The 5th Nikkei Asian Conference on Communicable Diseases 2018

‘Okinawa Communicable Diseases
Statement 2018’1

Table of contents

1. Introduction .................................................................................................................. 3
2. Report on Progress of Public-Private Partnership (P3) in Japan .................................. 4
2.1 Tuberculosis ............................................................................................................ 4
2.1.A P3 Initiative on Tuberculosis and its Background .......................................... 4
2.1.B Status of Progress ............................................................................................ 4
2.2 Ebola ....................................................................................................................... 5
2.2.A Ebola P3 Initiative and its Background .......................................................... 5
2.2.B Status of Progress ............................................................................................ 5
2.3 Malaria .................................................................................................................... 6
2.3.A Malaria P3 Initiative and its Background ....................................................... 6
2.3.B Status of Progress ............................................................................................ 6
3. New Challenges and Actions Needed ........................................................................... 7
3.1 Tuberculosis P3 Initiative: Issues and Actions Needed .......................................... 7
3.2 Ebola P3 Initiative: Issues and Actions Needed ..................................................... 8
3.3 Malaria P3 Initiative: Issues and Actions Needed .................................................. 8
4. New Challenges ............................................................................................................ 9
4.1 Asian Communicable Diseases Clinical Research Center ...................................... 9
4.2 Formation of Okinawa Communicable Diseases Research Center .......................11
4.3 Measures against Multidrug-Resistant Bacteria (AMR) ...................................... 12
4.4 Public Health and Infection Control ..................................................................... 12
4.5 Contribution of Logistics to Infection Control ..................................................... 13
4.6 Contribution of ICT and AI to Infection Control ................................................. 14
4.7 New seeds of technology ...................................................................................... 14
4.8 Incentive Promoting Private Sector Investment ................................................... 15
5. Conclusion .................................................................................................................. 15<Appendix> .................................................................................................................... 17

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1. Introduction
With progression of globalization, Japan and other countries, especially Asian countries, havebecome inseparable at every level, such as economics, society, and, culture. Threat of infectious
diseases, such as outbreaks of Zika virus and Ebola virus infections, spread of tuberculosis andmalaria, and raging of multidrug-resistant bacteria (AMR), are still major problems inside andoutside the country.
With an increase in international recognition of infectious diseases as the background,industry-academia-government key persons of infection control gathered in Okinawa on February 2
and 3, 2018, from countries all over the world and held the 5th Nikkei Asian Conference on
Communicable Diseases 2018. Through discussion, participants re-confirmed the necessity andeffectiveness of promoting measures against infections threatening people’s health and economic
activity through Public-Private Partnership (P3), as confirmed in previous conferences. Nikkei Asian
Conference on Communicable Diseases manages ‘Asia Medical Innovation Consortium (AMIC)’
comprised of several working groups throughout the year for the purpose of designing and executing
P3.
In the plenary session of the 5th conference, ‘AMIC Tuberculosis Working Group’reported that the
TB-LAMP method of Eiken Chemical made major progress, such as acquisition of the recommendation for theuse from the World Health Organization (WHO). The ‘AMIC Malaria Working Group’ prepared a
proposal to the government referring to that prepared by the Tuberculosis Working Group. To
establish a network of Asian bases for infection control including Okinawa and promote practicalapplication of new techniques, ‘AMIC Working Group for the Asian Communicable Diseases
Clinical Research Centers’ was founded last year. Its basic concept was discussed in the plenary
session to make a proposal on the Asian Communicable Diseases Clinical Research Center to thesociety.
In addition, issues concerning overseas activity for Japanese therapeutic drugs applying the lessons
learned from the outbreak of Ebola virus infection, actions taken to form the Okinawa Communicable
Diseases Research Center, issues concerning promotion of infection control against
multidrug-resistant bacteria (AMR), measures to improve public health, the importance of logistics
for infection control, and the way of utilizing information and communication technologies (ICT)and artificial intelligence (AI) were discussed. In addition, the necessity of innovation contributing
to international infection control was confirmed, and corresponding seeds from Japan wereintroduced. Through the discussions, expectation for development of this conference to contribute to
global infection control not limited to Asia was expressed.
Participants agreed to ‘Okinawa Communicable Diseases Statement 2018’ as the achievement of
the discussions. In addition to reporting the achievement of this conference to government-related
conferences, the statement will be widely sent in not only Japan but Asia and worldwide. With
deepening of international understanding, Japan will be needed to more strongly commit toworldwide infection control in the future. For the history of foundation of the Nikkei Asian
Conference on Communicable Diseases and content of conferences, please refer to past statements.
http://ac.nikkeibp.co.jp/4thnac/okinawa2017/pdf/okinawastatement2017_ja.pdf
http://ac.nikkeibp.co.jp/3rdnac/tokyo2016/pdf/3rdnac_tokyo2016_statement_jp.pdf
http://ac.nikkeibp.co.jp/bio/okinawa2015/pdf/OkinawaCommunicableDiseasesStatement2015.pdf
http://ac.nikkeibp.co.jp/bio/okinawa0214/pdf/OkinawaCommunicableDiseasesStatement2014.pdf

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2. Report on Progress of Public-Private Partnership(P3) in Japan
2.1 Tuberculosis
2.1.A P3 Initiative on Tuberculosis and its BackgroundAs deaths from a single infectious disease, the number of deaths from tuberculosis is the highest
in the world. In 2016, 10.4 million people newly developed tuberculosis and 1.7 million died. The
number of patients in the world tends to decrease but tuberculosis outbreaks still continue mainly indeveloping countries, and the prevalence in Japan is still high. Moreover, emergence ofmultidrug-resistant Mycobacterium tuberculosis due to inappropriate use of antituberculous drugs
has increased patients with difficulty in treatment. In ‘End TB Strategy’ formulated by the World
Health Organization (WHO), 90% reduction of the number of deaths from tuberculosis and 80%
reduction of the prevalence by 2030 setting the baseline at those in 2015 are targeted.
In Japan, countermeasures against tuberculosis after World War II succeeded because the network
comprised of the Japan Anti-Tuberculosis Association and nationwide health centers functioned andaccess to patients improved through the national health insurance system covering the whole nation.
In addition, simple and highly accurate diagnostic techniques and drugs against multidrug-resistanttuberculosis have been developed. These experience and innovation in Japan are expected tocontribute to the world’s countermeasures against tuberculosis.
The AMIC Tuberculosis Working Group attaches greater importance to the following items to end
tuberculosis: (1) Development of a simple technique capable of accurately diagnosing tuberculosis
which can be provided at a low-price and (2) reliable diagnosis of multidrug-resistant tuberculosis
and proper prescription and reliable taking of antituberculous drugs. For these, they consider that it
is essential to package diagnostic techniques and antituberculous drugs and realize a medical caredelivery system capable of seamlessly providing the packages to developing countries. This Working
Group proposed P3 Package for MDR-TB comprised of a simple and highly accurate genetic test
(TB-LAMP, Eiken Chemical) for screening, multidrug-resistant genetic test (Genoscholar, NIPRO)
capable of definitely diagnosing multidrug-resistant tuberculosis, and a new drug against
multidrug-resistant Mycobacterium tuberculosis (Delamanid, Otsuka Pharmaceutical).

2.1.B Status of Progress
Genoscholar, TB-LAMP, and Delamanid have acquired recommendation for the use from theWorld Health Organization (WHO). Regarding P3 Package, NIPRO and Eiken Chemicalcooperatively performed primary screening of tuberculosis using TB-LAMP in the Philippines as apart of the JICA Collaboration Program with the Private Sector for Disseminating JapaneseTechnologies, and proposed an algorithm to diagnose drug-resistant tuberculosis using Genoscholar.
Basic performance evaluation of each technique (Phase I) has been completed and it is now going toprogress to evaluation of the algorithm (Phase II). In the JICA program, a project to replace theconventional method (culture test) with Genoscholar of NIPRO to shorten the time required for
diagnosis is progressing in Indonesia, and P3 Package for MDR-TB into Afghanistan has alreadybeen introduced.
The public-private collaboration project started at various levels through approaches to theministries and agencies. The AMIC Tuberculosis Working Group had an opportunity in the firstministerial-level meeting concerning tuberculosis held in November 2017 in Russia, in which astatement of measures previously taken aiming at ending tuberculosis was distributed, sending
information to the countries.
Measures to make use of the techniques comprising P3 Package for countermeasures against
tuberculosis have also been in full progress in various countries and regions. TB-LAMP has been
confirmed to be highly sensitive compared with the conventional method (smear test) in a field test4

performed in Cameroon and the Ministry of Heath decided on replacement. We have a good prospect
for supply through utilizing the budget for The Global Fund to Fight AIDS, Tuberculosis andMalaria (Global Fund) and Global Drug Facility of Stop TB Partnership. Discussion on the spread of
the test is underway in several countries and national projects are moving in 3 countries.
Delamanid was included in the WHO Model List of Essential Medicines in 2015 and its supply toabout 100 countries through GDF became possible in 2016. Partnership with overseas
pharmaceutical companies became realized in 2017, and acquisition of approval in highly burdened
countries with high prevalence and population is planned. In addition, getting support by the Bill &Melinda Gates Foundation, development of a new regimen for tuberculosis based on delamanid anda novel therapeutic drug for tuberculosis (OPC-167832) will be proceeded.
The AMIC Tuberculosis Working Group will strengthen the public-private collaboration projectby getting opportunities for encouragement in high-level meetings, such as those in the United
Nations General Assembly held in September 2018.

2.2 Ebola
2.2.A Ebola P3 Initiative and its Background
Although it is currently calmed down, the risk of outbreak of Ebola virus infection is constantly
present. Although large-scale outbreaks were controlled, Japan should continue to provide necessary
support through public-private collaborative activity and have interest in cooperation with Asian andother countries worldwide.
In March 2017, a stock of ‘favipiravir (product name: Avigan)’ for about 2 million people, theupper limit of inpatients in estimation of the damage of novel influenza stipulated in the Government
Action Plan was decided in the ‘Guidelines for Measures against Novel Influenza’ revised by thegovernment. However, the stock is limited to the use against novel influenza and it cannot be used
for other diseases. To prepare for not only re-outbreak of Ebola virus infection but also otherinfectious diseases, it is urgently needed to construct a framework enabling a swift response, such asa system in which unapproved potential medical drugs and indications in clinical study steps areclosely examined beforehand and can be used irregularly for emergencies corresponding to thesituation.
Ebola P3 Initiative is a public-private collaboration project which started in 2014 getting financial
cooperation from the Ministry of Health, Labour and Welfare in response to a request for support
from the government of Guinea, an Ebola virus infection-affected country, and request forcollaborative research from a French research institute, Institut National de La Sante Et de La
Recherche Medicale (INSERM). One pillar of the project was to conduct a clinical study
demonstrating the treatment effect of favipiravir (product name: Avigan) on Ebola virus infection.
Upon presenting the animal study results of Avigan to a French delegation in the WHO meeting on
countermeasures against Ebola held in Summer 2014, a clinical study was planned in cooperation toutilize the drug against Ebola as early as possible. Agreement with Toyama Chemical for conduct ofa phase II clinical study administering favipiravir was obtained. The study was conducted incooperation with local medical NGO and INSERM taking responsibility for the execution under
permission by the French and Guinean Regulatory authorities. In this public-private collaboration
project, Cannon Medical Systems (former Toshiba Medical) and Nagasaki University provided theEbola virus diagnostic drug and device employing the RT-LAMP method and performed verification
tests in Guinea.

2.2.B Status of Progress
In the clinical study of favipiravir, favipiravir was administered to 126 patients between
December 2014 and May 2015. Fifty-five patients with a low viral load before administration

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survived, reducing the mortality rate as achievement of this clinical study, and 44 patients actuallysurvived. The final report was published in March 2016. Getting funds from AMED, Nagasaki
University, and Fuji Film/Toyama Chemical started the ‘study toward development of treatment,
diagnosis, and preventive methods against viral hemorrhagic fever’ targeting Crimean-Congo fever,Marburg disease, and Lassa fever in 2018. Favipiravir is also expected to be an effective therapeutic
drug for tick-borne ‘severe fever with thrombocytopenia syndrome (SFTS). The clinical study was
conducted being led by Masayuki Saijo, Director, Department of Virology 1, National Institute of
Infectious Diseases, and Masataka Yasukawa, Vice President of Ehime University, and findings
leading to the development of an effective treatment method were acquired. In response to this, aclinical trial aiming at acquisition of pharmaceutical approval is being prepared in Japan, and aclinical trial is also being planned in Korea.
Cannon Medical Systems has also provided for free the diagnostic kit employing the RT-LAMP
method for 10,000 tests and 9 diagnostic devices to the Guinean government through the Ministry ofForeign Affairs of Japan by 2017. However, there is no prospect of sales of the Ebola virus
diagnostic kit after 2018. With the financial cooperation of AMED, the company started
development of a Zika fever diagnostic kit in collaboration with Nagasaki University in June 2016. A
clinical study was conducted from March 2017 in Brazil with many infected patients and it wascompleted in November 2017. Approval for manufacturing and sales as a Zika fever diagnostic kit
was applied in January 2018 in Japan.
In addition to development of new treatment methods of emerging and re-emerging infectious
diseases, institutional measures based on the lessons from the Ebola outbreak are also being
discussed. Since favipiravir was approved as an anti-influenza drug, it was difficult to immediately
support overseas in the outbreak of Ebola virus infection. To solve this problem, ‘Scheme to provide
unapproved drugs to developing countries in an emergency’ was constructed under the initiative of
the Prime Minister's office in cooperation with the Ministry of Foreign Affairs and Ministry of
Health, Labour and Welfare and ‘adjustment meeting of the ministries concerning providing
unapproved drugs overseas’ and ‘expert committee’ thereof were held in July 2017.

2.3 Malaria
2.3.A Malaria P3 Initiative and its BackgroundThe number of malaria-infected persons reached 200 million in 2016, and the number of deaths
reached 440,000. Five percent of deaths of infants aged 5 years or younger were due to malaria, andit reached 10% in Sub-Saharan Africa. The Asia Pacific Leaders Malaria Alliance holds a high target
in a roadmap: elimination of malaria from 6 countries and prevention of infection of 40.3 million
people by 2016-2020 and elimination from 22 Asian countries by 2026-2030.
For elimination of malaria, Japan is able to provide a comprehensive solution by integrating
techniques of private companies in 3 fields: tests/diagnosis, development of new drugs, and vector
control for prevention. Supply of necessary medical drugs and medical devices depends oninternational supporting institutions such as the Global Fund, but these institutions request
acquisition of WHO-PQ certificate in many cases, for which the following items are essential: (1)Verification of the usefulness based on evidence data and application, (2) winning nomination by therecipient country, and (3) construction of a permanent network with international institutions, suchas WHO and Global Fund. However, these are difficult to realize by private companies alone.
Formation of P3 Initiative as seamless industry-academia-government collaboration is important.

2.3.B Status of Progress
The AMIC Malaria Working Group established in September 2016 has had many discussions andpointed out the importance of integration of the fields of tests/diagnosis, development of new drugs,
and vector control for prevention, and it was agreed that achievement being acquired in Asia should
be ensured and at the same time, active countermeasures are essential for the malaria endemic zone

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centering Africa.
However, the situation concerning malaria is different between Asia and Africa. Thus, after
discussion in the 4th conference, the Asia Task Force and Africa Task Force were established andissues were discussed corresponding to the situation in each region. In the Asia Task Force, aspecific strategy for acquisition of WHO-PQ certificate was discussed, and the results of a study on
application of a high-sensitivity test system developed by SYSMEX and Eiken Chemical wereshared. In addition, the Africa Task Force shared the results of a study in which therapeutic drugs
were administered in all regions with accumulated malaria patients, such as Kenya, and elimination
succeeded.
Regarding high-sensitive high-speed diagnostic techniques, in Japan, SYSMEX developed amultichannel automated blood cell analyzer utilizing flow cytometry and Eiken Chemical developed
a high-sensitive test system adopting the LAMP method capable of amplifying genes even in
outdoor fields. Regarding therapeutic drugs, Neopharma suggested that 5-aminolevulinic acid
(5-ALA) being developed may be combined with artemisin, for which acquisition of resistance has
recently been problematic. Getting support from GHIT Fund, Osaka University and Nobelpharmacompleted preparation for initiation of a new clinical study of BK-SE36 vaccine with adjuvant in
Burkina Faso and Germany. For vector control, Sumitomo Chemical developed a long-lasting
insect-controlling net, long-lasting indoor spray, and mosquito larvicide, and proposedcomprehensive vector control. The long-lasting indoor spray acquired WHO-PQ certificate in 2017.

3. New Challenges and Actions Needed
3.1 Tuberculosis P3 Initiative: Issues and Actions Needed[Issues]
Toward full-scale application of P3 Package, introduction should be proceeded corresponding toculture, language, and medical delivery system of each country in cooperation with local key opinion
leaders (KOL). In addition, it is difficult to continue the project in a profitable way by individualcompanies alone. To continuously provide diagnostic techniques and therapeutic drugs, it isimportant to acquire support from the government and external funds. Moreover, differences in theprocedure and conditions of application for approval among nations are obstacles of the spread.
Acceleration of research and development of new innovation aiming at ending tuberculosis is alsoneeded.

[Actions Needed]<For Consortium and Companies>
1) The AMIC Tuberculosis Working Group should develop close coordination with persons
concerned in Japan as well as sufficient coordination with target countries to facilitate providing P3
Package in a way appropriate for the condition of each country. The group should also acquire
cooperation from the government and external funds to continue the project.
2) It is necessary to accelerate development of a novel diagnostic technique (Fuji Film) to detect acomponent of Mycobacterium tuberculosis, lipoarabinomannan (LAM), in urine and therapeutic
drugs including OPC-167832 (Otsuka Pharmaceutical) with a novel action mechanism inhibiting
cellular synthetic enzyme of Mycobacterium tuberculosis.
3)Exploring new expansion of P3 projects is necessary.
<For Academia>
Measures to promote studies aiming at developing new diagnostic techniques and therapeutic
drugs for the future, such as construction of a genomic database of Mycobacterium tuberculosis,
should be performed by the National Institute of Infectious Diseases, Japan Anti-Tuberculosis
Association, and National Center for Global Health and Medicine in cooperation with each Asian
country.

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<For Government>
1) The government should constantly support the continuation of the project.
2) Harmonization of regulatory affairs with countries with high burden of tuberculosis, such as
developing countries, and preparation of a system to simplify examination in the target countries, if
approval has been acquired in Japan, are needed.

3.2 Ebola P3 Initiative: Issues and Actions Needed
Companies are performing clinical studies to make use of their products for not only Ebola virus
infection but also diagnosis and treatment of other new emerging and re-emerging infections.
Although the Ebola outbreak in West Africa has converged, the issues below were raised. By
investigating dealing with regulations and systems and support for companies, more effective controlof new emerging and re-emerging infections becomes possible.

[Issues]
1) The main organization responsible for fund-raising, planning, and execution of the clinical studyof favipiravir against Ebola virus infection in Guinea is INSERM, and INSERM took initiative withregard to the timing of disclosing the study results. Since the organization responsible for executing
the clinical study was not a Japanese government agency, grasping information and negotiation for
executing the study at the local site were difficult for one company.
2) Since Avigan is unapproved for treatment of Ebola virus infection, it was difficult to support in
the pandemic of Ebola virus infection.
3) There is no prospect of sales of the RT-LAMP kit as an Ebola virus diagnostic kit after 2018.
Since the market was temporary and unstable and it was an emergency action after the occurrence ofthe pandemic, construction of a business model was difficult.

[Actions Needed]
1) For execution of clinical studies overseas by companies, active involvement of the Japanese
government and cooperation with the government and regulatory authority of each country areneeded.
‘Scheme to provide unapproved drugs to developing countries in an emergency’ was establishedin 2017 under the initiative of the Prime Minister's office. It needs an expeditious response, such as
preparation in which unapproved medical drugs in clinical study steps and drugs with the possibilityof use without approval are closely examined beforehand in cooperation with pharmaceuticalcompanies to realize the plan to cope with infectious diseases for which no treatment method has
been established. In addition, cooperation with the governments of countries with high incidences ofinfection is important.
2) Consideration of procurement of drugs for infectious diseases and diagnostic kits by the Japanese
government and construction of the minimum market in Japan are necessary.
3) The government should further promote support for incorporation into the supply process ofinternational institutions, such as acquisition of WHO-PQ certificate.
4) Development of P3 Projects to target new emerging and re-emerging infections based on
experience of Ebola P3 project is necessary.

3.3 Malaria P3 Initiative: Issues and Actions Needed[Issues]
Countermeasures against malaria are now facing 4 issues: 1) Detection and treatment ofasymptomatic plasmodium carriers, 2) countermeasures against drug resistance/insecticide resistance3) securing financial resources, and 4) strengthening of health system. WHO also recognizes thenecessity of innovation overcoming these 4 issues. Japan is expected to take actions through P3
centering Issues 1) and 2).

81) Detection and treatment of asymptomatic plasmodium carriers: The presence of asymptomatic
malaria parasite carriers undetectable by the conventional diagnostic technique has been clarified. It
has been pointed out that although they are asymptomatic, they may develop the disease or serve as a
new source of infection, proposing the importance of high-sensitivity testing and early initiation oftreatment. At present, WHO attaches greater importance to the presence of evidence for reduction of
infection and death by intervention of asymptomatic cases. It is important to construct evidence forthe significance of high-sensitivity testing and early treatment.
2) Countermeasures against drug resistance/insecticide resistance: Emergence of vector mosquito
resistant to existing insecticides and malaria parasites resistant to anthelmintic has been confirmed.
For countermeasures, surveillance of drug sensitivity and introduction of a new drug are needed.
Since research and development of an insecticide requires 10 years, a scheme to recover theinvestment for research and development is needed.
3) Securing financial resources: Disparity of countermeasures against malaria is expanding between
Western countries which succeeded in elimination and some African and Asian countries. Difference
in investment has been pointed out as a cause of this bipolarization. Foundation to improve healthcare is insufficient in many developing countries requiring countermeasures against malaria, andthey inevitably depend on support from international aid organizations, such as WHO and Global
Fund.
4) Strengthening of health system: Health system necessary for malaria control is vulnerable incountries with the spread of malaria.

[Actions Needed]<For Consortium and Companies>
For detection and treatment of asymptomatic parasite carriers and countermeasures against drug
resistance /insecticide resistance described above, consortium and companies are needed to provide
comprehensive solutions for the following 3 fields: ‘Vector control exerting a strong effect on
insecticide-resistant mosquitoes’ which has been performed, in addition to ‘high-sensitive rapid
diagnosis’, ‘development of a new drug with high safety and effect on drug-resistant plasmodium’.
All fields require various lobbying activities and verification data collected in local regions toacquire the certificate of the WHO prequalification program (PQ). In addition, private companies
have to continue long-term investment while strengthening cooperation with academia.
<For Government>
To acquire WHO-PQ certificate, making efforts by private companies alone is limited, andindustry-academia-government collaboration is necessary. To perform a clinical study in Africa withthe most serious damage by malaria, construction of an implementation system, development of
human resources for negotiation with local medical institutions and communities, and cooperation
with policy advisors are important. To recover the high research cost, Japan-led establishment of a
procurement support route, such as support by buying out products which acquired WHO-PQ
certificate, is necessary.

4. New Challenges
4.1 Asian Communicable Diseases Clinical Research Center[History and Current Status]
To proceed specific discussion to construct the Asian Communicable Diseases Clinical ResearchCenter and Okinawa Communicable Diseases Research Center, ‘Working Group for the Asian
Communicable Diseases Clinical Research Center’ was founded in 2017 as a new AMIC working
group. The working group proposes the basic concept of the Asian Communicable Diseases ClinicalResearch Center as follows. This concept is consistent with ‘Asia Human Well-Being Initiative’promoted by the government.

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[What is a clinical study?]
Clinical study is defined as ‘an intervention study with humans’ in this concept. This is an
essential step in the research and development of new drugs and medical techniques. To develop
diagnostic and new drugs, cooperation with regions with actual incidences of infection is necessary.
To establish the Asian Communicable Diseases Clinical Research Center and get their work on track,
it is important to proceed multinational clinical studies by the spirit that Japan and each Asian
country are equal partners.
For new drugs developed in Japan, clinical studies up to the phase I study confirming the safety
will be performed in Japan, for which strengthening of cooperation with base institutions, such as the
National Center for Global Health and Medicine and Nagasaki University.
Phase II and later phase clinical studies judging the effect of new drugs have to be performed incooperation with each Asian country with many infected persons. Based on the data collected in thisway, approval of sales in each country and WHO-PQ certificate can be acquired and spread of the
new drug can be accelerated. Based on these results, phase III clinical study will be performed toapply it in actual clinical care in local regions, and inclusion in the infection control guidelines in the
country is also important. For preparation of the phase II and III study protocols, cooperation andagreement between countries including the regulatory authorities is desirable.
SATVI in South Africa is a preceding example of the Asian Clinical Research Center specialized
in clinical studies of tuberculosis vaccines. Clinical trials from Phase II and later phases oftuberculosis vaccine of the whole world are performed at this center.

[Issues]
Japan founded bases of basic studies on infection in Asia and Africa, mainly in universities,
through projects of JGRID and SATREPS. The Japan International Cooperation Agency (JICA) also
supports infection research facilities in other countries. In addition, the Japan Anti-Tuberculosis
Association has developed human resources for countermeasures against tuberculosis by inviting
physicians and researchers from all over the world with a focus on Asian countries for more than 50
years. In addition, the National Center for Global Health and Medicine started a project to form a
global clinical research network center in 2016 and clinical research and clinical trial centers arebeing formed in Asian countries.
However, cooperation with these centers and their capacity are not necessarily sufficient, and thecooperation system is fragile in Asia. In addition, for P3 Projects aiming at elimination of malaria
which has started, study concerning strengthening of similar base and network construction isnecessary for Africa with the most serious damage by malaria.

[Actions Needed]<For neighboring Asian countries>
The consensus process for this proposal will be initiated in close collaboration with countries
concerned as an industry-academia-government collaboration project.
<For Japan>
1) Strengthening of collaboration with the global clinical research network center formation projectof the National Center for Global Health and Medicine and Nagasaki University
2) Preparation of a system to perform clinical study and animal study using primates at the sametime in cooperation with the Tsukuba Primate Research Center, National Institutes of Biomedical
Innovation, Health and Nutrition
3) Formation of network of researchers preparing clinical study plans and assay systems for eachtarget disease to support the Asian Communicable Diseases Clinical Research Center.
4) Feasibility of establishing the Asian Communicable Disease Clinical Research Center should bestudied by all Japanese ministries.
5) Further discussion on the above items in the working group and close consideration of the specificpicture of the Asian Clinical Research Centers including request to the government are necessary.
6) The AMIC Malaria Working Group has to elaborate the concrete image of the Clinical ResearchCenter in Africa.

107) In addition, to realize the above, early operation of BSL4 in Nagasaki University is needed.

4.2 Formation of Okinawa Communicable Diseases ResearchCenter[History and Current Status]
Since Okinawa Prefecture is tourism-oriented, with the number of tourists visiting being in theregion of 9.40 million (including 2.54 million from abroad), and engaged in international distribution
connecting 11 cities in Japan and other countries centering on Naha Airport, ranked 4th in theinternational cargo volume in Japan, the risk of emerging and re-emerging infectious diseases
coming into the prefecture is high and infection control is an urgent issue. In addition, Okinawa isrich in biodiversity due to the natural characteristics of subtropical climate and creation of new
industries utilizing the bioresources, such as development of vaccines against infections andtherapeutic drugs, is expected. Okinawa also has a history of eradicating malaria and filaria. Making
use of these experiences and techniques is expected for international contribution and cooperation.
With this background, formation of Communicable Diseases Research Center is promoted based on
the comprehensive plan of the prefecture, “Okinawa 21st Century Vision Plan”.
In the national plan, setting the core at University of the Ryukyus Faculty of Medicine andHospital, scheduled to move to the former residential area in west Futenma in 2024, preparation ofbases of health and medical care in Okinawa is aimed at. In the Cabinet Office Council reportcompiled in April 2017, infection control is positioned as a pillar together with the bioinformationbank and bioresource library.
Okinawa Communicable Diseases Research Center and bases of health and medical care in
Okinawa should be prepared to contribute to improvement of health and medical care and welfare
for residents of Okinawa Prefecture. It is necessary to review the way of their function andcollaboration should be from these viewpoints.
[Issues]Specific consideration of the following items is necessary.
1) Preparation of an infectious disease epidemiology system (introduction of IT) by making use of
the characteristic of the prefecture, islands
2) Construction of bases contributing to improvement of health and medical care and welfare forresidents of Okinawa prefecture and superiority of the bases able to appeal to the world
Examples• Strategic logistic base in response to infection crisis utilizing the logistic hub• Preparation of a tropical and subtropical infectious disease surveillance system and collaboration
with bio-information bank
• Foundation of Communicable Diseases Diagnosis Center (tentative name) and improvement of thefunction of infection control• Development of human resources, such as physicians specialized in infection• Establishment of a diagnostic and treatment system covering the entire prefecture3) Collaboration with infection research bases in Japan and other countries, such as the National
Institute of Infectious Diseases
4) Utilization of bioresources in Okinawa
5) Strengthening of collaboration with research and medical institutions, such as Okinawa
Institute of Science and Technology Graduate University and infection-related companies[Actions Needed]
Based on the above items, the way that the Okinawa Communicable Diseases Research Center
should be will be further discussed in the working group and proposed in the 6th conference.

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4.3 Measures against Multidrug-Resistant Bacteria (AMR)[History and Current Status]
Emergence of drug-resistant bacteria due to improper use of antimicrobial drugs has recently beena social problem and many patients die due to drug-resistant bacteria, becoming a threat of mankind.
In May 2015, a global action plan concerning drug resistance was adopted in the annual general
meeting of WHO, and member nations were required to formulate an action plan. In addition toformulation of an action plan, international industry-academia-government actions to promoteresearch and development of new antimicrobial drugs are progressing in each country.
In Japan, ‘Action plan of countermeasures against drug resistance’ (2016-2021) was formulated in
April 2016, which presented the policy of taking countermeasures against drug resistance by
public-private union in cooperation between the agricultural and medical fields under the “one health”
concept. In the medical field, under this plan, ‘AMR Clinical Reference Center’ was launched in the
National Center for Global Health and Medicine, ‘Drug-resistant infectious disease control research
center’ was launched in the National Institute of Infectious Diseases, and implementation of
educational programs for medical care workers is progressing. Specific actions have become fullprogress, such as that ‘Antimicrobial Stewardship The 1st Edition’ was published in June 2017,
guidelines for proper treatment of infectious diseases for medical care workers were presented, andmedical treatment fee was set for explanation of antimicrobial drug prescription to patients.
Measures against multidrug-resistant bacteria reached the step of specific “active move” from
“idea”.

[Issues]
Further change in consciousness in the medical, agricultural, and environmental fields isnecessary in addition to that in general people. Moreover, although research and development ofnovel antimicrobial drugs, which once slowed down, is rising, the absolute number is still small andfunding to support research is insufficient. Industry-academia-government cooperation for researchand development of antimicrobial drugs and vaccines is a necessary step present ahead.
Development and spread of diagnostic drugs, thorough surveillance, and cooperation with theagricultural and environmental fields are also needed.

[Actions Needed]
1) Improvement of awareness of AMR threat by workers engaged in the medical care, agriculture,
forestry, fishery, and livestock industries and general people2) Education and enlightenment of medical care workers and general people in public health and useof antimicrobial drugs
3) Thorough execution of standard infection control (standard precaution) at medical practice sites
4) Change in consciousness of workers in the food industry, such as introduction of HACCP
5) Drastic change in consciousness of workers in the agriculture, forestry, fishery, and livestockindustries and attendance of Ministry of Agriculture, Forestry and Fisheries officials at the next
conference
6) Promotion of development of new antimicrobial drugs and vaccines including push- and pull-type
supports
7) Promotion of development of rapid diagnostic techniques
8) Full-scale research and development with international industry-academia-government
cooperation, such as activities of the Japan Pharmaceutical Manufacturers Association
9) Development and thorough strengthening of an international multidrug-resistant bacteria
surveillance system

4.4 Public Health and Infection Control
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[History and Current Status]
To secure safe water and apply it to infection control in Asia and Africa, approaches from 2
viewpoints: improvement of water infrastructure and hygienic behavior, are needed. The former
represents measures to improve sanitary facilities including waterworks and the latter includes
promotion of understanding hygienic behavior by residents, such as washing hands with soap andmaintenance of cleanliness around water supply facilities. At present, it is estimated that 663 million
people cannot access clean water in the world, and 2.4 billion people live in regions in which theycannot continuously use sanitary facilities such as a toilet.
When tap water was not developed before or immediately after the end of World War II, Japan
had problems with outbreaks of infectious diseases, such as cholera, dysentery, typhoid, andparatyphoid. However, incidences of drinking water-borne infectious diseases and death of infants
drastically decreased with the spread of waterworks supplying safe drinking water. Saraya has spreadhygienic habits, such as disinfection of the fingers and washing hands, in developing countries.

[Issues and Actions Needed]
To connect improvement of water infrastructure to improvement of public health including
infection control, improvement of water infrastructure is insufficient. To achieve the target, it isnecessary to cope with issues below:
1) Integrated design of waterworks, sewage, and waste disposal: It is necessary to integrate waterand sewer services and residential waste processing in the design, such as improvement ofwaterworks increases the inflow water volume into sewage. Construction of P3 realizing cooperation
beyond business entities is essential.
2) Strengthening of hygienic education of general people: It is necessary to promote it utilizing theschool health program, such as encouraging washing of hands.
3) Proper operation of sanitary facilities and strict enforcement of maintenance4) Stable utilization of financial resources: JICA promotes development of water infrastructure over
the world, but overall improvement cannot be achieved by this activity alone. To promote water
infrastructure development in broader regions, securing of funds is necessary.
5) Innovation in the public health field

4.5 Contribution of Logistics to Infection Control[History and Current Status]
In the outbreak of Ebola virus infection in 2014, insufficient distribution network supplying drugs
and medical devices and capacity of warehouses, lack of information related to the supply anddemand of materials, limited access to regions with infection due to closure of national borders, andoverlap and inefficiency of support due to insufficient public-private cooperation were problematic.
Learning from this lesson, international organizations, such as the United Nations World Food
Programme (WFP), WHO, and United Nations Children’s Fund (UNICEF), and private companies,
such as Johnson & Johnson of the US and NEC, participated from 2015 and formed ‘Global
Pandemic Supply Chain Network (PSC network)’.
Material supply chain is the basis of all emergency support activities. Formation of a system toefficiently supply materials at an appropriate timing is essential in preparation for outbreaks in the
future. Utilizing the geographical advantage of Okinawa prefecture, close location to Asia, formationof a major base of logistics, such as a 24 hour-operating airport, has been aimed at. Utilizing this
distribution network for pharmaceutical logistics, synergy between the bases of health and medicalcare in Okinawa and Communicable Diseases Research Center can be expected. Okinawa Prefecture
clarified a plan to form an international distribution center by concentrating on the airport/harbor siteindustries aiming at storage and distribution of high value-added products, such as drugs, in the“Okinawa 21st Century Vision Plan (revised)” in May 2017.

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[Issues]
1) (For drugs to be handled at a low temperature) The cold chain management system is inefficient.
2) Procuring international organizations are vertically segmented.
3) Emergency relief supply may be stopped in the custom of the country to be supported.
4) Information concerning supply demand of materials is lacking.
5) Formation of stockpile centers of anti-viral and antimicrobial agents in Japan and other countries
is necessary.

[Actions Needed]<For global>
1) Construction of an efficient cold chain management system
2) Strengthening of collaboration among international organizations involved in procurement andlogistics
3) Strengthening of logistics support system in Japan in usual time in preparation for pandemics
4) Commonalization of custom codes concerning emergency relief supply<For Japan>
1) Realization of formation of the international stockpile and logistic centers utilizing the geographic
advantage of Okinawa (under the initiative of private sector)
2) Verification experiment of new logistic techniques in Okinawa (cold chain, E traceability, and drone
in remote islands)<Common>1) Improvement of social recognition of the importance of the role of cold chain and pharmaceuticalwholesalers
2) Giving incentive to companies to promote creation of many innovations
3) Disclosure of information on the use of public budgets and information concerning cold chain
management
Participation in the 6th conference will be requested to pharmaceutical wholesalers to dig into specificmeasures.

4.6 Contribution of ICT and AI to Infection Control[Current Status and Issues]
Information and communication technologies (ICT) and artificial intelligence (AI) may bringabout a revolution in infection control. For example, the following items are expected: 1) Speed upof disease report in the early stage of a pandemic, 2) realization of remote medical care in regions
lacking resources, 3) shortening of the time required for research and development of new drugs.
However, a high-quality database or data set has not been constructed despite ICT and AI
techniques being available and human resources who uses these are also lacking. Research funds toconnect ICT and AI to information of infectious diseases are also insufficient. Moreover, no legal,social, or ethical framework has been established.
[Actions Needed]
In addition to construction of a high-quality database and data set, development of humanresources is essential, and launch of funds by the government to support these is needed. To promoteacquisition of regulatory approval of medical devices, deepening of discussion on regulatory scienceis also important. In addition, it is necessary to raise discussion on legal, social, and ethicalframeworks while obtaining the understanding of general people.
This will also be selected as a topic of the 6th conference in consideration of its importance.

4.7 New seeds of technology
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In this conference, seeds of technology from Japan which may contribute to infection control in
Asia were presented. It is necessary to determine whether development of the seeds of technology
below should be supported after reliable evaluation of the impact of these on infection control.
<Innovation needed>
1) UNICEF
2) UNITAID
3) Global Fund
4) GHIT Fund
<Innovation from Japan>
5) Development of antibodies using the EB virus method (Evec)
6) Antibody production using transgenic silkworms (Rimco)
7) Data analysis technique for the immunology field (KOTAI Biotechnologies)
8) Compound against drug-resistant H. pylori (KyotoBiken Laboratories), living marine
resource-derived compounds (OP Bio factory)9) Genomic analysis technology for development of advanced medicine (SENTAN PHARMA)
10) Mobile biosensor (Japan Radio)

4.8 Incentive Promoting Private Sector Investment[Current Status and Issues]
In the 5th Nikkei Asian Conference on Communicable Diseases 2018, problems with eachdisease: tuberculosis, emerging and re-emerging infectious diseases (Ebola, SFTS), malaria,
influenza, and AMR, and infrastructure of infection control: Asian Communicable Diseases ClinicalResearch Centers and Okinawa Communicable Diseases Research Center, public health, logistics,
ICT, and AI were discussed.
It was clarified through discussion by experts for 2 days that incentive promoting private sector
investment for infectious diseases is weak in all issues, and companies inevitably hesitate to copewith problems with infection in Asia and Africa.
The Global Antibiotic Research & Development Partnership (GARDP) proposed De-Risk(division of research and development expenditure by 3rd-party fund and company) and De-Link(separation between the drug price and reward received by company) as an attempt to solve these
problems, and development of antimicrobial drugs is progressing.

[Actions Needed]
Legal framework to correspond to these, for example, harmonization of regulations andinternational standardization of product specification, should be included in discussion. Further
deepening of discussion on specific measures necessary to promote P3 is needed by the next
conference.

5. Conclusion
In the present conference, AMIC Working Group for the Asian Clinical Research Centers, thebasis of infection control, was inaugurated and Working Group aiming at forming Infectious Disease
Research Center in Okinawa which acts in cooperation with the former was also established. In
addition, new technologies and functions contributing to infection control, such as logistics, ICT, andAI, were included in discussion from this conference.
Regarding measures against infectious diseases by industry-academia-government collaboration,achievement of certain results within a short time was confirmed. However, there are still many
issues to be overcome.

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The time has come to change the name of this conference from Conference on Asian
Communicable Diseases to a name reflecting the global viewpoint because frameworks ofpublic-private collaboration for the tuberculosis and malaria projects have spread to Africa andglobal actions are needed for ICT, AI, and logistics.
Concrete progress through efforts and strengthening of cooperation among persons concerned by
the 6th conference is expected (the contents of subcommittees are attached as appendices of thisstatement).
End[The 5th Nikkei Asian Conference on Communicable Diseases 2018]
 Organizer: Nikkei Inc.
 In cooperation with: Nikkei Business Publications, Inc., Nikkei Medical Publishing, Inc.
 Assistance from: Okinawa Prefecture Official Support: Ministry of Foreign Affairs, Ministry of Economy, Trade and Industry, Ministryof Health, Labour and Welfare, Ministry of Education, Culture, Sports, Science and Technology
 Sponsors with lunch/breakout session: Fuji Film/Toyama Chemical Co., Ltd., Neopharma Co.,
Ltd., Daiichi Sankyo Co., Ltd., Saraya Co., Ltd., Shionogi & Co., Ltd., Sumitomo Chemical Co.,
Ltd., SYSMEX Corporation
 Sponsors: Eiken Chemical Co., Ltd., Global Health Innovative Technology Fund (GHIT Fund),
Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Mitsubishi
Tanabe Pharma Corporation, NIPRO, UNITAID

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<Appendix>
Content of the 5th Nikkei Asian Conference on Communicable Diseases Luncheon session /subcommittee meeting
Luncheon session 1 (FUJIFILM • TOYAMA CHEMICAL)“Approaches to emerging infectious diseases by industries, government, and academia in
China, Japan, and Korea in the episode of Severe Fever with Thrombocytopenia Syndrome(SFTS)“Severe Fever with Thrombocytopenia Syndrome (SFTS)” is an infectious disease caused byvirulent virus. The same virus strain was identified in Japan, Korea, and China. Findings offavipiravir leading to development of an effective treatment method have been acquired in a study
led by Masayuki Saijo, Director, Department of Virology 1, National Institute of Infectious Diseases,
and Masataka Yasukawa, Vice President of Ehime University. In response to this, FUJIFILM andTOYAMA CHEMICAL are preparing for initiation of a clinical trial aiming at acquiring approval forthe indication.
However, it is desirable to perform a global clinical trial in China, Japan, and Korea because thenumber of patients is limited. The companies plan to initiate the trial in Japan, and preparation for a
trial is also progressing in Korea. Harmonization of the trials in the 2 countries is necessary. P3 in
China, Japan, and Korea is expected for the future.
Progression of studies on prevention, early diagnosis, and vaccine including those of
Crimean-Congo hemorrhagic fever is expected.
Luncheon session 2 (Neopharma)“What is Japan’s aim for measures against emerging and re-emerging infectious diseases?:
Toward platform construction concerning utilization of therapeutic drugs and vaccines indevelopmental step”
To develop therapeutic drugs and vaccines from Japan to overcome emerging and re-emerging
infectious diseases, clinical studies and examinations for pharmaceutical affairs have to be
performed at local sites, and providing these therapeutic drugs and vaccines to local residents byprivate companies alone is limited. Preparation by the country is needed, such as preparation of asystem to rapidly supply candidate compounds in response to occurrence of outbreak in Asia andAfrica and appropriately extrapolate the clinical data into development and becoming a reference
country to expand unapproved novel candidate therapeutic drugs in Asia and Africa and rapidly
acquire approval.
It is also difficult for manufacturers to keep large stock for overseas outbreaks because predictionof the time of occurrence is difficult. In addition, it is needed to expand measures to compensate foradverse events accompanying the use of unapproved drugs by having the country involved, notburdening on only companies. To overcome these issues, platform construction byindustry-government-academia collaboration including PMDA is necessary.
Subcommittee meeting A-1 (Saraya)“Let’s confront AMR! Possibility of HAND HYGIENE approach”
In Vietnam, more than 60% of the population is infected with drug-resistant ESBL-producing E.
coli, and more than 50% of livestock and marine products are contaminated. Colistin overdosing inchickens has been confirmed. An intervention study on washing hands with water and soap was
performed in Vietnam and clarified that both knowledge and practice were insufficient to prevent theinfection. Continuous training and monitoring and education of children are essential. In addition,
the “one health” approach across the boundary between humans and animals should be adopted.
Introduction alcohol-based hand rub (ABHR) is also valuable. At the same time, guidelines forlivestock facilities, supermarkets, and restaurants are also important to establish regional policies andsystems following the certification concerning food safety, HACCP.
To improve the state in Vietnam, Saraya plans to cooperate with the government of Vietnam. They
already initiated discussion on details of a pilot project and requested the Ministry of Agriculture ofVietnam to join the discussion.

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Subcommittee meeting A-2 (Okinawa Prefecture)“Approaches to form the Okinawa Communicable Diseases Research Center and Prospects”
The functions and roles needed for the Okinawa Communicable Diseases Research Center are as
follows: 1) Strengthening of surveillance in preparation for the risk of infection coming into
Okinawa during international exchange and large-scale event, 2) establishment of a Communicable
Diseases Diagnosis Center (tentative name) and enhancement of the infection control function of
Okinawa by collaboration with main research institutions in Japan, 3) epidemiological studies byusing the characteristics of islands and organic collaboration with bio-banks, 4) improvement ofclinical abilities of medical institutions in the prefecture and construction of an appropriate
diagnosis/treatment system concerning emerging infectious diseases, 5) progression from ‘researchbase’ to ‘research and countermeasure base’ in order to contribute to improvement of health andmedical care of residents of the prefecture and worldwide infection research and countermeasures.
Examing these ideas in detail is necessary in the future.
Subcommittee meeting B-1 (Shionogi & Co., Ltd.)“Current status and issues of influenza virus infection control”
Diverse viral types are detected in seasonal influenza every year including resistant strains. In
other countries, highly pathogenic avian influenza including H5N1 and H7N9 has emerged. Fatalcases have been reported and occurrence of pandemic is of concern. For these issues, the following
items are needed: (1) Collection and sharing of surveillance information, (2) prevention of infectionand expansion of infection by highly effective vaccines against seasonal/pre-pandemic/pandemic
influenza, (3) development and providing of a high-sensitive rapid diagnostic drug and ananti-influenza agent with a novel action mechanism.
Subcommittee meeting B-2 (Daiichi-Sankyo)“Needs for preventive and therapeutic drugs against infectious diseases in Asia andcontribution by companies”
In Asia, needs for vaccines and therapeutic drugs against various infections are still not satisfied.
Some countries try to develop and manufacture vaccines in their own country, but there are many
problems, such as inability to perform preclinical studies or construct a production system. For these
problems, pharmaceutical and health care industries in Japan as an Asian country may be able tocontribute by supporting preclinical studies, providing manufacturing techniques, and developing
therapeutic drugs. To overcome problems in Asia, devising to increase incentive of Japanesecompanies is also needed, such as strengthening of public funds widely promoting from research anddevelopment to manufacturing and preparation of a system to use vaccines and therapeutic drugs at alow price in Asia. Global Antibiotic Research & Development Partnership (GARDP) proposed
De-Risk (division of research and development expenditure by 3rd-party fund and company) and
De-Link (separation between the drug price and reward received by company) and introduction of
concrete examples of episodes provoking incentive of companies to develop preventive andtherapeutic drugs against infectious diseases.
Subcommittee meeting C-1 (SYSMEX)“Malaria elimination aimed by WHO: Contribution by new diagnostic technique”
The numbers of patients with malaria and deaths from malaria have decreased since 2000, but thedecreases became stagnated in the 2010s. Based on these results, WHO clarified their concern thatelimination of malaria is standing at a crossroads”. Japan is able to contribute in 3 fields: diagnosis,
new drug development, and vector control.
Especially, the high-sensitivity DNA test capable of amplifying specific DNA under a fixed
temperature condition and multichannel automated blood cell analysis capable of detecting infection
before disease onset and distinguishing highly malignant falciparum malaria from the other malaria
types are very sensitive testing techniques, and these are expected to exert strong power in picking
up asymptomatic parasite carriers. Regarding the significance of detecting pre-disease carriers, close
verification is desired.

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Subcommittee meeting C-2 (Sumitomo Chemical)“Current status and issues of vector control in Asia and Africa”
At present, vector control most strongly contributes to malaria elimination. Long-lasting
insecticidal mosquito nets, long-lasting indoor sprays, and mosquito larvae anthelmintic have been
introduced and made achievements. However, to overcome problems, such as drug-resistantmosquitoes, and emergence of a new vector (infection-mediating pests) active outdoors during
daytime from nocturnal mosquito species, it is important to continue introduction of a new drug. It isalso necessary to establish a method to monitor the effect of vector control in parallel to vector
control. To constantly advance vector control techniques, stable fundraising is also important andconstruction of a network with international institutions, such as WHO, UNITAID, and GHIT Fund,is essential for developers, for which Japanese industry-government-academia collaboration isnecessary.
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