Recommendation on screening for chlamydia and gonorrhea in primary care for individuals not known to be at high risk



## Key messages for the public
- Chlamydia and gonorrhea are common sexually transmitted infections that are treatable with antibiotics.
- If you are younger than age 30 and sexually active, your health care provider may offer screening for chlamydia and gonorrhea every year, even if you do not have symptoms.
- Screening is done to find and treat infections in people who aren't showing symptoms, which may reduce complications like pelvic inflammatory disease. These infections are often without symptoms.
- Talk to your doctor about screening more than once per year if you think you are at increased risk of infection (e.g., you have had a sexually transmitted infection, you have had unprotected sex, sex with multiple partners, or another reason).
- Chlamydia and gonorrhea infections are automatically reported to local public health units. This is to help with treatment for people who test positive and also with confidentially notifying sexual partners so that they may be tested and treated as required.
concerns.Opportunistic screening is distinct from a system atic population screening program, in which invitations for screening are sent to all eligible participants, monitored for uptake and evaluated through a centralized program, usually at the provincial level.
National guidance from the Public Health Agency of Canada currently recommends screening for chlamydia in pregnant women, annual screening for sexually active individuals younger than 25 years, and targeted screening of atrisk individ uals older than 25 years (e.g., those with previous STIs, sex trade workers).This guidance is not based on formal sys tematic reviews and does not include recommendations for gonorrhea screening.
The last guideline on chlamydia screening from the Canadian Task Force on the Periodic Health Examination (now Task Force on Preventive Health Care) was published in 1996;it also did not include recommendations on gonorrhea. Therefore, the task force identified a need for an updated Canadian guideline that considers current evidence on the potential harms, benefits, and patient values and preferences of screening for chlamydia and gonorrhea.

## Scope
This guideline is intended for clinicians in primary care settings who are positioned to offer opportunistic screening for chla mydia and gonorrhea directly to sexually active individuals who are not specifically seeking care for a possible STI and are not known to belong to a highrisk group. Readers should refer to rel evant national, provincial or local guidance for the screening of individuals known to have specific highrisk behaviours (these will vary by jurisdiction, but may include having multiple sexual partners, previous STIs or sex without condoms; testing of individuals seeking care for symptoms; pregnant individuals; and for selection of appropriate antibiotic treatment, partner notifi cation, retesting and forensic testing strategies. The terms "male" and "female," when used, refer to sex (i.e., biological attributes, particularly the reproductive or sexual anatomy at birth), unless otherwise indicated.

## Recommendation
We recommend opportunistic screening of sexually active individ uals younger than 30 years who are not known to belong to a high risk group, annually, for chlamydia and gonorrhea at primary care visits, using a self or cliniciancollected sample (conditional rec ommendation; very lowcertainty evidence).
A summary of the recommendation is provided in Box 1.
Providers should refer to relevant national, provincial or local guidance for screening of individuals known to belong to specific highrisk groups.
In the systematic review conducted for this guideline, all rel evant studies (9 randomized controlled trials [RCTs], 5,6,8,27-32 1 controlled clinical trial 33 and 2 retrospective cohort stud ieson the potential benefits of chlamydia screening pro vided indirect evidence (i.e., low applicability) on how and to whom screening would be offered in Canadian primary care. For example, 4 RCTs offered screening (regardless of uptake) by mailed invitation or through public education and screening encouragement 6,29 rather than via direct discussion, and 1 clus ter RCT provided cliniclevel interventions (packages to help encourage clinicians to offer screening) 5 rather than direct clin ician engagement, yielding low clinician participation and offers of screening. Three trials evaluated only those who accepted screening (acceptors of screening),and 1 trial evaluated an offer to screen among those preselected owing to an interest in screening (offer to screen, preselected),which is indirect to the varied screening interest and acceptance among Canadian primary care patients. No studies on the effects of screening for gonorrhea for any outcomes of interest were identi fied in generalrisk populations.
Eleven studies were identified on harms of screening for chlamydia. One RCT reported on adverse antibiotic events,and 10 uncontrolled cohort studies reported on psychosocial harms.No studies examined harms of screening for gonorrhea.
Fourteen studies examined values and preferences of screen ing for chlamydia or gonorrhea: 4 studies measured health state utility values (a measure of preference for being in a particular state of healthfor several of the benefit outcomes of screening for chlamydia and gonorrheainfection, and 10 (survey and qualitative) studies considered the relative importance of bene fits to harms of chlamydia screening.Benefits of screening Offer to screen, regardless of uptake Metaanalysis of 2 RCTs (n = 141 362) found very lowcertainty evidence for little to no difference in pelvic inflammatory disease rate among females aged 16-29 years, over 1 to 3 years using an annual offer of chlamydia screening via selfcollected vaginal samples (0.3 more in 1000 [95% confidence interval (CI) 7.6 fewer to 11 more]).One RCT (n = 15 459) found very uncertain effects on infertil ity and very lowcertainty evidence for little to no difference in ectopic pregnancy rates for females aged 21 to 24 years, over 9 years from a single offer of chlamydia screening via self collected vaginal samples (0.2 more in 1000 [95% CI 2.2 fewer to 3.9 more]). 6

## Box 1: summary of recommendation for clinicians, policy-makers and patients
We recommend opportunistic screening of sexually active individuals younger than 30 years who are not known to belong to a highrisk group, annually, for chlamydia and gonorrhea at primary care visits, using a self or cliniciancollected sample (conditional recommendation; very lowcertainty evidence).
Providers should refer to relevant national, provincial or local guidance for screening of individuals known to belong to specific highrisk groups.
Metaanalysis of 3 RCTs (n = 41 709) found lowcertainty evidence for little to no difference in chlamydia transmission for individuals aged 15-29 years, over 1 to 3 years from a sin gle offer of chlamydia screening via selfcollected vaginal or urine samples fewer per 1000 [95% CI 21.0 fewer to 12.6 more]). Offer to screen, preselected individuals interested in screening One RCT (n = 2607) -among females aged 18-34 years (81% younger than 24 yr) preselected based on completing a pre screening questionnaire on chlamydia risk and then accepting an offer of a primary care appointment (suggesting an interest in being screened) -found lowcertainty evidence that offering a single chlamydia screening via cliniciancollected cervical swabs may reduce pelvic inflammatory disease 

## Harms of screening
One RCT (n = 37 543 tested; n = 4574 patients who received a diagnosis of chlamydia; number treated not reported) reported no adverse events from antibiotic treatment for chlamydia (very lowcertainty evidence).Cohort studies 20,36-44 reported on a vari ety of psychosocial harms of screening that were synthesized narratively; low or very lowcertainty evidence indicated that undergoing screening may lead to feelings of stigmatization (e.g., guilt, embarrassment, social disapproval) or anxiety about future infertility, sexuality or risk of infection in a small to moderate proportion of individuals (50-400 per 1000 individuals screened). The number of individuals affected in the entire eligible screen ing population is likely smaller. The exact duration and severity of these symptoms is unknown.

## Patient values and preferences
Considering benefits relative to harms, surveys and qualitative studies found that individuals considering screening (n = 777)or undergoing screening (n = 77) 56-58 placed greater relative importance on potential reproductive health and decreased transmission benefits than on anxiety or stigma of screening (very lowcertainty evidence). No studies considered patient val ues related to adverse events from medication.
Similarly, the patient engagement study that the task force conducted for this guideline (described in Methods) showed that patients likely prioritize potential benefits of screening (all rated critical or important) over harms (all rated important) and have a strong preference to be screened; this was the case even when participants were presented with the evidence and its uncertainty.Considering the relative prioritization of different screening benefits, studies reporting health state utilities found that while utility values are similar across benefit outcomes, 11,46-48 when considering durations of the health states, the avoidance of infertility and chronic pelvic pain may be more important to females than ectopic pregnancy, pelvic inflammatory disease or cervicitis (lowtomoderate certainty). 61

## Resource use
The task force did not conduct a systematic review on resource use or costeffectiveness. In the judgment of the task force, the recommendation to screen all eligible patients at opportunistic visits could involve additional (moderate) costs, largely because of additional clinician time at these encounters and testing costs.
Costeffectiveness estimates based on opportunistic screen ing scenarios suggest that high versus low rates of screening may improve costeffectiveness,and that screening may be cost effective in Canada provided that the probability of chlamydia progressing to pelvic inflammatory disease is at least 10%,although this is of very low certainty.

## Feasibility, acceptability, cost and equity
Screening is currently a part of primary care practice and there fore judged to be feasible and likely acceptable to primary care practitioners and patients. Notably, 1 included RCT showed that patients accepted screening 80% of the time that it was offered(although the overall screening rate in this trial was low [24%] because of lack of offer).The task force anticipates that public health and other policy makers will find the recommendation to screen acceptable, given the number of people affected, increasing incidence of chlamydia and gonorrhea infection,and availability of effective treatment.
In the judgment of the task force, the recommendation would likely improve health equity by normalizing screening as routine for sexually active individuals and thereby reducing important barriers to screening, such as fear of disapproval or discrimina tion and feelings of stigmatization.Additionally, because females carry most of the burden of the clinical consequences of infection, screening of males (a reservoir of infection for females) may improve health equity for females.

## Rationale

## Benefits
The indirectness (low applicability) of available evidence to inform opportunistic screening in Canada represents a major source of uncertainty, in addition to the very uncertain or lack of evidence for some outcomes of interest for chlamydia screening and for all outcomes of interest for gonorrhea screening. All evi dence on benefits was of low or very low certainty, largely because of concerns about indirectness as well as imprecision (Appendix 1, available at www.cmaj.ca/lookup/doi/10.1503/ cmaj.201967/tabrelatedcontent). Pelvic inflammatory disease may be reduced for those accepting and undergoing chlamydia screening 8,28,33 and for those interested in being screened who are offered it (low certainty). Very uncertain evidence found little to no difference in pelvic inflammatory disease when chlamydia screening was offered, via mailed invitation or clinic level packages that encouraged screening. The task force judged that the true benefit of chlamydia screening when offered directly by Canadian primary care practitioners, who are posi tioned to identify those eligible and to offer screening oppor tunistically, would likely lie within this observed range of screen ing effectiveness.
The recommendation to screen individuals younger than 30 years is based on the fact that almost all of the underlying evi dence comes from studies of individuals in this age group. Fur ther, the rates of chlamydia and gonorrhea are increasing among those aged 25-29 years in Canada, with rates and total cases sim ilar to those aged 15-19 years.Conversely, rates of chlamydia for those aged 30-39 years are less than 50% of those for individ uals 15-19 and 24-29 years, and less than 25% of those for indi viduals aged 20-24 years.Similarly, rates in those aged 40-59 years are less than 25% of those in individuals aged 30-39 years.Considering the properties of sexual networks, this recom mendation to screen sexually active males as well is intended to reduce chlamydia and gonorrhea infection and its negative con sequences in females, through their role in the transmission of these infections (although there were no available studies informing this rationale).
The task force made the recommendation to screen for gon orrhea as well (despite the lack of available evidence) given that many gonorrhea cases are asymptomatic;up to 40% of those with gonorrhea may have concurrent chlamydia; 67-69 and current Canadian clinical and laboratory practice is to combine testing for gonorrhea with chlamydia using a single sample (most commercial nucleic acid amplification test [NAAT] assays test for both organisms simultaneously with a single speci men. The incremental costs of screening for both chlamydia and gonorrhea (versus, for example, chlamydia alone) is uncer tain but likely minimal, as some provincial schedules already include NAAT for chlamydia and gonorrhea together under a single price. 70

## Harms
The task force placed a lower priority on the very uncertain evi dence of no serious adverse effects of antibiotic treatment for chlamydia and gonorrhea and uncertain evidence for psycho social harms of screening (anxiety, shame and stigma) that are likely to be experienced by a small proportion of those eligible for screening.
The task force judged that the potential benefits of screening for chlamydia and gonorrhea to reduce pelvic inflammatory dis ease in females, albeit very uncertain, outweigh possible harms. Evidence suggests that most Canadian patients also prioritize the benefits over the harms of screening for chlamydia and gon orrhea, even when provided with the evidence and its uncer tainty.Therefore, considering the balance of benefits and harms as well as evidence uncertainty, the task force provides a conditional recommendation in favour of opportunistic screen ing for chlamydia and gonorrhea in primary care for individuals younger than 30 years.

# Methods
The Canadian Task Force on Preventive Health Care is an inde pendent panel of clinicians and methodologists that makes rec ommendations on primary and secondary prevention in pri mary care (www.canadiantaskforce.ca). A working group of 6 task force members developed this recommendation, with scientific support from the science team at the Public Health Agency of Canada. The working group established the research questions and the analytical framework for the systematic review (Appendix 2, available at www.cmaj.ca/lookup/doi/10.1503/cmaj.201967/tab relatedcontent). The Evidence Review and Synthesis Centre at the University of Alberta (Edmonton) conducted the systematic review on which the recommendation is based, which evaluated the effectiveness of chlamydia and gonorrhea screening and the relative importance of screening outcomes (benefits and harms) to patients.A search for eligible studies was conducted using Ovid MEDLINE, Ovid Embase, Wiley Cochrane Library, CINAHL via EBSCOhost, and Ovid PsycINFO from database inception to Jan. 26, 2020, with supplemental searches for grey literature. For the relative importance of potential benefit outcomes, a 2013 review on health state utility values was also updated.The sys tematic review was registered (PROSPERO CRD42018100733), and a protocol for the review was published.In the systematic review, potential benefits of screening examined included reduced pelvic inflammatory disease, ectopic pregnancies, cervicitis and chronic pelvic pain in females; and for both females and males, reduced infertility and transmission (prevalence). Potential harms examined included serious adverse antibiotic reactions and negative psychosocial implica tions of screening (e.g., anxiety, sexual relationship distress including partner violence, stigmatization, blame). Thresholds for minimally important differences in benefit outcomes were determined before the task force examined the results. Details can be found in the systematic review.The task force used the Grading of Recommendations, Assess ment, Development and Evaluation (GRADE) approach to deter mine the certainty of evidence and strength of recommendation (Box 2). See Appendix 3, available at www.cmaj.ca/lookup/ doi/10.1503/cmaj.201967/tabrelatedcontent. The entire task force approved the recommendations. More information about the task force's methods are avail able at the task force website (http://canadiantaskforce.ca/ methods).

## Patient engagement
The Knowledge Translation team at St. Michael's Hospital (Toronto) engaged members of the public from across Canada, recruited via advertisements on public websites (i.e., Craigslist and Kijiji), on behalf of the task force at 2 stages of guideline development. As a first step, 16 sexually active participants (9 identified as female, and 7 identified as male) aged 24-38 years rated the importance of screening outcomes via online survey and participated in a focus group to share their rationale for their ratings and discuss factors that affect the per ceived importance of various outcomes.Outcomes con sidered critical and important to decisionmaking by both partici pants and task force members were included in the systematic review. After the evidence review was completed, 17 different sexually active participants aged 24-38 years (13 participants

## Box 2: grading of recommendations
Recommendations are graded according to the Grading of Recommendations Assessment, Development and Evaluation system (GRADE).Whether a recommendation is strong or conditional is based on considerations such as certainty in the effects of an intervention, including magnitude, as well as estimates of how patients value and prioritize outcomes, variability of these estimates and wise use of resources.

## Strong recommendations
- Strong recommendations are those for which the Canadian Task Force on Preventive Health Care is confident that the desirable effects of an intervention outweigh its undesirable effects (strong recommendation for an intervention) or that the undesirable effects of an intervention outweigh its desirable effects (strong recommendation against an intervention). A strong recommendation implies that most people will be best served by the recommended course of action.
- Strong recommendations are typically based on highcertainty evidence (i.e., high confidence in the estimate of the effect of an intervention). Strong recommendations may recommend in favour of an intervention (when there is high confidence of net benefit) or against an intervention (when there is high confidence of net harm). However, there are circumstances in which a strong recommendation may be considered based on low or very low certainty evidence, or when there is absence of evidence.- When there is an absence of evidence to provide confidence that there is benefit from implementing a new prevention service or when a conclusion of possible benefit requires a high level of speculation on linkages of uncertain evidence, but there is high certainty that some patients would be harmed or scarce health care resources expended, the task force may make a strong recommendation against service implementation. 74 This is consistent with the GRADE approach, in which strong recommendations are sometimes made with lowcertainty evidence combined with high certainty of harm or resource implications, and with the value that the task force places on using scarce primary care resources wisely. 74

## Conditional recommendations
- Conditional recommendations are those for which the desirable effects probably outweigh the undesirable effects (conditional recommendation in favour of an intervention) or undesirable effects probably outweigh the desirable effects (conditional recommendation against an intervention) but appreciable uncertainty exists. Conditional recommendations are made when the certainty of evidence is lower, when the margin between desirable and undesirable consequences is small and the balance depends on patient values and preferences, or when there is high variability in the values and preferences of patients. Conditional recommendations may also be applied when the balance of cost and benefits is ambiguous, key stakeholders differ about the acceptability or feasibility of the implementation, or the effects on health equity are unclear.
- In certain cases where a conditional recommendation for an intervention is made, clinicians are encouraged to engage in shared decisionmaking, to recognize that different choices will be appropriate for individual patients, and to help each person arrive at a management decision consistent with their values and preferences.
Evidence is graded as high, moderate, low or very lowcertainty, based on how confident the task force is that the estimates of effect are correct. identified as male, 3 identified as female, and 1 identified as non binary) rated the importance of screening outcomes via online survey, this time after being provided with a summary of system atic review results.Knowledge translation tools to support recommendation implementation, informed by feedback from clinicians and patients, were developed (available at https://canadiantaskforce. ca/toolsresources/chlamydiaandgonorrhea/).

## External and content expert review
The protocol,systematic reviewand draft guideline were each reviewed by stakeholders, peer reviewers, and clinical and con tent experts (see Acknowledgements). Clinical and content experts served as advisors to the working group; they partici pated in working group meetings and reviewed documents for accuracy, but did not have input into or vote on the direction or strength of recommendations.

## Management of competing interests
The task force follows Guidelines International Network prin ciples for disclosures of interests and management of compet ing interests.The task force's oversight committee for evaluating and adjudicating competing interests consists of the task force chair and vicechair and the director of the Global Health and Guidelines Division of the Public Health Agency of Canada.Funding for the task force is provided by the Public Health Agency of Canada. The task force did not consider the views of the funding body in developing the guideline.
All task force members are required to disclose financial and other relevant interests annually when new topics are selected and at each inperson meeting of the task force (3 times per year). These disclosures are available on the task force website (https://canadiantaskforce.ca/about/members/). There were no conflicts of interest among task force members for this guideline.
Clinical and content experts also disclose relevant interests at the outset of their participation and annually thereafter (see Appendix 4, available at www.cmaj.ca/lookup/doi/10.1503/ cmaj.201967/tabrelatedcontent). The task force did not judge any disclosures to represent conflicts of interest that precluded participation as a clinical or content expert.

## Implementation
To implement this screening recommendation, clinicians in primary care settings are advised to identify individuals who are eligible for screening (sexually active individuals younger than 30 years) and not seeking testing for a possible STI, and to offer chlamydia and gonorrhea screening opportunistically (i.e., without requiring a separate screening visit, and not only during sexual health visits). As noted above, results from 1 RCT suggest that patient acceptance of screening is high when offered.As individuals at high risk of chlamydia and gonor rhea infection may not always readily selfidentify or be easily identified by clinicians, this routine offer of screening applies to all sexually active individuals without clinician knowledge of their membership of a highrisk group. Sexually transmitted infections are associated with shame, embarrassment and substantial stigma, which could prevent patients from seeking screening and treatment.Routinely offering screening to all sexually active individuals has been suggested as one way to reduce stigma associated with STI testing.Those seeking testing or who are known to belong to a highrisk group should be managed according to relevant national, provincial or local guidance applicable to those populations. Sexual activity can be generally defined as ever having oral, vaginal or anal intercourse.
Informed consent, which is required for STI testing, is an additional implementation consideration. The main issues to address are those related to privacy, reporting of positive test results to local public health offices, and potential partner notification. Screening for sexually transmitted infection may cause embarrassment and anxiety for some patients. Offering screening requires sensitivity to stigmatization and fear of social disapproval, especially regarding gender, culture, behaviour and other vulnerabilities.
Although the optimal screening interval is unknown, an annual offer of screening may be appropriate for individuals at general risk, recognizing that encounters with primary care may occur less frequently. Most identified studies used annual screeningand, in 1 study, most pelvic inflammatory disease cases occurring within 1 year were in individuals who were chlamydia negative at baseline (general risk).A falsepositive result could cause harm without benefit to some individuals. This is particularly relevant when prevalence of chlamydia in the population is lower (e.g., 2%-3%), where the number of false positives from NAAT tests may be quite high (e.g., about 30%-60% at specificities of 97%-99%).
Although we did not identify evidence that would allow rec ommendation of specific screening strategies, acceptability and uptake of screening 79-81 may be improved by minimally invasive sample collection methods, of which selfcollected vaginal swabs from females and urine samples from males are the most accu rate (NAAT).Cliniciancollected swabs are likely acceptable and feasible during certain encounters (e.g., Pap testing).Ulti mately, patient preference and the clinical scenario will likely dictate the preferred sampling method. Clinicians are reminded to consider pharyngeal and rectal swabs if clinically warranted, although we did not identify any evidence to evaluate screening using samples from these sites.
In cases of actual or suspected child abuse, clinicians are directed to their local, provincial and territorial authorities (pub lic health offices, child protection services, pediatricians and clinical experts), for STI testing, treatment, reporting and management.

## Monitoring and evaluation
Rates of offer and uptake of screening among patients in primary care settings are a key performance measure for this guideline. Rates of reported chlamydia and gonorrhea infections represent another performance metric.

## Sexually active women
The USPSTF recommends screening for chlamydia in sexually active women aged 24 years and younger and in older women who are at increased risk for infection (Grade B recommendation).
The USPSTF recommends screening for gonorrhea in sexually active women aged 24 years and younger and in older women who are at increased risk for infection (Grade B recommendation).

## Sexually active men
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for chlamydia and gonorrhea in men (I statement).
Public Health England (2018)Chlamydia Annually or on change of sexual partner, tests should be offered to men and women younger than 25 years who have ever been sexually active. Providers should use every opportunity to offer chlamydia screening across primary care and access to services for sexual and reproductive health and genitourinary medicine.

## Other guidelines
Guidelines from several groups within Canadaand inter nationallysimilarly recommend that clinicians opportunis tically offer screening to sexually active individuals for chla mydia. Some, but not all, also include recommendations to screen for gonorrhea. The present recommendation extends to age 29 years (see recommendation rationale above),whereas other guidelines recommend screening to age 25 years, except for Australia, which recommends screening to age 30 years.

## Gaps in knowledge
We did not identify any trials that carried out screening for chla mydia or gonorrhea in a manner consistent with how screening is offered directly to patients, opportunistically, in Canadian pri mary care. There was also limited evidence on health outcomes of screening for chlamydia or gonorrhea in males or their specific female partners (considering sexual networks). Almost no stud ies included participants older than 30 years (which may be because of the low prevalence in this population). Studies com paring the impacts of different screening intervals or different screening strategies in primary care settings on health outcomes are required.

# Limitations
Thresholds for a minimally important difference were devel oped for benefit outcomes of interest to determine the magni tude of effect and certainty of the evidence. These thresholds were created by task force clinicians and topic experts, taking into account Canadian epidemiologic and natural history data. 13,We did not seek patient input on these thresholds, which for some preventive interventions with substantial harms would be useful to identify patient perspectives of the threshold of benefit. We did not assess the impact of gonorrhea treatment on antimicrobial resistance, as we focused on patientimportant outcomes of screening. It is not necessarily a limitation, but the task force has made a priori choices to pool study data in a way that may differ from other groups. We did not deter mine the average effect of screening across all included trials because of our predetermined interest in the effects of an offer to screen, regardless of uptake, and the large variability between the trial designs in this respect. Decisionmakers less concerned about this variability may have analyzed the data and judged the magnitude of effects differently, although the direction of this recommendation would not likely change.

# Conclusion
Opportunistic screening for chlamydia and gonorrhea among sexually active individuals younger than 30 years confers uncer tain but potentially important benefits, particularly for preven tion of pelvic inflammatory disease in females. Psychosocial harms of screening are anticipated to be relatively mild, and patients likely prioritize potential screening benefits over harms. The task force conditionally recommends in favour of screening, at primary care visits, sexually active individuals younger than 30 years who are not known to belong to a high risk group for chlamydia and gonorrhea. Informed consent is required for screening.