Porcine-derived pancreatic enzyme replacement therapy may be linked to chronic hepatitis E virus infection in cystic fibrosis lung transplant recipients.

OBJECTIVES: In high-income countries hepatitis E virus (HEV) is an uncommonly diagnosed porcine-derived zoonoses. After identifying disproportionate chronic HEV infections in persons with cystic fibrosis (pwCF) postlung transplant, we sought to understand its epidemiology and potential drivers. DESIGN: All pwCF post-transplant attending our regional CF centre were screened for HEV. HEV prevalence was compared against non-transplanted pwCF and with all persons screened for suspected HEV infection from 2016 to 2022 in Alberta, Canada. Those with chronic HEV infection underwent genomic sequencing and phylogenetic analysis. Owing to their swine derivation, independently sourced pancreatic enzyme replacement therapy (PERT) capsules were screened for HEV. RESULTS: HEV seropositivity was similar between transplanted and non-transplanted pwCF (6/29 (21%) vs 16/83 (19%); p=0.89). Relative to all other Albertans investigated for HEV as a cause of hepatitis (n=115/1079, 10.7%), pwCF had a twofold higher seropositivity relative risk and this was four times higher than the Canadian average. Only three chronic HEV infection cases were identified in all of Alberta, all in CF lung transplant recipients (n=3/29, 10.3%). Phylogenetics confirmed cases were unrelated porcine-derived HEV genotype 3a. Ninety-one per cent of pwCF were taking PERT (median 8760 capsules/person/year). HEV RNA was detected by RT-qPCR in 44% (47/107) of PERT capsules, and sequences clustered with chronic HEV cases. CONCLUSION: PwCF had disproportionate rates of HEV seropositivity, regardless of transplant status. Chronic HEV infection was evident only in CF transplant recipients. HEV may represent a significant risk for pwCF, particularly post-transplant. Studies to assess HEV incidence and prevalence in pwCF, and potential role of PERT are required.

Case Series of Jamestown Canyon Virus Infections with Neurologic Outcomes, Canada, 2011-2016.

Jamestown Canyon virus (JCV) is a mosquitoborne orthobunyavirus in the California serogroup that circulates throughout Canada and the United States. Most JCV exposures result in asymptomatic infection or a mild febrile illness, but JCV can also cause neurologic diseases, such as meningitis and encephalitis. We describe a case series of confirmed JCV-mediated neuroinvasive disease among persons from the provinces of British Columbia, Alberta, Quebec, and Nova Scotia, Canada, during 2011-2016. We highlight the case definitions, epidemiology, unique features and clinical manifestations, disease seasonality, and outcomes for those cases. Two of the patients (from Quebec and Nova Scotia) might have acquired JCV infections during travel to the northeastern region of the United States. This case series collectively demonstrates JCV's wide distribution and indicates the need for increased awareness of JCV as the underlying cause of meningitis/meningoencephalitis during mosquito season.

Pediatric antibody responses to SARS-CoV-2 after infection and vaccination in Calgary, Canada.

BACKGROUND: There are few reports of longitudinal serologic responses in children following Sars-CoV-2 infection and vaccination. This study describes longitudinal SARS-CoV-2 antibody responses following infection, vaccination, or both (hybrid immunity) in a cohort of Canadian children. The objectives of our study were to compare antibody levels following SARS-CoV-2 infection, vaccination, and hybrid immunity and to examine antibody decline after final antigen exposure. METHODS: The Alberta Childhood COVID-19 Cohort (AB3C) study was a prospective longitudinal cohort study conducted from July 2020 to September 2022 with repeat sampling across 5 visits. Children under 18 years of age were enrolled for serial measurement of antibody responses to SARS-CoV-2 virus vaccine and infection. RESULTS: The final sample size was 919; participants were 50.5% female, 48.2% were > 12 years and 88.5% were white ethnicity. The median peak spike IgG level of those with only infection was not different from those with no vaccination or infection (233 AU/mL (IQR: 99-944 AU/mL) vs. 3 AU/mL (IQR: 1-5 AU/mL; P = 0.1765). Participants with infections after vaccination had higher IgG levels than those where infection preceded vaccination (median: 36,660 (IQR: 22,084 - 40,000 AU/mL) vs. 17,461 AU/mL (IQR: 10,617 - 33,212 AU/mL); P < 0.0001). In a linear mixed methods model, children with infection-only had low levels of antibody that stayed stable over the study duration without further antigen exposures. Those with infection after vaccination had the slowest rate of antibody decline over time at 4% (95%CI: 2-5%) per week, compared with children where infection preceded vaccine 7% (95%CI: 6-8%) per week. CONCLUSIONS: Children with hybrid immunity conferred through vaccination (2 + doses) followed by a SARS-CoV-2 infection had the highest and longest lasting antibody levels, compared to children who had an infection followed by vaccination, vaccination-only, or infection-only. The longer-term clinical importance of these findings, related to prevention of repeated infections and severe outcomes and need for further vaccine doses, is not yet known.

Evaluation of Diagnostic Accuracy of Eight Commercial Assays for the Detection of Rubella Virus-Specific IgM Antibodies.

Rubella and congenital rubella syndrome are caused by the rubella virus and are preventable through vaccination, making disease eradication possible. Monitoring of progress toward global eradication and local elimination requires high-quality, sensitive disease surveillance that includes laboratory confirmation of cases. Previous evaluations of anti-rubella IgM detection methods resulted in the broad adoption of the Enzygnost (most recently manufactured by Siemens) enzyme-linked immunosorbent assay (ELISA) kits within WHO's global measles and rubella laboratory network, but they have been discontinued. This study evaluated seven comparable ELISAs from six manufacturers (Trinity Biotech, Euroimmun, Clin-Tech, NovaTec and Virion\Serion) as well as one automated chemiluminescent assay (CLIA) from DiaSorin. These assays include three IgM capture assays and five indirect ELISAs. A panel of 238 sera was used for the evaluation that included 38 archival rubella IgM-positive sera and 200 sera collected from patients with symptomatically similar diseases, such as measles, dengue, parvovirus B19 infection, and roseola. With this panel of sera, the sensitivity of the methods ranged from 63.2% to 100% and the specificity from 80.0% to 99.5%. No single method had both sensitivity and specificity of >90%, unless sera with equivocal results were considered presumptively positive. Some assays, particularly the Serion ELISA, had a large number of false positives with parvovirus B19 IgM-positive sera as well as sera from confirmed measles cases. The performance characteristics identified in this evaluation serve as a reminder to not rely solely on rubella IgM results for case confirmation in elimination settings.

Evaluation of Diagnostic Accuracy of Eight Commercial Assays for the Detection of Measles Virus-Specific IgM Antibodies.

The World Health Organization (WHO) has targeted measles for global eradication through mass immunization. For effective monitoring of eradication targets, high-quality surveillance is needed. The detection of IgM antibodies, specific to the measles virus, with the use of commercial enzyme-linked immunosorbent assays (ELISA or EIA) is broadly used within the WHO global measles and rubella laboratory network for laboratory confirmation, and in particular, ELISA kits manufactured by Siemens (Enzygnost kits) have been primarily used. Spurred by the discontinuation of these kits, this study aims to report on the clinical sensitivity and specificity of comparable commercial ELISA kits and one automated chemiluminescent immunoassay (CLIA) method. A panel of 239 serum samples was assembled that included sera from confirmed measles cases (n = 50) and probable post-MMR vaccine response (n = 2). Measles-negative sera (n = 187) were collected from individuals presenting with other fever and rash illnesses. A total of 7 ELISA kits (Euroimmun native antigens and recombinant nucleoprotein, IBL, Clin-Tech Microimmune, NovaTec NovaLisa, Serion, and Siemens Enzygnost) and one CLIA method (DiaSorin LIAISON XL) were evaluated. The ELISA kits included two IgM capture methods and five indirect methods. Calculated sensitivities and specificities ranged from 75.0% to 98.1% and 86.6% to 99.5%, respectively. The parvovirus B19 IgM positive sera were noted to cause false-positive results, particularly for the ELISA kits from Serion and NovaLisa; specificities for this subset of samples ranged from 51.4% to 100.0%. The capture IgM ELISA methods provided the best combination of sensitivity and specificity.

Experience with a triplex arbovirus nucleic acid test (NAT) at a Canadian Public Health Laboratory.

BACKGROUND: Dengue, chikungunya and zika infections occur in tropical and subtropical regions of the world. We describe the utilization of an in-house nucleic acid test (NAT) targeting all three viruses for febrile returning travelers in Alberta, Canada. METHODS: NAT was performed until 40 days from symptom onset or exposure due to the prolonged duration of zika virus RNA detection. From Sept 1, 2017 to August 31, 2019, 2552 specimens from 1932 patients were tested. RESULTS: Approximately 2% of patients tested were NAT positive for dengue virus (n = 42), chikungunya virus (n = 4), and zika virus (n = 1). The majority presented with fever, myalgia and rash. Regions with the most frequent travel included SouthEast Asia (68.5%), South America (25%) and the Caribbean (6.5%). Ct values were stronger (~ 1.5 logs) for patients within 1-3 days following onset of clinical symptoms than those presenting later. Nineteen patients had urine and plasma submitted; 5 were positive for both specimens and 2 were positive only for dengue virus in the urine. Also, Ct values were lower for plasma when compared to the corresponding urine. RNA was detected until 10 days and 5 days post-exposure in plasma and urine respectively for dengue virus. CONCLUSIONS: Owing to dengue viremia detected beyond the conventional 7 days and low levels of circulating zika virus globally, a cutoff of 14 days from symptom onset to NAT is sufficient to diagnose acute cases. Inclusion of a zoonotic history form that collects appropriate clinical history results in improved test utilization.

A Public Health Laboratory Response to the Pandemic.

An outbreak of coronavirus disease 2019 (COVID-19) caused by a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) began in Wuhan, Hubei, China, in December 2019 and spread rapidly worldwide. The response by the Alberta Precision Laboratories, Public Health Laboratory (ProvLab), AB, Canada, included the development and implementation of nucleic acid detection-based assays and dynamic changes in testing protocols for the identification of cases as the epidemic curve increased exponentially. This rapid response was essential to slow down and contain transmission and provide valuable time to the local health authorities to prepare appropriate response strategies. As of May 24, 2020, 236,077 specimens were tested, with 6,475 (2.74%) positives detected in the province of Alberta, Canada. Several commercial assays are now available; however, the response from commercial vendors to develop and market validated tests is a time-consuming process. In addition, the massive global demand made it difficult to secure a reliable commercial supply of testing kits and reagents. A public health laboratory serves a unique and important role in the delivery of health care. One of its functions is to anticipate and prepare for novel emerging pathogens with a plan for pandemic preparedness. Here, we outline the response that involved the development and deployment of testing methodologies that evolved as SARS-CoV-2 spread worldwide, the challenges encountered, and mitigation strategies. We also provide insight into the organizational structure of how a public health response is coordinated in Alberta, Canada, and its benefits.

Evaluation of Six Commercial Mid- to High-Volume Antibody and Six Point-of-Care Lateral Flow Assays for Detection of SARS-CoV-2 Antibodies.

Coronavirus disease (COVID) serological tests are essential to determine the overall seroprevalence of a population and to facilitate exposure estimates within that population. We performed a head-to-head assessment of enzyme immunoassays (EIAs) and point-of-care lateral flow assays (POCTs) to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Demographics, symptoms, comorbidities, treatment, and mortality of patients whose sera were used were also reviewed. Six EIAs (Abbott, Affinity, Bio-Rad, DiaSorin, Euroimmun, and Roche) and six POCTs (BTNX, Biolidics, Deep Blue, Genrui, Getein BioTech, and Innovita) were evaluated for the detection of SARS-CoV-2 antibodies in known COVID-19-infected individuals. Sensitivity of EIAs ranged from 50 to 100%, with only four assays having overall sensitivities of >95% after 21 days after symptom onset. Notably, cross-reactivity with other respiratory viruses (parainfluenza virus [PIV-4] [n = 5], human metapneumovirus [hMPV] [n = 3], rhinovirus/enterovirus [n = 1], CoV-229E [n = 2], CoV-NL63 [n = 2], and CoV-OC43 [n = 2]) was observed; however, overall specificity of EIAs was good (92 to 100%; all but one assay had specificity above 95%). POCTs were 0 to 100% sensitive >21 days after onset, with specificity ranging from 96 to 100%. However, many POCTs had faint banding and were often difficult to interpret. Serology assays can detect SARS-CoV-2 antibodies as early as 10 days after symptom onset. Serology assays vary in their sensitivity based on the marker (IgA/IgM versus IgG versus total) and by manufacturer; however, overall only 4 EIAs and 4 POCTs had sensitivities of >95% >21 days after symptom onset. Cross-reactivity with other seasonal coronaviruses is of concern. Serology assays should not be used for the diagnosis of acute infection but rather in carefully designed serosurveys to facilitate understanding of seroprevalence in a population and to identify previous exposure to SARS-CoV-2.

Health services restructuring in Alberta and the 2009 pandemic influenza-An untimely concurrence.

In the last 12 years, every Canadian province and territory has undertaken significant health services restructuring, with the pace of change accelerating recently. When the H1N1 Pandemic Influenza (PI) hit Alberta in the spring of 2009, the province had just begun a restructuring of health services of a scale unprecedented in Canada. The new province-wide entity, Alberta Health Services (AHS), was faced with mounting an effective response to a global communicable disease outbreak during a time of great organizational flux. In this retrospective, the authors reflect on challenges and opportunities presented during the AHS PI response related to the coordination of public health, laboratory services, emergency and disaster management, communications, and health services delivery. Lessons learned are shared that may be helpful to other provinces and territories as they continue to evolve their systems, so that they may be better prepared to respond to an untimely event such as a pandemic.

Vaccine Effectiveness Against Lineage-matched and -mismatched Influenza B Viruses Across 8 Seasons in Canada, 2010-2011 to 2017-2018.

Vaccine effectiveness (VE) against influenza B was derived separately for Victoria and Yamagata lineages across 8 seasons (2010-2011 to 2017-2018) in Canada when trivalent influenza vaccine was predominantly used. VE was ≥50% regardless of lineage match to circulating viruses, except when the vaccine strain was unchanged from the prior season.

Simultaneous Detection and Differentiation between Wild-Type and Vaccine Measles Viruses by a Multiplex Real-Time Reverse Transcription-PCR Assay.

Measles is one of the most contagious viral respiratory infections and was declared to be eliminated from Canada in 1998; however, measles cases and outbreaks still occur every year through reintroduction from other parts of the world. Laboratory confirmation of measles virus (MV) RNA by real-time PCR provides a definitive diagnosis, and molecular analysis to determine the genotype is the only way to distinguish between wild-type and vaccine strains. This distinction is important since live attenuated vaccine strains are able to replicate in the patient and can be associated with rash and fever but are poorly transmissible, if at all. Prompt reporting of measles cases to local authorities, including differentiation between wild-type and vaccine strains, allows for optimal management and contact tracing. The development and validation of a multiplex real-time reverse transcription-PCR (rtRT-PCR) assay for the simultaneous detection and differentiation of the Moraten and Schwarz vaccine strains from presumptive wild-type MV in a format that can be easily implemented for high-throughput testing of patient samples are reported here. This assay is sensitive, specific, reproducible, and 100% accurate in comparison with the gold standard comparator assay.

Age-Related Differences in Influenza B Infection by Lineage in a Community-Based Sentinel System, 2010-2011 to 2015-2016, Canada.

Age-related differences in influenza B lineage detection were explored in the community-based Canadian Sentinel Practitioner Surveillance Network (SPSN) from 2010-2011 to 2015-2016. Whereas >80% of B(Victoria) cases were <40 years old, B(Yamagata) cases showed a bimodal age distribution with 27% who were <20 years old and 61% who were 30-64 years old, but with a notable gap in cases between 20 and 29 years old (4%). Overall, the median age was 20 years lower for B(Victoria) vs B(Yamagata) cases (20 vs 40 years; P < .01). Additional phylodynamic and immuno-epidemiological research is needed to understand age-related variation in influenza B risk by lineage, with potential implications for prevention and control across the lifespan.

Serial Vaccination and the Antigenic Distance Hypothesis: Effects on Influenza Vaccine Effectiveness During A(H3N2) Epidemics in Canada, 2010-2011 to 2014-2015.

Background: The antigenic distance hypothesis (ADH) predicts that negative interference from prior season's influenza vaccine (v1) on the current season's vaccine (v2) protection may occur when the antigenic distance is small between v1 and v2 (v1 ≈ v2) but large between v1 and the current epidemic (e) strain (v1 ≠ e). Methods: Vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza A(H3N2) illness was estimated by test-negative design during 3 A(H3N2) epidemics (2010-2011, 2012-2013, 2014-2015) in Canada. Vaccine effectiveness was derived with covariate adjustment across v2 and/or v1 categories relative to no vaccine receipt among outpatients aged ≥9 years. Prior vaccination effects were interpreted within the ADH framework. Results: Prior vaccination effects varied significantly by season, consistent with the ADH. There was no interference by v1 in 2010-2011 when v1 ≠ v2 and v1 ≠ e, with comparable VE for v2 alone or v2 + v1: 34% (95% confidence interval [CI] = -51% to 71%) versus 34% (95% CI = -5% to 58%). Negative interference by v1 was suggested in 2012-2013 with nonsignificant reduction in VE when v1 ≈ v2 and v1 ≠ e: 49% (95% CI = -47% to 83%) versus 28% (95% CI = -12% to 54%). Negative effects of prior vaccination were pronounced and statistically significant in 2014-2015 when v1 ≡ v2 and v1 ≠ e: 65% (95% CI = 25% to 83%) versus -33% (95% CI = -78% to 1%). Conclusions: Effects of repeat influenza vaccination were consistent with the ADH and may have contributed to findings of low VE across recent A(H3N2) epidemics since 2010 in Canada.

Fatal Infection with Murray Valley Encephalitis Virus Imported from Australia to Canada, 2011.

Murray Valley encephalitis virus (MVEV), a flavivirus belonging to the Japanese encephalitis serogroup, can cause severe clinical manifestations in humans. We report a fatal case of MVEV infection in a young woman who returned from Australia to Canada. The differential diagnosis for travel-associated encephalitis should include MVEV, particularly during outbreak years.

Live Attenuated Versus Inactivated Influenza Vaccine in Hutterite Children: A Cluster Randomized Blinded Trial.

BACKGROUND: Whether vaccinating children with intranasal live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in providing both direct protection in vaccinated persons and herd protection in unvaccinated persons is uncertain. Hutterite colonies, where members live in close-knit, small rural communities in which influenza virus infection regularly occurs, offer an opportunity to address this question. OBJECTIVE: To determine whether vaccinating children and adolescents with LAIV provides better community protection than IIV. DESIGN: A cluster randomized blinded trial conducted between October 2012 and May 2015 over 3 influenza seasons. (ClinicalTrials.gov: NCT01653015). SETTING: 52 Hutterite colonies in Alberta and Saskatchewan, Canada. PARTICIPANTS: 1186 Canadian children and adolescents aged 36 months to 15 years who received the study vaccine and 3425 community members who did not. INTERVENTION: Children were randomly assigned according to community in a blinded manner to receive standard dosing of either trivalent LAIV or trivalent IIV. MEASUREMENTS: The primary outcome was reverse transcriptase polymerase chain reaction-confirmed influenza A or B virus in all participants (vaccinated children and persons who did not receive the study vaccine). RESULTS: Mean vaccine coverage among children in the LAIV group was 76.9% versus 72.3% in the IIV group. Influenza virus infection occurred at a rate of 5.3% (295 of 5560 person-years) in the LAIV group versus 5.2% (304 of 5810 person-years) in the IIV group. The hazard ratio comparing LAIV with IIV for influenza A or B virus was 1.03 (95% CI, 0.85 to 1.24). LIMITATION: The study was conducted in Hutterite communities, which may limit generalizability. CONCLUSION: Immunizing children with LAIV does not provide better community protection against influenza than IIV. PRIMARY FUNDING SOURCE: The Canadian Institutes for Health Research.

Integrated Sentinel Surveillance Linking Genetic, Antigenic, and Epidemiologic Monitoring of Influenza Vaccine-Virus Relatedness and Effectiveness During the 2013-2014 Influenza Season.

BACKGROUND: Canada's Sentinel Physician Surveillance Network links genetic, antigenic, and vaccine effectiveness (VE) measures in an integrated platform of influenza monitoring, described here for the 2013-2014 influenza season of resurgent A(H1N1)pdm09 and late-season type B activity. METHODS: VE was estimated as [1 - odds ratio] × 100% and compared vaccination status between individuals who tested positive (cases) and those who tested negative (controls) for influenza virus. Vaccine-virus relatedness was assessed by genomic sequence analysis and hemagglutination inhibition assays. RESULTS: Analyses included 1037 controls (of whom 33% were vaccinated) and 663 cases (of whom 14% were vaccinated). A total of 415 cases tested positive for A(H1N1)pdm09 virus, 15 tested positive for A(H3N2) virus, 191 tested positive for B/Yamagata-lineage virus, 6 tested positive for B/Victoria-lineage virus, and 36 tested positive for viruses of unknown subtype or lineage. A(H1N1)pdm09 viruses belonged to clade 6B, distinguished by a K163Q substitution, but remained antigenically similar to the A/California/07/2009-like vaccine strain, with an adjusted VE of 71% (95% confidence interval [CI], 58%-80%). Most B/Yamagata-lineage viruses (83%) clustered phylogenetically with the prior (ie, 2012-2013) season's B/Wisconsin/01/2010-like clade 3 vaccine strain, while only 17% clustered with the current (ie, 2013-2014) season's B/Massachusetts/02/2012-like clade 2 vaccine strain. The adjusted VE for B/Yamagata-lineage virus was 73% (95% CI, 57%-84%), with a lower VE obtained after partial calendar-time adjustment for clade-mismatched B/Wisconsin/01/2010-like virus (VE, 63%; 95% CI, 41%-77%), compared with that for clade-matched B/Massachusetts/02/2012-like virus (VE, 88%; 95% CI, 48%-97%). No A(H3N2) viruses clustered with the A/Texas/50/2012-like clade 3C.1 vaccine strain, and more than half were antigenically mismatched, but sparse data did not support VE estimation. CONCLUSIONS: VE corresponded with antigenically conserved A(H1N1)pdm09 and lineage-matched B/Yamagata viruses with clade-level variation. Surveillance linking genotypic, phenotypic, and epidemiologic measures of vaccine-virus relatedness and effectiveness could better inform predictions of vaccine performance and reformulation.

Systematic community- and hospital-based surveillance for enterovirus-D68 in three Canadian provinces, August to December 2014.

Respiratory specimens collected from outpatients with influenza-like illness in three Canadian provinces (British Columbia (BC), Alberta and Quebec) participating in a community-based sentinel surveillance network were prospectively screened for enterovirus-D68 (EV-D68) from 1 August to 31 December 2014 and compared to specimens collected from 1 October 2013 to 31 July 2014. Eighteen (1%) of 1,894 specimens were EV-D68-positive: 1/348 (0.3%) collected from October to December 2013 and 11/460 (2.4%) from October to December 2014, an eight-fold increase in detection rates (p=0.01), consistent with epidemic circulation in autumn 2014. The remaining EV-D68 detections were in September 2014 (6/37). Enhanced passive surveillance was also conducted on all inpatient and outpatient EV-D68 cases (n=211) detected at the BC provincial reference laboratory from 28 August to 31 December 2014. Incidence of hospitalisations was 3/100,000 overall and 21, 17, 4 and 1/100,000 among those<5, 5-9, 10-19 and ≥20-years-old with male-to-female ratios>1 among paediatric but not adult cases. Three cases in BC with comorbidity or co-infection died and five exhibited neurological features persisting >9 months. Active surveillance in outpatient and inpatient settings is needed from more areas and additional seasons to better understand EV-D68 epidemiology and potential at-risk groups for severe or unusual manifestations.

Canadian Public Health Laboratory Network laboratory guidelines for the diagnosis of neurosyphilis in Canada.

Neurosyphilis refers to infection of the central nervous system by Treponema pallidum, which may occur at any stage. Neurosyphilis has been categorized in many ways including early and late, asymptomatic versus symptomatic and infectious versus non-infectious. Late neurosyphilis primarily affects the central nervous system parenchyma, and occurs beyond early latent syphilis, years to decades after the initial infection. Associated clinical syndromes include general paresis, tabes dorsalis, vision loss, hearing loss and psychiatric manifestations. Unique algorithms are recommended for HIV-infected and HIV-uninfected patients, as immunocompromised patients may present with serologic and cerebrospinal fluid findings that are different from immunocompetent hosts. Antibody assays include a VDRL assay and the FTA-Abs, while polymerase chain reaction for T. pallidum can be used as direct detection assays for some specimens. This chapter reviews guidelines for specimen types and sample collection, and identifies two possible algorithms for use with immunocompromised and immunocompetent hosts using currently available tests in Canada, along with a review of treatment response and laboratory testing follow-up.

La neurosyphilis désigne l'infection du système nerveux central par le Treponema pallidum à tout stade de la maladie. Elle est classée de diverses façons, y compris précoce ou tardive, asymptomatique ou symptomatique, infectieuse ou non infectieuse. La neurosyphilis tardive touche principalement le parenchyme du système nerveux central et se manifeste après une syphilis latente précoce, des années ou même des décennies après l'infection initiale. Des syndromes cliniques s'y associent, y compris la parésie générale, le tabes dorsalis, la perte d'acuité visuelle et auditive et les manifestations psychiatriques. Des algorithmes différents sont recommandés pour les patients infectés ou non infectés par le VIH, car les manifestations sérologiques et céphalorachidiennes des patients immunodéprimés peuvent différer de celles des patients immunocompétents. Les tests de détection des anticorps incluent le VDRL et le FTA-Abs, tandis que pour certains prélèvements, la réaction en chaîne de la polymérase peut servir de test de détection du T. pallidum. Ce chapitre traite des directives sur les types de prélèvement et leur collecte et présente deux algorithmes qui peuvent être utilisés auprès des hôtes immunodéprimés et immunocompétents à l'aide des tests offerts au Canada. Il contient également une analyse de la réponse thérapeutique et du suivi des tests de laboratoire.

Canadian Public Health Laboratory Network laboratory guidelines for congenital syphilis and syphilis screening in pregnant women in Canada.

Despite universal access to screening for syphilis in all pregnant women in Canada, cases of congenital syphilis have been reported in recent years in areas experiencing a resurgence of infectious syphilis in heterosexual partnerships. Antenatal screening in the first trimester continues to be important and should be repeated at 28 to 32 weeks and again at delivery in women at high risk of acquiring syphilis. The diagnosis of congenital syphilis is complex and is based on a combination of maternal history and clinical and laboratory criteria in both mother and infant. Serologic tests for syphilis remain important in the diagnosis of congenital syphilis and are complicated by the passive transfer of maternal antibodies which can affect the interpretation of reactive serologic tests in the infant. All infants born to mothers with reactive syphilis tests should have nontreponemal tests (NTT) and treponemal tests (TT) performed in parallel with the mother's tests. A fourfold or higher titre in the NTT in the infant at delivery is strongly suggestive of congenital infection but the absence of a fourfold or greater NTT titre does not exclude congenital infection. IgM tests for syphilis are not currently available in Canada and are not recommended due to poor performance. Other evaluation in the newborn infant may include long bone radiographs and cerebrospinal fluid tests but all suspect cases should be managed in conjunction with sexually transmitted infection and/or pediatric experts.

Même si toutes les femmes du Canada ont accès au test de dépistage de la syphilis, des cas de syphilis congénitale ont été déclarés ces dernières années dans des régions où l'on constate une résurgence de la syphilis infectieuse chez des partenaires hétérosexuels. Il est toujours important de procéder à un dépistage anténatal pendant le premier trimestre, de le reprendre entre 28 et 32 semaines de grossesse, puis à l'accouchement chez les femmes très vulnérables à la syphilis. Le diagnostic de syphilis congénitale est complexe. Il repose sur l'histoire de la mère ainsi que sur des critères cliniques et des critères de laboratoire à la fois chez la mère et le nourrisson. Les tests sérologiques de la syphilis s'imposent toujours pour diagnostiquer la syphilis congénitale, mais ils sont compliqués par le transfert passif des anticorps maternels qui peut nuire à l'interprétation des résultats réactifs chez le nourrisson. Tous les nourrissons nés d'une mère dont les tests de syphilis sont réactifs devraient subir des tests non tréponomiques (TNT) et des tests tréponomiques (TT) conjointement aux tests de la mère. Un titrage du TNT au moins quatre fois plus élevé que la normale chez le nourrisson à l'accouchement est fortement évocateur d'une infection congénitale, mais l'absence d'un tel résultat n'en exclut pas la possibilité. Les tests d'IgM pour déceler la syphilis ne sont pas offerts au Canada. Ils ne sont pas recommandés en raison de leurs piètres résultats. Parmi les autres évaluations du nouveau-né, soulignons les radiographies des os longs et les tests du liquide céphalorachidien, mais il faut prendre en charge tous les cas présumés conjointement avec des pédiatres ou des spécialistes des infections transmises sexuellement.

Canadian Public Health Laboratory Network laboratory guidelines for the use of serological tests (excluding point-of-care tests) for the diagnosis of syphilis in Canada.

Syphilis, caused by the bacterium Treponema pallidum subsp. pallidum, is an infection recognized since antiquity. It was first reported at the end of the 15th century in Europe. Infections may be sexually transmitted as well as spread from an infected mother to her fetus or through blood transfusions. The laboratory diagnosis of syphilis infection is complex. Because this organism cannot be cultured, serology is used as the principal diagnostic method. Some of the issues related to serological diagnoses are that antibodies take time to appear after infection, and serology screening tests require several secondary confirmatory tests that can produce complex results needing interpretation by experts in the field. Traditionally, syphilis screening was performed using either rapid plasma reagin or Venereal Disease Research Laboratory tests, and confirmed by treponemal tests such as MHA-TP, TPPA or FTA-Abs. Currently, that trend is reversed, ie, most of the laboratories in Canada now screen for syphilis using treponemal enzyme immunoassays and confirm the status of infection using rapid plasma reagin or Venereal Disease Research Laboratory tests; this approach is often referred to as the reverse algorithm. This chapter reviews guidelines for specimen types and sample collection, treponemal and non-treponemal tests utilized in Canada, the current status of serological tests for syphilis in Canada, the complexity of serological diagnosis of syphilis infection and serological testing algorithms. Both traditional and reverse sequence algorithms are recommended and the algorithm used should be based on a combination of local disease epidemiology, test volumes, performance of the proposed assays and available resources.

La syphilis, causée par la bactérie Treponema pallidum sous-espèce pallidum, est une infection connue depuis l'antiquité. Elle a été signalée pour la première fois en Europe, à la fin du XVe siècle. Les infections peuvent être transmises sexuellement, par une mère infectée à son fœtus ou par des transfusions sanguines. Il est difficile de diagnostiquer la syphilis en laboratoire. Puisque cet organisme ne peut pas être mis en culture, la sérologie est la principale méthode diagnostique. Parmi les problèmes liés aux diagnostics sérologiques, soulignons qu'il faut du temps pour que les anticorps fassent leur apparition après l'infection et que les tests de dépistage sérologique doivent s'associer à plusieurs tests de confirmation secondaires qui peuvent produire des résultats complexes devant être interprétés par des experts dans le domaine. Habituellement, la syphilis était dépistée au moyen du test rapide de la réagine plasmatique ou du test Veneral Disease Research Laboratory et était confirmée par les tests tréponémiques comme le MHA-TP, le TP-PA ou le FTA-Abs. Cette tendance s'inverse actuellement, car la plupart des laboratoires du Canada dépistent la syphilis au moyen d'épreuves immunoenzymatiques tréponémiques et confirment le statut de l'infection au moyen du test rapide de la réagine plasmatique ou du test Veneral Disease Reseach Laboratory. Cette approche est souvent désignée par le terme algorithme inversé. Ce chapitre analyse les directives sur les types de prélèvements et la collecte des échantillons, les tests tréponémiques et non tréponémiques utilisés au Canada, le statut actuel des tests sérologiques de la syphilis au Canada, la complexité du diagnostic sérologique d'infection par la syphilis et les algorithmes des tests sérologiques. Tant l'algorithme habituel que l'algorithme inversé sont recommandés, et l'algorithme utilisé devrait tenir compte à la fois de l'épidémiologie locale de la maladie, du volume de tests, de l'exécution des tests proposés et des ressources disponibles.