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Vaccine Demand and Willingness-to-pay for Arbovirus Vaccines

A Cross-sectional Survey in Rural Guatemala

Olson, Daniel, MD*,†,‡,§; Rick, Anne-Marie, MD, MPH*,‡; Krager, Steven, MD§; Lamb, Molly, PhD*,§; Asturias, Edwin J., MD*,†,‡,§

The Pediatric Infectious Disease Journal: November 2018 - Volume 37 - Issue 11 - p 1184–1189
doi: 10.1097/INF.0000000000002169
Vaccine Reports

Background: Arboviruses including dengue (DENV), chikungunya (CHIKV) and Zika cause significant morbidity in Latin America. With multiple arbovirus vaccines in development, better understanding of community attitudes and acceptability for these vaccines is needed.

Methods: In September 2016, a cross-sectional survey assessed arbovirus knowledge, attitudes, vaccine demand and willingness-to-pay (WTP) at the conclusion of a DENV/norovirus surveillance study in rural Guatemala with high arbovirus endemicity. Factors associated with vaccine demand and WTP were assessed with regression analysis.

Results: Among 564 surveyed households, DENV knowledge was high. There was great concern for arboviruses, particularly CHIKV. Overall vaccine attitudes were positive with <5% identifying significant barriers, hesitancy or refusing previous vaccination. At 50% and 75% efficacy, 75% and 88% of respondents wanted arbovirus vaccines, respectively. DENV vaccine demand at 50% efficacy was associated with increased housing density, nonhealth postvaccination location, older children and medical source for information. For each vaccine, 52–55% of respondents were WTP $0–$3.40, while 16–17% were WTP ≥$6.81. WTP at $3.40 and $6.81 levels for all vaccines was associated positively with parental education but negatively with good DENV knowledge. History of purchasing and identifying barriers to vaccines was associated with WTP ≥$6.81.

Conclusions: Demand for potential DENV, CHIKV and Zika vaccines is high at 50% and 75% efficacy in this Guatemalan community. Associated factors could be leveraged to optimize arbovirus vaccine implementation. Overall low WTP given current cost of Dengvaxia (Sanofi Pasteur, Lyon, France) suggests that government subsidization may be necessary in resource-poor regions, though a small private market may be supported.

From the *Center for Global Health, University of Colorado School of Public Health, Aurora, Colorado

Division of Pediatric Infectious Diseases, Children’s Hospital Colorado, Aurora, Colorado

Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado

§Department of Epidemiology, University of Colorado School of Public Health, Aurora, Colorado.

Accepted for publication July 6, 2018.

Supported by an Investigator-Initiated Sponsored Research Grant from Takeda Pharmaceuticals (grant number IISR-2014–100647); National Institutes of Health (NIH)/National Center for Advancing Translational Sciences Colorado Clinical and Translational Science Institute (grant number UL1 TR001082) to D.O.; and the Children’s Hospital of Colorado Research Scholar Award to D.O. A.-M.R. is supported by NIH National Research Service Award T32 HP22240. Contents are the authors’ sole responsibility and do not necessarily represent official National Institutes of Health view.

E.J.A. has served on an Advisory Board for Takeda Vaccines Inc. and is partially supported by research grants from GlaxoSmithKline Biologicals and Takeda Vaccines Inc. M.L. is partially supported by grants from GlaxoSmithKline Biologicals and Pantheryx Inc. D.O. is partially supported by a grant from Takeda Vaccines Inc. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. The other authors have no conflicts of interest to disclose.

D.O. and A.-M.R. are co-first authors.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Address for correspondence: Edwin J. Asturias, MD, Center for Global Health, 13199 East Montview Blvd, Suite 310, Aurora, CO 80045. E-mail: or Daniel Olson, MD, Center for Global Health, 13199 East Montview Blvd, Suite 310, Aurora, CO 80045. E-mail:

Arboviruses including dengue virus (DENV), chikungunya virus (CHIKV) and Zika virus (ZIKV) cause millions of infections worldwide annually, resulting in significant morbidity and sequelae, including deaths.1–7 Transmitted primarily by Aedes mosquitoes, DENV, CHIKV and ZIKV overlap geographically, especially in the Americas, and their acute clinical presentations are indistinguishable. Numerous arbovirus vaccine candidates are in clinical trials, including 6 DENV, 4 CHIKV and 6 ZIKV candidates.8–11 The first registered DENV vaccine, chimeric yellow fever virus-derived tetravalent dengue vaccine (CYD-TDV) CYD-TDV (Sanofi-Pasteur), demonstrated vaccine efficacy of 59.2% against symptomatic DENV infection and has been suggested for sero-positive children >9 years in endemic settings where seroprevalence is ≥70% by that age.8,11–13

Introduction of these arbovirus vaccines will require efficacy for meaningful public health outcomes, long-term safety, as well as political willpower, feasibility, efficient programmatic implementation and favorable community demand/acceptance.14 Understanding factors affecting community acceptance and willingness-to-pay (WTP) for arbovirus vaccines can provide policy-makers with important insight for vaccine implementation as well as mechanisms of financial sustainability. Furthermore, vaccine hesitancy, a growing concern worldwide, is impacting local vaccine perceptions and acceptance.15,16 As there are few studies examining these factors in Latin America, we aimed to assess vaccine demand and WTP for 3 potential arbovirus vaccines—DENV, CHIKV, ZIKV—within a rural community in Guatemala with high arbovirus endemicity.

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Study Setting and Population

A community-based cross-sectional survey was administered at the conclusion of a DENV and norovirus surveillance study to households within a 200 km2 catchment area along the coastal lowlands of Guatemala known as the southwest Trifinio region, intersecting San Marcos, Quetzaltenango and Retalhuleu departments which suffers high endemicity of DENV, CHIKV and ZIKV.17,18 Simultaneous outbreaks of DENV and CHIKV in these regions in 2014 saw infection rates between 66 and 96 and 127 and 338 per 100,000 people, respectively, decreasing in 2016 to 53 and 31 per 100,000 people, respectively.17–20 Local ZIKV transmission started in November 2015 infecting 5–34 per 100,000 people with current endemicity estimated at 19 per 100,000 people.17

Eligible households with children 6 weeks to 17 years of age were enrolled into 1 of 2 surveillance programs, as previously described21: (1) a 12-month prospective participatory surveillance (PSS) system using a weekly smartphone-based symptom diary with DENV diagnostic testing performed for self-reported fever; or (2) 2 separate rapid active cross-sectional sampling (RAS) surveys conducted over the course of 4–6 weeks.

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Survey Design and Administration

A 66-question survey, adapted from previous arbovirus surveys22–25 and the World Health Organization Strategic Advisory Group of Experts (SAGE) tool on vaccine hesitancy,15 was designed and administered to all consenting households in September 2016 by trained study nurses (Table, Supplemental Digital Content 1, Besides the consent process and a DENV and norovirus brochure provided at enrollment, participants’ parents did not receive additional information about arbovirus infections. The survey was conducted via in-person interview using a smartphone application (Integra IT, Bogota, Colombia) and included demographics, health history and sources of health information, general vaccine attitudes, DENV knowledge, arbovirus (DENV, CHIKV, ZIKV) attitudes and prevention practices (KAP), arbovirus vaccine acceptance and WTP from parent perspective for a child, and participant experience with the surveillance study. For KAP, a scoring system used in previous studies was adapted, assigning one point for each preferred response, a half point for partial preferred responses and zero for all other responses.24,26,27 A higher total score indicated better KAP.

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Arbovirus Vaccine Acceptance and WTP

To assess participant acceptance of arbovirus vaccines, a hypothetical scenario was provided to participants for each of the 3 arbovirus vaccines (DENV, CHIKV, ZIKV), which assumed the vaccine was free and available. Acceptance of the vaccine was evaluated at both 50% (protecting 2 of 4 people) and 75% (protecting 3 of 4 people) efficacy. Participant WTP for DENV, CHIKV and ZIKV vaccines was assessed using a hypothetical scenario with a 75% vaccine efficacy and increasing price ranges of US $0–$3.40 (0–25 Guatemalan Quetzals (Q), June 14, 2017 exchange rate), $3.41–$6.81 (26–50 Q), $6.82–$10.21 (51–75 Q), $10.22–$13.62 (76–100 Q) and >$13.63 (>100 Q). Participants were asked to pick the range containing their maximum WTP. Ranges were determined based on cost of other vaccines provided by the National Immunization Program (pentavalent $3.4 per dose, rotavirus $7 per dose) and local cost of other health-care interventions (25 Q per Funsalud clinic visit, 100 Q for private clinic visits). Private market values of vaccines were not used for WTP questions as they are only available to the upper 10% of the population in Guatemala and would be completely inaccessible to parents from these low-income communities.

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Statistical Analysis

Demographic, health information, general vaccine attitudes and KAP were characterized with descriptive statistics. PSS and RAS surveillance groups were compared using χ2 and Student’s t tests to identify baseline differences potentially influenced by the different surveillance methodologies. Vaccine demand and WTP responses for each vaccine were then modeled as a survival function using the proposed intervals with an estimated upper limit of $17.02 (125 Q).

Scores for KAP were calculated with each participant receiving a summary score for DENV knowledge (range, 0–10), DENV attitudes (range, 1–6), CHIKV attitudes (range, 1–6), ZIKV attitudes (range, 1–6) and arbovirus prevention practices (range, 0–11). Individuals were further categorized as having “good” or “poor” KAP using a cutoff of 80% of the total possible score (eg, good DENV knowledge score ≥8), which was then included in regression modeling.24

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Regression Modeling

Generalized linear regression was used to identify prevalence ratios (PRs) for associated factors with vaccine demand and WTP for each potential arboviruses vaccines using Poisson distribution and a log link.28 A robust variance option was included in all analyses to correct for overestimation of the error when using Poisson distribution to estimate PRs for binomial data.28,29

The dependent variables for vaccine demand at 50% and 75% efficacy were dichotomous (ie, “yes” vs. “no”). Participants who responded “do not know” were excluded. WTP was also examined as a dichotomous response variable using 2 cutoffs: above/below US $3.40 (25 Q) as a median and $6.81(50 Q) as an upper quartile of responses. Respondents who did not know or did not want vaccine at 75% efficacy were excluded. Independent variables were selected “a priori” based on plausibility and previous literature. Collinearity was then explored and multilevel categorical variables with <10 observations were consolidated whenever possible. Variables with significance P <0.10 on univariate analysis were included in multivariate analysis. Final models were obtained using manual step-wise model reduction based on least significant terms and coefficient changes. Variance inflation factors to assess multicollinearity were below 10.0 in the final models. All tests were 2-tailed, and P < 0.05 was considered statistically significant. All statistical analyses were completed using STATA 12.0 (College Station, TX).

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Ethical Approval

The study was approved by the Colorado Multiple Institutional Review Board, Universidad del Valle de Guatemala Institutional Review Board, and the Ministry of Public Health of Guatemala National Ethics Committee on Health and reviewed and agreed by the local Southwest Trifinio Community Advisory Board for Research.

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Demographics and Health History

A total of 564 (90%) of 627 households completed the survey, including 179 from the PSS cohort and 385 from the 2 RAS cohorts (Table, Supplemental Digital Content 2, Baseline characteristics were overall similar between the 2 surveillance groups, except RAS households reporting more adults and less crowding. Most households relied on and trusted the Ministry of Health for information on vaccines and arboviruses, but >50% also identified nonmedical primary sources for information on arboviruses (Fig., Supplemental Digital Content 3,

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General Vaccine Attitudes

General attitudes towards vaccines were positive overall, with 99% of parents recognizing that vaccines prevent serious diseases in children and less than 5% identifying significant barriers to, ever hesitating or refusing previous vaccination (Table, Supplemental Digital Content 4,

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DENV Knowledge, Arbovirus Attitudes and Prevention Practices

While vector and symptom recognition were high for DENV, understanding of DENV transmission remained limited and multiple breeding areas were underrecognized (Table, Supplemental Digital Content 4, Mean DENV knowledge scores were 6.9 out of 10 [95% confidence interval (CI): 6.8–7.1] with 29% having “good” DENV knowledge. Arbovirus attitudes reflected high concern for all 3 viruses, although CHIKV was perceived as being the most prevalent in the area (92% vs. DENV 76% and ZIKV 64%). Overall arbovirus attitude scores for DENV, CHIKV and ZIKV were 5.5 (95% CI: 5.4–5.6), 5.8 (95% CI: 5.7–5.8) and 5.4 (95% CI: 5.4–5.5) out of 6, respectively, with higher mean CHIKV score compared with DENV and ZIKV (both P < 0.001; DENV vs. ZIKV P = 0.169). The most common arbovirus prevention practices reported were generally those that require minimal resources [emptying (70%) and covering (60%) water containers, picking up trash (93%)] with the exception of bed nets (94%). Less frequently reported were changing water containers (23%), wearing long clothes (40%), spraying insecticide (38%), using repellant (22%) and window screens (2%). Average prevention practice scores were low at 5.67 out of 11 (95% CI: 5.53–5.80), with 4.6% reporting “good” prevention practices.

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Arbovirus Vaccine Demand and WTP

At 50% efficacy, approximately 75% of respondents wanted the vaccines, which increased to 88% at 75% efficacy. The proportion of participants WTP for each arbovirus vaccine at each monetary interval was similar across the 3 arboviruses with just over half of participants (52–55%) WTP the lowest suggested price interval ($0–$3.40) for each vaccine, while 28–30% were WTP $3.41–$6.81 (Fig. 1). Approximately 16–17% of respondents were WTP >$6.81.



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Associated Factors With Arbovirus Vaccine Demand

Table 1 shows associations between predictor variables and vaccine demand for arbovirus vaccine at assumed 50% and 75% efficacy on multivariate analysis (refer to Table, Supplemental Digital Content 5, for univariate analysis). While some factors are common to the 3 different arbovirus vaccines, important differences exist which may bear relevance to individual vaccine implementation strategies. For DENV vaccine at 50% efficacy, participants were more likely to want the vaccine if they lived in more densely populated areas, obtained childhood vaccines at a nonhealth post-location, had older children or reported receiving information on arboviruses from a medical source. Respondents who reported receiving public health care for their child were less likely to want the vaccine. Both CHIKV and ZIKV vaccine demand were also positively associated with higher density areas and negatively associated with receiving public health care for a child (Table 1). Respondents with “good” CHIKV vaccine attitudes were 40% more likely to want the vaccine (PR: 1.4; 95% CI: 1.0–2.0; P = 0.040).



Similar associations were found for DENV vaccine at the 75% efficacy level, though associations were somewhat attenuated compared with those at 50% efficacy (Table 1). Both CHIKV and ZIKV vaccine demand at 75% efficacy were positively associated with those who vaccinated at nonhealth post-locations and who had “good” CHIKV and ZIKV attitudes, respectively. Respondents with a family member who had experienced ZIKV infection were less likely to want the vaccine (PR: 0.9; 95% CI: 0.8–1.0; P = 0.021).

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Associated Factors With Arbovirus Vaccine WTP

Table 2 shows the associations between predictor variables and WTP for an arbovirus vaccine above $3.40 and $6.81 for multivariate analysis (refer to Table, Supplemental Digital Content 6, for univariate analysis). Increased WTP above $3.40 for DENV vaccine was associated with both the mother and father having higher education. However, more children in a household as well as good DENV knowledge and attitudes were associated with decreased WTP for the vaccine. Similar associations were found with WTP above $3.40 for CHIKV and ZIKV vaccines, as well as a positive association between WTP and history of purchasing a vaccine for a child.



WTP above $6.81 for DENV vaccine showed even stronger associations with higher levels of maternal education. Furthermore, respondents were nearly twice as likely to have WTP if they declared a history of “other pressures in your life,” as defined by the SAGE tool preventing on-time child vaccination or had a history of previously purchasing a vaccine. “Good” DENV knowledge reduced WTP (PR: 0.6; 95% CI: 0.4–0.9, P = 0.027). Similar associations were found with WTP above $6.81 for both the CHIKV and ZIKV vaccines.

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Overall, vaccine demand in this rural community in Guatemala was high for all 3 arbovirus vaccines, with 75% of the population wanting the vaccine even at 50% efficacy, increasing to 88% at 75% efficacy. Other studies have found DENV vaccine acceptance between 77% and 95% when assuming 100% efficacy.22,26 While these data suggest that lower efficacy may correlate with a drop in demand, a hypothetical vaccine with 50–75% efficacy provides a more realistic panorama of acceptability in this endemic area given the current DENV licensed vaccine efficacy at 60%.11

While urban living is associated positively with vaccine demand,26 it is possible that even among rural communities, community density impacts acceptability. The influence of medical source of health information on DENV vaccine acceptability reinforces the effects of provider information for vaccine acceptability.22,30,31 This may have significant implications for future communication and introduction of arbovirus vaccines, whereby using existing health infrastructure to promote key information about arboviruses and vaccines may lead to higher uptake. The positive associations found between vaccine demand and vaccinating at a nonhealth post (private clinic or pharmacy) and inverse association with receiving public health care may reflect differences in socio-economic status (SES), parental concern or health-care access. However, the relationship between SES and vaccine acceptance is inconsistent throughout the literature.16,22,26

The positive correlation between “good” arbovirus attitudes and vaccine demand at the 50% and 75% efficacy levels continues to support previous evidence that a population’s higher concern for, or risk of, infection leads to higher demand for a vaccine and decreased hesitancy.26,32 Interestingly, “good” DENV knowledge and prevention practices did not influence vaccine demand in our study, which is an inconsistent finding across diseases, including DENV.22,26,33 This may suggest that perception of risk or severity is more important in individual vaccine decision-making than disease knowledge.

Over 50% of participants who wanted the vaccines were only WTP the lowest interval ($0–$3.40), while 16–17% had WTP greater than $6.81. This probably reflects the SES of these low-income rural communities. It is not possible from our data to know what percentage of participants would only want the vaccine if it were completely free, as $0 by itself was not a response option. Yet, in a country where 60–70% of health-care expenses are out-of-pocket even for the poorest, their WTP reflects the cost-benefit value that rural parents could attribute to future arbovirus vaccines. We did not obtain direct indicators of SES, ...though household income and economic status were identified as powerful determinants of... WTP in other studies.22,34,35 These data also indicate that to achieve good vaccination coverage, any arbovirus vaccine introduced to this area would likely require heavy government subsidies. Importantly, most childhood vaccines in Guatemala are already provided at no cost to families through the National Immunization Program, and thus, low WTP for arbovirus vaccines may be reflective of the vaccination expectations in Guatemala. This also makes it challenging to know how WTP for arbovirus vaccines compares to WTP for other routine vaccinations. Paying for vaccines is uncommon in these communities, reflected by the fact that only 3.4% of respondents reported previously purchasing any vaccine. Nonetheless, purchasing a vaccine was strongly associated with WTP higher amounts for CHIKV and ZIKV at the $3.40 level (over 40% increased likelihood) and for all 3 arboviruses at the $6.81 level (over 2-fold increase), similar to findings by Lee et al34 for DENV. This may indicate that some families with a higher SES, even within these impoverished communities, may influenced in their future choices for arbovirus prevention.

Contrary to vaccine demand, parental education was associated with higher WTP, particularly maternal education. While parental education may be a confounder for SES, this association may also reflect the differential value given by better educated parents to cost-beneficial interventions like vaccination. In other DENV studies, parental education level is inconsistently associated with WTP.26,34,35 Respondents with more children showed decreased WTP for vaccines, possibly because of financial constraints among larger families. Furthermore, respondents with good arbovirus knowledge and attitudes generally had decreased WTP. Other DENV studies have shown mixed results.22,26,35 Harapan et al26 propose that these differential findings may in part be because of content of knowledge being measured.

Overall vaccine attitudes were positive in this community, but approximately 4–5% of families either hesitated at some point to administer or refused vaccines for their child in the past. Follow-up questions to explore these responses were not included in this survey; however, it reiterates the importance of understanding local vaccine confidence and compliance as part of planning and implementation of future vaccination programs. Some individual-level questions from the SAGE questionnaire (hesitated for vaccine, impediments to vaccination, other pressures) were significantly associated with outcomes in both the univariate and multivariate models in our analysis, yet high collinearity existed between these questions. While validation studies of the SAGE questionnaire have found that these questions do help identify vaccine-hesitant parents,36 it may be valuable to further develop this tool into a scoring system to provide quantitative measures that allow more meaningful and comparable inferences into vaccine hesitancy.

Although a high percentage of participants were found to have “good” arbovirus attitudes, overall attitude score was highest for CHIKV. Additionally, half to two-thirds of participants reported a personal or family history of CHIKV infection, which was nearly 2–3 times higher than DENV and 5 times higher than ZIKV, consistent with the higher rates of symptomatic disease experienced by affected CHIKV subjects from the recent 2014–2015 outbreak in the country.19,20 However, current local epidemiology estimates higher DENV infection rates (53 cases per 100,000) compared with CHIKV (31 cases per 100,000),17 though it is likely that CHIKV infections are underreported given the scarcity of clinical and surveillance testing. Local perception of arbovirus disease may also explain the counterintuitive finding of decreased vaccine demand among those with a ZIKV-exposed family member, whereby most child and adult ZIKV infections are asymptomatic or mild and congenital ZIKV while severe remains a relatively rare event. Regardless, community perceptions of these diseases, as well as their clinical and economic impact, may be important when designing vaccine introduction programs, as they will impact vaccine demand.

Several limitations should be acknowledged. First, this is very poor rural population with high arboviruses prevalence, so results may not be generalizable to other settings. Second, because of the exposure of this population to the DENV and norovirus surveillance study before the administration of this survey, knowledge of arboviruses, specifically DENV, may have been influenced by contact with study personnel as demonstrated in the differences between PSS and RAS populations. However, participants were intentionally not provided extensive information on arboviruses before the survey to capture current community-based KAPs. The relationships developed between study personnel and respondents, however, also likely accounts for the high completion rate of the survey. Furthermore, a selection bias effect may exist as the survey was only administered to those enrolled in the parent surveillance study, which was randomized but had an enrollment rate of 58%.21 Presentation of price intervals for WTP in ascending order may have created an “anchoring effect” resulting in underestimation of WTP. The majority response of WTP 0–25 Q may also support utilizing smaller price intervals (ie, 10 Q scale) to reflect more accurately WTP in this low SES region where individuals have limited experience paying for health services. Finally, the hypothetical situations presented to the participants only included limited information because of survey feasibility. Providing more contextual information (ie, price of current vaccine, vaccine safety and schedule) and infection worst-case scenarios (ie, microcephalic newborn) may be important to understanding the nuances of vaccine demand and WTP before vaccine implementation.

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The authors thank the following personnel for their significant contributions to this research: CU Trifinio Research Team led by Neudy Rojop, Andrea Chacon and Carlos Alvarez Guillen; Celia Cordon-Rosales, Maria Renee Lopez and Mirsa Ariano (Universidad del Valle de Guatemala); and Ricardo Zambrano-Perilla and Sergio Ricardo Rodríguez-Castro (Integra IT Colombia).

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arbovirus; dengue; Zika; chikungunya; vaccine acceptability; vaccine attitudes

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