Veterinary Epidemiology Unit

Drug resistance is known to include direct selection, in which drug-resistant bacteria are selected against the antibiotic used, cross-selection, in which bacteria resistant to the same type of drug are selected, and co-selection, in which bacteria resistant to different type of drugs are selected. Our unit has been collaborating with the antimicrobial drug resistance monitoring system of MAFF, JVARM, to predict the patterns of co-selection using statistical analysis. The analysis has predicted the possibility of co-selection of colistin resistance before transmission of the resistance gene, mcr is publicly known. Furthermore, we are trying to understand more detailed mechanism of co-selection by conjugative transfer tests for the association suggested by the statistical analyses.

Research Collaboration

• Collaborative research with MAFF National Veterinary Assay Laboratory (2012-present) (Makita, Co-PI, PI)

In livestock and fisheries, the Ministry of Agriculture, Forestry and Fisheries has been monitoring the use of antibiotics and the prevalence of drug-resistant bacteria. A survey was also initiated through the Japanese Veterinary Medical Association on the use of antibiotics in companion animal clinics, following the WHO Global Action Plan for Antimicrobial Drug Resistance published in 2015.
From the first survey, it became clear that human antibiotics were being used extensively in companion animal clinics. Research and analysis are ongoing.

Research Grants

• Japanese Veterinary Medical Association (2018-Present) (Makita, PI)

Vegetables are often eaten raw, so if there are drug-resistant bacteria attached to vegetables or in the body of vegetables, people ingest them. Vegetable-derived food poisoning has occurred in Europe, and it has been reported that the causative Escherichia coli was a drug-resistant bacterium.
A risk assessment was conducted to determine how much β-lactamase-producing E. coli remained in the vegetable body and on the vegetable surface when immature compost was applied to the field, after β-lactamase-producing E. coli was selected by using β-lactam antibiotics in dairy cows in Hokkaido Prefecture, using the monitoring data of Japanese cow-derived E. coli, published papers, experimental data, and medical records of dairy cows in Hokkaido. As a result of the evaluation, it was found that the risk of intake of β-lactamase-producing E. coli by eating raw vegetables is quite low. However, prudent use of antibiotics and careful washing of vegetables before consumption remain important.

Research Grants

• Food Safety Commission Research Program for Risk Assessment Study on Food Safety (JPCAFSC20202002) “Quantitative assessment of vegetable contamination via aquatic and soil environments by drug-resistant bacteria derived from livestock and research on its transmission to humans” (2020-2021) (Makita, Co-PI)

Immediately after the occurrence of the Great East Japan Earthquake in March 2011, Rakuno Gakuen University has been assisting in the reconstruction of tsunami-affected Ofunato City in Iwate Prefecture and Ishinomaki City in Miyagi Prefecture. In Ishinomaki City, our unit collaborated with Rakuno Gakuen University School of Veterinary Medicine, College of Agriculture, Food and Environmental Sciences, students, local NPOs, and international NPOs to confirm that the tsunami-affected areas were not highly contaminated by microorganisms and heavy metals. However, given the increase in rodents, it was advised that outbreaks of associated infections should be prevented. We also conducted a survey on the mental health of people living in temporary housing and listened closely to their feelings.

Research Grants

• Mitsui Environment Fund (2022-2013) (Makita, Co-PI)
  
• NPO APCAS (2011)
  
• Rakuno Gakuen University (2011-2012)
  
• Ishinomaki Environment-Net (2011-2012)

The foot-and-mouth disease that broke out in Miyazaki Prefecture on April 20, 2010 ended with the death of about 290,000 animals. A foot-and-mouth disease outbreak occurred just 20 days after our unit opened. Shortly after the end of the epidemic, together with veterinarians, mental health specialists, and on-site public health nurses who were involved in epidemic prevention, we gradually clarified the "psychological" damage caused by foot-and-mouth disease. The results of the research are later used in the care of animal disease control workers, and are also used as a reference outside of Japan.

Research Grants

• Rakuno Gakuen University Collaborative Research Grant (2011) (Makita, PI)
  
• MHLW Grant-in-Aid for Scientific Research (2010-2013) (Makita, Co-PI)
  

Veterinarians strive to ensure that the public can eat safe meat and milk as much as they need. Eating is a culture and a source of health. In Japan and Côte d'Ivoire, a comparative research on healthy "aging" and "food" was conducted by talking with the elderly, involving a nutritionist and a cultural anthropologists.
Economically, Japanese elderly people relied on pensions and health insurance to stabilize themselves, while Ivorian elders relied on their children and their own social networks. While the elderly in Japan worry to get sick as they age and trouble the younger generation, in Côte d'Ivoire, the elderly were valued by society for their wisdom. In Japan, there are many educational activities related to exercise and food for the elderly, but in Côte d'Ivoire, there are almost no such efforts. In Japan, people tend to eat small amounts of meat, fermented beans, and vegetables in a well-balanced manner. In Cote d'Ivoire, they ate the same high-calorie carbohydrate staples and small amounts of protein as their families.
Exercise, a balanced diet, and intergenerational support in society are necessary for healthy aging. Through mutual learning between Japan and Côte d'Ivoire, we were able to recognize what is necessary for the sustainable development of mutual countries.

Research Grants

• JSPS Colloquium (2018) (Makita, Resource person)
  
• Wellcome Trust, Afrique One ASPIRE (2018-2021) (Makita, Resource person)
  
• Rakuno Gakuen University Guest Researcher Program (2018) (Makita, PI)

Brucellosis is one of the most widely distributed zoonotic diseases in the world. It causes significant economic loss in livestock through abortion and milk yield reduction, and chronic illness such as undulant fever, fatigue and arthritis to humans, which take labor force away. Through research activities in sub-Saharan Africa, Southeast Asia, and South Asia, it has become clear that human brucellosis and livestock brucellosis are deeply related to socioeconomics, such as people's pastoralism and lifestyle. In endemic countries, our unit is working on One Health/Eco-Health initiatives in cooperation with medical professionals, veterinarians, and communities, and considering control methods using epidemiology, socio-economics and infectious disease mathematical modelling. As the World Organization for Animal Health (WOAH) Collaborating Center consortium for Food Safety, we contribute to the control of brucellosis in the Asia-Pacific region, together with the WOAH Brucellosis Reference Laboratories in Asia and Europe.

Research Grants

• University of Edinburgh (2004-2009) (Makita, PhD student)
  
• UK DfID (2004-2009) (Makita, PhD student)
  
• JICA Long-term Training (2004-2006) (Makita, PhD student)

Rapid urbanization is a common phenomenon in all developing countries, with large numbers of people moving from subsistence rural areas to shanty towns in search of cash income. In Uganda, East Africa, a multifaceted examination of the risk of zoonotic diseases in urbanization revealed that livestock-derived zoonotic diseases such as food poisoning, brucellosis, and zoonotic tuberculosis occurred frequently in urban areas. The study warned that management should not only focus on urban livestock farming, but should take a system approach by characterizing the value chain to assess the risks brought in urban areas from rural areas.

Research Grants

• University of Edinburgh (2004-2009) (Makita, PhD student)
  
• UK DfID (2004-2009) (Makita, PhD student)
  
• JICA Long-term Training (2004-2006) (Makita, PhD student)

Japan enacted the Rabies Prevention Act in 1950 and achieved rabies-free status in 1957. The vaccination rate, which had been maintained high for some time, has continued to decline, and in recent years has fallen to nearly 40%. Although Japan has a strong quarantine system, she is surrounded by rabies-contaminated countries and the risk of rabies incursion through animal smuggling cannot be denied.
For this reason, Hokkaido and Ibaraki prefectures were selected, and in collaboration with Professor Katie Hampson of the University of Glasgow, the world-renowned expert on rabies epidemiology, we conducted a computer simulation of the spread of infection for the scenario of introduction of a rabies-infected dog into Japan. Currently in Japan, many dogs live indoors and walk on leashes, so the possibility of a large-scale epidemic is low. However, the probability of a large-scale epidemic will increase if dog rabies enters to unowned stray dog populations or if vaccination is abolished.

Research Grants

• MHLW Health and Labour Sciences Research, Research on Emerging and Reemerging Infectious Diseases and Immunisation (Grant No. H25-Shinko-Shitei-004) (2013-2015) (Makita, Co-PI)
  
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The methodology of epidemiology has been developed in the discipline of human medical science. We Veterinary Epidemiology Unit have the word “Veterinary” in our name but are also interested in human epidemiology. An example of our interest on human epidemiology is expressed in the mathematical analysis of the effectiveness of school closure as a collaborative study with Hiroshima University. Dr. Matsuyama and collaborators are also conducting a survey on the impact of the acute febrile illness and the effect of school closure among Japanese households. We aim to develop the method to optimize the school closure.

Research Grants

• JSPS21K17250“Development of optimal method to clarify the cost-effectiveness of school closure against acute febrile illnesses” (PI: Ryota Matsuyama), JSPS20K11120 (CoI: Ryota Matsuyama)

Echinococcosis is a zoonotic disease caused by the oral ingestion of eggs of Echinococcus multilocularis, a parasite that maintains a life cycle between the red fox (Vulpes Vulpes schrencki) and the vole (Myodes rufocanus bedfordiae), which are widely distributed in Hokkaido. Infected people become intermediate hosts and develop severe liver dysfunction. In Hokkaido, about 20 new infected patients occur every year.
From 2013 to 2018, we conducted field surveys in the Nemuro area and conducted epidemiological analysis to predict the number of fox feces on paved roads based on ecological conditions. We will continue to analyze data from Hokkaido and contribute to the control of echinococcosis.

Research Collaboration

• Hokkaido Research Institute of Public Health
  
• Hokkaido Echinococcosis Countermeasures Council

Although there are records suggesting rabies virus infection in wild animals in Japan long time ago, there have been no reports of rabies infection in wild animals since the eradication of rabies. However, rabies is maintained in wildlife populations in many parts of the world, making it difficult to control. In this study, epidemiological analyses of rabies outbreaks records and genome information of preserved virus strains in dogs, wildlife, and humans over the past 20 years (1998-2017) in northern South Africa were conducted to clarify the transmission between different species and humans.
In northern South Africa, virus spillover and maintenance occurred between dogs and jackals. Although rabies vaccination of dogs and cats is encouraged, climatic conditions that have emerged as risk factors are areas of subsistence farming. Poverty hinders vaccination of dogs, and canine rabies outbreaks would occur, resulting in deaths in humans from rabies.

Research Grants

• JSPS-NRF Bilateral Exchange Program “Spatio-temporal analysis of animal and human rabies outbreaks in South Africa during 1998-2017” (2018-2019) (Makita, PI)

Globally, a “Zero by 30” initiative to eliminate human deaths from rabies by 2030 is promoted. In Vietnam, rabies vaccination for dogs is subsidized by the government, but rabies deaths in humans continue. Therefore, a questionnaire survey was conducted in Nguyen County, Thailand, under the collaboration between veterinary epidemiology and economics to elucidate the decision-making process that leads to vaccinating dogs and to estimate willingness to pay for vaccines.
As a result, it became clear that rabies epidemics in dogs continue due to the fact that information about vaccination campaigns is not well communicated in villages where ethnic minorities live, creating spots where vaccination is not progressing.

Research Grants

• Rakuno Gakuen University Collaborative Research “Consideration of elimination methods in rabies-endemic areas based on One Health promotion” (2017) (Makita, PI)

Rabies, a terrifying infectious disease with a fatality rate of 100%, is still widely distributed around the world and kills 59,000 people every year. Japan is one of the few countries in Asia that has achieved elimination of rabies. Dr. Kageaki Tojinbara, the graduate of Rakuno Gakuen University, has collected books on rabies records and past prefectural reports and newspaper articles stored in libraries throughout the country for many years, and compiled the history of rabies, in order to prevent the memory of rabies fading from Japan. In our unit, many students have participated in digitalizing rabies record which Dr. Tojinbara collected, and conducting epidemiological analyses.
An analysis of an outbreak in Osaka during the Taisho period clarified the measures and their effectiveness before and after the Japan's development of the world's first canine rabies vaccine and its use. After the World War II, from the outbreak in Kanto to the elimination in Japan, we have analyzed in detail using spatial epidemiology and infectious disease mathematical modelling. This information is used to help planning rabies elimination in developing countries.

Research Grants

• MHLW Health and Labour Sciences Research, Research on Emerging and Reemerging Infectious Diseases and Immunisation (Grant No. H25-Shinko-Shitei-004) (2013-2015) (Makita, Co-PI)

Colistin is an antibiotic called as the last resort that is effective against multidrug-resistant bacteria. In Japan, it has been used as a therapeutic agent for diarrhea and for growth promotion purposes in livestock, but in 2015, it was approved as a human therapeutic agent in anticipation of multidrug-resistant bacteria. Also in 2015, it was reported from China that the colistin resistance gene mcr-1 was transmitted via a plasmid, and in Japan, risk management measures were taken to discontinue the use of colistin as a feed additive and switch to a second-choice drug.
Food Safety Commission immediately conducted a qualitative food safety risk assessment for the risk caused by the use of colistin in livestock, and following that, our unit participated in the quantitative risk assessment for colistin resistant Escherichia coli in pig farms. A computer simulation verified that the risk management was appropriate.

Research Grants

• Food Safety Commission Research Program for Risk Assessment Study on Food Safety “Research on emergence and characterization of colistin-resistant bacteria” (2017-2018) (Makita, Co-PI)
  
• MAFF Development of livestock disease control technology to deal with drug resistance problems “Assessment of the effect of discontinuation of antibiotic use on pig farms on the rate of resistant E. coli derived from pigs” (2018-2022) (Makita, Co-PI)
  

In September 2018, classical swine fever broke out at a pig farm in Gifu Prefecture for the first time in 26 years in Japan. In addition to classical swine fever, African swine fever is spreading in neighboring countries in Asia, and the virus has been detected in pork caught in quarantine in Japan.
Our unit collaborates with Hokkaido University to conduct risk assessments for classical swine fever and African swine fever. As for countermeasures at pig farms, we have jointly created a swine fever vaccination simulation model with Gifu Prefecture, and Gifu Prefecture is undertaking consultations from all over the country. We also calculate useful measures for epidemic prevention at pig farms using infectious disease mathematical modelling. Furthermore, using socioeconomic methods, we are working on research to encourage producers to voluntarily implement effective epidemic prevention measures. Regarding measures against wild boars, in collaboration with Hokkaido University, we are conducting research on excess mortality due to classical swine fever virus infection, the effects of bait vaccines, and the goal of dissemination efforts, using infectious disease mathematical modelling.

Research Grants

• MAFF Regulatory Science “Development of new comprehensive control technology for CSF” (2020-2024) (Makita, Matsuyama, Co-PIs)

In dairy farms, to prevent infectious mastitis, one cow one cloth teat wiping, disinfection of teats before milking, and dipping after milking. At one point, a cheap and convenient disinfectant that could be used both before and after milking came on the market. However, we received a report from a veterinarian that staphylococcal mastitis seems to be increasing in dairy farms.
Which is more economical, the conventional expensive dipping agent or the new inexpensive and convenient dipping agent? In order to answer this question, we used an economic analysis called the decision analysis method to show that using conventional expensive dipping agents would result in less economic loss.

Research Collaboration

• Hokkaido Okhotsk Agricultural Mutual Aid Association (2012-2013)

In order to control and prevent infectious diseases in livestock, it is very important not only for veterinarians who provide guidance but also for livestock producers to advance hygiene measures with a positive attitude and a focus on the purpose. However, it is not easy for a veterinarian to motivate producers to implement hygiene measures.
In this research, in addition to KAP, which links knowledge (K) to attitude (A) and attitude to practice (P), we clarified the decision-making mechanism that capacity such as labor force and equipment are necessary to facilitate knowledge and practice, using statistics. We are also working on research on the economic effects of hygiene measures and nudges that encourage behavioral change. Through this series of initiatives, it is expected that the Ministry of Agriculture, Forestry and Fisheries as well as prefectural livestock hygiene centers and livestock clinics will improve the sophistication and efficiency of guidance methods for producers.

Research Grants

• MAFF Project to improve food safety and animal health “Development of technology necessary for rapid and accurate quarantine measures against important livestock diseases” (2013-2017) (Makita, Co-PI)
  
• Betsukai Town Commission Project “Economic analysis of dairy hygiene” (Makita, PI)
  
• MAFF Comprehensive Regulatory Science Research Promotion Commissioned Project for Stable Supply of Safe Agricultural, Livestock and Fishery Products “Development of new comprehensive control technology for CSF” (2020-2024) (Makita and Matsuyama, Co-PI)

Mycoplasma mastitis is a dreaded infectious disease that spreads widely in the herd without being noticed, and causes many cows to become alactic when it starts to develop. At Rakuno Gakuen University, a diagnostic method using PCR was developed by Professor Higuchi, and tests are being conducted in Hokkaido for early detection. A case-control study was conducted in the Nemuro area to prevent infection, a further step to early detection.
As a result, it was clarified that careful wiping of teat openings with paper towels before milking is effective for prevention, and that the introduction of cows and the occurrence of mastitis of unknown cause in the past are risk factors. In order to prevent this disease, in addition to thorough milking hygiene, it is extremely important to isolate cows at the time of introduction and to inspect them at the time of the first birth.

Research Grants

• Nemuro Region Mycoplasma mastitis countermeasure meeting (2015) (Makita, Resource person)

In October 2013, amid the porcine epidemic diarrhea (PED) pandemic in many countries around the world, an outbreak occurred in Japan in Okinawa Prefecture, and after invading Kagoshima Prefecture in December 2013, it spread nationwide. In order to investigate the cause of the rapid spread despite Japan's enhanced Standard of Hygiene Rearing Management after the experience of foot-and-mouth disease, a case-control study using a questionnaire was conducted in Kagoshima and Miyazaki prefectures in collaboration with Miyazaki University. As a result of the analysis, it was revealed that the virus was brought into the infected farms mechanically, such as by entering a private vehicle into the hygiene control area, and using a common compost station or a livestock excrement transport services. At that time, there was a shortage of vaccines, and a folk remedy called "feedback feeding", in which minced meat derived from dead suckling pigs was fed to sows, was practiced. We also published the economic damage and consideration of countermeasures using infectious disease mathematical modelling.

Research Grants

• MAFF Investigation on effectiveness of breeding hygiene management standards (2014)(Makita, PI)
  
• JSPS Grant-in-Aid for Scientific Research C (2022-2024) (Makita, PI)
  

Bovine leukemia, a neglected infectious disease, has spread widely throughout Japanese cattle herds without integrated countermeasures. In anticipation of consensus building toward its control, we are working on creating an individual-based infectious disease simulator on the farm to enable exchanges of opinions between producers and veterinarians on site, and consultations among concerned parties.
We are also working on research using animal health economics to see if the perception that "the economic damage can be ignored", which is the basis for neglecting animals, is correct. In Hokkaido, the annual economic losses in dairy industry due to bovine leukemia virus infection through increase of mastitis and decrease of carcass body weight were six million US dollars and 1.4 million US dollars, respectively. We will gradually clarify the economic loss caused by condemnation of dairy carcasses due to bovine infectious lymphoma, the decrease in reproductive efficiency in dairy cattle, and the damage to beef cattle.

Research Grants

• Hokkaido Research Organization Priority Research “Establishment of virus transmission prevention technology system for eliminating bovine leukemia virus” (2017-2019) (Makita, Co-PI)
  
• Hokkaido Higashi Agricultural Mutual Relief Association (2017)
  
• JSPS Grant-in-Aid for Scientific Research C (2022-2024) (Makita, PI)

Southwestern Uganda is a dairy farming area with vast pasturelands. Dairy farming is Uganda's main export industry and plays an important role in earning foreign currency. At the beginning of the JICA Safe Milk Promotion in Mbarara Project, dairy farmers believed that their cows did not have mastitis, but we found that over 60% of cows suffer from subclinical mastitis. Many of the ticks that transmit East Coast fever, which is fatal to calves, are multidrug-resistant to acaricides, but epidemiological analyzes have shown that poor quality of the cattle crush and the acaricide sprayers are risk factors for the disease. Milk production increased by 20% by introducing one-cloth-one-cow teat wiping and improving cattle crush and acaricide sprayers through self-funding of the producers. After this project, JICA Overseas Cooperation Volunteers have been dispatched to Mbarara District since 2022 to continue technical assistance.

Research Grants

• JICA Overseas Program (2015) (Makita, PI)
  
• JICA Partnership Program, Safe Milk Promotion in Mbarara Project (2016-2019) (Makita, PI)
  
• JICA/JOCV University Collaboration (2022-)

Worldwide, 2 billion cases of diarrhea occur, and 1.5 million children under the age of five lose their lives each year. Foods of animal origin account for the largest cause of foodborne illnesses, including non-diarrheal diseases. Since its inception, this unit has worked with the International Livestock Research Institute (ILRI) to develop a method for assessing the risks in informal food value chains in developing countries, and to reduce the food safety risks in Asia and Africa. In addition, as the World Organization for Animal Health (WOAH) Collaborating Center consortium for Food Safety, we are developing human resources in the Asian and African regions.

Research Grants

• BMZ, Germany (2008-2012) (Makita, ILRI Postdoctoral scientist, Scientist)
  
• ACIAR, Australia (2012-2018) (Makita, ILRI Joint Appointment Scientist)
  
• JIRCAS Supporting Grant for Young Researchers (2014-2015) (Makita, PI)
  
• World Bank Food Safety Risk Assessment Task Force in Vietnam (2016-2017) (Makita, ILRI Joint Appointment Scientist)
  
• JSPS RONPAKU Program (2017) (Makita, PI)
  
• Swedish University of Agricultural Science Graduate School Program (2021) (Makita, Resource person)

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