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Risk factors associated with the within-farm transmission of bovine viral diarrhea virus and the incidence of persistently infected cattle on dairy farms from Ibaraki prefecture of Japan
Journal Pre-proof Risk factors associated with the within-farm transmission of bovine viral diarrhea virus and the incidence of persistently infected cattle on dairy farms from Ibaraki prefecture of Japan
Masataka Akagami, Satoko Seki, Yuki Kashima, Kaoru Yamashita, Shoko Oya, Yuki Fujii, Mariko Takayasu, Yuji Yaguchi, Atsushi Suzuki, Yoshiko Ono, Yoshinao Ouchi, Yoko Hayama PII:
S0034-5288(19)30749-0
DOI:
https://doi.org/10.1016/j.rvsc.2020.02.001
Reference:
YRVSC 3969
To appear in:
Research in Veterinary Science
Received date:
26 July 2019
Revised date:
30 December 2019
Accepted date:
10 February 2020
Please cite this article as: M. Akagami, S. Seki, Y. Kashima, et al., Risk factors associated with the within-farm transmission of bovine viral diarrhea virus and the incidence of persistently infected cattle on dairy farms from Ibaraki prefecture of Japan, Research in Veterinary Science (2019), https://doi.org/10.1016/j.rvsc.2020.02.001
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© 2019 Published by Elsevier.
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Risk factors associated with the within-farm trans mission of bovine viral diarrhea virus and the incidence of persistently infected cattle on dairy farms from Ibaraki Prefecture of Japan Masataka Akagamia,b, Satoko Sekia, Yuki Kashimaa, Kaoru Yamashitaa, Shoko Oyaa,
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Yuki Fujiia, Mariko Takayasua, Yuji Yaguchia, Atsushi Suzukia, Yoshiko Onoa,
Ibaraki Prefecture Kenpoku Livestock Hygiene Service Center, Ibaraki, Japan
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Yoshinao Ouchia, Yoko Hayamac,* [email protected]
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Ibaraki Prefecture Kennan Livestock Hygiene Service Center, Ibaraki, Japan Viral Disease and Epidemiology Research Division, National Institute of Animal
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Corresponding author: Viral Disease and Epidemiology Research Division, National
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Health, National Agriculture and Food Research Organization, Ibaraki, Japan.
Institute of Animal Health, National Agriculture and Food Research Organization, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856, Japan. ABSTRACT For understanding the factors affecting bovine viral diarrhea virus (BVDV) transmission, this study investigated the distribution of BVDV and the epidemiological features of persistently infected (PI) cattle in Ibaraki Prefecture of Japan, and identified farm- level risk factors associated with BVDV infection, with a focus on within- farm transmission
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and PI animal detection.
Among all 377 dairy farms, forty- four PI cattle were identified on 22 farms. Thirty-eight and six PI cattle were born on their current farms or purchased, respectively.
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Twenty-six PI cattle were born from pregnancies on their current farms, seven from
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pregnancies in summer pastures, and eight from pregnancies on other farms. The
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within- farm seroprevalence on farms with PI animals was significantly higher than that
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on farms without PI cattle.
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Of 333 farms holding homebred cattle without movement records, antibody-positivity in
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homebred cattle was observed on 194 farms; these cattle were likely infected by within- farm transmission. Herd size, summer pasturing, and BVDV infection status of the nearest dairy farm were risk factors associated with within- farm transmission. Likewise, herd size, summer pasturing, and the proportion of purchased cattle were related to PI animal occurrence.
This study shows the risk of within- farm transmission and occurrence of PI animals after the introduction of BVDV via purchasing and summer pasturing, and illustrates the
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significant role of PI cattle in circulating BVDV. More effective measures for screening BVDV infection and PI animals, including intensive tests targeting moved cattle and newborn calves, and bulk milk surveillance, are required to control the spread of BVDV
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in Japan.
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Key words
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bovine viral diarrhea virus, Japan, persistently infected cattle, risk factors for
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within- farm transmission
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1. Introduction The genus Pestivirus of the family Flaviviridae comprises four recognized species: bovine viral diarrhea virus (BVDV)-1, BVDV-2, classical swine fever virus (CSFV), and border virus (Simmonds et al., 2012). Additionally, putative and unclassified
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species, including Giraffe virus, Pronghorn virus, Bungowannah virus, and HoBi- like
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virus (also referred to as BVDV-3 or atypical bovine pestivirus), have been identified
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recently (Bauermann et al., 2015; Blome et al., 2017).
Pestivirus infection in cattle, BVDV-1 and BVDV-2, are widespread and represent
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major concerns throughout the world (Evans et al., 2019; Gillespie et al., 1960; Houe,
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1999). Bovine viral diarrhea (BVD) caused by BVDV may take an inapparent course or lead to different clinical signs such as fever, diarrhea, transient immunosuppression, decrease in milk yield, respiratory symptoms, and reproductive disease (Houe, 1994; Houe, 2003). The reduction of milk production following reproductive disorders involving abortion and poor breeding performance, and increased mortality of calves due to respiratory disease and weakness, causes a significant economic impact on infected farms (Lindberg, 2003; Ridpath et al., 2010). Furthermore, if a pregnant dam is infected with BVDV, persistently infected (PI) calves may result (Ridpath et al., 2010).
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Many PI cattle suffer from ill- thrift and/or develop fatal mucosal disease (Evans et al, 2019). Because PI cattle continue to excrete large amounts of BVDV throughout their lives, PI cattle are an important source of infection within and between farms (Lindberg,
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2003).
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In Europe, the spread of BVDV infection in the cattle population has mostly been
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caused by BVDV-1 (Lindberg et al., 2006; Yesilbag et al., 2017), although outbreaks of
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BVDV-2 have also been recently reported in Germany and Poland (Gethmann et al., 2015; Polak et al., 2014; Strong et al., 2018). In some European countries, national or
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regional coordinated control and eradication programs for BVDV have already been
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established. These programs, involving mandatory testing of calves using tissue samples as well as bulk milk surveillance, have contributed to decrease numbers of PI cattle and of BVDV infection prevalence, and have accelerated the eradication of BVDV (Houe et al., 2006). In Japan, BVDV infection of cattle is a notifiable disease, and about 100–300 cattle are diagnosed every year (MAFF, 2019).
In Japan various genotypes of BVDV, such as Ia, Ib, Ic, and IIa, are distributed throughout the country. BVDV-1 is the dominant strain (Abe et al., 2016; Matsuno et al.,
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2007; Seki et al., 2008), while no evidence of HoBi- like viruses have been observed according to an investigation of cattle between 2012 and 2017 (Kozasa et al., 2018). Because of the increased number of BVDV infection cases, the Japanese animal health authority, the Ministry of Agriculture, Forestry, and Fisheries (MAFF) strengthened the
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prevention and control measures against BVDV by establishing BVDV control
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guidelines in 2016 (MAFF, 2016). This program relies on accurate identification and
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prompt removal of PI cattle as well as vaccination for prevention of the disease on a
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voluntary basis. Based on the program, prefectural government officers guide farmers to implement appropriate biosecurity for BVDV and encourage them to participate in the
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inspection of cattle for screening BVDV infection.
Risk factors associated with BVDV infection have been actively studied in European countries. Several epidemiological studies have reported that large-scale dairy farms, cattle purchases, summer pasturing, high density dairy farming, and production of dairy calves are risk factors related to generating PI cattle (Amelung et al., 2018; Graham et al., 2013; Presi et al., 2011). Additionally, detection of PI cattle, presence of the pregnant cattle, and the total number of dairy cattle on a farm have been identified as risk factors associated with farm- level infection of BVDV (Humphry et al., 2012;
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Sarrazin et al., 2013). Graham et al. (2016) also revealed that the presence of BVDV infected farms in the neighborhood also posed a risk of local disease spread.
In Japan, epidemiological studies of BVDV have mainly been conducted in Hokkaido
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Prefecture, which is the largest dairy farming area located in the northern part of Japan.
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Hokkaido Prefecture contains almost 40% of dairy farms and 60% dairy cattle in the
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country (MAFF, 2018). Because of the flourishing dairy industry, selling pregnant
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heifers to other prefectures and accepting young cattle from other prefectures for rearing on summer grazing pastures are very common in Hokkaido. To evaluate the control
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measures for BVDV in this region, the effectiveness of mass vaccination, inspection
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prior to communal pasture grazing in summer, and bulk milk herd screening tests have been examined using a scenario tree model (Isoda et al., 2017; Isoda et al., 2019). However, in prefectures other than Hokkaido Prefecture, epidemiological studies for understanding the prevalence of BVDV and occurrence of PI animals, as well as the risk factors associated with BVDV infection, have been inadequate. According to European studies, variation in the background factors affecting BVDV status among the regions, such as BVDV prevalence, quality of veterinary service, and density of dairy farms, may result in differences in regional risk factors (Amelung et al., 2018; Graham et al.,
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2013). Considering the differences in dairy farming between Hokkaido Prefecture and other prefectures in Japan, it is important to understand the factors that influence the risk of BVDV infection at the regional level.
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Therefore, in this study, with a view to establishing effective BVDV control measures
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that is suitable for dairy farm management, we firstly conducted a survey of BVDV,
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targeting dairy cattle in Ibaraki Prefecture, Japan, between 2014 and 2017. Next, based
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on the survey data, the distribution of BVDV and epidemiological features of PI cattle were descriptively analyzed. Furthermore, epidemiological analysis was conducted to
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assess the farm- level risk factors associated with BVDV infection and the occurrence of
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PI animals. We focused on the risks associated with the infection of homebred cattle (i.e., within- farm transmission). Epidemiological analysis was conducted with consideration of herd management, biosecurity measures, and geographical features of the dairy farms.
2. Materials and methods 2.1. Study population and study design
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In Japan, 1,380,000 dairy cattle are raised on 15,700 farms (MAFF, 2018). In this study, we targeted the dairy farms in the Ibaraki Prefecture, located in eastern Japan. In Ibaraki Prefecture, almost 23,800 dairy cattle are raised on 361 farms, as of February 2018, and the numbers of dairy cattle and farms in Ibaraki Prefecture is the eighth-highest in the
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country (MAFF, 2018).
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First, to determine the exposure status on all dairy farms in Ibaraki Prefecture, serum
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samples of dairy cattle (≥ 12-month-old) from 377 dairy farms, which were collected by the local veterinary officers between April 2014 to March 2017, were studied. The
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serum samples were randomly collected on each farm from a sample size that can detect
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more than 10% sero-positive prevalence (26 samples per farm with fewer than 100 animals, and maximum 35 samples per farm with 100 or more animals) (Cannon and Roe, 1982); thus, 9,016 sera were collected. Because these serum samples were collected randomly on each farm, samples from cattle that did not have any movement records (i.e., cattle were born and raised on the same farm) as well as samples from cattle with movement records, including purchase from another farm or sending to and returning from summer pastures, were included. The collected serum samples were tested for anti-BVDV antibody using blocking ELISA (VDPro BVDV ab ELISA,
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Median Diagnostics, Chuncheon, Korea). The serum samples of all dairy cattle on 302 farms that were found to be antibody-positive were subsequently tested for BVDV antigen using sandwich ELISA (IDEXX BVDV ag ELISA, Japan, IDEXX laboratories) (Masuda et al., 2017). BVDV antigen-positive cattle were re-tested after 3 weeks, and
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cattle that were antigen-positive on both tests were diagnosed as PI cattle. On the farms
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where PI cattle were identified, after removal of the PI cattle from the herds, all calves
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born in the ensuing 10 months underwent follow-up tests for BVDV antigen as
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described above.
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The BVDV genotype was distinguished by RT-PCR and restriction fragment length
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polymorphism (RFLP) analysis on the PCR products from PI cattle, based on the protocol of Yamaguchi et al. (1997) and Harpin et al. (1995). This method rapidly discriminates the PCR products of pestivirus from CSFV, BVDV-1, and BVDV-2 using restriction endonucleases (Bgl I and Pst I). Viral RNA was extracted from buffy coat samples collected from PI animals using fully automated instrumentation with an in-tip nucleic acid extractor (magLEAD 12gC; Precision System Science Co., Chiba, Japan). RT-PCR amplification of 5’-UTR was carried out with the published primers 324 and 326 (Vilcek et al., 1994) using the One Step RT-PCR Kit (QIAGEN, Hilden, Germany)
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according to the manufacturer’s instructions. RFLP analysis of amplified PCR products was performed via two-step digestion (Bgl I followed by Pst I). Briefly, viral RNA in which the Bgl I cleavage site was present was designated as CSFV, and viral RNA that was not cleaved was designated as BVDV. Among the BVDV samples, the viral RNA
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with the Pst I cleavage site was determined to be BVDV-1, and the sample that was not
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2.2. Categorization of farm-level status
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cleaved was BVDV-2.
This study focused on the risk of within- farm transmission of BVDV. Thus, in this study,
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“within- farm transmission” was defined as BVDV transmission to homebred cattle
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without movement records. Because we could not determine the infection status of homebred cattle without movement records on farms where all sampled cattle had movement records, these farms were excluded from the epidemiological analysis. Additionally, farms where BVD vaccination had been conducted
were excluded.
Specifically, based on the data of 9,016 sampled cattle, 44 farms, including 5 farms where vaccination was conducted; 22 farms where all sampled cattle were purchased from other farms; and 17 farms where all sampled cattle had records of summer
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pasturing in another region, were excluded, and the remaining 7,969 cattle on 333 farms were used for the epidemiological analysis.
Farm-level status was categorized according to the results of antibody tests and antigen
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tests. When at least one homebred animal without movements record was
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antibody-positive on a farm, the farm was defined as a “BVDV-circulated- farm”. On a
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BVDV-circulated- farm, the infected homebred cattle were recognized as having been
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infected from an infection source on the farm. Among the BVDV-circulated- farms, farms with PI cattle were defined as “PI-farms”. We defined
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“BVDV-non-circulated-farms” as farms on which no seropositive animals were detected
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among the sampled cattle, except for those that were vaccinated and those that had movement records of being purchased or moved for summer pasturing. If all sampled cattle tested antibody-negative, the farm was categorized as a “BVDV antibody-free farm”.
2.3. Collection of epidemiological information To investigate the risk factors associated with the within- farm transmission of BVDV and the occurrence of PI animals, epidemiological information on the dairy farms were
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collected, focusing on the herd management, feeding and biosecurity measures, and geographical features (Table 1). For herd management and biosecurity measures, the farmers were interviewed. Herd management factors included herd size (number of female cattle > 2 years old), proportion of purchased cattle, summer pasturing, and
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presence of other animal species. The herd size was categorized into large-sized or
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small-sized cattle farms, based on the median number of adult cattle (the cut-off value
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for a small-sized farm was fewer than 30 animals).
The use of communal summer pasturing is common in Japan, that is, dairy cattle are
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temporarily sent to and reared on grazing farms in areas with a cool climate suitable for
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dairy cattle during summer, such as Hokkaido Prefecture. Some of the cattle are bred during summer pasturing, mostly via artificial insemination. Because many cattle are gathered on the grazing farm, summer pasturing is considered to be a potential risk factor for BVDV infection. Movement of cattle, such as purchasing and summer pasturing, were obtained from the National Database on Individual Cattle Identification System.
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Feeding and biosecurity measure factors included disinfection of vehicles, use of footbaths, the somatic cell count in milk, the conception rate of the cattle, occurrence of abortion and stillbirth, and control of contact with wild animals.
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In terms of geographical features, geographical information about the farms was
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obtained using the GIS system developed by the prefectural government, and the
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distances from the nearest dairy farm, beef farm, and sheep or goat farm, as well as the
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infection status of BVDV on the nearest dairy farm, were examined.
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Additionally, detailed information about PI cattle, including birth date and place, age at
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diagnosis of PI, and the place where their dam was impregnated (mostly by artificial insemination), were obtained.
2.4. Statistical analysis To assess the risk factors associated with the within-farm transmission of BVDV, BVDV-circulated- farms and BVDV-non-circulated- farms were compared. Likewise, PI-farms and BVDV-antibody- free farms were compared to assess the risk factors associated with the occurrence of PI animals. Initially, a univariable analysis was
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performed using the chi-square or Fisher’s exact test for categorical data and the Mann–Whitney U test for numerical data. Only variables with a p-value < 0.1 and with a pairwise correlation coefficient < 0.5 were entered into the multivariable logistic regression models. The final models were constructed using a manual and backward and
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forward variable selection approach. The goodness-of-fit of the estimated models was
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compared using Akaike’s information criterion (AIC). The models with the smallest
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AIC were deemed to be the best-fitting model. All statistical analyses were conducted
3. Results
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using R version 3.5.2 (R Core Team, 2018).
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3.1 Identification and epidemiological features of PI cattle Forty-four PI cattle were identified on 22 of 377 farms (5.8%). According to the results of the RFLP analysis, 43 cattle were infected with BVDV-1, and there was a single case of infection with BVDV-2. These PI cattle were categorized by month of age: 20 animals (45.5%) were calves < 6- months old, 7 (15.9%) were calves aged 6–12 months, 8 (18.2%) were heifers (12–24-months old) and 9 (20.4%) were milking cows (> 24-months old). In the follow-up test on the PI detected farms, 10 newborn calves on 7 farms were diagnosed as being PI animals. Figure 1 shows the number of PI cattle alive,
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including 34 cattle identified by the survey and 10 cattle identified in the follow- up test, during the period between January 2011 and March 2018. At least 13 PI cattle were present in the prefecture at the start of the survey (April 2014), and a maximum of 19 PI cattle were alive during the study period. One or more PI cattle were raised for seven
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years until the end of the period. Table 2 shows the place of birth of PI cattle and their
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dam. Six PI cattle (13.6%) were introduced from other farms, and 38 PI cattle (86.4%)
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were born on their current farms. In terms of the dams of PI cattle, 4 (9.1%) and 7
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(16.9%) were introduced from farms within or outside the prefecture, respectively; and 33 (75.0%) were born on their current farms. In terms of the location of impregnation of
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the dams of PI cattle, 2 (4.6%) and 13 (29.5%) were impregnated on farms within or
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outside the prefecture, respectively. Among these, 7 were impregnated during summer pasturing. Twenty-nine dams of PI cattle (65.9%) were impregnated on their current farms.
3.2. Sero-prevalence of BVDV Of 333 farms holding homebred cattle without movement records, antibody-positive cattle were observed on 194 farms (58.3%), and these farms were categorized as BVDV-circulated-farms. The remaining 139 farms (41.7%) were antibody-negative,
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except for some sampled cattle that had movement records or vaccinated record, and were categorized as BVDV-non-circulated farms. Among these, on 75 farms (22.5%), BVDV antibody was not detected in any of the sampled cattle, and these were
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categorized as BVDV antibody-free farms.
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Individual level seroprevalence was 29.8% (95% CI: 28.8–30.8%) (Table 3). The
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within- farm seroprevalence was significantly higher on PI-farms (78.6%, 95% CI:
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75.7–81.5%) than on farms in other categories (p < 0.001). In BVDV-non-circulated
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8.0–10.0%) (p < 0.001).
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farms, the within- farm sero-prevalence was significantly lower (9.0%, 95% CI:
3.3. Factors associated with within-farm transmission of BVDV and PI occurrence In the analysis of within-farm transmission of BVDV, three variables—herd size, summer pasturing, and BVDV-infection status of the nearest dairy farm—showed a positive relationship with the within- farm transmission in univariable analysis (p-value < 0.1) and remained in the final multivariable analysis model (Table 4). The results showed that cattle on large-sized farms had a 2.09 times higher risk of being serologically positive to BVDV via within- farm transmission (odds ratio (OR) 2.09, p =
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0.002). Farms that used summer pasturing also had an increased risk of within-farm transmission of BVDV, which was 2.22 times greater compared to those that did not (p = 0.004). When the nearest dairy farm was infected with BVDV, the risk of within- farm transmission increased by 2.07 times (p = 0.003). According to the depth-interviews
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conducted with the farmers, there was some cooperation between farmers in the same
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neighborhood, with regards to looking after their cattle and sharing equipment. For
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example, they reported helping each other with calving difficulties and the dehorning of
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calves.
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Moreover, the following five variables showed a relationship with the occurrence of PI
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cattle, according to univariable analysis: herd size, proportion of purchased cattle, summer pasturing, the BVDV-infection status of the nearest dairy farm, and the distance to the nearest dairy farm with BVDV infection. Multivariable analysis showed that, similar to the results of within-farm transmission analysis, large-sized herds (OR 8.42, p = 0.006) and using summer pasturing (OR 5.80, p = 0.019) significantly increased the risk of the occurrence of PI cattle (Table 4). Increasing the proportion of purchased cattle was also associated with the occurrence of PI cattle (OR 1.06, p = 0.001).
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4. DISCUSSION This study demonstrated the distribution of BVDV and epidemiological features of PI cattle by surveying dairy cattle in the Ibaraki Prefecture of Japan. Furthermore, risk factors associated with the within- farm transmission of BVDV and the occurrence of PI
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cattle were revealed by analysis of features of herd management, biosecurity measures,
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and geography.
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The survey showed that BVDV was circulating on 194 farms (58.3%). On these farms, homebred cattle without movement records appeared to contract infection from the
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infected cattle residing on the farm. Among these BVDV-circulated farms, PI cattle
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were identified on 22 farms (5.8%). The incidence rate of PI cattle in this region was almost similar to that on country-level (7.6%, 95% CI:3.1%–16.4%) (Kameyama et al., 2016). During the period of 2010–2019, one or more PI cattle (maximum, 19 cattle) were raised on the farms in this region. This result indicates that PI cattle are constantly present in this region and that cattle on dairy farms are consistently at risk of exposure to PI cattle and BVDV infection.
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Because of the high level of virus shedding by PI cattle, once PI cattle have been introduced to a farm, a cycle is initiated in which new PI cattle are likely to be born within the farm, resulting in the continued spread of BVDV on the farm (Lindberg, 2003; Yasutomi et al., 2004). The results of our survey demonstrated that the
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within- farm seroprevalence on PI farms (78.6%, 95% CI:75.7–81.5%) was significantly
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higher than that on farms in other categories, suggesting that PI cattle was a significant
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source of BVDV transmission. In the epidemiological investigation of 44 PI cattle, 38
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PI animals (86.4%) and 33 of their dams (75.0%) were born at their current farm. This result suggests that PI newborn calves were constantly being produced on these farms.
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Thus, identifying PI cattle as early as possible and removing them from the herd is
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important for the prevention and control of BVDV transmission within a farm.
Multivariable analysis identified that a large herd size and a high proportion of purchased cattle are significantly associated with the occurrence of PI animals. Several previous studies have demonstrated a significant association between herd size and the risk of BVDV infection (Amelung et al., 2018; Bishop et al., 2010; Graham et al., 2016; Presi et al., 2011). Additionally, the risk of introduction of disease posed by purchasing animals is well-recognized (Amelung et al., 2018; Graham et al., 2016; Kaiser et al.,
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2017). In Japan, dairy farms are growing in farm size, and numerous pregnant cattle are introduced from Hokkaido, the largest dairy farming area in the Japan. Our results suggest that there is a growing risk for the occurrence of PI animals due to the movement of cattle accompanying the upsizing of dairy farms in the Ibaraki Prefecture
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(Kadohira et al., 2006; Yasutomi et al., 2004).
seroconversion to BVDV in
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Summer pasturing was found to be associated with both
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cattle without movement records via within-farm transmission and the occurrence of PI animals in this study. Summer pasturing was also thought to play an important role in
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maintaining and transmitting BVDV in Switzerland (Presi et al., 2011). During summer
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pasturing, many cattle from different farms are kept together, with multiple opportunities for contact. Additionally, most heifers return to their original farms after breeding on the grazing farms. Thus, if infected or PI cattle were kept together on the pasturing farm, transmission of BVDV is highly likely to occur, and cattle pregnant with PI calves return to their home farms. This result strongly suggests that summer pasturing poses a high risk of infection with BVDV and pregnancy with PI calves, causing within-farm transmission and generation of PI cattle after returning to the original farms.
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In terms of risk factors associated with within- farm BVDV transmission, BVDV-infection of the nearest dairy farm was significantly associated with within-farm infection, as was herd size and summer pasturing. In a previous study, the risks posed by
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the presence of BVDV-infected cattle on neighboring farms were identified (Graham et
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al., 2016). Thus, it is possible that BVDV-infection on the neighboring farms is a
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potential risk for introduction of the disease, although the specific transmission
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pathways were not clarified. According to interviews conducted with the farmers in this study, some farmers in the neighborhood cooperated in looking after their cattle and in
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sharing equipment. Thus, these types of indirect transmission via movement of persons
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or equipment might cause transmission of the disease among neighboring farms.
However, BVDV-infection on the nearest dairy farm was not significantly associated with the occurrence of PI animals. Because the temporal window for PI of calves is limited (between 20 and 120 days of gestation (Baker, 1987; Done et al., 1980)), even if BVDV transmission occurs between neighboring farms, it does not seem to relate clearly to the occurrence of PI animals.
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Clinical signs of BVDV infection, such as abortion and still birth, were not significantly associated with the transmission of BVDV infection within farms in this study. This result suggests that detection of circulating BVDV within farms based on clinical signs alone would be difficult (Sarrazin et al., 2013). Furthermore, although a risk of infection
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by other animals, such as beef cattle, sheep, and goats, were not identified in our study,
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these factors should not be disregarded as a potential source of the virus (Braun et al.,
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2014).
In this study, the risk of within- farm transmission following the introduction of BVDV
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via the movement of cattle during purchase and summer pasturing was revealed, and the
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significant role of PI cattle in circulating BVDV within dairy farms were recognized. In order to prevent the introduction and spread of BVDV by PI cattle, it is important to conduct inspections of cattle that are to be introduced to a farm or are to be sent for summer pasturing. In the case of summer pasturing in Hokkaido Prefecture, the cattle are required to undergo voluntary inspection before they are sent to the grazing farms. Thus, the risk of generating PI cattle during summer pasturing is likely to be reduced. On the other hand, if BVDV is maintained within a farm due to the presence of an infection source, such as PI cattle on the farm itself, inspection targeting only the cattle
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to be introduced will not be sufficient to suppress the occurrence of PI animals. In European countries, to detect PI cattle, a surveillance program for calves, using tissue samples (ear notch), has been implemented (Amelung et al., 2018; Houe et al., 2006). However, this surveillance method is not applied in Japan, although the practical use of
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bulk milk screening for BVDV on dairy farms has been investigated (Kozasa et al.,
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2005; Saino et al., 2013). More effective measures for screening BVDV infection and PI
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cattle, such as intensive tests targeting movement cattle and newborn calves, or bulk
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milk surveillance, are required to prevent and control the spread of BVDV in Japan.
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Acknowledgments We thank all of the livestock owners for their cooperation in this study. This work was supported by grant projects related to the promotion of regional research and development by the Ministry of Education, Culture, Sports, Science and Technology in
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Japan.
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Conflicts of interests
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The authors declare that there are no potential conflicts of interest with respect to the
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research, authorship, and/or publication of this article.
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22, 184-191. Saino, H., Kawauchi, K., Usui, A., Ohno, H., Sakoda, Y., Tajima, M., 2013. Implementation and verification of the effectiveness of a regional control program for bovine viral diarrhea virus infection in Hokkaido, Japan. J. Jpn. Vet. Med. Assoc. 66,
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Simmonds, P., Becher, P., Collett, M.S., Gould, E.A., Heinz, F.X., Meyers, G., Monath, T., Pletnev, A., Rice, C.M., Stiasny, K., Thiel, H-J., Weiner, A., Bukh, J., 2012. Family Flaviviridae, in: King, A.M.Q., Adams M.J., Carstens E.B., Lefkowitz E.J. (Eds.), Virus Taxonomy Ninth Report of the International Commitee on Taxonomy of Viruses. Elsevier Academic Press, San Diego. pp. 1003-1020.
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viral diarrhea virus infection with evaluating risk factors. J. Vet. Epidemiol. 8, 77-83. (in Japanese)
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Yesilbag, K., Alpay, G., Becher, P., 2017. Variability and global distribution of
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subgenotypes of bovine viral diarrhea virus. Viruses 9,128.
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Figure legend Figure 1: Number of persistently infected (PI) cattle alive between January 2011 and
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March 2018.
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Table 1 Epidemiological information collected in the bovine diarrhea virus (BVDV) survey on dairy cattle farms
Herd management Proportion of purchased cattle Summer pasturing (Yes/No) Grazing beef cattle or other species (sheep, goats, pigs, horses) (Yes/No) Feeding and biosecurity measures
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Disinfection of vehicle (Yes/No) Use of footbath (Yes/No)
Conception rate in cattle Occurrence of abortion and stillbirth
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Control of contact with wild animals
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Somatic cell count in milk
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Geographical features
Distance from the nearest dairy farm (km) Distance from the nearest beef farm (km)
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Distance from the nearest sheep or goat farm (km)
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Infection status of BVDV on the nearest dairy farm
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Table 2 Number of persistently infected (PI) cattle by their birthplace, their dam's birthplace, and the place of pregnancy
Birthplace of PI
Dam's birthplace
Place of pregnancy
38 (86.4%)
33 (75%)
29 (65.9%)
4 (9.1%)
7 (15.9%)
13 (29.6%)
2 (4.5%)
4 (9.1%)
cattle Current farm Other farms or grazing places outside of Ibaraki
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Prefecture
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Other farms within Ibaraki
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Prefecture
2 (4.5%)
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Table 3 Individual level seroprevalence of bovine diarrhea virus (BVDV)
Farm type
All farms BVDV-circulated-far m*
No. of inspected
No. of positive
Prevalence (95%
farms
animals
animals
CI)**
333
7,969
2,378
172
4,092
1,479
22
790
621
139
3,087
farm
*Persistent infection (PI) farms were excluded.
278
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BVDV-non-circulated
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PI farm
No. of
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**Values sharing a letter are not statistically different.
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95% CI, 95% confidence interval
29.8% (28.8–30.8)a 36.1% (34.7–37.6)a 78.6% (75.7–81.5)b 9.0% (8.0–10.0)c
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Table 4 Results of multivariable logistic regression models for the within-farm transmission of bovine diarrhea virus (BVDV) and the occurrence of persistently infected (PI) cattle Variable
Levels
No. of farms
No. of
(% po
Small (<30 adult cattle)
167
81 (4
Large(≥30 adult cattle)
165
113 (
No
241
127 (
Yes
92
67 (7
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Within-farm transmission of BVDV Farm size
Not infected
105
49 (4
Infected
228
145 (
Small (<30 adult cattle)
53
4(
Large (≥30 adult cattle)
44
18 (
f
Summer pasturing
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Infection status of BVDV on the nearest dairy farm
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Occurrence of PI cattle
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Farm size
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Summer pasturing
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Percentage of purchased cattle
1
(numerical variable) 3 No
80
13 (1
Yes
17
9 (5
Distance from the nearest dairy farm (km)
(numerical variable) 4
Infection status of BVDV on the nearest dairy farm
Not infected
34
5 (1
Infected
63
17 (2
Positive means "seropositive farm" in the model of within-farm transmission BVDV, and "PI farm"
in the model of occurrence of PI cattle. 2
95% CI, 95% confidence interval.
3
Percentages of purchased cattle in PI farm and non-PI farm (median, 2.5 -97.5 percentile) were
th
th
21.7% (0-98.0%) and 0% (0-47.3%), respectively. 4
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Distances from the nearest dairy farm in PI farm and non-PI farm (median, 2.5th-97.5th percentile)
were 1.5 km (0.1-11.0 km) and 0.9 km (0.09-9.1 km), respectively.
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Highlights
Farm- level bovine viral diarrhea virus (BVDV) seroprevalence was 58.3% on dairy farms in Ibaraki Prefecture, Japan Persistently infected (PI) cattle were identified on 5.8% of dairy farms
Herd-size, summer pasturing, and neighboring farm with BVDV-infection were risk
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Herd-size, summer pasturing, and cattle purchases were risk factors for PI animals
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in a herd
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factors for herds being serologically positive
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Masataka Akagami, Satoko Seki, Yuki Kashima, Kaoru Yamashita, Shoko Oya, Yuki Fujii, Mariko Takayasu, Yuji Yaguchi, Atsushi Suzuki, Yoshiko Ono, Yoshinao Ouchi, Yoko Hayama PII:
S0034-5288(19)30749-0
DOI:
https://doi.org/10.1016/j.rvsc.2020.02.001
Reference:
YRVSC 3969
To appear in:
Research in Veterinary Science
Received date:
26 July 2019
Revised date:
30 December 2019
Accepted date:
10 February 2020
Please cite this article as: M. Akagami, S. Seki, Y. Kashima, et al., Risk factors associated with the within-farm transmission of bovine viral diarrhea virus and the incidence of persistently infected cattle on dairy farms from Ibaraki prefecture of Japan, Research in Veterinary Science (2019), https://doi.org/10.1016/j.rvsc.2020.02.001
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© 2019 Published by Elsevier.
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Risk factors associated with the within-farm trans mission of bovine viral diarrhea virus and the incidence of persistently infected cattle on dairy farms from Ibaraki Prefecture of Japan Masataka Akagamia,b, Satoko Sekia, Yuki Kashimaa, Kaoru Yamashitaa, Shoko Oyaa,
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Yuki Fujiia, Mariko Takayasua, Yuji Yaguchia, Atsushi Suzukia, Yoshiko Onoa,
Ibaraki Prefecture Kenpoku Livestock Hygiene Service Center, Ibaraki, Japan
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a
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Yoshinao Ouchia, Yoko Hayamac,* [email protected]
b
c
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Ibaraki Prefecture Kennan Livestock Hygiene Service Center, Ibaraki, Japan Viral Disease and Epidemiology Research Division, National Institute of Animal
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Corresponding author: Viral Disease and Epidemiology Research Division, National
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*
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Health, National Agriculture and Food Research Organization, Ibaraki, Japan.
Institute of Animal Health, National Agriculture and Food Research Organization, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856, Japan. ABSTRACT For understanding the factors affecting bovine viral diarrhea virus (BVDV) transmission, this study investigated the distribution of BVDV and the epidemiological features of persistently infected (PI) cattle in Ibaraki Prefecture of Japan, and identified farm- level risk factors associated with BVDV infection, with a focus on within- farm transmission
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and PI animal detection.
Among all 377 dairy farms, forty- four PI cattle were identified on 22 farms. Thirty-eight and six PI cattle were born on their current farms or purchased, respectively.
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Twenty-six PI cattle were born from pregnancies on their current farms, seven from
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pregnancies in summer pastures, and eight from pregnancies on other farms. The
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within- farm seroprevalence on farms with PI animals was significantly higher than that
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on farms without PI cattle.
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Of 333 farms holding homebred cattle without movement records, antibody-positivity in
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homebred cattle was observed on 194 farms; these cattle were likely infected by within- farm transmission. Herd size, summer pasturing, and BVDV infection status of the nearest dairy farm were risk factors associated with within- farm transmission. Likewise, herd size, summer pasturing, and the proportion of purchased cattle were related to PI animal occurrence.
This study shows the risk of within- farm transmission and occurrence of PI animals after the introduction of BVDV via purchasing and summer pasturing, and illustrates the
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significant role of PI cattle in circulating BVDV. More effective measures for screening BVDV infection and PI animals, including intensive tests targeting moved cattle and newborn calves, and bulk milk surveillance, are required to control the spread of BVDV
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in Japan.
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Key words
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bovine viral diarrhea virus, Japan, persistently infected cattle, risk factors for
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within- farm transmission
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1. Introduction The genus Pestivirus of the family Flaviviridae comprises four recognized species: bovine viral diarrhea virus (BVDV)-1, BVDV-2, classical swine fever virus (CSFV), and border virus (Simmonds et al., 2012). Additionally, putative and unclassified
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species, including Giraffe virus, Pronghorn virus, Bungowannah virus, and HoBi- like
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virus (also referred to as BVDV-3 or atypical bovine pestivirus), have been identified
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recently (Bauermann et al., 2015; Blome et al., 2017).
Pestivirus infection in cattle, BVDV-1 and BVDV-2, are widespread and represent
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major concerns throughout the world (Evans et al., 2019; Gillespie et al., 1960; Houe,
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1999). Bovine viral diarrhea (BVD) caused by BVDV may take an inapparent course or lead to different clinical signs such as fever, diarrhea, transient immunosuppression, decrease in milk yield, respiratory symptoms, and reproductive disease (Houe, 1994; Houe, 2003). The reduction of milk production following reproductive disorders involving abortion and poor breeding performance, and increased mortality of calves due to respiratory disease and weakness, causes a significant economic impact on infected farms (Lindberg, 2003; Ridpath et al., 2010). Furthermore, if a pregnant dam is infected with BVDV, persistently infected (PI) calves may result (Ridpath et al., 2010).
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Many PI cattle suffer from ill- thrift and/or develop fatal mucosal disease (Evans et al, 2019). Because PI cattle continue to excrete large amounts of BVDV throughout their lives, PI cattle are an important source of infection within and between farms (Lindberg,
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2003).
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In Europe, the spread of BVDV infection in the cattle population has mostly been
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caused by BVDV-1 (Lindberg et al., 2006; Yesilbag et al., 2017), although outbreaks of
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BVDV-2 have also been recently reported in Germany and Poland (Gethmann et al., 2015; Polak et al., 2014; Strong et al., 2018). In some European countries, national or
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regional coordinated control and eradication programs for BVDV have already been
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established. These programs, involving mandatory testing of calves using tissue samples as well as bulk milk surveillance, have contributed to decrease numbers of PI cattle and of BVDV infection prevalence, and have accelerated the eradication of BVDV (Houe et al., 2006). In Japan, BVDV infection of cattle is a notifiable disease, and about 100–300 cattle are diagnosed every year (MAFF, 2019).
In Japan various genotypes of BVDV, such as Ia, Ib, Ic, and IIa, are distributed throughout the country. BVDV-1 is the dominant strain (Abe et al., 2016; Matsuno et al.,
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2007; Seki et al., 2008), while no evidence of HoBi- like viruses have been observed according to an investigation of cattle between 2012 and 2017 (Kozasa et al., 2018). Because of the increased number of BVDV infection cases, the Japanese animal health authority, the Ministry of Agriculture, Forestry, and Fisheries (MAFF) strengthened the
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prevention and control measures against BVDV by establishing BVDV control
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guidelines in 2016 (MAFF, 2016). This program relies on accurate identification and
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prompt removal of PI cattle as well as vaccination for prevention of the disease on a
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voluntary basis. Based on the program, prefectural government officers guide farmers to implement appropriate biosecurity for BVDV and encourage them to participate in the
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inspection of cattle for screening BVDV infection.
Risk factors associated with BVDV infection have been actively studied in European countries. Several epidemiological studies have reported that large-scale dairy farms, cattle purchases, summer pasturing, high density dairy farming, and production of dairy calves are risk factors related to generating PI cattle (Amelung et al., 2018; Graham et al., 2013; Presi et al., 2011). Additionally, detection of PI cattle, presence of the pregnant cattle, and the total number of dairy cattle on a farm have been identified as risk factors associated with farm- level infection of BVDV (Humphry et al., 2012;
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Sarrazin et al., 2013). Graham et al. (2016) also revealed that the presence of BVDV infected farms in the neighborhood also posed a risk of local disease spread.
In Japan, epidemiological studies of BVDV have mainly been conducted in Hokkaido
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Prefecture, which is the largest dairy farming area located in the northern part of Japan.
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Hokkaido Prefecture contains almost 40% of dairy farms and 60% dairy cattle in the
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country (MAFF, 2018). Because of the flourishing dairy industry, selling pregnant
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heifers to other prefectures and accepting young cattle from other prefectures for rearing on summer grazing pastures are very common in Hokkaido. To evaluate the control
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measures for BVDV in this region, the effectiveness of mass vaccination, inspection
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prior to communal pasture grazing in summer, and bulk milk herd screening tests have been examined using a scenario tree model (Isoda et al., 2017; Isoda et al., 2019). However, in prefectures other than Hokkaido Prefecture, epidemiological studies for understanding the prevalence of BVDV and occurrence of PI animals, as well as the risk factors associated with BVDV infection, have been inadequate. According to European studies, variation in the background factors affecting BVDV status among the regions, such as BVDV prevalence, quality of veterinary service, and density of dairy farms, may result in differences in regional risk factors (Amelung et al., 2018; Graham et al.,
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2013). Considering the differences in dairy farming between Hokkaido Prefecture and other prefectures in Japan, it is important to understand the factors that influence the risk of BVDV infection at the regional level.
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Therefore, in this study, with a view to establishing effective BVDV control measures
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that is suitable for dairy farm management, we firstly conducted a survey of BVDV,
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targeting dairy cattle in Ibaraki Prefecture, Japan, between 2014 and 2017. Next, based
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on the survey data, the distribution of BVDV and epidemiological features of PI cattle were descriptively analyzed. Furthermore, epidemiological analysis was conducted to
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assess the farm- level risk factors associated with BVDV infection and the occurrence of
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PI animals. We focused on the risks associated with the infection of homebred cattle (i.e., within- farm transmission). Epidemiological analysis was conducted with consideration of herd management, biosecurity measures, and geographical features of the dairy farms.
2. Materials and methods 2.1. Study population and study design
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In Japan, 1,380,000 dairy cattle are raised on 15,700 farms (MAFF, 2018). In this study, we targeted the dairy farms in the Ibaraki Prefecture, located in eastern Japan. In Ibaraki Prefecture, almost 23,800 dairy cattle are raised on 361 farms, as of February 2018, and the numbers of dairy cattle and farms in Ibaraki Prefecture is the eighth-highest in the
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country (MAFF, 2018).
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First, to determine the exposure status on all dairy farms in Ibaraki Prefecture, serum
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samples of dairy cattle (≥ 12-month-old) from 377 dairy farms, which were collected by the local veterinary officers between April 2014 to March 2017, were studied. The
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serum samples were randomly collected on each farm from a sample size that can detect
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more than 10% sero-positive prevalence (26 samples per farm with fewer than 100 animals, and maximum 35 samples per farm with 100 or more animals) (Cannon and Roe, 1982); thus, 9,016 sera were collected. Because these serum samples were collected randomly on each farm, samples from cattle that did not have any movement records (i.e., cattle were born and raised on the same farm) as well as samples from cattle with movement records, including purchase from another farm or sending to and returning from summer pastures, were included. The collected serum samples were tested for anti-BVDV antibody using blocking ELISA (VDPro BVDV ab ELISA,
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Median Diagnostics, Chuncheon, Korea). The serum samples of all dairy cattle on 302 farms that were found to be antibody-positive were subsequently tested for BVDV antigen using sandwich ELISA (IDEXX BVDV ag ELISA, Japan, IDEXX laboratories) (Masuda et al., 2017). BVDV antigen-positive cattle were re-tested after 3 weeks, and
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cattle that were antigen-positive on both tests were diagnosed as PI cattle. On the farms
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where PI cattle were identified, after removal of the PI cattle from the herds, all calves
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born in the ensuing 10 months underwent follow-up tests for BVDV antigen as
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described above.
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The BVDV genotype was distinguished by RT-PCR and restriction fragment length
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polymorphism (RFLP) analysis on the PCR products from PI cattle, based on the protocol of Yamaguchi et al. (1997) and Harpin et al. (1995). This method rapidly discriminates the PCR products of pestivirus from CSFV, BVDV-1, and BVDV-2 using restriction endonucleases (Bgl I and Pst I). Viral RNA was extracted from buffy coat samples collected from PI animals using fully automated instrumentation with an in-tip nucleic acid extractor (magLEAD 12gC; Precision System Science Co., Chiba, Japan). RT-PCR amplification of 5’-UTR was carried out with the published primers 324 and 326 (Vilcek et al., 1994) using the One Step RT-PCR Kit (QIAGEN, Hilden, Germany)
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according to the manufacturer’s instructions. RFLP analysis of amplified PCR products was performed via two-step digestion (Bgl I followed by Pst I). Briefly, viral RNA in which the Bgl I cleavage site was present was designated as CSFV, and viral RNA that was not cleaved was designated as BVDV. Among the BVDV samples, the viral RNA
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with the Pst I cleavage site was determined to be BVDV-1, and the sample that was not
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2.2. Categorization of farm-level status
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cleaved was BVDV-2.
This study focused on the risk of within- farm transmission of BVDV. Thus, in this study,
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“within- farm transmission” was defined as BVDV transmission to homebred cattle
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without movement records. Because we could not determine the infection status of homebred cattle without movement records on farms where all sampled cattle had movement records, these farms were excluded from the epidemiological analysis. Additionally, farms where BVD vaccination had been conducted
were excluded.
Specifically, based on the data of 9,016 sampled cattle, 44 farms, including 5 farms where vaccination was conducted; 22 farms where all sampled cattle were purchased from other farms; and 17 farms where all sampled cattle had records of summer
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pasturing in another region, were excluded, and the remaining 7,969 cattle on 333 farms were used for the epidemiological analysis.
Farm-level status was categorized according to the results of antibody tests and antigen
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tests. When at least one homebred animal without movements record was
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antibody-positive on a farm, the farm was defined as a “BVDV-circulated- farm”. On a
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BVDV-circulated- farm, the infected homebred cattle were recognized as having been
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infected from an infection source on the farm. Among the BVDV-circulated- farms, farms with PI cattle were defined as “PI-farms”. We defined
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“BVDV-non-circulated-farms” as farms on which no seropositive animals were detected
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among the sampled cattle, except for those that were vaccinated and those that had movement records of being purchased or moved for summer pasturing. If all sampled cattle tested antibody-negative, the farm was categorized as a “BVDV antibody-free farm”.
2.3. Collection of epidemiological information To investigate the risk factors associated with the within- farm transmission of BVDV and the occurrence of PI animals, epidemiological information on the dairy farms were
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collected, focusing on the herd management, feeding and biosecurity measures, and geographical features (Table 1). For herd management and biosecurity measures, the farmers were interviewed. Herd management factors included herd size (number of female cattle > 2 years old), proportion of purchased cattle, summer pasturing, and
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presence of other animal species. The herd size was categorized into large-sized or
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small-sized cattle farms, based on the median number of adult cattle (the cut-off value
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for a small-sized farm was fewer than 30 animals).
The use of communal summer pasturing is common in Japan, that is, dairy cattle are
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temporarily sent to and reared on grazing farms in areas with a cool climate suitable for
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dairy cattle during summer, such as Hokkaido Prefecture. Some of the cattle are bred during summer pasturing, mostly via artificial insemination. Because many cattle are gathered on the grazing farm, summer pasturing is considered to be a potential risk factor for BVDV infection. Movement of cattle, such as purchasing and summer pasturing, were obtained from the National Database on Individual Cattle Identification System.
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Feeding and biosecurity measure factors included disinfection of vehicles, use of footbaths, the somatic cell count in milk, the conception rate of the cattle, occurrence of abortion and stillbirth, and control of contact with wild animals.
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In terms of geographical features, geographical information about the farms was
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obtained using the GIS system developed by the prefectural government, and the
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distances from the nearest dairy farm, beef farm, and sheep or goat farm, as well as the
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infection status of BVDV on the nearest dairy farm, were examined.
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Additionally, detailed information about PI cattle, including birth date and place, age at
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diagnosis of PI, and the place where their dam was impregnated (mostly by artificial insemination), were obtained.
2.4. Statistical analysis To assess the risk factors associated with the within-farm transmission of BVDV, BVDV-circulated- farms and BVDV-non-circulated- farms were compared. Likewise, PI-farms and BVDV-antibody- free farms were compared to assess the risk factors associated with the occurrence of PI animals. Initially, a univariable analysis was
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performed using the chi-square or Fisher’s exact test for categorical data and the Mann–Whitney U test for numerical data. Only variables with a p-value < 0.1 and with a pairwise correlation coefficient < 0.5 were entered into the multivariable logistic regression models. The final models were constructed using a manual and backward and
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forward variable selection approach. The goodness-of-fit of the estimated models was
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compared using Akaike’s information criterion (AIC). The models with the smallest
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AIC were deemed to be the best-fitting model. All statistical analyses were conducted
3. Results
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using R version 3.5.2 (R Core Team, 2018).
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3.1 Identification and epidemiological features of PI cattle Forty-four PI cattle were identified on 22 of 377 farms (5.8%). According to the results of the RFLP analysis, 43 cattle were infected with BVDV-1, and there was a single case of infection with BVDV-2. These PI cattle were categorized by month of age: 20 animals (45.5%) were calves < 6- months old, 7 (15.9%) were calves aged 6–12 months, 8 (18.2%) were heifers (12–24-months old) and 9 (20.4%) were milking cows (> 24-months old). In the follow-up test on the PI detected farms, 10 newborn calves on 7 farms were diagnosed as being PI animals. Figure 1 shows the number of PI cattle alive,
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including 34 cattle identified by the survey and 10 cattle identified in the follow- up test, during the period between January 2011 and March 2018. At least 13 PI cattle were present in the prefecture at the start of the survey (April 2014), and a maximum of 19 PI cattle were alive during the study period. One or more PI cattle were raised for seven
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years until the end of the period. Table 2 shows the place of birth of PI cattle and their
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dam. Six PI cattle (13.6%) were introduced from other farms, and 38 PI cattle (86.4%)
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were born on their current farms. In terms of the dams of PI cattle, 4 (9.1%) and 7
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(16.9%) were introduced from farms within or outside the prefecture, respectively; and 33 (75.0%) were born on their current farms. In terms of the location of impregnation of
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the dams of PI cattle, 2 (4.6%) and 13 (29.5%) were impregnated on farms within or
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outside the prefecture, respectively. Among these, 7 were impregnated during summer pasturing. Twenty-nine dams of PI cattle (65.9%) were impregnated on their current farms.
3.2. Sero-prevalence of BVDV Of 333 farms holding homebred cattle without movement records, antibody-positive cattle were observed on 194 farms (58.3%), and these farms were categorized as BVDV-circulated-farms. The remaining 139 farms (41.7%) were antibody-negative,
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except for some sampled cattle that had movement records or vaccinated record, and were categorized as BVDV-non-circulated farms. Among these, on 75 farms (22.5%), BVDV antibody was not detected in any of the sampled cattle, and these were
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categorized as BVDV antibody-free farms.
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Individual level seroprevalence was 29.8% (95% CI: 28.8–30.8%) (Table 3). The
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within- farm seroprevalence was significantly higher on PI-farms (78.6%, 95% CI:
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75.7–81.5%) than on farms in other categories (p < 0.001). In BVDV-non-circulated
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8.0–10.0%) (p < 0.001).
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farms, the within- farm sero-prevalence was significantly lower (9.0%, 95% CI:
3.3. Factors associated with within-farm transmission of BVDV and PI occurrence In the analysis of within-farm transmission of BVDV, three variables—herd size, summer pasturing, and BVDV-infection status of the nearest dairy farm—showed a positive relationship with the within- farm transmission in univariable analysis (p-value < 0.1) and remained in the final multivariable analysis model (Table 4). The results showed that cattle on large-sized farms had a 2.09 times higher risk of being serologically positive to BVDV via within- farm transmission (odds ratio (OR) 2.09, p =
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0.002). Farms that used summer pasturing also had an increased risk of within-farm transmission of BVDV, which was 2.22 times greater compared to those that did not (p = 0.004). When the nearest dairy farm was infected with BVDV, the risk of within- farm transmission increased by 2.07 times (p = 0.003). According to the depth-interviews
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conducted with the farmers, there was some cooperation between farmers in the same
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neighborhood, with regards to looking after their cattle and sharing equipment. For
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example, they reported helping each other with calving difficulties and the dehorning of
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calves.
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Moreover, the following five variables showed a relationship with the occurrence of PI
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cattle, according to univariable analysis: herd size, proportion of purchased cattle, summer pasturing, the BVDV-infection status of the nearest dairy farm, and the distance to the nearest dairy farm with BVDV infection. Multivariable analysis showed that, similar to the results of within-farm transmission analysis, large-sized herds (OR 8.42, p = 0.006) and using summer pasturing (OR 5.80, p = 0.019) significantly increased the risk of the occurrence of PI cattle (Table 4). Increasing the proportion of purchased cattle was also associated with the occurrence of PI cattle (OR 1.06, p = 0.001).
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4. DISCUSSION This study demonstrated the distribution of BVDV and epidemiological features of PI cattle by surveying dairy cattle in the Ibaraki Prefecture of Japan. Furthermore, risk factors associated with the within- farm transmission of BVDV and the occurrence of PI
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cattle were revealed by analysis of features of herd management, biosecurity measures,
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and geography.
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The survey showed that BVDV was circulating on 194 farms (58.3%). On these farms, homebred cattle without movement records appeared to contract infection from the
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infected cattle residing on the farm. Among these BVDV-circulated farms, PI cattle
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were identified on 22 farms (5.8%). The incidence rate of PI cattle in this region was almost similar to that on country-level (7.6%, 95% CI:3.1%–16.4%) (Kameyama et al., 2016). During the period of 2010–2019, one or more PI cattle (maximum, 19 cattle) were raised on the farms in this region. This result indicates that PI cattle are constantly present in this region and that cattle on dairy farms are consistently at risk of exposure to PI cattle and BVDV infection.
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Because of the high level of virus shedding by PI cattle, once PI cattle have been introduced to a farm, a cycle is initiated in which new PI cattle are likely to be born within the farm, resulting in the continued spread of BVDV on the farm (Lindberg, 2003; Yasutomi et al., 2004). The results of our survey demonstrated that the
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within- farm seroprevalence on PI farms (78.6%, 95% CI:75.7–81.5%) was significantly
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higher than that on farms in other categories, suggesting that PI cattle was a significant
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source of BVDV transmission. In the epidemiological investigation of 44 PI cattle, 38
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PI animals (86.4%) and 33 of their dams (75.0%) were born at their current farm. This result suggests that PI newborn calves were constantly being produced on these farms.
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Thus, identifying PI cattle as early as possible and removing them from the herd is
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important for the prevention and control of BVDV transmission within a farm.
Multivariable analysis identified that a large herd size and a high proportion of purchased cattle are significantly associated with the occurrence of PI animals. Several previous studies have demonstrated a significant association between herd size and the risk of BVDV infection (Amelung et al., 2018; Bishop et al., 2010; Graham et al., 2016; Presi et al., 2011). Additionally, the risk of introduction of disease posed by purchasing animals is well-recognized (Amelung et al., 2018; Graham et al., 2016; Kaiser et al.,
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2017). In Japan, dairy farms are growing in farm size, and numerous pregnant cattle are introduced from Hokkaido, the largest dairy farming area in the Japan. Our results suggest that there is a growing risk for the occurrence of PI animals due to the movement of cattle accompanying the upsizing of dairy farms in the Ibaraki Prefecture
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(Kadohira et al., 2006; Yasutomi et al., 2004).
seroconversion to BVDV in
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Summer pasturing was found to be associated with both
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cattle without movement records via within-farm transmission and the occurrence of PI animals in this study. Summer pasturing was also thought to play an important role in
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maintaining and transmitting BVDV in Switzerland (Presi et al., 2011). During summer
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pasturing, many cattle from different farms are kept together, with multiple opportunities for contact. Additionally, most heifers return to their original farms after breeding on the grazing farms. Thus, if infected or PI cattle were kept together on the pasturing farm, transmission of BVDV is highly likely to occur, and cattle pregnant with PI calves return to their home farms. This result strongly suggests that summer pasturing poses a high risk of infection with BVDV and pregnancy with PI calves, causing within-farm transmission and generation of PI cattle after returning to the original farms.
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In terms of risk factors associated with within- farm BVDV transmission, BVDV-infection of the nearest dairy farm was significantly associated with within-farm infection, as was herd size and summer pasturing. In a previous study, the risks posed by
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the presence of BVDV-infected cattle on neighboring farms were identified (Graham et
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al., 2016). Thus, it is possible that BVDV-infection on the neighboring farms is a
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potential risk for introduction of the disease, although the specific transmission
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pathways were not clarified. According to interviews conducted with the farmers in this study, some farmers in the neighborhood cooperated in looking after their cattle and in
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sharing equipment. Thus, these types of indirect transmission via movement of persons
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or equipment might cause transmission of the disease among neighboring farms.
However, BVDV-infection on the nearest dairy farm was not significantly associated with the occurrence of PI animals. Because the temporal window for PI of calves is limited (between 20 and 120 days of gestation (Baker, 1987; Done et al., 1980)), even if BVDV transmission occurs between neighboring farms, it does not seem to relate clearly to the occurrence of PI animals.
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Clinical signs of BVDV infection, such as abortion and still birth, were not significantly associated with the transmission of BVDV infection within farms in this study. This result suggests that detection of circulating BVDV within farms based on clinical signs alone would be difficult (Sarrazin et al., 2013). Furthermore, although a risk of infection
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by other animals, such as beef cattle, sheep, and goats, were not identified in our study,
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these factors should not be disregarded as a potential source of the virus (Braun et al.,
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2014).
In this study, the risk of within- farm transmission following the introduction of BVDV
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via the movement of cattle during purchase and summer pasturing was revealed, and the
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significant role of PI cattle in circulating BVDV within dairy farms were recognized. In order to prevent the introduction and spread of BVDV by PI cattle, it is important to conduct inspections of cattle that are to be introduced to a farm or are to be sent for summer pasturing. In the case of summer pasturing in Hokkaido Prefecture, the cattle are required to undergo voluntary inspection before they are sent to the grazing farms. Thus, the risk of generating PI cattle during summer pasturing is likely to be reduced. On the other hand, if BVDV is maintained within a farm due to the presence of an infection source, such as PI cattle on the farm itself, inspection targeting only the cattle
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to be introduced will not be sufficient to suppress the occurrence of PI animals. In European countries, to detect PI cattle, a surveillance program for calves, using tissue samples (ear notch), has been implemented (Amelung et al., 2018; Houe et al., 2006). However, this surveillance method is not applied in Japan, although the practical use of
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bulk milk screening for BVDV on dairy farms has been investigated (Kozasa et al.,
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2005; Saino et al., 2013). More effective measures for screening BVDV infection and PI
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cattle, such as intensive tests targeting movement cattle and newborn calves, or bulk
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milk surveillance, are required to prevent and control the spread of BVDV in Japan.
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Acknowledgments We thank all of the livestock owners for their cooperation in this study. This work was supported by grant projects related to the promotion of regional research and development by the Ministry of Education, Culture, Sports, Science and Technology in
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Japan.
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Conflicts of interests
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The authors declare that there are no potential conflicts of interest with respect to the
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research, authorship, and/or publication of this article.
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Strong, R., Graham, S.P., La Rocca, S.A., Raue, R., Vangeel, I., Steinbach, F., 2018. Establishment of a bovine viral diarrhea virus type 2 intranasal challenge model for assessing vaccine efficacy. Front. Vet. Sci. 5, 24. Yamaguchi O, Sakoda Y, Sato M, Nakamura S, Fukusho A., 1997. Gene detection and
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Jpn. Vet. Med. Assoc. 50, 639-644. (in Japanese)
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discrimination of pestivirus strains by RT-PCR and restriction endonuclease analysis. J.
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Yasutomi, I., Okazawa, M., Hara, Y., 2004. Epidemiological investigation of bovine
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viral diarrhea virus infection with evaluating risk factors. J. Vet. Epidemiol. 8, 77-83. (in Japanese)
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Yesilbag, K., Alpay, G., Becher, P., 2017. Variability and global distribution of
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subgenotypes of bovine viral diarrhea virus. Viruses 9,128.
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Figure legend Figure 1: Number of persistently infected (PI) cattle alive between January 2011 and
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March 2018.
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Table 1 Epidemiological information collected in the bovine diarrhea virus (BVDV) survey on dairy cattle farms
Herd management Proportion of purchased cattle Summer pasturing (Yes/No) Grazing beef cattle or other species (sheep, goats, pigs, horses) (Yes/No) Feeding and biosecurity measures
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Disinfection of vehicle (Yes/No) Use of footbath (Yes/No)
Conception rate in cattle Occurrence of abortion and stillbirth
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Control of contact with wild animals
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Somatic cell count in milk
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Geographical features
Distance from the nearest dairy farm (km) Distance from the nearest beef farm (km)
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Distance from the nearest sheep or goat farm (km)
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Infection status of BVDV on the nearest dairy farm
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Table 2 Number of persistently infected (PI) cattle by their birthplace, their dam's birthplace, and the place of pregnancy
Birthplace of PI
Dam's birthplace
Place of pregnancy
38 (86.4%)
33 (75%)
29 (65.9%)
4 (9.1%)
7 (15.9%)
13 (29.6%)
2 (4.5%)
4 (9.1%)
cattle Current farm Other farms or grazing places outside of Ibaraki
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Prefecture
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Other farms within Ibaraki
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Prefecture
2 (4.5%)
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Table 3 Individual level seroprevalence of bovine diarrhea virus (BVDV)
Farm type
All farms BVDV-circulated-far m*
No. of inspected
No. of positive
Prevalence (95%
farms
animals
animals
CI)**
333
7,969
2,378
172
4,092
1,479
22
790
621
139
3,087
farm
*Persistent infection (PI) farms were excluded.
278
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BVDV-non-circulated
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PI farm
No. of
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**Values sharing a letter are not statistically different.
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95% CI, 95% confidence interval
29.8% (28.8–30.8)a 36.1% (34.7–37.6)a 78.6% (75.7–81.5)b 9.0% (8.0–10.0)c
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Table 4 Results of multivariable logistic regression models for the within-farm transmission of bovine diarrhea virus (BVDV) and the occurrence of persistently infected (PI) cattle Variable
Levels
No. of farms
No. of
(% po
Small (<30 adult cattle)
167
81 (4
Large(≥30 adult cattle)
165
113 (
No
241
127 (
Yes
92
67 (7
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Within-farm transmission of BVDV Farm size
Not infected
105
49 (4
Infected
228
145 (
Small (<30 adult cattle)
53
4(
Large (≥30 adult cattle)
44
18 (
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Summer pasturing
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Infection status of BVDV on the nearest dairy farm
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Occurrence of PI cattle
Pr
Farm size
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Summer pasturing
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Percentage of purchased cattle
1
(numerical variable) 3 No
80
13 (1
Yes
17
9 (5
Distance from the nearest dairy farm (km)
(numerical variable) 4
Infection status of BVDV on the nearest dairy farm
Not infected
34
5 (1
Infected
63
17 (2
Positive means "seropositive farm" in the model of within-farm transmission BVDV, and "PI farm"
in the model of occurrence of PI cattle. 2
95% CI, 95% confidence interval.
3
Percentages of purchased cattle in PI farm and non-PI farm (median, 2.5 -97.5 percentile) were
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21.7% (0-98.0%) and 0% (0-47.3%), respectively. 4
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Distances from the nearest dairy farm in PI farm and non-PI farm (median, 2.5th-97.5th percentile)
were 1.5 km (0.1-11.0 km) and 0.9 km (0.09-9.1 km), respectively.
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Highlights
Farm- level bovine viral diarrhea virus (BVDV) seroprevalence was 58.3% on dairy farms in Ibaraki Prefecture, Japan Persistently infected (PI) cattle were identified on 5.8% of dairy farms
Herd-size, summer pasturing, and neighboring farm with BVDV-infection were risk
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Herd-size, summer pasturing, and cattle purchases were risk factors for PI animals
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in a herd
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factors for herds being serologically positive
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