【豬譯館】生物安全科學:了解病原體進入豬群的機制以及如何實施有效的生物安全改進計劃(上)

譯者的話

非瘟在中國大陸發生以來，養豬界被提到稀爛的一個詞就是「生物安全」，甚至被無限制地上綱上線，公貨、私貨皆可一股腦塞進至高無上的「生物安全」，「生物安全官員」一度風頭無倆，至於邏輯關係、因果轉承、統計分析等均可度勢而用。但，自然科學終究是要回到事實的本質或者無限接近本質—科學地應用生物安全：通過病原載體進入事件組織流行病學調查和風險評估，遵循正確的「準備-瞄準-開火」順序，以此為基礎進行/改進實踐方可達建立和實施「生物安全」之初衷。

生物安全科學：了解病原體進入豬群的機制以及如何實施有效的生物安全改進計劃（上）

Science of biosecurity: understanding the mechanisms of pathogen entry into pig populations, and how to implement effective biosecurity improvement programs - Part 1

作者 Authors：Iowa State University, College of Veterinary Medicine, Ames, Iowa, USA.引入 Introduction在過去的30到40年裡，全球養豬業經歷了一場革命。40年前，養豬生產在地理上是集中的(即所有生產活動都是集中在一起的)小規模豬場和戶外養殖。生產者知道許多領域的知識，但沒有一個領域是精通的，並且豬場很少有僱員。養豬生產現在已經發生了轉變，許多生產活動在地理上分散到專業的養豬設施裡。生產階段在地理上也是分開的，配種到斷奶、保育和育成(或育肥)階段的生產在獨立的設施進行。公豬站也獨立了，公豬精液在採集和處理之後被運送到母豬場，為豬場提供飼料的大型飼料加工廠也是獨立的。小規模的戶外養殖已經被完全在室內飼養的大規模體系所取代。現在母豬數量超過10萬頭的養豬公司全球超過31家(Hess, 2019年。據National Hog Farmer 2020年6月初發表的數據，母豬數量超過10萬頭的養豬公司已達到34家，詳情請見豬譯館《2020年全球10萬頭母豬企業排行榜》)。單個豬場的規模也在擴大。例如，在美國，1994年有27%的養豬場被認為是大型豬場(超過5000頭豬)(美國農業部，2015年)。在僅僅20年之後的2014年，超過93%的豬場被認為是大型豬場。隨著豬場規模和養豬企業規模的擴大，它們變得更加專業化，也更加依賴僱傭勞動力。在許多養豬場，農場主不再長時間在農場工作。大型的養豬企業也會僱傭非常專業的人員，包括獸醫、營養學家、生殖生理學家和動物福利專家。大型養豬企業可以共享設備，如生豬卡車/拖車和飼料卡車，以更有效地利用這些資源(不讓其閒置)，並獲得巨大的規模經濟效益。這些變化對生物安全意味著什麼？當病原體被引入豬群時，以上提及的所有變化都導致了損失規模的大幅增加，以及引入這些病原體的機會頻率的增加。對於一個母豬數量為4000頭或以上的豬群，每次PRRS爆發帶來的損失可超過100萬美元。各種形式的專業化、以及生產和輔助生產活動(如飼料廠、公豬站和後備母豬擴繁場)的地理隔離導致了病原體進入豬群事件的發生頻率大幅增加。病原體進入豬群的途徑包含但不限於：飼料、公豬精液和定期引進的後備母豬，以及運送它們的司機、車輛和拖車。The global swine production industry has experienced a revolution in the last 30 to 40 years. Forty years ago, production was geographically centralized (i.e., all production activities were centrally located), small scale and outdoors. Producers were knowledgeable in many areas, but a specialist in none and few had employees. Swine production has now transitioned to where many of the production activities are geographically decentralized at specialized facilities. The stages of production are geographically segregated where the breed-to-wean, nursery (or rearing) and finishing (or fattening) stages of production occur at separate locations. Other examples include boar studs where semen is collected, processed and delivered to sow farms and large-scale feed mills that mill and deliver feed to many farms. Small scale, outdoor production has been replaced by large-scale systems where pigs are raised entirely indoors. There are now over 31 production companies globally that have at least 100,000 sows (Hess, 2019). The size of individual farms has also grown. In the United States, for example, 27 percent of swine farms were considered large (>5,000 head) in 1994 (USDA, 2015). By 2014, just 20 years later, over 93 percent were considered large. As the size of farms and production companies increased, they became more specialized and more reliant on employed labor. On many swine farms, the owner(s) no longer regularly works on the farm. The larger production companies now hire very specialized labor, including veterinarians, nutritionists, reproductive physiologists, and animal welfare specialists. The larger production companies have opportunities to share equipment, such as livestock trailers and feed trucks, to use these resources more efficiently (i.e., not sitting idle) and capture significant economies of scale. What have these changes meant for biosecurity? All have resulted in major increases in the size of losses when pathogens are introduced into a herd and the frequency of opportunities to introduce those pathogens. It is not uncommon in herds with at least 4,000 sows to have losses that exceed US$1,000,000 after an outbreak of PRRS. The various forms of specialization and geographic segregation of production and ancillary production activities (e.g., feed mills, boar studs and gilt multiplication farms) have led to a major increase in the frequency of events where pathogens can be introduced into a herd. A list of examples, that is by no means all-inclusive, includes feed, semen and replacement gilts that are routinely delivered to sow farms, and with them the drivers, vehicles and trailers that deliver them.豬病和疾病管理在過去的30到40年裡也有了發展。20世紀80年代PRRSV的出現可以說是大多數人畢生所經歷的最重大的豬病事件。但近兩年非洲豬瘟病毒(ASFV)的傳播可能在未來十年刷新我們的認知。生長豬採用全進全出的生產模式，以及注重母豬群豬病淨化（如豬繁殖和呼吸症候群病毒(PRRSV)、豬流行性腹瀉病毒(PEDV)和肺炎支原體(Mhp)等），也增加了生物安全的價值。如果一群生長豬對某些病原體呈陰性且在斷奶時缺乏免疫力，那麼將這些病原體排除在豬群之外是極其重要的。當我們在淨化母豬場病原體方面進行投入/投資，防止這些病原體重新引入的價值是巨大的。對於PRRSV來說，異源免疫保護通常不佳，因此，即使母豬群已經感染了一些分離株，防止新的分離株被引入到該豬群還是極其重要的。Swine diseases and disease management have also evolved in the last 30 to 40 years. The emergence of PRRSV in the 1980s was arguably the most significant swine disease event to occur in most of our lifetimes. The recent spread of African swine fever virus (ASFV) may alter our collective opinions about that in the next  decade. The adoption of all-in-all-out production of growing pigs and the emphasis on eliminating swine pathogens, such as porcine reproductive and respiratory syndrome virus (PRRSV), porcine epidemic diarrhea virus (PEDV) and Mycoplasma hyopneumoniae (Mhp) from sow herds have also increased the value of biosecurity. When groups of growing pigs are negative for certain pathogens and lacking immunity at placement, the value of keeping those pathogens  out is immense. When investments are made to eliminate pathogens from sow farms, the value of preventing the reintroduction of the pathogens is enormous. In the case of PRRSV, where heterologous immunity is often sub-par, the value of not introducing new isolates into sow herds is large, even if the herd is already infected with other isolates.

隨著世界各國聯繫越來越緊密，全球貿易越來越重要，對於目前沒有特定病原體的國家，例如，美國無ASFV、口蹄疫病毒(FMDV)和假狂犬病病毒(PRV)，阻止這些跨國界病原體入境並迅速傳播的重要性也進一步增加。最近在東南亞和東歐蔓延的ASFV使世界整個養豬行業處於高度警戒狀態。For countries that are presently free of specific pathogens, such as ASFV, foot and mouth disease virus (FMDV) and pseudorabies virus (PRV) in the United States, the need to prevent these transboundary pathogens from entering and spreading rapidly has also increased in importance as the world has become more connected and global trade more important. The recent spread of ASFV in Southeast Asia and Eastern Europe has put the world pork industry on high-alert.儘管養豬業對生物安全在豬場的重要性意識有所提高，但應對卻並不及時，進展緩慢。原因何在？在過去的15年裡，我的研究和服務工作主要集中在生物安全、生物安全風險評估和疫情調查方面。在那期間，我觀察到養豬戶和獸醫的生物安全方案是「準備-開火-瞄準」（即：準備好了，就開一搶，然後再找目標，而非找到目標後再開槍）。而我自己也是如此。然而，「準備-開火-瞄準」是正確的順序嗎？答案並沒有那麼顯而易見。企業家們經常因為按照這種順序做事而獲利並受到讚揚，特別是在那些顛覆性的技術領域，首先進入市場就是王道。但是，這是採取生物安全措施的正確順序嗎？我認為，這種方法導致了資源分配不當，在改善生物安全和減少PRRS和其他疾病爆發頻率方面進展非常緩慢。While the need for biosecurity on swine farms has increased, the industry has been slow to respond to the new calculus. Why has progress been slow? For the last 15 years, I have focused much of my research and outreach on biosecurity, biosecurity risk assessments and outbreak investigations. During that time, I have observed swine producers and veterinarians use a "ready-fire-aim" approach to biosecurity. I have been guilty of it myself. However, is "ready- fire-aim" the right order? The answer is not readily apparent. Entrepreneurs are frequently celebrated and rewarded for approaching things in this order, especially with disruptive technologies where being first-to-market is everything. However, is it the right order to approach biosecurity? I believe that it has led to misallocation of resources and very slow progress on improving biosecurity and reducing the frequency of outbreaks of PRRS and other diseases.「準備-開火-瞄準」法是以實驗研究為指導的。當一項新研究表明，例如：生豬拖車、水鞋、昆蟲或氣溶膠能在豬群之間傳播病原體時，養豬業剛一得到這個消息，在對生豬拖車、水鞋、昆蟲或氣溶膠在豬群之間傳播病原體能力的強弱知之甚少的情況下就全力開火了。能傳播病原，並不意味著這些媒介就會頻繁傳播病原。如果不把資源都花在這些方面，而是花在應對和處理其他能在豬群間傳播病原的事情上，結果豈不是更好嗎？The ready-fire-aim approach has been guided by experimental research. When a new study was published demonstrating that, for example, livestock trailers, boots, insects or aerosols are capable of carrying pathogens from herd-to-herd, the industry has opened fire with only a rudimentary understanding of how much livestock trailers, or boots, or insects or aerosol were contributing to the herd-to-herd transmission of pathogens. Just because they can, does not mean that they frequently do. Were resources being spent on these when they would have been better spent addressing other things that can carry pathogens from herd-to-herd?正確的順序應該是「準備-瞄準-開火」。這一過程中的「瞄準」究竟是什麼？簡單地說，就是找出病原體進入豬群的最常見方式，然後優先改進生物安全以解決這些問題。要先確定豬場上最嚴重的漏洞，再確定下一步應該採取什麼措施。實驗研究對確定病原體最常見的傳播方式沒有幫助。要研究這個問題，我們必須觀察正在發生的事情。然而，採取專門措施進行生物安全風險評估和疫情調查是不夠的。通過觀察更快地學習需要一種更系統、更全面和更一致的方法。The better order is "ready-aim-fire." What does the aim step in ready-aim-fire look like? Very simply, it is trying to identify the most frequent ways by which pathogens are being introduced into herds and then prioritizing improvements in biosecurity to address them. It is taking time to identify the most significant vulnerabilities on farms to determine what should be done next. Experimental research studies are no help for identifying the most frequent ways that pathogens are introduced. To study this question, we have to observe what is happening. However, ad-hoc approaches to biosecurity risk assessments and outbreak investigations are not sufficient. Learning faster from observing requires a more systematic, comprehensive and consistent approach.21世紀初，我參與生產動物疾病風險評估項目(PADRAP) (Holtkamp et. al., 2012)的經歷讓我備受挫折。該調查有助於確定存在或不存在的特定風險因素以及已實施或未實施的特定生物安全措施。這可能會告訴我們一點「開槍要打什麼」的信息，然而，它對於確定優先順序(即目標)幾乎沒有任何作用。在PADRAP中，針對每一個回答的問題都會得到一個分值，這個分值會顯示哪些/哪項風險因素或操作實踐的風險更高。事實證明，PADRAP中的綜合風險評分對預測PRRSV的引入導致疫情發生頻率更高的豬群具有一定的價值。但風險評分系統有幾個缺點。首先，對於每個問題答案的評分相對於調查問卷中其他問題的答案是獨立的，並不相互影響。例如，在每一車斷奶豬之間不清洗拖車的得分與拖車是本場專用的還是20個豬場共用的得分是相同的。並且，每個問題答案的評分也獨立於調查中沒有涵蓋的大量其他信息。例如：運輸斷奶仔豬的司機中是否有工作場所與運輸淘汰母豬的司機在一個地方的。目前沒有一項調查（並且也永遠不會有）能夠涵蓋每一個農場在所有情況下的所有重要信息。這也是為什麼大型觀察性研究（通過調查收集關於生物安全措施和風險因素的數據）對農場最重要的措施和風險因素給出了相互矛盾的答案(Holtkamp et.al., 2010; Holtkamp et. al., 2012; Bottoms et. al., 2012)。PADRAP系統在組織上也很差，它是根據攜帶病原體的載體（比如卡車和人）以及發生在豬場的事件（比如公豬精液和員工的入場）隨意組合的。 PADRAP對於確定病原體進入豬群的最常見方式並沒有太大幫助。它並沒有幫助優先考慮下一步該把時間和其他資源花在哪裡。My experience with the Production Animal Disease Risk Assessment Program (PADRAP) (Holtkamp et. al., 2012) in the early 2000s left me frustrated. The survey was useful for identifying specific risk factors that were present or absent and specific biosecurity practices that were done or not done. That may have provided some sense of what to fire at; however it offered little in the way of prioritizing (i.e., aiming). In PADRAP, a score was assigned to each response to the questions which conveyed a sense that some risk factors or practices were more important than others. The aggregated risk scores in PADRAP did prove to have some value for predicting herds where introduction of PRRSV, causing outbreaks, occurred more frequently. But the risk scoring system had several shortcomings. First, the score assigned to a specific response was independent of the response to other questions in the survey. For example, the score for not washing livestock trailers between every load of weaned pigs was the same whether the trailer was dedicated to the farm or used to haul pigs from 20 other sow farms. The score for any given response was also independent of a host of other information that was not addressed in the survey. For example, if one of the trailers that hauled weaned pigs was driven by someone who also worked at a market where culls sows were commingled. There is no survey that does, or ever will, account for all of the important information for every farm under every circumstance. That is also why large observational studies where surveys are used to collect data on biosecurity practices and risk factors give conflicting answers about the most significant practices and risk factors on farms (Holtkamp et.al., 2010; Holtkamp et. al., 2012; Bottoms et. al., 2012). PADRAP was also poorly organized according to a haphazard combination of pathogen carrying agents, such as trucks and people, and events, such as entry of semen and entry of employees, which occur on swine farms. PADRAP was not very helpful for identifying the most frequent ways by which pathogens were being introduced into herds. It did not help prioritize where to spend time and other resources next.

方法：不同的方法
Methods: A different approach使用PADRAP的經驗還告訴我，生產者和獸醫最感興趣的是評估生物安全性，並在疫情爆發後採取行動進行改善。面對危機或威脅時反應最迅速是人類的天性。然而，我們不應該等到疫情爆發才去改善生物安全，這是一個很有討論性的話題，但很少有人會採取前瞻性的措施。在愛荷華豬肉生產者協會的資助下，我和我的學生們開發了一種方法，以系統、全面和一致的方式對疫情爆發進行流行病學調查。所產生的方法和用於指導該方法的表單也被證明對進行前瞻性風險評估有價值。Experience with PADRAP also taught me that producers and veterinarians were most interested in assessing biosecurity and taking action to improve it in the aftermath of an outbreak. It is human nature to be most responsive in the face of a crisis or threat. It makes a great talking point to say that we should not wait for an outbreak to improve biosecurity, but it rarely works that way. With funding from the Iowa Pork Producers Association, my students and I developed an approach to conduct epidemiological investigations of outbreaks in a systematic, comprehensive and consistent manner. The resulting approach, and forms used to guide the approach, has also proven valuable for conducting risk assessments prospectively.該方法以流行病學和風險評估為基礎，考慮了豬病原體如何從一個豬群傳播到另一個豬群。由於細菌和病毒病原體不能移動，必須有東西把病原體從一個豬群帶到另一個豬群。「病原載體」一詞適用於任何可能攜帶病毒進入繁殖群的物體、動物或人。病原載體可以通過感染直接傳播病原，也可以通過被病原汙染間接傳播病原。對於疾病爆發的流行病學調查和預期風險評估，目標是確定正在調查或評估的豬場的漏洞。因此，調查或評估是從被調查或評估的豬場的角度進行的。試想一下，你站在農場中央，觀察攜帶病原體進入農場的潛在病原載體。攜帶病原體的病原載體入場，以它們穿過豬場的邊界為界，可以被認定為一個事件。「病原載體入場事件」是指一個或多個潛在病原載體越過豬場邊界（實體邊界或抽象邊界）的事件。病原載體入場事件通常發生在繁殖場，事件包括：公豬精液的交付、替換後備動物的入場、淘汰母豬和公豬的出場、斷奶仔豬離場、死豬處理、飼料入場、垃圾收取、物資入場、員工入場、去豬舍內工作的維修/服務工作人員入場、去豬舍內外工作的維修/服務工作人員入場、訪客入場、食物入場、糞汙處理、其他動物入場（家豬和野豬之外的其他動物）、昆蟲入場、空氣和水入場。某些病原載體入場事件，如空氣和水的進入，是持續不斷的。對於易於觀察和記錄的離散事件，如精液的進入和糞便的處理，可以確定一段時間內的日期或頻率。對於其他離散但不總是能觀察到的情況，如齧齒動物和其他野生動物的進入，可以對它們發生的頻率或密集程度進行主觀評估。The approach developed was based on the basics of epidemiology and risk assessment and considered how swine pathogens are transmitted from one herd to another. Since bacterial and viral pathogens are not capable of locomotion, something must carry the pathogens from one herd to another. The term 「pathogen carrying agent」 was applied to any object, animal, or person that may carry a virus into the breeding herd. A pathogen carrying agent may directly transmit the pathogen by being infected or indirectly by being contaminated with the pathogen. For epidemiological investigations of outbreaks and prospective risk assessments, the objective is to identify vulnerabilities on the farm being investigated or assessed. Therefore, the investigation or assessment is made from the perspective of the farm being investigated or assessed. Imagine standing in the middle of the farm, observing the potential pathogen carrying agents entering the farm. The entry of pathogen carrying agents, delineated by when they cross the outer perimeter of the farm, can be characterized as events. A "carrying agent entry event」 is defined as an event where one or more potential pathogen carrying agents crosses the outer perimeter, physical or abstract, of the swine farm. Carrying agent entry events that typically occur on sow farms include delivery of semen, entry of breeding replacements, removal of cull animals, removal of weaned pigs, disposal of carcasses, delivery of feed, collection of garbage, delivery of supplies, entry of on-farm employees, entry of repair/service personnel working inside barns, entry of repair/service personnel working outside barns, entry of other visitors, entry of food, removal of manure, entry of other animals (non- swine domestic and wild), entry of insects, and entry of air and water. Some carrying agent entry events, such as   entry of air and water, occur continuously. For discrete events that are easily observed and recorded, such as entry of semen and removal of manure, a date(s) or frequency over some period of time can be determined. For others that are discrete but not always observed, such as entry of rodents and other wild animals, a subjective assessment of how frequently or intensively they occur can be made.通過病原載體進入事件組織流行病學調查和風險評估已證明非常有效。目前，PADRAP和許多可用的生物安全風險評估調查都是通過病原載體和載體入場事件的組合來組織的，令人困惑。保持一致是很重要的，可以通過病原載體來統一組織。但是，進入豬場的潛在病原載體太多，根據定義的精細程度，進入母豬場的病原載體有超過100種。通過病原載體組織流行病學調查和風險評估變得勢在必行。Organizing epidemiological investigations and risk assessments by carrying agent entry events has proven to work very well. PADRAP and many of the biosecurity risk assessment surveys available today are confusingly organized by combinations of pathogen carrying agents and carrying agent entry events. It is essential to be consistent. The alternative is to organize them by pathogen carrying agents consistently. However, there are too many potential pathogen carrying agents that enter farms; over one-hundred on sow farms depending on the level of resolution used to define them. Organizing epidemiological investigations and risk assessments by pathogen carrying agents becomes overwhelming.

未完待續

To be continued...

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