Clinical Manifestations and Molecular Characterization of Pertactin-Deficient and Pertactin-Producing Bordetella pertussis in Children, Philadelphia 2007-2014.

BACKGROUND: Bordetella pertussis strains lacking expression of pertactin, a bacterial adhesin and vaccine target, are emerging. There are limited data on disease manifestations of mutant strains in children. We sought to compare clinical manifestations of pertactin-deficient and pertactin-producing B. pertussis infection in infants and describe corresponding molecular characteristics. METHODS: Molecular characterization of archived B. pertussis isolates (collected January 2007 to March 2014) included Western blot analysis, pulsed-field gel electrophoresis (PFGE), polymerase chain reaction, and pertactin gene sequencing. Medical record review compared epidemiologic and clinical courses of pertactin-producing and pertactin-deficient B. pertussis infections. RESULTS: Sixty of 72 B. pertussis isolates were viable for analysis. Within the cohort of infants, the median age was 95 days, 90% received ≤1 dose of vaccine, and 72% were hospitalized. Pertactin deficiency was first noted in 2008, and its prevalence increased over time (68% overall prevalence). There were no statistically significant differences in presenting symptoms or signs, hospitalization, intensive care, respiratory support, or laboratory results related to pertactin expression. Illness length was shorter in pertactin-deficient group (mean difference, 3.2 days; P = .04); no difference was noted in the subgroup of infants <4 months old. Molecular analyses identified 11 PFGE profiles (Centers for Disease Control and Prevention profile No. 002 predominant, 47%). In 41 pertactin-deficient strains, sequencing identified 2 stop codon and 3 IS481 locations disrupting the prn gene. Mutations and nucleotide positions were not unique to PFGE type, nor were they clustered in time. CONCLUSIONS: In this cohort of predominantly unimmunized infants, clinical disease did not differ between infection with pertactin-deficient and those with pertactin-producing B. pertussis. Molecular analyses demonstrated remarkable PFGE strain diversity, with multiple mechanisms and molecular sites of pertactin inactivation.

Variation in pediatric and adolescent electronic health data sharing practices under the 21st Century Cures Act.

OBJECTIVE: To describe real-world practices and variation in implementation of the Information Blocking provisions amongst healthcare organizations caring for pediatric patients. MATERIALS AND METHODS: An online survey regarding implementation practices was distributed to representatives from 10 participating US healthcare organizations located in 6 different states. The survey was followed by structured interviews conducted through video conference. Information was gathered about implementation practices at each organization, with a focus on patient and proxy portal access to, and segmentation capabilities of, certain data classes listed in the United States Core Data for Interoperability Version 1. RESULTS: All organizations had implemented the information blocking provisions at their institution. All organizations utilized different portal account types for proxies and users. All organizations reported the capability of sharing labs, medications, problem lists, imaging, and notes with the parent/guardian of the non-adolescent minor user with differences in how sensitive elements within the data classes were protected. Variability existed in how data was shared with the remaining user types. DISCUSSION: Significant variability exists in how organizations have implemented the information blocking rules. Variation in data sharing and data access between institutions can result in privacy breaches and create confusion about completeness of data for patients and families. CONCLUSION: Healthcare organizations have utilized varying strategies to comply with the information blocking provisions of the 21st Century Cures Act. Increased clarity from the Office of the National Coordinator for Health Information Technology on minor, adolescent, and caregiver privacy and improved segmentation capabilities from Electronic Health Record vendors is needed.

Antimicrobial Susceptibility and Molecular Detection of Pertactin-producing and Pertactin-Deficient Bordetella pertussis.

Resurgence of Bordetella pertussis in recent years in the United States has coincided with a dramatic rise in pertactin-deficient strains. Limited data exist on detectability by nucleic acid amplification testing and antimicrobial susceptibility of pertactin-deficient B. pertussis. This study compares 15 pertactin-producing and 15 pertactin-deficient B. pertussis isolates. Pertactin-producing and pertactin-deficient strains were equally detected by nucleic acid amplification testing and were susceptible to antibiotics.

A 12-year-old African American girl with subacute bilateral ophthalmoplegia.

A twelve-year-old African-American female presented with two week history of progressively worsening headache and fatigue, and vision difficulties for the past week. The physical examination was normal. The neurological evaluation was normal, except for cranial nerves (CN) testing, which showed bilateral restriction of adduction (CN III) and up gaze (CN IV) motions, vertical nystagmus, and left side facial paresis of central origin (CN VII). The bilateral exotropia and ophthalmoplegia are characteristics of WEBINO (Wall-Eyed Bilateral Intranuclear Ophthalmoplegia) syndrome, associated to a brain stem structural lesion. The following causes were evaluated and ruled out: tumor, infection, ischemic stroke, non-infectious inflammation. Pediatric Acquired Demyelinating Syndromes were then considered. Neuromyelitis Optica was ruled out in the absence of neuritis and normal spinal cord MRI. The differential diagnosis between Clinically Isolated Syndrome and Acute Demyelinating Encephalomyelitis, causing an isolated brain stem syndrome, is discussed.

Herpes simplex virus infection in young infants during 2 decades of empiric acyclovir therapy.

OBJECTIVE: To describe the clinical presentation of HSV-infected young infants and to seek distinctive features that could permit a targeted approach to empiric use of acyclovir. METHODS: Case study of neonatal HSV during a 22-year period of an institutional strategy of consistent use of acyclovir empirically in all infants with onset of an illness at ≤ 21 days of age for which antibiotics were given empirically. Multiple sources were used to optimize HSV case data, and to estimate the rate of HSV infection in empirically treated infants. RESULTS: A total of 32 infants with perinatally acquired HSV infection were identified. All received acyclovir empirically at admission. At presentation, 50% of infants had only nonspecific complaints, which was fever in 75%. After testing, 75% of infants with HSV had central nervous system (CNS) infection, including 40% who presented with mucocutaneous lesions, 83% with seizures, and 94% with nonspecific complaints. Cerebrospinal fluid (CSF) polymerase chain reaction confirmed CNS infection in 16 of 22 (73%) patients tested. Cultures of mucocutaneous lesion yielded HSV in 8 of 10 cases, but culture of CSF was negative in all 26 cases tested, and screening cultures of unaffected mucosal sites were the only HSV-confirmatory test in a single patient. Laboratory and CSF findings were not distinctive in patients with HSV. Age of ≤ 21 days at onset of symptoms captured 90% of all infants with HSV and 94% of those with nonspecific complaints. An estimated 1.3% of empirically treated patients had HSV infection. CONCLUSIONS: Early manifestations of perinatally acquired HSV are frequently nonspecific, yet CNS infection is common. Empiric acyclovir strategy narrowly restricted to infants with onset of illness at ≤ 21 days of age, who would receive antibiotics empirically, captured 90% of HSV cases and anticipated a rate of HSV CNS infection similar to that of bacterial meningitis.