First reported case of multidrug-resistant Candida auris in Canada.

Candida auris is a fungal pathogen that has recently emerged as a global threat to public health. It was first described in Japan in 2009 and has since been reported in 17 countries on five continents. This case report describes the first reported case of multidrug-resistant C. auris in Canada. In May 2017, a 64-year-old individual was evaluated for chronic otitis externa. Past medical history included a recent hospitalization in India for elective oral surgery that was complicated by an odontogenic brain abscess. Upon return to Canada, the individual was admitted to a hospital for neurosurgical drainage of the brain abscess and parenteral antibiotics. Early during hospitalization, the patient was identified as a carrier of carbapenem-resistant Enterobacteriaceae and was placed on contact precautions. Also early during this hospitalization, a chronic otitis media was managed with placement of a typanostomy tube with drainage of clear fluid from the ear, which continued through the admission and after discharge to a post-neurosurgical rehabilitation facility. During outpatient follow-up, swabs of the ear discharge cultured C. auris that was resistant to fluconazole and amphotericin B. There was no clinical response to ototopical antifungal therapy. Surgical evaluation for management of the otomastoiditis is pending. There is a potential for C. auris to cause infection in health care settings. It can persist in hospital environments, has the potential for transmission and can cause invasive disease. It is difficult to identify and is often resistant to antifungal medications. The application of infection prevention and control recommendations can help prevent nosocomial transmission. It is now prudent to consider the risk of C. auris, in addition to the known risk of other antimicrobial resistant organisms, in any traveller who has been hospitalized while outside the country. When identified, contacting local public health can assist in the tracking and management of this emerging disease.

Periprosthetic soft tissue recurrence of chondroblastoma after attempted en bloc excision from the proximal humerus.

A case of soft tissue recurrence of chondroblastoma after attempted en bloc excision and endoprosthetic replacement is described. This tumor in the proximal humerus recurred after initial curettage and was subsequently treated by attempted en bloc excision with positive microscopic margins. The patient then presented with a large soft tissue recurrence surrounding the endoprosthesis. This periprosthetic recurrence necessitated re-excision and revision of the endoprosthesis. Recurrence is not uncommon following curettage of chondroblastoma. However, less is known about soft tissue recurrence after en bloc resection of this tumor with positive margins. A subset of chondroblastoma may exist with more locally aggressive behavior.

Circulation patterns of group A and B human respiratory syncytial virus genotypes in 5 communities in North America.

Human respiratory syncytial virus (HRSV) is a major cause of serious lower respiratory tract illness in infants, young children, and the elderly. To characterize the circulation patterns of HRSV strains, nucleotide sequencing of the C-terminal region of the G protein gene was performed on 34-53 isolates obtained from 5 communities during 1 epidemic year, representing distinct geographical locations in North America. Phylogenetic analysis revealed that 5-7 HRSV genotypes, including 1 or 2 predominant strains, circulated in each community. The patterns of genotypes were distinct between communities, and less diversity was seen between strains of the same genotype within than between communities. These findings are consistent with HRSV outbreaks' being community based in nature, although transmission of viruses between communities may occur. Several strains are probably introduced or circulate endemically in communities each year, and local factors-possibly immunity induced by previous years' strains-determine which strains predominate during an HRSV season.

The evolving epidemiology of chlamydial and gonococcal infections in response to control programs in Winnipeg, Canada.

OBJECTIVES: The purpose of this study was to describe and compare the transmission dynamics of chlamydia and gonorrhea in Winnipeg, Manitoba, Canada, and to assess implications for control programs. METHODS: Chlamydia and gonorrhea surveillance case reports (1988 through 1995) and contact-tracing reports (1991 through 1995) were examined. RESULTS: High incidence rates of both chlamydia and gonorrhea clustered in geographic core areas characterized by low socioeconomic status. A decline in the number of reported cases of chlamydia (61%) and gonorrhea (64%) occurred between 1988 and 1995. For chlamydia, the decline was most prominent in non-core area cases, while for gonorrhea it was similar in core and non-core areas. CONCLUSIONS: Chlamydia and gonorrhea appear to be evolving through different epidemic phases, with chlamydia transmission, in response to a newly introduced control program, becoming more core dependent and gonorrhea transmission becoming more sporadic in the face of a sustained control effort. Focused control programs, based on an understanding of the transmission dynamics of chlamydia and gonorrhea, may make their elimination a feasible goal.

Association of phenotypic changes in B cell lymphocytes and plasma viral load in human immunodeficiency virus-infected patients.

Many B cell abnormalities have been reported in human immunodeficiency virus (HIV)-infected patients, including changes in the expression of mu, gamma, and CD22 molecules on the cell surface. Phenotypic changes in these markers on B cells isolated from HIV-seropositive patients with high or low levels of plasma viremia were measured. The phenotypic changes in B cells isolated from such patients were compared with the markers on B cells isolated from HIV-seronegative individuals using three-color flow cytometry. HIV patients showed a reduction in the proportion of mature B cells isolated from peripheral blood mononuclear cells compared with B cells isolated from HIV-seronegative individuals. An increase in the proportion of B cells expressing both mu and gamma molecules on the cell surface was also seen in association with high-HIV plasma viremia. A low plasma viral load was accompanied by a reduction in the proportion of B cells expressing both mu and gamma molecules to a level comparable to those seen in HIV-seronegative individuals. HIV-seropositive individuals demonstrated an increase in the proportion of committed B cells, as indicated by an increase in the proportion of B cells expressing gamma molecules. This observation may explain the poor humoral response of HIV seropositive patients to neo-antigens. Our results demonstrate that phenotypic changes indicative of in vivo B cell activation and an increase in immature cells are associated with HIV infection, particularly with a high plasma viral load. Phenotypic changes in B cell markers may correlate with functional deficits of B cells.

Local succession of adenovirus strains in pediatric gastroenteritis.

Assessment of the current incidence of different adenovirus types in local gastroenteritis involved the examination of over 1,000 stool specimens annually from 1988-1992. Adenoviruses were detected by electron microscopy and/or cell culture in 32% of the specimens in which a viral pathogen was detected. The identification of every adenovirus isolate to type by neutralization with specific antisera against the first 6 types and by restriction analysis of nonneutralized isolates was started in 1990. Samples from 1988 and 1989 were examined retrospectively. Adenovirus strains were compared to those isolated in a study between 1980-1983. Enumeration of individual adenovirus types revealed a number of trends, demonstrating that rapid changes in the local incidence of several strains were occurring in Manitoba. The incidence of adenovirus type 40 (Ad40) as a cause of gastroenteritis was found to have fallen dramatically in recent years. The predominant cause of gastroenteritis in Manitoba is a variant strain of Ad41, increasing in predominance each year and now responsible for over a third of the symptomatic cases examined since 1990. The majority of restriction site differences of the Ad41 variant strain from the prototype strain Tak were mapped to the hexon and fiber genes, both of which code for the neutralizable external viral epitopes. The probability of the observed pattern of mutations occurring by chance was calculated as P < 0.0005, indicating a strong pressure for selection of these immunologically significant alterations to the viral proteins responsible for cell attachment.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of detection methods for adenovirus from enteric clinical specimens.

Fecal samples submitted for virus examination over July 1990 to June 1991 from children < 3 years of age were examined by electron microscopy (EM), virus culture (VC), and enzyme immunoassay [EIA, group-reactive and adenovirus (Ad) 40/41 specific; Cambridge BioScience] to compare the detection rate of adenovirus from pediatric fecal specimens. Ad isolates of serotypes 1-7 grown in HEp-2 or primary rhesus monkey kidney cells were identified by neutralization. Graham 293 cell cultures were used only when specimens were found to be positive for Ad by EM, type-specific Ad40/41 EIA, and for isolates not identified by neutralization. Ads grown in 293 cells were identified by DNA restriction endonuclease analysis. Of the 1187 specimens examined, 105 (9%) were found to be positive for Ad. VC detected 93, while 12 additional positives were detected by EM or EIA. The relative sensitivity of VC, EIA, and EM for the 105 specimens was 89% (93), 45% (47), and 35% (37), respectively. Among the 105 positive specimens, enteric Ad, nonenteric Ad, and untypeable Ad were 28% (29), 65% (68), and 7% (8), respectively. Of 37 EM positives, 62% (23) were enteric Ad; 27% (10) were nonenteric including serotypes 2, 3, 4, 5, 12, and 31, with 4, 1, 1, 2, 1, and 1 isolates of each type positive, respectively; and 11% (4) were detectable only by EM. Five isolates were identified as variant of Ad 2(3), Ad 3(1) and Ad 31(1). Over a 1-year period, a single Ad41 variant strain was the most frequently detected enteric Ad in Winnipeg, Manitoba, Canada.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of enteric adenoviruses with synthetic oligonucleotide probes.

The abilities of hybridization probes to detect all human adenovirus types and to identify enteric adenovirus types were evaluated. The efficiency of hybridization was compared to other tests currently in routine laboratory use on clinical specimens from young children with gastroenteritis. Probes were derived from various regions of the adenovirus types 2 and 41 genomes, and were evaluated by hybridization with a series of DNA quantities from 1 microgram to 10 pg of one adenovirus type from each human subgenus, lambda phage, and HEp 2 cells. The sensitivity of hybridization with the HPII probe (92.7%), containing the conserved hexon gene, compared well with EM (54.6%), culture and neutralization (45.5%), and enzyme immunoassay (61.8%). The sensitivity of detection of enteric adenovirus isolates by the cloned Bg/II D fragment probe (92.9%) and by a synthetic probe (85.7%), manufactured from type-specific sequences of the Ad41 hexon gene were comparable to Ad40/Ad41 specific enzyme immunoassay (84.6%). Hybridization was found to be a sensitive method of adenovirus detection in comparison to traditional methods of laboratory diagnosis. Synthetic oligonucleotides enable specific detection of individual enteric adenovirus types. Hybridization had additional advantages over other tests in identifying cases of infection with more than one adenovirus type and in allowing an estimate of the concentration of adenovirus in the specimen.

Effects of acetaminophen on adverse effects of influenza vaccination in health care workers.

OBJECTIVE: To evaluate the effects of acetaminophen on the incidence of adverse effects to, and the immunogenicity of, whole-virus influenza vaccine in health care workers. DESIGN: Prospective, randomized, double-blind placebo-controlled trial. SETTING: Health Sciences Centre, an acute care teaching hospital in Winnipeg. PARTICIPANTS: Of 474 hospital personnel who agreed to undergo influenza vaccination during the 1990-91 season 262 volunteered to participate in the study. INTERVENTIONS: A dose of 0.5 mL of inactivated trivalent whole-virus influenza vaccine was injected into the deltoid muscle. Volunteers were randomly assigned to ingest two capsules of acetaminophen in a half dose (162.5 mg per capsule) or a full dose (325 mg per capsule) or two identical placebo capsules. Capsules were to be taken at vaccination and at 4, 8 and 12 hours afterward. Subjects were asked to answer questions regarding six symptoms in a diary for the 3 days after vaccination and to record their ingestion of the study medication. MAIN OUTCOME MEASURES: Incidence of local (sore arm) and systemic (headache, fever, muscle ache, nausea and diarrhea) side effects as well as serum titres of hemagglutination inhibition (HAI) antibody to vaccine antigens before vaccination and 2 weeks and 6 months afterward. RESULTS: A total of 87, 87 and 88 subjects received the half dose, full dose and placebo respectively; 96% returned the diaries, 83% ingested all four doses of medication, and 87% volunteered all blood samples. Compared with the placebo group the incidence of sore arm was 25% to 28% lower in the half-dose and full-dose groups respectively at 24 hours after vaccination, and the rate of nausea was 90% lower in the full-dose group. The HAI titres were similar among the groups at the three test times. CONCLUSIONS: The full dose of acetaminophen significantly reduced the incidence of sore arm and nausea without affecting the antibody response. Acetaminophen use may increase the acceptance of influenza vaccine by health care workers in whom concern about side effects is an impediment to vaccination.

Clinical effectiveness of influenza vaccination in Manitoba.

OBJECTIVE: To assess the clinical effectiveness of influenza vaccination in preventing influenza-associated hospitalization and death. DESIGN: Case-control study. SETTING AND PATIENTS: Noninstitutionalized persons aged 45 years or older living in Manitoba, on December 1, 1982, and December 1, 1985. METHODS: Linked records of the Manitoba population registry, hospital-discharge abstracts, physician claims for ambulatory-patient visits and influenza vaccination, and vital statistics were used. A matched-set analysis estimated the clinical effectiveness of influenza vaccination in preventing hospital admissions and deaths from influenza-associated conditions during influenza A (H3N2) outbreak periods in 1982 to 1983 (12 weeks) and 1985 to 1986 (10 weeks). The analysis adjusted for hospital discharge and ambulatory care for high-risk conditions within the previous 15 months and 3 months, respectively. RESULTS: Influenza vaccination prevented 32% to 39% of hospital admissions with pneumonia and influenza and 15% to 34% of admissions with all respiratory conditions. Vaccination was 43% to 65% effective in preventing hospital deaths with these conditions (all listed diagnoses) and 27% to 30% effective in preventing deaths from all causes. CONCLUSION: Influenza vaccination has substantial clinical effectiveness in preventing hospital admission and death from influenza-associated conditions in noninstitutionalized individuals.

Development of oligonucleotide primers and probes against structural and regulatory genes of human immunodeficiency virus type 1 (HIV-1) and their use for amplification of HIV-1 provirus by using polymerase chain reaction.

The polymerase chain reaction is a powerful technique for amplifying a few copies of double-stranded genetic material to millions of copies in a few hours. The sensitivity and specificity of the polymerase chain reaction technique depend to some extent on the nucleotide sequences of the oligonucleotide primer pair used in the amplification. We report new oligonucleotide primers and probes which can be used for the amplification and detection of human immunodeficiency virus type 1 provirus sequences of not only structural but also regulatory genes. These primers are very sensitive and specific and can be used for the detection of African and North American strains of human immunodeficiency virus type 1.

Restriction analysis of the prototype strain of enteric adenovirus type 41 using exonuclease III.

Enteric adenoviruses 40 and 41 (Ad40 and Ad41) are a prominent cause of gastroenteritis in young children. Diagnosis of these enteric types by conventional means is complicated by their fastidious growth characteristics. Enteric adenovirus growth was enhanced by cocultivation. Typing of enteric isolates currently entails analysis of the extracted viral DNA with restriction enzymes. Restriction endonuclease fragments of the Ad41 strain Tak genome were ordered by (i) double digestion, (ii) release of restriction fragments from plasmids containing 84% of the Ad41 genome in EcoRI fragments A, B and C, (iii) hybridization of Southern blotted Ad41 fragments with EcoRI fragment containing plasmids and various segments of the Ad2 genome, (iv) sequential reduction of the genome beginning with terminal restriction fragments with exonuclease III and S1 nuclease. The termini of adenovirus genomes are difficult to clone and the use of exonuclease III is a useful alternative to conventional restriction mapping. DNA restriction patterns, fragment sizes and restriction maps of the Ad4 1 strain Tak with enzymes BamHI, BglII, ClaI, EcoRI, HindIII, PstI, SalI, SmaI and XhoI are presented. Prototype strain restriction maps should enable better understanding of adenovirus type 41 and its epidemiology.

Conserved sequences of the adenovirus genome for detection of all human adenovirus types by hybridization.

The application of DNA hybridization directly to clinical specimens has the potential of improving the diagnosis of fastidious types of adenovirus. In this study, the genome of one adenovirus type from each human subgenus (A to F) was systematically evaluated by hybridization for homologous sequences to find the optimal common probe for detection of all human adenovirus types. The area of cross-hybridization, most closely defined with adenovirus type 2 (Ad2), mapped from map units 11.4 to 16.1 and 26.9 to 29.7 and, principally, to a central area of the genome between map units 47.5 and 65.2. The last area, enclosing the hexon gene, was highly conserved. Cloned probes generated from this area demonstrated the greatest homology to heterologous types by hybridization analysis. A HindIII-BglII clone containing the hexon gene of Ad2 within narrow confines reacted most evenly with all adenoviral types and detected the DNA of all other subgenera with a sensitivity 2 logs greater than that of a complete genomic Ad2 probe. The most homologous adenoviral gene sequences were observed in genes involved with DNA replication or intimately connected to the hexon in the early capsid formation. These results show that the hexon gene constitutes the best single region of the adenovirus genome for use as a genus-specific probe for the diagnosis of all human adenoviral subgenera by DNA hybridization.

The Medstone STS: a technical review.

The Medstone STS does not require the urologist to compromise his lithotripsy success because of insufficient power, inadequate imaging, or restrictions caused by patient positioning. The attention to the details required for success in treatment in the investigators opinion make the Medstone STS a very attractive device for the performance of lithotripsy.

Seroprevalence and demographic characteristics of injection drugs users among individuals at risk for HIV infection in Winnipeg, Manitoba, Canada.

From June 1986 to March 1990, a prospective seroprevalence survey and questionnaire of individuals at risk for HIV infection was conducted with volunteers in Winnipeg. Of 610 individuals enrolled, 146 were injected drug users (IDU). Fifteen IDU were in a methadone treatment program and all were seronegative. Three of 131 remaining IDU were HIV-1 seropositive (2.3%), a rate similar to 2.2% positive (20+ of 927) in diagnostic specimens from IDU tested in the province. Demographics and behaviour of 131 IDU were compared with 335 individuals, of whom 112 were gay/bisexual [24 of whom also had sexually transmitted diseases (STD)] and 223 heterosexuals who had STD. Males enrolled were significantly older than females. Multivariate analysis showed that factors independently associated with IDU were: a younger age, less education, mental health counselling, unemployment, and a history of jaundice or hepatitis. Drugs most commonly used were Ritalin/Talwin, cocaine, and heroin. Over 90% of individuals admitted to sharing needles. In spite of the low seroprevalence of HIV-1 infections, these individuals are important for the potential spread of HIV because of multiple means of acquiring and transmitting HIV and a high rate of needle sharing.

Comparison of immunogenicity of two yeast-derived recombinant hepatitis B vaccines.

A comparison was conducted of the immunogenicity of two yeast recombinant vaccines with different doses [10 micrograms Recombivax-HB (Merck Sharpe & Dohme Ltd) vs. 20 micrograms Engerix-B (Smith Kline Biologicals)]. This was conducted as a randomized, blinded study in healthy preclinical medical students, negative for hepatitis B markers. The geometric mean titres (GMT) showed a wide individual variability for both vaccines, and approximately a two- to threefold greater GMT of anti-HBs in recipients of the 20 micrograms vaccine. However, the 95% confidence interval showed an overlap of the means of the GMT for both vaccine groups, and in this study there was no significant difference in immunogenicity of these two vaccines. At 6-7 months after completion of immunization, antibody levels fell to one-third of the levels of one month post-immunization. A case report of an allergic urticarial reaction to one of the recombinant vaccines is presented.

Excretion of mutagens following chemotherapy.

The mutagenic activity of urine was evaluated in children receiving single and multiple agent chemotherapy to determine the duration of carcinogenic risk to health care personnel and family contacts. Urine samples from 21 children were evaluated before and daily for 5 days after chemotherapy administration. Mutagenic activity, a sensitive though not specific indicator of carcinogenic risk, was assayed using mutant strains of Salmonella typhimurium (the "Ames test"). Validity of the assay was confirmed by demonstrating mutagenic activity in urine samples from 17 adult cigarette smokers but not from 21 adult nonsmokers (24/24 versus 0/37, p less than 0.001). None of the 21 children tested demonstrated mutagenic activity before chemotherapy administration. Following single agent dactinomycin, cyclophosphamide, daunorubicin, doxorubicin, methotrexate, or vincristine, mutagenic activity was demonstrated for 2 days (5/5 at 1 and 2 days and 0/5 at 3 days). Following multiple agent chemotherapy using two or three of the latter drugs on a single day, mutagenic activity was demonstrated for 4 or 5 days (16/16 at 1, 2, 3, and 4 days, and 4/16 at 5 days). Based on these observations with urine, and presumably other body fluids, precautions are recommended for 2 days following single agent and at least 5 days following multiple agent chemotherapy.

Prevalent enteric adenovirus variant not detected by commercial monoclonal antibody enzyme immunoassay.

A commercial monoclonal antibody enzyme immunoassay for the detection of enteric adenovirus type 40 and 41 (Ad40 and Ad41) in stool specimens was evaluated. Twenty-one stool specimens from children with gastroenteritis, with adenovirus particles visible by electron microscopy, and reference strains Ad40 Dugan and Ad41 Tak were tested by Ad40- and Ad41-specific and adenovirus group-reactive immunoassays. All stool specimens tested positive in the group-reactive immunoassay. However, only six specimens, containing isolates of Ad40 strain Hovi-X, an Ad40 genomic variant, and Ad41 strain Tak, reacted with the specific immunoassay, besides the reference strains. Fifteen stool specimens determined by restriction analysis to contain a genomic variant of Ad41 were negative by specific immunoassay. The positions of restriction site differences from the prototype strain Ad41 Tak were analyzed, and four mutations were mapped within the hexon gene; two others may occur in the fiber gene. The Ad41 genomic variant not detected by the enteric test is presently the most frequent cause of local adenoviral gastroenteritis. Highly specific monoclonal antibodies can fail to detect genomic variants of enteric adenoviruses, probably because of alteration of external neutralizable epitopes under immunological pressure to vary.

Six-year retrospective surveillance of gastroenteritis viruses identified at ten electron microscopy centers in the United States and Canada.

To identify the prevalence, seasonality and demographic characteristics of patients with viral gastroenteritis, we reviewed 6 years of retrospective data on viral agents of gastroenteritis screened by electron microscopy at 10 centers in the United States and Canada. From 52,691 individual electron microscopic observations, a virus was detected in 16% of specimens, and the yearly positive detection rate among centers ranged from 8 to 34%. Rotavirus was the agent most commonly observed (26 to 83%), followed by adenoviruses (8 to 27%, respiratory and enteric combined), and small round viruses (SRVs) (0 to 40%) which were second most common at two of the centers. Rotavirus and astrovirus detections occurred more often in the winter but seasonal trends in detection were not apparent for the other viruses. Of all astroviruses detected 64% were found in infants (less than 1 year); unlike the other agents studied SRVs were detected in a large percentage of infants (48%) and older children and adults (20%). Among hospitalized patients a majority of all astroviruses, caliciviruses and SRVs were detected 7 days or more after admission in contrast to both rotaviruses and adenoviruses which were more likely to be detected earlier. The data suggest that SRVs are common agents of gastroenteritis and may be important causes of nosocomial infections. Because of the relative insensitivity of direct electron microscopy as a screening method for SRVs, astroviruses and caliciviruses, these data probably underestimate the true prevalence of disease caused by these agents.