Faculty Bibliography

BACKGROUND AND AIM: Varicella is normally a self-limited disease of childhood that does not require hospitalization. In the prevaccine era varicella caused >9000 hospitalizations per year. To determine whether the varicella vaccine, licensed in 1995, has decreased hospitalizations because of varicella, we examined national rates of varicella-related hospital discharges (VRHD) covering a 12-year period that included pre- and postvaccine data. METHODS: Data from the 1988 to 1999 National Hospital Discharge Survey and population estimates from the National Center for Health Statistics were used to calculate biennial rates of VRHD. To control for coding consistency, rates of invasive disease caused by were calculated for the same time period. RESULTS: The rate of VRHD for 1998 to 1999 (4.42 hospitalizations per 100 000 person-years) was the lowest of any of the periods measured, but this difference was not statistically significant. The same was true of VRHD limited to cases with varicella coded as the primary diagnosis. A trend toward a decrease in VRHD was observed in all age groups examined, although none was statistically significant. Calculated rates from this national data set were in agreement with prior studies using active surveillance, and the previously documented fall in hospitalizations caused by invasive disease was demonstrated using these methods. CONCLUSIONS: Although it is uncommon for children with varicella to require hospitalization, these cases are an important contributor to cost and morbidity of varicella. In contrast to predictions of prelicensure mathematical models, there has not been a significant decrease in total or first diagnosis VRHD since the vaccine became available. Current coverage levels are below those used in prelicensure models. Increased acceptance of the varicella vaccine by parents and practitioners may aid in the further decrease of varicella-related hospitalizations.

Hospital-acquired infections caused by viruses are a cause of considerable morbidity and occasional mortality in critically ill neonates. The intensive care environment allows for efficient spread of viral pathogens, and secondary cases among both patients and healthcare workers are frequently observed. We review the common viral causes of hospital-acquired infections in neonates, including rotavirus, respiratory syncytial virus, and others, discuss epidemiology and clinical syndromes, and summarize recommendations for control in outbreak situations. Chemoprophylaxis, isolation procedures, and care of affected staff are also addressed.

The respiratory epithelium provides both a physical and an immunological barrier to inhaled pathogens. In the normal host, innate defences prevent bacteria from activating inflammation by providing efficient muco-ciliary clearance and antimicrobial activity. Bacteria that persist in the airway lumen, as in cystic fibrosis, activate both the professional immune cells in the respiratory mucosa as well as the more abundant airway epithelial cells. As most of the bacteria become entrapped in airway mucin, shed bacterial products such as pili, flagella, peptidoglycan and lipopolysaccharide from lysed bacteria are likely to be the stimuli most important in activating epithelial signalling. The airway cells respond briskly to bacterial components through several signalling systems which activate epithelial expression of pro-inflammatory cytokines and chemokines. These signals recruit neutrophils to the airways where they eliminate the contaminating bacteria causing inflammation and the ensuing clinical signs of infection.

Much of the pulmonary disease in cystic fibrosis is associated with polymorphonuclear leukocyte-dominated airway inflammation caused by bacterial infection. Respiratory epithelial cells express the polymorphonuclear chemokine interleukin-8 (IL-8) in response to ligation of asialylated glycolipid receptors, which are increased on damaged or regenerating cells and those with cystic fibrosis transmembrane conductance regulator mutations. Because both Pseudomonas aeruginosa and Staphylococcus aureus, the most common pathogens in cystic fibrosis, bind asialylated glycolipid receptors such as asialoGM1, we postulated that diverse bacteria can activate a common epithelial signaling pathway to elicit IL-8 expression. P. aeruginosa PAO1 but not pil mutants and S. aureus RN6390 but not the agr mutant RN6911 stimulated increases in [Ca(2+)](i) in 1HAEo- airway epithelial cells. This response stimulated p38 and ERK1/2 mitogen-activated protein kinase (MAPK) signaling cascades resulting in NF-kappaB activation and IL-8 expression. Ligation of the asialoGM1 receptor or thapsigargin-elicited Ca(2+) release activated this pathway, whereas P. aeruginosa lipopolysaccharide did not. The rapid kinetics of epithelial activation precluded bacterial invasion of the epithelium. Recognition of asialylated glycolipid receptors on airway epithelial cells provides a common pathway for Gram-positive and Gram-negative organisms to initiate an epithelial inflammatory response.

We describe a nosocomial rotavirus outbreak among pediatric cardiology patients and the impact of a prospective, laboratory-based surveillance program for rotavirus in our university-affiliated, quartenary-care pediatric hospital in New York City. Improved compliance with infection control and case-finding among patients and healthcare workers halted the outbreak.

Plesiomonas shigelloides is a rare cause of self-limiting gastroenteritis. We report a case of extraintestinal P. shigelloides infection in an adolescent with sickle-cell disease who presented with bacteremia complicated by a splenic abscess. Despite the high mortality rate reported in extraintestinal P. shigelloides infection, the patient survived after drainage of the abscess and treatment with antibiotics.

Airway epithelial cells can respond to infection by activating several signaling pathways. We examined the induction of apoptosis in response to Pseudomonas aeruginosa PAO1 in normal cells and several cystic fibrosis (CF) and corrected cell lines. Epithelial cells in monolayers with tight junctions, confirmed by apical ZO-1 staining demonstrated by confocal microscopy, were entirely resistant to PAO1-induced apoptosis. In contrast, cell lines such as 9HTEo(-) cells that do not form tight junctions were susceptible, with 50% of the population apoptotic after 6 h of exposure to PAO1. CF transmembrane conductance regulator (CFTR) dysfunction caused by different mechanisms (trafficking mutations, overexpression of the regulatory domain or antisense constructs) did not alter rates of apoptosis, nor were differences apparent in terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling detection of apoptotic airway cells from PAO1 infected cftr -/- or control mice. Bacterial expression of specific adhesins, complete lipopolysaccharide, and a functional type III secretion system were all necessary to evoke apoptosis even in susceptible epithelial cells. Unlike other mucosal surfaces, the airway epithelium is highly resistant to apoptosis, and this response is activated only when the appropriate epithelial conditions are present as well as fully virulent P. aeruginosa capable of coordinately expressing both adhesins and cytotoxins.

PMN-dominated airway inflammation is a major component of cystic fibrosis (CF) lung disease. Epithelial cells respond to organisms such as Pseudomonas aeruginosa, the major pathogen in CF, by expressing the leukocyte chemokine IL-8. Experiments were performed using several different types of respiratory epithelial cells that demonstrate that ligation of ceramide-associated receptors on epithelial surfaces by P. aeruginosa pili is a major stimulus for the translocation of transcription factor nuclear factor (NF)-kappaB and initiation of IL-8 expression by epithelial cells. Using electrophoretic mobility shift assays and Western hybridizations, nuclear NF-kappaB was found shortly after epithelial cells were stimulated by either whole organisms, isolated pili, or antibody to the pilin receptor asialoGM1. IB3 cells, which express mutations in cystic fibrosis transmembrane conductance regulator (CFTR) (DeltaF508/W1282X), were noted to have significantly greater amounts of endogenous nuclear NF-kappaB, but not the transcription factor C/EBP, than CF cells corrected by episomal copies of normal CFTR (C-38) or IB3 cells grown at a permissive temperature (25 degreesC). Activation of NF-kappaB and subsequent IL-8 expression in epithelial cells can result from activation of at least two pathways: an exogenous signaling cascade that is activated by ligation of ceramide-associated adhesins such as P. aeruginosa pilin, or endogenous stimulation, suggested to be a consequence of cell stress caused by the accumulation of mutant CFTR in the endoplasmic reticulum.