Shigella flexneri serotype 1 infections in men who have sex with men in Vancouver, Canada.

OBJECTIVES: Outbreaks of shigellosis have been documented in men who have sex with men (MSM), associated with interpersonal transmission and underlying HIV infection. We observed a rise in Shigella flexneri isolates identified in a downtown tertiary-care hospital laboratory located within the city centre community health area (CHA-1) of Vancouver, Canada. The objectives of this study were to evaluate clinical outcomes of shigellosis cases among MSM admitted to hospital and to evaluate trends in Shigella cases within Vancouver, Canada. METHODS: Adult rates of shigellosis were analysed by gender and health region, from 2005 to 2011, followed by retrospective chart review of all hospital laboratory-identified S. flexneri cases from 2008 to 2012. Serotyping and pulsed-field gel electrophoresis (PFGE) were performed on these isolates. RESULTS: Although shigellosis rates in men within CHA-1 did not change from 2005 to 2011 (range 33.4-68.5 per 100 000; P = 0.74), they were significantly higher than in other regions within the city of Vancouver (P ≤ 0.001) and the province of British Columbia (P ≤ 0.001). Shigella flexneri rates in men within CHA-1 increased significantly (range 2.3-51.4 per 100 000; P < 0.001), starting in 2008, and were higher than in other regions within Vancouver (P ≤ 0.01). Seventy-nine isolates of S. flexneri from 72 patients were identified by a single hospital laboratory. All patients were male and predominantly MSM (91.7%) and HIV-infected (86.1%), with most (92.6%) demonstrating CD4 counts ≥ 200 cells/µL. In total, 38.0% required hospitalization. Most (87.3%) had S. flexneri serotype 1 infection, with 72.9% of these representing a single PFGE pattern. CONCLUSIONS: We identified high levels of transmission of a primarily clonal strain of S. flexneri serotype 1 in our local MSM population, resulting in a substantial burden of illness and health care resource use secondary to hospital admissions.

Surveillance summary of hospitalized pediatric enterovirus D68 cases in Canada, September 2014.

BACKGROUND: Enterovirus D68 (EV-D68) has been detected infrequently and has not been associated with severe disease in Canada. In the early fall of 2014, following an unusual case increase in the United States, clusters of EV-D68 among children and some adults manifesting severe symptoms were reported in Canada. OBJECTIVE: To provide an initial epidemiological summary of pediatric cases hospitalized with EV-D68 in Canada. METHODS: A time-limited surveillance pilot was conducted collecting information on pediatric cases (less than 18 years of age) hospitalized with EV-D68 between September 1 and 30, 2014. RESULTS: In total, 268 cases were reported from Ontario (n=210), Alberta (n=45), and British Columbia (n=13). Of the 268 reported cases, 64.9% (n=174) were male; the sex difference was statistically significant (p<0.01). Age was reported for 255 cases, with a mean age for males of 5.4 years and for females of 5.3 years. For cases with data available, 6.8% (18/266) were admitted to an intensive care unit. Of those where clinical illness was recorded, respiratory illness alone was present in 98.3% (227/231), neurologic illness alone was present in 0.4% (n=1), and both illnesses were present in 0.9% of cases (n=2); cases with neither respiratory nor neurologic illness were rare (n=1). Of the 90 cases with additional clinical information available, 43.3% were reported as having asthma. No deaths were reported among the 268 cases. CONCLUSION: The EV-D68 outbreak in Canada in September 2014 represents the beginning of a novel outbreak associated with severe illness in children. These findings provide the first epidemiological summary of severe cases of EV-D68 as an emergent respiratory pathogen in Canada. The continued investigation of this pathogen is necessary to build on these results and capture the full spectrum of associated illness.

Pertussis Surveillance Trends in British Columbia, Canada, over a 20-year Period: 1993-2013.

OBJECTIVE: To provide a surveillance update on overall and age-related pertussis trends in British Columbia (BC), Canada, spanning the 20-year period from 1993-2013. METHODS: Provincial surveillance data for confirmed pertussis cases were extracted from January 1, 1993 to October 31, 2013. Annual and age-specific incidence rates were derived using provincial and regional population estimates. RESULTS: BC experienced substantial pertussis epidemics in the late 1990s and early 2000s with incidence ranging from 20 to 40 per 100,000 overall and peaking in pre-teens aged 10-13 years at >200 per 100,000 during the epidemic of 2000. Overall incidence dropped to historical lows ranging from 1 to 6 per 100,000 between 2005 and 2011. This low-level activity was followed by resurgence in 2012 driven by outbreaks in Lower Mainland regions of BC with overall provincial incidence reaching 10 per 100,000. Age-specific incidence in 2012 was highest among infants <1 year old (64 per 100,000) and children 12-13 years old (56-57 per 100,000), with a shift in the age distribution away from preschool-aged children toward pre-teens and young teens evident since 2000. Adult incidence remained <10 per 100,000 throughout the study period and was 5 per 100,000 in 2012. Year-to-date provincial incidence rates overall for 2013 are 6 per 100,000, with ongoing asynchronous activity observed primarily on Vancouver Island. CONCLUSIONS: Pertussis activity in BC showed expected cyclical fluctuations, with a peak incidence observed in 2012, mostly affecting infants and pre-teens/teens but at lower levels than prior peaks. Following substantial epidemics in the 1990s and early 2000s and the incorporation of acellular pertussis vaccine into the routine immunization program, the immuno-epidemiology of pertussis may still be in transition. Further monitoring and evaluation are needed to guide possible program changes for BC.

Rapid subcutaneous immunoglobulin administration every second week results in high and stable serum immunoglobulin G levels in patients with primary antibody deficiencies.

Subcutaneous immunoglobulin G (SCIG) infusions as life-long replacement therapy in patients with primary antibody deficiences (PAD) is being applied increasingly. However, only a few published pharmacokinetic studies are available for this route of administration. Therefore, the pharmacokinetics of a 16% immunoglobulin G (IgG) preparation intended for subcutaneous use were investigated in patients with common variable immunodeficiency and X-linked agammaglobulinaemia. SCIG infusions (200 mg/kg body weight) were administered to 12 adult patients every 14 days for 24 weeks (total of 144 infusions). Pharmacokinetic parameters were determined based on serum IgG trough levels and antibody levels against tetanus. The median half-life of the total serum IgG and for the tetanus antibodies was 40.6 and 23.3 days respectively. Median in vivo recovery of serum IgG and tetanus immunoglobulins were 36% and 46% respectively. Median, preinfusion serum IgG trough levels per patient were high without major variations between infusions and ranged from 7.24 to 7.86 g/l. Safety, in terms of adverse events including systemic adverse reactions and local tissue reactions at infusions sites, was monitored throughout the study. Six mild, local tissue reactions were observed during the study in one patient. No systemic adverse reactions related to the study drug were observed and no serious other adverse event occurred during the study. It is concluded that the bi-weekly SCIG therapy was well tolerated in the study and that it results in high and stable serum IgG levels, offering an alternative therapy regimen to patients suffering from PAD.

Methicillin-resistant Staphylococcus aureus nasal carriage among injection drug users: six years later.

A survey in 2000 to detect methicillin-resistant Staphylococcus aureus (MRSA) colonization in Vancouver downtown east side injection drug users (IDUs) revealed an MRSA nasal colonization incidence of 7.4%. This is a follow-up study to determine the current prevalence of MRSA colonization and to further characterize the isolates and risk factors for colonization. In this point prevalence study of MRSA nasal carriage among IDUs, nasal swabs were cultured to detect S. aureus. Isolates were studied for their antimicrobial susceptibility patterns and the presence of mecA and Panton-Valentine leukocidin (PVL) genes and by pulsed-field gel electrophoresis (PFGE). S. aureus was isolated from 119 of 301 (39.5%) samples; three (2.5%) participants had both methicillin-sensitive S. aureus (MSSA) and MRSA, resulting in 122 isolates. Of these, 54.1% were MSSA and 45.9% were MRSA, with an overall MRSA rate of 18.6%. USA-300 (CMRSA-10) accounted for 75% of all MRSA isolates; 25% were USA-500 (CMRSA-5). None of the USA-500 isolates were positive for PVL; 41 (97.6%) USA-300 isolates contained PVL. One MSSA isolate, from an individual also carrying USA-300, was positive for PVL. The PFGE pattern of this MSSA isolate was related to that of the MRSA strain. The antibiograms of USA-300 compared to USA-500 isolates showed 100% versus 7.1% susceptibility to trimethoprim-sulfamethoxazole (TMP-SMX) and 54.8% versus 7.1% susceptibility to clindamycin. MRSA nasal colonization in this population has increased significantly within the last 6 years, with USA-300 replacing the previous strain. Most of these strains are PVL positive, and all are susceptible to TMP-SMX.

Express subcutaneous IgG infusions: decreased time of delivery with maintained safety.

The aims of the study were to evaluate the safety and feasibility of weekly express subcutaneous replacement IgG self-infusions (E-SCIG, 35 mL/h/syringe driver) in 50 patients and to evaluate their perceptions of the therapy. A total of 4900 E-SCIG infusions at separate infusion sites were given on 1228 treatment occasions. The most commonly reported local tissue reactions were swelling (n = 37), redness (n = 25), and soreness (n = 24). A majority of these patients reported the local reactions as less intense or unchanged compared to those arising from rapid SCIG (20 mL/h) infusions. The patients reported a median score of 16 (visual analogue scale, VAS; 1, not troublesome at all) regarding their overall perceptions of the local reactions. They were positive toward the home therapy regime (median VAS score 96; 100, very positive) and anxious to continue with the E-SCIG infusions (median VAS score 98; 100, very anxious). The E-SCIG method seems to be safe, with few pronounced local reactions, and is appreciated by the patients. Express delivery could also potentially facilitate IgG delivery in a wide variety of diseases, such as autoimmune and autoimmune-like conditions of a neurological or rheumatological character.

Lock acquisition of a gravitational-wave interferometer.

Interferometric gravitational-wave detectors, such as the Laser Interferometer Gravitational Wave Observatory (LIGO) detectors currently under construction, are based on kilometer-scale Michelson interferometers, with sensitivity that is enhanced by addition of multiple coupled optical resonators. Reducing the relative optic motions to bring the system to the resonant operating point is a significant challenge. We present a new approach to lock acquisition, used to lock a LIGO interferometer, whereby the sensor transformation matrix is dynamically calculated to sequentially bring the cavities into resonance.

Chronic mild neutropenia in adults: relation to IgG3 deficiency and infection susceptibility.

OBJECTIVES: Chronic mild neutropenias (NP, i.e. absolute neutrophil blood counts/ANC/0.5-1.5 x 10(9) L(-1)) are accompanied by a variable infection susceptibility, which may or may not be as a result of concomitant conditions. Here, we assessed whether such patients also displayed an immunoglobulin deficiency and if this condition contributed to infection proneness. DESIGN, SETTING AND SUBJECTS: Thirty consecutive adult Caucasian patients with chronic mild NP were followed at one university hospital for up to 28 years. Comparisons were made with 49 IgG3 deficiency patients at an immunodeficiency clinic. MAIN OUTCOME MEASURES: Recorded infections, ANC and serum immunoglobulin levels; flow cytometry assessments of blood lymphocyte subsets and tests for autoimmunity were run to determine neutropenia subtypes. RESULTS: Forty per cent of the NP patients were treated for severe or recurrent infections. The mean IgG3 value for the NP patients was significantly lower than for healthy controls (P < 0.005) and 33% of the patients displayed IgG3 values below the reference values (i.e. below 0.21 g L(-1)), and an additional 13% had IgG3 values within the range others consider low (0.21-0.41 g L(-1)). Unexpectedly, neutropenic IgG3 deficiency patients exhibited less infection proneness than those with normal IgG3 values (P=0.03). Patients with autoimmune, large granular lymphocyte-associated or idiopathic NP had IgG3 deficiency in 63, 44 and 38%, respectively. In addition, none of IgG3 deficiency patients followed at the immunodeficiency clinic displayed neutropenia. CONCLUSION: IgG3 deficiency is common amongst chronic mild neutropenia patients, particularly in those with autoimmune background, but contributes not significantly to infection susceptibility.

Tick-borne encephalitis in Sweden and climate change.

BACKGROUND: The incidence of tick-borne encephalitis (TBE) in Sweden has substantially increased since the mid-1980s. During the same period the climate has become milder and ticks have become more abundant. We investigated whether there is a link between the change in climate and the increase in incidence of TBE. METHODS: Since the late 1950s all cases of encephalitis admitted in Stockholm County have been serologically tested for TBE. We analysed the period 1960-98 with multiple regressions. The number of days per season with temperatures of known importance for tick prevalence and pathogen transmission were studied. 2 years of temperature data were related to each TBE incidence rate to account for the tick's long life-span. FINDINGS: Increases in disease incidence was significantly related (R(2)=0.58; p<0.0001) to a combination of two consecutive mild winters, temperatures favouring spring development (8-10 degrees C) and extended autumn activity (5-8 degrees C) in the year prior to the incidence year, and temperatures allowing tick activity (5-8 degrees C) early in the incidence year. INTERPRETATIONS: The findings indicate that the increase in TBE incidence since the mid-1980s is related to the period's change towards milder winters and early arrival of spring. Other factors may have influenced TBE incidence such as more people in endemic locations, and increases in host animal populations; factors which are partly climate related. Access to TBE vaccination since 1986 and increased awareness of ticks might have caused an underestimation of the links found. Our findings also suggest that the incidence of other tick-borne zoonoses might have been affected by the milder climate.

Rapid subcutaneous IgG replacement therapy at home for pregnant immunodeficient women.

The use of slow or rapid, subcutaneous, IgG (SCIG) infusions in pregnant women with primary antibody deficiencies has been described earlier, though only in single-case reports. In this study, we have evaluated the effect of rapid, SCIG infusions during 11 pregnancies in nine women [six women with common variable immunodeficiency (CVID), two with IgG-subclass deficiencies, and one with combined IgA and IgG2 deficiency]. The weekly infusions were given by the women themselves at a dose of 100 mg/kg/week throughout the pregnancy. No adverse systemic reactions or pronounced, local tissue reactions were recorded during or after the more than 400 infusions. The 11 babies were healthy and were born after 38-42 weeks of uneventful gestation. The concentrations of maternal S-IgG at the time of delivery in the four women with CVID ranged from 6.0 to 8.3 g/L, with cord/maternal S-IgG ratios of 1.0-1.5. The IgG subclasses were transferred to the infants. The SCIG home-therapy regime was greatly appreciated by the women.

Impact of IgG replacement therapy and antibiotic treatment on the colonization of non-encapsulated Haemophilus influenzae in the nasopharynx in patients with hypogammaglobulinaemia.

Non-typable Haemophilus influenzae (NTHI) and Streptococcus pneumoniae are regarded as the main pathogens in patients with humoral immunodeficiency. These patients have been given IgG replacement therapy since the 1950s. However, a number of individuals still suffer from recurrent episodes of respiratory tract infections. Nasopharyngeal cultures were obtained on a regular basis over a 3-6-month period from 11 patients with common variable immunodeficiency disease in 1989 and 1998. The proportion of cultures positive for NTHI decreased from 56% in 1989-90 to 16% in 1998-99 (p < 0.003). After 9 y of IgG therapy, 7 of the 11 patients were free from NTHI in the nasopharynx. Specific NTHI strains were analysed by pulsed-field gel electrophoresis and compared, with regard to genetic relatedness, on an intra-individual basis. In 1 patient the same NTHI strain was found in both 1989 and 1999. The apparent absence of NTHI from the nasopharynx in most of the patients was assumed to be due to subcutaneous IgG treatment, as well as adequate antibiotic treatment.

New limit on CPT violation

A search for antiproton decay has been made at the Fermilab Antiproton Accumulator. Limits are placed on fifteen antiproton decay modes. The results are used to place limits on the characteristic mass scale m(X) that could be associated with CPT violation accompanied by baryon number violation.

Evaluation of posttonsillectomy hemorrhage and risk factors.

BACKGROUND: A 13-year retrospective study was undertaken to determine the incidence of posttonsillectomy hemorrhage, to evaluate potential risk factors, and to assess the efficacy and safety of ambulatory tonsillectomy. METHODS: From January 1985 to December 1997, 4662 patients underwent tonsillectomy at our institution. Ninety patients with posttonsillectomy bleeding were identified. For each patient with posttonsillectomy bleeding, 2 nonbleeding control subjects were selected and matched by age and sex to evaluate potential risk factors. RESULTS: Age was the only factor found to be statistically significant among the bleeding patients and the control group. The highest incidence (3.61%) of posttonsillectomy hemorrhage occurred in patients 21 to 30 years of age. In our experience, secondary hemorrhage was more common than primary hemorrhage, presenting most frequently on postoperative days 5 to 7. CONCLUSIONS: The incidence of posttonsillectomy bleeding in this review was 1.93%, and about half (47%) of the patients with posttonsillectomy hemorrhage returned to the operating room for hemorrhage control. The highest incidence (3.61%) of posttonsillectomy hemorrhage occurred in patients 21 to 30 years of age. Patients with posttonsillectomy hemorrhage, regardless of management, had a 12% incidence of subsequent hemorrhage. We found no difference in the incidence of posttonsillectomy bleeding between outpatient and inpatient procedures.

Nalmefene to prevent epidural narcotic side effects in pediatric patients: a pharmacokinetic and safety study.

STUDY OBJECTIVE: To determine the pharmacokinetics and preliminary efficacy of nalmefene in children in preventing epidural-induced narcotic side effects. DESIGN: Double-blind, placebo-controlled study. SETTING: University-affiliated children's hospital. PATIENTS: Thirty-four children (aged 2-12 yrs) undergoing cardiothoracic surgery with epidural anesthesia. INTERVENTIONS: Patients were randomized to receive intravenous bolus nalmefene 1 microg/kg or placebo. MEASUREMENTS AND MAIN RESULTS: Six blood samples (one before nalmefene administration and five from 13 randomly designated time points) from each patient were assayed to determine plasma nalmefene concentrations. Patients were assessed for pain, nausea, vomiting, and urinary retention for 24 hours after administration. Concentration-time data were analyzed by a limited sampling strategy with adult pharmacokinetic parameters used as Bayesian priors. A two-compartment, first-order model was fitted to the data using ADAPT II. Pharmacokinetic parameter estimates in these patients were similar to values reported in adults. The initial disposition half-life (t(1/2alpha)) was 0.36+/-0.11 hour, the terminal elimination half-life (t(1/2beta)) 8.7+/-2.3 hours, clearance 0.729+/-0.172 L/kg/hr, and steady-state volume of distribution 7.21+/-2.49 L/kg. Ability to prevent epidural narcotic-induced side effects could not be documented at the 1-microg/kg dose. No statistically significant differences were noted between study and placebo groups with regard to pain, nausea, vomiting, or urinary retention. CONCLUSION: Nalmefene has similar pharmacokinetics in children as in adults. It was administered safely to these patients and did not produce unmanageable pain.

Analgesia for pediatric thoracostomy tube removal.

Eutectic mixture of local anesthetics (EMLA; Astra Pharmaceuticals, Wayne, PA) has been shown to reduce the pain of blood draws in children. We investigated the use of EMLA versus IV morphine for providing analgesia during chest tube removal (CTR) in children. One hundred twenty pediatric cardiothoracic surgery patients were enrolled. Patients were randomly assigned to receive either morphine (0.1 mg/kg up to 10 mg IV 30 min before CTR) or EMLA cream (5 g per chest tube cutaneously 3 h before CTR). A single, trained observer rated the patient's pain before, during, and after CTR using a 10-cm visual analog scale. The sites were evaluated for adverse effect. Methylhemoglobin levels were monitored in infants. Before CTR, the pain scores of the children who received morphine were rated lower than those who received EMLA (P < 0.01). During CTR, there was no difference in the pain score between the morphine or EMLA group. The change from baseline pain score in the morphine group was significantly larger than in the EMLA group (P < 0.01). We conclude that EMLA is safe and useful for blunting the pain of CTR.

Effect of fibrin glue on lymphatic drainage after modified radical mastectomy: a prospective randomized trial.

Fibrin as a tissue sealant has been used since the turn of the century for hemostasis. The development of cryoprecipitate and the resultant availability of higher concentrations of fibrinogen have led to a resurgence of interest in this material. Fibrin glue has since been shown to be effective for numerous applications throughout the field of surgery. Animal studies have shown fibrin glue to be effective at reducing drain output after mastectomy. Human studies, however, have been equivocal. Our objectives were to determine whether the use of fibrin glue would decrease lymphatic drainage after modified radical mastectomy and subsequently reduce time to drain removal. A prospective randomized trial was conducted consisting of 27 women. All women received modified radical mastectomy. At the completion of the mastectomy they were randomized to receive either standard closure or the application of fibrin glue before standard closure. Patients were then monitored for daily drain output, time to drain removal, and wound complications. A total of 14 women received fibrin glue and 13 received no glue. Those patients receiving fibrin glue had a significantly higher average drain output than patients who did not receive glue (1308 vs 754 cm3; P = 0.012). Time to drain removal was also increased by 4 days, although this did not reach statistical significance. The overall complication rate was higher for the fibrin glue group, although again, this did not reach significance. The application of fibrin glue significantly increased drain total drain output after modified radical mastectomy. Time to drain removal was increased as was the complication rate. On the basis of these data fibrin glue cannot be recommended for routine use in modified radical mastectomy.

Increased susceptibility to gingival colonization by specific HACEK microbes in children with congenital heart disease.

It is well established that infective endocarditis (IE) involving the HACEK (Hemophilus, Actinobacillus, Cardiobacter, Eikenella, Kingella) group of microbes occurs in patients with congenital heart defects (CHD) and in those with prosthetic grafts. Dental caries and gingival disease have been presumed to be the focus of microbial shedding. The purpose of this study was to determine if children with CHD had a more severe gingival inflammatory condition and harbored the HACEK group of microbes to a greater extent than normal children. Two groups of 12 age and sex matched children were selected for this study. The experimental group consisted of twelve children with CHD, 1-1/2 to 8 years of age. The control group consisted of 12 healthy children 2 to 8 years of age. Each child had a gingival index score recorded as described by Massler. Subgingival cultures were obtained. Gingival samples were cultured for HACEK microbes and total Streptococcus (spp) using standard techniques. Fisher's exact test was performed with significance defined at P < 0.05. Children with CHD had more severe gingival inflammatory index than the control group (P < 0.05). 8/12 CHD patient had Actinobacillus actinomycetemcomitans (A.a.) as compared with 2/12 controls (P < 0.05). Furthermore, all cyanotic CHD patients (4/4) had A.a. whereas, only 2/12 controls did (P < 0.05). 4/12 CHD patients harbored Eikenella corrodens (E.c.) compared to 1/12 controls (N.S.). There was no significant difference in colonization with E.c. or A.a. between cyanotic and acyanotic patients. No significant difference in total Streptococcus (spp) was found between the two groups. This study suggests that children with CHD have a more severe gingival inflammatory index and are colonized with specific HACEK microbes more so than normal children.