Dynamics of serological status.

Rabies control remains challenging in low and middle-income countries, mostly due to lack of financial resources, rapid turnover of dog populations and poor accessibility to dogs. Rabies is endemic in Cambodia, where no national rabies vaccination program is implemented. The objective of this study was to assess the short and long-term vaccination-induced immunity in Cambodian dogs under field conditions, and to propose optimized vaccination strategies. A cohort of 351 dogs was followed at regular time points following primary vaccination only (PV) or PV plus single booster (BV). Fluorescent antibody virus neutralization test (FAVNT) was implemented to determine the neutralizing antibody titer against rabies and an individual titer ≥0·5 IU/mL indicated protection. Bayesian modeling was used to evaluate the individual duration of protection against rabies and the efficacy of two different vaccination strategies. Overall, 61% of dogs had a protective immunity one year after PV. In dogs receiving a BV, this protective immunity remained for up to one year after the BV in 95% of dogs. According to the best Bayesian model, a PV conferred a protective immunity in 82% of dogs (95% CI: 75–91%) for a mean duration of 4.7 years, and BV induced a lifelong protective immunity. Annual PV of dogs less than one year old and systematic BV solely of dogs vaccinated the year before would allow to achieve the 70% World Health Organization recommended threshold to control rabies circulation in a dog population in three to five years of implementation depending on dog population dynamics. This vaccination strategy would save up to about a third of vaccine doses, reducing cost and time efforts of mass dog vaccination campaigns. These results can contribute to optimize rabies control measures in Cambodia moving towards the global goal of ending human death from dog-mediated rabies by 2030.

狂犬病防控在中低收入国家仍面临严峻挑战，主要归因于财政资源匮乏、犬只种群快速更替以及犬只可及性不佳。柬埔寨为狂犬病地方性流行国家，尚未实施全国性狂犬病疫苗接种计划。本研究旨在评估野外实际条件下柬埔寨犬只接种疫苗后诱导的短期与长期免疫效果，并提出优化的疫苗接种策略。本研究纳入351只犬只构建研究队列并开展定期随访，受试犬仅接受初次免疫接种（primary vaccination, PV）或初次免疫联合单次加强免疫接种（booster, BV）。本研究采用荧光抗体病毒中和试验（Fluorescent antibody virus neutralization test, FAVNT）检测犬只抗狂犬病中和抗体滴度，当个体抗体滴度≥0.5 IU/mL时判定为具有保护效力。采用贝叶斯模型评估犬只个体抗狂犬病保护持续时长，以及两种不同接种策略的有效性。结果显示，初次免疫接种后1年，61%的犬只仍维持保护性免疫；在接受加强免疫接种的犬只中，95%的个体在加强免疫后1年内仍保有保护性免疫。基于最优贝叶斯模型，初次免疫接种可使82%的犬只获得保护性免疫（95%置信区间：75%~91%），平均保护时长为4.7年；而加强免疫接种可诱导终身保护性免疫。若对1岁以下犬只实施年度初次免疫接种，仅对前一年完成接种的犬只开展系统性加强免疫，依据犬只种群动态调整实施进度，即可在3至5年内达到世界卫生组织（World Health Organization, WHO）推荐的70%免疫覆盖率阈值，从而实现犬群中狂犬病传播的防控。该接种策略可节省约三分之一的疫苗剂量，降低大规模犬只免疫接种活动的成本与人力投入。本研究结果可为柬埔寨优化狂犬病防控措施提供支撑，助力实现2030年全球消除犬源性人类狂犬病死亡的宏伟目标。