Risk factors for pneumococcal endocarditis.

Bacteremia is one of the most common manifestations of invasive pneumococcal disease (IPD). One complication of bacteremia is endocarditis; yet, few studies have evaluated the overall incidence and risk factors for IPD-associated endocarditis. Thus, we evaluated the overall incidence and risk factors of endocarditis compared to those without endocarditis in a large population of IPD patients. We prospectively collected all IPD cases from 2000 to 2014 in Northern Alberta, Canada. Descriptive statistics were used to compare sociodemographic variables, clinical characteristics, and IPD-related outcomes between patients with and without endocarditis. Endocarditis complicated the course of only 28 (0.3%) of 3251 adult patients with IPD. Endocarditis patients were more likely to use illicit drugs and have a higher severity of illness at presentation (i.e., higher rate of altered mental status and rate of intensive care unit [ICU] utilization, p < 0.05); however, no other major risk factors were identified. New murmur development among endocarditis patients was common: 39.3% compared to 2.2% of non-endocarditis patients (p < 0.001). The mortality rate of 39.3% was more than twice that of the rate of 14.7% for the patients with IPD but without endocarditis. There was no pneumococcal serotype predilection for endocarditis. Endocarditis is an uncommon complication of IPD, but, when present, is associated with a significantly increased risk of mortality. Overall, few specific risk factors were identified for IPD-related endocarditis, with the exception of illicit drug use.

Molecular Assay for Detection of Ciprofloxacin Resistance in Neisseria gonorrhoeae Isolates from Cultures and Clinical Nucleic Acid Amplification Test Specimens.

We developed a real-time PCR assay to detect single nucleotide polymorphisms associated with ciprofloxacin resistance in specimens submitted for nucleic acid amplification testing (NAAT). All three single nucleotide polymorphism (SNP) targets produced high sensitivity and specificity values. The presence of ≥2 SNPs was sufficient to predict ciprofloxacin resistance in an organism.

Molecular Assay for Detection of Genetic Markers Associated with Decreased Susceptibility to Cephalosporins in Neisseria gonorrhoeae.

The incidence of antimicrobial-resistant Neisseria gonorrhoeae continues to rise in Canada; however, antimicrobial resistance data are lacking for approximately 70% of gonorrhea infections that are diagnosed directly from clinical specimens by nucleic acid amplification tests (NAATs). We developed a molecular assay for surveillance use to detect mutations in genes associated with decreased susceptibility to cephalosporins that can be applied to both culture isolates and clinical samples. Real-time PCR assays were developed to detect single nucleotide polymorphisms (SNPs) in ponA, mtrR, penA, porB, and one N. gonorrhoeae-specific marker (porA). We tested the real-time PCR assay with 252 gonococcal isolates, 50 nongonococcal isolates, 24 N. gonorrhoeae-negative NAAT specimens, and 34 N. gonorrhoeae-positive NAAT specimens. Twenty-four of the N. gonorrhoeae-positive NAAT specimens had matched culture isolates. Assay results were confirmed by comparison with whole-genome sequencing data. For 252 N. gonorrhoeae strains, the agreement between the DNA sequence and real-time PCR was 100% for porA, ponA, and penA, 99.6% for mtrR, and 95.2% for porB. The presence of ≥2 SNPs correlated with decreased susceptibility to ceftriaxone (sensitivities of >98%) and cefixime (sensitivities of >96%). Of 24 NAAT specimens with matched cultures, the agreement between the DNA sequence and real-time PCR was 100% for porB, 95.8% for ponA and mtrR, and 91.7% for penA. We demonstrated the utility of a real-time PCR assay for sensitive detection of known markers for the decreased susceptibility to cephalosporins in N. gonorrhoeae. Preliminary results with clinical NAAT specimens were also promising, as they correlated well with bacterial culture results.

Donor-derived bacteremia in liver transplant recipients despite antibiotic prophylaxis.

As the disparity between the number of candidates listed for transplant and the number of donors continues to grow, marginal organ donors are increasingly utilized. This includes bacteremic donors which may carry an increased risk of transmission of infection. It is recommended that recipients of organs from bacteremic donors receive antibiotic prophylaxis based on the susceptibilities of the donor isolate to prevent transmission. Here, we present four cases of donor-derived bacteremia, despite appropriate antimicrobial prophylaxis, in four liver transplant recipients. Transmitted pathogens included Staphylococcus aureus in two cases, and Escherichia coli and Group B Streptococcus each in one case. Interestingly, none of the nonhepatic organs (n=10) utilized from these bacteremic donors resulted in transmissions. These cases highlight the fact that risk of transmission from bacteremic donors is not eliminated with antimicrobial therapy in the donor and recipient. As no transmissions occurred in recipients of nonhepatic organs from these donors, these cases also suggest that liver recipients may be at higher risk of donor transmitted bacteremia.

Prevalence of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) in food samples associated with foodborne illness in Alberta, Canada from 2007 to 2010.

Consumption of foods containing Staphylococcus aureus can cause severe gastro-intestinal illness. Given the fact that over the past decade, Canada has seen increasing rates of methicillin-resistant S. aureus (MRSA) carriage and infection, the objective of this study was to investigate the impact of methicillin-susceptible S. aureus (MSSA) and MRSA on foodborne illness in Alberta, Canada. Between January 2007 and December 2010, there were 693 food samples associated with foodborne investigations submitted to the Alberta Provincial Laboratory for Public Health (ProvLab). These foods were screened for: Bacillus cereus, Clostridium perfringens, S. aureus, Aeromonas spp., Campylobacter spp., Escherichia coli O157:H7, Salmonella, Shigella spp., and Yersinia spp. S. aureus was identified in 10.5% (73/693) of samples, and of these, 59% (43/73) were co-contaminated with at least one other organism on the screening panel. The S. aureus positive samples included 29 meat, 20 prepared foods containing meat, 11 prepared foods not containing meat, 10 dairy, and three produce. Methicillin-resistance was not detected in any isolates tested. These findings indicate that the presence of S. aureus in food associated with foodborne investigations is a cause for concern, and although MRSA was not found, the potential for outbreaks exists, and ongoing surveillance should be sustained.

Alteration of the glycolipid binding specificity of the pig edema toxin from globotetraosyl to globotriaosyl ceramide alters in vivo tissue targetting and results in a verotoxin 1-like disease in pigs.

All members of the verotoxin (VT) family specifically recognize globo-series glycolipids on the surface of susceptible cells. Those toxins that are associated with human disease, VT1, VT2, and VT2c, bind to globotriaosyl ceramide (Gb3) while VT2e, which is associated with edema disease of swine, binds preferentially to globotetraosyl ceramide (Gb4). We were recently able to identify, using site-directed mutagenesis, amino acids in the binding subunit of these toxins that are important in defining their glycosphingolipid (GSL) binding specificity (Tyrrell, G. J., K. Ramotar, B. Boyd, B. W. Toye, C. A. Lingwood, and J. L. Brunton. 1992. Proc. Natl. Acad. Sci. USA. 89:524). The concomitant mutation of Gln64 and Lys66 in the VT2e binding subunit to the corresponding residues (Glu and Gln, respectively) found in VT2 effectively converted the GSL binding specificity of the mutant toxin from Gb4 to Gb3 in vitro. We now report that the altered carbohydrate recognition of the mutant toxin (termed GT3) has biological significance, resulting in a unique disease after intravascular injection into pigs as compared with classical VT2e-induced edema disease. The tissue localization of radiolabeled GT3 after intravascular injection was elevated in neural tissues compared with VT2e accumulation, while localization of GT3 to the gastrointestinal tract was relatively reduced. Accordingly, the pathological lesions after challenge with GT3 involved gross edema of the cerebrum, cerebellum, and brain stem, while purified VT2e caused hemorrhage and edema of the cerebellum, and submucosa of the stomach and large intestine. In addition, both radiolabeled toxins bound extensively to tissues not directly involved in the pathology of disease. VT2e, unlike GT3 or VT1, bound extensively to red cells, which have high levels of Gb4. The overall tissue distribution of VT2e was thus found to be influenced by regional blood flow to each organ and not solely by the Gb4 levels of these tissues. Conversely, the distribution of GT3 (and VT1), which cleared more rapidly from the circulation, correlated with respective tissue Gb3 levels rather than blood flow. These studies indicate the primary role of carbohydrate binding specificity in determining systemic pathology, suggest that the red cells act as a toxin carrier in edema disease, and indicate that red cell binding does not protect against the pathology of systemic verotoxemia.

Increased risk of invasive pneumococcal disease in haematological and solid-organ malignancies.

Large-scale population-based studies have reported a significant increase in invasive pneumococcal disease (IPD) in those with underlying haematological or solid-organ malignancy, but limited condition-specific data are available on rates of IPD in the adult population. A retrospective chart review of all patients with IPD (identified prospectively) in the province of Alberta, Canada (population ~3·3 million) was conducted from 2000 to 2004 to study the epidemiology of IPD. Rates of IPD in patients with various haematological and solid-organ malignancies were determined by obtaining the number of these patients at risk from the provincial cancer registry. Compared to the attack rate of IPD in the adult population aged ≥18 years (11·0 cases/100,000 per year, 95% CI 10·44-11·65), there were significantly increased rates of IPD in those with lung cancer (143·6 cases/100,000 per year, OR 13·4, 95% CI 9·3-19·4, P<0·001) and multiple myeloma (673·9 cases/100,000 per year, OR 62·8, 95% CI 39·6-99·8, P<0·001). More modestly increased rates of IPD were found in those with chronic lymphocytic leukaemia, acute myeloid leukaemia, acute lymphoblastic leukaemia, and Hodgkin's and non-Hodgkin's lymphoma. There was an increased prevalence of serotype 6A in those with these underlying malignancies, but no other serotypes predominated. Fifty-three percent (48/83) of cases were caused by serotypes in the investigational 13-valent pneumococcal conjugate vaccine (PCV13), and 57/83 (69%) of the cases were caused by serotypes in the 23-valent pneumococcal polysaccharide vaccine (PPV23). The incidence of IPD in adults with certain haematological and solid-organ malignancies is significantly greater than the overall adult population. Such patients should be routinely given pneumococcal polysaccharide vaccine; this population could also be targeted for an expanded valency conjugate vaccine.

Use of the QuantiFERON-TB Gold test to confirm latent tuberculosis infection in a Canadian tuberculosis clinic.

SETTING: Capital Health Tuberculosis (TB) Clinic, Edmonton, Alberta, Canada. OBJECTIVE: To analyze the QuantiFERON-TB Gold In-Tube test (QFT) results after implementation as a routine test for tuberculin skin test (TST) positive patients. DESIGN: From November 2004 until January 2007, patients who were TST-positive and were eligible for preventive treatment based on Canadian guidelines, were offered a QFT. RESULTS: Of 1446 TST-positive patients, only 566 (39.6%) were QFT-positive. Categorized by reason for TST testing, 43.1% of 304 contacts, 32.8% of 348 employment screens and 24.2% of 298 post secondary school screens were QFT-positive. In contrast, 59.7% of 290 immigration screens were QFT-positive. A multivariate analysis found that QFT positivity was associated with older age, larger TST size, high-incidence TB region of birth, history of TB and chest X-ray findings suggestive of previous TB. CONCLUSION: Implementation of the QFT as a secondary test for latent TB infection (LTBI) can significantly reduce the number of patients given LTBI treatment in a low-incidence country such as Canada.

Increase in ST-11 serogroup W Neisseria meningitidis invasive meningococcal disease in Canada, 2016-2018.

BACKGROUND: Many countries have experienced increases in invasive meningococcal disease (IMD) due to a serogroup W Neisseria meningitidis (MenW) strain of the multilocus sequence type (ST)-11 clonal complex (CC). MenW ST-11 was first reported in Ontario, Canada, in 2014. By 2016, this strain caused IMD in five provinces and was responsible for 18.8% of the IMD cases in Canada. OBJECTIVE: To provide an update on invasive MenW disease in Canada including the strain characteristics, specimen source of isolates, age, sex and geographic distribution of cases. METHODS: N. meningitidis from culture-positive IMD cases are routinely submitted to the National Microbiology Laboratory (NML) for serogroup, serotype, serosubtype and sequence type analysis. The data from January 1, 2016 to December 31, 2018 were analyzed by calculating the proportion of IMD cases caused by MenW compared with other serogroups. In addition, trends based on age, sex and geographic distribution of cases and specimen source of isolates were analyzed based on information on specimen requisition forms. RESULTS: Over the 3-year period, 292 individual IMD case isolates were analyzed. The percentage of IMD case isolates typed as MenW more than doubled from 19% (n=15) to 44% (n=51) in 2018 when MenW became the most common serogroup, exceeded the number of MenB, MenC or MenY. In total, 93 MenW case isolates were identified, 91% (n=85) belonged to the ST-11 CC. The increase in MenW affected all age groups (but was most common in those older than 60) and both sexes, and occurred across the country but most prevalent in western Canada. The most common specimen source was blood. CONCLUSION: In 2018, MenW was the most common serogroup for isolates received by the NML from culture-positive IMD cases in Canada. Over 90% of the MenW serogroup isolates belonged to the ST-11 CC. The quadrivalent ACWY meningococcal conjugate vaccine protects against IMD caused by strains in the A, C, W or Y serogroups and therefore may protect against IMD caused by the new MenW ST-11 strain; however, more research is needed. The emergence of variant strains highlight the importance of strain characterization in IMD surveillance and research.

A comparison of three real-time PCR assays for the confirmation of Neisseria gonorrhoeae following detection of N. gonorrhoeae using Roche COBAS AMPLICOR.

Three different real-time PCR assays were evaluated as confirmatory tests for Neisseria gonorrhoeae after initial screening using the COBAS AMPLICOR Chlamydia trachomatis and N. gonorrhoeae duplex assay. The target genes used for the confirmation were the gyr, cppB and 16S rRNA genes. Analytical specificity was determined by testing 60 strains belonging to different bacterial species and/or serogroups. The primers chosen from the 16S rRNA gene for confirmation of N. gonorrhoeae were highly specific, showed no cross-reactivity with other bacteria included in the study, and had an analytical sensitivity of 1 CFU. Of 192 clinical specimens that were positive for N. gonorrhoeae according to the COBAS AMPLICOR assay, 42 were confirmed as positive using the 16S rRNA gene target, 26 were confirmed using the cppB target, and 30 were confirmed using the gyr target. It was concluded that the real-time PCR assay targeting the 16S rRNA gene is a useful confirmatory assay to complement the COBAS AMPLICOR screening test for N. gonorrhoeae.

Invasive Pneumococcal Disease: Still Lots to Learn and a Need for Standardized Data Collection Instruments.

Background. Large studies of invasive pneumococcal disease (IPD) are frequently lacking detailed clinical information. Methods. A population-based 15-year study of IPD in Northern Alberta. Results. 2435 patients with a mean age of 54.2 years formed the study group. Males outnumbered females and Aboriginal and homeless persons were overrepresented. High rates of smoking, excessive alcohol use, and illicit drug use were seen. Almost all (87%) had a major comorbidity and 15% had functional limitations prior to admission. Bacteremia, pneumonia, and meningitis were the most common major manifestations of IPD. Almost half of the patients had alteration of mental status at the time of admission and 22% required mechanical ventilation. Myocardial infarction, pulmonary embolism, and new onset stroke occurred in 1.7, 1.3, and 1.1% of the patients, respectively; of those who had echocardiograms, 35% had impaired ventricular function. The overall in-hospital mortality was 15.6%. Conclusions. IPD remains a serious infection in adults. In addition to immunization, preventative measures need to consider the sociodemographic features more carefully. A standard set of data need to be collected so that comparisons can be made from study to study. Future investigations should target cardiac function and pulmonary embolism prevention in this population.

Interim laboratory testing guidance for the detection of non-tuberculous Mycobacterium (NTM) infections in post-operative patients exposed to heater-cooler units.

The advice contained in this document should be read in conjunction with relevant federal, provincial, territorial and local legislation, regulations, and policies. Recommended measures should not be regarded as rigid standards, but principles and recommendations to inform the development of guidance. This advice is based on currently available scientific evidence and adopts a precautionary approach where the evidence is lacking or inconclusive. It was approved for publication on December 5, 2016. It is subject to review and change as new information becomes available. The main changes to this version include additions to: Case load reported to date, Sarcoidosis-like disease as an Indicator, Whole Genome Sequencing effort, links to Provincial and Territorial Lab Services and Health Canada reporting.

Hospital-acquired invasive group a streptococcal infections in Ontario, Canada, 1992-2000.

BACKGROUND: A significant proportion of invasive group A streptococcal infections are hospital acquired. No large, prospective studies have characterized this subgroup of cases and evaluated the risk of transmission in hospitals. METHODS: We conducted prospective, population-based surveillance of invasive group A streptococcal infections in Ontario, Canada, from 1992 to 2000. Epidemiologic and microbiologic investigations were conducted to identify cross-transmission. RESULTS: We identified 291 hospital-acquired cases (12.4%) among 2351 cases of invasive group A streptococcal disease. Hospital-acquired invasive group A streptococcal infections are heterogeneous, including surgical site (96 cases), postpartum (86 cases), and nonsurgical, nonobstetrical infections (109 cases). Surgical site infections affected 1 of 100,000 surgical procedures and involved all organ systems. Postpartum infections occurred at a rate of 0.7 cases per 10,000 live births and exhibited an excellent prognosis. Nonsurgical, nonobstetrical infections encompassed a broad range of infectious syndromes (case-fatality rate, 37%). Nine percent of cases were associated with in-hospital transmission. Transmission occurred from 3 of 142 patients with community-acquired cases of necrotizing fasciitis requiring intensive care unit (ICU) admission, compared with 1 of 367 patients with community-acquired cases without necrotizing fasciitis admitted to the ICU and 1 of 1551 patients with other cases (P<.001). Fifteen outbreaks were identified; 9 (60%) involved only 2 cases. Hospital staff were infected in 1 of 15 outbreaks, but colonized staff were identified in 6 (60%) of 10 investigations in which staff were screened. CONCLUSIONS: Presentation of hospital-associated invasive group A streptococcal infections is diverse. Cross-transmission is common; illness occurs in patients but rarely in staff. Isolation of new cases of necrotizing fasciitis and intervention after a single nosocomial case may also prevent transmission.

Positive and negative symptoms in schizophrenia. A critical reappraisal.

We reexamined the validity of subdividing schizophrenia into categorical subtypes using the predominance of positive and negative symptoms as the characteristic defining features. Using diagnostic criteria proposed in 1982, we again found that the negative subtype may be characterized by a variety of hypothesized correlates of structural brain abnormality, including poor premorbid adjustment, early age at onset, lower educational achievement, poor performance on cognitive testing, and poor response to treatment; a preponderance were also male and unemployed. The patients with negative symptoms did not have a significantly larger ventricular-brain ratio than did those with mixed or positive symptoms, however. As an alternative approach, patients were also classified by ventricle size (large and small); this classification had less predictive validity, with the use of hypothesized indexes of structural brain abnormality, than did the classification based on phenomenology.

T1 and T2 relaxation times in schizophrenia as measured with magnetic resonance imaging.

T1 and T2 relaxation times were measured in ten brain regions on the right and left side in a sample of 27 schizophrenic patients and 37 normal controls. The schizophrenic patients showed a prolongation of T2 relaxation time, and to a lesser extent of T1 relaxation time, which was more predominantly localized in the right hemisphere and in gray matter structures. These results may indicate that metabolic, physiological, or neurochemical brain function in schizophrenia is related in some way to a change in tissue fluid in neuronal cell bodies or interstitial gray matter.

Effects of errors in a multicenter medical study: preventing misinterpreted data.

Large research projects offer significant advantages for research, but they pose special data quality problems. Data gathered in such projects may contain a greater absolute number of mistakes because of the people collecting data, the complexity of data processing, and the collation required. We wanted to learn from the types and frequencies of errors encroaching on data in a multicenter field trial, and to assess the effects of these errors had they passed through. We used extensive error trapping while processing 688 forms from seven sites in the field trial. Snapshots of the dataset were taken at several points in the process, before and after checking and correcting. We discovered 2.4% of the received data to be mistaken. These errors would have affected the data's reliability, decisions based on the study, and possibly the choice of analysis. Almost all of the mistakes were made at the time of measurement and may be related to raters' perceived importance of the variables. We found that communication and education effectively reduced the number of mistakes and their impact on the study over the course of the field trial. While an estimate of the overall error rate is important, the number of mistakes, in general, is only imperfectly related to the errors' effects on the study's results. Our results also suggest that statistical models that treat mistakes as simple independent events can be misleading.

Old age and its behavioral manifestations: a study on two species of macaque.

Observations from two studies on the behavior of stumptail and Japanese macaques revealed that old females were generally less active and involved in fewer social interactions than young adult females. Old females typically avoided or maintained sufficient distance from others to decrease the possibility of interaction, but were neither excluded from social interactions nor out-competed in rank-related situations. The data strongly suggest that the old females selectively withdrew from social interactions and maintained their rank over younger members of the group. Three possible explanations are discussed for the differences in behavior between old and young adult macaque females. (1) Old females with older offspring are less likely to interact with others than old females with younger offspring; (2) old females obtain fewer benefits from social interaction than young adult females, and (3) older females have less energy to disburse for social interaction due to physiological deterioration. The age of the youngest offspring did not account for the decline in social interactions among old females. It was concluded that active withdrawal from social interactions on the part of old females is likely to be the result of both a decrease in the benefits obtained from sociality and an overall physiological deterioration.

Identification and characterization of IS1476, an insertion sequence-like element that disrupts VanY function in a vancomycin-resistant Enterococcus faecium strain.

The vanY gene of vancomycin-resistant enterococci encodes a D,D-carboxypeptidase. By using a PCR detection strategy, a VanA Enterococcus faecium clinical isolate was found to have an insertion sequence (IS)-like element designated IS1476 in vanY. The activity of the VanY D,D-carboxypeptidase in this isolate was decreased in a fluorometric fluoraldehyde o-phthalaldehyde assay with diacetyl-L-Lys-D-Ala-D-Ala as the substrate. This, to our knowledge, is the first report of an IS-like element in a vancomycin resistance gene.

Comorbidity of substance abuse and schizophrenia: the role of pre-morbid adjustment.

Co-morbid substance use and abuse is common in schizophrenic patients, and the role of substance abuse in initiating and maintaining psychosis has important definitional and aetiological implications. We investigated the issue in a cohort of 131 schizophrenic patients. We found non-users (N = 67) were similar to pathological users (N = 64) in current symptomatology and clinical history. The pathological users did, however, have better pre-morbid adjustment levels. Only alcohol use and to some extent cannabis use contributed to this effect; use of stimulants or hallucinogens did not. These results indicate the importance of evaluating the various types of substance used when attempting to explore the significance of co-morbidity. The results also suggest that co-morbidity of substance abuse and schizophrenia may be explained by a common factor antecedent to both: better pre-morbid adjustment. A two-stage model is proposed to explain these findings: increased sociability increases exposure to opportunities of substance use in a subset of patients; subsequent onset of psychotic illness accelerates the use to a pathological level as the individual attempts to cope with the stress of the developing mental illness.