Paul Van Caeseele

University of Manitoba, Winnipeg, Manitoba, Canada

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Publications (32)144.83 Total impact

  • Clinical Infectious Diseases 05/2014; · 9.42 Impact Factor
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    ABSTRACT: Influenza vaccine effectiveness (VE) is generally interpreted in the context of vaccine match/mismatch to circulating strains with evolutionary drift in the latter invoked to explain reduced protection. During the 2012-13 season, however, detailed genotypic and phenotypic characterization shows that low VE was instead related to mutations in the egg-adapted H3N2 vaccine strain rather than antigenic drift in circulating viruses. Component-specific VE against medically-attended, PCR-confirmed influenza was estimated in Canada by test-negative case-control design. Influenza A viruses were characterized genotypically by amino acid (AA) sequencing of established haemagglutinin (HA) antigenic sites and phenotypically through haemagglutination inhibition (HI) assay. H3N2 viruses were characterized in relation to the WHO-recommended, cell-passaged vaccine prototype (A/Victoria/361/2011) as well as the egg-adapted strain as per actually used in vaccine production. Among the total of 1501 participants, influenza virus was detected in 652 (43%). Nearly two-thirds of viruses typed/subtyped were A(H3N2) (394/626; 63%); the remainder were A(H1N1)pdm09 (79/626; 13%), B/Yamagata (98/626; 16%) or B/Victoria (54/626; 9%). Suboptimal VE of 50% (95%CI: 33-63%) overall was driven by predominant H3N2 activity for which VE was 41% (95%CI: 17-59%). All H3N2 field isolates were HI-characterized as well-matched to the WHO-recommended A/Victoria/361/2011 prototype whereas all but one were antigenically distinct from the egg-adapted strain as per actually used in vaccine production. The egg-adapted strain was itself antigenically distinct from the WHO-recommended prototype, and bore three AA mutations at antigenic sites B [H156Q, G186V] and D [S219Y]. Conversely, circulating viruses were identical to the WHO-recommended prototype at these positions with other genetic variation that did not affect antigenicity. VE was 59% (95%CI:16-80%) against A(H1N1)pdm09, 67% (95%CI: 30-85%) against B/Yamagata (vaccine-lineage) and 75% (95%CI: 29-91%) against B/Victoria (non-vaccine-lineage) viruses. These findings underscore the need to monitor vaccine viruses as well as circulating strains to explain vaccine performance. Evolutionary drift in circulating viruses cannot be regulated, but influential mutations introduced as part of egg-based vaccine production may be amenable to improvements.
    PLoS ONE 03/2014; 9(3):e92153. · 3.53 Impact Factor
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    ABSTRACT: An increasing prevalence since 2010 of Serratia marcescens harbouring the Ambler class A carbapenemase SME prompted us to further characterize these isolates. Isolates harbouring blaSME were identified by PCR and sequencing. Phenotypic analysis for carbapenemase activity was carried out by a modified Hodge test and a modified Carba NP test. Antimicrobial susceptibilities were determined by Etest and Vitek 2. Typing was by PFGE of macrorestriction digests. Whole-genome sequencing of three isolates was carried out to characterize the genomic region harbouring the blaSME-type genes. All S. marcescens harbouring SME-type enzymes could be detected using a modified Carba NP test. Isolates harbouring blaSME were resistant to penicillins and carbapenems, but remained susceptible to third-generation cephalosporins, as well as fluoroquinolones and trimethoprim/sulfamethoxazole. Isolates exhibited diverse genetic backgrounds, though 57% of isolates were found in three clusters. Analysis of whole-genome sequence data from three isolates revealed that the blaSME gene occurred in a novel cryptic prophage genomic island, SmarGI1-1. There has been an increasing occurrence of S. marcescens harbouring blaSME in Canada since 2010. The blaSME gene was found on a genomic island, SmarGI1-1, that can be excised and circularized, which probably contributes to its dissemination amongst S. marcescens.
    Journal of Antimicrobial Chemotherapy 03/2014; · 5.34 Impact Factor
  • Euro surveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 02/2014; 19(5). · 4.66 Impact Factor
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    ABSTRACT: Background. We estimate vaccine effectiveness (VE) against both influenza A/subtypes and B/lineages in Canada for the 2011-12 trivalent inactivated influenza vaccine (TIV) with components entirely unchanged from 2010-11 and in the context of phenotypic and genotypic characterization of circulating viruses.Methods. In a test-negative case-control study VE was estimated as [1-adjustedOddsRatio]X100 for RT-PCR-confirmed influenza in vaccinated versus non-vaccinated participants. Viruses were characterized by hemagglutination-inhibition (HI) and sequencing of antigenic sites of the hemagglutinin (HA) gene.Results. There were 1507 participants. VE against A(H1N1)pdm09 was 80%(95%CI:52-92%): circulating viruses were HI-characterized as vaccine-matched and bore just 2 amino-acid (AA) differences from vaccine. VE against A/H3N2 was 51%(95%CI:10-73%): circulating viruses were HI-characterized as vaccine-related but bore ≥11AA differences from vaccine. VE against influenza/B was 51%(95%CI:26-67%): 71%(95%CI:40-86%) for lineage-matched B/Victoria and 27%(95%CI-21-56%) for lineage-mismatched B/Yamagata. For both influenza A and B types, VE was similar among recipients of either 2010-11 or 2011-12 TIV alone, higher when vaccinated both seasons.Conclusions. Phenotypic and genotypic characterization of circulating and vaccine viruses enhances understanding of TIV performance, shown in 2011-12 to be substantial against well-conserved A(H1N1)pdm09 and lineage-matched influenza/B, suboptimal against genetic-variants of A/H3N2 and further reduced against lineage-mismatched influenza/B. With unchanged vaccine components, protection may extend beyond a single season.
    The Journal of Infectious Diseases 01/2014; · 5.85 Impact Factor
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    ABSTRACT: The monitoring of antimicrobial susceptibilities in Neisseria gonorrhoeae isolates and characterization of N. gonorrhoeae multiantigen sequence types (NG-MAST, ST) provide important surveillance data as resistance rates continue to rise. A total of 2970 N. gonorrhoeae isolates were collected by Canadian provincial public health laboratories in 2010, and 1233 were submitted to the National Microbiology Laboratory for testing. The NG-MAST and minimum inhibitory concentration (MIC) by agar dilution were determined for each isolate. Of the 2970 isolates, 25.1% were resistant to penicillin, 34.6% resistant to tetracycline, 31.5% resistant to erythromycin, 35.9% resistant to ciprofloxacin, and 1.2% resistant to azithromycin. Decreased susceptibility to cefixime (MIC ≥ 0.25 mg/L) and ceftriaxone (MIC ≥ 0.125 mg/L) was identified in 3.2% and 7.3% of the isolates, respectively. The most common STs found in Canada were ST1407 (13.3%), ST3150 (11.3%), and ST3158 (9.0%), with 249 different STs identified among the isolates. Within the ST1407 group, 19.5% and 43.3% isolates have decreased susceptibility to cefixime and ceftriaxone, respectively. ST1407, the most prevalent NG-MAST in Canada in 2010, has been associated with high-level ceftriaxone MICs and with cefixime treatment failure cases worldwide. Identification and monitoring of STs and corresponding antimicrobial resistance profiles may be useful in surveillance programs and be used to inform public health actions.
    Canadian Journal of Microbiology 10/2013; 59(10):671-678. · 1.18 Impact Factor
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    ABSTRACT: It is rapidly becoming apparent that many E. coli pathotypes cause a considerable burden of human disease. Surveillance of these organisms is difficult because there are few or no simple, rapid methods for detecting and differentiating the different pathotypes. MALDI-TOF mass spectroscopy has recently been rapidly and enthusiastically adopted by many clinical laboratories as a diagnostic method because of its high throughput, relatively low cost, and adaptability to the laboratory workflow. To determine whether the method could be adapted for E. coli pathotype differentiation the Bruker Biotyper methodology and a second methodology adapted from the scientific literature were tested on isolates representing eight distinct pathotypes and two other groups of E. coli. A total of 136 isolates was used for this study. Results confirmed that the Bruker Biotyper methodology that included extraction of proteins from bacterial cells was capable of identifying E. coli isolates from all pathotypes to the species level and, furthermore, that the Bruker extraction and MALDI-TOF MS with the evaluation criteria developed in this work was effective for differentiating most pathotypes.
    Journal of microbiological methods 06/2013; · 2.43 Impact Factor
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    ABSTRACT: The laboratory system in Manitoba for routine cervical screening is outdated and costly. We developed a costing framework for the implementation of new cervical cancer screening technology models. The direct healthcare costs in the baseline model, the conventional Papanicolaou smear test, were compared with estimates of two newer technology platforms, liquid-based cytology and human papillomavirus (HPV) testing. The findings revealed that HPV testing as a primary screening model for women aged 30 years and older represented the least-cost strategy. Liquid-based cytology would be used for routine screening of women under 30 years of age and to triage women 30 years and older whose results were HPV positive.
    Healthcare quarterly (Toronto, Ont.) 01/2013; 16(1):77-85.
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    ABSTRACT: The 2012/13 influenza season in Canada has been characterised to date by early and moderately severe activity, dominated (90%) by the A(H3N2) subtype. Vaccine effectiveness (VE) was assessed in January 2013 by Canada’s sentinel surveillance network using a test-negative case–control design. Interim adjusted- VE against medically attended laboratory-confirmed influenza A(H3N2) infection was 45% (95% CI: 13–66). Influenza A(H3N2) viruses in Canada are similar to the vaccine, based on haemagglutination inhibition; however, antigenic site mutations are described in the haemagglutinin gene.
    Euro surveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 01/2013; 18(5). · 4.66 Impact Factor
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    ABSTRACT: This study assesses the detection performance of CHROMagar™ STEC relative to a reference cytotoxin assay and describes the current relative prevalence of O157 and non-O157 STEC serotypes within the province of Manitoba, Canada. Over a 10 month period, 205 non-frozen routine stool submissions to Cadham Provincial Laboratory (CPL) were used to assess the performance of of CHROMagar STEC. Of the 205 stools, 14 were identified as true positive by a cytotoxin assay, with resultant CHROMagar STEC sensitivity, specificity, positive predictive value and negative predictive values of 85.7%, 95.8%, 60.0% and 98.9%. Using a separate panel of 111 STEC, CHROMagar STEC was shown to support the growth of 96 (86.5%) isolates. To assess relative prevalence, attempts were made to isolate by any means all STEC identified at CPL over a 17 month period. Of 49 isolates (representing 86.0% of all STEC infections detected) only 28.6% were O157 STEC. Of the 35 non-O157 STEC, 29 were subjected to further molecular analysis. In contrast to earlier results from our area carriage of stx2 appears to have increased. Overall, although not recommended as a primary screen, our results indicate that CHROMagar STEC is an effective supplemental medium for the isolation of probable STEC. Increased isolation of these serotypes is warranted to better understand their prevalence, clinical characteristics, and epidemiology and aid in the development or enhancement of food safety control programs targeting all STEC serotypes.
    Journal of clinical microbiology 11/2012; · 4.23 Impact Factor
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    ABSTRACT: Please cite this paper as: Kim et al. (2012) Characteristics of respiratory viral infections during influenza season in Canadian Hutterite Communities. Influenza and Other Respiratory Viruses DOI:10.1111/irv.12021. Objectives:  To determined the pathogen-specific incidence of respiratory virus infection in Hutterite communities occurring over the 2008-2009 influenza season and assess temporal characteristics of respiratory illness related to infection. Methods:  3273 participants community members enrolled in a cluster randomized trial of influenza vaccine were studied. Results:  One hundred forty-nine participants had laboratory-confirmed influenza, and 595 had at least one episode of laboratory-confirmed respiratory viral infection other than influenza. Entero/rhinovirus had the highest incidence among children <5 years. Conclusions:  A decline in the incidence of infections with age was observed for influenza as well as for most other respiratory viruses.
    Influenza and Other Respiratory Viruses 10/2012; · 1.47 Impact Factor
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    ABSTRACT: We conducted a multicenter trial in Canada to assess the value of using trueness controls (TC) for rubella virus IgG and hepatitis B virus surface antibody (anti-HBs) serology to determine test performance across laboratories over time. TC were obtained from a single source with known international units. Seven laboratories using different test systems and kit lots included the TC in routine assay runs of the analytes. TC measurements of 1,095 rubella virus IgG and 1,195 anti-HBs runs were plotted on Levey-Jennings control charts for individual laboratories and analyzed using a multirule quality control (MQC) scheme as well as a single three-standard-deviation (3-SD) rule. All rubella virus IgG TC results were "in control" in only one of the seven laboratories. Among the rest, "out-of-control" results ranged from 5.6% to 10% with an outlier at 20.3% by MQC and from 1.1% to 5.6% with an outlier at 13.4% by the 3-SD rule. All anti-HBs TC results were "in control" in only two laboratories. Among the rest, "out-of-control" results ranged from 3.3% to 7.9% with an outlier at 19.8% by MQC and from 0% to 3.3% with an outlier at 10.5% by the 3-SD rule. In conclusion, through the continuous monitoring of assay performance using TC and quality control rules, our trial detected significant intra- and interlaboratory, test system, and kit lot variations for both analytes. In most cases the assay rejections could be attributable to the laboratories rather than to kit lots. This has implications for routine diagnostic screening and clinical practice guidelines and underscores the value of using an approach as described above for continuous quality improvement in result reporting and harmonization for these analytes.
    Clinical and vaccine Immunology: CVI 08/2012; 19(10):1624-32. · 2.37 Impact Factor
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    Canadian Journal of Infectious Diseases and Medical Microbiology. 07/2012; Summer 2012;23(2).
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    ABSTRACT: In Canada before 2005, large outbreaks of pneumococcal disease, including invasive pneumococcal disease caused by serotype 5, were rare. Since then, an epidemic of serotype 5 invasive pneumococcal disease was reported: 52 cases during 2005, 393 during 2006, 457 during 2007, 104 during 2008, and 42 during in 2009. Of these 1,048 cases, 1,043 (99.5%) occurred in the western provinces of Canada. Median patient age was 41 years, and most (659 [59.3%]) patients were male. Most frequently representing serotype 5 cases (compared with a subset of persons with non-serotype 5 cases) were persons who were of First Nations heritage or homeless. Restriction fragment-length polymorphism typing indicated that the epidemic was caused by a single clone, which multilocus sequence typing identified as sequence type 289. Large pneumococcal epidemics might go unrecognized without surveillance programs to document fluctuations in serotype prevalence.
    Emerging Infectious Diseases 05/2012; 18(5):733-40. · 7.33 Impact Factor
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    ABSTRACT: We conducted a population-based study in Manitoba, Canada, to investigate whether use of inactivated trivalent influenza vaccine (TIV) during the 2008-09 influenza season was associated with subsequent infection with influenza A(H1N1)pdm09 virus during the first wave of the 2009 pandemic. Data were obtained from a provincewide population-based immunization registry and laboratory-based influenza surveillance system. The test-negative case-control study included 831 case-patients with confirmed influenza A(H1N1)pdm09 virus infection and 2,479 controls, participants with test results negative for influenza A and B viruses. For the association of TIV receipt with influenza A(H1N1)pdm09 virus infection, the fully adjusted odds ratio was 1.0 (95% CI 0.7-1.4). Among case-patients, receipt of 2008-09 TIV was associated with a statistically nonsignificant 49% reduction in risk for hospitalization. In agreement with study findings outside Canada, our study in Manitoba indicates that the 2008-09 TIV neither increased nor decreased the risk for infection with influenza A(H1N1)pdm09 virus.
    Emerging Infectious Diseases 05/2012; 18(5):801-10. · 7.33 Impact Factor
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    ABSTRACT: Most pediatric adenovirus respiratory infections are mild and indistinguishable from other viral causes. However, in a few children, the disease can be severe and result in substantial morbidity. We describe the epidemiologic, clinical, radiologic features and outcome of adenovirus lower respiratory tract infections (LRTI) in Aboriginal and Non-Aboriginal children in Manitoba, Canada during the years 1991 and 2005. This was a retrospective study of 193 children who presented to the department of pediatrics at Winnipeg Children's Hospital, Manitoba, Canada with LRTI and had a positive respiratory culture for adenovirus. Patients' demographics, clinical and radiologic features and outcomes were collected. Adenovirus serotype distributions and temporal associations were described. Approximate incidence comparisons (detection rates) of adenovirus LRTI among Aboriginal and Non-Aboriginal children were estimated with 95% confidence intervals. Adenovirus infections occurred throughout the year with clusters in the fall and winter. Serotypes 1 to 3 were the predominant isolates (two thirds of the cases). The infection was more frequent among Canadian Aboriginals, as illustrated in 2004, where its incidence in children 0-4 years old was 5.6 fold higher in Aboriginals (13.51 vs. 2.39 per 10,000, p < 0.000). There were no significant differences in length of hospitalization and use of ventilator assistance between the two groups (p > 0.185 and p > 0.624, respectively) nor across serotypes (p > 0.10 and p > 0.05, respectively). The disease primarily affected infants (median age, 9.5 months). Most children presented with bronchiolitis or pneumonia, with multi-lobar consolidations on the chest x-ray. Chronic (residual) changes were documented in 16 patients, with eight patients showing bronchiectasis on the chest computerized tomography scan. Adenovirus infection is associated with significant respiratory morbidities, especially in young infants. The infection appears to be more frequent in Aboriginal children. These results justify a careful follow-up for children with adenovirus LRTI.
    BMC Infectious Diseases 03/2012; 12:55. · 2.56 Impact Factor
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    ABSTRACT: Little is known about the determinants of pandemic H1N1 (pH1N1) infection in Canada among low-income, inner city populations. To inform future influenza planning, the seroprevalence of pH1N1 antibodies among inner city clinic attendees in Winnipeg (Manitoba) according to sociodemographic and risk factor characteristics were estimated and vaccination rates were explored. Adults presenting to three inner city community clinics in Winnipeg from October 2009 to December 2009 were recruited as study participants (n=458). A questionnaire was administered to collect demographic, risk factor and symptom information, and a venous blood sample was collected for hemagglutination inhibition assay testing to detect the presence of antibodies against pH1N1. Approximately one-half (53%) of the study participants reported an annual household income of <$10,000/year, and 65% identified as Aboriginal. pH1N1 positivity was 5.7% among those enrolled early in the study and 15.5% among those enrolled later in the study. Positivity was higher among participants who were female, Aboriginal and in contact with children ≤5 years of age. The overall pH1N1 vaccination rate was 28%. pH1N1 positivity was high among low-income adults accessing clinics in Winnipeg's inner city compared with the general population. Of further concern were the low rates of uptake of both seasonal and pH1N1 influenza vaccinations. When planning for future influenza outbreaks, it is important to incorporate strategies for the prevention, control, and care of influenza among low-income and inner city adults.
    The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale / AMMI Canada 01/2012; 23(2):65-70. · 0.49 Impact Factor
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    ABSTRACT: Excellent immune responses following 1 or 2 doses of the monovalent inactivated pandemic H1N1 vaccines have been documented, but the effectiveness of these vaccines against laboratory-confirmed H1N1 infections in the general population is not clear. We evaluated the effectiveness of the pandemic H1N1 and seasonal trivalent influenza vaccines (TIV) used during the 2009 mass vaccination campaign in Manitoba (Canada) in preventing laboratory-confirmed H1N1 infections. A population-based case-control study using data from Cadham Provincial Laboratory (CPL) and the Manitoba Immunization Monitoring System (MIMS). All Manitoba residents ≥6 months of age who had a respiratory specimen tested at CPL for H1N1 were included in the study. Cases were individuals who tested positive for pandemic H1N1 influenza A by reverse transcriptase-PCR (N=1435). Controls were individuals who tested negative for both influenza A and B (N=2309). Information on receipt of TIV or H1N1 vaccine was obtained by record linkage with MIMS, the population-based province-wide immunization registry. Overall, the adjuvanted H1N1 vaccine was 86% (95%CI 75-93%) effective in preventing laboratory-confirmed H1N1 infections when vaccination occurred ≥14 days before testing. Effectiveness seemed lower among older (≥50 years) individuals [51% (-51 to 84%)] and among those with immunocompromising conditions [67% (-13 to 90%)]. There was also evidence that the H1N1 vaccine might be less effective among those who had received the 2009/10 TIV. The adjuvanted H1N1 vaccine used during Manitoba's H1N1 mass vaccination campaign was highly effective against laboratory-confirmed pandemic H1N1 infection, especially among children and younger adults.
    Vaccine 08/2011; 29(45):7975-81. · 3.49 Impact Factor
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    ABSTRACT: Administrative databases provide efficient methods to estimate influenza vaccine effectiveness (IVE) against severe outcomes in the elderly but are prone to intractable bias. This study returns to one of the linked population databases by which IVE against hospitalization and death in the elderly was first assessed. We explore IVE across six more recent influenza seasons, including periods before, during, and after peak activity to identify potential markers for bias. Acute respiratory hospitalization and all-cause mortality were compared between immunized/non-immunized community-dwelling seniors ≥65 years through administrative databases in Manitoba, Canada between 2000-01 and 2005-06. IVE was compared during pre-season/influenza/post-season periods through logistic regression with multivariable adjustment (age/sex/income/residence/prior influenza or pneumococcal immunization/medical visits/comorbidity), stratification based on prior influenza immunization history, and propensity scores. Analysis during pre-season periods assessed baseline differences between immunized and unimmunized groups. The study population included ∼140,000 seniors, of whom 50-60% were immunized annually. Adjustment for key covariates and use of propensity scores consistently increased IVE. Estimates were paradoxically higher pre-season and for all-cause mortality vs. acute respiratory hospitalization. Stratified analysis showed that those twice consecutively and currently immunized were always at significantly lower hospitalization/mortality risk with odds ratios (OR) of 0.60 [95%CI0.48-0.75] and 0.58 [0.53-0.64] pre-season and 0.77 [0.69-0.86] and 0.71 [0.66-0.77] during influenza circulation, relative to the consistently unimmunized. Conversely, those forgoing immunization when twice previously immunized were always at significantly higher hospitalization/mortality risk with OR of 1.41 [1.14-1.73] and 2.45 [2.21-2.72] pre-season and 1.21 [1.03-1.43] and 1.78 [1.61-1.96] during influenza circulation. The most pronounced IVE estimates were paradoxically observed pre-season, indicating bias tending to over-estimate vaccine protection. Change in immunization habit from that of the prior two years may be a marker for this bias in administrative data sets; however, no analytic technique explored could adjust for its influence. Improved methods to achieve valid interpretation of protection in the elderly are needed.
    PLoS ONE 07/2011; 6(7):e22618. · 3.53 Impact Factor
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    ABSTRACT: Neisseria gonorrhoeae strains that fail to produce the enzyme prolyliminopeptidase have been identified in Canada. Commercial test panels use prolyliminopeptidase activity for identification and to avoid the misdiagnosis of gonorrhea, at least 2 distinct methods for the confirmatory identification of N. gonorrhoeae is imperative.
    Sexually transmitted diseases 01/2011; 38(1):40-2. · 2.58 Impact Factor