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Center for Animal Disease Control/CADIC,
University of Miyazaki
20230202@BBSKP
Prof. Tamaki Okabayahshi,
Vice Director of CADIC
BRIN visiting Professor.
2022Nov@ Miyazaki
Dr. HARIMURTI NURADJI
Center for Animal Disease Control “CADIC”
In Japan Pork Broiler Beef
Market share 9.2 % 17.2 % 10.1 %
Ranking 2 2 3
Miyazaki, Japan
FMD
BL
BRDC
PED
PRRS
Avi-Flu
Outbreaks of FMD in Miyazaki, 2010
In Japan Pork Broiler Beef
Market share 9.2 % 17.2 % 10.1 %
Ranking 2 2 3
Total Economic loss USD 3 billions
1362 farmers, 297,808 animals
“The Disasters”
Why has CADIC established?
Open sore on dental pad
Vesicles
Vesicles
Peel of skin on feet (pig)
Clinical signs
•Loss of appetite
•Fever
•Lameness
•Drooling of saliva
•Vesicles
•Erosion
•Ulcer
●Lack in recognition for an entry of malignant epidemics
in the globalization
●Importance of the practical experience
●Importance to develop international education programs
●Lack of veterinarians who are practiced in the handling
of the farm animals
●Need to develop international network between
foreign countries, especially Asian countries,
on countermeasures for prevention of emerging and
transboundary infections
What we learned from FMD outbreak
Div. of Livestock Science &
Support
Div. of Infectious Diseases
Research & Inspection
Div. of International
Cooperation & Education
Current Director
Dr. Ayako Yoshida
(2021Oct.~)
Div. HEAD: Dr. Sekiguchi
Div. HEAD: Dr. Mekata
Div. HEAD: Dr. Okabayashi
Div. HEAD: Dr. Iguchi
Pathological autopsy
Div. of Disease Control
Set up of CADIC in Miyazaki since Oct.2011
Practice of epidemiology using GIS
Emergency response training
Former Director
Dr. Naoaki Misawa
(2011Oct.~)
University of Miyazaki
Fac. Education
Fac. Engineering
Fac. Medicine
Fac. Agriculture
Graduate School
• Grad. Sch. of Agriculture Masters course
• Grad. Sch. of Education
• Grad. Sch. of Medicine
• Grad. Sch. of Engineering
• Interdisciplinary Grad. Sch. of Agriculture
and Engineering
• Interdisciplinary Grad. Sch. of Medicine and
Veterinary Medicine
Fac. Regional
Innovation
University of Miyazaki
Hospital
Frontier Scientific Research Center
Center for Animal Disease Control
Technical development for
livestock food product
Advanced research for
disease control
Regional & international
contributions for disease control
Development of
global human resources for
leader of disease control
Based on the past experiences of trans-boundary malignant
epidemics, like FMD and HPAI…
CADIC is aiming at
INTERNATIONAL DISEASE CONTROL NETWORK
MOU
27 countries, 89 institutes
Missions of CADIC
Center for Animal Disease Control (CADIC)
October 1, 2011
Center of Livestock Research and Education
November 21, 2013
BSL3 ➔ ABSL3
Pathological autopsy HPAI diagnosis
Emergency response training
Sampling and transfer of lab specimens
Operation in safety cabinet
Practice of epidemiology using GIS
Practice for handling of cattle
Diagnosis of rabies Lecture by a foreign researcher
Development of human resources especially for young experts
Promoting science and technology
Enhance the exchange of youths in Asian countries and Japan
who will play a crucial role in the field of science and technology.
Raising the interest of Asian youths toward the leading Japanese science
and technologies at Japanese universities
2016 IPB@UOM
International collaboration research activities
International collaboration of CADIC
JSPS Core-to-Core Program
(Asia-Africa Science Platforms)
2017Apr.-2021Mar.
Enhancement of the livestock productivity and reinforcement of
countermeasure for prevention of animal infectious diseases in
Southeast Asia by a cooperation with research bases with a hub function
Dr. Naoaki Misawa
Director of CADIC,
University of Miyazaki
Dr. Pranee Rodtian
Acting Director,
OIE reference laboratory of FMD-SEA
Dr. Bambang Pontjo Priosoeryanto
Professor,
Bogor Agricultural University
Livestock Revolution in ASEAN for a Kitchen of the World:
Development of Novel Technologies Yielding Stable Livestock Production
and Food Safety
2020-2015
1. International Cooperation
2. Addressing Global Issues and Advancing Science
3. Capacity Development
Science and Technology Research Partnership
for Sustainable Development
International collaboration of CADIC
Since 2020
三澤尚明 教授
CADICセンター⻑
Dr. Lerdchai
VRDC-ER所⻑
•
•
•
•
E
A
-
(
D C
三澤尚明 教授
CADICセンター⻑
•
•
•
•
A
-
(
D C
Dis-contamination
system
Development of
Multiple/Rapid/High sensitive
diagnosis for livestock diseases
Simulation model
livestock diseases
Anti-FMDV drug screening
Collaboration topics in SATREPS
Monitoring system for FMDV
JSPS International meeting
2017Oct@Bangkok
Joint seminar
Workshop for
future collaboration
The 20th FAVA /The 18th IVMA Congress,
30 Oct-4 Nov 2018, Bali, Indonesia
2018Oct
Fish Quarantine and Inspection Agency (Indonesia)
@2018Oct.
➔2021Nov. MOU
Global countermeasure against transboundary diseases
What can we do next?
Diagnosis tools from CADIC
Immunochromatography test kit
(antigen/antibody)
Multiple qRT-PCR Mobile PCR
Luciferase-linked
antibody capture assay (LACA)
Droplet Digital-PCR
Mobile Real-Time PCR “PicoGene™ PCR1100”
15 min, 7 USD / One reaction
DNA and RNA measuring anywhere
Freeze Dried PCR mastermix
Non-cold-chain transport of reagents for filed application
Same primers/probe for desktop qRT-PCR
Correlation between
Picogene and desktop-qPCR
(PCV2 virus)
https://jvi.asm.org/content/89/1/594
Tick borne diseases (TBD)
Sever Fever with Thrombocytopenia Syndrome
20221122
China in 2011
China2011
(2007~?)
Japan
2013
(2003~?)
Korea
2012~
Taiwan
2019~
Vietnam
2019~
Thailand
2020~
Pakistan
2020~
Myanmar
2020~
SFTS virus
Dabie bandavirus,
genus Bandavirus,
family Phenuiviridae
SFTS virus
L segment
M
S
L
Polymerase (RdRp)
Gc
Gn
S segment
M segment
N
NSs
Nucleoprotein
Glycoproteins
RNA
クリミアコンゴ出⾎熱
BSL4
腎症候性出⾎熱
BSL3
CCHF
HFRS
SFTS
RVF
Clinical characteristics of SFTS
https://link.springer.com/chapter/10.1007/978-
981-13-9562-8_11
Age and sex distribution of the SFTS
incidence and CFRs in China.
https://www.researchgate.net/figure/Age-and-sex-distribution-of-the-
SFTS-incidence-and-CFRs-in-China_fig1_275360196
https://www.jmaj.jp/detail.php?id=10.31662%2Fjmaj.2019-0073
Japanese SFTS cases reported by month
CFR
16-27%
CFR
11.2-30%
Takahashi et al., Uirus, 65,1,2015
http://www.smsl.co.nz/Pests/Ticks+TickBorne+Diseases.html
Transmission cycle of Tick borne diseases (TBD)
https://animalbattles.wealthyblogs.com/?p=14312
Chine Korea Japan
(%) antibody PCR antibody PCR antibody PCR
cattle 28.2-73.7 26.3 ND ND 2.2 ND
pig 3.1-6 ND ND 1.7 ND ND
chicken 1-52.1 ND ND ND ND ND
goat 57-83 9.1 6.9-14.4 2-2.44 ND ND
deer ND ND 23.8 ND 25 ND
wild boar ND ND 1.9 3.7 25-51 ND
dog 6-37.9 ND 13.9 0.5 9.1-14.3 ND
cat ND ND ND 0.2-4.8 ND ND
https://www.nature.com/articles/s12276-021-00610-1.pdf改変
Prevalence of SFTSV in animals, China, Korea, and Japan
2021
Take home message
Sylvatic cycle
(tick-wild life)
Urban cycle
(tick-cat-human)
Infection cycles of SFTS from endemic areas, Miyazaki, Japan
➔Risks of epidemics in Asia
Director, Prof. Ayako Yoshida
1) Development of novel diagnosis system for food-born parasitic zoonosis
2) Epidemiology of food-born parasitic zoonosis in Japan
3) Study on the mechanisms of ascarid larval migration in host animals
Dr. Satoshi Sekiguchi
Strategy of animal infectious disease control
Bovine leukosis, BVD-MD
Dr. Hirohisa Mekata
1) Studies on bovine leukemia virus infection
2) Studies on Trypanosoma evansi infection
Dr. Kentaro Yamada
1) Studies on Rabies
2) Bio-imaging
Dr. Akatsuki Saito
1) Studies on HIV
2) ZIKA, Flavivirus,COVID-19
20230124
Prof. Tamaki Okabayashi,
Vice Director of CADIC, University of Miyazaki, Japan
Zoonotic Lessons
Emergence, Transmission, and Potential Therapeutic for the COVID-19
Pandemic Associated with the Human-Animal-Environment Interaction
Center for Animal Disease Control “CADIC”
http://www.oie.int/en/for-the-media/onehealth/
ヒト感染症のうち、
人獣共通感染症の
割合
新興感染症のうち、
動物に由来する感染
症の割合
毎年増える新しいヒ
トの感染症5つのうち、
3つは動物由来感染症
生物兵器応用が考え
られている病原体の
80%が動物由来
http://www.oie.int/en/for-the-media/onehealth/
BSL3 ➔ ABSL3
COVID-19 Zoonosis or Emerging Infectious Disease?
2022/1/24 https://coronavirus.jhu.edu/map.html
https://www.enzolifesciences.com/browse/coronavirus/covid-19-
therapeutic-development/
SARS-CoV
2002
MERS-CoV
2012
SARS-CoV-2
2019
?
Bat CoV
Primary Host Intermediate Host
Origin of SARS-CoV-2 and potential transmission routes to humans.
https://www.news.com.au/technology/science/animals/miami-gorilla-tested-for-
coronavirus-after-fight-with-brother/news-story/2dcecf8ecd05d8186cd752bc9d164f21
https://www.furfreealliance.com/covid-19-
first-detected-in-european-mink-farms-a-year-
ago-ngos-and-the-public-urge-the-eu-to-act/
https://www.youtube.com/watch?v=2atBQBs-2xo
Risk of people spreading SARS-CoV-2 to animals
SARS-CoV
2002
MERS-CoV
2012
SARS-CoV-2
2019
?
Bat CoV
?
Primary Host Intermediate Host
Origin of SARS-CoV-2 and potential transmission routes to humans.
https://onlinelibrary.wiley.com/doi/10.1111/tbed.13791 modified
Timelines of the emergence of animal CoVs in animals
IBV
1930s
TGEV
1946
FECV
CCOV
1950-1970
BCOV
1973
FIP
1976
PEDV
PRCV
1980
CROV
2003
PDCOV
2009
SARS
2002
https://onlinelibrary.wiley.com/doi/10.1111/tbed.13791
Coronavirus Diseases are not EIDs in animals
PEDV, TGEV, PRCV
IBV
CCoV
FECV, FIPV
BCoV
MHV
PDCoV
CRCoV Cold-like
SARS
MERS
COVID-19
PHEV
Evolution History of the beta Coronaviruses ~Spike gene~
Homology
・BCoV vs HCoV-OC43 = 95.4%
・BCoV vs CRCoV = 97.3%
Evolution History of the beta Coronaviruses ~Spike gene~
Homology
・BCoV vs HCoV-OC43 = 95.4%
・BCoV vs CRCoV = 97.3%
1951
1899
Bovine coronavirus(BCoV)
➔Pneumoenteric virus
Bovine Coronavirus
Clinical symptom
1. Calf diarrhea
2. Winter dysentery in adult cattle
3. Respiratory infections in cattle of various ages
➔Bovine Respiratory Disease Complex(BRDC)
caused by co-infection of multiple viral and bacterial agents
BCoV infection
ICAM-1
PAFR
Bovine respiratory epithelial cells
Bovine coronavirus enhances bacterial adherence
on bovine respiratory epithelial cells
P. multocida
by upregulating expression of cellular receptors on bovine respiratory epithelial cells
https://onlinelibrary.wiley.com/doi/10.1111/tbed.13791 modified
Timelines of the emergence of animal CoVs in animals
IBV
1930s
TGEV
1946
FECV
CCOV
1950-1970
BCOV
1973
FIP
1976
PEDV
PRCV
1980
CROV
2003
PDCOV
2009
SARS
2002
BCoV produces SARS-CoV-3?
https://www.frontiersin.org/articles/10.3389/fvets.2021.643220/ful
OC43 PRCV
https://onlinelibrary.wiley.com/doi/10.1111/tbed.13791
Attachment Factors and Receptors
SARS-
CoV-2
vs %
PED/TGEV Canine Feline PHEV BCoV Chicken PDCov
Genome 43 44 43 49 49 43 40
S protein
Nuc. 37-38 38-40 39 43 43 40 39
Amino
acid
20 20 20 29 29 22 22
Comparison of S protein identify between animal coronavirus and SARS-CoV-2
Attachment Factors and Receptors
https://www.technologynetworks.com/genomics/news/genomic-analysis-reveals-many-
animal-species-may-be-vulnerable-to-sars-cov-2-infection-338896
SARS-CoV-2 in Cattle
SARS-CoV-2
1x10^5 TCID50, IN
https://wwwnc.cdc.gov/eid/article/26/12/20-3799_article
Anti-SARS-CoV-2 approaches in University of Miyazaki, Japan
Leaf of Blue Berry
Natto DUV/ Ozone Water
20180601 岡林/大淀川/右足膝裏ふくらはぎ上部 20220603 都井岬/フラッグ
御崎馬
(2021Sep)
Tick
https://doi.org/10.1101/2021.01.28.21250676
The cumulative number of studies that collected data about tick-borne
disease
Tick borne diseases
Tick research
https://doi.org/10.1101/2021.01.28.21250676
tick-borne disease
マダニ疾患調査/研究論文数
アフリカ豚熱
バベシア症
回帰熱
バーボンウイルス
クリミア-コンゴ出血熱
エルリキア症
ハートランドウイルス
SFTS
ヒトアナプラズマ症
キャサヌル森林病
跳躍病
ライム病
地中海紅斑熱
ナイロビ羊病
Q熱
回帰熱
リケッチアペルカリ
ロッキー紅斑熱
ダニ脳炎
野兎病
https://jvi.asm.org/content/89/1/594
Tick borne diseases (TBD)
Heart land virus disease
Signs and symptoms of Heartland virus disease (Heartland) are often
similar to those of other tickborne illnesses, such
as ehrlichiosis or anaplasmosis.
Fever, fatigue (feeling tired), decreased appetite, headache, nausea,
diarrhea, and muscle or joint pain.
Leukopenia, Thrombocytopenia
Lone Star tick (Amblyomma americanum)
Heartland virus is a Bandavirus first discovered as a cause of
human illness in 2009 in Missouri.
treatment with doxycycline.
Geneticrelationships among the tick-borne, mosquito-
borne, and sand-fly-borne phleboviruses.
Sever Fever with Thrombocytopenia Syndrome
20221122
China in 2011
China2011
(2007~?)
Japan
2013
(2003~?)
Korea
2012~
Taiwan
2019~
Vietnam
2019~
Thailand
2020~
Pakistan
2020~
Myanmar
2020~
SFTS virus
Dabie bandavirus,
genus Bandavirus,
family Phenuiviridae
SFTS virus
L segment
M
S
L
Polymerase (RdRp)
Gc
Gn
S segment
M segment
N
NSs
Nucleoprotein
Glycoproteins
RNA
クリミアコンゴ出⾎熱
BSL4
腎症候性出⾎熱
BSL3
CCHF
HFRS
SFTS
RVF
Takahashi et al., Uirus, 65,1,2015
http://www.smsl.co.nz/Pests/Ticks+TickBorne+Diseases.html
Transmission cycle of Tick borne diseases (TBD)
https://animalbattles.wealthyblogs.com/?p=14312
Vectors of SFTSV infection to human
Haemaphysalis longcornis
Amblyomma testudinarium
Haemaphysalis flava
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004574
Chine Korea Japan
(%) antibody PCR antibody PCR antibody PCR
cattle 28.2-73.7 26.3 ND ND 2.2 ND
pig 3.1-6 ND ND 1.7 ND ND
chicken 1-52.1 ND ND ND ND ND
goat 57-83 9.1 6.9-14.4 2-2.44 ND ND
deer ND ND 23.8 ND 25 ND
wild boar ND ND 1.9 3.7 25-51 ND
dog 6-37.9 ND 13.9 0.5 9.1-14.3 ND
cat ND ND ND 0.2-4.8 ND ND
https://www.nature.com/articles/s12276-021-00610-1.pdf改変
Prevalence of SFTSV in animals, China, Korea, and Japan
2021
Clinical characteristics of SFTS
https://link.springer.com/chapter/10.1007/978-
981-13-9562-8_11
Age and sex distribution of the SFTS
incidence and CFRs in China.
https://www.researchgate.net/figure/Age-and-sex-distribution-of-the-
SFTS-incidence-and-CFRs-in-China_fig1_275360196
https://www.jmaj.jp/detail.php?id=10.31662%2Fjmaj.2019-0073
Japanese SFTS cases reported by month
CFR
16-27%
CFR
11.2-30%
SFTS in Japan
Deadly tick!!
Tick borne diseases
20220731, N=763
Miyazaki➔
Japan, 2013
(2003~?)
https://www.niid.go.jp/niid/ja/2014-02-19-09-27-24/2242-disease-
based/sa/sfts/idsc/iasr-news/4428-pr4094.html改変
SFTS detected in tick
No SFTS in tick
Not tested
SFTSV in deer and ticks, Japan
https://www.mhlw.go.jp/content/10900000/000690808
SFTSV in Miyazaki, Japan
PCR
Antibody
1/9(11.1%)
64/147(43.5%)
8/105(7.5%)
44/105(41.9%)
Around patient housing
0/20(0%) MIR12.9%
Kirino et al., Vet. Med. Sci, 2022
Sato et al., VBD, 2018
?
A. testudinarium
H. formosensis
H. kitaokai
H. hystricis
H. megaspinosa
H. flava
First isolation of SFTSV from tick in Japan
New transmission cycle of SFTS?
Cat to Human?
Human to Human?
(2022年3月31日現在)
ネコ イヌ
石川県 0 1
静岡県 7 2
三重県 9 0
滋賀県 1 1
京都府 12 1
大阪府 1 0
兵庫県 2 2
和歌山県 8 1
岡山県 26 0
広島県 28 0
鳥取県 0 1
島根県 3 0
山口県 22 3
徳島県 13 1
香川県 4 0
愛媛県 16 0
高知県 14 0
福岡県 14 1
佐賀県 20 1
長崎県 93 1
熊本県 14 0
大分県 11 5
宮崎県 47 2
鹿児島県 83 1
不明 1 0
総数 449 24
First case of SFTS in Cat, 2017
SFTS incidence in cats and dogs, Japan 2017Apr-2022Mar.
Epidemic mainly in western Japan.
➔Expansion to eastern Japan?
Cheetahs died of SFTS, 2017
Cat Dog
Miyazaki➔
Dr. Maeda, NIID, Japan
Direct transmission of SFTSV from cat to human
Oral swab
1.8x104/ml
SFTSV gene copies
Serum
8.7x108/ml
Anal swab
5.6x104/ml
H9 Miyazaki 2018
H10 Miyazaki 2018
Cat Miyazaki 2018
SPL089A Yamaguchi 2013
SPL055A Yamaguchi 2013
SPL075A Kochi 2013
SPL069A Ehime 2013
SPL035A Ehime 2012
SPL107A Hiroshima 2013
SPL053A Saga 2012
SPL108A Tokushima 2013
SPL060A Tokushima 2013
SPL104A Kagoshima 2013
SPL128A MIyazaki 2014
SPL124A Miyazaki 2013
SPL121A Miyazaki 2013
SPL010A Nagasaki 2005
SPL105A Miyazaki 2013
SPL086A Miyazaki 2013
SPL003A Ehime 2012
YG1 Yamaguchi 2012
KH1 Korea 2015
SPL071A Hiroshima 2013
ArtSp Hiroshima 2017
SkrP Hiroshima 2017
SPL114A Hiroshima 2013
SPL005A Hiroshima 2012
SPL032A Nagasaki 2005
SPL030A Saga 2010
SPL066A Miyazaki 2013
SPL070A Ehime 2013
SPL054A Kagoshima 2013
SPL120A Ehime 2012
SPL106A Ehime 2013
SPL084A Okayama 2013
SPL077A Ehime 2013
SPL117A Kumamoto 2013
SPL090A Okayama 2013
SPL067A Kagoshima 2013
SPL062A Kumamoto 2013
SPL082A Nagasaki 2013
SPL112A Hiroshima 2013
SPL078A Kumamoto 2013
CB1 Korea 2014
SPL129A Miyazaki 2014
SPL004A Miyazaki 2012
SPL057A Yamaguchi 2013
SPL100A Hyogo 2013
SPL097A Hyogo 2013
HB29 China 2010
HB154 China 2011
Gangwon Korea 2012
SPL161A Wakayama 2014
SPL087A Shimane 2013
HL/Injected China 2013
JS2011-004 China 2011
100
100
100
100
100
100
76
62
29
100
100
64
100
100
54
40
100
57
32
30
100
100
100
100
100
100
99
89
100
76
100
53
100
43 99
100
100
100
97
88
58
70
39
50
67
64
46
38
0.0050
(c) L segment
* P<0.05 error bar: CI
Veterinarians
in Miyazakiki
3/90
Ordinary Citizen, Miyazaki
Hinoura et al., 2016
1/651
Ordinary Citizen, Kagoshima
Gokuden et al., 2016
1/521
Hunters
Gokuden et al., 2016
1/125
10
8
6
4
2
0
Health people from
Red Cross, Miyazaki
0/1,000
Ordinary Citizen,
Kagoshima
Gokuden et al., 2018
0/1,000
Farmers
Shinomiya et al., 2016
2/694
*
*
3.3
%
0.0
%
Infection risk assessment of SFTSV in Veterinarians
Antibody
positive
rate(%)
Take home message
Sylvatic cycle
(tick-wild life)
Urban cycle
(tick-cat-human)
Infection cycles of SFTS from endemic areas, Miyazaki, Japan
➔Risks of epidemics in Asia
Global countermeasure against transboundary diseases
What can we do next?
Director, Prof. Ayako Yoshida
1) Development of novel diagnosis system for food-born parasitic zoonosis
2) Epidemiology of food-born parasitic zoonosis in Japan
3) Study on the mechanisms of ascarid larval migration in host animals
Dr. Satoshi Sekiguchi
Strategy of animal infectious disease control
Bovine leukosis, BVD-MD
Dr. Hirohisa Mekata
1) Studies on bovine leukemia virus infection
2) Studies on Trypanosoma evansi infection
Dr. Kentaro Yamada
1) Studies on Rabies
2) Bio-imaging
Dr. Akatsuki Saito
1) Studies on HIV
2) ZIKA, Flavivirus,COVID-19
PROF TAMAKI OKABAYASHI (1).pdf

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PROF TAMAKI OKABAYASHI (1).pdf

  • 1. Center for Animal Disease Control/CADIC, University of Miyazaki 20230202@BBSKP Prof. Tamaki Okabayahshi, Vice Director of CADIC BRIN visiting Professor.
  • 3. Center for Animal Disease Control “CADIC”
  • 4. In Japan Pork Broiler Beef Market share 9.2 % 17.2 % 10.1 % Ranking 2 2 3 Miyazaki, Japan
  • 5. FMD BL BRDC PED PRRS Avi-Flu Outbreaks of FMD in Miyazaki, 2010 In Japan Pork Broiler Beef Market share 9.2 % 17.2 % 10.1 % Ranking 2 2 3 Total Economic loss USD 3 billions 1362 farmers, 297,808 animals “The Disasters” Why has CADIC established?
  • 6. Open sore on dental pad Vesicles Vesicles Peel of skin on feet (pig) Clinical signs •Loss of appetite •Fever •Lameness •Drooling of saliva •Vesicles •Erosion •Ulcer
  • 7. ●Lack in recognition for an entry of malignant epidemics in the globalization ●Importance of the practical experience ●Importance to develop international education programs ●Lack of veterinarians who are practiced in the handling of the farm animals ●Need to develop international network between foreign countries, especially Asian countries, on countermeasures for prevention of emerging and transboundary infections What we learned from FMD outbreak
  • 8. Div. of Livestock Science & Support Div. of Infectious Diseases Research & Inspection Div. of International Cooperation & Education Current Director Dr. Ayako Yoshida (2021Oct.~) Div. HEAD: Dr. Sekiguchi Div. HEAD: Dr. Mekata Div. HEAD: Dr. Okabayashi Div. HEAD: Dr. Iguchi Pathological autopsy Div. of Disease Control Set up of CADIC in Miyazaki since Oct.2011 Practice of epidemiology using GIS Emergency response training Former Director Dr. Naoaki Misawa (2011Oct.~)
  • 9. University of Miyazaki Fac. Education Fac. Engineering Fac. Medicine Fac. Agriculture Graduate School • Grad. Sch. of Agriculture Masters course • Grad. Sch. of Education • Grad. Sch. of Medicine • Grad. Sch. of Engineering • Interdisciplinary Grad. Sch. of Agriculture and Engineering • Interdisciplinary Grad. Sch. of Medicine and Veterinary Medicine Fac. Regional Innovation University of Miyazaki Hospital Frontier Scientific Research Center Center for Animal Disease Control
  • 10. Technical development for livestock food product Advanced research for disease control Regional & international contributions for disease control Development of global human resources for leader of disease control Based on the past experiences of trans-boundary malignant epidemics, like FMD and HPAI… CADIC is aiming at INTERNATIONAL DISEASE CONTROL NETWORK MOU 27 countries, 89 institutes Missions of CADIC
  • 11. Center for Animal Disease Control (CADIC) October 1, 2011 Center of Livestock Research and Education November 21, 2013
  • 13. Pathological autopsy HPAI diagnosis Emergency response training Sampling and transfer of lab specimens Operation in safety cabinet Practice of epidemiology using GIS Practice for handling of cattle Diagnosis of rabies Lecture by a foreign researcher Development of human resources especially for young experts
  • 14. Promoting science and technology Enhance the exchange of youths in Asian countries and Japan who will play a crucial role in the field of science and technology. Raising the interest of Asian youths toward the leading Japanese science and technologies at Japanese universities 2016 IPB@UOM International collaboration research activities
  • 15. International collaboration of CADIC JSPS Core-to-Core Program (Asia-Africa Science Platforms) 2017Apr.-2021Mar. Enhancement of the livestock productivity and reinforcement of countermeasure for prevention of animal infectious diseases in Southeast Asia by a cooperation with research bases with a hub function Dr. Naoaki Misawa Director of CADIC, University of Miyazaki Dr. Pranee Rodtian Acting Director, OIE reference laboratory of FMD-SEA Dr. Bambang Pontjo Priosoeryanto Professor, Bogor Agricultural University
  • 16. Livestock Revolution in ASEAN for a Kitchen of the World: Development of Novel Technologies Yielding Stable Livestock Production and Food Safety 2020-2015 1. International Cooperation 2. Addressing Global Issues and Advancing Science 3. Capacity Development Science and Technology Research Partnership for Sustainable Development
  • 17. International collaboration of CADIC Since 2020 三澤尚明 教授 CADICセンター⻑ Dr. Lerdchai VRDC-ER所⻑ • • • • E A - ( D C 三澤尚明 教授 CADICセンター⻑ • • • • A - ( D C Dis-contamination system Development of Multiple/Rapid/High sensitive diagnosis for livestock diseases Simulation model livestock diseases Anti-FMDV drug screening Collaboration topics in SATREPS Monitoring system for FMDV
  • 18. JSPS International meeting 2017Oct@Bangkok Joint seminar Workshop for future collaboration The 20th FAVA /The 18th IVMA Congress, 30 Oct-4 Nov 2018, Bali, Indonesia
  • 19. 2018Oct Fish Quarantine and Inspection Agency (Indonesia) @2018Oct. ➔2021Nov. MOU
  • 20. Global countermeasure against transboundary diseases What can we do next?
  • 21. Diagnosis tools from CADIC Immunochromatography test kit (antigen/antibody) Multiple qRT-PCR Mobile PCR Luciferase-linked antibody capture assay (LACA) Droplet Digital-PCR
  • 22. Mobile Real-Time PCR “PicoGene™ PCR1100” 15 min, 7 USD / One reaction DNA and RNA measuring anywhere Freeze Dried PCR mastermix Non-cold-chain transport of reagents for filed application Same primers/probe for desktop qRT-PCR Correlation between Picogene and desktop-qPCR (PCV2 virus)
  • 24. Sever Fever with Thrombocytopenia Syndrome 20221122 China in 2011 China2011 (2007~?) Japan 2013 (2003~?) Korea 2012~ Taiwan 2019~ Vietnam 2019~ Thailand 2020~ Pakistan 2020~ Myanmar 2020~
  • 25. SFTS virus Dabie bandavirus, genus Bandavirus, family Phenuiviridae SFTS virus L segment M S L Polymerase (RdRp) Gc Gn S segment M segment N NSs Nucleoprotein Glycoproteins RNA クリミアコンゴ出⾎熱 BSL4 腎症候性出⾎熱 BSL3 CCHF HFRS SFTS RVF
  • 26. Clinical characteristics of SFTS https://link.springer.com/chapter/10.1007/978- 981-13-9562-8_11 Age and sex distribution of the SFTS incidence and CFRs in China. https://www.researchgate.net/figure/Age-and-sex-distribution-of-the- SFTS-incidence-and-CFRs-in-China_fig1_275360196 https://www.jmaj.jp/detail.php?id=10.31662%2Fjmaj.2019-0073 Japanese SFTS cases reported by month CFR 16-27% CFR 11.2-30%
  • 27. Takahashi et al., Uirus, 65,1,2015 http://www.smsl.co.nz/Pests/Ticks+TickBorne+Diseases.html Transmission cycle of Tick borne diseases (TBD) https://animalbattles.wealthyblogs.com/?p=14312
  • 28. Chine Korea Japan (%) antibody PCR antibody PCR antibody PCR cattle 28.2-73.7 26.3 ND ND 2.2 ND pig 3.1-6 ND ND 1.7 ND ND chicken 1-52.1 ND ND ND ND ND goat 57-83 9.1 6.9-14.4 2-2.44 ND ND deer ND ND 23.8 ND 25 ND wild boar ND ND 1.9 3.7 25-51 ND dog 6-37.9 ND 13.9 0.5 9.1-14.3 ND cat ND ND ND 0.2-4.8 ND ND https://www.nature.com/articles/s12276-021-00610-1.pdf改変 Prevalence of SFTSV in animals, China, Korea, and Japan 2021
  • 29. Take home message Sylvatic cycle (tick-wild life) Urban cycle (tick-cat-human) Infection cycles of SFTS from endemic areas, Miyazaki, Japan ➔Risks of epidemics in Asia
  • 30. Director, Prof. Ayako Yoshida 1) Development of novel diagnosis system for food-born parasitic zoonosis 2) Epidemiology of food-born parasitic zoonosis in Japan 3) Study on the mechanisms of ascarid larval migration in host animals Dr. Satoshi Sekiguchi Strategy of animal infectious disease control Bovine leukosis, BVD-MD Dr. Hirohisa Mekata 1) Studies on bovine leukemia virus infection 2) Studies on Trypanosoma evansi infection Dr. Kentaro Yamada 1) Studies on Rabies 2) Bio-imaging Dr. Akatsuki Saito 1) Studies on HIV 2) ZIKA, Flavivirus,COVID-19
  • 31.
  • 32.
  • 33. 20230124 Prof. Tamaki Okabayashi, Vice Director of CADIC, University of Miyazaki, Japan Zoonotic Lessons Emergence, Transmission, and Potential Therapeutic for the COVID-19 Pandemic Associated with the Human-Animal-Environment Interaction
  • 34. Center for Animal Disease Control “CADIC”
  • 38. COVID-19 Zoonosis or Emerging Infectious Disease? 2022/1/24 https://coronavirus.jhu.edu/map.html https://www.enzolifesciences.com/browse/coronavirus/covid-19- therapeutic-development/
  • 39. SARS-CoV 2002 MERS-CoV 2012 SARS-CoV-2 2019 ? Bat CoV Primary Host Intermediate Host Origin of SARS-CoV-2 and potential transmission routes to humans.
  • 41. SARS-CoV 2002 MERS-CoV 2012 SARS-CoV-2 2019 ? Bat CoV ? Primary Host Intermediate Host Origin of SARS-CoV-2 and potential transmission routes to humans.
  • 42. https://onlinelibrary.wiley.com/doi/10.1111/tbed.13791 modified Timelines of the emergence of animal CoVs in animals IBV 1930s TGEV 1946 FECV CCOV 1950-1970 BCOV 1973 FIP 1976 PEDV PRCV 1980 CROV 2003 PDCOV 2009 SARS 2002
  • 43. https://onlinelibrary.wiley.com/doi/10.1111/tbed.13791 Coronavirus Diseases are not EIDs in animals PEDV, TGEV, PRCV IBV CCoV FECV, FIPV BCoV MHV PDCoV CRCoV Cold-like SARS MERS COVID-19 PHEV
  • 44. Evolution History of the beta Coronaviruses ~Spike gene~ Homology ・BCoV vs HCoV-OC43 = 95.4% ・BCoV vs CRCoV = 97.3%
  • 45. Evolution History of the beta Coronaviruses ~Spike gene~ Homology ・BCoV vs HCoV-OC43 = 95.4% ・BCoV vs CRCoV = 97.3% 1951 1899
  • 46. Bovine coronavirus(BCoV) ➔Pneumoenteric virus Bovine Coronavirus Clinical symptom 1. Calf diarrhea 2. Winter dysentery in adult cattle 3. Respiratory infections in cattle of various ages ➔Bovine Respiratory Disease Complex(BRDC) caused by co-infection of multiple viral and bacterial agents
  • 47. BCoV infection ICAM-1 PAFR Bovine respiratory epithelial cells Bovine coronavirus enhances bacterial adherence on bovine respiratory epithelial cells P. multocida by upregulating expression of cellular receptors on bovine respiratory epithelial cells
  • 48. https://onlinelibrary.wiley.com/doi/10.1111/tbed.13791 modified Timelines of the emergence of animal CoVs in animals IBV 1930s TGEV 1946 FECV CCOV 1950-1970 BCOV 1973 FIP 1976 PEDV PRCV 1980 CROV 2003 PDCOV 2009 SARS 2002
  • 50. https://onlinelibrary.wiley.com/doi/10.1111/tbed.13791 Attachment Factors and Receptors SARS- CoV-2 vs % PED/TGEV Canine Feline PHEV BCoV Chicken PDCov Genome 43 44 43 49 49 43 40 S protein Nuc. 37-38 38-40 39 43 43 40 39 Amino acid 20 20 20 29 29 22 22 Comparison of S protein identify between animal coronavirus and SARS-CoV-2
  • 51. Attachment Factors and Receptors https://www.technologynetworks.com/genomics/news/genomic-analysis-reveals-many- animal-species-may-be-vulnerable-to-sars-cov-2-infection-338896
  • 52. SARS-CoV-2 in Cattle SARS-CoV-2 1x10^5 TCID50, IN https://wwwnc.cdc.gov/eid/article/26/12/20-3799_article
  • 53. Anti-SARS-CoV-2 approaches in University of Miyazaki, Japan Leaf of Blue Berry Natto DUV/ Ozone Water
  • 54. 20180601 岡林/大淀川/右足膝裏ふくらはぎ上部 20220603 都井岬/フラッグ 御崎馬 (2021Sep) Tick
  • 55. https://doi.org/10.1101/2021.01.28.21250676 The cumulative number of studies that collected data about tick-borne disease Tick borne diseases Tick research
  • 58. Heart land virus disease Signs and symptoms of Heartland virus disease (Heartland) are often similar to those of other tickborne illnesses, such as ehrlichiosis or anaplasmosis. Fever, fatigue (feeling tired), decreased appetite, headache, nausea, diarrhea, and muscle or joint pain. Leukopenia, Thrombocytopenia Lone Star tick (Amblyomma americanum) Heartland virus is a Bandavirus first discovered as a cause of human illness in 2009 in Missouri. treatment with doxycycline.
  • 59. Geneticrelationships among the tick-borne, mosquito- borne, and sand-fly-borne phleboviruses.
  • 60. Sever Fever with Thrombocytopenia Syndrome 20221122 China in 2011 China2011 (2007~?) Japan 2013 (2003~?) Korea 2012~ Taiwan 2019~ Vietnam 2019~ Thailand 2020~ Pakistan 2020~ Myanmar 2020~
  • 61. SFTS virus Dabie bandavirus, genus Bandavirus, family Phenuiviridae SFTS virus L segment M S L Polymerase (RdRp) Gc Gn S segment M segment N NSs Nucleoprotein Glycoproteins RNA クリミアコンゴ出⾎熱 BSL4 腎症候性出⾎熱 BSL3 CCHF HFRS SFTS RVF
  • 62. Takahashi et al., Uirus, 65,1,2015 http://www.smsl.co.nz/Pests/Ticks+TickBorne+Diseases.html Transmission cycle of Tick borne diseases (TBD) https://animalbattles.wealthyblogs.com/?p=14312
  • 63. Vectors of SFTSV infection to human Haemaphysalis longcornis Amblyomma testudinarium Haemaphysalis flava https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004574
  • 64. Chine Korea Japan (%) antibody PCR antibody PCR antibody PCR cattle 28.2-73.7 26.3 ND ND 2.2 ND pig 3.1-6 ND ND 1.7 ND ND chicken 1-52.1 ND ND ND ND ND goat 57-83 9.1 6.9-14.4 2-2.44 ND ND deer ND ND 23.8 ND 25 ND wild boar ND ND 1.9 3.7 25-51 ND dog 6-37.9 ND 13.9 0.5 9.1-14.3 ND cat ND ND ND 0.2-4.8 ND ND https://www.nature.com/articles/s12276-021-00610-1.pdf改変 Prevalence of SFTSV in animals, China, Korea, and Japan 2021
  • 65. Clinical characteristics of SFTS https://link.springer.com/chapter/10.1007/978- 981-13-9562-8_11 Age and sex distribution of the SFTS incidence and CFRs in China. https://www.researchgate.net/figure/Age-and-sex-distribution-of-the- SFTS-incidence-and-CFRs-in-China_fig1_275360196 https://www.jmaj.jp/detail.php?id=10.31662%2Fjmaj.2019-0073 Japanese SFTS cases reported by month CFR 16-27% CFR 11.2-30%
  • 66. SFTS in Japan Deadly tick!! Tick borne diseases 20220731, N=763 Miyazaki➔ Japan, 2013 (2003~?)
  • 67. https://www.niid.go.jp/niid/ja/2014-02-19-09-27-24/2242-disease- based/sa/sfts/idsc/iasr-news/4428-pr4094.html改変 SFTS detected in tick No SFTS in tick Not tested SFTSV in deer and ticks, Japan https://www.mhlw.go.jp/content/10900000/000690808
  • 68. SFTSV in Miyazaki, Japan PCR Antibody 1/9(11.1%) 64/147(43.5%) 8/105(7.5%) 44/105(41.9%) Around patient housing 0/20(0%) MIR12.9% Kirino et al., Vet. Med. Sci, 2022 Sato et al., VBD, 2018 ? A. testudinarium H. formosensis H. kitaokai H. hystricis H. megaspinosa H. flava First isolation of SFTSV from tick in Japan
  • 69. New transmission cycle of SFTS? Cat to Human? Human to Human?
  • 70. (2022年3月31日現在) ネコ イヌ 石川県 0 1 静岡県 7 2 三重県 9 0 滋賀県 1 1 京都府 12 1 大阪府 1 0 兵庫県 2 2 和歌山県 8 1 岡山県 26 0 広島県 28 0 鳥取県 0 1 島根県 3 0 山口県 22 3 徳島県 13 1 香川県 4 0 愛媛県 16 0 高知県 14 0 福岡県 14 1 佐賀県 20 1 長崎県 93 1 熊本県 14 0 大分県 11 5 宮崎県 47 2 鹿児島県 83 1 不明 1 0 総数 449 24 First case of SFTS in Cat, 2017 SFTS incidence in cats and dogs, Japan 2017Apr-2022Mar. Epidemic mainly in western Japan. ➔Expansion to eastern Japan? Cheetahs died of SFTS, 2017 Cat Dog Miyazaki➔ Dr. Maeda, NIID, Japan
  • 71. Direct transmission of SFTSV from cat to human Oral swab 1.8x104/ml SFTSV gene copies Serum 8.7x108/ml Anal swab 5.6x104/ml H9 Miyazaki 2018 H10 Miyazaki 2018 Cat Miyazaki 2018 SPL089A Yamaguchi 2013 SPL055A Yamaguchi 2013 SPL075A Kochi 2013 SPL069A Ehime 2013 SPL035A Ehime 2012 SPL107A Hiroshima 2013 SPL053A Saga 2012 SPL108A Tokushima 2013 SPL060A Tokushima 2013 SPL104A Kagoshima 2013 SPL128A MIyazaki 2014 SPL124A Miyazaki 2013 SPL121A Miyazaki 2013 SPL010A Nagasaki 2005 SPL105A Miyazaki 2013 SPL086A Miyazaki 2013 SPL003A Ehime 2012 YG1 Yamaguchi 2012 KH1 Korea 2015 SPL071A Hiroshima 2013 ArtSp Hiroshima 2017 SkrP Hiroshima 2017 SPL114A Hiroshima 2013 SPL005A Hiroshima 2012 SPL032A Nagasaki 2005 SPL030A Saga 2010 SPL066A Miyazaki 2013 SPL070A Ehime 2013 SPL054A Kagoshima 2013 SPL120A Ehime 2012 SPL106A Ehime 2013 SPL084A Okayama 2013 SPL077A Ehime 2013 SPL117A Kumamoto 2013 SPL090A Okayama 2013 SPL067A Kagoshima 2013 SPL062A Kumamoto 2013 SPL082A Nagasaki 2013 SPL112A Hiroshima 2013 SPL078A Kumamoto 2013 CB1 Korea 2014 SPL129A Miyazaki 2014 SPL004A Miyazaki 2012 SPL057A Yamaguchi 2013 SPL100A Hyogo 2013 SPL097A Hyogo 2013 HB29 China 2010 HB154 China 2011 Gangwon Korea 2012 SPL161A Wakayama 2014 SPL087A Shimane 2013 HL/Injected China 2013 JS2011-004 China 2011 100 100 100 100 100 100 76 62 29 100 100 64 100 100 54 40 100 57 32 30 100 100 100 100 100 100 99 89 100 76 100 53 100 43 99 100 100 100 97 88 58 70 39 50 67 64 46 38 0.0050 (c) L segment
  • 72. * P<0.05 error bar: CI Veterinarians in Miyazakiki 3/90 Ordinary Citizen, Miyazaki Hinoura et al., 2016 1/651 Ordinary Citizen, Kagoshima Gokuden et al., 2016 1/521 Hunters Gokuden et al., 2016 1/125 10 8 6 4 2 0 Health people from Red Cross, Miyazaki 0/1,000 Ordinary Citizen, Kagoshima Gokuden et al., 2018 0/1,000 Farmers Shinomiya et al., 2016 2/694 * * 3.3 % 0.0 % Infection risk assessment of SFTSV in Veterinarians Antibody positive rate(%)
  • 73. Take home message Sylvatic cycle (tick-wild life) Urban cycle (tick-cat-human) Infection cycles of SFTS from endemic areas, Miyazaki, Japan ➔Risks of epidemics in Asia
  • 74. Global countermeasure against transboundary diseases What can we do next?
  • 75. Director, Prof. Ayako Yoshida 1) Development of novel diagnosis system for food-born parasitic zoonosis 2) Epidemiology of food-born parasitic zoonosis in Japan 3) Study on the mechanisms of ascarid larval migration in host animals Dr. Satoshi Sekiguchi Strategy of animal infectious disease control Bovine leukosis, BVD-MD Dr. Hirohisa Mekata 1) Studies on bovine leukemia virus infection 2) Studies on Trypanosoma evansi infection Dr. Kentaro Yamada 1) Studies on Rabies 2) Bio-imaging Dr. Akatsuki Saito 1) Studies on HIV 2) ZIKA, Flavivirus,COVID-19