The Resurgence of Lymphogranuloma Venereum: Changing Presentation of Lymphogranuloma Venereum in the Era of HIV Preexposure Prophylaxis, 2004 to 2022.

BACKGROUND: Before the early 2000s, the sexually transmitted infection lymphogranuloma venereum (LGV) was rare in high-income countries. Initially, most cases in these countries were among symptomatic men who have sex with men (MSM) living with HIV. In the context of widespread HIV preexposure prophylaxis (PrEP), LGV's epidemiology may be changing. We aimed to characterize the epidemiology and clinical presentation of LGV in the PrEP era. METHODS: A retrospective chart review was performed on all LGV cases occurring between November 2004 to October 2022 in British Columbia (BC), Canada. Cases were stratified by having occurred before (2004-2017) or after widespread PrEP availability in BC (2018-2022). Annual rates and test positivity percentages were calculated. Bivariate logistic regression was performed to identify drivers of asymptomatic infection in the PrEP era. RESULTS: Among 545 cases identified, 205 (37.6%) occurred pre-PrEP and 340 (62.4%) occurred during the PrEP era. Most cases were among MSM (97.2%). The estimated rate of LGV has doubled from 2018 to 2022, reaching 1535.2 cases per 100,000 PrEP users. Most PrEP-era cases were among HIV-negative individuals (65.3%), particularly those on PrEP (72.6%). Cases in the PrEP era were often asymptomatic compared with pre-PrEP (38.6% vs. 19.3%; P < 0.001). Users of PrEP were more likely to experience asymptomatic infection compared with HIV-negative PrEP nonusers (odds ratio, 2.07; 95% confidence interval, 1.07-3.99). CONCLUSIONS: In the context of increased asymptomatic testing, LGV may be increasing in BC. Most infections now occur among HIV-negative MSM. A high proportion of infections are asymptomatic.

Examining the impacts of a syphilis awareness campaign among gay, bisexual, and other men who have sex with men (gbMSM) in British Columbia, Canada.

OBJECTIVES: Syphilis rates have increased in BC and disproportionately affect gay, bisexual, and other men who have sex with men (gbMSM). A social marketing campaign (Syphistory) ran from January to September 2017 with the primary goal of increasing syphilis knowledge and a secondary goal of increasing syphilis screening among gbMSM in BC. METHODS: We used pre- and post-campaign surveys to assess changes in syphilis knowledge from a convenience sample of clients attending STI clinics using one-sided t-tests. We used online Piwik metrics to examine the campaign reach, and provincial testing data to examine trends in syphilis screening. We used data from the Engage Study to examine factors associated with campaign awareness and associations with syphilis testing. RESULTS: Of the 2155 visitors to the Syphistory website with known geography, 79.4% were from BC. Moreover, STI clinic participants who saw the campaign demonstrated a greater knowledge of syphilis (9.7/12, 80.8%) than those who did not see the campaign (mean 8.9/12, 74%) (p < 0.001). Provincial syphilis testing rates were 8764 and 9749 in the 12 months before and after the campaign; however, we did not find an overall trend in testing before versus after the campaign (p = 0.147). Among Engage participants, 12.7% reported seeing the campaign and we found an association between campaign exposure and recent syphilis testing (aOR = 2.73; 95% CI = 1.51, 4.93). CONCLUSION: gbMSM who saw the campaign were more likely to report being tested for syphilis in the previous 6 months. STI clinic attendees who reported seeing the campaign also had higher syphilis knowledge compared to those who did not.

RéSUMé: OBJECTIFS: Les taux de syphilis ont augmenté en Colombie-Britannique et affectent de manière disproportionnée les hommes gais, bisexuels et autres hommes ayant des relations sexuelles avec des hommes (gbHARSAH). Une campagne de marketing social (Syphistory) a été mené de janvier à septembre 2017 avec pour objectif principal d'informer sur la syphilis et pour objectif secondaire d'augmenter le dépistage de la syphilis chez les gbHARSAH en Colombie-Britannique. MéTHODES: Nous avons réalisé deux sondages, l'un avant et l'autre après la campagne, sur un échantillon de convenance constitué de patients fréquentant des cliniques ITS, pour évaluer les changements dans les connaissances sur la syphilis à l'aide de tests t unilatéraux. Nous avons utilisé les mesures Piwik en ligne pour examiner la portée de la campagne et les données provinciales sur les tests pour examiner les tendances quant au dépistage de la syphilis. Nous avons utilisé les données de l'étude Engage à Vancouver, pour identifier les facteurs associés à la sensibilisation lors de la campagne et les associations avec le dépistage de la syphilis. RéSULTATS: Sur les 2 155 visiteurs du site Web Syphistory dont la position géographique était connue, 79,4 % provenaient de la Colombie-Britannique. De plus, les participants aux cliniques ITS ayant vu la campagne ont démontré une meilleure connaissance de la syphilis (9,7/12, 80,8 %) par rapport à ceux n'ayant pas vu la campagne (moyenne 8,9/12, 74 %) (p<0,001). Les taux provinciaux de dépistage de la syphilis étaient de 8 764 et 9 749 au cours des 12 mois précédant et suivant la campagne; cependant, nous n'avons pas trouvé de tendance globale à la hausse des dépistages suite à la campagne (p=0,147). Parmi les participants Engage, 12,7 % ont déclaré avoir vu la campagne en ligne et nous avons trouvé une association entre l'exposition à la campagne et le dépistage récent de la syphilis (RCa=2,73; IC à 95 %=1,51, 4,93). CONCLUSION: Les gbHARSAH qui ont vu la campagne étaient plus susceptibles de déclarer avoir été testés pour la syphilis au cours des six derniers mois. Les participants aux cliniques ITS qui ont déclaré avoir vu la campagne avaient également une meilleure connaissance de la syphilis que ceux qui ne l'ont pas vue.

British Columbia's Experience after Implementation of the Treponema pallidum Reverse Algorithm and PCR Detection, 2015 to 2020.

British Columbia (BC) implemented the syphilis reverse screening algorithm and Treponema pallidum PCR testing in 2014. We summarize the performance characteristics of the algorithm, together with PCR direct detection, and report on syphilis cases identified from 2015 to 2020. Prior to 2015, samples for syphilis diagnosis were first screened by rapid plasma reagin (RPR). As of 2015, sera were screened by the Siemens Advia Centaur syphilis assay (enzyme immunoassay [EIA]). Positive and equivocal samples were reflex tested by a T. pallidum passive particle agglutination assay (TPPA) and RPR. We used T. pallidum DNA PCR on clinical samples and restriction fragment length polymorphism analysis to identify azithromycin resistance mutations. Case/epidemiological data were obtained from the BC surveillance system. Of 1,631,519 samples screened by the EIA, 72,492 (4.4%) were positive and 187 (<0.1%) were equivocal. Of EIA-positive/equivocal samples, 10.6% were false positive, and false positivity was higher at lower EIA indices. The reverse algorithm detected 4,693 late latent syphilis cases that likely would have been missed by RPR screening. PCR had a very high sensitivity of 100% versus 52.9% and 52.4% for dark-field (DF) and immunofluorescence (IF) microscopy, respectively. The azithromycin resistance mutation A2058G was identified in 96% of PCR-positive samples, and A2059G was identified in 4%. Annually, there were 944 to 1,467 syphilis cases, with 62% in men who reported male sexual partners. The reverse algorithm had a low false-positive rate and very few equivocal screening results but did identify previously undiagnosed late latent syphilis cases. PCR was more sensitive than both DF and IF microscopy for direct diagnosis and enabled monitoring for azithromycin resistance. IMPORTANCE In this study, we summarize the performance characteristics of the algorithm, together with PCR direct detection and epidemiological analysis, and report on syphilis cases identified from 2015 to 2020. This allowed us to paint a complete picture of the outcome of the utilization of the reverse algorithm for diagnosing syphilis cases. The study clearly showed that the reverse algorithm had a low false-positive rate and very few equivocal screening results but did identify previously undiagnosed late latent syphilis cases. PCR was more sensitive than both DF and IF microscopy for direct diagnosis and enabled monitoring for azithromycin resistance.

Characterizing female infectious syphilis cases in British Columbia to identify opportunities for optimization of care.

Introduction: The rate of infectious syphilis continues to increase among females in British Columbia (BC) and Canada, raising concerns of increased incidence of congenital syphilis. We characterized syphilis cases among females in BC to identify opportunities to prevent syphilis and optimize its care. Methods: All cases of infectious syphilis diagnosed in BC between March 13, 2018 and December 31, 2020 and reported as female gender were reviewed. Demographics, risk factors and concurrent conditions were collected from a provincial surveillance system. Subgroup analyses comparing cases with and without housing instability, substance use, mental illness and a recent sexually transmitted infection (STI) were conducted to understand differences between these subgroups. Statistical associations were calculated using chi-square or t-tests. Results: There were 226 reported cases of female infectious syphilis in BC during this period: 38 (16.8%) in 2018; 74 (32.7%) in 2019; and 114 (50.4%) in 2020. Mean age was 32 years (range 15-75 years). Of those who reported concurrent conditions, most cases had experiences with housing instability (71.1%), substance use (68.2%) and mental illness (83.9%), while 42.9% had a recent STI. Cases who reported housing instability or substance use were significantly more likely to have experiences with a recent STI, street involvement, transactional sex, mental illness and income assistance (all p<0.01). Conclusion: Our findings highlight the importance of fostering an enabling environment for syphilis care. Concurrent services to support individuals with syphilis as well as housing instability, substance use and mental illness, may help prevent syphilis and improve wellbeing.

Population-Level Outcomes of Partner Notification Among Gay, Bisexual, and Other Men Who Report Sex With Men Diagnosed With Infectious Syphilis in British Columbia, Canada.

BACKGROUND: Syphilis testing, treatment, and partner notification (PN) are centrally coordinated in British Columbia (BC), Canada. Public health (PH) nurses (PHNs) contact almost all syphilis patients and either notify partners of syphilis exposure (PH-initiated PN) or support patients to notify their own partners (patient-initiated PN). In the context of an ongoing syphilis epidemic among gay, bisexual, and other men who report sex with men (gbMSM), we measured population-level yields and compared PN approaches to inform prevention and control efforts. METHODS: All gbMSM diagnosed with infectious syphilis in 2016 in BC were included. We calculated indicators of engagement with PN among patients and PN outcomes among notifiable partners using a cascade-of-care framework. χ2 Tests compared indicators between PN approaches. RESULTS: Of the 759 syphilis diagnoses, 85.4% (648/759) were among gbMSM and 94.7% (614/648) were treated within 30 days of testing (mean [SD], 5.5 [5.2] days). Among patients, 87.7% (568/648) discussed PN with PHNs and 49.5% (281/568) named at least 1 notifiable partner, for a total of 1094 partners (mean [SD], 3.9 [5.5] partners/patient). Compared with PH-initiated PN, patient-initiated PN resulted in a greater proportion of partners notified (70.1% [573/817] vs. 89.8% [211/235]; P = 1.88 × 10-9), but there was no difference in the proportion of partners tested and/or treated (90.2% [517/573] vs. 86.7% [183/211]; P = 0.203), and diagnosed (12.8% [66/517] vs. 16.4% [30/183]; P > 0.271). CONCLUSIONS: Public health- and patient-initiated PN had similarly high yields of partners tested and/or treated, and diagnosed, demonstrating that gbMSM can contribute to syphilis PN when supported by resource-equipped PHNs.

Human Immunodeficiency Virus Seropositivity and Early Syphilis Stage Associated With Ocular Syphilis Diagnosis: A Case-control Study in British Columbia, Canada, 2010-2018.

BACKGROUND: The incidence of syphilis has been increasing worldwide in the last 20 years, disproportionately impacting those living with human immunodeficiency virus (HIV). Alongside this increase, several jurisdictions have reported increasing incidences of syphilis-related complications, including ocular syphilis. We sought to characterize ocular syphilis cases in British Columbia (BC), Canada. METHODS: This case-control study compared ocular syphilis cases, matched (1:4) to syphilis controls, that were diagnosed in BC between January 2010 and December 2018. Multivariable logistic regression was used to identify potential correlates of ocular syphilis, where variables were included in the final model if significant (P ≤ .05). RESULTS: During the study period, there were 6716 syphilis diagnoses, including 66 (0.98%) ocular syphilis cases. The median age of cases was 49.5 years (interquartile range 39-59). Most (87.8%) patients were male, where 54.6% identified as men who have sex with men. The most common ophthalmologic diagnosis was panuveitis (42.4%). Of ocular syphilis patients, 48.5% were living with HIV at the time of their syphilis diagnosis, compared to 26.4% of controls (P = .001). The proportion of syphilis cases with ocular syphilis increased from 0.48% in 2010 to 0.83% in 2018. The final multivariable model demonstrated correlates between ocular syphilis and early syphilis stage, including primary/secondary (odds ratio [OR] 4.96, 95% confidence interval [CI] 1.86-13.24) and early latent (OR 4.29, 95% CI 1.62-11.34) stages, and HIV serostatus (OR 2.16, 95% CI 1.14-4.09). CONCLUSIONS: Ocular syphilis increased over the study period, both in absolute numbers and as a proportion of all syphilis cases, a finding consistent with other jurisdictions. These findings highlight the importance of vigilance for ocular syphilis, to avoid diagnostic and treatment delays.

Spatial-Temporal Epidemiology of the Syphilis Epidemic in Relation to Neighborhood-Level Structural Factors in British Columbia, 2005-2016.

BACKGROUND: Spatial clusters of syphilis have been observed within several jurisdictions globally; however, the degree to which they are predicted by the spatial distributions of gay, bisexual, and other men who have sex with men (GBM) and testing remains unknown. We sought to describe the spatial-temporal epidemiology of infectious syphilis and identify associations between neighborhood-level factors and rates of syphilis, in British Columbia, Canada. METHODS: We used ArcGIS to map infectious syphilis cases among men (2005 to 2016), SaTScan to detect areas with significantly elevated rates of syphilis, and spatial regression to identify associations between neighborhood-level factors and rates of syphilis. RESULTS: Five clusters were identified: a core in downtown Vancouver (incidence rate ratio [IRR], 18.0; 2007-2016), 2 clusters adjacent to the core (IRR, 3.3; 2012-2016; and IRR, 2.2; 2013-2016), 1 cluster east of Vancouver (IRR, 2.1; 2013-2016), and 1 cluster in Victoria (IRR, 4.3; 2015-2016). Epidemic curves were synchronized across cluster and noncluster regions. Neighborhood-level GBM population estimates and testing rates were both associated with syphilis rates; however, the spatial distribution of syphilis was not fully explained by either of these factors. CONCLUSIONS: We identified two novel ecologic correlates of the spatial distribution of infectious syphilis-density of GBM and rates of syphilis testing-and found that these factors partially, though not entirely, explained the spatial distribution of clusters. Residual spatial autocorrelation suggests that greater syphilis testing coverage may be needed and low-barrier GBM-affirming testing should be expanded to regions outside the core.

Estimating Respiratory Syncytial Virus-associated Hospitalization in the First Year of Life Among Infants Born at 32-35 Weeks of Gestation.

BACKGROUND: Prophylaxis against respiratory syncytial virus-associated hospitalization (RSV-H) with anti-RSV monoclonal antibody is not considered cost-effective for routine use in most jurisdictions. The aim of this study was to develop a scoring tool to estimate local risk of RSV-H in the first year of life among moderately premature infants to assist in prophylaxis decision making. METHODS: A retrospective cohort was constructed from population-based databases in Nova Scotia, Canada, to follow 32- to 35-week gestation infants from the prenatal period to <12 months of age, from 1998 to 2008. Potential risk factors were entered into the logistic regression model, where the dependent variable was RSV-H. Receiver operator characteristic analysis demonstrated cutoff scores producing the highest predictive accuracy, and the likelihood ratio test was used to select the final set of variables for the predictive tool. RESULTS: In 2811 eligible infants, the overall RSV-H rate was 3.1% (88/2811). Of 17 variables considered, 3 were used to create the scoring tool: birth during December to February, household smoke exposure and household crowding. The positive likelihood ratios of predictive tool scores for high, moderate and low of RSV-H were 3.57, 3.38 and 1.95, whereas posttest probabilities (risk of RSV-H) were 11.4%, 10.8% and 1.6%, respectively. CONCLUSIONS: While able to predict infants at low risk of RSV-H, the tool did not discriminate high from moderate risk infants. The tool could be used in anticipatory care to help educate families about reducing risk of serious RSV illness in their newborn.