The research team, led by Xin Su and Qilin Wu of the Guangzhou Center for Disease Control and Prevention and colleagues at district-level CDCs across the city, surveyed parents of children aged five years or younger at ten community health centers. Using stratified multi-stage sampling designed to capture a representative slice of Guangzhou’s diverse urban population, the investigators measured parental knowledge, attitudes and practices related to the EV-A71 vaccine, along with physician recommendation behavior. The headline finding is sobering: 28.95 percent of parents surveyed exhibited vaccine hesitancy toward the EV-A71 shot—a voluntary, self-paid vaccine in China’s immunization landscape, which makes parental decision-making particularly consequential.

The demographic patterns the team uncovered through logistic regression with cluster-robust standard errors reveal who is most likely to balk. Mothers were markedly less hesitant than fathers, with an odds ratio of 0.46, suggesting that the primary caregivers most often managing children’s health decisions hold more favorable views of the vaccine. Parents holding a college or associate degree were also less hesitant (odds ratio 0.53), consistent with the broader observation that educational attainment often correlates with greater vaccine acceptance. On the other side of the ledger, parents who were not healthcare workers were more than twice as hesitant (odds ratio 2.38), and—perhaps most tellingly—parents whose children had no history of HFMD were over three times as hesitant (odds ratio 3.45). That last finding hints at a paradox of prevention: families spared direct experience of the disease may perceive less need for a vaccine against it.

To move beyond simple associations, the researchers employed structural equation modeling (SEM), a statistical framework that allows latent psychological variables—constructs that cannot be directly observed but are inferred from multiple survey items—to be tested in a network of direct and indirect causal pathways. Exploratory factor analysis, preceded by principal component assessment and Kaiser-Meyer-Olkin sampling adequacy checks, first identified the underlying latent dimensions in the data. The SEM then revealed three psychological constructs exerting significant negative direct effects on hesitancy: vaccine confidence (standardized coefficient -0.39), trust in vaccination services (-0.17), and perceived risk of the disease (-0.17). In plain terms, parents who trusted the vaccine’s safety and effectiveness, trusted the health system delivering it, and felt the disease posed a real threat to their child were substantially less likely to hesitate.

One of the study’s most technically interesting results concerns knowledge. Parental knowledge about EV-A71 and the vaccine showed no direct effect on hesitancy at all. Yet its total indirect effect, transmitted through the three mediating constructs, was substantial (standardized coefficient -0.45)—actually larger than any single direct effect in the model. This dissociation between direct and indirect pathways carries a crucial message for public health practice: simply handing parents facts does not by itself reduce hesitancy. Facts work only when they reshape confidence, trust and risk perception. A parent who learns that EV-A71 remains capable of causing severe neurological complications may update their risk assessment; a parent who learns how the inactivated vaccine was tested may grow in confidence. Knowledge is the raw material, but attitude change is the mechanism.

The team also examined how physician recommendation interacts with parental psychology, using a cross-level interaction term in the regression framework that specifically tested whether the enthusiasm of healthcare providers’ recommendations modifies the effect of parental vaccine confidence. The interaction was marginally significant (coefficient 2.10, P = 0.08), a result the authors interpret cautiously but which suggests that provider communication style may amplify or buffer the effects of confidence on hesitancy. In the context of a voluntary, self-paid vaccine, where no school-entry mandate or national program force exists to drive uptake, the enthusiasm with which a community health center physician recommends the shot may matter considerably—particularly for parents whose confidence is already wavering.

The epidemiological backdrop gives these findings their urgency. Before the vaccine era, EV-A71 was the pathogen most feared in HFMD outbreaks, capable of causing brainstem encephalitis, acute flaccid paralysis and death in small children. Large vaccination campaigns in China demonstrably reduced severe EV-A71 disease. But enterovirus ecology is competitive: with EV-A71 suppressed, other serotypes expanded, and the HFMD pathogen spectrum shifted. This shift is a textbook example of how successful vaccines can alter pathogen dynamics in ways that complicate continued vaccine acceptance. Parents who cannot distinguish between HFMD caused by EV-A71 and HFMD caused by coxsackieviruses see only that their vaccinated child still developed blisters, fever and mouth ulcers—fueling the perception that the vaccine does not work.

The Guangzhou study’s methodological rigor strengthens its conclusions. The stratified multi-stage sampling design captured parents across ten community health centers, and the combination of factor analysis, SEM and cluster-robust logistic regression allowed the team to disentangle demographic risk factors from psychological pathways. The ethics protocol was approved by the Guangzhou CDC ethics committee, and written informed consent was obtained from all participants. The work was supported by a self-financed research project with funding from Sinovac Biotech, the manufacturer of one of the inactivated EV-A71 vaccines, though the funder had no role in study design, data collection, analysis or publication decisions—an arrangement the authors disclose transparently.

What does the study recommend? The authors argue that communication and counseling strategies targeting the three mediating constructs—confidence, service trust and risk perception—are more likely to support informed parental decisions than knowledge campaigns alone. For a voluntary vaccine, where uptake depends entirely on parental willingness, the psychological pathway is the practical pathway. Health providers in Guangzhou and beyond may need to move beyond fact sheets and toward conversations that address the specific doubts the pathogen shift has created: explaining that the vaccine targets the most dangerous HFMD pathogen, that breakthrough HFMD caused by other enteroviruses is typically milder, and that EV-A71 remains a threat capable of re-emergence.

The broader lesson extends past HFMD. Vaccine hesitancy is not a static phenomenon; it evolves with epidemiological reality. As pathogens shift, so do parental perceptions of relevance, and public health systems must adapt their communication accordingly. The Guangzhou findings offer a quantitative template for understanding how knowledge, confidence, trust and risk perception interact in the minds of parents weighing a voluntary vaccine against a disease whose face has changed. With nearly 29 percent of parents hesitant, the stakes of getting that communication right are considerable—not only for EV-A71 vaccination in southern China, but for every voluntary vaccine program navigating the shifting terrain of post-vaccine pathogen ecology.

Subject of Research: Parental vaccine hesitancy toward the EV-A71 vaccine amid shifting hand, foot and mouth disease pathogens in Guangzhou

Article Title: Parental EV-A71 vaccine hesitancy amid shifting HFMD pathogens: a cross-sectional study in Guangzhou

Article References: Su, X., Gao, Z., Zhong, J., Bai, C., Xie, R., Luo, L., & Wu, Q. (2026). Parental EV-A71 vaccine hesitancy amid shifting HFMD pathogens: a cross-sectional study in Guangzhou. BMC Public Health. https://doi.org/10.1186/s12889-026-29951-0

Image Credits: AI Generated

DOI: 10.1186/s12889-026-29951-0

Keywords: EV-A71, hand foot and mouth disease, vaccine hesitancy, structural equation modeling, Guangzhou, enterovirus, parental confidence, vaccine confidence, HFMD pathogens, BMC Public Health, physician recommendation, public health