Introduction

Monkeypox (mpox) is caused by the monkeypox virus, which belongs to the Poxviridae family. The disease is primarily found in Central and West African countries. In May 2022, a series of monkeypox cases was identified in nonendemic countries (Gessain et al., 2022). A gay, bisexual, or other same-gender loving man who has sex with men was identified as a contributing factor in the current mpox outbreak (Mitjà et al., 2023; Thornhill et al., 2022). Although transmission was suspected to have occurred through sexual activity in most cases, mpox can be transmitted through respiratory secretions, direct contact, percutaneous transmission, and vertical transmission (Mitjà et al., 2023). Consequently, there is also a risk of transmission among health care workers and those who are in close contact with mpox cases or contaminated objects.

During the 2022 global outbreak of mpox, most cases occurred in sexual and gender minority (SGM) groups, especially men who have sex with men (MSM) (Gessain et al., 2022). Mpox stigma among MSM has become a global issue, further aggravating the existing discrimination against the SGM community. In 2019, Taiwan became the first Asian country to legalize same-sex marriage. Yet, legalization appears at odds with referendum results, which showed a majority of Taiwanese citizens opposed lesbian, gay, bisexual, transgender, and queer or questioning (LGBTQ+) acceptance. A need for creating safe spaces for the SGM community still remains (Au, 2022). Since the mpox outbreak, the SGM community was erroneously held responsible for spreading the disease, making it even more difficult to deal with discrimination in Taiwan.

To stop the transmission of mpox, the World Health Organization (WHO) issued guidance for vaccines and immunization (Vaccines & immunization for monkeypox: Interim guidance, 2022). JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic, MVA-BN) is a live, attenuated smallpox and mpox vaccine utilized to protect against mpox worldwide. As the global monkeypox outbreak escalated, the Taiwan Centers for Disease Control (CDC) confirmed the first case of monkeypox virus infection detected in Taiwan on June 24, 2022. The individual was a 20-year-old man who had returned to Taiwan from Germany. He developed symptoms including fever, sore throat, muscle pain, lymph node swelling in the groin, and a skin rash (Yang et al., 2022). To combat the spread of mpox, Taiwan's CDC permitted the import of the JYNNEOS vaccine and opened vaccination registration to those who were laboratory personnel working with orthopoxviruses, individuals in close contact with mpox cases, sex workers, SGM who have had sexually transmitted diseases, multiple sexual partners and sex at a commercial sex venue, and health workers at risk of exposure.

A report by the WHO showed that one of the challenges faced in preventing mpox transmission was a lack of knowledge of the disease (Monkeypox-United Kingdom of Great Britain & Northern Ireland, 2022). A study in Indonesia assessed the knowledge of mpox among general practitioners and concluded that the knowledge level of mpox was relatively low (Harapan et al., 2020). Another study investigated knowledge of mpox among MSM in China and revealed that only 36.9% of participants had mpox-related knowledge (Zheng et al., 2023). A study also demonstrated that social media might provide incomplete, inaccurate information on mpox (Dong et al., 2023). Moreover, Owens and Hubach (2023; see also Hubach & Owen, 2022) discovered that the mpox behaviors and attitudes among MSM differ between rural and urban populations. The intention of mpox vaccination remains suboptimal among rural populations. It is noteworthy that an increased knowledge of mpox was associated with a higher willingness to vaccinate (März et al., 2022). As a result, a lack of knowledge could potentially reduce the willingness to receive mpox vaccination. In addition to insufficient knowledge, misperception and stigmatization also influenced the opinions people possessed about vaccination. The mpox outbreak resulted in increased stigmatization of the LGBTQ+ community (März et al., 2022). A study based on Tweet analysis showed that a part of the population believed that only the LGBTQ+ community was susceptible to the virus (Rajkhowa et al., 2023). Some people feared the labeling they would obtain if they were vaccinated (Rajkhowa et al., 2023). Curtis et al. (2023) found that subjects who had higher degrees of fear of social rejection owing to mpox vaccination acquisition tended to be unvaccinated individuals in the United States. In Taiwan, when discussing Mpox cases, people often associate it with the SGM community. Since most recipients of the Mpox vaccine at public expense are MSM, the acceptance of the vaccine may be compromised by fear of being labeled due to the injection mark and a lack of knowledge about Mpox.

The standard regimen for the JYNNEOS vaccine is a subcutaneous route of injection with an injection volume of 0.5 mL (Vaccine JYNNEOS, 2022). People with a history of developing keloid scars are recommended to receive subcutaneous injection (Vaccine JYNNEOS, 2022). An alternative regimen with an intradermal administration route has also been approved (Vaccine JYNNEOS, 2022). The injection volume is only 0.1 mL, thus increasing the amount of available vaccine doses by up to fivefold. The alternative regimen is typically performed in the forearm, but may also be performed at other sites such as the deltoid. Mpox vaccine regimens currently available in Taiwan included subcutaneously in the deltoid, intradermally in the deltoid and intradermally in the forearm. In light of vaccine supply constraints, the intradermal administration in the forearm is a preferred option in many countries (WHO, 2022). However, some people declined mpox vaccination because of the stigma associated with the visible mark left on their forearm (Press Briefing by White House Monkeypox Response Team & Public Health Officials, 2022).

To investigate mpox vaccine-related stigma, our study conducted an online survey to compare the detailed items of physical and psychological impacts of different regimens among individuals who had received the first dose of the mpox vaccine and were scheduled to receive the second dose at clinics. From our clinical observations, individuals were particularly concerned about the visibility of the injection on the forearm. Therefore, we hypothesized that different vaccine regimens may lead to varying levels of stigma perception among vaccinee, and that the vaccine-related stigma may influence the preference for mpox vaccine regimens.

Method

Participants

The inclusion criteria of the participants were as follows: (1) aged 18 years or older, (2) eligible for free public mpox vaccines, including sex workers, SGM individuals who have had sexually transmitted diseases, multiple sexual partners, sex at a commercial sex venue and sex associated with large public events within the geographic area where mpox transmission occurred in the past 6 months, individuals who have had sexual contact with mpox cases (after completing a 21-day self-health monitoring under the supervision of health bureau), mpox virus laboratory staff, or health care staff, (3) completion of first mpox vaccine dose at least 4 weeks earlier, (4) capable of independently comprehending and finishing the self-administered questionnaire, and (5) willing to take the survey.

Measures and Procedure

We conducted a descriptive cross-sectional self-administered survey from May 2023 to June 2023. Data were collected from individuals who received the first mpox vaccine dose at least 4 weeks prior and visited the monkeypox vaccine clinic for a scheduled second dose of preexposure mpox vaccination in a medical center in northern Taiwan. Consent to participate in the study was obtained with the submission of the online questionnaire via mobile device. Anonymity and confidentiality were maintained throughout the completion of the online questionnaire with strict measures.

A literature review was conducted to identify common local and systemic adverse events (AEs) of mpox vaccination. Local AEs (pain, itching, erythema, lump, swelling, discoloration and scarring) as well as systemic AEs (myalgia, headache, fatigue, nausea, fever and dizziness) were investigated in this study. Each adverse event was evaluated for physical and psychological impact on a severity scale of absent, mild, moderate and high.

The questionnaire was divided into two sections. The demographic information of the participants was collected in the first section, which included age, sex, marital status, sexual orientation, education level, reason for vaccination, medical history, interval between two vaccinations, regimen of first mpox vaccine dose, preference for second mpox vaccine regimen and knowledge of the mpox vaccine. The second section consisted of two subsections as follows: (1) physical and psychological impacts of the first mpox vaccination AE and (2) preference for the second mpox vaccine dose regimen and a multiple-choice question for factors influencing the preference. Since we hypothesized that different vaccine regimens may lead to varying levels of stigma perception among vaccinee, our study divided the participants into four groups based on their preference for the second mpox vaccine dose regimen: subcutaneously in the deltoid, intradermally in the deltoid, regardless of the route in the deltoid and intradermally in the forearm. The factors influencing the preference included beauty, scar, others’ view, effect of protection, local AE severity, systemic AE severity, injection dosages, propensity of keloids. “Beauty” referred to the cosmetic outcomes of the local injection sites. “Scar” stated for the long-term scar tissue formation at the injection sites. "Others’ view" in this article referred to the perception of others regarding a person receiving mpox vaccination. The severity of physical impact was defined from the physical discomforts developed after vaccination. Absent: no symptoms or ignorable symptoms; Mild: symptoms required no treatment; Moderate: symptoms required treatment or consultation with a health professional; Severe: symptoms required hospital admission. The severity of psychological impact was defined as the frequency of feeling nervous, anxious or on the edge after vaccination. Absent: not at all; Mild: several days; Moderate: more than half the days; Severe: nearly every day. Open-ended questions were included at the end of the questionnaire to encourage participants to speak freely about their vaccination experiences and feelings.

Statistical Analysis

Continuous variables are presented as the mean ± SD, and categorical variables are presented as numbers (percentages). Kruskal–Wallis H tests were used to examine the differences in AEs between different vaccination regimens. Spearman’s rank correlation was performed to identify the relationship between the physical and psychological impacts of vaccination AEs. A multinomial logistic regression was conducted to model the effects of local adverse event-related physical and psychological impacts on different mpox vaccine regimens. The outcome variables were different mpox vaccine regimens, and the explanatory variables were local adverse event-related physical and psychological impacts. Collinearity among the variables was evaluated to ensure the independence of explanatory variables in the analysis. Multinomial logistic regression allowed us to simultaneously contrast different injection routes in the deltoid against intradermally injection in the forearm (the reference group). Another multinomial logistic regression was used to model the effects of various factors on different vaccination regimens. The outcome variables were different injection regimens, and the explanatory variables were factors influencing preference for injection regimens. Statistical analyses were conducted with SPSS statistical software (V.27, SPSS, Chicago, Illinois, USA). A p value of < .05 was set to be statistically significant.

Results

Demographic Characteristics

The basic characteristics of all participants are shown in Table 1. A total of 2,827 participants completed the questionnaire. The respondents had a mean age of 37.2 ± 7.9 years, with the majority being male (98.4%), single (93.3%), and identifying as MSM/WSW (86.4%). The most common reason reported by most individuals for receiving public expense vaccines was sexual orientation and the related sexual experiences in the past 6 months (73.8%). In addition, 18.6% of the respondents had a medical history of human immunodeficiency virus (HIV) infection. Furthermore, approximately half of the respondents (48.6%) received the first mpox vaccine dose by intradermal injection in the forearm. Nevertheless, only 15.9% of respondents preferred intradermal administration in the forearm for their second inoculation.

Table 1 Basic characteristics of all participants (N = 2827)
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Physical and Psychological Impacts of Mpox Vaccination

Table 2 shows the physical and psychological impacts of mpox vaccination AEs. Among all the vaccination regimens, the highest percentage of subjects receiving intradermal injection in the forearm reported physical and psychological impacts of local AEs. Discoloration was the most common local AE, with 93.1% and 58.3% of individuals reporting physical and psychological impacts, respectively. Regardless of the vaccination regimens, subjects disclosed fewer systemic AEs than local AEs. Kruskal–Wallis H tests revealed that there were statistically significant differences in all local AEs between different vaccination regimens. The post hoc tests demonstrated that all local AE-related physical and psychological impacts, with the exception of pain, were significantly greater in those who received intradermal injection in the forearm. Kruskal–Wallis H tests also revealed statistically significant differences in the physical impacts of systemic AEs, including myalgia and fever. Figures 1 and 2 show the percentages of respondents reporting vaccination AE with the severity scale from absent, mild, moderate to severe.

Table 2 Physical and psychological impacts of mpox vaccination
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Figure. 1
figure 1

Adverse event-related physical impacts of different mpox vaccination regimens. A subcutaneously in the deltoid, B intradermally in the deltoid, C unknown routes in the deltoid and D intradermally in the forearm. The severity of physical impact was defined from the physical discomforts developed after vaccination. Absent: no symptoms or ignorable symptoms; Mild: symptoms required no treatment; Moderate: symptoms required treatment or consultation with a health professional; Severe: symptoms required hospital admission

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Figure. 2
figure 2

Adverse event-related psychological impacts of different mpox vaccination regimens. A subcutaneously in the deltoid, B intradermally in the deltoid, C unknown routes in the deltoid and D intradermally in the forearm. The severity of psychological impact was defined as the frequency of feeling nervous, anxious or on the edge after vaccination. Absent: not at all; Mild: several days; Moderate: more than half the days; Severe: nearly every day

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Table 3 shows a multinomial logistic regression analysis for local AE-related physical and psychological impacts of different injection regimens. Intradermal injection in the forearm was used as a reference. Due to the collinearity between “scar” and “discoloration,” “scar” was removed from the analysis. Compared to intradermal injection in the forearm, the physical impacts of discoloration were significantly less in intradermal, subcutaneous and unknown routes in the deltoid groups. The odds ratios were 0.41 (95% CI 0.29–0.57), 0.33 (95% CI 0.23–0.48), and 0.41 (95% CI 0.26–0.63), respectively. Psychological impacts of discoloration were also significantly less in intradermally, subcutaneously and unknown routes in the deltoid groups. The odds ratios were 0.71 (95% CI 0.54–0.95), 0.56 (95% CI 0.39–0.81), and 0.50 (95% CI 0.32–0.77), respectively.

Table 3 Multinomial logistic regression analysis for local adverse event-related physical and psychological impacts of different injection regimens. Intradermally in the forearm is the reference
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Preferences of Mpox Vaccination Regimens

The results showed that 15.9%, 31.7%, 29.7% and 22.6% of the participants preferred to be injected intradermally in the forearm, intradermally in the deltoid, subcutaneously in the deltoid and regardless of the route in the deltoid, respectively (Table 1). Participants filled out the factors influencing their preferences by responding to multiple-choice questions. The frequency of each factor is shown in Fig. 3. “Beauty,” “scar,” and “others’ view” were the three factors with the highest frequencies. A multinomial logistic regression analysis was performed to examine the preference for injection regimens from variables. Intradermally in the forearm was used as a reference. Compared to intradermal injection in the forearm, subjects who cared about “others’ view” were likely to prefer vaccination in the deltoid. The odds ratio for preferring intradermally injection in the deltoid over in the forearm was 1.88 (95% CI 1.38–2.56). The odds ratio for preferring subcutaneous injection in the deltoid over intradermally injection in the forearm was 1.69 (95% CI 1.23–2.32). The odds ratio for preferring intradermally injection in the deltoid regardless of the route over intradermally injection in the forearm was 2.11 (95% CI 1.53–2.92). Additionally, subjects who cared about “local AE severity” were also more likely to prefer vaccination in the deltoid to the forearm, regardless of whether they preferred intradermal, subcutaneous or regardless of the route injection. The odds ratios were 1.61 (95% CI 1.16–2.24), 2.02 (95% CI 1.46–2.81), and 1.54 (95% CI 1.09–2.16), respectively. Furthermore, individuals who deemed “scar” as an important factor tended to choose subcutaneous and regardless of the route vaccination in the deltoid, with odds ratios of 1.30 (95% CI 1.00–1.68) and 1.64 (95% CI 1.25–2.15), respectively. It is also noteworthy that subjects with a propensity for keloids were more likely to choose subcutaneous administration than intradermal injection in the forearm (OR: 5.88; 95% CI 3.18–10.86) (Table 4).

Figure. 3
figure 3

Factors influencing preference for second mpox vaccination regimens

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Table 4 Factors influencing preference for injection regimens using a multinomial logistic regression analysis. Intradermally in the forearm is the reference
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Discussion

In our survey, the majority of respondents were male (98.4%), single (93.3%), and identified as MSM/women who have sex with women (WSW) (86.4%), and 18.6% of the respondents had a medical history of HIV. In this study group, local AEs were significantly greater among subjects receiving intradermal injection in the forearm in terms of both physical and psychological impacts. In addition, discoloration was the most commonly reported local AE, which was significantly lower when injected in the deltoid, regardless of the route of injection. Additionally, subjects who cared about “local AE severity” were more likely to prefer vaccination in the deltoid, regardless of the route of administration. Most importantly, we discovered that “beauty,” “scar” and “others’ view” held the highest significant frequencies that influenced subjects’ preferences, while there were no differences in “effect of protection” and “injection dosage.”

Many clinical trials have been conducted in people who received the JYNNEOS vaccination, and AEs were examined. For example, a double-blind randomized controlled study evaluated the safety of subcutaneous JYNNEOS injection (Overton et al., 2018; Vaccines & immunization for monkeypox: Interim guidance, 2022). A total of 84.9% of subjects in the trial reported pain after vaccination, followed by redness, which was reported by 60.8% of people. Because the physical impacts of vaccine AE have been evaluated thoroughly in previous studies, our study placed more emphasis on assessing the psychological impacts. Some studies have compared the AEs of different regimens of vaccination (Deng et al., 2023; Duffy et al., 2022). A previous study collected data from Australia’s vaccine safety surveillance system and demonstrated that the local AE rate varied between subcutaneous and intradermal administration (Deng et al., 2023). Our study found that both the physical and psychological impacts of most local AEs were significantly greater in those who received intradermal injections in the forearm. Deng et al. (2023) analyzed the AE of subcutaneous and intradermal mpox vaccination and revealed similar results. The AE rate was highest following intradermal injection in the forearm (53%). For the impacts of local AEs among different injection regimens, both the physical and psychological impacts of discoloration were significantly lower when injected in the deltoid, regardless of the route of injection. The result echoed a previous study comparing the formulations and injection routes of modified vaccinia Ankara (MVA) (Frey et al., 2015), which disclosed prolonged local reactions in the intradermal group, with injection site discoloration over the forearm lasting ≥ 6 months in 36% of subjects. Our study, along with previous research, demonstrated that intradermal injection in the forearm results in more physical impacts of local AEs. We further confirmed that psychological impacts yielded similar results.

Our study further investigated the preference for mpox vaccination regimens. Although intradermal injection in the forearm was recommended in many countries for dose sparing, the lowest percentage (15.9%) of participants in our study preferred the regimen. A multiple-choice question was designed to recognize factors influencing the preference for regimens. We discovered that “Beauty,” “Scar” and “Others’ view” were most frequently cited. For the preference of injection regimens, subjects who cared about “local AE severity” were more likely to prefer vaccination in the deltoid, regardless of the route of administration. We mentioned earlier that local AEs were more severe in subjects with intradermal injection in the forearm. Therefore, this regimen was not favored by the participants due to its unpleasant local reactogenicity. In our study, subjects who cared about “others’ view” were more likely to prefer vaccination in the deltoid. In other words, people tended to have a preference against injection in the forearm with respect to others’ view. This finding could probably explain why our study exhibited greater psychological impacts of local AE in individuals whose vaccinations were administered intradermally in the forearm. We supposed that the psychological impacts resulted from the stigma surrounding the mpox. Since the 2022 mpox outbreak, the majority of cases have involved SGM groups, especially men who have sex with men (MSM) (Gessain et al., 2022). Consequently, the LGBTQ+ communities have been stigmatized by mpox (März et al., 2022). Some people mistakenly believed that only the LGBTQ+ community was susceptible to mpox acquisition (Rajkhowa et al., 2023; Sah et al., 2022). A study based on Tweet analysis revealed that one part of the population feared the labeling they would obtain after being vaccinated (Rajkhowa et al., 2023). A qualitative study carried out by Agroia et al. summarized the reasons for vaccine hesitancy. One of the reasons was stigma associated with receiving the vaccine. People worried about being labeled as “gay” by the public and the scars on forearm seen as branding (Agroia et al., 2023). Curtis et al. (2023) also stated that some individuals did not seek out the mpox vaccine for fear of being labeled as a member of the LGBTQ+ community. A systemic review demonstrated that the acceptance of mpox vaccines was only 43% in the general population owing to the associated stigma (Ulloque-Badaracco et al., 2022). Compared to the forearm, the area of the deltoid was more often covered by clothes. Hence, it seemed understandable that people who cared about “others’ view” preferred to be injected in the deltoid to avoid being stigmatized by the visible mark.

Previous studies have discussed the stigma surrounding the SGM community and the misperception of mpox virus. To our knowledge, no prior studies have examined the psychological impacts and stigma generated from mpox vaccine AE. According to the press briefing by White House monkeypox response team and public health officials on September, 28, 2022, many jurisdictions and advocates stated the decline of mpox vaccination willingness due to the visible mark left on their forearm (Press Briefing by White House Monkeypox Response Team & Public Health Officials, 2022). The statement echoed our study result. This is the first study to identify people’s preference for intradermal vaccination in the forearm. Besides the severity of local AEs, their preference was strongly influenced by “others’ view,” which was related to the fear of being labeled. It is noteworthy that each individual considered different factors when it comes to choosing vaccination regimens. The integrim guidance released by WHO mentioned about the dose sparing option of intradermal administration (WHO, 2022). The United States Food and Drug Administration issued an Emergency Use Authorization for the use of MVA-BN by intradermal injection. The European Medicines Agency Emergency Task Force also stated that intradermal use of MVA-BN vaccine was acceptable in light of the significant vaccine shortage. However, our study revealed that the higher local reactogenicity on the forearm following intradermal administration might be seen as branding and thus increased the psychological pressure of vaccinated individuals.

Regarding the potential stigma and personal issues, we recommend that the governments provide individuals the opportunities to select their injection regimens. As far as the author knows, health authorities worldwide have begun to adopt this approach (WHO, 2022). The CDC in the US announced updated guidance that suggested alternative mpox injection sites, such as the upper back and the deltoid (Vaccine JYNNEOS, 2022), which are often covered by clothes. According to a statement released by the European Medicines Agency Emergency Task Force, local reactogenicity following intradermal administration might decrease the willingness to receive the second dose, leading to reduced protection (Considerations on posology for the use of the vaccine Jynneos/Imvanex (MVA-BN) against monkeypox, 2022). It is crucial for public health officials to balance optimal vaccination use, acceptance and feasibility of administration.

Our study had several limitations. First, participants filled out the online questionnaire more than four weeks after receiving the first dose of the mpox vaccine. Therefore, the possibility of recall bias cannot be ignored. Second, this was a self-administered survey. Consequently, only individuals willing to share their opinions and experiences were included in the survey, causing selection bias. Third, our study recruited subjects who visited the clinic for a second dose of the mpox vaccine. As a result, selection bias occurred when subjects skipping the second dose of vaccine were not included in our study. Although individuals not included in the study were more likely to experience stigma, the existing research still achieved statistical significance. This means that if individuals who experienced stigma had been recruited for the study, the result might have been even more significant. To prevent labeling and stigma and enhance vaccination willingness among the SGM community, we suggest not injecting mpox intradermally at any visible injection site, such as the forearm. Additional research is required to further explore the process of destigmatization. In conclusion, our research provides important insights into how different mpox vaccine regimens affected individuals’ lives and the factors associated with their preference for vaccine regimens.

Conclusions

This study demonstrated the adverse events of different mpox vaccination regimens and their association with stigma. From policy perspective, recognizing the factors affecting the preference for a vaccine is important for formulating effective vaccination strategies and promoting the acceptance of vaccines. Addressing stigma and mpox vaccine-related psychological impacts can enhance public health outcomes, including mental hygiene.