Monti G E, Frankena K
Quantitative Veterinary Epidemiology Group, Wageningen Institute of Animal Sciences Wageningen, P.O. Box 338, 6700 AH Wageningen, The Netherlands.
Prev Vet Med. 2005 May 10;68(2-4):241-62. doi: 10.1016/j.prevetmed.2005.01.009.
Bovine Leukemia virus (BLV) is a ubiquitous retrovirus that affects mainly cattle. Knowledge of the precise moment of infection is fundamental for identification and evaluation of factors related to BLV transmission. Systematic reviews and meta-analyses provide good evidence on the effects of medical interventions. The objectives were to estimate time to sero-conversion after experimental infection using data from retrieved literature and to detect factors that may influence the length of that interval using survival analysis on pooled data. An analysis using aggregate data from 36 studies totalling 438 observations was performed. From this, four sets were created and analysed by interval-censored accelerated failure time models (AFT) with different distributions (exponential, Weibull, log-logistic, lognormal and generalized gamma), and some variants of the Cox model (Andersen-Gill, smoothing splines) with and without a frailty effect. The AFT gamma model fit best and the estimated median time to sero-conversion in the null model was 57 days (95% confidence interval (CI): 49; 75) using all data and 47 days (95% CI: 39; 55) when only studies using experimental inoculation were considered. Some factors were consistently associated with time to sero-conversion. These included exposure by animal-to-animal contact (resulting in a seven-fold increase in time to sero-conversion compared to direct inoculation), diagnostic method to detect sero-conversion (time to sero-conversion was 1.4 times shorter when AGID was used compared to ELISA), and transmission by insect bites (biological media) delayed sero-conversion 2.3 times compared transmission via needles or other inanimate media. After fitting a frailty Cox model, results showed that sero-conversion in susceptible animals after infection using donors, in which presence of virus before the experiment started was confirmed, increased the hazard of sero-conversion two times in comparison with donors in which virus presence was not confirmed before start of the experiment. Inoculation with blood decreased the hazard 2.5 times in comparison with lymphocyte suspensions. Heterogeneity due to different research groups was also present. Finally, a Cox model with smoothing splines contained three variables: research group, route of inoculation and a non-linear spline for infective dose. In conclusion, it can be stated some factors that influence the time to sero-conversion were identified and quantified and that a moderate influence of research centre existed. These results may contribute to the estimation of the most probable times of infection in field conditions and in a better evaluation of control measures.
牛白血病病毒（BLV）是一种普遍存在的逆转录病毒，主要感染牛。了解感染的确切时间对于识别和评估与BLV传播相关的因素至关重要。系统评价和荟萃分析为医学干预的效果提供了有力证据。目的是利用检索文献中的数据估计实验感染后血清转化的时间，并通过对汇总数据进行生存分析来检测可能影响该间隔时间长度的因素。对来自36项研究共438个观察值的汇总数据进行了分析。据此，创建了四组数据，并通过具有不同分布（指数分布、威布尔分布、对数逻辑分布、对数正态分布和广义伽马分布）的区间删失加速失效时间模型（AFT）以及具有和不具有脆弱效应的Cox模型的一些变体（安德森-吉尔模型、平滑样条模型）进行分析。AFT伽马模型拟合效果最佳，在空模型中，使用所有数据估计的血清转化中位时间为57天（95%置信区间（CI）：49；75），仅考虑使用实验接种的研究时为47天（95%CI：39；55）。一些因素始终与血清转化时间相关。这些因素包括动物间接触感染（与直接接种相比，血清转化时间增加了7倍）、检测血清转化的诊断方法（与ELISA相比，使用AGID时血清转化时间缩短了1.4倍）以及昆虫叮咬（生物媒介）传播导致血清转化延迟是通过针头或其他无生命媒介传播的2.3倍。拟合脆弱Cox模型后，结果显示，使用在实验开始前已确认存在病毒的供体感染后，易感动物的血清转化风险与在实验开始前未确认病毒存在的供体相比增加了两倍。与淋巴细胞悬液相比，接种血液使风险降低了2.5倍。不同研究组之间也存在异质性。最后，具有平滑样条的Cox模型包含三个变量：研究组、接种途径和感染剂量的非线性样条。总之，可以确定并量化一些影响血清转化时间的因素，并且研究中心存在一定影响。这些结果可能有助于估计现场条件下最可能的感染时间，并更好地评估控制措施。
