotoxic and produce clinical manifestations such as encephalopathy, motor abnormalities, and seizures. Many of these diseases also produce radiculoneuropathies and vasculopathies (stroke). As a result, chronic neurologic conditions may result and are frequently associated with psychiatric disturbances and situational depression.

In this study, we searched for evidence for reactivation of three latent herpesviruses, Epstein-Barr virus (EBV), herpes simplex virus type-1 (HSV-1), and human herpesvirus 6 (HHV-6), in West Point cadets experiencing two different stressors. Blood samples were obtained from cadets before and after a 6-week training period known as "Cadet Basic Training" (CBT), at a baseline prior to final examinations, and then once again during the week of final examinations. Antibody titers to latent HSV-1, EBV, and HHV-6 were determined as a measure of the steady-state expression of latent virus. EBV virus capsid antigen (VCA) IgG antibody titers were unchanged in blood samples obtained prior to and immediately after CBT. However, EBV antibody titers were significantly higher in the blood sample obtained during examination week than in the baseline period before examination; they were also higher than antibody titers before/after CBT. None of the serum samples were positive for EBV VCA IgM antibodies, indicating that the changes in antibody titers to EBV were not associated with recent EBV infections in the class. No significant changes in antibody titers to HSV-1 or HSV-6 were found over the identical time periods, including examination week. Academic stress but not CBT modulated the steady-state expression of latent EBV, resulting in the reactivation of latent virus. The same stressors, however, did not affect the steady-state expression of latent HSV-1 or HSV-6, at least as measured by changes in antibody titers. The data provide additional evidence of the impact of different psychological stressors on the steady-state expression of latent herpesviruses., (Copyright 1999 Academic Press.)

We investigated the use of the Directigen Respiratory Syncytial Virus test performed under 'Stat Laboratory' conditions, in the management of infants after admission from the Paediatric Emergency Department (ED). The study group consisted of 242 consecutive paediatric ED patients tested by Directigen in the Stat laboratory during the winter 1995-1996 respiratory virus season. Specimens were submitted to the Virology Laboratory for confirmatory consensus testing utilizing in part, an in-house multiplex immunofluorescence assay (IFA) and conventional virus isolation methodologies. The sensitivity, specificity, positive and negative predictive values for Directigen, IFA, and isolation, were 71, 91, 85, 80%; 98, 100, 100, 99%; and 51, 100, 100, 72% respectively. Re-testing of 17 discordant original NP aspirates using Directigen, suggested that errors were due to technologist interpretation as well as to overt assay failure. The low analytical sensitivity and specificity of Directigen precludes its use in the clinical setting described in this study. Evening or weekend specimen collection, followed by IFA testing in a centralized Virology Laboratory at the start of the next working day, produces reliable test results. Among the small number of pediatric patients who might be candidates for antiviral therapy IFA testing should be made available on an on-call basis by Virology Laboratory.

Background: Hospitalization for respiratory syncytial virus (RSV) bronchiolitis is considered a risk factor for reactive airway disease and/or abnormal pulmonary function tests (PFTs) later in childhood. This study attempted to assess this observation with newer PFTs and to determine whether ribavirin therapy of initial RSV infection may affect the long term outcome., Methods: Medical records of all infants hospitalized with RSV infection in 1986 and 1987 at six institutions (North Shore University Hospital, Children's Hospital of Buffalo, University Florida-Gainesville, University of Connecticut, Children's Hospital National Medical Center, Denver Children's Hospital) were requested. Patients who could be contacted were recalled in 1993 and 1994 for PFTs and given a pulmonary status questionnaire., Results: One hundred patients were evaluated. Overall PFTs were within normal ranges. There was less "bronchitis" over the interval years in the ribavirin-treated patients (13 of 33) vs. those who did not receive ribavirin (44 of 67, P < 0.01). There was no difference for the diagnosis of reactive airway disease (15 of 33 ribavirin vs. 36 of 67 no ribavirin). Patients who received ribavirin were then matched by age (within 2 weeks) at initial RSV infection and underlying risk factor (bronchopulmonary dysplasia, heart disease). Of the 27 patients matched, the ribavirin patients had longer intensive care unit stays (median (25 to 75% interquartile range): 2 (0 to 7) vs. 0 (0 to 0), P < 0.05). On follow-up evaluation there were no significant differences in PFTs or reactive airway disease between the 2 groups. There was a trend toward lower forced expiratory volume at 1 s and midexpiratory flow rate (25 to 75%) in the ribavirin-treated group, and there were more reported pneumonias on follow-up in the ribavirin patients., Conclusion: During our 5- to 6- year follow-up of children, status post bronchiolitis, we noted a good long term prognosis. No long term adverse effects on pulmonary function were detected. Despite being potentially sicker at presentation as assessed by intensive care unit stay, ribavirin recipients were doing equally well at the time of follow-up.

Background: The purpose of this study was to design and implement a comprehensive infection control program and measure its effects on the number and types of infectious illnesses experienced by children attending a specialized preschool program., Methods: Participants in the study were children with Down syndrome enrolled in a school-based early intervention program. The ages of the children ranged from 6 weeks to 5 years. Through a series of parental questionnaires, the number and types of infections in the children were chronicled for a year before and a year after the implementation of an infection control intervention program. Interventions included infection control lectures, handouts, posters, and attention to environmental cleaning and disinfection, with an emphasis on toys. Compliance with these measures was monitored and recorded., Results: During the interventional year the median number of total illnesses/child/month decreased significantly from the baseline year (0.70 vs 0.53, p < 0.05), with a trend toward a decrease in the number of respiratory illnesses (0.67 vs 0.42, p < 0.07). Significant decreases were also seen for the median number of physician visits (0.50 vs 0.33, p < 0.05), courses of antibiotics administered (0.33 vs 0.28, p < 0.05), and days of school missed as a result of respiratory illness (0.75 vs 0.40, p < 0.05)., Conclusions: This study demonstrates a decrease in infection rates with the implementation of a comprehensive educational and environmental infection control program in a day care setting.

Behavior problems and family functioning were investigated in a sample of 10 adolescent girls with chronic fatigue syndrome (CFS), 10 matched healthy adolescent girls, and 10 adolescents with childhood cancer in remission. Based on the adolescent girls' reports, the CFS group had significantly higher scores than the cancer and healthy comparison adolescent girls on somatic complaints and also significantly higher scores than the cancer controls on internalizing symptoms and depression. Parent reports resulted in significantly higher scores in the CFS group than the adolescent girls from the healthy comparison groups on internalizing scores and somatic complaints. There were no significant differences on any family variables.

We evaluated febrile convulsions prospectively in 42 children to investigate the association between acute human herpesvirus-6 (HHV-6) infection and first-time febrile convulsions, using both virologic and serologic methods. Eight children had primary HHV-6 infection documented by viral culture and an additional three by acute- and convalescent-phase serologic studies. These findings indicate that acute HHV-6 infection is a frequent cause of febrile convulsions in young children.