译者的话<<

猪群规模与疾病风险之间关系实例

Examples of the relationship between herd size and disease risk<<

猪群规模和管理系统相互关联，且管理因素影响疾病的发生，所以猪群规模可能与疾病的发生不存在因果关系。本部分，根据在丹麦养猪生产的经验提供一些实例，以说明猪群规模如何单独地或联合相关管理因素对疾病风险造成影响。丹麦的很多研究表明，与许多其他国家相比，丹麦在养猪生产上采取的管理因素更为统一。因此，在将丹麦关于猪群规模和疾病风险的研究成果应用于其他国家的生产系统时，必须谨慎。

Herd size might be non-causally (spuriously) associated with disease occurrence, because herd size and management systems are interrelated and management factors influence disease occurrence. In this section, we give some examples, based mainly on our experience in Danish swine production, to demonstrate how herd size might influence disease risk independently or in association with other management risk factors. We note that most of the studies are from Denmark, where the swine population is more homogeneous with respect to management factors than in many other countries. Hence, caution must be used in extrapolating findings from Danish studies of herd size and disease risk to production systems in other countries.

管理变量与猪群规模相混杂

Confounding of management variable associations by herd size<<

猪群规模和管理变量之间的效应修正

Effect modification between herd size and management variables<<

当两个变量对疾病风险的联合效应大于或小于其各自预测效应时，即发生效应修正（统计学上也称为“交互作用”）。可以根据疾病结果的建模方式，以加性或乘性尺度评估交互作用。交互作用可以表现为特定层优势比不同，原始优势比介于风险因素不同类别（层）的值之间。

Effect modification (also termed ‘interaction’, when used in a statistical context) occurs when the joint effect of two variables on disease risk is greater or less than that predicted from their individual effects. Interaction can be assessed on an additive or multiplicative scale depending on how the disease outcome is modeled. One manifestation of interaction is a difference in stratum-specific odds ratios, with the crude odds ratio intermediate between the values for the different categories (strata) of the risk factor.

以下两个例子可以说明猪群规模与管理因素之间的交互作用。Aalund等（1976年）表明，大规模猪群（每年屠宰量大于 400头）中，有腹泻病史的猪群似乎可以预防慢性胸膜炎（优势比= 0.6），而小规模猪群中，有腹泻病史的猪群患胸膜炎的几率增加了两倍。他们认为特定层的估计差异是猪群腹泻病史、猪群规模以及慢性胸膜肺炎几率之间交互作用的证据。另外，此交互作用与研究组群的猪是购买还是饲养无关。Pointon等（1985年）发现，与大于100头的母猪群相比（大栏载畜率和空间载畜率），20-70头的母猪群之间的肺炎高患病率相关因素有所不同（母猪淘汰率、育肥猪购买、每棚猪和每组猪数量）。这些研究虽然没有采用分层分析确定是否与猪群规模相混杂和/或交互作用或管理因素相互关联，但是研究结果证实环境和管理因素的影响通常取决于猪群规模。

  We present two examples to demonstrate that interaction between herd size and management factors is possible. Aalund et al. (1976) showed that, in large herds (＞400 fatteners slaughtered per year), a herd history of diarrhea seemed to protect (odds ratio = 0.6) against chronic pleuritis, whereas in small herds a history of diarrhea contributed to a two-fold increase in the odds of pleuritis. This difference in stratum-specific estimates was considered evidence of interaction between a herd history of diarrhea and herd size, and the odds of chronic pleuritis. Moreover, this interaction was independent of whether the pigs were purchased or raised in the study herd. Pointon et al. (1985) found that factors associated with high prevalences of pneumonia were different in herds of 20-70 sows (sow culling rate, purchase of pigs for finishing, pigs per shed section, and pigs per group) compared with herds of >100 sows (pen stocking rate and air-space stocking rate). Stratified analyses were not done by the authors to determine whether confounding and/or interaction with herd size occurred or whether the management factors were interrelated, but their findings confirm that the impact of environmental and management factors often depends on herd size.

管理和病原的关联取决于猪群规模

Management and infectious agent associations that are dependent on herd size<<

在丹麦，猪群规模、健康状况（SPF猪群或一般猪群）、传染病的发生和生产系统（育肥猪群或从分娩至育肥猪群）之间相互关系复杂。重新分析Mousing等人(1990)使用的数据，以证明这些相互关系，同时发现对管理变量进行管控后，会出现其余的猪群规模关联。虽然很少进行管理因素的评估，但本研究的独特之处在于它认为接触感染胸膜炎的猪是导致屠宰时发现病变的风险因素。本研究对一项包含2718个记录的子集[所有变量值无缺失、无胸膜肺炎链球菌血清2型（AP2）疫苗接种史]进行再分析，以证明将病原（特别是AP2）的暴露纳入血清学数据可以从某种程度上解释猪群规模效应。分析时，将猪群规模按四分位数分组（每年屠宰小于620头（参考组）、620至1200头、1201至2000头以及大于2000头猪群）。在双变量分析中，AP2血清阳性使得患胸膜炎的几率增加9.9倍，且仅对最大猪群规模（优势比= 2.4）来说，胸膜炎优势比大于1。将AP2的感染状态纳入多元logistic回归分析后，虽然预估置信区间仍然不包含1，但是最大猪群发生胸膜炎的几率显著降低(优势比为1.4)。此两类中等规模猪群的估计值本质上无变化。无法通过其他检测因素（猪群类型以及接触其他已感染胸膜炎的猪群）解释最大规模猪群的剩余效应，但是由于只评估了少数因素，其他未加以衡量的管理因素也许可以对其进行解释。

In Denmark, complex interrelationships exist between herd size, health status (SPF or conventional), the occurrence of infectious agents, and production system (fattening herd or farrow-to-finish herd). The data used by Mousing et al. (1990) were reanalysed to demonstrate these interrelationships and to show that a residual herd size association can exist after controlling for management variables. Although few management factors were evaluated, the study was unique because it considered exposure to known infectious causes of pleuritis as risk factors for slaughter lesions. A subset of 2718 records [no missing values on any variables and no history of vaccination against A. pleuropneumoniae serotype 2 (AP2)] were reanalysed to demonstrate how the incorporation of serological data on exposure to infectious agents (specifically AP2) may explain at least part of the herd-size effect. For the analysis, herd sizes were grouped in quartiles [<620 (reference category), 620-1200, 1201-2000 and >2000 pigs slaughtered per year). In bivariable analysis, seropositivity to AP2 increased the odds of pleuritis 9.9 times and the odds ratio for pleuritis was greater than 1 only for the largest herd-size quartile (odds ratio = 2.4). After inclusion of AP2 serostatus in the multiple logistic regression analysis, the odds of pleuritis were substantially reduced in the largest herds (odds ratio= 1.4), although the confidence interval for the estimate still excluded 1. Estimates for the two intermediate herd size categories were essentially unchanged. The residual effect of the largest herd size category could also not be explained by other factors examined (herd type and exposure to other known infectious causes of pleuritis), but since only a few factors were evaluated it is possible that unmeasured management factors were at least part of the explanation.

猪群规模与疾病之间的伪相关性

Spurious associations between herd size and disease<<

对于某些疾病，若将猪群密度、猪只密度和管理等其他重要的风险因素纳入分析时，则可对明显的猪群规模效应进行充分解释。在德国北部集中免疫地区的育肥猪群中发生PRV的循环传播，Leontides等人（1994b）对其传播的相关因素进行了研究。经粗略分析后，发现猪群规模与感染PRV风险呈正相关（猪群内增加100头猪时，对应的优势比为1.69），但将相关猪只数量和管理变量[从出生至育肥或育成至育肥阶段的猪（猪群类别）以及每平方公里内猪只数量]等因素纳入logistic回归模型进行分析，疾病与猪群规模的相关性不再明显（优势比为1.02）。

For some diseases, an apparent effect of herd size may be adequately explained when other important risk factors, such as herd density, pig density and management factors, are included in analyses. Leontides et al. (1994b) studied factors associated with PRV circulation in fattening herds in an intensively vaccinated area of northern Germany. Herd size increased the risk of PRV (odds ratio=1.69 for a 100-pig increase in herd size) in crude analyses, but when the related demographic and management variables [farrow-to-finish or feeder-to-finish (herd type) and pigs/km2] were included in logistic regression models, the herd size association was no longer significant (odds ratio= 1.02).

对今后猪群规模研究的建议

Recommendations for future herd size studies<<

过去的十年中，国际养猪生产发生了很大变化，包括更多地采用全进全出、多点式和按日龄分群的生产系统，以及在饲养育肥猪时更多采用隔间，从而减少病原体传播。这些变化大多更容易在大型猪群中实现，因此，猪群规模大与疾病风险之间的正相关关系也许不复存在。

In the last decade there have been substantial changes in swine production internationally, including the increased implementation of all-in, all-out, multisite and age-segregated production systems, and greater use of compartments for finishing pigs to reduce pathogen transmission. Many of these changes can be implemented more readily in large herds, and hence the historic positive relationships between larger herd size and disease risk may no longer exist.

虽然已发表研究和数据集的再分析大多是关于丹麦的养猪生产，但涉及的基本问题却广泛适用于其他国家及生产系统。因此，针对猪群规模、猪群密度、猪的饲养密度以及其他管理和环境因素，有必要采取更科学的方法来确定其对疾病风险造成的影响。对于疾病控制而言，尤其要注意确定猪群规模效应的真伪，以便给出适当的缓解建议。

  Although many of the published studies and data sets that we reanalysed involved Danish swine production, the underlying issues are widely applicable to other countries and production systems. Accordingly, we believe that more structured approaches are necessary to determine how herd size, herd density, pig stocking density and other management and environmental factors affect disease risk. For disease control decisions, it is especially important to determine whether any herd-size effect is real or spurious so that appropriate advice about mitigations can be given.

为确保今后关于猪群规模与疾病之间关系的研究成果达到最大效用，现提出如下建议。

To ensure the greatest utility of findings from future studies on the relationship between herd size and disease, we make the following recommendations.

（i）在对猪群规模进行度量时，最好是能站在疾病或生产利益的角度阐述群体所处的风险。对于病原而言，理论上是指易感猪只数量，但实际上，可能仅是每栋建筑物或隔间内猪只数量或总数。特别是对断奶猪和育成/育肥猪的疾病，建议测量猪只的密度（就所占面积和空间而言）。针对各类规模度量的复合评估或单项评估，应包含于猪群规模相关的分析结果中。饲养密度及空间的标准已得到广泛认可，相比其他猪群规模的度量方法，其相对稳定且分类更加固定，强烈建议将此类评估应用于所有传染病研究中。此外，改进对猪群规模的描述，有利于剔除诸如“大”这样的随意猪群分类，以便可以更好地比较不同国家间的研究成果。

(i) Herd size should be measured in ways that best characterize the population at risk for the disease or productivity measure of interest. For infectious agents, this would ideally be the number of susceptible pigs, but in practice only the total number and number per building or compartment will probably be available. In addition, we recommend measurement of pig density (in terms of floor and air space occupied) especially for diseases of weaned and grower/ finisher pigs. Results of analyses of the herd-size associations should include evaluation of the joint and individual contributions of each type of herd size measure. Because standards for stocking density and air space are well accepted, relatively stable and less subject to arbitrary categorization than other herd size measures, we strongly recommend their evaluation in all studies of infectious disease. Also, improved characterization of herd size will help remove the rather arbitrary classification of herds as 'large' and allow better comparison of results among studies in different countries.

（ii）在猪群、建筑物或隔间层面评估管理相关的风险因素时，若无法证明猪群规模是否为相关因素，应将其视为潜在的混杂因素。如果用猪群规模代表其中单个或多个无法衡量的管理风险因素，则尤其要注意调整猪群规模后残留混杂因素可能依旧存在，除非猪群规模与这些变量之间具有极大相关性（格陵兰岛和纽特拉岛，1980年），但此类情况在养猪生产中极不可能发生。此外，由于同一地区猪群规模与猪群（猪只）密度通常相关，因此应弄清两者之间的关系。

(ii) Studies that evaluate management-related risk factors at the level of herd, building or compartment should consider herd size as a potential confounder, unless there is adequate prior evidence to suggest that herd size is not a causal factor. If herd size is used as a surrogate for one or more unmeasured management risk factors, it is important to be aware that residual confounding may still exist after adjustment for herd size, unless herd size is a perfect correlate for these variables (Greenland and Neutra, 1980), a situation that we believe is most unlikely in swine production systems. In addition, the relationship between herd size and herd (and pig) density in an area should be clarified since these two variables are often associated.

（iii）根据猪只数量研究管理因素之间的内在联系，需对猪群规模、猪群密度和猪只密度进行研究。虽然所选统计模型的形式与基本生物学过程之间关系复杂，但多元统计技术的有效性可以更好地定义这些关系（Greenland，1989）。最近，Dohoo等人（1997）对流行病学研究中用于处理大量自变量的统计技术作出文献综述。

(iii) Population-based studies of the interrelationships among management factors and between management factors, herd size, herd density and pig density are needed. The availability of multivariable statistical techniques provides a powerful tool to better define these relationships, although no simple relationship exists between forms of the selected statistical models and the underlying biological processes (Greenland, 1989). Statistical techniques to deal with a large number of independent variables in epidemiological studies have been reviewed recently by Dohoo et al. (1997).

（iv）应假设出所有与猪群规模相关的生物学原因。此外，应该充分讨论研究潜在的偏差和限制，这些偏差和限制会影响猪群规模与疾病风险之间的正相关性或负相关性或无相关性的因果解释(Savitz, 1992)。这样有助于改进研究设计，从而对成功干预的可能性进行更为严格的评估。

(iv) Likely biological reasons for any herd size association should be postulated. Moreover, there should be adequate discussion of the potential biases and limitations of the study that affect the causal interpretation of a positive or negative association or no association between herd size and disease risk (Savitz, 1992). Such candor should also facilitate improvements in study design and lead to a more critical assessment of the likelihood of successful interventions.

（v）当所研究猪群的规模分布与源种群不同时，至少是应提及所研究国家或地区猪群规模的中值(理想情况下应提及猪群规模分布)。风险计算偏离猪群规模中值(连续变量)或将猪群规模中值作为参照组，此应作为阐述猪群规模相关性的标准方法。此方法能够解释猪群规模在不同时期出现的改变，以及小于最低规模时，猪群有可能消失的原因。

(v) Whenever the herd size distribution of study herds differs from that of the source population, authors should report at least the median herd size (and ideally the distribution of herd size) for the country or region of the study. For risk calculations deviations from the median herd size (continuous variable) or the use of the category with the population median herd size as the reference group should be used as a standard way to report herd size associations. Such an approach will account for shifts in herd size distribution with time and the likely disappearance of herds smaller than a certain minimum herd size.

致谢

Acknowledgments<<

此研究得到了丹麦农业部（KVL-VEL-4），美国农业部：动植物检疫局：兽医处（合作协议第12-34-99-0020-CA号）以及加利福尼亚戴维斯分校—食用动物健康中心的资助。感谢Sten Mortensen和ClaesEnøe的技术支持，以及审稿人对初稿提出的建设性意见。

This research was supported by funds from the Danish Ministry of Agriculture (KVL-VEL-4), USDA: APHIS:VS (Cooperative Agreement No. 12-34-99-0020-CA) and the Center for Food Animal Health, University of California, Davis. The authors thank Sten Mortensen and Claes Enøe for technical assistance, and the reviewers for their constructive suggestions for improving the manuscript.