開放禽類接種禽流感疫苗對臺灣養殖業禽流感疫情的影響：系統性回顧與數理模式研究

Abstract

背景： 禽流感是家禽重要的病毒性傳染病，其中部分病毒株對於鳥類具有高致病力與高致死率，除了影響鳥類健康之外，也間接造成禽產品的損失。目前，臺灣禽流感防治政策以撲殺與養禽場生物安全措施為主，禁止養殖雞農給家禽接種禽流感疫苗，但究竟接種禽流感疫苗對臺灣養殖業禽流感疫情會造成何種影響目前還不清楚。本研究擬分成兩個部分，第一部分使用文獻回顧與統合分析的方法，系統回顧近十年疫苗對於雞隻的保護效力的研究，第二部分使用動態數理模式 (dynamic model) 分析若開放業者給養殖禽類施打禽流感疫苗，對家禽群體疫情的影響，以利建構最有效之禽流感預防方式與防疫策略，達成控制 高病原性禽流感與維持禽類產品產量的目標。

方法： 本研究預計在評估施打禽流感疫苗對台灣禽流感疫情動態變化，並將分成兩個部分： 第一部分，藉由文獻回顧方法蒐集近年已發表之禽用禽流感疫苗研究，選取符合標準之攻毒實驗的研究數據，將疫苗的保護效力區分成預防感染與預防死亡兩個面向，分別統合出兩面向之禽流感疫苗保護效力參數，並根據疫苗種類、疫苗對於同源與異源病毒株保護效力與施打時間等進行次族群分析。 第二部分，建立傳染病學SAIR模型，模擬禽流感病毒於一假設之20,000隻蛋雞的禽場內的傳播情形，並模擬疫苗介入、具低病原性禽流感交叉保護與不同進雞方式對疫情所造成的影響。

結果： 第一部分文獻回顧與統合分析結果將疫苗的保護效力區分成預防感染與預防死亡，在未考量疫苗種類與是否上市之下，近十年禽流感疫苗對於死亡的保護效力為87%，但存在高異質性(I2=93%)，若將疫苗依照研究技術區分後，可以得到去活化疫苗對於死亡的保護效力為90%且異質性明顯降低(I2=35%)。至於疫苗對於預防感染的保護效力，去活化疫苗對於同源病毒的效力為82%(I2=89%)，至於異源病毒則降為0%(I2=0%)。 第二部分透過動態數理模型（SAIR model）模擬施打疫苗於田野間對於禽流感疫情的影響，其中模型的建構與部分的參數設定根據已發表之國際期刊或流行病學調查結果，疫苗保護效力參數則依據本研究第一部分之結果。若假設一平飼20,000隻蛋雞的農場，在未施打疫苗時疫情於第17天結束，共計造成17.8k隻雞隻死亡，即使有低病原性禽流感對高病原性禽流感的交叉保護效益，死亡數目仍會達到通報標準，而在疫苗覆蓋下可以有效減少死亡數目成280隻（同源疫苗）或4.64k（異源疫苗），但卻會延長疫情持續時間至70天（同源疫苗）或56天（異源疫苗）。考量到養雞場長期營運需要引進新的雞隻，在有施打疫苗的情況下，以每日少量持續進雞會導致疫情持續蔓延，搭配生物安全措施中分批進雞的方式則可終結疫情於該場內並控制死亡數。

討論： 結合兩個部分的結果，疫苗介入可以有效減少單一場內雞隻死亡率，但卻會延長疫情持續時間。其中，同源疫苗的保護力較佳，但卻容易因為缺乏死亡數上升等明顯指標使得農戶無法察覺疫情，造成禽流感疫情無聲的傳播，若進雞方式沒有進行管理（如統進統出或依年齡分批入場），容易使得病毒長期存於田野間。是故疫苗雖對於單一雞場，需要搭配其他生物安全方式才能達到控制高病原性禽流感的目標。

Introduction: Avian influenza is a highly contagious viral disease affecting food-producing poultry (including chickens, ducks, etc.). Currently, Taiwan adopts a mass culling policy and biosecurity to control avian influenza in poultry, and the vaccination of avian influenza is banned. Besides, the effect of vaccines for avian influenza in poultry on the poultry industry is unclear. We would conduct a systematic review and a dynamic mathematical model to analyze how the vaccine for avian influenza affects poultry immunity.

Method: To evaluate the effect of avian influenza vaccines on avian influenza endemic, this study would be divided into two parts: First, to evaluate the vaccine efficacy of avian influenza, we collected the published studies and performed a meta-analysis. Besides, we separated the efficacy for preventing infection and avoiding death and use subgroup analysis for considering different techniques of the vaccines, virus strains of vaccine seed and challenging viruses, and different intervals of the challenge time. In the second part, we would build a SAIR model to predict the transmission of the virus in a proposed layer farm with 20,000 layers, to evaluate the effect of prior infection, intervention of vaccination, or the way to introduction of chickens in the avian influenza epidemic

Result: According to the meta-analysis, the overall vaccine efficacy was 87%, which showed obvious mortality reduction; however, high heterogeneity (93%) existed between studies, and publication bias existed. Subgroup analyses were performed based on the types of vaccines. The efficacy of the majority type of commercial vaccines, inactivated vaccines, was 90% (heterogeneity: I2=35%). Except for reducing mortality, vaccines for avian influenza in poultry can also reduce the risk of infection and the amount of shedding of virus particles after being infected. The efficacy of preventing infection of inactivated vaccine for homologous virus was 82% (heterogeneity: I2=62%), however, for heterologous virus, the vaccine efficacy was 0%. In the part of the dynamic model, we used the SAIR model to stimulate a barn-laid farm with 20,000 egg layers. Without the intervention of vaccination, the predicted dead number from HPAI was 17.8k, and even with the help of the cross-protection of LPAI, still meets the criteria of being reported and culled. As for the intervention of vaccination, the predicted dead number from HPAI could reduce to 280 (100% coverage of homologous vaccine), or 4.64k (100% coverage of heterologous vaccine); and by the day that the HPAI epidemic is extinct (defined as the number of layers in A and I states are both less than 1) would increase to 70 days (100% coverage of homologous vaccine) or 56 days (100% coverage of heterologous vaccine), indicated that after vaccination, the duration of the epidemic becomes longer. In concern of farm management, it’s essential to introduce new poultry into the flock. If using the strategy of continuous introduction, no matter whether administrating the vaccination, the simulating epidemic would persist, however, using the strategy of staged introduction, the epidemic extinct.

Discussion: Combining two parts of analysis, vaccination for layers to decrease the deaths from HPAI is a feasible approach in a certain farm, however, but prolongs the duration of the HPAI epidemic, especially of homologous vaccines, which may lead to the silent spread of HPAI and virus evolution. Therefore, vaccination needs to be implemented along with biosafety procedures (for example, all-in and all-out or the staged introduction), to eradicate the HPAI epidemic in poultry.