Time-motion observations to characterize the developmental environment in a paediatric post-acute care hospital.

BACKGROUND: Chronically hospitalized children are at risk for neurodevelopmental delay, compounded by restricted social interactions, movement and environmental stimulation. We measured patients' movements and interactions to characterize developmentally relevant aspects of our inpatient environment and identify opportunities for developmental enrichment. METHODS: As part of a quality improvement initiative to inform neurodevelopmental programming for children with medical complexity at our paediatric post-acute care specialty hospital, we conducted >232 hours of time-motion observations. Trained observers followed 0- to 5-year-old inpatients from 7 am to 7 pm on weekdays, categorizing observations within five domains: Where, With, Position, State and Environment. Observations were collected continuously utilizing REDCap on iPads. A change in any domain initiated a new observation. RESULTS: Patients were median 1 year and 8 months of age (range 2 months to 3 years 9 months) with a median length of hospitalization of 514 days (range 66-1298). In total, 2636 unique observations (or median 134 observations per patient-day [range 95-210]) were collected. Patients left their rooms up to 4 times per day for median 1 h and 34 min (range 41 min to 4 h:30 min). Patients spent 4 h:6 min (2 h:57 min to 6 h:30 min) interacting with someone and 3 h:51 min (57 min to 6 h:36 min) out of bed each day. Patients were simultaneously out of their beds, interacting with someone and awake for 2 h:21 min (51 min to 4 h:19 min) each day. CONCLUSIONS: Despite a care model prioritizing time out of bed and social interaction, time-motion observations indicate patients spent many of their waking hours in bed and alone. Quantifying our inpatients developmental opportunities will inform neurodevelopmental programming initiatives.

A 5-Year-Old With Fever, Headache, Neck Stiffness, and Leg Pain.

A 5-year-old boy presented with fever, headache, fatigue, neck stiffness, and 2 episodes of nocturnal urinary incontinence, prompting a visit to the emergency department. He had experienced intermittent frontal headaches and leg and buttock pain for several months, which had worsened over the previous 2 weeks. His history was notable for a spinal hemangioma with vascular tract, but he was otherwise healthy. On examination, he was febrile and tachycardic. He held his neck slightly rotated to the right with limited range of motion in all directions due to pain. No focal neurologic deficits were noted, and sensation and deep tendon reflexes were intact bilaterally. He was able to bear weight on both legs. There was no spinal tenderness or limitation in range of motion of his back and hips. There were no cutaneous manifestations, including no sacral dimple. A complete blood count with differential revealed leukocytosis of 31.98 × 103/µL (78.6% neutrophils, 16% bands). C-reactive protein was elevated at 2.4 mg/dL (0-1 mg/dL), and serum electrolytes, liver function tests, uric acid, and lactate dehydrogenase were within normal limits for age. Blood cultures were obtained before admission. Here we present his case, diagnostic evaluation, ultimate diagnosis, and complications.

Prevention of Recurrent Staphylococcal Skin Infections.

Staphylococcus aureus infections pose a significant health burden. The emergence of community-associated methicillin-resistant S aureus has resulted in an epidemic of skin and soft tissue infections (SSTI), and many patients experience recurrent SSTI. As S aureus colonization is associated with subsequent infection, decolonization is recommended for patients with recurrent SSTI or in settings of ongoing transmission. S aureus infections often cluster within households, and asymptomatic carriers serve as reservoirs for transmission; therefore, a household approach to decolonization is more effective than measures performed by individuals alone. Novel strategies for the prevention of recurrent SSTI are needed.

Contamination of environmental surfaces with Staphylococcus aureus in households with children infected with methicillin-resistant S aureus.

IMPORTANCE: Household environmental surfaces may serve as vectors for the acquisition and spread of methicillin-resistant Staphylococcus aureus (MRSA) among household members, although few studies have evaluated which objects are important reservoirs of MRSA. OBJECTIVES: To determine the prevalence of environmental MRSA contamination in households of children with MRSA infection; define the molecular epidemiology of environmental, pet, and human MRSA strains within households; and identify factors associated with household MRSA contamination. DESIGN, SETTING, AND PARTICIPANTS: Fifty children with active or recent culture-positive community-associated MRSA infection were enrolled from 2012 to 2013 at St Louis Children's Hospital and at community pediatric practices affiliated with the Washington University Pediatric and Adolescent Ambulatory Research Consortium in St Louis, Missouri. MAIN OUTCOMES AND MEASURES: Samples of participants' nares, axillae, and inguinal folds were cultured to detect S aureus colonization. Samples of 21 household environmental surfaces, as well as samples obtained from pet dogs and cats, were cultured. Molecular typing of S aureus strains was performed by repetitive-sequence polymerase chain reaction to determine strain relatedness within households. RESULTS: Methicillin-resistant S aureus was recovered from samples of environmental surfaces in 23 of the 50 households (46%), most frequently from the participant's bed linens (18%), television remote control (16%), and bathroom hand towel (15%). It colonized 12% of dogs and 7% of cats. At least 1 surface was contaminated with a strain type matching the participant's isolate in 20 households (40%). Participants colonized with S aureus had a higher mean (SD) proportion of MRSA-contaminated surfaces (0.15 [0.17]) than noncolonized participants (0.03 [0.06]; mean difference, 0.12 [95% CI, 0.05-0.20]). A greater number of individuals per 1000 ft 2 (93 m2) were also associated with a higher proportion of MRSA-contaminated surfaces (ß = 0.34, P = .03). The frequency of cleaning household surfaces was not associated with S aureus environmental contamination. CONCLUSIONS AND RELEVANCE: Methicillin-resistant S aureus strains concordant with infecting and colonizing strains are present on commonly handled household surfaces, a factor that likely perpetuates MRSA transmission and recurrent disease. Future studies are needed to determine methods to eradicate environmental contamination and prevent MRSA transmission in households.

Fatal human herpesvirus 6-associated encephalitis in two boys with underlying POLG mitochondrial disorders.

BACKGROUND: Human herpesvirus 6 is a significant cause of the febrile illness roseola infantum in young children. Infection with human herpesvirus 6 typically causes a self-limited febrile illness but occasionally is associated with central nervous system manifestations, including febrile seizures and encephalitis. Host factors associated with severe manifestations of human herpesvirus 6-associated neurological disease remain poorly characterized. CASE REPORTS: We report two previously healthy young boys with human herpesvirus 6-associated encephalitis who developed a progressive, and ultimately fatal, encephalopathy with refractory movement disorder concurrent with acquisition of acute human herpesvirus 6 infection. Both children were treated with the antiviral ganciclovir without improvement of their neurological symptoms, although quantitative human herpesvirus 6 polymerase chain reaction of cerebrospinal fluid and/or blood confirmed a decline in viral load with treatment. The clinical course in both cases was most consistent with Alpers-Huttenlocher syndrome, given the intractable seizures, developmental regression, and, ultimately, death due to liver and renal failure. In support of this, postmortem analysis identified both children to be compound heterozygous for mutations in the mitochondrial polymerase γ gene, POLG. CONCLUSIONS: POLG mutations are associated with Alpers-Huttenlocher syndrome; however, no prior studies have examined the role of acute human herpesvirus 6 infection in these patients presenting with severe neurological disease. It is possible the POLG mutation phenotype was unmasked and/or exacerbated by human herpesvirus 6 infection in these two patients, potentially contributing to a more rapid clinical deterioration. This report provides new insight into a previously unrecognized association between POLG mutations and poor neurological outcome after human herpesvirus 6 infection.

Molecular epidemiology of methicillin-resistant Staphylococcus aureus isolated in serial cultures from the respiratory tract of children with cystic fibrosis.

BACKGROUND: Little is known about strain relatedness of methicillin-resistant Staphyloccocus aureus (MRSA) isolated at serial time points from the respiratory tract of patients with cystic fibrosis (CF). The objectives are to interrogate the genetic diversity of MRSA recovered in serial cultures from children with CF and to correlate strain relatedness with clinical characteristics. METHODS: We performed a retrospective analysis of children with CF from whom MRSA was isolated from serial respiratory cultures from 2005 to 2011. Within individual patients, relatedness of isolated strains was determined by repetitive-sequence polymerase chain reaction, and the staphylococcal cassette chromosome mec type of each isolate was characterized. Medical records corresponding to the MRSA cultures were reviewed. RESULTS: We identified 54 CF patients with serial MRSA cultures (145 distinct cultures). Over time, 45 (83%) patients maintained the same strain type and 9 (17%) possessed at least 2 distinct strain types. A total of 91 pairs of isolates were analyzed for strain relatedness. Of these, 81 (89%) were identical and 10 (11%) were distinct strain types. About 117 (83%) isolates were staphylococcal cassette chromosome mec type II, 24 (17%) were staphylococcal cassette chromosome mec type IV and 4 were other types not resolvable with our assay. Clinical factors, including time interval and prescription of antibiotics effective against MRSA between positive cultures, did not correlate with acquisition of a distinct MRSA strain by individual patients. CONCLUSIONS: Our data suggest that sustained presence of MRSA in CF patients is most commonly attributable to identical strain types. Acquisition of distinct MRSA strains in the airway is infrequent.

Molecular Epidemiology of Recurrent Cutaneous Methicillin-Resistant Staphylococcus aureus Infections in Children.

We assessed the relatedness by repetitive-sequence polymerase chain reaction of isolates obtained from children with recurrent methicillin-resistant Staphylococcus aureus cutaneous infections over 6 years. Ninety percent of the cases could be attributed to recurrence of the same strain type, suggesting that optimized decolonization methods in children might effectively prevent recurrent infection.

A serologic correlate of protective immunity against community-onset Staphylococcus aureus infection.

BACKGROUND: Staphylococcus aureus is among the leading causes of human infection. Widespread drug resistance, emergence of highly virulent strains, and the ability of S. aureus to colonize >30% of the human population contribute to this organism's pathogenic success. Human serologic responses to S. aureus and their relationship to protective immunity remain incompletely defined, challenging the strategic development of efficacious vaccines. METHODS: We measured humoral responses to 2 staphylococcal exotoxins, α-hemolysin (Hla) and Panton-Valentine leukocidin (PVL; LukF-PV/LukS-PV subunits), both premier targets of current vaccine and immunotherapy development. We correlated acute and convalescent serum antibody levels with incidence of recurrent infection over 12 months follow-up in 235 children with S. aureus colonization, primary or recurrent skin and soft tissue infection, or invasive disease. RESULTS: Cutaneous infection elicited transient increases in anti-Hla and anti-PVL antibodies; however, subsequent infection risk was similar between primary and recurrent cutaneous infection cohorts. Patients with invasive infections had the lowest preexisting titers against Hla and LukF but displayed the highest convalescent titers. Across cohorts, convalescent anti-Hla titers correlated with protection against subsequent S. aureus infection. CONCLUSIONS: Cutaneous S. aureus infection does not reliably provoke durable, protective immune responses. This study provides the first link between protection from disease recurrence and the humoral response to Hla, a virulence factor already implicated in disease pathogenesis. These observations can be utilized to refine ongoing vaccine and immunotherapy efforts and inform the design of clinical trials.

Congenital pancytopenia and absence of B lymphocytes in a neonate with a mutation in the Ikaros gene.

BACKGROUND: Congenital pancytopenia is a rare and often lethal condition. Current knowledge of lymphoid and hematopoietic development in mice, as well as understanding regulators of human hematopoiesis, have led to the recent discovery of genetic causes of bone marrow failure disorders. However, in the absence of mutations of specific genes or a distinct clinical phenotype, many cases of aplastic anemia are labeled as idiopathic, while congenital immune deficiencies are described as combined immune deficiency. PROCEDURE: We describe the case of a 33-week gestation age male with severe polyhydramnios, hydrops, and ascites who was noted to be pancytopenic at birth. Bone marrow examination revealed a hypocellular marrow with absent myelopoiesis. An immune workup demonstrated profound B lymphopenia, near absent NK cells, and normal T cell number. Due to the similarity of the patient's phenotype with the IKAROS knockout mouse, studies were performed on bone marrow and peripheral blood to assess a potential pathogenic role of Ikaros. RESULTS: DNA studies revealed a point mutation in one allele of the IKAROS gene, resulting in an amino acid substitution in the DNA-binding zinc finger domain. Functional studies demonstrated that the observed mutation decreased Ikaros DNA-binding affinity, and immunofluorescence microscopy revealed aberrant Ikaros pericentromeric localization. CONCLUSIONS: Our report describes a novel case of congenital pancytopenia associated with mutation of the IKAROS gene. Furthermore, these data suggest a critical role of IKAROS in human hematopoiesis and immune development.

Graphium basitruncatum fungemia in an immunosuppressed child post stem-cell transplantation.

Graphium basitruncatum is genetically and morphologically distinct from other Graphium and Scedosporium species, and has been reported only once previously as a cause of human disease. We report a case of Graphium basitruncatum fungemia in a two year old child with dyskeratosis congenita who underwent stem cell transplantation two months prior to infection.