key: cord-0309457-s7c5zi2v
authors: Sri-Pathmanathan, C.; Nhamo, D.; Mamvuto, T.; Chapwanya, G.; Terris-Prestholt, F.; Mahaka, I.; Marks, M.; Tucker, J. D.
title: Syphilis self-testing to expand test uptake among men who have sex with men: a theoretically informed mixed methods study in Zimbabwe
date: 2020-11-30
journal: nan
DOI: 10.1101/2020.11.30.20240788
sha: 166518ad744da20d15c16031beda687d9abe0baa
doc_id: 309457
cord_uid: s7c5zi2v

Objectives: Self-testing for STIs such as HIV and syphilis may empower sexual minorities and expand uptake of STI testing. While much is known about HIV self-testing (HIVST), less is known about syphilis self-testing, particularly in low-income settings. The objective of this study is to determine context-specific facilitators and barriers for self-testing and to assess the usability of syphilis self-testing in Zimbabwe among men who have sex with men (MSM). Methods: This mixed methods study was conducted in Harare as part of a larger syphilis self-testing trial. The study included in-depth interviews (phase one) followed by usability testing and a second interview (phase two). In-depth interviews were conducted with MSM and key informants prior to syphilis self-testing. The same MSM then used the syphilis self-test, quantitatively assessed its usability and participated in a second in-depth interview. Phase one data was analysed using a thematic approach, guided by an adapted Social Ecological Model conceptual framework. Phase two interviews were analysed using Rapid Assessment Procedure qualitative methodology, and usability was assessed using a pre-established index, adapted from existing HIVST evaluation scales. Results: Twenty MSM and 10 key informants were recruited for phase one in-depth interviews and 16 of these MSM participated in phase two by completing a syphilis self-test kit. Facilitating factors for self-testing included the potential for increased privacy, convenience, autonomy and avoidance of social and healthcare provider stigma. Barriers included the fear to test and uncertainty about linkage to care and treatment. Data from the usability index suggested high usability (89.6% on a 0-100 scale) among the men who received the self-test. Conclusions: MSM in Zimbabwe were willing to use syphilis self-test kits and many of the barriers and facilitators were similar to those observed for HIVST. Syphilis self-testing may increase syphilis test uptake among sexual minorities in Zimbabwe and other low- and middle-income countries.

Provenance and peer review : Not commissioned; awaiting external peer review.

Data availability statement -Data are available upon reasonable request : All individual patient data 62 collected that underlie the results reported in this article will be available (text, tables, figures and 63 appendices). Analytic codebooks and consent forms are also available upon request. This data will be 64 available immediately following publication to researchers who provide a methodologically sound proposal.

In 2016, WHO estimated 19.9 million cases of syphilis worldwide, with the highest prevalence in the WHO 72 African region (1) . In the same year, the Global Health Sector Strategy on Sexually Transmitted Infections 73 sets an impact goal to reduce syphilis infections by 90% globally between 2016-2030. As syphilis is often 74 asymptomatic, testing is essential to effectively interrupting transmission and innovative strategies are needed 75 to expand syphilis test uptake (2). Syphilis is more common among men who have sex with men (MSM), with 76 the WHO reporting a median seroprevalence of 6.0% in this group, estimated from 2016-2017 Global AIDS 77 Monitoring data (3). A 2020 biobehavioural survey in Zimbabwe found that 5.1% of Harare MSM had 78 positive treponemal and non-treponemal tests (4). In addition, syphilis and HIV share common sexual risk 79 behaviours and syphilis facilitates HIV transmission, making syphilis co-infection particularly prevalent in 80 HIV-infected MSM (2)(5). As PrEP becomes increasingly available in LMIC, risk behaviours may also 81 change and inadvertently facilitate STI transmission (6). As a result, the WHO strongly recommends routine 82 syphilis screening among MSM (7).

MSM face unique health care challenges because of lack of funding for MSM health, lack of testing, legal and 85 cultural barriers, and stigmatisation, particularly in low-and middle-income countries (LMIC) (8). Stigma 86 associated with same sex relationships may also extend to healthcare facilities and professionals (9). There is 87 also a considerable gap in evidence to guide MSM health programs in many LMICs (10). As a result, despite 88 WHO recommendations, MSM are frequently excluded from syphilis testing services in many LMICs (2).

One way to expand MSM syphilis test uptake is self-testing. Syphilis self-testing is an approach whereby a 91 person performs a rapid syphilis test themselves and interprets the result in private. Self-testing may overcome 92 some of the barriers associated with facility-based testing, promoting early diagnosis, interrupting disease 93 progression, and reducing syphilis transmission (11).

HIVST is recommended by the WHO to expand test uptake among stigmatised key populations (7) 

All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted November 30, 2020. ; https://doi.org/10. 1101 /2020 Zimbabwe. The purpose of this study was to determine facilitators and barriers for syphilis self-testing and to 107 assess the usability of syphilis self-testing as reported by Zimbabwean men who have sex with men (MSM).

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A two-phased mixed methods study was conducted among MSM in Zimbabwe. We focused on Harare 110 because of the strong network of MSM community-based organisations in the city. The first phase was prior 111 to syphilis self-testing and the second phase was after syphilis self-testing. The formative data from both 112 phases informed a trial protocol aiming to compare syphilis self-testing to facility-based testing in MSM in 113 Zimbabwe (16).

In phase one, in-depth interviews were conducted amongst MSM and key informants, by trained and 116 experienced researchers from the Pangaea Zimbabwe Aids Trust (PZAT), between March and April 2020. We 117 recruited MSM using snowball sampling (17). Participants needed to meet the following inclusion criteria: 16 118 years or older, living in Harare, ever had anal or oral sex with another man, born biologically male, and able 119 to provide informed consent. All MSM were referral facilitators, responsible for offering community support 120 to individuals who are harder-to-reach. Key informants were healthcare professionals and were purposively 121 sampled to include providers who had experience with HIV and/or syphilis testing.

Interviews were conducted using a structured guide, lasted approximately 30 minutes and were audio-124 recorded. The MSM interview guide was developed to explore prior syphilis-and HIV-testing experiences, 125 facilitating and deterring factors, and self-testing intervention preferences. Socio-demographic data were also 126 collected. The key informant interview guide included healthcare provider experiences with HIV and syphilis 127 testing and treatment services, including population served and challenges faced.

Interviews were translated and transcribed by PZAT researchers. Transcripts were then entered into Dedoose 

In phase two, the syphilis self-test distributed to MSM consisted of a STANDARD Q Syphilis Ab treponemal 139 blood-based rapid test, adapted for individual use and interpretation. Individual lancets and buffer samples were 140 packaged into sealed plastic pouch, together with an individual test device and an infographic, created to explain 141 step-by-step use and appropriate disposal of the kit. An instructional video was created and disseminated to 142 facilitate independent use. Tests were distributed by researchers from PZAT to the same MSM who had 143 completed in-depth interviews in phase one. It emerged that insufficient quantities of buffer were provided in 144 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted November 30, 2020. ; https://doi.org/10.1101/2020.11.30.20240788 doi: medRxiv preprint distribution of additional buffer samples.

In phase two (August 2020), PZAT researchers interviewed a sample of 16 MSM who successfully completed 164 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted November 30, 2020. ; https://doi.org/10.1101/2020.11.30.20240788 doi: medRxiv preprint

Twenty MSM and 10 key informants were recruited for in-depth interviews in phase one. In phase two, the 166 whole cohort was contacted but four MSM were lost to follow-up due to relocation or communication 167 difficulties. Sixteen MSM were therefore invited to conduct the self-test independently and were 168 subsequently interviewed. In phase one, 18 of 20 MSM had previously used HIVST ( Table 1 ). All of these 169 MSM had at least secondary-level education and all but three self-identified as MSM. We observed the 170 following themes in qualitative data: prior STI and HIV testing experiences, both with self-testing and 171 facility-based services; usability of the syphilis self-test and how it compares to HIV self-testing; MSM-172 specific facilitators and barriers for self-testing.

In phase one, eighteen MSM had experienced HIV self-testing before using the oral HIV test. Ten participants 176 stated they used HIVST every three to six months. In addition, thirteen of the 18 HIVST-experienced MSM 177 had then attended a facility and were empowered to seek facility-based services. Key informants confirmed 178 that syphilis testing is usually reserved for pregnant women, and only three had received training on how to 179 work with MSM, suggesting MSM are largely neglected by STI services. Some providers recommended 180 syphilis testing should be mandatory for key populations.

Of the 16 participants in phase two, two (12.5%) tested positive for syphilis. Fifteen participants reported the 184 clarity of explanations provided in the infographic and video were instrumental to successful test completion.

Overall, MSM reported 89.6% usability for the syphilis self-test on a 0-100 scale. This is described in detail in 186 Table 2 . The main challenge with the test kit, reported by 11 of the 16 participants, was the blood draw using 187 the capillary pipette. Participants nonetheless felt this particular challenge was warranted for the test to 188 function. One participant had difficulties extracting the buffer because insufficient quantities were provided.

Four participants had to repeat the test, as they did not provide enough blood for the test to show a result.

Comparing syphilis self-testing to HIVST 192 Phase two participants felt that the syphilis and HIV self-test kits had many similarities, including the 193 potential for privacy and convenience. The major challenge cited was that syphilis self-testing uses a blood 194 sample whilst most HIVST kits use oral samples. Two MSM reported a preference for HIVST compared to 195 syphilis self-testing because of this issue. However, fifteen (94%) participants felt that they trusted the 196 syphilis test result more because it was blood-based. They also preferred the syphilis self-test because of the 197 clarity of instructions compared to prior HIVST instructional material.

All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted November 30, 2020. ; https://doi.org/10. 1101 /2020 Facilitating and deterring factors for self-testing were categorised into individual, community and structural-201 level factors (Table 3) . Convenience, privacy, and autonomy were the most cited reasons why MSM preferred 202 self-testing over facility-based testing.

The following factors were facilitators for both HIVST and syphilis self-testing: privacy, autonomy and 206 empowerment, convenience, user-friendliness, high perceived trust in blood-based tests, avoidance of social 207 and healthcare provider stigma, monetary and time savings, and reduced contact with facility-based services 208 in the COVID-19 context. All MSM participants felt comfortable testing alone and stated they would prefer 209 doing their next test at home, in order to be the first to see their results. In comparison, three participants 210 stated that facility-based testing did not provide adequate levels of privacy. MSM liked that they could 211 conduct their test without the involvement of a healthcare provider and the convenience of it.

MSM highlighted that the lengthy waiting periods for in-facility testing are an important deterring factor. A 214 rapid self-test could contribute to speeding up diagnosis, reducing treatment delay and more efficiently 215 interrupting syphilis transmission. Seven participants in fact mentioned that HIV self-testing empowered them 216 to test more frequently and take control of their sexual health. All phase two participants stated that the blood 217 draw increased their trust in the syphilis self-test. Two MSM noted the blood draw for syphilis facility-based 218 testing is more painful than the self-test, due to the nature of the self-testing lancets provided, and thus would 219 opt for the self-test. Participants explained that they preferred the pressure-activated lancets provided in the 220 study self-test kits, in comparison to the twist-top universal lancets used in-facility.

Participants liked that they were able to avoid being identified at a facility and stigmatized by members of 223 their own community. Additionally, several MSM observed that self-testing prevented hostility from 224 providers or other society members, therefore decreasing test-associated stigma. Key informants in phase one 225 explained they valued self-testing because of the potential to reduce contact with clients, especially in the 226 context of the COVID-19 pandemic.

Themes related to barriers included the following: the challenge of self-sampling blood, reluctance to test due 230 to poor awareness, stigma at community-level following at-home testing, indefinite linkage to care and 231 treatment availability. Twelve participants experienced difficulty with the blood draw that they attributed to 232 inexperience. One participant was concerned about the bio-hazard potential with test-kit material disposal.

Some MSM mentioned that self-test uptake is jeopardised among the wider community of MSM by poor 234 awareness and the perception that they do not have STIs. MSM also expressed concerns over the fact they 235 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted November 30, 2020. ; https://doi.org/10.1101 https://doi.org/10. /2020 could be profiled or stigmatised within their own community following at-home self-testing. Participants 236 reported that they would seek confirmatory testing if trusted information was provided on where to go and 237 what to expect in-facility. These are legitimate concerns that align with phase one qualitative data, which 238 showed that provider discrimination and treatment shortages exist at structural level. Multiple key informants 239 also reported frequent unavailability of the facility-based syphilis tests required for confirmatory testing, as 240 these are reserved for antenatal care.

All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted November 30, 2020. ; https://doi.org/10.1101 https://doi.org/10. /2020 Our study expands on the limited literature on syphilis self-testing, includes qualitative and 243 quantitative data, and follows MSM prior to and after self-testing. We found that syphilis self-testing 244 was feasible and highly acceptable among MSM in Zimbabwe. The high usability index (89.6%) 245 suggests that syphilis self-testing would be acceptable in this subgroup of MSM. Overall, 12.5% of 246 phase two MSM tested positive for syphilis, a high proportion considering the relatively small number 247 of participants. Participants reported self-testing was a convenient method that provided increased 248 privacy, autonomy and diminished vulnerability in comparison to facility-based testing. The testing 249 challenges associated with the amount of test buffer were transient and were improved by increasing 250 the quantity of buffer provided.

Study findings are consistent with HIV self-testing data in Zimbabwe, as well as syphilis self-testing 253 data from China (23) and the Netherlands (15). Our qualitative data suggested that many of the same 254 facilitators and barriers for syphilis self-testing exist for HIV self-testing. Self-testing is a private and 255 convenient method that is preferred over facility-base testing, especially for higher risk individuals.

This is reflected in the large body of evidence that exists for HIV self-testing, which is now well 257 established in Zimbabwe (24). We found that syphilis self-testing was the first ever syphilis test for 258 half of our study participants. This is consistent with data from China suggesting that syphilis self-259 testing may increase test uptake among MSM (23). Recent data from HIVSTAR in Malawi, Zambia 260 and Zimbabwe also show that HIVST also encourages first-time HIV testing (25).

Our qualitative data suggest that syphilis self-testing can empower MSM to test when, where, and 263 with whom they wish. This is consistent with a global HIVST qualitative literature showing how self-264 testing gives agency to those who test (12)(26). Existing research also shows self-testing can improve 265 testing frequency (27,28). Providing autonomy, control and creating a culture of testing among 266 vulnerable MSM could potentially help to build trust in the local health system, which is relatively 267 low according to recent evidence (9).

One barrier to syphilis self-testing was the uncertainty of linking to confirmatory testing and treatment perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted November 30, 2020. ; https://doi.org/10.1101 https://doi.org/10. /2020 coverage (25) 

This study has implications for research and policy. It has revealed that more research is needed on 293 how we can integrate syphilis self-testing into established networks of HIV self-testing services to 294 facilitate implementation. Syphilis self-testing cannot effectively contribute to interrupting syphilis 295 transmission if facility-based confirmatory testing and treatment is not made accessible to MSM.

Clinical trials are needed to assess the effectiveness and risks of syphilis self-testing in practice. From 297 a policy perspective, many of the existing HIVST policies could be expanded to cover syphilis self-298 testing. Further policy development will help national leadership to embrace syphilis self-testing as a 299 tool for expanding syphilis testing. Improving testing among key populations can reduce the bridging 300 of syphilis into the general population, likely having an impact on the overall prevalence of syphilis, 301 with the potential of reducing mother-to-child transmission.

In conclusion, the findings from this study suggest that syphilis self-testing may decrease user 304 perceived test-associated stigma and empower MSM in an area where same sex relations are 305 condemned. As PrEP is expanded in Zimbabwe and other LMIC settings, leading to a possible shift in 306 sexual risk behaviours, syphilis prevalence may increase. Innovative tools such as syphilis self-testing 307 are needed to expand syphilis test uptake, especially for marginalised populations of MSM. 308 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted November 30, 2020. ; https://doi.org/10.1101/2020.11.30.20240788 doi: medRxiv preprint 412 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in Tested positive for syphilis 2 (12.5)

In person via community-based organisation Through messaging via WhatsApp 6 (37.5) 9 (56.25) 415 All rights reserved. No reuse allowed without permission.

perpetuity.

preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in 418 ‡ The usability index (UI) was calculated based on the method used in the HIVST paper from which the index itself was extracted. The original UI is based on WHO literature on Diagnostic Assessment for submission to prequalification. Like in the HIVST study, we tracked all successful steps, in order to quantify a usability index, expressed as a percentage (20) All rights reserved. No reuse allowed without permission.

perpetuity.

preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in

The copyright holder for this this version posted November 30, 2020. ; https://doi.org/10. 1101 /2020 

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Comment: On Respondent-Driven Sampling and Snowball Sampling in Hard

Autonomy and selfempowerment