Mediation analysis results, DRC.

Livestock are important reservoirs for many zoonotic diseases, however the effects of livestock on human and environmental health extend well beyond direct disease transmission. In this retrospective ecological cohort study we use pre-existing data and the parametric g-formula, which imputes potential outcomes to quantify mediation, to estimate three hypothesized mechanisms by which livestock can influence human African trypanosomiasis (HAT) risk: the reservoir effect, where infected cattle and pigs are a source of infection to humans; the zooprophylactic effect, where preference for livestock hosts exhibited by the tsetse fly vector of HAT means that their presence protects humans from infection; and the environmental change effect, where livestock keeping activities modify the environment in such a way that habitat suitability for tsetse flies, and in turn human infection risk, is reduced. We conducted this study in four high burden countries: at the point level in Uganda, Malawi, and Democratic Republic of Congo (DRC), and at the county level in South Sudan. Our results indicate cattle and pigs play a reservoir role for the rhodesiense form (rHAT) in Uganda (rate ratio (RR) 1.68, 95% CI 0.84, 2.82 for cattle; RR 2.16, 95% CI 1.18, 3.05 for pigs), however zooprophylaxis outweighs this effect for rHAT in Malawi (RR 0.85, 95% CI 0.68, 1.00 for cattle, RR 0.38, 95% CI 0.21, 0.69 for pigs). For the gambiense form (gHAT) we found evidence that pigs may be a competent reservoir (RR 1.15, 95% CI 0.92, 1.72 in Uganda; RR 1.25, 95% CI 1.11, 1.42 in DRC). Statistical significance was reached for rHAT in Malawi (pigs and cattle) and Uganda (pigs only) and for gHAT in DRC (pigs and cattle). We did not find compelling evidence of an environmental change effect (all effect sizes close to 1).畜禽是多种人畜共患病的重要储存宿主，然而畜禽对人类与环境健康的影响远不止直接的疾病传播。本回顾性生态队列研究利用现有数据与参数化g公式（parametric g-formula）——该方法通过估算潜在结局以量化中介效应——对畜禽影响非洲人类锥虫病（Human African Trypanosomiasis, HAT）感染风险的三种假说机制进行了估算：其一为储存宿主效应，即受感染的牛与猪是人类感染的传染源；其二为动物预防性保护效应（zooprophylactic effect），作为HAT传播媒介的采采蝇更偏好畜禽宿主，因此畜禽的存在可对人类起到感染防护作用；其三为环境改变效应，即畜禽养殖活动会改变环境，降低采采蝇的栖息地适宜性，进而降低人类感染风险。本研究在四个疾病高负担国家开展：乌干达、马拉维与刚果民主共和国（DRC）采用点位级分析，南苏丹采用县级分析。研究结果显示，在乌干达，牛与猪对罗得西亚型非洲人类锥虫病（rHAT）起到储存宿主作用（牛的率比（RR）为1.68，95%置信区间（95% CI）为0.84~2.82；猪的RR为2.16，95% CI为1.18~3.05）；但在马拉维，动物预防性保护效应的作用强于储存宿主效应（牛的RR为0.85，95% CI为0.68~1.00；猪的RR为0.38，95% CI为0.21~0.69）。针对冈比亚型非洲人类锥虫病（gHAT），本研究发现猪可能是其有效储存宿主（乌干达的RR为1.15，95% CI为0.92~1.72；刚果民主共和国的RR为1.25，95% CI为1.11~1.42）。马拉维的rHAT（牛与猪）、乌干达的rHAT（仅猪）以及刚果民主共和国的gHAT（牛与猪）均达到统计学显著性水平。本研究未发现支持环境改变效应的有力证据（所有效应量均接近1）。