Retrospective Review of Prenatal Gonorrhea and Chlamydia Screening in Alberta: 2018-2022.

A retrospective 5-year province-wide evaluation of prenatal Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) screening in Alberta, Canada, was carried out to assess compliance with the provincial recommendations for universal prenatal screening as a prevention for neonatal ophthalmia. Screening generally improved across the province each year, 82.1% in 2018 and reaching 87.3% in 2022. Women in the age group under 25 years were the most likely to not have the recommended first-trimester screening and demonstrated the highest prevalence of GC and CT infections. The results of this investigation demonstrate that continued improvements are needed to achieve universal prenatal GC/CT screening in Alberta.

Use of genome sequencing to resolve differences in gradient diffusion and agar dilution antimicrobial susceptibility testing performance of Neisseria gonorrhoeae isolates in Alberta, Canada.

Agar dilution is the gold standard method for phenotypic antimicrobial susceptibility testing (AST) for Neisseria gonorrhoeae. However, this method is laborious and requires expertise, so laboratories that perform N. gonorrhoeae AST may choose alternative methods such as disk diffusion and gradient diffusion. In this study, we retrospectively compare the performance of gradient diffusion to agar dilution for 2,394 unique N. gonorrhoeae isolates identified in Alberta from 2017 to 2020 against azithromycin, cefixime, ceftriaxone, ciprofloxacin, penicillin, and tetracycline. Genome sequencing was utilized to resolve discrepancies between AST methods, detect antimicrobial resistance markers, and identify trends between error rates and sequence types (STs) of isolates. Over 90% of N. gonorrhoeae isolates were susceptible to azithromycin, cefixime, and ceftriaxone, whereas decreased susceptibility was observed for ciprofloxacin, penicillin, and tetracycline. Categorical (CA) and essential agreement (EA) was poorest between the two methods for penicillin (CA: 86.02%; EA: 77.69%) and tetracycline (CA: 47.22%; EA: 55.96%); however, the low CA was primarily attributed to minor errors. Antimicrobial agents with errors outside of acceptable limits included azithromycin (very major error: 18.42%; major error: 7.73%) and tetracycline (very major error: 6.17%). Genome sequencing on a subset of isolates resolved 30.3% of the azithromycin major errors and confirmed the azithromycin or tetracycline very major errors. Significant associations between certain STs and error types for azithromycin and tetracycline were also identified. Overall, gradient diffusion compared well to agar dilution for cefixime, ceftriaxone, and ciprofloxacin, and genome sequencing was identified as a useful tool to arbitrate discrepant susceptibility testing results between gradient diffusion and agar dilution for N. gonorrhoeae.

Case Series of Stillbirths Due to Syphilis in Edmonton, Alberta, Canada.

BACKGROUND: Data on the incidence and characteristics of stillbirths attributed to congenital syphilis were collected. METHODS: We extracted data on stillbirths in the Edmonton Zone on January 1, 2015, through June 30, 2021, born to persons diagnosed with infectious syphilis (primary, secondary, early latent, or early neurosyphilis) during pregnancy or at the time of delivery. RESULTS: Of 314 infants documented to be exposed to infectious syphilis during gestation, 16 (5.1%) were stillborn. Three of the 16 females with stillbirths were diagnosed with syphilis during pregnancy but not treated, 12 were diagnosed only at the time of stillbirth (1 of whom was treated early in pregnancy and presumably reinfected), and 1 had a stillbirth in the week after one dose of benzathine penicillin G. CONCLUSIONS: Stillbirths due to congenital syphilis were all due to failure to treat syphilis in pregnancy. Innovative strategies to prevent syphilis in the community and to reach those experiencing barriers to care are urgently required to not miss opportunities to diagnose and treat syphilis as early as possible during pregnancy.

Serologic follow-up of solid organ transplant recipients who received organs from donors with reactive syphilis tests: A retrospective cohort study.

The increased procurement of organs from donors with risk factors for blood-borne diseases and the expanding syphilis epidemic have resulted in a growing number of organs transplanted from donors with reactive syphilis serology in our center. Based on guidelines, recipients typically receive therapy shortly after the transplant, but data on outcomes are limited. The primary objective of this study was to determine syphilis seroconversion rates at three months post-transplant in recipients of solid organs procured from donors with reactive syphilis serology. Organ donors and recipients were tested for syphilis antibody; positive results were confirmed with Treponema pallidum Particle Agglutination (TPPA). Eleven donors with reactive syphilis antibody donated organs to 25 syphilis negative recipients. Three recipients seroconverted at post-transplant month 3. All of them had received therapy shortly after transplant. TPPA was negative in all 3. Despite post-transplant treatment, 3 of 25 (12%) syphilis negative recipients of organs from syphilis positive donors seroconverted at 3 months. All remained TPPA negative possibly reflecting passive antibody transfer or differing test sensitivity to low level treponemal antibodies. Further studies are needed to assess optimal syphilis transmission prevention strategies and follow up recipient testing in organ transplantation.

Retrospective Cohort Study Examining the Correlates of Reported Lifetime Stimulant Use in Persons Diagnosed With Infectious Syphilis in Alberta, Canada, 2018 to 2019.

BACKGROUND: We sought to examine the correlates for stimulant use in persons diagnosed with infectious syphilis during an outbreak in Alberta to help guide public health interventions. METHODS: Infectious syphilis data were extracted from the Communicable Disease and Outbreak Management database from January 1, 2018, to December 31, 2019. Behavioral, demographic, and lifetime reported stimulant use data were obtained. Descriptive analyses and logistic regression were performed for 3 subpopulations (gay, bisexual, and other men who have sex with men; men who have sex with women; and women). RESULTS: Of 3627 individuals diagnosed with infectious syphilis, 23.9% (n = 867) cases were not interviewed for substance use and were removed from further analysis. Of the remaining 2759 people, 41.8% (n = 1153) self-reported lifetime stimulant use. Gay, bisexual, and other men who have sex with men reported stimulant use less often than women (24.6% vs. 44.1%; P < 0.0001) and men who have sex with women (24.6% vs. 46.2%; P < 0.0001). Multivariable analyses demonstrated that stimulant use was associated with persons who injected drugs, had correctional involvement, or reported multiple sex partners. Men who have sex with women were more likely to self-report First Nations ethnicity (adjusted odds ratio, 1.76 [95% confidence interval, 1.25-2.49]), and women were more likely to have a concurrent gonorrhea infection (adjusted odds ratio, 1.62 [95% confidence interval, 1.15-2.28]). CONCLUSIONS: Nearly half of infectious syphilis cases in Alberta reported lifetime nonprescription stimulant use. Infectious syphilis cases with stimulant use were associated with injection drug use, multiple sex partners, and correctional involvement. Our observations highlight the need for integration of sexual health services into programs for people who use substances and those in corrections custody.

Retrospective Cohort Study of the Incidence and Outcomes of Jarisch-Herxheimer Reactions After Treatment of Infectious Syphilis in Late Pregnancy.

ABSTRACT: Of 39 pregnant women at ≥20 weeks' gestation treated with benzathine penicillin G for infectious syphilis, we identified only 2 mild Jarisch-Herxheimer reactions. There were no immediate fetal sequelae. Data from our study do not support the recommendation for routine admission for the treatment of infectious syphilis in late pregnancy.

Molecular Surveillance and Prediction of Antimicrobial Resistance of Neisseria gonorrhoeae in Northern Alberta, Canada, 2015 to 2018.

BACKGROUND: The aims of this study was to describe molecular surveillance of Neisseria gonorrhoeae in the North Zone of Alberta (NZ) and to determine its value in predicting antimicrobial resistance. METHODS: Sequence types (STs) and single-nucleotide polymorphism (SNP) assays were performed on nucleic acid amplification testing (NAAT) samples. Sequence types of NAATs were matched to ST of cultures from across Alberta. Antimicrobial resistance prediction of NAATs for cephalosporins, azithromycin, and ciprofloxacin using SNP was compared with matching ST culture results using agar dilution and whole-genome sequencing. RESULTS: Of 2755 eligible specimens (2492 cases), 61.9% (1646 specimens) were sent for sequence typing, identifying 196 unique ST. Antimicrobial resistance data for 1307 additional cases were available using matching cultures. Decreased susceptibility (DS) to antimicrobials used for gonorrhea treatment was rare in the NZ; according to the SNP assay, none of the specimens had predicted DS to cephalosporins or azithromycin resistance. However, of the NZ NAAT samples tested in this study, 10.7% (131 of 1220) were predicted to have intermediate cephalosporin minimum inhibitory concentrations and 9.6% (115 of 1204) were resistant to ciprofloxacin. Based on cultures, the proportions of resistance in all of Alberta were as follows: DS to cephalosporins, 0.6% (20 of 3373); DS to intermediate cephalosporin, 16.9% (570 of 3373); azithromycin resistance, 1.2% (41 of 3373); and ciprofloxacin resistance, 32.2% (1087 of 3373). CONCLUSIONS: Our results highlight our ability to use culture-independent methods to predict antimicrobial resistance in N. gonorrhoeae.

Examination of Care Milestones for Preventing Congenital Syphilis Transmission Among Syphilis-Infected Pregnant Women in Alberta, Canada: 2017-2019.

BACKGROUND: An infectious syphilis outbreak in Alberta has resulted in increased congenital syphilis (CS) cases. To shed light on potential risk factors, we used administrative data sets to examine care milestones for the prevention of CS among pregnant women diagnosed with syphilis, as well as correlates of women giving birth to infants with CS. METHODS: Provincial administrative databases were used to identify and describe pregnant women diagnosed with any stage of infectious or noninfectious syphilis who gave birth in Alberta between January 1, 2017, and December 31, 2019. Data on prenatal care, syphilis screening, and syphilis medication dispensation were used to evaluate the care milestones. Clinical care and maternal demographics were assessed using logistic and linear regression analyses to determine correlates for missed care milestones or a newborn outcome of CS. RESULTS: Of 182 syphilis-infected pregnant women, 63 (34.6%) delivered a newborn with CS. Overall, in the first trimester, 136 (75.1%) women had a health care visit, 72 (39.6%) had a prenatal care visit, 71 (39.0%) were screened for syphilis, and 44 (24.2%) were treated. Gestational time to treatment initiation (adjusted odds ratio, 1.04; 95% confidence interval, 1.02-1.06) and older maternal age at diagnosis (adjusted odds ratio: 1.28, 95% confidence interval, 1.08-1.50) were independently associated with CS outcomes. No variables were found to be independently associated with a health care visit, prenatal screening, or initiation of treatment. CONCLUSIONS: Although nearly two-thirds of CS cases were prevented, there remained missed opportunities in the prevention of CS. Early treatment, which relies on timely access to prenatal care and screening, was the most important for the prevention of CS.

Genetic Characterization and Enhanced Surveillance of Ceftriaxone-Resistant Neisseria gonorrhoeae Strain, Alberta, Canada, 2018.

In July 2018, a case of Neisseria gonorrhoeae associated with ceftriaxone treatment failure was identified in Alberta, Canada. We identified the isolate and nucleic acid amplification testing (NAAT) specimen as the ceftriaxone-resistant strain multilocus sequence type 1903/NG-MAST 3435/NG-STAR 233, originally identified in Japan (FC428), with the same penA 60.001 mosaic allele and genetic resistance determinants. Core single-nucleotide variant (SNV) analysis identified 13 SNVs between this isolate and FC428. Culture-independent surveillance by PCR for the A311V mutation in the penA allele and N. gonorrhoeae multiantigen sequence typing directly from NAAT transport media positive for N. gonorrhoeae by NAAT did not detect spread of the strain. We identified multiple sequence types not previously detected in Alberta by routine surveillance. This case demonstrates the benefit of using culture-independent methods to enhance detection, public health investigations, and surveillance to address this global threat.

Gonococcal Conjunctivitis in Adults: Case Report and Retrospective Review of Cases in Alberta, Canada, 2000-2016.

BACKGROUND: A case of gonococcal conjunctivitis (GC) prompted us to review the reported cases and treatment regimens of GC in Alberta, Canada. METHODS: Gonococcal cases reported from 2000 to 2016 were extracted from the provincial sexually transmitted infection reporting database. The diagnosis of GC was based on a positive culture and/or nucleic acid amplification test from the eye. RESULTS: A total of 45 cases of GC were reported in adults. Three quarters (75.6%; n = 34) of the cases were diagnosed using culture, 57.8% (n = 26) of cases were among men, and 55.5% (n = 25) were diagnosed since 2014. Very few (13.3%; n = 6) of the cases were treated according to current Canadian Guidelines on Sexually Transmitted Infections, using 2 g of ceftriaxone in combination with azithromycin or doxycycline. Results of test of cures were available for 15.6% (n = 7) of the cases and occurred within 10 to 79 days (median = 26 days) after treatment; all were negative. CONCLUSIONS: Gonococcal conjunctivitis was relatively uncommon in our region, but given its potential for severe manifestations and sequelae coupled with the rising rates of gonorrhea; it remains important to consider this diagnosis in sexually active individuals presenting with purulent conjunctivitis. Additional studies are needed to inform treatment recommendations and to evaluate outcomes of infection.

Gonococcal and Chlamydial Cases of Pelvic Inflammatory Disease at 2 Canadian Sexually Transmitted Infection Clinics, 2004 to 2014: A Retrospective Cross-sectional Review.

One hundred thirteen patients with gonococcal and chlamydial pelvic inflammatory disease were reviewed at 2 Canadian sexually transmitted infection clinics. Most patients (81%) with pelvic inflammatory disease were diagnosed as having chlamydia alone. Three treatment failures were seen in patients treated with ofloxacin.

Increasing incidence of syphilis among patients engaged in HIV care in Alberta, Canada: a retrospective clinic-based cohort study.

BACKGROUND: Syphilis is a global health concern disproportionately affecting HIV-infected populations. In Alberta, Canada, the incidence of syphilis in the general population has recently doubled with 25% of these infections occurring in HIV-infected patients. The Southern Alberta HIV Clinic (SAC) and Calgary STI Program (CSTI) analyzed the epidemiologic characteristics of incident syphilis infections in our well-defined, HIV-infected population over 11 years. METHODS: Since 2006, as routine practice of both the Southern Alberta Clinic (SAC) and Calgary STI Programs (CSTI), syphilis screening has accompanied HIV viral load measures every four months. All records of patients who, while in HIV care, either converted from being syphilis seronegative to a confirmed seropositive or were re-infected as evidenced by a four-fold increase in rapid plasma reagin (RPR) after past successful treatment, were reviewed. RESULTS: Incident syphilis was identified 249 times in 194 HIV-infected individuals. There were 36 individuals with repeated infections (28.5% of episodes). Following a prior decline in annual incident syphilis rates, the rates have tripled from 8.08/1000 patient-years (95% confidence interval (CI): 4.14-14.75) in 2011, to 27.04 per 1000 person-years (95% CI: 19.45-36.76) in 2016. Half of the syphilis episodes were asymptomatic. Patients diagnosed with syphilis were twice as likely not to be taking ART and had a higher likelihood of having plasma HIV RNA viral loads > 1000 copies/mL (19%). Incident syphilis was seen predominantly in Caucasians (72%, P < 0.001), males (94%, P < 0.001) and men who have sex with men (MSM) as their HIV risk activity (75%, P < 0.001). CONCLUSIONS: We have highlighted the importance of a regular syphilis screening program in HIV-infected individuals demonstrated by increasing rates of incident syphilis in our region. Targeted preventative strategies should be directed towards HIV-infected populations identified at highest risk, including; MSM, prior alcohol abuse, prior recreational drug use and those with prior syphilis diagnoses.

Retrospective Review of Gonococcal and Chlamydial Cases of Epididymitis at 2 Canadian Sexually Transmitted Infection Clinics, 2004-2014.

Fifty-seven cases of gonococcal and chlamydial infections complicated by acute epididymitis seen at 2 Alberta STI clinics from 2004 to 2014 were reviewed. The majority responded to treatment recommended by national guidelines. Three of 6 treatment failures were not treated according to guidelines.

Use of the APTIMA Combo 2 Assay and a Secondary Algorithm to Detect and Confirm Chlamydia trachomatis in Rectal-Only Infections.

We sought to confirm the results of 81 rectal specimens positive for Chlamydia trachomatis by the APTIMA Combo 2 assay among patients with concurrently collected negative genitourinary specimens. A total of 79 (97.5%) samples were confirmed by the APTIMA single target assay and/or sequencing of the C. trachomatis ompA gene.

Trichomonas vaginalis Prevalence and Correlates in Women and Men Attending STI Clinics in Western Canada.

Trichomonas vaginalis prevalence (2.8%) in female sexually transmitted infection clinic attendees was within the prevalence of chlamydia (5.8%) and gonorrhea (1.8%), while being very low for male attendees (0.2%). Correlates among women were indigenous ethnicity, other ethnicity, and being symptomatic.

A Retrospective Review of Treatment Failures Using Azithromycin and Doxycycline in the Treatment of Rectal Chlamydia Infections in Women and Men Who Have Sex With Men.

We examined the prevalence of rectal chlamydia treatment failures in men who have sex with men and women attending Alberta sexually transmitted infection clinics. Among those completing a test of cure, there was no significant difference among patients treated initially with azithromycin (treatment failure, 39/460 [8.5%]; 95% confidence interval, 5.9%-11.0%) compared with patients treated with doxycycline (0/16; 95% confidence interval, 0%-0.2%; P = 0.63).

Evidence for increased Chlamydia case finding after the introduction of rectal screening among women attending 2 Canadian sexually transmitted infection clinics.

BACKGROUND: Chlamydia trachomatis is the most common notifiable disease in Canada, and extragenital sites are believed to serve as hidden reservoirs for ongoing transmission of infection. There are no specific Canadian screening guidelines for asymptomatic individuals from extragenital sites. We sought to determine the prevalence and factors associated with rectal C. trachomatis among female sexually transmitted infection (STI) clinic attendees in Alberta, Canada. METHODS: Between 20 July and 31 December 2012, all female attendees at 2 Provincial STI clinics receiving a pelvic examination, regardless of a history of anal intercourse, were screened for rectal C. trachomatis using the Gen-Probe Aptima COMBO 2 Assay. Demographic and behavior variables were compared between rectal-only chlamydia cases and genitourinary cases using χ(2) or Fisher exact test, Mann-Whitney test, and logistic regression. RESULTS: A total of 3055 women were screened for rectal chlamydia. The prevalence of rectal chlamydia ranged from 11.7% to 13.5%. There were 133 rectal-only cases, increasing case detection by 44.3% from 300 genitourinary cases to 433 total cases, ranging from 21.7% to 88.2% by clinic. Women who were a contact to an STI were less likely to have rectal-only chlamydia for both clinics (P ≤ .001). CONCLUSIONS: Our findings add to the growing body of evidence supporting universal rectal screening in high-risk women such as those undergoing pelvic exams at STI clinics.

Impact of Introducing Triage Criteria for Express Testing at a Canadian Sexually Transmitted Infection Clinic.

The implementation of express testing in an sexually transmitted infection (STI) clinic reduced the length of visit time compared with other visit types and increased the proportion of STIs diagnosed at clinic visits. Express testing did not impact the time to treatment for asymptomatic patients diagnosed as having an STI.

Gonorrhea Treatment Failures With Oral and Injectable Expanded Spectrum Cephalosporin Monotherapy vs Dual Therapy at 4 Canadian Sexually Transmitted Infection Clinics, 2010-2013.

BACKGROUND: Antimicrobial resistance has developed to all antibiotics used to treat gonorrhea (GC), and trends in GC antimicrobial resistance have prompted changes in treatment guidelines. We examined treatment failures in sexually transmitted infection clinics. METHODS: Four Canadian sexually transmitted infection clinics reviewed treatment regimens, minimum inhibitory concentrations for cephalosporins and azithromycin, anatomical infection sites, and treatment outcomes for GC infections between January 2010 and September 2013, in individuals who returned for test of cure within 30 days of treatment. Treatment failure was defined as the absence of reported sexual contact during the posttreatment period and (i) positive for Neisseria gonorrhoeae on culture of specimens taken at least 72 hours after treatment or (ii) positive nucleic acid amplification test specimens taken at least 2 to 3 weeks after treatment, and matching sequence type pretreatment and posttreatment. χ Test and Fisher exact test were used to assess association of categorical variables. RESULTS: Of 389 specimens reviewed, GC treatment failures occurred in 13 specimens treated with cefixime 400-mg single dose (17.8% treatment failure rate regardless of anatomical site) and in 1 oropharyngeal specimen treated with cefixime 800-mg single dose. No treatment failures occurred using either ceftriaxone monotherapy or cefixime/ceftriaxone combined with azithromycin or doxycycline. CONCLUSIONS: In contrast to oral cefixime monotherapy, no treatment failures were identified with injectable ceftriaxone monotherapy or combination GC treatment. Our data support the use of combination treatment of GC with an extended spectrum cephalosporin (including oral cefixime) with azithromycin or doxycycline as well as ceftriaxone monotherapy.