Rodney E. Willoughby

Updated Guidance for Palivizumab Prophylaxis Among Infants and Young Children at Increased Risk of Hospitalization for Respiratory Syncytial Virus Infection

Palivizumab was licensed in June 1998 by the Food and Drug Administration for the reduction of serious lower respiratory tract infection caused by respiratory syncytial virus (RSV) in children at increased risk of severe disease. Since that time, the American Academy of Pediatrics has updated its guidance for the use of palivizumab 4 times as additional data became available to provide a better understanding of infants and young children at greatest risk of hospitalization attributable to RSV infection. The updated recommendations in this policy statement reflect new information regarding the seasonality of RSV circulation, palivizumab pharmacokinetics, the changing incidence of bronchiolitis hospitalizations, the effect of gestational age and other risk factors on RSV hospitalization rates, the mortality of children hospitalized with RSV infection, the effect of prophylaxis on wheezing, and palivizumab-resistant RSV isolates. This policy statement updates and replaces the recommendations found in the 2012 Red Book.

Infection, inflammation and the risk of cerebral palsy.

The balance of current evidence indicates that intrauterine exposure to infection and inflammation contributes to the risk of cerebral palsy. The mechanisms involved are not well understood and may differ in very immature versus term infants. Term infants exposed to maternal infection are predisposed to delivery room depression and neonatal encephalopathy.

Clostridium difficile Infection in Infants and Children

Infections caused by Clostridium difficile in hospitalized children are increasing. The recent publication of clinical practice guidelines for C difficile infection in adults did not address issues that are specific to children. The purpose of this policy statement is to provide the pediatrician with updated information and recommendations about C difficile infections affecting pediatric patients.

Recommendations for Prevention and Control of Influenza in Children, 2012–2013

The purpose of this statement is to update recommendations for routine use of trivalent seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children. The key points for the upcoming 2012–2013 season are: (1) this year’s trivalent influenza vaccine contains A/California/7/2009 (H1N1)–like antigen (derived from influenza A [H1N1] pdm09 [pH1N1] virus); A/Victoria/361/2011 (H3N2)–like antigen; and B/Wisconsin/1/2010–like antigen (the influenza A [H3N2] and B antigens differ from those contained in the 2010–2011 and 2011–2012 seasonal vaccines); (2) annual universal influenza immunization is indicated; and (3) an updated dosing algorithm for administration of influenza vaccine to children 6 months through 8 years of age has been created. Pediatricians, nurses, and all health care personnel should promote influenza vaccine use and infection control measures. In addition, pediatricians should promptly identify influenza infections to enable rapid treatment, when indicated, to reduce morbidity and mortality.

Polymorphisms of the Cytomegalovirus (CMV)–Encoded Tumor Necrosis Factor–α and β-Chemokine Receptors in Congenital CMV Disease

Some congenital cytomegalovirus (CMV) infections lead to neonatal disease, whereas others have no associated sequelae. To explore a possible role for viral genes as determinants of virulence, portions of the UL144 tumor necrosis factor (TNF)–a–like receptor gene, the US28 bchemokine receptor gene, and the UL55 envelope glycoprotein B gene from 33 patients with congenital CMV infection were sequenced. Three major UL144 subtypes (A, B, and C) and 2 recombinants (A/C and A/B) were detected. Infection with the least common UL144 subtypes (A, C, A/C, and A/B) was associated with unfavorable disease outcome ( ). There was P p .04 no association between specific subtypes of the US28 and UL55 genes and outcome (P p and , respectively). Multiple genotypes (implying multiple infections) were detected .864 P p .765 in tissues from 8 of 10 autopsies. Therefore, polymorphism in the CMV-encoded TNF-a–like receptor appears to be associated with congenital CMV disease. Other CMV polymorphisms should be further evaluated for potential relevance to neonatal infection, transplantation, and acquired immunodeficiency syndrome–associated CMV diseases. Cytomegalovirus (CMV) is the most common congenital infection, affecting 1% of infants born in the United States. Why some infants have fatal or multisystem disease and others have no clinical evidence of CMV-related abnormalities, either during the neonatal period or later, is not clear [1]. The severity of fetal disease varies widely, ranging from stillbirth or neonatal death due to multisystem disease to no abnormalities. Similarly, the outcome of congenital CMV infection ranges from no apparent impairments to significant central nervous system (CNS) damage, manifested as mental retardation, cerebral palsy, hearing loss, and impaired vision, appearing alone or in combination. Although clinical and epidemiological factors associated with a greater risk of CNS damage have been identified [2, 3], the role of putative viral virulence genes as determinants of the outcome of congenital CMV infection has not been explored. A substantial portion of the human CMV genome encodes proteins with the potential to affect virulence through immune evasion, molecular mimicry, or interference with host chemokines

Strategies for Prevention of Health Care-Associated Infections in the NICU

Health care–associated infections in the NICU result in increased morbidity and mortality, prolonged lengths of stay, and increased medical costs. Neonates are at high risk of acquiring health care–associated infections because of impaired host-defense mechanisms, limited amounts of protective endogenous flora on skin and mucosal surfaces at time of birth, reduced barrier function of their skin, use of invasive procedures and devices, and frequent exposure to broad-spectrum antibiotic agents. This clinical report reviews management and prevention of health care–associated infections in newborn infants.

Clinical and epidemiologic characteristics of children hospitalized with 2009 pandemic H1N1 influenza A infection.

Background: In 2009, pandemic H1N1 influenza caused significant morbidity and mortality worldwide. We describe the clinical and epidemiologic characteristics of children and adolescents hospitalized for 2009 H1N1 infections in Milwaukee, Wisconsin from April 2009 to August 2009. Methods: We conducted retrospective chart reviews of hospitalized patients with laboratory-confirmed 2009 H1N1 infections. Data on financial burden associated with these infections were obtained and analyzed. Results: A total of 75 children hospitalized for 2009 pandemic H1N1 infections were identified; the median age was 5 years (range, 2 months–19.2 years); 56% were males; 56% were Non-Hispanic Blacks; and 75% had at least one underlying medical condition. Twenty-four percent had only upper respiratory symptoms. Bacterial coinfections occurred in 1.3%. All but one patient received antivirals, 80% of patients received antibacterials, 18.6% were admitted to the intensive care unit, 6% required mechanical ventilation, 2.6% required extracorporeal membrane oxygenation, and 2.6% died. The total charges incurred for H1N1 influenza hospitalizations were

Improved detection of rotavirus shedding by polymerase chain reaction

4,454,191, with individual charges being highest for children >12 years of age. Conclusions: The majority of children with pandemic H1N1 influenza-associated hospitalizations had uncomplicated illness despite the frequent presence of high-risk conditions in our patient population. Laboratory-confirmed 2009 pandemic H1N1 influenza hospitalizations resulted in substantial health care and economic burden during the first wave of the pandemic in spring 2009.

Chorioamnionitis and brain injury

To improve identification of children excreting rotavirus a method for the amplification of rotavirus RNA by the polymerase chain reaction (PCR) was developed. The assay was compared with a solid-phase enzyme immunoassay in the detection of rotavirus shedding by infants in hospital during the winter peak of rotavirus infections. Forty children were studied in an intermediate care unit after transfer from intensive care units. Only two were admitted primarily because of diarrhoea; the other thirty-eight were admitted for management of various other disorders. Rotavirus shedding was detected by enzyme immunoassay in twenty of the infants, and nine of these (aged 1 week to 8 months) remained in hospital for more than 5 days after the initial detection of rotavirus and could be studied long term. Of 103 faecal samples from the nine infants, 60 (58%) contained rotavirus RNA detected by reverse-transcriptase (RT)/PCR, whereas only 37 (36%) were positive for rotavirus antigen by the immunoassay (chi 2 = 10.3, p less than 0.002). The geometric mean time of rotavirus shedding was 9.5 (range 1-19) days as detected by RT/PCR and 5.7 (range 1-17) days by the immunoassay (p less than 0.018). In five of the nine children, RT/PCR detected rotavirus shedding for 2-7 days longer than the immunoassay and in four children RT/PCR was positive 1 or more days before rotavirus antigen was detected. Further studies should attempt to find out whether infected infants are capable of spreading wild-type virus during periods when they are not shedding antigen as detectable by enzyme immunoassay.

HPV Vaccine Recommendations

The limited available evidence supports a strong association of chorioamnionitis with neonatal encephalopathy and CP in the term infant. The association of chorioamnionitis with depressed Apgar scores or neonatal seizures and with CP is equivocal in the preterm infant. Different study results may be related to differences in study populations, perhaps specifically to differences in susceptibility by stages of neurologic development as well as differences in gene frequencies associated with inflammation and thrombophilia. We require further understanding of the normal roles of cytokines in brain development, pregnancy, and inflammatory homeostasis before clinical interventions directed at cytokines, their receptors, or the inflammatory process are considered.