Preplanned Studies: Cost-effectiveness Assessment of A Smart Health Education Pillbox for Canine Echinococcosis Control During A Cluster-Randomized Trial — Western China, 2023–2024

Introduction: Echinococcosis is a zoonotic parasitic disease that necessitates regular deworming of canines. The efficacy of the conventional manual deworming (CMD) is impeded by geography, the workforce, and severe weather conditions. This study evaluated the effectiveness and cost-effectiveness of the smart health education pillbox (SHEP) compared to CMD in canine echinococcosis control.

Methods: A 12-month cluster randomized trial was conducted across nine endemic Chinese counties, where townships were randomly assigned to either the SHEP or CMD group. The primary outcomes included Echinococcus antigen positivity rates in dog feces, deworming frequency, and cost components. Data analysis was conducted using SPSS 27.0, employing Generalized Estimating Equations (GEE), odds ratios (OR), relative risk (RR), relative risk reduction (RRR), and protective efficacy (1/RR).

Results: SHEP implementation significantly reduced Echinococcus infection risk by 35.45% and demonstrated 1.55-fold higher protective efficacy than CMD. The total deworming costs decreased by 22.62%, with substantial savings in personnel (53.15%), transportation (79.48%), and operational time requirements (30.13%). The proportion of dogs that achieved the target annual deworming frequency (9–12 times) increased from 51.89% to 91.38%, representing a relative improvement of 52.59%.

Conclusion: SHEP, which integrates automated reminders of praziquantel (PZQ) tablet delivery, is a promising tool for diminishing resource utilization and mitigating Echinococcus transmission in endemic areas.

Echinococcosis, a zoonotic parasitic disease designated by the World Health Organization as a neglected tropical disease, manifests predominantly in cystic (CE) and alveolar (AE) forms, caused by Echinococcus granulosus sensu lato and E. multilocularis, respectively. Both forms impose substantial public health burdens, with dogs serving as the definitive hosts for transmission. Despite the nationwide monthly praziquantel (PZQ) deworming initiative for dogs implemented in China in 2006, which led to a decrease in canine fecal antigen prevalence from 4.25% to 0.50% (1–2), persistent operational obstacles such as veterinary workforce shortages, logistical barriers, and financial constraints in remote regions persistently impede consistent deworming coverage and frequency. Surveys have revealed suboptimal deworming frequency (ranging from 21.7%–68.9%) (3–6) as a key factor contributing to sustained high rates of canine infection (ranging from 0.15%–1.60%) (2). These fluctuations in infection rates contribute to ongoing environmental transmission risks. Therefore, there is a need to explore novel approaches to enhance adherence to canine deworming regimens and mitigate environmental contamination.

From 2023 to 2024, a 12-month cluster randomized trial was conducted across nine endemic counties: Xiji County, Ningxia Hui Autonomous Region, Yushu City, Qinghai Province; Emin County, Hejing County, Artux City, Qapqal Xibe Autonomous County, Xinjiang Uygur Autonomous Region; Shangri-La City, Yunnan Province; Tianzhu Xizang Autonomous County, Gansu Province; and Fourth Division, Xinjiang Production and Construction Corps. Within each county, two townships were randomly assigned to interventions: one to the smart health education pillbox (SHEP) group and the other to the conventional manual deworming (CMD) group, with 150 eligible households with dogs randomly selected as study participants in each group. The SHEP group received an automated SHEP reminder and dog owner deworming scheme, where each targeted household received a pre-programmed SHEP and a deworming schedule (e.g., monthly deworming on the 5th day of each month, totaling 12 times annually). On designated deworming days, the SHEP delivered five sequential one-minute reminders combining auditory prompts (“Owner, please administer deworming PZQ chewable tablet to your dog”) and visual cues (flashing red indicator light). Successful completion of all five steps — 1) opening the SHEP lid, 2) removing the PZQ chewable tablets, 3) administering them to the dog, 4) returning unused tablets to the compartment, and 5) closing the lid — is necessary to activate the green light and receive an auditory acknowledgment (“Congratulations! The deworming work has been successfully completed”). Failure to execute all five steps within the scheduled day (e.g., due to dog owner absence) would activate persistent reminders for three consecutive days. In the CMD group, conventional manual deworming procedures were followed in which health workers (veterinarians) from the township or village visited households on scheduled deworming dates to administer door-to-door PZQ chewable tablets. Additionally, stratified training, including canine fecal testing and questionnaire administration, was conducted for all participants across both the SHEP and CMD cohorts.

The primary indicators included the Echinococcus antigen-positive rate in dog feces, deworming frequency, and cost components. Data analysis was conducted using SPSS (version 27.0, IBM Corp., NY, USA), employing Generalized Estimating Equations (GEE), odds ratios (OR), relative risk (RR), relative risk reduction (RRR), and protective efficacy (1/RR). The distribution of deworming frequencies between groups was assessed using the Cochran-Armitage test, employing two-tailed testing, with statistical significance set at P<0.05.

Dog fecal samples were collected twice from each enrolled dog in both groups: at baseline in 2023 and at a 12-month follow-up in 2024. Copro-ELISA was performed at 9 county CDC locations. Baseline fecal testing of 2,643 samples (SHEP group: 1,310; CMD group: 1,333) revealed no significant intergroup variance in Echinococcus antigen positivity (OR=0.86, [95% confidence interval (CI): 0.30, 2.48, P=0.78]. At the 12-month follow-up (2,270 samples: SHEP group, 1,169; CMD group: 1,101), no significant efficacy difference was observed between the two groups (OR=0.74, 95% CI: 0.18, 3.04, P=0.68). Both groups demonstrated significant risk reduction compared to the baseline (SHEP group: OR=0.273, 95% CI: 0.04, 0.96, P=0.048; CMD group: OR=0.30, 95% CI: 0.11, 0.80, P=0.016). GEE accounting for repeated measures and cluster effects (9 counties) indicated that the SHEP group yielded a 35.45% greater risk reduction than the CMD group (RRR=35.45%, 95% CI: –63.78%, –15.21%), with a protective efficacy ratio (1/RR) of 1.55-fold (95% CI: 0.75, 0.97, P=0.046) (Table 1).

At the 12-month follow-up, the deworming frequency in the SHEP group was assessed by enumerating residual PZQ chewable tablets in the SHEP compartments, while in the CMD group, cross-verification of township/village health worker (veterinarian) deworming logs against dog owner interview records was performed. Furthermore, SHEP functionality was monitored, and the annual 12 PZQ tablets were replenished in the SHEP group (each SHEP had a three-year service period). Statistical analysis using the Cochran–Armitage test revealed a significantly higher deworming frequency in the SHEP group than in the CMD group (Z=16.78, P<0.001). All frequency bands showed significant differences (P<0.001), with SHEP achieving a 52.59% increase in high-frequency adherence (9–12 times/year; OR=6.61, 95% CI: 5.41, 8.08) and a 95.35% reduction in low-frequency risk (≤3 times/year, OR=0.036, 95% CI: 0.02, 0.07) (Table 2).

Throughout the study, expenses related to materials, personnel, transportation, and time allocation for the delivery of PZQ chewable tablets were meticulously documented. The SHEP yielded a 22.62% reduction in the overall cost of dog deworming, resulting in annual savings of 53.15% in labor costs, 79.48% in transportation costs, 30.13% in time costs and the commuting efficiency increased by 83.33% (Table 3).

The persistence of canine echinococcosis, despite China’s nationwide monthly deworming program initiated in 2006, highlights systemic challenges. While the prevalence of antigens in dogs has decreased from 4.25% (1) to 0.50% (2), achieving the WHO’s advocated dog infection rate targets (<0.01%) remains a formidable task (7). Conventional manual door-to-door deworming efforts by township/village health workers encounter persistent obstacles, such as geographic isolation, severe weather conditions, and shortages of veterinary professionals in endemic regions such as Xinjiang and Qinghai. Deworming frequency adherence — ranging from 21.7% to 47.5% (3,6) (12 times per year) — and deworming coverage in individual townships, varying from 24% to 84% in Ningxia (4), illustrate the challenges faced. Moreover, cultural customs (e.g., non-harm principles), strong human-dog relationships, and limited health literacy impede compliance, while issues such as overreported deworming records by health workers (veterinarians) lead to data inaccuracies. These factors contribute to sustained environmental egg contamination, with canine infection rates persistently fluctuating between 0.15% and 1.60% across the endemic provincial-level administrative divisions (PLADs) (2).

The SHEP addresses these gaps using a multifaceted approach. Its automated reminder system, featuring monthly light and voice alerts that persist for three days if unacknowledged, mitigates forgetfulness and seasonal mobility (e.g., pastoral transhumance). The dedicated compartment prevents PZQ chewable tablet loss, which is a critical failure point in dog-owner-administered programs. Additionally, daily health broadcasts enhance dog owners’ awareness and facilitate the transition from mere knowledge of control measures to the adoption of healthy behaviors, countering cultural resistance by emphasizing the link between deworming and the reduction of zoonotic risks. This integrated design aligns with the One Health principle, concurrently targeting behavioral, logistical, and educational obstacles.

This trial highlights the superior efficacy of SHEP on both fronts. SHEP reduced canine Echinococcus antigen positivity to 0.09% (compared to 0.18% in conventional delivery; OR=0.273, 95% CI: 0.040–0.960), achieving near-elimination levels. This significant reduction in infected dogs was presumed to decrease environmental egg contamination by approximately 2.1 million eggs/dog annually, considering that each infected dog sheds approximately 40,000 eggs daily during peak transmission seasons (8–9). The resulting decline in soil egg burdens reduced human exposure risk, driving the basic reproduction number (R₀) below 1.0 when canine prevalence falls below 0.1%. SHEP interrupts sustained transmission cycles and aligns with the WHO elimination objectives through source-level decontamination. From an economic standpoint, SHEP significantly improved the deworming frequency distribution, achieving a high adherence rate of 91.38% (9–12 times/year), compared to 59.89% with door-to-door manual delivery. The 6.6-fold increase in the odds of optimal adherence indicated that automated reminders effectively addressed habitual noncompliance, leading to a 95.35% reduction in low-frequency deworming risks. These improvements were realized alongside an 83.33% increase in commuting efficiency, and notable reductions of 53.15%, 79.48%, and 30.13% in labor, transportation, and time costs, respectively. These advancements are particularly crucial for regions with limited personnel and resources, such as highland pastoral areas. The 22.6% cost savings achieved by SHEP facilitate its scalable deployment in hyper-endemic areas, such as Qinghai and Sichuan. The adherence efficacy of SHEP aligns with the WHO’s emphasis on sustaining deworming frequency and effectively supports the control objectives outlined in the “National Implementation Plan for Comprehensive Prevention and Control of Echinococcosis and Other Key Parasitic Diseases (2024–2030)” (10).

This study had several limitations. First, the assumed 3-year device lifespan requires field validation. Additionally, corrosion or damage in extreme environments may increase long-term costs. Second, the deworming frequency adherence in the CMD group relied on unverified self-reporting. Finally, factors, such as county variability, dog attrition within the target population, and limited temporal sampling, may have introduced bias into the estimates. Future iterations should focus on product optimization, integration of deworming strategies, and implementation of spatiotemporal covariance structures through stratified models and multiple imputations to address these limitations and enhance canine echinococcosis control measures.

In conclusion, the SHEP effectively addresses the fundamental challenges associated with conventional deworming practices by promoting verifiable and cost-efficient adherence. By targeting the crucial dog-human-animal interface, SHEP directly interrupts the transmission cycle, providing a scalable solution to attain a sub-0.01% canine infection target. This is recommended as the preferred intervention to improve dog deworming adherence. The integration of SHEP into national programs has the potential to optimize resource utilization and expedite efforts towards the elimination of echinococcosis.

The Shangri-La CDC, Xiji County CDC, Emin County CDC, Hejing County CDC, Artux City CDC, Yushu Xizang Autonomous Prefecture CDC, Qapqal Xibe Autonomous County CDC, and the Disease Control and Prevention Center of the Fourth Division of Xinjiang Production and Construction Corps for distributing the Smart Health Education Pillboxes and facilitating on-site dog fecal collection and testing. We also thank all the participants for contributing their time and support to this study.

Approval by the National Institute of Parasitic Diseases, China CDC (Ethical Review Committee No. 2021019)