Comparison of molecular detection methods for pertussis in children during a state-wide outbreak.

A state-wide pertussis outbreak occurred in Washington during the winter-spring months of 2012, concurrent with respiratory viral season. We compared performance characteristics of a laboratory-developed pertussis PCR (LD-PCR for Bordetella pertussis, Bordetella parapertussis, and Bordetella holmesii) and rapid multiplex PCR (RM-PCR) for respiratory viruses (FilmArray™, BioFire, B. pertussis data unblinded following FDA approval post outbreak). We analyzed three cohorts of patients using physician testing orders as a proxy for clinical suspicion for pertussis or respiratory viruses: Cohort 1, tested by LD-PCR for pertussis pathogens only by nasopharyngeal swab; Cohort 2, by RM-PCR for respiratory viruses only by mid-nasal turbinate swab; and Cohort 3, by both methods. B. pertussis was detected in a total of 25 of the 490 patients in Cohort 3 in which LD-PCR detected 20/25 (80 %) cases and the RM-PCR detected 24/25 (96 %; p = 0.2). Pertussis pathogens were detected in 21/584 (3.6 %) of samples from Cohort 1 where clinicians had a relatively strong suspicion for pertussis. In contrast, B. pertussis was detected in only 4/3071 (0.1 %) specimens from Cohort 2 where suspicion for pertussis was lower (p < 0.001 for comparison with Cohort 1). In summary, the two laboratory methods were comparable for the detection of B. pertussis.

Hepatitis due to human herpesvirus 6B after hematopoietic cell transplantation and a review of the literature.

Human herpesvirus 6B (HHV-6B) is an opportunistic pathogen associated with a growing number of complications in immunocompromised patients. Multiple reports of HHV-6B-associated hepatitis following primary HHV-6 infection and liver transplantation have appeared, but this has only been well documented in 1 patient after hematopoietic cell transplantation (HCT). This report describes a case of acute hepatitis likely caused by HHV-6B in an HCT recipient who was successfully treated with ganciclovir. HHV-6B DNA was demonstrated in plasma and hepatic tissue using quantitative polymerase chain reaction and immunohistochemical stains. Chromosomal integration was ruled out. We review the literature reporting HHV-6B-associated hepatitis, which may be an underappreciated cause of liver disease after HCT.

Human herpesvirus 6B reactivation and delirium are frequent and associated events after cord blood transplantation.

Human herpesvirus 6B (HHV-6B) frequently reactivates after cord blood transplantation (CBT). We previously reported an association between HHV-6B reactivation and delirium after hematopoietic cell transplantation. In this prospective study, 35 CBT recipients underwent twice-weekly plasma PCR testing for HHV-6 and thrice-weekly delirium assessment until day 84. There was a quantitative association between HHV-6B reactivation and delirium in univariable (odds ratio, 2.88; 95% confidence interval (CI), 0.97-8.59) and bivariable models. In addition, intensified prophylaxis with high-dose valacyclovir mitigated HHV-6B reactivation (adjusted hazard ratio, 0.39; 95% CI, 0.14-1.08). Larger trials are needed to explore the utility of HHV-6B prophylaxis after CBT.

A trade-off analysis of routine newborn circumcision.

BACKGROUND: The risks associated with newborn circumcision have not been as extensively evaluated as the benefits. OBJECTIVES: The goals of this study were threefold: 1) to derive a population-based complication rate for newborn circumcision; 2) to calculate the number needed to harm for newborn circumcision based on this rate; and 3) to establish trade-offs based on our complication rates and published estimates of the benefits of circumcision including the prevention of urinary tract infections and penile cancer. METHODS: Using the Comprehensive Hospital Abstract Reporting System for Washington State, we retrospectively examined routine newborn circumcisions performed over 9 years (1987-1996). We used International Classification of Diseases, Ninth Revision codes to identify both circumcisions and complications and limited our analyses to children without other surgical procedures performed during their initial birth hospitalization. RESULTS: Of 354, 297 male infants born during the study period, 130,475 (37%) were circumcised during their newborn stay. Overall 287 (.2%) of circumcised children and 33 (.01%) of uncircumcised children had complications potentially associated with circumcision coded as a discharge diagnosis. Based on our findings, a complication can be expected in 1 out every 476 circumcisions. Six urinary tract infections can be prevented for every complication endured and almost 2 complications can be expected for every case of penile cancer prevented. CONCLUSIONS: Circumcision remains a relatively safe procedure. However, for some parents, the risks we report may outweigh the potential benefits. This information may help parents seeking guidance to make an informed decision.

A case-control study of necrotizing fasciitis during primary varicella.

OBJECTIVE: An increase in the incidence of necrotizing fasciitis (NF) occurring in previously healthy children with primary varicella was noted in the Washington State area between December 1993 and June 1995. Our objective was to investigate ibuprofen use and other risk factors for NF in the setting of primary varicella. METHODS: Case-control study. Demographic information, clinical parameters, and potential risk factors for NF were compared for cases and controls. Cases of NF were analyzed to identify potential determinants of NF complicated by renal insufficiency and/or streptococcal toxic shock syndrome. Multivariate logistic regression was used to evaluate the association between ibuprofen use and NF. A case was defined as a child with NF hospitalized within 3 weeks of primary varicella (n = 19). Controls were children hospitalized with a soft tissue infection other than NF within 3 weeks of primary varicella (n = 29). Odds ratios (ORs) of ibuprofen, as well as other potential risk factors were evaluated. In addition, demographic and clinical data as well as other potential risk factors were compared between cases and controls. RESULTS: After controlling for gender, age, and group A streptococcus isolation, cases were more likely than controls to have used ibuprofen before hospitalization (OR, 11. 5; 95% confidence interval, 1.4 to 96.9). In most children, ibuprofen was initiated after the onset of symptoms of secondary infection. Children with NF complicated by renal insufficiency and/or streptococcal toxic shock syndrome were more likely than children with uncomplicated NF to have used ibuprofen (OR, 16.0; 95% confidence interval, 1.0 to 825.0). Children with complicated NF also had a higher mean maximum temperature (40.9 degrees C vs 39.3 degrees C), and a longer mean duration of secondary symptoms (1.7 days vs 0.6 days) before admission than children with uncomplicated NF. CONCLUSION: Ibuprofen use was associated with NF in the setting of primary varicella. Additional studies are needed to establish whether ibuprofen use has a causal role in the development of NF and its complications during varicella.

Predictors of physician compliance with a published guideline on management of febrile infants.

BACKGROUND: Previous studies have demonstrated clinicians' poor compliance with published management strategies and protocols, but the reasons why physicians often choose to vary their management of the febrile infant from published guidelines are poorly understood. OBJECTIVE: We conducted a study of physicians to learn more about the issues that influence their decisions in the management of febrile infants. METHODS: A survey study of pediatricians, emergency physicians and family physicians randomly selected from a list of licensed physicians in the United States. Chi square and Kruskal-Wallis tests were used to measure differences in responses by specialty. Odds ratios from logistic regression were used to measure differences in compliance with a recently published guideline. RESULTS: We received 193 completed surveys from pediatricians, 177 from emergency physicians and 104 from family physicians. After controlling for other variables, odds for compliance with a recently published guideline were higher for pediatricians [odds ratio (OR) = 9.13] and emergency physicians (OR = 2.5) than for family physicians (P < 0.001). Factors associated with decreased odds of compliance included more years since graduation from medical school (OR = 0.93), a higher proportion of office visits by children < 1 year of age (OR = 0.97) and increased comfort diagnosing serious bacterial illness (OR = 0.35). Factors associated with increased odds of compliance included a higher perceived likelihood of serious bacterial illness in febrile infants (OR = 1.01) and better reported knowledge of the recently published guideline (OR = 2.01). CONCLUSIONS: We found that specialty as well as other factors were associated with physician compliance with a recently published guideline. This information may facilitate guideline development and implementation by providing a better understanding of what motivates physicians in their clinical decision making.

Providers' perceptions of an immunization registry.

OBJECTIVE: To determine providers' perceptions of a statewide immunization registry. DESIGN: Mail survey. SETTING: King County, Washington. METHODS: A random sample of 700 pediatricians, family physicians, and RN/NPs were surveyed. In addition to their perceptions of registries, respondents reported their immunization procedures in the absence of immunization histories. RESULTS: Of 544 eligible participants, 344 returned surveys (63% response rate). Seventy-seven percent of RN/NPs, 60% of pediatricians and 47% of family physicians (p < 0.001) responded that they thought that electronic immunization registries represented the "best chance to solve the lack of documentation problem." Fifty-seven percent of RN/NPs, 61% of pediatricians, and 43% of family physicians reported that the incompleteness of registry data presented a barrier to their using one (p < 0.01). Fewer than 14% of all specialties had concerns about potential compromises of patient confidentiality as a result of registries, although RN/NPs were more concerned about this possibility than both pediatricians and family physicians (p = 0.02). In a multivariate analysis, pediatricians were 43% less likely (p = 0.15) and family physicians were 73% less likely (p < 0.01) than RN/NPs to think registries are the solution to the lack of documentation problem. Familiarity with the existing registry was associated with a significant decrease in the likelihood of thinking that registries are the solution (OR .49 [.26-.90]) and an increase in the likelihood of thinking that registries will take a long time to become of practical value (OR 2.21 [1.09-4.29]). CONCLUSIONS: Specialties differ with respect to their opinions regarding the promise immunization registries hold. Immunization registries appear to be well regarded in theory but may disappoint in practice. Incompleteness of immunization data may be the largest obstacle for registries to overcome.

Advances in antiviral therapy.

Multiple agents for the treatment and prevention of viral illnesses have been developed during the past few years. While in many cases this has been in direct response to the human immunodeficiency virus type 1 epidemic, a number of new antiviral agents are relevant to the practice of general pediatrics. This article reviews recent advances in the therapy of some common and a few unusual viral illnesses of children. The indication and efficacy of the newly developed agents valacyclovir, famciclovir, cidofovir, oral and intraocular ganciclovir, adefovir, respiratory syncytial virus immune globulin, palivizumab, and imiquimod are discussed, as well new uses of acyclovir, lamivudine, and ribavirin. Many of the antivirals discussed, including valacyclovir and cidofovir, have not yet been studied in children, but they hold promise for improving the treatment of pediatric viral infections.

Circadian fluctuations of period protein immunoreactivity in the CNS and the visual system of Drosophila.

When the protein encoded by the period (per) gene, which influences circadian rhythms in Drosophila melanogaster, was labeled with an anti-per antibody in adult flies sectioned at different times of day, regular fluctuations in the intensity of immunoreactivity were observed in cells of the visual system and central brain. These fluctuations persisted in constant darkness. Time courses of the changing levels of staining were altered in the per-short mutant: in light/dark cycles, the phase was earlier than in wild-type, and in constant darkness the period was shorter. In a per-long mutant and in behaviorally subnormal germline transformants (involving transduced per DNA), staining intensities were much fainter than in wild-type. Factors involved in initiating or maintaining the per protein cycling were investigated by examining the immunoreactivity in visual system mutants and by exposing wild-type flies to altered light/dark regimes. These genetic and environmental manipulations affected the expression of the per protein in ways that usually parallelled their effects on circadian behaviors.

Introduction of the new Centers for Disease Control and Prevention group B streptococcal prevention guideline at a large West Coast health maintenance organization.

OBJECTIVE: Our purpose was to assess the impact of new consensus guidelines issued by the Centers for Disease Control and Prevention, The American College of Obstetricians and Gynecologists, and the American Academy of Pediatrics to prevent perinatal group B streptococcal disease. STUDY DESIGN: We performed a descriptive analysis and a before-and-after analysis of implementation of the group B streptococcal disease prevention guidelines among singleton-birth pregnancies in 2 Group Health Cooperative hospitals from October 1, 1995, through December 31, 1997. We studied the speed and completeness of implementation and the effect on pregnancy care practices including intrapartum antibiotic use, test ordering, and maternal and neonatal health. RESULTS: Guideline implementation occurred rapidly. The proportion of term pregnancies screened according to the guideline increased markedly, and overall intrapartum antibiotic use more than doubled. Among group B streptococci-positive women, intrapartum antibiotic prophylaxis increased from 24% before to 74% after guideline implementation. Median duration of treatment before delivery increased from 1.8 to 4.3 hours. The rate of rash did not increase, and there were no cases of anaphylaxis or pseudomembranous colitis. The proportion of infants undergoing evaluation decreased after implementation of the neonatal guidelines; among infants of group B streptococci-negative women, test ordering dropped by almost 40%. CONCLUSIONS: Implementation of the new guidelines is feasible and can be accomplished rapidly. The guidelines were associated with increased maternal intrapartum antibiotic use, particularly among women at highest risk, and with a decrease in laboratory use for infants.

Sensitive method for detection of human herpesviruses 6 and 7 in saliva collected in field studies.

To facilitate studies of the epidemiology and natural history of human herpesviruses 6 and 7 in infants, a practical method for collecting and quantifying the DNA of these viruses was developed. Saliva was collected using small strips of filter paper, and virus was detected using a real-time quantitative fluorescent-probe PCR assay. The sensitivity and specificity of this method even after prolonged drying of the specimens compared favorably to those of our traditional method of collecting and assaying saliva.

Human herpesvirus 6 reactivation and encephalitis in allogeneic bone marrow transplant recipients.

To determine whether receipt of an investigational anti-CD3 monoclonal antibody (BC3) increased the risk of human herpesvirus 6 (HHV-6) reactivation and development of encephalitis in bone marrow transplant (BMT) recipients, persons who had and had not received BC3 were compared. Odds of HHV-6 reactivation were higher among BC3 recipients than among control patients (odds ratio, 2.5; 95% confidence interval [CI], 1.3-4.7). In addition, BC3 recipients were more likely than control patients to develop encephalitis (risk ratio [RR], 3.5; 95% CI, 1.3-9.5), and this association followed a BC3 dose-dependent relationship (P=.03, by Mantel-Haenszel chi(2) test). In a multivariable model, HHV-6 reactivation and receipt of BC3 were associated with increased risk of encephalitis (RR, 5.4; 95% CI, 1.9-15.3, and RR, 3.3; 95% CI, 1.2-9.1, respectively). In conclusion, both HHV-6 reactivation and receipt of BC3 for prophylaxis of acute graft-versus-host disease independently increased the risk of encephalitis in allogeneic BMT recipients. Prospective studies to better define the relationship between HHV-6 reactivation and encephalitis in allogeneic BMT recipients are warranted.