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.

Evaluation of the roche AMPLICOR enterovirus PCR assay in the diagnosis of enteroviral central nervous system infections.

BACKGROUND: Enteroviruses cause a substantial number of cases of aseptic meningitis annually in the USA. While culture has been useful in the detection of patients with viral meningitis it is time-consuming and lacks sensitivity. Detection of viral nucleic acid in patient specimens has been demonstrated to improve enteroviral detection. OBJECTIVES: A research use only commercial amplification assay, the Roche AMPLICOR EV test, was compared to culture for the diagnosis of enteroviral meningoencephalitis. STUDY DESIGN: Four-hundred and sixty-five consecutive CSF samples sent prospectively for suspicion of enteroviral infection were evaluated by PCR and shell-vial culture. Clinical information and CSF analysis were used to resolve PCR positive, culture negative samples. Sensitivity and specificity were calculated using resolved data. RESULTS: There were 138 samples which met the definition of a true positive. Of these culture detected 77 (sensitivity 55.8%) and PCR detected 136 (sensitivity 98.6%). PCR missed two culture positive samples. Upon repeat testing, these CSF samples were found to contain inhibitors. CONCLUSIONS: The Roche AMPLICOR EV-PCR test was statistically more sensitive than culture (P<0.001) in the detection of enteroviruses in CSF in patients suspected of having enteroviral meningitis. This assay also has the advantage of a rapid turnaround time of 5-6 h compared to 3-5 days for culture.

Bacillus cereus infections among oncology patients at a children's hospital.

BACKGROUND: Bacillus cereus can cause severe infections in immunocompromised persons. METHODS: We report 3 cases of bacteremia/septicemia (1 fatal) among oncology patients in a children's hospital. Because all cases occurred during a 10-day period, a common source outbreak was suspected. An epidemiologic investigation was performed. Molecular comparison of patient and environmental isolates was performed by using pulsed-field gel electrophoresis. RESULTS: After an extensive investigation, no common hospital source could be found. Pulsed-field gel electrophoresis proved that the isolates were not related. CONCLUSION: Sporadic infections in immunocompromised persons do occur and can be associated with significant morbidity.

Yersinia enterocolitis mimicking Crohn's disease in a toddler.

A 31/2-year-old girl presented with persistent abdominal pain, fever, vomiting, and diarrhea accompanied by rash, oral ulceration, anemia, and an elevated sedimentation rate. Initial evaluation revealed no pathogens and was extended to include abdominal ultrasound and computed tomography showing marked ileocecal edema and mesenteric adenopathy. Colonoscopy revealed focal ulceration from rectum to cecum with histology of severe active colitis with mild chronic changes. Enteroclysis demonstrated a nodular, edematous terminal ileum. Because of the patient's clinical deterioration despite antibiotics, these features were construed consistent with Crohn's disease, and glucocorticoid therapy was begun. By the ninth hospital day, admission cultures grew Yersinia enterocolitica, and trimethoprim/sulfamethoxazole was begun followed by prompt clinical improvement. The delay in diagnosis afforded an unusually comprehensive clinical description of the presentation and diagnosis of Yersinia enterocolitis in childhood.

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.

Investigation of a measles outbreak in a fully vaccinated school population including serum studies before and after revaccination.

A measles outbreak in early 1989 among approximately 4200 students at a high school and two intermediate schools in suburban Houston, TX, was investigated to evaluate reasons for vaccine failure and to predict the efficacy of a booster dose of measles vaccine. Seventy-seven cases occurred (71 at the high school, 6 at intermediate schools; attack rate, 3.2 and 0.3%, respectively). Vaccination in the first year of life an 13 to 14 years since last vaccination were independent risk factors for being a case. Forty-three (18%) of 239 sera collected from students just before revaccination during the outbreak were negative by enzyme immunoassay; a neutralization assay confirmed these 43 lacked antibody predicting protection against measles infection. Of 43 enzyme immunoassay-negative students 24 gave another blood sample 9 to 10 months after revaccination. Revaccination appeared to reduce the portion of all students with neutralization titers predicting susceptibility to measles illness with rash from 7.9% to 3.0% and left the portion predicted to be susceptible to illness without rash unchanged (45%).