Pertussis antibodies in postpartum women and their newborns.

OBJECTIVE: To (1) determine the proportion of mothers and infants who had levels of IgG antibody to pertussis antigens predicted to be potentially protective at delivery; (2) evaluate the efficiency of maternal-infant antibody transport; (3) extrapolate infant antibody titers at 6 weeks; and (4) identify maternal factors associated with potentially protective infant antibodies. STUDY DESIGN: Sera from mother-infant pairs from February 2006 through to April 2007 were tested for antibody to pertussis antigens by standardized ELISA (enzyme-linked immunosorbent assay). Potentially protective antibody levels were defined as >5 ELISA units (EU) for pertussis toxin (PT), and >10 EU for fimbriae (FIM) and pertactin (PRN). Serological evidence of previous maternal infection was defined from antibody to four antigens by k-means cluster analysis. RESULT: In total, 21% (17/81) of mothers and 26% (21/81) of infants had potentially protective antibody levels at delivery. Mean infant-maternal antibody ratios for PT, FIM and PRN were 1.26, 1.36 and 1.31, respectively. At 6 weeks, 11% (9/81) of infants were predicted to have potentially protective antibody levels. Using cluster analysis, 9% (7/81) of mothers had evidence of previous pertussis infection. Infants born to these mothers were predicted to be more likely to have potentially protective antibodies at 6 weeks (43%) than those born to mothers without previous infection (8%) (P=0.03). CONCLUSION: Approximately 75% of infants were born with pertussis antibody levels lower than the modest levels associated with potential protection. Despite effective antibody transfer, nearly 90% of infants were predicted to have little antibody by 6 weeks. Maternal immunization before or during pregnancy might simulate previous pertussis infection and help protect infants through the first months of life.

Continued early onset group B streptococcal infections in the era of intrapartum prophylaxis.

OBJECTIVE: The objective of the study was to determine the rate of early onset group B streptococcus (EOGBS) infection in Utah and identify potential areas of failure in EOGBS prevention. STUDY DESIGN: We queried the microbiology records of Intermountain Healthcare for infants with culture-confirmed EOGBS between 1 January 2002 and 31 May 2006 and calculated rates of EOGBS per 1000 deliveries. We reviewed the infant and maternal records of each EOGBS case to identify possible failures in EOGBS prevention. RESULT: There were 54 cases of EOGBS among the 127 205 births (0.42/1000 births). Of all, 12 were preterm. Of the 39 (93%) women prenatally screened for GBS, 31 (79%) had negative results and 7/8 (88%) women with positive prenatal GBS screens either did not receive intrapartum antibiotic prophylaxis (IAP) or received inadequate IAP. Of the 54 infants with EOGBS, 3 (6%) died. CONCLUSION: Utah's rates of EOGBS were higher than the national average. Factors associated with EOGBS include missed screening opportunities, inadequate IAP, and false-negative maternal GBS culture.

Invasive serotype a Haemophilus influenzae infections with a virulence genotype resembling Haemophilus influenzae type b: emerging pathogen in the vaccine era?

OBJECTIVE: Haemophilus influenzae type b causes severe disease in nonimmune infants and young children; other serotypes are uncommon pathogens and thought to have low virulence. Some have hypothesized that with the virtual elimination of H influenzae type b, other serotypes might acquire virulence traits and emerge as important pathogens of children. We describe the clinical, epidemiologic, and molecular biologic features of 5 cases of severe disease attributable to Haemophilus influenzae type a. METHODS: After observing 4 cases of invasive disease caused by H influenzae type a, we reviewed microbiology records at 3 reference laboratories that perform all serotyping in Utah and surveillance databases. Strains of H influenzae type a and control strains were examined by Southern blotting with the use of the cap probe pUO38 and by pulsed-field gel electrophoresis. The putative virulence mutation, the IS1016-bexA deletion, was detected by polymerase chain reaction amplification and sequencing. RESULTS: During a 10-month period, we observed 5 children with severe invasive disease caused by H influenzae type a. No isolates of H influenzae type a had been submitted to the reference laboratories between 1992 and 1998. The median age of patients was 12 months (range: 6-48 months). Four of 5 had meningitis and bacteremia; 1 had purpura fulminans. Three isolates, representing 1 of 2 pulsed-field gel electrophoresis patterns, contained the IS1016-bexA deletion and were associated with particularly severe disease. CONCLUSIONS: We describe an unusual cluster of severe disease caused by H influenzae type a that resembles the clinical and epidemiologic features of H influenzae type b disease. Our data support the hypothesis that the IS1016-bexA deletion may identify more virulent strains of H influenzae. Haemophilus influenzae, epidemiology, virulence, serotyping, pathogenicity.

An examination of the unintended consequences of the rule-out sepsis evaluation: a parental perspective.

In order to document unintended consequences of the "rule-out" sepsis (ROS) evaluation, a survey of parents of infants who had undergone such an evaluation at Primary Children's Medical Center in 1997 was conducted. Sixty parents were interviewed. Parental perceptions of the sepsis evaluation and its impact on their families were recorded. Specific data evaluated included parental anxiety, impact on breastfeeding, perceived complications, financial stress, and parental preferences. The majority of parents found the ROS evaluation very stressful. Parental perception of illness increased significantly after being told the infant would require an ROS evaluation, with nearly 30% of parents, after speaking with a physician, believing their infant might die. Breastfeeding problems were reported by 36% of the mothers. Iatrogenic complications were reported by 33%. Although all infants were covered by some form of insurance, 43% of parents reported financial stress. Forty-two percent of parents would have preferred to be treated at home and all parents would prefer an evaluation that could be accomplished in 24 hours. We conclude that unintended consequences of the ROS evaluation included excessive parental anxiety, cessation of breastfeeding, iatrogenic complications, and financial stress. Suggestions to decrease these adverse consequences are given.

A polymerase chain reaction-based epidemiologic investigation of the incidence of nonpolio enteroviral infections in febrile and afebrile infants 90 days and younger.

OBJECTIVE: Enteroviruses are important pathogens in infants, but their true contribution to febrile illness in infants

Enhancement of the AMPLICOR enterovirus PCR test with a coprecipitant.

The incorporation of a commercially available coprecipitant into the AMPLICOR enterovirus PCR test specimen preparation enhanced the sensitivity and reproducibility of this assay. Fifty-five previously tested archived cerebrospinal fluids (CSF) specimens were tested in a blind study in duplicate with and without Pellet Paint coprecipitant (Novagen, Inc., Madison, Wis.). Of these specimens, 26 had previously been determined to be positive and 29 had previously been determined to be negative. All previously positive CSF specimens were positive when Pellet Paint was used and only 18 were positive without Pellet Paint. No previously negative specimens were positive on repeat testing with or without Pellet Paint. The background signal was not affected by the addition of Pellet Paint. These data support the utility of a coprecipitant in minimizing false-negative results.

Sepsis evaluations in hospitalized infants with bronchiolitis.

OBJECTIVES: To define variation in the decision to perform a sepsis evaluation in hospitalized infants with bronchiolitis, to define predictors of the decision and to measure the clinical and cost outcomes. METHODS: Retrospective chart review of all nonintensive care unit infants < or = 60 days with any discharge diagnosis of bronchiolitis (n = 282 from 1993 to 1995 in a 232-bed pediatric hospital. Process variables included temperature at sepsis work-up or Tmax if no sepsis workup. Outcome variables were charges, length of stay, sepsis workup and serious bacterial infection. RESULTS: There was no difference in mean temperature between groups with or without sepsis evaluation (38.1 degrees C, P = 0.75). Of 282 infants 140 had a sepsis workup; 5 (1.8%) had serious bacterial infection. Infants with sepsis workup had an average total charge of $4507 and length of stay of 3.4 days compared with $2998 and 2.8 days for those without (P = 0.0001 and P = 0.002, respectively). A multivariate logistic regression model was constructed with sepsis workup as the dichotomous dependent variable. Significant (P < or = 0.05) predictor variables with a positive coefficient were: higher bronchiolitis score and normal chest roentgenogram. Significant variables with a negative coefficient were: admission diagnosis of bronchiolitis, chest roentgenogram typical for bronchiolitis and age > 28 days. CONCLUSIONS: Temperature was not a predictor of sepsis evaluation. Infants with respiratory distress and normal chest roentgenogram were more likely to receive sepsis evaluations; those with recognized typical bronchiolitis and those > 28 days of age were less likely. Risk of serious bacterial infection is low; the costs of a sepsis evaluation outweigh the benefits in infants with obvious bronchiolitis.

Entamoeba histolytica: computer-assisted modeling of phosphofructokinase for the prediction of broad-spectrum antiparasitic agents.

Pyrophosphate-dependent phosphofructokinase (PPi-PFK) is the rate-limiting glycolytic enzyme found in the pathogenic protists Entamoeba histolytica, Giardia lamblia, Toxoplasma gondii, Trichomonas vaginalis, and Naegleria fowleri. The enzyme differs significantly from ATP-dependent phosphofructokinases found in humans and as such represents an important drug target. Current therapy for infections caused by these pathogens is inadequate, especially for children, pregnant women, and the immune compromised. The development of more selective, safer agents in imperative, as parasitic infections are currently a significant health threat worldwide and will likely become increasingly common agents of disease in the future. For the purpose of designing drugs to treat parasitic infections, we have constructed a model of PPi-PFK from E. histolytica based on the three-dimensional structure of the ATP-dependent PFK from Bacillus stearothermophilus. The model was used with the computer program Dock 3.5 (University of California, San Francisco) to predict the binding of pyrophosphate and selected bisphosphonates to the enzyme. The predicted drug-enzyme interactions suggested that two of these compounds would be competitive inhibitors of pyrophosphate. These drugs were tested against E. histolytica and inhibited the growth of amebae in vitro. This class of compounds may have broad-spectrum antiparasitic activity and, in the future, may facilitate the treatment of serious parasitic infections.