Arega Sintayehu, Conan Anne, Sabeta Claude T, Crafford Jan E, Wentzel Jeanette, Reininghaus Bjorn, Biggs Louise, Leisewitz Andrew L, Quan Melvyn, Toka Felix, Knobel Darryn L
Center for Conservation Medicine and Ecosystem Health, Ross University School of Veterinary Medicine, Basseterre, Saint Kitts and Nevis.
Agricultural Research Council-Onderstepoort Veterinary Institute, OIE Rabies Reference Laboratory, Onderstepoort 0110, South Africa.
Trop Med Infect Dis. 2020 Mar 12;5(1):45. doi: 10.3390/tropicalmed5010045.
To achieve global elimination of human rabies from dogs by 2030, evidence-based strategies for effective dog vaccination are needed. Current guidelines recommend inclusion of dogs younger than 3 months in mass rabies vaccination campaigns, although available vaccines are only recommended for use by manufacturers in older dogs, ostensibly due to concerns over interference of maternally-acquired immunity with immune response to the vaccine. Adverse effects of vaccination in this age group of dogs have also not been adequately assessed under field conditions. In a single-site, owner-blinded, randomized, placebo-controlled trial in puppies born to mothers vaccinated within the previous 18 months in a high-mortality population of owned, free-roaming dogs in South Africa, we assessed immunogenicity and effect on survival to all causes of mortality of a single dose of rabies vaccine administered at 6 weeks of age. We found that puppies did not have appreciable levels of maternally-derived antibodies at 6 weeks of age (geometric mean titer 0.065 IU/mL, 95% CI 0.061-0.069; = 346), and that 88% (95% CI 80.7-93.3) of puppies vaccinated at 6 weeks had titers ≥0.5 IU/mL 21 days later ( = 117). Although the average effect of vaccination on survival was not statistically significant (hazard ratio [HR] 1.35, 95% CI 0.83-2.18), this effect was modified by sex ( = 0.02), with the HR in females 3.09 (95% CI 1.24-7.69) and the HR in males 0.79 (95% CI 0.41-1.53). We speculate that this effect is related to the observed survival advantage that females had over males in the unvaccinated group (HR 0.27; 95% CI 0.11-0.70), with vaccination eroding this advantage through as-yet-unknown mechanisms.
为在2030年前实现全球消除犬类传播的人类狂犬病目标，需要有基于证据的有效犬类疫苗接种策略。当前指南建议在大规模狂犬病疫苗接种活动中纳入3个月龄以下的犬只，尽管现有疫苗仅被制造商推荐用于年龄较大的犬只，表面原因是担心母源抗体干扰疫苗免疫反应。在野外条件下，也尚未充分评估该年龄组犬只接种疫苗的不良反应。在南非一个高死亡率的自有散养犬种群中，对前18个月内接种过疫苗的母犬所生幼犬进行了一项单地点、主人盲法、随机、安慰剂对照试验，我们评估了6周龄时接种单剂狂犬病疫苗的免疫原性及其对各种死因存活率的影响。我们发现，幼犬在6周龄时母源抗体水平不高（几何平均滴度0.065 IU/mL，95%可信区间0.061 - 0.069；n = 346），6周龄接种疫苗的幼犬中，88%（95%可信区间80.7 - 93.3）在21天后滴度≥0.5 IU/mL（n = 117）。尽管接种疫苗对存活率的平均影响无统计学意义（风险比[HR] 1.35，95%可信区间0.83 - 2.18），但该影响存在性别差异（P = 0.02），雌性的HR为3.09（95%可信区间1.24 - 7.69），雄性的HR为0.79（95%可信区间0.41 - 1.53）。我们推测，这种影响与未接种疫苗组中雌性比雄性具有的存活优势有关（HR 0.27；95%可信区间0.11 - 0.70），接种疫苗通过尚不清楚的机制削弱了这种优势。
