Measuring waning protection from seasonal influenza vaccination during nine influenza seasons, Ontario, Canada, 2010/11 to 2018/19.

BackgroundWaning immunity from seasonal influenza vaccination can cause suboptimal protection during peak influenza activity. However, vaccine effectiveness studies assessing waning immunity using vaccinated and unvaccinated individuals are subject to biases.AimWe examined the association between time since vaccination and laboratory-confirmed influenza to assess the change in influenza vaccine protection over time.MethodsUsing linked laboratory and health administrative databases in Ontario, Canada, we identified community-dwelling individuals aged ≥ 6 months who received an influenza vaccine before being tested for influenza by RT-PCR during the 2010/11 to 2018/19 influenza seasons. We estimated the adjusted odds ratio (aOR) for laboratory-confirmed influenza by time since vaccination (categorised into intervals) and for every 28 days.ResultsThere were 53,065 individuals who were vaccinated before testing for influenza, with 10,264 (19%) influenza-positive cases. The odds of influenza increased from 1.05 (95% CI: 0.91-1.22) at 42-69 days after vaccination and peaked at 1.27 (95% CI: 1.04-1.55) at 126-153 days when compared with the reference interval (14-41 days). This corresponded to 1.09-times increased odds of influenza every 28 days (aOR = 1.09; 95% CI: 1.04-1.15). Individuals aged 18-64 years showed the greatest decline in protection against influenza A(H1N1) (aORper 28 days = 1.26; 95% CI: 0.97-1.64), whereas for individuals aged ≥ 65 years, it was against influenza A(H3N2) (aORper 28 days = 1.20; 95% CI: 1.08-1.33). We did not observe evidence of waning vaccine protection for individuals aged < 18 years.ConclusionsInfluenza vaccine protection wanes during an influenza season. Understanding the optimal timing of vaccination could ensure robust protection during seasonal influenza activity.

A Practical Workflow for the Identification of Aspergillus, Fusarium, Mucorales by MALDI-TOF MS: Database, Medium, and Incubation Optimization.

There is an increasing body of literature on the utility of MALDI-TOF MS in the identification of filamentous fungi. However, the process still lacks standardization. In this study, we attempted to establish a practical workflow for the identification of three clinically important molds: Aspergillus, Fusarium, and Mucorales using MALDI-TOF MS. We evaluated the performance of Bruker Filamentous Fungi database v3.0 for the identification of these fungi, highlighting when there would be a benefit of using an additional database, the MSI-2 for further identification. We also examined two other variables, namely, medium effect and incubation time on the accuracy of fungal identification. The Bruker database achieved correct species level identification in 85.7% of Aspergillus and 90% of Mucorales, and correct species-complex level in 94.4% of Fusarium. Analysis of spectra using the MSI-2 database would also offer additional value for species identification of Aspergillus species, especially when suspecting species with known identification limits within the Bruker database. This issue would only be of importance in selected cases where species-level identification would impact therapeutic options. Id-Fungi plates (IDFP) had almost equivalent performance to Sabouraud dextrose agar (SDA) for species-level identification of isolates and enabled an easier harvest of the isolates with occasional faster identification. Our study showed accurate identification at 24 h for Fusarium and Mucorales species, but not for Aspergillus species, which generally required 48 h.

A Prolonged Outbreak of Human Adenovirus A31 (HAdV-A31) Infection on a Pediatric Hematopoietic Stem Cell Transplantation Ward with Whole Genome Sequencing Evidence of International Linkages.

A surge in hematopoietic stem cell transplantation (HSCT) human adenovirus A31 (HAdV-A31) infections was initially observed in late 2014/2015 at SickKids (SK) Hospital, Toronto, Canada. In response, enhanced laboratory monitoring for all adenovirus infections was conducted. Positive samples underwent genotyping, viral culture, and, in selected cases, whole-genome sequencing (WGS). HAdV-A31 specimens/DNA obtained from four international pediatric HSCT centers also underwent WGS. During the SK outbreak period (27 October 2014 to 31 October 2018), 17/20 HAdV-A31 isolates formed a distinct clade with 0 to 8 mutations between the closest neighbors. Surveillance before and after the outbreak detected six additional HAdV-A31 HSCT cases; three of the four sequenced cases clustered within the outbreak clade. Two SK outbreak isolates were identical to sequences from two patients in an outbreak in England. Three SK non-outbreak sequences also had high sequence similarity to strains from three international centers. Environmental PCR testing of the HSCT ward showed significant adenovirus contamination. Despite intense infection control efforts, we observed re-occurrence of infection with the outbreak strain. Severe but nonfatal infection was observed more commonly with HAdV-A31 compared to other genotypes, except HAdV-C1. Our findings strongly implicate nosocomial spread of HAdV-A31 over 10 years on a HSCT unit and demonstrate the value of WGS in defining and mapping the outbreak. Close linkages among strains in different countries suggest international dissemination, though the mechanism is undetermined. This large, extended outbreak emphasizes the pre-eminent role of HAdV-A31 in causing intractable pediatric HSCT outbreaks of severe illness worldwide.

Assessment of panfungal PCR performance with formalin-fixed paraffin-embedded tissue specimens†.

We reviewed the performance of a panfungal ITS-2 PCR and Sanger sequencing assay performed on 88 FFPE specimens at The Hospital for Sick Children (Toronto, Canada) in 2019. A potential fungal pathogen was identified by ITS PCR in 62.7 and 2.9% of positive and negative direct slide examination of tissue specimens, respectively. ITS amplicons were detected in 87/88 specimens, with 53/88 (60.2%) considered as 'positive-contaminants' and 34/88 (38.6%) as 'positive-potential pathogen' upon sequencing. Potential pathogens included Blastomyces dermatitidis (17.1%), Cryptococcus neoformans (17.1%), Histoplasma capsulatum (14.3%) and Mucormycetes (11.4%). Laboratories should only perform ITS PCR on FFPE tissues if fungal elements have been confirmed on histopathology slides. LAY SUMMARY: In this study, we examined how well a DNA-based test could detect DNA from fungi in archived human biopsy tissues. The best performance was achieved if fungi were seen in the tissue under a microscope before being tested. Our results indicate that we should only use this test if these conditions are met.

Antibiotic Prescription Practice for Pediatric Urinary Tract Infection in a Tertiary Center.

OBJECTIVES: Prescribing antibiotics for suspected urinary tract infection (UTI) is common practice and may lead to unnecessary antibiotic exposure. We aimed to review UTI diagnosis and management in the emergency department and to identify targets for antimicrobial stewardship. METHODS: Single-center, retrospective cohort study of children aged 12 weeks to younger than 18 years discharged from the emergency department with a diagnosis of UTI between October and December 2016. Children with genitourinary malformations were excluded. Clinical information, urine collection method, laboratory findings, and urine culture results were gathered. The sensitivity and specificity of nitrite and leukocyte esterase for UTI diagnosis were calculated. The relationship between urinalysis characteristics and confirmed UTI was examined using logistic regression. RESULTS: A total of 183 children with a median (interquartile range) age of 4.2 (1.1-7.5) years were included; 82.5% were female. Almost all children were discharged home on antibiotics (n = 180, 98%) for a median (interquartile range) duration of 7 (7-10) days. A total of 85 patients (46.4%) received antibiotics despite negative urine cultures leading to 525 unnecessary antibiotic days. The presence of nitrites was the strongest predictor of UTI (odds ratio = 20.22, P < 0.001) and was highly specific. CONCLUSIONS: Current practice in managing suspected pediatric UTIs in our ED resulted in significant and unnecessary antibiotic exposure. We identified targets to reduce unnecessary antibiotic exposure including improving the diagnostic accuracy of UTIs, a process to discontinue antibiotics for negative cultures and standardizing antimicrobial duration.

Influenza Vaccine Effectiveness in Preventing Hospitalizations in Older Patients With Chronic Obstructive Pulmonary Disease.

BACKGROUND: Annual influenza immunization is recommended for people with chronic obstructive pulmonary disease (COPD) by all major COPD clinical practice guidelines. We sought to determine the seasonal influenza vaccine effectiveness (VE) against laboratory-confirmed influenza-associated hospitalizations among older adults with COPD. METHODS: We conducted a test-negative study of influenza VE in community-dwelling older adults with COPD in Ontario, Canada using health administrative data and respiratory specimens collected from patients tested for influenza during the 2010-11 to 2015-16 influenza seasons. Influenza vaccination was ascertained from physician and pharmacist billing claims. Multivariable logistic regression was used to estimate the adjusted odds ratio of influenza vaccination in people with, compared to those without, laboratory-confirmed influenza. RESULTS: Receipt of seasonal influenza vaccine was associated with an adjusted 22% (95% confidence interval [CI], 15%-27%) reduction in laboratory-confirmed influenza-associated hospitalization. Adjustment for potential misclassification of vaccination status increased this to 43% (95% CI, 35%-52%). Vaccine effectiveness was not found to vary by patient- or influenza-related variables. CONCLUSIONS: During the studied influenza seasons, influenza vaccination was at least modestly effective in reducing laboratory-confirmed influenza-associated hospitalizations in people with COPD. The imperfect effectiveness emphasizes the need for better influenza vaccines and other preventive strategies.

The impact of repeated vaccination using 10-year vaccination history on protection against influenza in older adults: a test-negative design study across the 2010/11 to 2015/16 influenza seasons in Ontario, Canada.

IntroductionAnnual influenza vaccination is recommended for older adults, but evidence regarding the impact of repeated vaccination has been inconclusive.AimWe investigated vaccine effectiveness (VE) against laboratory-confirmed influenza and the impact of repeated vaccination over 10 previous seasons on current season VE among older adults.MethodsWe conducted an observational test-negative study in community-dwelling adults aged > 65 years in Ontario, Canada for the 2010/11 to 2015/16 seasons by linking laboratory and health administrative data. We estimated VE using multivariable logistic regression. We assessed the impact of repeated vaccination by stratifying by previous vaccination history.ResultsWe included 58,304 testing episodes for respiratory viruses, with 11,496 (20%) testing positive for influenza and 31,004 (53%) vaccinated. Adjusted VE against laboratory-confirmed influenza for the six seasons combined was 21% (95% confidence interval (CI): 18 to 24%). Patients who were vaccinated in the current season, but had received no vaccinations in the previous 10 seasons, had higher current season VE (34%; 95%CI: 9 to 52%) than patients who had received 1-3 (26%; 95%CI: 13 to 37%), 4-6 (24%; 95%CI: 15 to 33%), 7-8 (13%; 95%CI: 2 to 22%), or 9-10 (7%; 95%CI: -4 to 16%) vaccinations (trend test p = 0.001). All estimates were higher after correcting for misclassification of current season vaccination status. For patients who were not vaccinated in the current season, residual protection rose significantly with increasing numbers of vaccinations received previously.ConclusionsAlthough VE appeared to decrease with increasing numbers of previous vaccinations, current season vaccination likely provides some protection against influenza regardless of the number of vaccinations received over the previous 10 influenza seasons.

Adenovirus-Associated Central Nervous System Disease in Children.

OBJECTIVE: To characterize the spectrum and salient clinical features of adenovirus-associated neurologic disease in immunocompetent children. STUDY DESIGN: Previously healthy children (aged 1 month-18 years) with central nervous system (CNS) disease associated with adenovirus infection were identified via the Encephalitis Registry (1996-2016) and Microbiology Database (2000-2016) at The Hospital for Sick Children, Toronto, and by systematic review of the literature. The data were pooled and analyzed to identify the spectrum of illness, clinical outcome, and risk factors for death or neurologic impairment. RESULTS: Neurologic complications associated with adenovirus infection in our institution included febrile seizures, encephalitis, acute disseminated encephalomyelitis, and aseptic meningitis. A total of 48 immunocompetent children with adenovirus-associated CNS disease were included in the pooled analysis-38 from the literature and 10 from our institution. In 85% of cases, the virus was detected in the respiratory or gastrointestinal tract, but not the cerebrospinal fluid. Eighteen of the 48 (38%) patients either died or suffered permanent neurologic sequelae. Predictors of adverse outcome included younger age, coagulopathy, the absence of meningismus, serotype 2 virus, and the presence of seizures. After multivariable adjustment, only seizures remained a significant risk factor. CONCLUSION: Adenovirus is a rare cause of CNS disease in immunocompetent children. Disease spectrum is variable, ranging from mild aspetic meningitis and fully reversible encephalopathy to severe, potentially fatal, acute necrotizing encephalopathy.

The yield of monitoring adenovirus in pediatric hematopoietic stem cell transplant patients.

Human adenovirus (HAdV) is recognized as a serious pathogen after allogeneic hematopoietic stem cell transplantation (HSCT), causing morbidity and mortality. Currently, there is no universal agreement regarding routine HAdV surveillance after HSCT. We assessed the impact of HAdV weekly monitoring by polymerase chain reaction (PCR) on HAdV viremia rates and the risk factors that influence survival. Three-hundred and fifty-six pediatric allogeneic HSCT were done between 2007 and 2015. Until July 2011, HAdV testing was performed based on clinical suspicion (cohort 1, n = 175) and from August 2011, weekly blood-HAdV monitoring was done (cohort 2, n = 181) until day +100. Twenty-three patients (4 [2.3%] from cohort 1 and 19 [10.5%] from cohort 2, p = .001) were found with HAdV viremia and seven of them died. Both cohorts had a similar incidence of HAdV-associated mortality (3/175; 1.7% in cohort 1 and 4/181; 2.2% in cohort 2). Respiratory failure was the cause of death in all patients. Clinical symptoms appeared prior to or within 5 days of HAdV detection in cohort 2. In summary, weekly monitoring was associated with higher detection of HAdV. The study could not assess survival benefit due to small numbers of HAdV-positive cases. In many instances, symptoms occurred with the development of positive HAdV blood PCR results and hence, symptomatology could have triggered the test. Future studies are needed to provide data that help establishing a uniform approach for regular monitoring of HAdV post-transplant.

Epidemiology and Geographic Distribution of Blastomycosis, Histoplasmosis, and Coccidioidomycosis, Ontario, Canada, 1990-2015.

Endemic mycoses represent a growing public health challenge in North America. We describe the epidemiology of 1,392 microbiology laboratory-confirmed cases of blastomycosis, histoplasmosis, and coccidioidomycosis in Ontario during 1990-2015. Blastomycosis was the most common infection (1,092 cases; incidence of 0.41 cases/100,000 population), followed by histoplasmosis (211 cases) and coccidioidomycosis (89 cases). Incidence of blastomycosis increased from 1995 to 2001 and has remained elevated, especially in the northwest region, incorporating several localized hotspots where disease incidence (10.9 cases/100,000 population) is 12.6 times greater than in any other region of the province. This retrospective study substantially increases the number of known endemic fungal infections reported in Canada, confirms Ontario as an important region of endemicity for blastomycosis and histoplasmosis, and provides an epidemiologic baseline for future disease surveillance. Clinicians should include blastomycosis and histoplasmosis in the differential diagnosis of antibiotic-refractory pneumonia in patients traveling to or residing in Ontario.

Early-Onset Invasive Candidiasis in Extremely Low Birth Weight Infants: Perinatal Acquisition Predicts Poor Outcome.

BACKGROUND: Neonatal invasive candidiasis (IC) presenting in the first week of life is less common and less well described than later-onset IC. Risk factors, clinical features, and disease outcomes have not been studied in early-onset disease (EOD, ≤7 days) or compared to late-onset disease (LOD, >7 days). METHODS: All extremely low birth weight (ELBW, <1000 g) cases with IC and controls from a multicenter study of neonatal candidiasis enrolled from 2001 to 2003 were included in this study. Factors associated with occurrence and outcome of EOD in ELBW infants were determined. RESULTS: Forty-five ELBW infants and their 84 matched controls were included. Fourteen (31%) ELBW infants had EOD. Birth weight <750 g, gestation <25 weeks, chorioamnionitis, and vaginal delivery were all strongly associated with EOD. Infection with Candida albicans, disseminated disease, pneumonia, and cardiovascular disease were significantly more common in EOD than in LOD. The EOD case fatality rate (71%) was higher than in LOD (32%) or controls (15%) (P = .0001). The rate of neurodevelopmental impairment and mortality combined was similar in EOD (86%) and LOD (72%), but higher than in controls (32%; P = .007). CONCLUSIONS: ELBW infants with EOD have a very poor prognosis compared to those with LOD. The role of perinatal transmission in EOD is supported by its association with chorioamnionitis, vaginal delivery, and pneumonia. Dissemination and cardiovascular involvement are common, and affected infants often die. Empiric treatment should be considered for ELBW infants delivered vaginally who have pneumonia and whose mothers have chorioamnionitis or an intrauterine foreign body.

Diagnosis of Urinary Tract Infections in Children.

Urinary tract infections (UTIs) are a common occurrence in children. The management and laboratory diagnosis of these infections pose unique challenges that are not encountered in adults. Important factors, such as specimen collection, urinalysis interpretation, culture thresholds, and antimicrobial susceptibility testing, require special consideration in children and will be discussed in detail in the following review.

Low Utility of Pediatric Isolator Blood Culture System for Detection of Fungemia in Children: a 10-Year Review.

The use of the Wampole Isolator 1.5-ml pediatric blood culture tube for the detection of fungemia in children was assessed by a 10-year retrospective review at two pediatric hospitals, The Hospital for Sick Children in Toronto, Canada, and the Children's Medical Center of Dallas, Texas. Over this period, a total of 9,442 pediatric Isolator specimens were processed, with yeast or yeast-like organisms recovered in 297 (3.1%) of the specimens (151 [1.6%] unique clinical episodes) and filamentous or dimorphic fungi recovered in 31 (0.3%) of the specimens (25 unique clinical episodes). Only 18 of the 151 clinical episodes of fungemia attributable to yeast were not detected by automated blood culture systems. The majority of isolated yeast were Candida spp., which were usually detected by automated systems, whereas the most common non-Candida yeast was Malassezia furfur, which the automated system failed to detect. Filamentous or dimorphic fungi were detected in 25 episodes, of which only 9 (36%) episodes were deemed clinically significant after chart review, indicating that in the majority of cases (16/25, 64%) fungal isolation represented contamination. In five of the nine clinically significant episodes, the isolated fungus (Histoplasma capsulatum, Coccidioides immitis/posadasii, Fusarium oxysporum, Aspergillus spp., and Bipolaris spp.) was also identified in other clinical specimens. Over the 10-year study period, the use of the pediatric Isolator system, at the discretion of the treating physician, only rarely provided useful clinical information for the diagnosis of fungemia in children, with the exception of M. furfur and possibly endemic mycoses.

Neurological Complications of PCR-Proven M. pneumoniae Infections in Children: Prodromal Illness Duration May Reflect Pathogenetic Mechanism.

BACKGROUND: The spectrum of neurologic disease attributable to Mycoplasma pneumoniae in children is incompletely understood in part because of limitations of microbiologic diagnostic methods. Our objective was to characterize the neurologic complications of M. pneumoniae in children using stringent diagnostic criteria. METHODS: All children admitted to the Hospital for Sick Children over a 16-year period with acute neurologic manifestations and polymerase chain reaction (PCR)-confirmed M. pneumoniae infection were eligible for inclusion. Cases were categorized as definite, probable, or possible according to strength of evidence implicating M. pneumoniae. Children with underlying noninfectious neurologic conditions or an alternative infectious cause were excluded. RESULTS: A total of 365 children had M. pneumoniae detected in the cerebrospinal fluid (CSF) or respiratory tract by PCR, 42 (11.5%) of whom had neurologic disease attributable to M. pneumoniae. The most common clinical syndromes were encephalitis (52%), acute disseminated encephalomyelitis (12%), transverse myelitis (12%), and cerebellar ataxia (10%). Two distinct disease patterns were observed, one with a prolonged prodrome (≥7 days), respiratory manifestations, an immunoglobulin M (IgM) response in peripheral blood, and detection of M. pneumoniae in the respiratory tract, but not the CSF, and one with a brief (<7 days) or no prodrome, less frequent respiratory manifestations and IgM response, and detection of M. pneumoniae in the CSF, but not the respiratory tract. CONCLUSIONS: Our findings support the hypothesis of two separate pathogenetic mechanisms for M. pneumoniae-associated neurologic disease, one related to direct infection of the central nervous system and one indirect, likely immunologically mediated.

Antimicrobial susceptibility among clinical Nocardia species identified by multilocus sequence analysis.

Antimicrobial susceptibility patterns of 112 clinical isolates, 28 type strains, and 9 reference strains of Nocardia were determined using the Sensititre Rapmyco microdilution panel (Thermo Fisher, Inc.). Isolates were identified by highly discriminatory multilocus sequence analysis and were chosen to represent the diversity of species recovered from clinical specimens in Ontario, Canada. Susceptibility to the most commonly used drug, trimethoprim-sulfamethoxazole, was observed in 97% of isolates. Linezolid and amikacin were also highly effective; 100% and 99% of all isolates demonstrated a susceptible phenotype. For the remaining antimicrobials, resistance was species specific with isolates of Nocardia otitidiscaviarum, N. brasiliensis, N. abscessus complex, N. nova complex, N. transvalensis complex, N. farcinica, and N. cyriacigeorgica displaying the traditional characteristic drug pattern types. In addition, the antimicrobial susceptibility profiles of a variety of rarely encountered species isolated from clinical specimens are reported for the first time and were categorized into four additional drug pattern types. Finally, MICs for the control strains N. nova ATCC BAA-2227, N. asteroides ATCC 19247(T), and N. farcinica ATCC 23826 were robustly determined to demonstrate method reproducibility and suitability of the commercial Sensititre Rapmyco panel for antimicrobial susceptibility testing of Nocardia spp. isolated from clinical specimens. The reported values will facilitate quality control and standardization among laboratories.

Late-onset group B streptococcal meningitis has cerebrovascular complications.

OBJECTIVE: To describe cerebrovascular diseases related to late-onset group B Streptococcus (GBS) meningitis. STUDY DESIGN: Retrospective case series. Patients treated for cerebrovascular complication of late-onset GBS meningitis over 5 years were identified through neuroradiology and microbiology databases. Patient charts were reviewed with regard to clinical presentation, laboratory findings, including GBS subtype, treatment, clinical course, and outcome. Cerebral magnetic resonance imaging was reviewed with special emphasis on stroke pattern and cerebrovascular findings. RESULTS: Fourteen patients were identified. In 6 out of 9 patients serotype III was causative and positive for surface protein hvgA in 5. Ten had arterial ischemic stroke accompanied by a cerebral sinovenous thrombosis in 2 patients. Evidence of cerebral vasculopathy was found in 4 cases. The stroke pattern was variable with cortical, multifocal ischemia, basal ganglia involvement, or had a clear territorial arterial infarction. Ten patients were treated with anticoagulation. No significant bleeding complications, and no recurrent strokes occurred. Twelve patients had clinical and/or subclinical seizures. Developmental outcome was good in 8 cases. Six patients had moderate to severe developmental delay. Central nervous system complications included subdural empyema, hydrocephalus, epilepsy, microcephaly, and hemiplegia. CONCLUSIONS: Late-onset GBS meningitis can be complicated by severe cerebrovascular disease, including arterial ischemic stroke and cerebral sinovenous thrombosis. These complications may be underestimated. We recommend a low threshold for cerebral imaging in these cases. Future studies on the exact incidence, the role of GBS subtypes, and on safety and efficiency of preventive anticoagulation therapy are warranted.

The yield of monitoring for HSV and VZV viremia in pediatric hematopoietic stem cell transplant patients.

Reactivation of HSV and VZV is common following HSCT. Consensus guidelines do not support the use of routine screening for viremia following HSCT in adults, but no such clear guidelines exist in pediatrics. In our center, routine practice was to screen patients weekly for HSV and VZV viremia until engraftment in autologous transplant patients and up to day +100 in allogeneic transplant patients. We conducted a retrospective study of over 500 patients to establish whether this screening identified any patients with HSV or VZV viremia who would not have been identified by clinical signs or symptoms. Over a 4.5-yr period, routine screening identified three cases of HSV viremia and one case of VZV viremia. Two patients had persistent, unexplained fever and two patients had skin or mucosal lesions suggestive of HSV/VZV. We conclude that routine screening for HSV and VZV viremia in pediatric HSCT patients has a very low yield and that viremia can be reliably identified by targeted testing in patients with vesicular skin lesions, oral or genital ulceration, unexplained fever, neurological symptoms, or unexplained abnormal liver transaminases.

Central nervous system complications of varicella-zoster virus.

OBJECTIVE: To describe the spectrum of central nervous system complications of varicella-zoster virus (VZV) in children admitted to The Hospital for Sick Children between January 1999 and December 2012. STUDY DESIGN: Children aged 1 month to 18 years (n = 84) admitted with neurologic manifestations associated with a characteristic VZV rash or a confirmatory laboratory test (positive lesion scraping or cerebrospinal fluid polymerase chain reaction) were included in the study. Acute neurologic complications were included if they occurred within 4 weeks of VZV infection. Stroke was considered related to VZV if it occurred within 6 months of VZV infection, the neuroimaging was characteristic, and other causes were excluded. RESULTS: Clinical syndromes included acute cerebellar ataxia (n = 26), encephalitis (n = 17), isolated seizures (n = 16), stroke (n = 10), meningitis (n = 10), Guillain-Barré syndrome (n = 2), acute disseminated encephalomyelitis (n = 2), and Ramsay Hunt syndrome (n = 1). In those with acute complications (nonstroke), neurologic symptoms occurred a median of 5 days after rash onset (range -6 to +16). The time between rash onset and stroke ranged from 2 weeks to 26 weeks (median 16.0 weeks). Three children with encephalitis died. Residual neurologic sequelae at one year occurred in 9 of 39 (23%) of children with follow-up data. Only 4 children were reported to have received the varicella vaccine. CONCLUSION: Neurologic complications of VZV infection continue to occur despite the availability of an effective vaccine. Neurologic symptom onset can predate the appearance of the VZV exanthem and in rare cases may occur in the absence of an exanthem.

Effective method for the heat inactivation of Blastomyces dermatitidis.

Manipulation of Blastomyces dermatitidis requires the use of containment level 3 (CL3) practices. However, access to CL3 laboratories is limited and working conditions are restrictive. We describe the validation of a "heat-killing" method to inactivate B. dermatitidis, thus allowing cellular material to be removed from the CL3 laboratory for subsequent DNA isolation that is suitable for genetic applications.

Invasive candidiasis in low birth weight preterm infants: risk factors, clinical course and outcome in a prospective multicenter study of cases and their matched controls.

BACKGROUND: This multicenter prospective study of invasive candidiasis (IC) was carried out to determine the risk factors for, incidence of, clinical and laboratory features, treatment and outcome of IC in infants of birth weight <1250 g. METHODS: Neonates <1250 g with IC and their matched controls (2:1) were followed longitudinally and descriptive analysis was performed. Survivors underwent neurodevelopmental assessment at 18 to 24 months corrected age. Neurodevelopmental impairment (NDI) was defined as blindness, deafness, moderate to severe cerebral palsy, or a score <70 on the Bayley Scales of Infant Development 2nd edition. Multivariable analyses were performed to determine risk factors for IC and predictors of mortality and NDI. RESULTS: Cumulative incidence rates of IC were 4.2%, 2.2% and 1.5% for birth-weight categories <750 g, <1000 g, <1500 g, respectively. Forty nine infants with IC and 90 controls were enrolled. Necrotizing enterocolitis (NEC) was the only independent risk factor for IC (p=0.03). CNS candidiasis occurred in 50% of evaluated infants, while congenital candidiasis occurred in 31%. Infants with CNS candidiasis had a higher mortality rate (57%) and incidence of deafness (50%) than the overall cohort of infants with IC. NDI (56% vs. 33%; p=0.017) and death (45% vs. 7%; p=0.0001) were more likely in cases than in controls, respectively. IC survivors were more likely to be deaf (28% vs. 7%; p=0.01). IC independently predicted mortality (p=0.0004) and NDI (p=0.018). CONCLUSION: IC occurred in 1.5% of VLBW infants. Preceding NEC increased the risk of developing IC. CNS candidiasis is under-investigated and difficult to diagnose, but portends a very poor outcome. Mortality, deafness and NDI were independently significantly increased in infants with IC compared to matched controls.