Volume 6 Issue 1, February 2023, pp. 70-75

Abstract

BACKGROUND: Alberta routinely screens pregnant patients for select communicable diseases. Hepatitis C virus (HCV) was added to the prenatal screening panel as part of a provincial pilot program in February 2020. This retrospective cross-sectional study aimed to characterize the prevalence of syphilis coinfections in prenatal patients infected with HCV following implementation of the pilot program. METHODS: Routine prenatal HCV and syphilis testing data were extracted from the Public Health Laboratory Information System over a 21-month period. HCV positivity was defined as HCV enzyme immunoassay (EIA) reactive with detected HCV ribonucleic acid (RNA) following molecular confirmation, and positive results were examined for syphilis coinfections. All patients reactive on a syphilis EIA and confirmatory Treponema pallidum particle agglutination (TPPA) or follow-up rapid plasma reagin (RPR) test were considered positive for syphilis. Descriptive statistics for coinfected patients were analyzed. RESULTS: Eighty-seven prenatal patients were identified to be positive for HCV. Of those, 19 (21.8%) were reactive on the syphilis EIA and 17 (19.5%) had confirmed infections with the TPPA or RPR tests. For HCV/syphilis coinfected patients, the majority resided in metropolitan regions (64.6%), were from the lowest income quintile neighbourhoods (47.1%) and had previously tested positive for HCV (82.4%) and syphilis (64.6%) at the public health laboratory. CONCLUSIONS: The prevalence of syphilis coinfections in prenatal patients infected with HCV is high in Alberta. HCV/syphilis coinfection prevalence should be further investigated in other jurisdictions and prenatal cohorts to better understand testing and treatment options for prevention of congenital transmission.

The Alberta Prenatal Screening Program routinely tests pregnant patients for select communicable diseases including human immunodeficiency virus (HIV), hepatitis B virus (HBV), rubella, varicella, and syphilis (1). Currently, Canadian guidelines recommend risk-based screening for Hepatitis C virus (HCV) during pregnancy (2). However, there has been recent discussion on shifting towards routine prenatal screening for HCV due to the ongoing opioid crisis, which has resulted in an increased HCV incidence among patients of child-bearing age (3). During this same time, Alberta has experienced a syphilis outbreak resulting in a surge of congenital syphilis cases not seen in decades (4).

Alberta implemented a pilot HCV prenatal screening program on February 27, 2020 by amending the Alberta Prenatal Screening Program to include HCV (5). This brief report summarizes preliminary data on HCV/syphilis coinfections in prenatal patients testing positive for HCV during the pilot program.

Prenatal screening in Alberta

Communicable disease screening for prenatal patients is typically done during the first trimester of pregnancy and is very robust in Alberta, with >97% of pregnant patients receiving prenatal screening (6). All routine provincial prenatal screening for HBV, HIV, syphilis, rubella, and varicella, as well as the prenatal pilot HCV screening, is performed centrally at Alberta Precision Laboratories (APL). Data for analyses was provided by the APL surveillance team.

HCV testing

Serum samples are screened for HCV antibodies on the Abbott ARCHITECT i2000SR (Architect Anti-HCV, Abbott Laboratories, Illinois, USA) and if positive, are reflex tested on the Roche cobas 6800 (cobas HCV, Roche Diagnostics, Indiana, USA) for molecular confirmation. A patient is diagnosed as having an infection if they are reactive for HCV antibodies and have detected HCV RNA. A continuous computational lookback (CCL) code with personal health numbers (PHNs) is utilized to identify whether an HCV infection is a newly reported case, or whether the patient previously tested positive for HCV within the Provincial Public Health Laboratory Information System (ProvLab LIS).

Syphilis testing

Serum samples are screened for syphilis antibodies using an enzyme immunoassay (EIA) (Architect Syphilis TP Microparticles, Abbott Laboratories, Illinois, USA). If positive, a CCL code with PHNs is used to identify newly reported versus previously reported results of syphilis serology in the ProvLab LIS. Patients with newly positive EIA serology receive reflex rapid plasma reagin (RPR) (Macro-Vue RPR kit, Becton Dickinson Microbiology Systems, Ontario, Canada) and Treponema pallidum particle agglutination (TPPA) testing (Serodia Treponema Pallidum Particle Agglutination, Fujirebio, Pennsylvania, USA). Those who have a previous reactive TPPA result in the ProvLab LIS receive only reflex RPR testing. Newly reported infections requiring public health follow-up were defined as 1) newly identified cases with newly EIA and TPPA results (regardless of RPR results) or 2) previously identified patients with RPR quantitative titres ≥4-fold increase from previous serological testing.

Evaluating HCV/syphilis coinfections

Prenatal HCV and syphilis testing data were extracted from the ProvLab LIS 21 months after implementing the pilot routine screening program for HCV. A cohort of HCV positive prenatal patients was assessed for syphilis coinfections. Descriptive statistics for HCV/syphilis coinfected patients were analyzed. Geographic region (rural, urban, or metropolitan) and neighbourhood income quintiles were determined using postal code associated data from 2016 Alberta census estimates. Coinfected patients were also assessed for HIV and HBV infections. All data was collated and analyzed in Stata v15.1 (StataCorp, College Station, Texas, USA).

From >50,000 prenatal patients screened via the pilot HCV screening program over 21 months, we identified 87 patients positive for HCV (Figure 1). Of those, 19 (21.8%) had reactive syphilis EIA results, with 17 (19.5%) confirmed as having syphilis infections (6 with newly reported TPPA results and 11 with at least a 4-fold increase in RPR dilutions). Of the remaining two patients, one did not have serological evidence of a new syphilis infection (no rise in RPR titres) and one had insufficient sample volume to complete testing. Most coinfected patients had previously reported reactive HCV (82.4%) and syphilis (64.6%) serology results in the ProvLab LIS (Table 1). No coinfected patients were also infected with either HIV or HBV.

Figure 1: Analysis of syphilis coinfections among a cohort of prenatal patients infected with HCV in Alberta; syphilis infections were defined as either newly identified cases with newly reactive EIA and TPPA results or previously identified patients whose RPR results were ≥4-fold increase in quantitative titres from previous serological testing

HCV = Hepatitis C virus; EIA = Enzyme immunoassay; RPR = Rapid plasma reagin test; TPPA = Treponema pallidum particle agglutination test; TPPA reactive = Newly identified cases; RPR reactive = Previously identified cases
Table

Table 1: Descriptive statistics of HCV/syphilis coinfected prenatal patients from Alberta (n = 17)

Table 1: Descriptive statistics of HCV/syphilis coinfected prenatal patients from Alberta (n = 17)

no. (%) of HCV/syphilis coinfected prenatal patients
Age, y
    20–25 3 (17.6)
    26–30 7 (41.2)
    31–35 5 (29.4)
    36–40 2 (11.8)
Health zone
    North 3 (17.6)
    Edmonton 10 (58.8)
    Central 4 (23.6)
    Calgary 0 (0.00)
    South 0 (0.00)
Geographic region*
    Metropolitan 11 (64.6)
    Rural 2 (11.8)
    Urban 4 (23.6)
Income quintile
    Q1 8 (47.1)
    Q2 1 (5.88)
    Q3 5 (29.4)
    Q4 2 (11.8)
    Q5 1 (5.88)
HCV history
    Newly reported 3 (17.6)
    Previously reported 14 (82.4)
HCV/syphilis/HIV infection 0 (0.00)
HCV/syphilis/HBV infection 0 (0.00)
Syphilis history §
    Newly reported 6 (35.4)
    Previously reported 11 (64.6)

* Metropolitan corresponds to Edmonton and Calgary regions while urban corresponds to all other major cities

Neighbourhood income quintiles; Q1 is the lowest income quintile and Q5 is the highest

A newly reported HCV case is classified as an infection first identified with prenatal screening in Alberta, while a previously reported case is classified as previously reported reactive HCV serology in the ProvLab LIS

§ A newly reported syphilis case is classified as an infection first identified with prenatal screening in Alberta, while a previously reported case is classified as previously reported reactive syphilis serology in the ProvLab LIS, including those with previous treatment or a patient with a syphilis re-infection

Among coinfected patients, the majority (41.2%) were aged 26–30 years and resided in the Edmonton health zone (58.8%; Table 1). No coinfected patients resided in the Calgary or South health zones. Rural regions had the lowest proportion of coinfections (11.8%). Patients residing in neighbourhoods from the lowest income quintile (Q1) comprised the largest percentage of coinfected patients (47.1%).

The Alberta Prenatal Screening Program is an effective way to test patients for communicable diseases during pregnancy. After piloting routine screening for HCV, we discovered that 19.5% of our prenatal HCV cohort was coinfected with syphilis. This is significantly higher than syphilis coinfections in our HIV and HBV prenatal cohorts (0.00% and 0.93%; data not shown), suggesting an overlapping population at high-risk for acquiring both HCV and syphilis. Although we were unable to map specific risk factors to patients in our cohort, a recent publication from Alberta showed that among women with infectious syphilis, 56.6% were aged 25–40 (child-bearing age), 26.2% had a history of injection drug use, 13.6% were involved in sex work, 22.4% had a history of correctional involvement, and 66.2% self-reported Métis or First Nations ethnicity (7). Because these are also overlapping risk factors and populations more likely to be positive for HCV, it is highly probable the coinfected patients in our cohort represent a range of these factors.

As current national screening guidelines for prenatal HCV are based on risk-factors (2), history of syphilis infection could be considered in future HCV risk-based screening guideline discussions. Although populations infected with HCV and syphilis share risk factors that are already considered for HCV risk-based screening (eg, high-risk sexual behaviours and drug use), studies have shown people are less likely to disclose their involvement in behaviours that are stigmatized (8), and therefore may be overlooked for HCV screening with current guidelines. Incorporating history of syphilis infection, which is routinely screened for during pregnancy in Canada (9), as a risk factor could identify a higher proportion of prenatal patients infected with HCV, particularly given that time and resources are required for guidelines to shift entirely to routine HCV screening.

The literature on HCV and syphilis coinfection is generally limited to men who have sex with men, and essentially non-existent among prenatal populations (10). Given the high prevalence of coinfection in our study and that both HCV and syphilis can lead to congenital infections (11), our data also warrants further research into ways of engaging at-risk populations to testing and treatment for both syphilis and HCV prior to conception to prevent congenital outcomes. This is highlighted by our results, which show that the majority of HCV and syphilis infections were identified in patients who had tested positive prior to prenatal screening. Patients were still testing positive for these infections during pregnancy, suggesting a lack of treatment before conceiving or incidence of reinfection. Until outcomes can be improved before pregnancy through holistic care in women of child-bearing age, screening for sexually transmitted and bloodborne infections should continue to remain a priority during the prenatal period.

One limitation of our data is that a syphilis outbreak was declared in Alberta in 2019 (12), likely contributing to our high prevalence of coinfection, especially in the Edmonton area. However, syphilis outbreaks have recently been declared in eight other provinces and territories, suggesting our outcomes may be applicable across Canada where other syphilis outbreaks are occurring. Another limitation is that without clinical data, it is difficult to determine source of infections, which infections may have been previously reported or treated outside of Alberta, and whether HCV or syphilis was acquired first. Regardless, our data shows a high prevalence of HCV/syphilis coinfection in our HCV positive cohort. Although the overall number of coinfected patients over our study period was low and none were identified in some regions of the province, these patients represent those at high risk for perinatal and congenital outcomes, emphasizing the importance of screening and monitoring during pregnancy. Additionally, pregnancy represents an ideal period where patients can be engaged into health care services for their infections, which could be particularly beneficial for those who might otherwise be overlooked. Further research from other provinces and territories is ultimately imperative to identify the extent of HCV/syphilis coinfections among prenatal populations in the country and to identify the cost-effectiveness of incorporating a history of syphilis infection into HCV risk-based screening guidelines.

The authors would like to thank the staff at Alberta Precision Laboratories (APL) for their dedication to prenatal and communicable disease testing and the APL surveillance team for continuously updating and providing us with prenatal testing data.

Conceptualization, LA Thompson, SS Plitt, J Gratrix, CL Charlton; Methodology, LA Thompson, SS Plitt, CL Charlton; Software, LA Thompson; Validation, LA Thompson, SS Plitt, J Gratrix, CL Charlton; Formal Analysis, LA Thompson; Investigation, LA Thompson, CL Charlton; Resources, CL Charlton; Data Curation, LA Thompson; Writing – Original Draft, LA Thompson; Writing – Review & Editing, LA Thompson, SS Plitt, J Gratrix, CL Charlton; Visualization, LA Thompson; Supervision, SS Plitt, CL Charlton; Project Administration, CL Charlton; Funding, CL Charlton.

Ethics was approved through the University of Alberta Research Ethics Board Pro00092635.

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Funding for this study was provided by the Canadian Institutes of Health Research (CIHR) Frederick Banting and Charles Best Canada Graduate Scholarship-Master’s (LA Thompson), CIHR Vanier Canada Graduate Scholarship (LA Thompson), a Killam Trust Scholarship (LA Thompson), the University of Alberta Doctoral Recruitment Scholarship (LA Thompson), a Women and Children’s Health Research Institute (WCHRI) Graduate Studentship (LA Thompson), and the M.S.I. Foundation (CL Charlton).

J Gratrix received support from the Public Health Agency of Canada to attend the National Advisory Committee of STBBI meeting in 2019. She is also a member of the National Advisory Committee of STBBI. The other authors have nothing to disclose.

This manuscript has been peer reviewed.

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