Title: Meatal swab yourself with testing for infections collectively (MYSTIC): Diagnostic accuracy study of rectal and pharyngeal swabs pooled with meatal swabs, or first-pass urine, for chlamydia and gonorrhoea detection
Funder: Department of Health and Social Care

Abstract: Background: 3-monthly testing for chlamydia and gonorrhoea, of pharyngeal, rectal and first catch urine (FCU) samples is recommended in men who have sex with men (MSM), and trans-women, taking HIV Pre-Exposure Prophylaxis (PrEP) and in MSM at higher risk of acquiring sexually transmitted infections (STIs). Many services struggle to afford the three sample costs, four-times per year, which may restrict numbers given PrEP. Our recent research showed the 3 samples can be combined into one pooled specimen to accurately diagnose gonorrhoea. However, the pooled chlamydia sensitivity was reduced to 92% versus 99% for the 3 samples. Pooled specimens were much more cost-effective due to reduced diagnostic costs. This study aims to improve the pooled chlamydia diagnostic accuracy by comparing two new pooling methods with 3 samples tested separately. Design: A study comparing sensitivity of self-taken rectal and pharyngeal swabs pooled 1. with a reduced amount of FCU, and 2. with a meatal swab instead of FCU, versus 3 samples tested separately, for gonorrhoea and chlamydia diagnosis. Setting: Leeds Sexual Health services Population: MSM and trans-women who have a penis Inclusion criteria: 18 years and over Willing to perform self-taken swabs in addition to any clinician required swabs Able to provide informed consent Exclusion criteria: Antibiotics taken in past 14 days Interventions: Self-taken rectal and pharyngeal swabs pooled with a self-taken meatal swab Self-taken rectal and pharyngeal swabs pooled with 1ml FCU Control: Clinician, or self-taken, rectal and pharyngeal swabs, and FCU, analysed separately The sampling order will be randomised. Microbiology: Samples will be tested for gonorrhoea and chlamydia using Aptima Combo2 and positives confirmed with Aptima GC and Aptima CT respectively. Patient infected status will be defined as at least two positive confirmed samples. Primary Outcome: Sensitivity and specificity for gonorrhoea, chlamydia, and lymphogranuloma venereum (LGV) diagnosis using NAATs Secondary Outcomes: Acceptability of using meatal swabs compared with FCU for the diagnosis of gonorrhoea, chlamydia, and LGV Acceptability of using pooled samples compared with individually analysed samples for the diagnosis of gonorrhoea, chlamydia, and LGV Sample size: 1250 participants will result in 193 with chlamydia infection assuming chlamydia prevalence of 15.4%. Assuming a 99% sensitivity for the 3 samples tested separately, 193 chlamydia positive participants will allow detection of a significant difference between sensitivities of 92% and 99% with 90% power and 5% Type I error rate. Recruitment: Projected recruitment is 89-90 participants per month over 14 months. During January 2021, when services were reduced due to staff redeployment, sickness, shielding and isolating, we were still seeing 45-50 MSM face to face per week for 3-sample testing. In our recent study, less than 2% of MSM approached declined to participate so we expect good recruitment. Timetable: Month 0-6: set up Month 7-20: recruitment Month 21-24: data analysis, manuscript preparation Dissemination: The results will be presented at national and international conferences and submitted for publication to medical journals. The results will be shared with LGBTQ+ community groups, Local Authority public health teams, and national STI organisations.

Lay abstract: Testing for chlamydia and gonorrhoea in men who have sex with men (MSM) and trans-women is recommended every 3 months for those taking HIV Pre-Exposure Prophylaxis (PrEP) and in other MSM at higher risk of catching sexually transmitted infections (STIs). Testing requires throat and bottom samples, and samples from the urethra (wee-pipe), usually a urine sample. However, many sexual health services struggle to afford the costs of these three samples, four-times per year, which may restrict numbers given PrEP. Our previous research has shown that the 3 samples (throat, bottom, urine) can be combined into one pooled specimen to accurately find gonorrhoea and reduce laboratory costs. However, the chlamydia results of pooled samples were not as good, finding only 92 out of 100 infections compared with 99 out of 100 with 3 separate samples. This study aims to improve the accuracy of chlamydia results by comparing two new pooling methods with the 3 samples tested separately. MSM, and trans-women who have a penis, aged 18 years or over, attending our clinics for STI testing will be invited to take part in the study. The pooling methods will be: 1) pooling with a smaller amount of urine to reduce the dilution of the other samples; and 2) pooling with a swab sample from the outside of the tip of the penis (meatal swab) instead of urine. Meatal swabs are taken by the men themselves. The swab does not go inside the penis so is easy to do and not painful. Studies suggest meatal swabs may be better at finding chlamydia than urine samples. We will recruit 1250 participants. This is a large enough number to show if either of the pooling methods can detect more chlamydia than 92 out of 100 infections. To ensure an accurate comparison, the order of taking the two pooling method samples, and the 3 samples tested separately, will be randomised. The samples will be tested for chlamydia and gonorrhoea. Participants will be informed of their test results and receive the usual treatment for any infections. Public contributors will contribute to the participant information sheet, other participant documents and questionnaires. They will also attend study management meetings and particularly advise on any recruitment issues. The study results will be presented at national and international conferences and submitted for publication to medical journals. The results will be shared with LGBTQ+ community groups, Local Authority public health teams, and national STI organisations. If the results identify a pooling method that is as good at finding gonorrhoea and chlamydia as the 3 samples tested separately, this could be done at one-third the laboratory costs, meaning 3-monthly STI testing would be more affordable and PrEP could be offered to more people.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION