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Biomedical subjects

Susan Richardson

Publications and source records attributed to Susan Richardson.

15 recordsLinked to original sources

Human herpesvirus 7 in pediatric hematopoietic stem cell transplantation.

BACKGROUND: Little is known about the significance of human herpesvirus 7 (HHV-7) in pediatric hematopoietic stem cell transplantation (HSCT). OBJECTIVE: To evaluate children post autologous and allogeneic HSCT, with a positive PCR or immunohistochemistry for HHV-7 either from blood, cerebrospinal fluid (CSF) or any other pathology specimen. Clinical data for these patients were collected examining symptoms and signs, engraftment, acute infectious complications, graft versus host disease (GVHD) where applicable, and survival. RESULTS: Between June 1999 and June 2003, 265 HSCT were performed in The Hospital for Sick Children, Toronto, allogeneic (n = 163) and autologous (n = 102). Nine children were positive for HHV-7 at a median of 21 days (range 16-27 days) post-HSCT. All had allogeneic transplantation. The most common underlying diagnosis was acute leukemia and 7 had matched unrelated donor (MUD) transplantation. Eight of the nine patients had grade II-IV acute GVHD and all of them had multiple infectious episodes with fungal, bacterial and other viral pathogens. Although not fully attributed to HHV-7, the clinical syndrome varied from fever, vomiting and diarrhea to septic shock. Four patients died due to GVHD and sepsis. CONCLUSION: HHV-7 was uncommon post-HSCT. It was associated with severe GVHD and sepsis secondary to severe immunosuppression.

Acute Disease↗

Adenoviral infections in pediatric transplant recipients: a hospital-based study.

OBJECTIVE: To assess the disease burden and outcomes resulting from adenoviral infections among pediatric transplant recipients. METHODS: This was a retrospective study of adenoviral infections among pediatric transplant recipients who were hospitalized at our center between 1993 and 2003. Patients were defined as having adenoviral infection if the virus was demonstrated in stool, urine, respiratory, blood, or biopsy tissue samples in the presence of attributable clinical findings. Data were obtained from the hospital's medical records and laboratory databases. RESULTS: There were 55 patients with single episodes of adenovirus infection: 28 (50.9%) solid organ transplant (SOT) and 27 (49.1%) hematopoietic stem cell transplant (HSCT) recipients. The prevalence rates among SOT and HSCT recipients were 1 per 16 and 1 per 24 transplants performed, respectively. The median age of patients with adenovirus infections was 3.66 years (range, 0.25-17.25). Infection occurred at a median of 1.6 months posttransplantation (range, 0.03-153.). Adenovirus was most frequently demonstrated from the gastrointestinal tract (78%). Other sites infected included the respiratory tract, liver, blood and urinary tract. Overall mortality was 14.6%. All deaths occurred among HSCT recipients (mortality, 29.6%). Deaths were more likely among patients with adenovirus identified at >or=2 sites than in those having localized disease (P < 0.01). CONCLUSION: Mortality from adenoviral infection was a greater risk for HSCT than SOT recipients. Early onset of infection after transplantation suggests the possibility of reactivation of adenovirus rather than new acquisition in at least of proportion of cases. This is important for surveillance of this infection in transplant recipients.

Adenoviridae↗

Pediatric Epstein-Barr virus-associated encephalitis: 10-year review.

Many neurologic manifestations of Epstein-Barr virus (EBV) infection have been documented, including encephalitis, aseptic meningitis, transverse myelitis, and Guillain-Barré syndrome. These manifestations can occur alone or coincidentally with the clinical picture of infectious mononucleosis. Since 1994, The Hospital for Sick Children has maintained a prospective registry of all children admitted with acute encephalitis. This report summarizes all cases of Epstein-Barr virus-associated encephalitis compiled from 1994 to 2003. Twenty-one (6%) of 216 children, median age 13 years (range 3-17 years), in the Encephalitis Registry were identified as having evidence of Epstein-Barr virus infection. This evidence consisted of convincing Epstein-Barr virus serology and/or positive cerebrospinal fluid polymerase chain reaction (PCR). One patient had symptoms of classic infectious mononucleosis; all others had a nonspecific prodrome, including fever (n = 17; 81%) and headache (n = 14; 66%). Slightly less than half (n = 10; 48%) had seizures and often had electroencephalograms showing a slow background (n = 12; 57%). Many demonstrated cerebrospinal fluid pleocytosis (n = 17; 81%), and 71% (n = 15) had abnormal magnetic resonance imaging findings. Two patients died, 2 suffered mild deficits, and 16 were neurologically normal at follow-up. Most patients with Epstein-Barr virus encephalitis do not show typical symptoms of infectious mononucleosis. Establishing a diagnosis of Epstein-Barr virus encephalitis can be difficult, and, consequently, a combination of serologic and molecular techniques should be used when investigating a child with acute encephalitis. Most children make full recoveries, but residual neurologic sequelae and even death can and do occur.

Adolescent↗

Molecular diagnosis of severe acute respiratory syndrome: the state of the art.

Severe acute respiratory syndrome (SARS) first appeared in Guangdong Province, China, in November 2002. Although virus isolation and serology were useful early in the SARS outbreak for diagnosing new cases, these tests are not generally useful because virus culture requires a BSL-3 laboratory and seroconversion is often delayed until 2 to 3 weeks after infection. The first qualitative reverse transcriptase-polymerase chain reaction tests for SARS-coronavirus (CoV) were sensitive and capable of detecting 1 to 10 genome equivalents. These assays were quickly supplemented with quantitative real-time assays that helped elucidate the natural history of SARS, particularly the initial presence of low viral loads in the upper respiratory tract and high viral loads in the lower respiratory tract. The unique natural history of SARS-CoV infection dictates the testing of both respiratory and nonrespiratory specimens, the testing of multiple specimens from the same patient, and sending out positives to be confirmed by a reference laboratory. Commercially available reverse transcriptase-polymerase chain reaction tests for SARS have recently appeared; however, meaningful evaluations of these assays have not yet been performed and their true performance has not been determined. These and other issues related to diagnosis of SARS-CoV infection are discussed in this review.

Animals↗

Invasive pneumococcal disease in pediatric organ transplant recipients: a high-risk population.

There are few studies on invasive pneumococcal disease in pediatric transplant recipients. Given this fact plus the advent of pneumococcal conjugate vaccines, we conducted a retrospective study at a major pediatric transplant center. The objectives were to determine the incidence and outcomes of invasive pneumococcal diseases in the patient population and to examine the timing of these infections after transplantation. We determined that invasive disease occurred at a rate that was significantly greater than the rate extrapolated from generally healthy children <5 yr of age (176 episodes per 100 000 children per year vs. 35-68.3 per 100 000 children per year). In addition, disease occurred at a median of approximately 20 months after transplantation, thereby theoretically allowing enough time for vaccination with the 7-valent conjugate vaccine. The study also documented significant missed vaccination opportunities.

Child, Preschool↗

Nosocomial transmission of congenital tuberculosis in a neonatal intensive care unit.

Congenital tuberculosis is uncommon, and nosocomial transmission from a congenitally infected infant to another infant has not been reported in the English literature. We report an investigation of 2 infants with tuberculosis who were cared for in the same neonatal intensive care unit. Isolates from both infants were genetically indistinguishable. Transmission between the 2 infants was likely due to contaminated respiratory equipment.

Cross Infection↗

Predictors of viridans streptococcal shock syndrome in bacteremic children with cancer and stem-cell transplant recipients.

PURPOSE: To describe episodes of viridans streptococcal bacteremia (VSB) in a cohort of children with cancer and stem-cell transplant (SCT) recipients and to determine predictors of viridans streptococcal shock syndrome (VSSS) in this group of children. PATIENTS AND METHODS: For this retrospective review, we included episodes of VSB isolated between March 1997 and September 2002, in children (<or= 18 years) with a diagnosis of cancer or SCT patients. The primary outcome was VSSS, defined as hypotension requiring intravascular volume expansion or inotropic support and/or respiratory insufficiency necessitating assisted ventilation. RESULTS: Eighty-eight episodes of VSB occurred in 79 children. The mean age of the children was 6.7 years (range, 0.6 to 18.0 years). The most common underlying diagnosis was acute myelogenous leukemia (AML) in 31 (35%) of 88 episodes, and 38 (43%) of 88 had undergone SCT. VSSS occurred in 16 (18%) of 88 episodes, and two children died from VSSS. Two variables were predictive of VSSS, namely peak temperature at presentation (odds ratio [OR], 6.3; 95% CI, 2.1 to 19.0; P =.001) and inpatient status (OR, 5.9; 95% CI, 1.3 to 28.0; P =.02). Diagnosis of AML (OR, 1.1; 95% CI, 0.4 to 3.5; P =.8), receipt of SCT (OR, 1.9; 95% CI, 0.6 to 5.7; P =.2), high-dose cytarabine (OR, 0.6; 95% CI, 0.1 to 3.2; P =.6), and mucositis (OR, 0.8; 95% CI, 0.3 to 2.6; P =.7) were not predictive of VSSS. CONCLUSION: VSSS occurred in 18% of episodes of VSB in children with cancer or SCT recipients. Peak temperature before antibiotic therapy and inpatient status were predictive of VSSS.

Adolescent↗

Performance and Cost evaluation of one commercial and six in-house conventional and real-time reverse transcription-pcr assays for detection of severe acute respiratory syndrome coronavirus.

We evaluated seven reverse transcription-PCR (RT-PCR) assays, including six in-house assays and one commercial assay for the detection of severe acute respiratory syndrome coronavirus (SARS-CoV) RNA in clinical specimens. RT-PCR assays targeted different genomic regions and included three conventional assays (one nested and two non-nested) run on a conventional heat block and four real-time assays performed in a LightCycler (LC; Roche Diagnostics). All in-house assays were optimized for assay parameters, including MgCl2, primer, and probe concentrations. The commercial assay was the RealArt HPA CoV RT-PCR assay (Artus), which was run in the LC. Testing serial dilutions of cultured SARS-CoV showed that the analytical sensitivity of the assays ranged from 10(-8) to 10(-6), corresponding to 1 and 100 copies of viral RNA, respectively. Significant differences in analytical sensitivities were observed between assays (P < 0.01, probit regression analysis for 50% sensitivity levels for the top two assays versus the others). Testing 68 clinical specimens (including 17 respiratory tract specimens, 29 urine samples, and 22 stools or rectal swabs) demonstrated that six of the seven assays detected at least 17 of 18 positives (defined as positive in at least two assays), and two of the assays had a sensitivity of 100%. There were no significant differences in sensitivity between the assays (P = 0.5 [Cochrance Q test, least sensitive 15 of 18 versus 18 of 18]). The specificities of the assays ranged from 94.0 to 100% without significant differences (P = 0.25 to 0.5 [McNemar test]). The reagent and technologist cost of performing the in-house PCR assays ranged from $5.46 to $9.81 Canadian dollars (CDN) per test. The commercial assay cost was considerably higher at $40.37 per test. The results demonstrated good performance for all assays, providing laboratories that need to do SARS RNA testing with a choice of assay formats.

Costs and Cost Analysis↗

Serotypes of respiratory tract isolates of Streptococcus pneumoniae from Jamaican children.

BACKGROUND: Data are lacking on the pneumococcal serotypes present in many developing regions, including the Caribbean. We examined the serotypes of nasopharyngeal (NP) isolates of pneumococci obtained from Jamaican children. METHODS: We obtained NP samples from children seen in the Emergency Department at the Bustamante Children's Hospital. The samples were transported to Canada for isolation and serotyping of pneumococci. RESULTS: We obtained 94 isolates from 276 children; median age 3.4 years. The majority (57%) had symptoms of acute respiratory infection at the time of sampling. The main serotypes carried were 6B (20.5%), 19F (14.5%), and 14 (8.4%). Non-typable isolates accounted for 10.8% of the isolates. Fifty-nine per cent of the serotypes were present among the 11 being considered for candidate pneumococcal conjugate vaccines (95% CI 48-70%); the corresponding proportion present in the recently licensed 7-valent vaccine was 57% (95% CI 45-67%). A significant proportion of the serotypes found is absent from those to be included in future conjugate vaccines (P<0.0001; reference=85% expected serotype representation). Less than 5% of isolates were non-susceptible to penicillin (3.2%), cefotaxime-ceftriaxone (3.2%) and cefuroxime (3.2%), while 8.4% and 1.l% of isolates were resistant to trimethoprim-sulfamethoxazole and erythromycin respectively. There were three isolates with resistance to two or more classes of drug. These isolates were all resistant to penicillin (MIC 2 micro g/mL); the serotypes were 14, 23F, and 19F. CONCLUSION: A significant proportion of the serotypes found is absent from those to be included in future conjugate vaccines.

Adolescent↗

Mycoplasma pneumoniae ecephalitis.

Mycoplasma pneumoniae causes between 5 and 10 percent of acute childhood encephalitis in Europe and North America. Encephalitis due to this organism may be caused by direct infection of the brain, immune-mediated brain injury or thromboembolic phenomenon. The prognosis is guarded with 20 to 60 percent suffering neurologic sequelae. The diagnosis of M. pneumoniae encephalitis should be based on strong evidence of M. pneumoniae infection that includes detection of the organism in culture or using molecular detection techniques in addition to serology and exclusion of other potential etiologies. Antibiotic therapy should be considered for all children with suspected M. pneumoniae encephalitis; antibiotics with good central nervous system (CNS) penetration such as ciprofloxacin, doxycycline, chloramphenicol or azithromycin are appropriate under most circumstances. Immune modulating therapies, such as corticosteroids, intravenous immune globulin or plasmapharesis, should be considered in those with immune-mediated syndromes such as acute disseminated encephalomyelitis.

Anti-Bacterial Agents↗

Investigation of Staphylococcus aureus isolates identified as erythromycin intermediate by the Vitek-1 System: comparison with results obtained with the Vitek-2 and Phoenix systems.

We identified 69 Staphylococcus aureus isolates that were erythromycin intermediate as reported by the Vitek-1 system using the GPS-105 card. Of the 57 strains that were available for further testing, all were erythromycin resistant by broth microdilution and the Phoenix system, while the Vitek-2 system identified 55 of 57 strains (96%) as erythromycin resistant. The majority of isolates (54 of 57 [95%]) exhibited the inducible MLS (macrolide-lincosamide-streptogramin family) phenotype, as shown by the double-disk test. We recommend that all S. aureus strains determined as erythromycin intermediate by the Vitek-1 system be interpreted as resistant to erythromycin.

Anti-Bacterial Agents↗

Children hospitalized with severe acute respiratory syndrome-related illness in Toronto.

OBJECTIVE: An outbreak of severe acute respiratory syndrome (SARS) occurred in the greater Toronto area between February and June 2003. We describe the clinical, laboratory, and epidemiologic features of children who were admitted to the Hospital for Sick Children, Toronto, with a presumptive diagnosis of suspect or probable SARS. METHODS: A prospective investigational study protocol was established for the management of children with a presumptive diagnosis of suspect or probable SARS. All were ultimately classified as having probable SARS, suspect SARS, or another cause on the basis of their epidemiologic exposure, clinical and radiologic features, and results of microbiologic investigations. RESULTS: Twenty-five children were included; 10 were classified as probable SARS and 5 were classified as suspect SARS, and in 10 another cause was identified. The exposure consisted of direct contact with at least 1 adult probable SARS case in 11 children, travel from a World Health Organization-designated affected area in Asia in 9 children, and presence in a Toronto area hospital in which secondary SARS spread had occurred in 5 children. The predominant clinical manifestations of probable cases were fever, cough, and rhinorrhea. With the exception of 1 teenager, none of the children developed respiratory distress or an oxygen requirement, and all made full recoveries. Mild focal alveolar infiltrates were the predominant chest radiograph abnormality. Lymphopenia; neutropenia; thrombocytopenia; and elevated alanine aminotransferase, aspartate aminotransferase, and creatine kinase were present in some cases. Nasopharyngeal swab specimens were negative for the SARS-associated coronavirus by an in-house reverse transcriptase-polymerase chain reaction in all 25 children. CONCLUSIONS: Our results indicate that SARS is a relatively mild and nonspecific respiratory illness in previously healthy young children. The presence of fever in conjunction with a SARS exposure history should prompt one to consider SARS as a possible diagnosis in children irrespective of the presence or absence of respiratory symptoms. Reverse-transcriptase polymerase chain reaction analysis of nasopharyngeal specimens seems to be of little utility for the diagnosis of SARS during the early symptomatic phase of this illness in young children.

Adolescent↗

Risk of ruling out severe acute respiratory syndrome by ruling in another diagnosis: variable incidence of atypical bacteria coinfection based on diagnostic assays.

BACKGROUND: Severe acute respiratory syndrome (SARS) caused the first epidemic of the 21st century and continues to threaten the global community. OBJECTIVE: To assess the incidence of coinfection in patients confirmed to have SARS-associated coronavirus (SARS-CoV) infection, and thus, to determine the risk of ruling out SARS by ruling in another diagnosis. METHODS: The present report is a retrospective study evaluating the incidence and impact of laboratory-confirmed SARS-CoV and other pulmonary pathogens in 117 patients. These patients were evaluated in a Toronto, Ontario, community hospital identified as the epicentre for the second SARS outbreak. RESULTS: Coinfection with other pulmonary pathogens occurred in patients with SARS. Seventy-three per cent of the patient population evaluated had laboratory-confirmed SARS-CoV infection. Serology showing acute or recent Chlamydophila pneumoniae or Mycoplasma pneumoniae infection revealed an incidence of 30% and 9%, respectively, in those with SARS. These rates are similar to previously published studies on coinfection in pneumonia. All nucleic acid diagnostic assays were negative for C pneumoniae and M pneumoniae in respiratory samples from patients with SARS having serological evidence for these atypical pathogens. CONCLUSIONS: Diagnostic assays for well-recognized pulmonary pathogens have limitations, and ruling out SARS-CoV by ruling in another pulmonary pathogen carries significant risk. Despite positive serology for atypical pathogens, in a setting where clinical suspicion for SARS is high, specific tests for SARS should be performed to confirm or exclude a diagnosis.

Adolescent↗