牛アカバネ病の疫学的研究 Epidemiological studies on Akabane disease

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著者

    • 白石, 忠昭 シライシ, タダアキ

書誌事項

タイトル

牛アカバネ病の疫学的研究

タイトル別名

Epidemiological studies on Akabane disease

著者名

白石, 忠昭

著者別名

シライシ, タダアキ

学位授与大学

麻布大学

取得学位

獣医学博士

学位授与番号

乙第269号

学位授与年月日

1988-03-09

注記・抄録

博士論文

従来,牛の異常産の原因として,感染性のものにはTrichomonas fetus,Campylobacter fetus,Brucella abortus,Leptospira interrogans,牛ウイルス性下痢・粘膜病ウイルス(BVD・MDV),牛伝染性鼻気管炎ウイルス,パラインフルエンザウイルス3型などがあり,一方,非感染性のものとしては,遺伝学的致死因子あるいは奇形因子,植物・飼料・農薬などによる中毒,飼育管理の失宜,さらに妊娠期間中のgestagenの失調がよく知られていた。 1972年夏頃から,乳用牛・肉用牛を問わず流産・早産・死産の多発が注目され始め,冬から春にかけては関節彎曲症と内水頭症(A-H症候群)を伴う異常子牛の出産というパターンを示すものが,比較的長期にわたって認められた。1975年,本症はBunyaviridae科のBunyavirus属・SimbuのAkabane Vlrpsによる新しい感染病であることが明らかとなり,Akabane diseaseと呼称されることとなった。 アカバネ病の発生はオーストラリア,イスラエルでも報告されているが,わが国でも本症と類似の疾病が1949~1950年,1959~1960年および1964~1967年の3度にわたって発生していた経緯がある。 このようなことから,著者はアカバネ病の発生実態を解明する目的で,野外における異常産の発生とアカバネ病の伝播,流行との関係を血清疫学的に精査し,牛の抗体保有率の低下とアカバネ病の発生が密接に関連していることを明らかにした。 本研究の概要は次のとおりである。1. 牛異常産の発生状況 1972年8月から1986年3月までの14年間にわたり島根県下の牛(乳用牛,肉用牛)について,.異常産の発生状況を調査した。14年間の異常産母牛延頭数は4,509頭で,年次別発生頭数は,1972年;403頭,1973年;503頭,1974年;441頭,1975年;186頭,1976年;119頭,1977年;699頭,1978年;245頭,1979年;290頭,1980年;181頭,1981年;191頭,1982年;331頭,1983年;489頭,1984年;313頭,1985年;118頭であった。 そこで,肉用牛(黒毛和種)における子牛生産頭数に対する異常産発生率を求めたところ異常産発生率は異常産発生頭数の多かった年が高く,発生頭数の少なかった年が低かった。すなわち,発生頭数の多かった1972年;3.19%,1973年;2.42%,1974年;1.82%,1977年;2.69%,1978年;1.39%,1979年;1.66%,1982年;1.73%.1983年;2.14%.1984年;1.74%と高率であった。 異常産の発生には周期性が認められ,1972~1974年度,1977~1979年度および1982~1984年度に多発傾向を示し,発生周期は5年であった。 異常産多発年度における発生状況には季節性が認められ,秋季~冬季に多発し,特に1月から4月をピークとするA-H症候群を示す先天性異常子牛の出産を特徴とした。2. 野外発生例の病理学的・微生物学的・血清疫学的検索 1972年8月から1986年7月までの14年間に原因検索のために送付された流死産例;205例,先天性異常例;200例計405例を中心にして,病理,細菌および血清疫学的検索などを行った。 病理学的検索は流死産胎子;96例,先天性異常子牛;91例について,病理解剖学的および病理組織学的検査を実施した結果,発生例の主要な病理学的所見としては,流死産胎子では胸腹水の貯溜,内臓の脆弱化,皮下の膠様浸潤,皮下および内臓の出血などがみられ,異常子牛では脳水腫,関節彎曲症,関節機能障害および小眼球症などであった。 微生物学的検索は流死産胎子,先天性異常子牛およびこれらの臓器,胎膜,母牛の悪露,腟粘液などの150例について細菌検査を実施した結果,異常産に関与したとみなすべき純培養状の分離例は49例(32.7%)で,分離菌はE.coliが27例でもっとも多く,次いでStreptococcusとActinomycesの各4例,Proteusの3例,EnterobacterとPseudomonasの各2例などであった。 アカバネウイルス抗体の検索は,異常産母牛血清;370例,先天性異常子牛および流死産胎子;198例について中和試験を実施した結果,異常産母牛血清では240例(64.9%),異常子牛血清および流死産胎子心血では119例(60.1%)が抗体陽性であった。 アカバネ病の流行とベクターとの関連から,1972~1985年までの14年間にわたる気象条件を県東部(松江気象台)および県西部(浜田測候所)について,毎年8~10月の3か月間の月別平均気温と月間降水量を島根県農業気象年報から引用した。また,異常産発生と牛の遺伝的要因を検討する目的で,発生例の交配種雄牛との関係の有無について,3代の血統を調べ近交係数を求めた。その他の異常産要因としては,飼料添加剤・給与飼料・農薬・肥料などの影響についても調査し,その他,BVD・MDVの中和抗体についても検索した。 アカバネ病の流行における年次および地域差は,抗体保有率の差のみによるとは考え難く,ベクター発生の大小の関与が疑われたので,アカバネ病の流行期である8~10月の3か月間の月別平均気温と月間降水量を調べた結果,高温と寡雨はアカバネ病の有力なべクターの1つと考えられているCulicoides oxystoma(ウシヌカカ)の活動,ひいてはウイルスの伝播に好適な条件となり得るものと判断された。 以上の検査成績から,野外発生例405例(流死産例;205例,先天性異常例;200例)を発生要因別に区分すれば,アカバネ病;103例(25.4%),遺伝的奇形;55例(13.6%),細菌感染;49例(12.1%),BVD・MDV感染;3例(0.7%),アイノウイルス感染;1例(0.2%),原因不明;194例(47.9%)で,アカバネ病によるものが,圧倒的に多かった。3. アカバネウイルスの抗体保有率 アカバネウイルスの抗体保有率については,1974~1985年の12年間にプルセラ病検査用に採取された乳用牛血清のうち,毎年,1,0000~2,000例を県下全域から無作為に抽出した19,531例を用い,中和抗体価を測定した。 抗体保有率と牛異常産発生頭数およびアカバネ病の流行との関係を検討するとともに,抗体保有率を正産牛と異常産牛別,異常産内訳別,年齢別,地域別および農家別に比較した。また,一部の牛群については,2~3年間にわたり,抗体価の推移を追跡した。 正産牛と異常産牛の抗体保有率には差がみられず,妊娠中にアカバネウイルスの感染を受けても必ずしも異常産を起こすことなく,不顕性感染が多いことがうかがわれた。このことはアカバネ病の非流行地から導入され,妊娠中に本ウイルスの感染を受けた牛群の分娩成績からも裏付けられ,また,感染時の胎齢と異常産発生との間に密接な関係が見られた。 異常産母牛の異常産内訳別抗体保有率の比較では,先天性異常子牛分娩母牛の抗体保有率が流産および死産母牛よりも高く,アカバネ病による異常産は,A-H症候群などを示す先天性異常との関連性が強いものとみなされた。 年齢別抗体保有率の比較では,本病流行前に生まれたものと流行後に生まれたものとの間に差がみられ,流行前に生まれたものが,流行後に生まれたものより高かった。また,地域別抗体保有率の比較では,アカバネ病流行直後の1974年および1978年とも,県西部が県東部より明らかに高く,地域差がみられた。 アカバネ病抗体保有率の年次別推移は,異常産発生に関連した傾向が認められ,抗体保有率が30%以下に減少した1977~1979年および1982~1984年に本病の再流行が起こり,異常産が多発したが,その周期は概ね5年であった。 アカバネ病抗体陽性牛147頭の抗体価の推移を,2~3年にわたって追跡した結果,抗体価の低下を認めなかったことから,自然感染牛の抗体は急速に消失することなく,長期間持続するものと判断された。4. アカバネ病の流行と飼養牛の更新率との関係 1979~1985年の7年間にわたって,毎年,100頭前後の「おとり牛」を配置し,アカバネ病の流行調査を行った結果,抗体陽転は毎年認められたが,年次により抗体陽転率に差が認められ,抗体陽転率が高かった1979年および1982~1984年に,異常産が多発した。 飼養牛の更新率については、1982~1986年の5か年にわたって,184戸の酪農家を対象に調査した結果,1年間に26.0%の牛が更新されていた。 以上に述べた成績から,牛異常産の発生とアカバネ病との関連性は,以下のとおり結論づけられた。 牛異常産の発生要因は多岐にわたるものの,主要な原因はアカバネ病によるものと判断され,異常産は概ね5年の周期で多発した。異常産の多発はアカバネ病によることが確認され,本病の流行に周期性が認められる要因として,牛の抗体保有率の低下との密接な関連性が明らかになり,抗体保有率が30%以下に減少すると,アカバネウイルスの再流行が起こり,異常産が多発した。 また,アカバネ病自然感染牛の抗体は,急速に消失することなく,長期間持続したことから,抗体保有率の減少は,同一個体の抗体陰転によるものとは考えられず,1年間に飼養牛の26%が更新されることに伴い,抗体陽性牛が淘汰されることによるものと判断された。 さらに,「おとり牛」によるアカバネ病の流行調査において,抗体陽転が毎年認められたことから,アカバネウイルスの流行期には毎年,ウイルスとベクターが存在するものと判断されたが,年次により抗体陽転率に著しい差が認められた。このような流行の年次および地域差は,牛の抗体保有率の高低によるのみとは考え難かったので,ベクターとの関係から気象条件を検討した結果,流行期における気温および降水量の影響が示唆され,アカバネ病の流行期である8~10月の高温と寡雨は,本病の有力なベクターの1つと考えられているウシヌカカの活動,ひいてはウイルスの伝播に好適な条件となり得るものと思われた。

Up to this time the following microorganisms have been regarded as causes of abnormal births of infectious nature in cattle: bovine viral diarrhea mucosal disease virus (B VD•MDV), Brucella abortus, Campylobacter fetus, Infectious bovine rhinotracheitis (IBR), Leptospira interrogans, Parainfluenza virus type 3, and Trichomonas fetus. On the hand as noninfectious causes of bovine abnormal births, the following factors have been well known: genetical fatal factor or teratogenic factor, the inappropriate feeding and management, poisoning of plants, feeds, and agricultural chemicals, and the unbalance in secretion of gestagen during the period of pregnancy. Around the summer of 1972 abortion, premature birth, and stillbirth began to occur frequently among dairy and beef cows. During a relatively long period in the winter and spring that followed, abnormal calves affected with the arthrogryposis-hydranencephaly (A-H) syndrome were born one after another over a rather long period. In 1975, it was clarified that this syndrome was caused by Akabane virus which belonged to the group Simbu of the genus Bunyavirus of the Family Bunyaviridae. Then, the disease caused by this virus has been i called Akabane disease. Outbreaks of Akabane disease have been reported in Australia and Israel. In Japan, a disease quite similar to this disease is known to have broken out three times up to this time; that is, in 1949 - 1950, in 1959 - 1960, and in 1964 - 1967. Such being the case, a detailed sero-epidemiological survey was conducted to elucidate the actual condition of outbreaks of Akabane disease in Japan. In it, investigation was made on the relationship between an occurrence of abnormalbirth in the field and the transmission or epidemic of Akabane virus. As a result, it was made clear that a decrease in the rate of possession of antibody in cows was closly related with an outbreak of Akabane disease. This paper deals with the outline of the present sero-epidemiological survey. 1. Incidence of bovine abnormal births. A survey on the incidence of abnormal births was conducted on cattle (dairy and beef cows) in Shimane prefecture over a fourteen-year period from august, 1972 to march, 1986. Over this period a total of 4,509 abnormal births were found among dams. Naturally, some dams were involved in more than one abnormal birth. Therefore, the number of abnormal births encountered over this period was larger than the actual number of dams surveyed over the same period. The number of dams involved in abnormal births in each year is as follows: 403 head in the 1972; 503 head in 1973; 441 head in 1974; 186 head in 1975; 119 head in 1976; 699 head in 1977; 245 head in 1978; 290 head in 1979; 181 head in 1980; 191 head in 1981; 331 head in 1982; 489 head in 1983; 313 head in 1984; 118 head in 1985. In beef cows (of the Japanese Black breed), the rate of calves involved in abnormal births to all the calves born alive or dead was determined. It was high in a year when the incidence of abnormal births was high. It was low in a year when this incidence was low. It was 3.19 % in 1972 when the incidence of abnormal births was high. It was 2.42 %, in 1974; 2.69 % in 1977; 1.39 % in 1978; 1.66 % in 1979; 1.73 % in 1982, 2.14 % in 1983; 1.74 % in 1984. The incidence of abnormal births was periodic in nature. It was found that abnormal births showed a tendency to prevail over a period of 1972 to 1974, over a period of 1977 to 1979, and over a period of 1982 to 1984 with a cycle of 5 years. In every year when abnormal births were prevalent, the incidence of these births was proved to be seasonal in nature. It was high over a period of autumn to winter. It was characteristic for birth of congenital abnormal calves manifesting the A-H syndrome to show a peak especially over a period of January to April. 2. Pathological, microbiological, and sero-epidemiological examinations of field cases. Over the fourteen-year period of Augaust, 1972 to July, 1986, a total of 405 specimens were received for etiological investigation. They consisted of 205 specimens of abortion and stillbirth and 200 specimens of congenital abnormalities. They were examined pathologically, bacteriologically, and serologically. A total of 96 aborted and stillborn fetuses and 91 congenitally abnormal calves were examined anatomicopathologically and histopathologically. As a result, main pathological findings of the aborted and stillborn fetuses were the deposition of ascites and pleural effusion, fragility of visceral organs, subcutaneous gelatinous infiltration, and hemorrhage in the subcutaneous tissue and visceral organs. Congenital abnormalities shown in the calves were hydranencephaly, arthrogryposis, articular dysfunction, and microphthalmia. Microbiological examination was coducted on 150 specimens collected from visceral organs and fetal membranes of the aborted and stillborn fetuses and the congenitally abnormal calves, and the lochia and vaginal mucus of dams involved in abnormal births. In the bacteriological examination organisms which were regarded as having participated in the occurrence of abnormal births were isolated in a pure culture from 49 specimens (32.7%). Eschericha coli was isolated most freqvently, or from 27 specimens. Actinomyces, Enterobacter, Proteus, Pseudomonus, and Streptococcus were isolated from 2-4 specimens each. Aeromonas, Listeria, Plesiomonas, Salmonella, and Staphylococcus were isolated from one specimen each. Antibody against Akabane virus was examined in 370 serum samples collected from the dams involved in abnormal births and in 198 serum samples collected from congenitally abnormal calves and the hearts, of aborted and stillborn fetuses. As a result, it was positive in 240 of the former 370 samples (64.9%) and in 119 of the latter 198 samples (60.1%). Then, studies were made on the relationship between an epidemic of Akabane disease and a vector of Akabane virus. In them, climatic conditions in Shimane Prefecture were examined over the fourteen-yera period of 1972 to 1985. The eastern and western parts of the prefecture are in the jurisdiction of the Matsue Weather Station and the Hamada Meteorological Observatory, respectively. Average monthly atmospheric temperature and precipitation in three months, or August to October, were checked every year, by referring to the Annual Agricultural Meteorological Report of Shimane Prefecture. Moreover, to clarify the relationship between the occurrence of abnormal births and hereditary factors of cattle, the pedigree of three generations was examined and determined an inbreeding coefficient. In this manner it was investigated whether there was a relationship between the animals involved in abnormal births and breeding bulls used or not. As miscellaneous causes of abnormal births, additives, a ration fed, agricultural chemicals, and fertilizers were checked. In addition, neutralizing antibodies against BVD•MDV, a virus seemingly participating in the occurrence of abnormal births, and Aino virus were also examined. It was hardly considered that the differences in year and area between any two epidemics of Akabane disease might be derived from the difference in the rate of possession of antibody in cattle concerned. It was then assumed that the occurrence of vectors might be related to some extent with the epidemic. Therefore, atmospheric temperature and precipitation in the epidmic period were examined. High temparature and low precipitation were considered to stimulate the activity of the mosquito, Culicoides oxystoma, which is one of the important vectors for Akabane disease, and consequently the transmission of the virus. In brief, 405 field cases were examined. They consisted of 205 cases of abortion and stillbirth and 200 cases of congenital abnormalities. On the basis of the causes of occurrence, they were classified as follows. Akabane disease in 103 cases (25.4%), hereditary deformity in 55 cases (13.6%), bacterial infection in 44 cases (10.9%), BVD•MDV infection in 3 cases (0.7%), Aino virus infection in one cases (0.3%), and unknown causes in 199 cases (49.1%). The causes of occurrence were diversified. The main cause of occurrence was judged to be Akabane disease. 3. Rate of possession of antibody against Akabane virus. Over a twelve-year period of 1974 to 1985 serum samples were collected from dairy cows in the whole Shimane Prefecture for the brucellosis test. Of them, 1,000 - 2,000 samples were extracted at random every year for a survey on the rate of possession of antibody against Akabane virus. In this manner a total of 19,531 samples were subjiected to the estimation of neutralizing antibody titers. Studies were made on the relationship between the epidemic of Akabane disease and the rate of possession of antibody or the incidence of bovine abnormal births. The rate of possession of antibody was analyzed by cows giving normal birth and those giving abnormal birth, by the type of abnormal birth, by age, by area, and by farm. Besides, a follow-up survey was made on some cow herds for 2 - 3 years to clarify a rise and fall in antibody titer. There was no significant difference in the rate of possession of antibody between cows having given normal birth and those having given abnormal birth. It was assumed that even when pregnant cows contracted infection with Akabane virus, they might not always give abnormal birth, but frequently took a from of inapparent infection. This assumption was supported by the results of parturition of cows which had been introduced from an area free from Akabane disease into another area contaminated with this disease and which had been attacked by the infection during pregnancy. Besides, there was an intimate relationship between the fetal age at the time of infection and the occurrence of abnormal birth. The rate of possession of antibody was compared among cows having given abnormal birth and classified by the type of abnormal birth. It was higher in cows having given birth to congenitally abnormal calves than cows presenting abortion or cows presenting stillbirth. It was considered that there might be a close relationship between the occurrence of abnormal births in Akabane disease and that of congenital abnormalitis manifesting the A-H syndrome. A follow-up survey was conducted on 147 antibody-positive cattle for 2 - 3 year to clarify a rise and fall in antibody titer. A no decrease in antibody titer was noticed in it, it was judged that antibody against Akabane virus developed by spontaneous infection did not decrease in titer rapidly, but remained at a constant level of titer for a long time. There was a tendency for an annual rise and fall in the rate of possession of antibody against Akabane virus to be related with the occurrence of abnormal births of the year. In a year when the rate of possession of antibody was reduced to less than 30%, a re-epidemic of Akabane disease broke out and abnormal births frequently occurred. Such year came almost every five years. 4. Relationship between an epidemic of Akabane disease and the rate of renewal of raising cattle. A survey on epidemic of Akabane disease was conducted every year in the whole Shimane Prefecture by using " decoy cattle." In it, about 100 antibody-negative cattle were distributed in the prefecture and examined for the appearance of antibody twice a year; that is, in May or June, a time before an expected epidemic of the disease, and in November, a time after the epidemic. The rate of renewal of raising cattle was examined on 184 dairy farms in the whole cities, towns, and villages in the jurisdiction of the Izumo Livestock Hygiene Service Center, Prefecture of Shimsne , over a five-year period of 1982 to 1986. In the epidemiological survey on Akabane disease conducted by using " decoy cattle ", a positive conversion of antibody was found every year. There was, however, a large difference in the rate of positive conversion of antibody between any two years. In the year ehen this rate was high, bovine abnormal births frequently occurred. In cattle infected spontaneously with Akabane disease, antibody did not disappear rapidly, but persisted for a long time. Therefore, it was presumed that a decrease in the rate of possession of antibody might have been induced not by a negative conversion of antibody in the same individuals but by the selection of antibody-positive cattle. In the survey on the rate of renewal of raising cattle, it was noticed that this rate was 26% in the course of a year. So that, the selection of antibody-positive cattle was judged to have contributed to the reduction of the rate of possession of antibody among raising cattle.

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