Introduction
Sexually Transmitted Infections (STIs) are a persistent and prevalent threat to health globally. Chlamydia, gonorrhea, syphilis, and trichomoniasis account for a significant proportion of STI cases. In 2016 alone, there were an estimated 127.2 million new chlamydia cases, 86.9 million new gonorrhea cases, 6.3 million new syphilis cases, and 156.0 million new trichomoniasis cases worldwide [
1]. Together, these four diseases averaged 1 million new infections every day [
1].
These infections can cause serious disease. Their effects range from genital ulceration and Pelvic Inflammatory Disease (PID) to cardiovascular and neurological disease [
1]. Pregnant people with chlamydia and gonorrhea have a higher risk of ectopic pregnancy and infertility [
1], trichomoniasis is associated with increased risk of preterm delivery and prelabour rupture of membranes [
2] and syphilis infections can lead to reduced fetal growth, spontaneous abortions, and perinatal deaths [
3]. This is particularly concerning, given the high rates of STIs among young, reproductive-age people. In the United States, for example, adolescents aged 15–24 years old, make up a quarter of the population, but account for half of new STI cases annually [
4].
Although chlamydia, gonorrhea, syphilis, and trichomoniasis are all “curable” with a course of antibiotics, they still spread readily in the population and contribute to significant health impacts for millions every year. Many cases of these STIs are asymptomatic or mildly symptomatic [
5], leading to underdiagnosis and treatment. Social stigma around sexual practices and disparities in access to testing and treatment further exacerbate this problem [
6‐
8].
Antimicrobial resistance (AMR) is also a rising problem for supposedly curable STIs, gonorrhea especially [
9]. Gonorrhea strains have already developed resistance to sulphonamides, penicillins, tetracyclines, macrolides, fluoroquinolones, and early-generation cephalosporins [
9],. In the United States alone, half of gonorrhea cases in 2018 were ARM resistant [
10]. This rapid escalation has made our ability to treat the 86.9 million new gonorrhea infections every year increasingly tenuous.
Interventions like screening, sexual education, and condom advocacy [
6] have had some success at increasing STI diagnosis and reducing spread, they have not yet been enough to mitigate the rampant incidence of STIs. Vaccines could be an additional tool for control of STIs. Already, the human papillomavirus (HPV) and hepatitis B vaccines – which protect against STIs – have had success in reduce associated morbidity and mortality. Other STI vaccines are on the horizon. In 2019 Abraham et al. published the results for the Phase I Trial of their chlamydia vaccine candidate [
11], and in recent years, there have been several trials examining the efficacy of
Neisseria meningitidis vaccine at preventing
Neisseria gonorrhoeae [
12,
13]. Mathematical models predicting the epidemiological impact of gonorrhea, chlamydia, and syphilis vaccines support this vaccine development push, indicating that effective vaccines could significantly reduce disease prevalence beyond existing interventions [
14‐
17].
However, the existence of a vaccine alone does not ensure coverage–attitudes towards STIs and vaccines are likely to influence STI vaccine uptake. Parents may have substantial dispreferences for STI vaccines versus non-STI vaccines [
18]. Additionally, parental concerns about vaccine safety and appropriateness, individuals’ sense of susceptibility, societal stigma around sexual activity, media misinformation, lack of awareness about vaccination, and degree of provider attitudes and vaccine endorsement are all frequently cited factors that contribute to hesitancy around both existing and hypothesized STI vaccines [
19‐
21].
Vaccine acceptability research is therefore crucial to anticipating public hesitancy for future STI vaccines. This need for research on how to roll-out an STI vaccine is already reflected in reports from the WHO [
22] and other researchers [
23]. With a chlamydia vaccine already in clinical trials and the rising evidence that meningococcal vaccines provide partial protection against gonorrhea [
12,
13,
24], there is a need to understand the scope of what we already know about STI vaccine acceptance.
The purpose of this scoping review is to identify existing studies examining chlamydia, gonorrhea, syphilis, and trichomoniasis acceptability, map out their content, and identify populations and contexts that remain unstudied. By identifying what evidence we have and what gaps exist, we hope to provide direction for future research and for the effective implementation of STI vaccine programs.
Methods
We modeled the protocol for this scoping analysis after Arksey and O’Malley’s framework [
25], guided also by Levac et al.’s recommended enhancements [
26] and the scoping review practices outlined in JBI’s Manual of Evidence Synthesis [
27]. The protocol for this scoping analysis is publicly available [
28].
Inclusion and exclusion criteria
We established a set of inclusion and exclusion criteria centered around the characteristics of a texts’ participants, concepts, and contexts to evaluate if texts returned by our searches were relevant to this review. Texts examining human participants’ willingness to receive chlamydia, gonorrhea, syphilis, and trichomoniasis vaccines for themselves, or their willingness to have their children/dependents vaccinated, were eligible for inclusion. To be eligible, texts also had to assess participants’ willingness to receive, or have one of their children/dependents receive, one or more of the vaccines of interest. Studies examining attitudes towards the disease itself or non-vaccination interventions were ineligible. Texts discussing researchers’ interest in developing or implementing the vaccines were excluded, as were texts examining healthcare worker’s willingness to recommend or provide vaccines.
To gather as many relevant texts as possible, studies examining human populations in any context were eligible for inclusion–opinions towards vaccines for bacterial/parasitic STIs in any geographic regions, cultures, communities, and focus groups were of interest. Any text published before database searches were initiated on August 8, 2022, were eligible for inclusion.
Table
1 documents the complete inclusion criteria for the scoping review.
Table 1
Inclusion and exclusion criteria for the review
Participants | • Study population is composed of any human participants | |
Vaccines of interest | • Includes chlamydia, gonorrhea, syphilis, and/or trichomoniasis vaccines | • Does not include disaggregated measures of interest for chlamydia, gonorrhea, syphilis, and/or trichomoniasis vaccines |
Concept | • Discusses participants’ willingness to receive one or several of the vaccines of interest • Discusses participants’ willingness to have a child/ward vaccinated with one or several of the vaccines of interest | • Does not specify which STIs are being examined |
Context | • Studies from any geographic context and any time before August 9th, 2022 | • Any studies published after August 9th 2022 |
Types of study
For this synthesis, we considered studies of any research design and publication type for inclusion, including both qualitative and quantitative studies. Applicable evidence syntheses, like systematic and scoping reviews, along with conference abstracts and non-peer-reviewed literature were also eligible for inclusion.
Identifying relevant studies
We used a three-step search strategy [
19] to test and refine our initial search terms in Scopus® and Pubmed®, conduct our final searches to identify texts of interest, and perform a reference search on our included texts to identify relevant texts we might have missed during the initial searches. We conducted our searches in PubMed®, Embase®, Scopus®, Cochrane Library®, PsychInfo®, Global Index Medicus, and Google Scholar®; all searches were conducted between August 8, 2022, and August 9, 2022. Most search terms were limited to title and abstract or title, abstract, and keyword searches, though given time limitations, the Google Scholar® search was limited to titles only. A copy of the Scopus® search strategy is available in Additional File
1. We exported all of the identified texts from our searches to Zotero (Corporation for Digital Scholarship, Vienna, Virginia), where we combined them into a singular list and checked them for duplicates before exporting them to Rayyan (Rayyan Systems Inc., Cambridge, MA), where we again checked for duplicates.
Study selection
Once we completed deduplication, reviewers C.G. and T.V. conducted a blinded pilot of the eligibility criteria on the abstracts of 25 randomly selected texts and achieved the > 75% agreement necessary to proceed with abstract reviews for all identified texts.
The reviewers conducted independent, blinded title and abstract reviews in Rayyan. Once abstract reviews were completed, the reviewers unblinded and resolved any disagreements through discussion or the opinion of a third reviewer, A.W. The reviewers acquired full text copies of any articles that were marked as “include” or “maybe” after discussion and conducted full text reviews to determine inclusion or exclusion from the synthesis. All disagreements were settled through discussion or the opinion of the third reviewer.
Charting the data
We developed a data abstraction form, which included title, year of publication, country of origin, country where the study was conducted, aims/purpose, population of interest, sample size and description, methodology, intervention, outcomes, and key findings. We expanded the extraction template to include a section for collecting information on the questions used to examine vaccine acceptability, including question(s) used, response scale used, if the acceptability measure was based on one question or an aggregate, and the word or phrase used to describe acceptability. Reviewers T.V. and C.G. conducted concurrent abstractions for each included text.
We also used a critical appraisal tool to examine the overall quality of the included studies. Given that the results of interest in the included studies were descriptive statistics for STI vaccine acceptability, we limited our evaluation to questions 1, 2, 7, and 8 of the JBI Critical Appraisal Tool for Analytical Cross Sectional Studies [
27], with additional clarifying criteria established by the review team (Additional File
2).
Collating, summarizing and reporting the results
We used the abstraction data to map the included studies’ characteristics and designs, as well as the relevant findings about vaccine acceptability. We then conducted basic thematic analyses of the survey instruments and questionnaires to provide insight into how investigators inquired about willingness to receive chlamydia, gonorrhea, syphilis, and/or trichomoniasis vaccines. For texts where the survey materials and/or vaccine acceptability questions were not available in the text or additional files, or where the geographic context of the research was unclear, investigators reached out to the texts’ authors to inquire about the questions utilized and geographic context. As of November 6, 2022, we had not received clarifying information on survey questions or study locations.
Discussion
Future roll-outs of STI vaccines could be an important tool in addressing the substantial burden of these diseases. This scoping review details the range of studies on acceptance of future vaccines for bacterial and parasitic diseases. Overall, the eight studies included in this analysis indicate relatively high levels of STI vaccine acceptability in the populations studied. A desire to protect oneself, one’s child, and one’s partner were common acceptability motivators [
38‐
40], and concerns about STIs and histories of STI infection were related to vaccine acceptability in several studies [
34,
35,
37,
40].
While the estimates of acceptability in the available studies is relatively high, the quantity of included texts underlines the dearth of knowledge we have about chlamydia, gonorrhea, syphilis, and trichomoniasis vaccines. As much of this research is at least one, if not two decades old, there could be changes in vaccine acceptability not reflected in the available data. Of note, all the included studies had data collection prior to the COVID-19 pandemic, and the pandemic could have impacted patterns of adult vaccine hesitancy (e.g., as seen for pediatric vaccinations [
42]).
There are some limitations to the generalizability of these studies. The studies are in the United States [
34‐
37,
40,
41] and in Canada [
38,
39]. Previous cross-national surveys have found substantial differences across countries for influenza [
43] and COVID-19 [
44] vaccine acceptance. Previous systematic reviews of HPV [
45], COVID-19 [
46,
47], and influenza [
48] vaccines show that acceptability and uptake of vaccines could vary based on factors that substantially differ across countries, including insurance / health care systems, religion, trust in authorities, political polarization in vaccination, and attitudes towards sexual behaviors.
Studies of the HPV vaccine [
32,
45], the mpox vaccine [
49], and other vaccines for MSMs like hepatitis A and hepatitis B [
50] might be the closest analogues for understanding the future roll-out of another STI vaccine. Notably, consistent and strong recommendations from health care providers are one of the most important factors in deciding whether someone will accept a vaccine [
45,
50]. Convenience of access to the vaccine site is important [
32]. For the mpox vaccine, greater perceived susceptibility, more cues for action, and more convenient access did increase vaccine uptake [
49]. However, the proportion who rejected a vaccine offered on site at a clinic visit can still be relatively high – 15% in one study of mpox [
49]. Mathematical modeling could determine whether that percentage could have a substantial epidemiological consequence.
Systematic reviews can be limited in their ability to explain the reasons behind significant findings [
51] due to lack of consistent measurement of various issues across studies. We acknowledge in this systematic study the lack of consistent measurement of certain factors that likely had a large impact on individual and collective levels of decision-making. Stigma in particular is important to define and research as it affects testing and treatment of STIs [
52‐
54], and could affect vaccine distribution [
55]. Parents also could be worried that STI vaccination could affect their child’s sexual behaviors [
31], although research does not suggest this occurs [
56].
There is also the concern that the acceptability measures we do have are skewed towards those who are more willing to seek medical care and who have better access to medical care. Many of the studies sampled participants from healthcare settings [
36,
39‐
41], and the rest sampled from larger health-based studies [
34,
35,
37,
38]. As such, there is the possibility that these studies are subject to selection bias, and might not accurately represent communities with lower access to healthcare or higher distrust in the healthcare system, including racial and ethnic minorities, sexual and gender minorities, low-income individuals, and non-English speakers [
57‐
60]. As such, additional research into vaccine acceptability among these populations, especially sampled outside of healthcare settings, could be crucial to having a better understanding of vaccine acceptability.
There is also a need to better understand how vaccine characteristics might impact receptivity [
23]. As shown with HPV vaccines, acceptability does not necessarily equate to uptake, initiation is often higher than completion, and timeliness of completion is not always to schedule [
50,
61,
62]. The included studies inquired about whether or not participants would receive certain STI vaccines. Differences between acceptance and uptake could result from the following reasons: yet-unknown features of the vaccination program, like number of doses required [
63]; cues to action and vaccination planning [
64]; social desirability bias in responding to questions in a certain way; and other factors. Further research into these and additional vaccine characteristics’ effects on vaccine acceptability is necessary to accurately predict vaccine uptake.
Limitations
One notable limitation of this study is that inclusion was limited to publications written in English, which could have excluded publications of interest written in other languages. Another limitation is breadth of search. While scoping analyses are meant to be comprehensive, they are not always exhaustive, and there is the potential that the databases we utilized were not fully representative of the literature relevant to our study. In the interest of the resource and time limits on this examination, we limited our Google Scholar search results to title searches only, cutting down on the number of texts we collected, but also potentially missing some texts of interest.
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