医療関連感染症・薬剤耐性菌感染症　共同研究（ベトナム拠点）

更新日：2017年2月3日

医療関連感染症・薬剤耐性菌感染症　共同研究（ベトナム拠点）

Information

現在、薬剤耐性（Antimicrobial Resistance: AMR）はグローバルな問題となっており、日本のAMRアクションプランにおいても、国際協力が大きな柱の1つとなっています。国立国際医療研究センター　国際感染症センター（DCC）および研究所は、2012年より、感染症研究国際ネットワーク推進プログラム（Japan Initiative for Global Research Network on Infectious Disease: J-GRID）の一環として、NCGMと医療技術協力関係にあるベトナムにおいて、医療関連感染症・薬剤耐性菌感染症の研究を行っています。

本研究は2012年に文部科学省のプログラムとして開始され、2015年からは国立研究開発法人日本医療研究開発機構（AMED）「感染症研究国際展開戦略プログラム（J-GRID）」に移行され研究を継続しています。

臨床、疫学、および微生物学の観点より、AMRをコントロールする為の科学的データを示す事を目的として掲げ、ベトナムの協力病院とともにベトナム各地で薬剤耐性菌の臨床・疫学・基礎研究を行っています。ベトナムの主な協力病院は、ハノイ市にあるバックマイ病院とホーチミン市にあるチョウライ病院です。

拠点紹介

メッセージ

国際的に脅威となる感染症の問題といえば、従来はエボラ出血熱等の出血熱や、マラリア・結核等が中心でした。しかし、世界各国での経済の発展とこれに伴う医療の発展の結果、医療関連感染症と抗菌薬耐性菌が大きな問題となっています。

この問題を放置すれば、医療そのものの継続性事態が危うくなり、将来多くの生命が失われかねません。世界のなかでもアジアでは医療関連感染症と抗菌薬耐性菌が大きな問題となっており、対策を行う事が急務です。

そこで私たちはベトナムの医療者と協力し、同国で医療関連感染症と抗菌薬耐性菌に関する研究開発を行う事と致しました。本プロジェクトは2012年より開始され、現在はハノイとホーチミンそれぞれで研究を行っています。 

NCGMとベトナムの医療技術協力関係

1995-2001　ベトナム北部　　チョウライ病院プロジェクト
2001-2007　ベトナム北部　　バックマイ病院プロジェクト
2005　　　　ベトナム北部　　ベトナム保健省の承認を得てバックマイ病院とNCGM間に協力協定締結
2006　　　　べトナム北部　　バックマイ病院にNCGM-バックマイ病院医療協力センター設立
2007　　　　ベトナム中部　　フエ中央病院プロジェクト
2006-2012　ベトナム全土　　院内感染対策プログラム
2014　　　　ベトナム南部　　ベトナム保健省の承認を得てチョウライ病院とNCGM間に協力協定締結

現在進行中

• ベトナム保健省　保健省アドバイザー派遣
• ベトナム南部　　地域保健医療人材能力向上プロジェクト
• ホアビン省　　　保険医療サービス強化プロジェクト
• ベトナム中部　　医療サービス向上プロジェクト
• バックマイ病院　文科省海外拠点形成プロジェクト
• バックマイ病院　地方医療人材研修能力

研究拠点病院の紹介

チョウライ病院

チョウライ病院は、ベトナム国ホーチミン市にある、南部最大の国立病院になります。1900年にベトナム保健省投資で設立されました。ベッド数は約1900床。入院患者数は約960,000人／年。外来患者数は約1,460,000人／年。手術件数は39000件／年。ベトナム南部のホーチミン市の拠点病院であり、多くの患者が搬送されてきます。

病院のホームページ:　http://choray.vn:81/

バックマイ病院

バックマイ病院は、ベトナム国ハノイ市にある、北部最大の国立病院になります。1911年にフランス統治政府によって設立され、保健省の管轄で現在も北部拠点病院になります。ベッド数は約1900床。入院患者数は約人100,000人／年。外来患者数は約900,000人／年。ベトナム北部のハノイ市の拠点病院であり、多くの患者が搬送されてきます。日本だけでなく、欧米からの支援や協力が多い国際的な病院です。

病院のホームページ:　http://bachmai.gov.vn/images/stories/en/index.html

スタッフの紹介

日本（DCC）スタッフ

大曲 貴夫, 早川 佳代子, 竹下 望, 忽那 賢志, 永松 麻希, 土屋 光広, 石金 正裕

日本（研究所）スタッフ

切替 照雄, 秋山 徹, 多田 達哉

ベトナム スタッフ（コーディネーター）

Pham Thi Phuong Thuy

研究概要

Project 1：ベトナムにおける医療関連感染症の実態を明らかにする疫学研究 

ベトナムをはじめアジアの医療機関では経済的な発展と共に医療関連感染症が大きな社会的負荷となっています。これらは治療と予防が困難な抗菌薬耐性菌による感染症ですが、臨床像・疾患負荷としての実体・伝播の様式は明らかではありません。本研究ではベトナムの主要病院複数を対象に血流感染症などの医療関連感染症の病院コホートを対象に疫学調査を施行しています。

Project 2：ベトナムにおける薬剤耐性菌治療オプションの開発に関する研究

現在世界的に多剤耐性菌に対する治療オプションの不足が指摘されており、欧米を中心に研究が施行中であるが、アジア地域や途上国を対象にした研究は希少です。このため、本研究では（1）アジア地域における多剤耐性菌治療の具体的なニーズを明らかにし、（2）多剤耐性菌の微生物学的検討により、可能性のある治療薬を特定し、（3）アジア人及び途上国の特性に合わせた薬剤耐性菌治療オプションの開発を行うことを目的としています。

Project 3：ベトナムにおける高度薬剤耐性菌の微生物学的な疫学情報を明らかにする研究

ベトナムをはじめアジアの医療機関では治療が困難である多剤耐性菌が高頻度に分離されることが明らかになっていますが、多剤耐性菌の微生物学情報は限られています。このため、本研究では、（1）高度多剤耐性菌を毎年収集し、それらの全ゲノム配列を決定することで、菌種同定と薬剤耐性因子保有状況の包括的な疫学情報を取得し、（2）これらの疫学情報を元に、最も対策が望まれる菌種や薬剤耐性因子について、抗原抗体反応を利用した検出または遺伝子診断による簡易検査法の開発を行うことを目的としています。

業績（論文）

2016

1. Multidrug-resistant ST235 Pseudomonas aeruginosa clinical isolates producing IMP-26 with increased carbapenem hydrolyzing activities in Vietnam.Tada T, Nhung PH, Miyoshi-Akiyama T, Shimada K, Tsuchiya M, Phuong DM, Anh NQ, Ohmagari N, Kirikae T.
   Antimicrob Agents Chemother. 2016 Sep 6. pii: AAC.01177-16.
2. Dissemination of clonal complex 2 Acinetobacter baumannii strains co-producing carbapenemases and 16S rRNA methylase ArmA in Vietnam.
   Tada T, Miyoshi-Akiyama T, Shimada K, Nga TT, Thu le TA, Son NT, Ohmagari N, Kirikae T.
   BMC Infect Dis. 2015 Oct 15;15:433.

2015

1. IMP-51, a novel IMP-type metallo-β-lactamase with increased doripenem- and meropenem-hydrolyzing activities, in a carbapenem-resistant Pseudomonas aeruginosa clinical isolate.
   Tada T, Nhung PH, Miyoshi-Akiyama T, Shimada K, Phuong DM, Anh NQ, Ohmagari N, Kirikae T.
   Antimicrob Agents Chemother. 2015 Nov;59(11):7090-3.
2. Evaluation of the Etest method for detecting colistin susceptibility of multidrug-resistant Gram-negative isolates in Vietnam.
   Nhung PH, Miyoshi-Akiyama T, Phuong DM, Shimada K, Anh NQ, Binh NG, Thanh do V, Ohmagari N, Kirikae T.
   J Infect Chemother. 2015 Aug;21(8):617-9.
3. The efficacy and nephrotoxicity associated with colistin use in an intensive care unit in Vietnam: Use of colistin in a population of lower body weight.
   Binh NG, Hayakawa K, Co DX, Tuan ND, Anh NH, Thuy NT, Phuong DM, Huong NT, Thuy PT, Chau NQ, Nhung PH,
   Gam do TH, Hai DT, Huong TT, Van Anh L, Takeshita N, Ohmagari N.
   Int J Infect Dis. 2015 Jun;35:18-23. doi: 10.1016/j.ijid.2015.03.020.

2014

1. Efforts Against Drug-Resistant Bacteria and Bacteremia in Vietnam.
   Takeshita N, Ohmagari N, Kirikae T, Oka S.
   Journal of Disaster Research. 2014; 9 (5), 836

2013

1. Emergence of 16S rRNA methylase-producing Acinetobacter baumannii and Pseudomonas aeruginosa isolates in hospitals in Vietnam.
   Tada T, Miyoshi-Akiyama T, Kato Y, Ohmagari N, Takeshita N, Hung NV, Phuong DM, Thu TA, Binh NG, Anh NQ, Nga TT, Truong PH, Xuan PT, Thu le TA, Son NT, Kirikae T.
   BMC Infect Dis. 2013 May 30;13:251.

業績（学会）

2016

1. 早川 佳代子, 竹下 望, 石金 正裕, 永松 麻希, 大曲 貴夫, Nguyen Quoc Anh, Doan Mai Phuong, Do Van Thanh, Pham Thi Phuong Thuy (会員外共同研究者)　“Epidemiology and outcomes of ventilator-associated pneumonia in intensive care unit in Vietnam”.
   第86回日本感染症学会西日本地方会学術集会, 沖縄, 2016/11
2. 石金 正裕, 早川 佳代子, 竹下 望, 永松 麻希, 大曲 貴夫, Nguyen Quoc Anh, Doan Mai Phuong, Do Van Thanh, Pham Thi Phuong Thuy (会員外共同研究者)　ベトナム三次医療機関1施設（バクマイ病院、ハノイ市）ICUにおける院内感染血流感染症の疫学的所見の検討：前向きコホート研究
   第86回日本感染症学会西日本地方会学術集会, 沖縄, 2016/11 

2015

1. Binh NG, Hayakawa K, Co DX, Tuan ND, Anh NH, Thuy NT, Phuong DM, Huong NT, Thuy PT, Chau NQ, Nhung PH, Gam do TH, Hai DT, Huong TT, Van Anh L, Takeshita N, Ohmagari N.
   “The low incidence of nephrotoxicity associated with colistin use in intensive care unit in Vietnam: Tailored use of colistin in a population with low body weight.” Presented as a poster presentation at European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Copenhagen, Denmark, April, 2015. 

2014

1. Nozomi Takeshita.
   Characteristic of Blood Cultures in Large Tertiary Care Hospital in North Vietnam.
   Asia Africa Research Forum 2014, 仙台, 2014/11

Collaboration Research on Healthcare-Associated Infections and Antimicrobial Resistance (Vietnam)

Information　

Antimicrobial Resistance (AMR) has become a global issue. The Japanese National Action Plan on AMR also specifies international cooperation as one of its mainstays. Since 2012, the Disease Control and Prevention Center (DCC) and Research Institute National Center for Global Health and Medicine (NCGM), has promoted research concerning healthcare-associated infections (HAIs) and AMR in Vietnam, which has a partnership with NCGM in healthcare technologies, as part of the Japan Initiative for Global Research Network on Infectious Disease (J-GRID).

The present research was started in 2012 as a program under the Ministry of Education, Culture, Sports, Science and Technology, which was then transferred to J-GRID under the Japan Agency for Medical Research and Development (AMED) in 2015 for continuous research.

Toward the goal of presenting scientific data for controlling AMR from the perspectives of clinical practice, epidemiology and microbiology, this program performs clinical, epidemiological and microbiological studies concerning AMR across Vietnam, in collaboration with local partner hospitals. The key local partner hospitals are the Bach Mai Hospital in Hanoi and the Cho Ray Hospital in Ho Chi Minh.

About us　

Message

The issues of internationally threatening infections used to be focused on Ebola and other hemorrhagic fevers, as well as on malaria and tuberculosis. Recently, as the economy has been developing around the world, accompanied by the global development of healthcare, HAIs and AMR have become major issues.

If these issues were left unattended, the continuity of healthcare itself might be threatened, resulting in the potential loss of many lives. Among other regions, HAIs and AMR have become serious problems in Asia, calling for urgent countermeasures.

Under these circumstances, we decided to promote research and development concerning HAIs and AMR in Vietnam, in collaboration with local healthcare professionals. This project was started in 2012, and research activities are in progress in Hanoi and in Ho Chi Minh.

Partnership between NCGM and Vietnam in Healthcare Technologies

1995 - 2001　　Northern Vietnam; Cho Ray Hospital Project
2001 - 2007　　Northern Vietnam; Bach Mai Hospital Project
2005　　　　　  Northern Vietnam; With approval of the Vietnamese Ministry of Health, a partnership agreement was concluded between the Bach Mai Hospital and NCGM
2006　　　　　  Northern Vietnam; An NCGM-Bach Mai Hospital Healthcare Cooperation Center was established in the Bach Mai Hospital
2007　　　　　  Central Vietnam; Hue Central Hospital Project
2006 - 2012　　Entire Vietnam; Infection prevention and control Program
2014　　　　　  Southern Vietnam; With approval of the Vietnamese Ministry of Health, a partnership agreement was concluded between the Cho Ray Hospital and NCGM

In progress

• Vietnamese Ministry of Health (MOH); Advisors dispatched to MOH
• Southern Vietnam; Local Healthcare Human Resource Ability Upgrading Project
• Hoa Binh Province; Insurance-covered Healthcare Service Strengthening Project
• Central Vietnam; Healthcare Service Improvement Project
• Bach Mai Hospital; MEXT Overseas Base Formation Project
• Bach Mai Hospital; Local healthcare human resource training abilities
  

 Hospitals as Research Sites

Cho Ray Hospital

The Cho Ray Hospital is the largest national hospital in Southern Vietnam, located in Ho Chi Minh City. The hospital was established in 1900, funded by the Vietnamese Ministry of Health. The Cho Ray Hospital has approx. 1,900 beds, treats approx. 960,000 inpatients and approx. 1,460,000 outpatients per year, and performs 39,000 surgical operations per year. It is the hub hospital in Ho Chi Minh, the central city in Southern Vietnam, and a number of patients are delivered to this hospital.

Hospital website: http://choray.vn:81/

Bach Mai Hospital

The Bach Mai Hospital is the largest national hospital in Northern Vietnam, located in Hanoi City. It was established by the French colonial government in 1911, and is now governed by the Vietnam Ministry of Health as the hub hospital in Northern Vietnam. The Bach Mai Hospital has approx. 1,900 beds, and treats approx. 100,000 inpatients and approx. 900,000 outpatients per year. It is the hub hospital in Hanoi, the central city in Northern Vietnam, and a number of patients are delivered to this hospital. It is an international hospital with many supporting and partner countries including Japan, Europe and the U.S.

Hospital website: http://bachmai.gov.vn/images/stories/en/index.html

Hospitals as Research Sites 

Japan staff (DCC) 

Norio Ohmagari, Kayoko Hayakawa, Nozomi Takeshita, Satoshi Kutsuna, Maki Nagamatsu, Mitsuhiro Tsuchiya, Masahiro Ishikane

Japan staff (Research Institute)

Teruo Kirikae, Tohru Miyoshi-Akiyama, Tastuya Tada

Vietnamese staff (coordinator)

Pham Thi Phuong Thuy 

Overview of Research　

Project 1: Epidemiological research to clarify the healthcare-associated infections in Vietnam

In medical institutions in Vietnam and other Asian countries where the economy has been developing, healthcare-associated infections have become substantial social burden. Such infections are caused by antimicrobial resistant bacteria with difficulty in treatment and prevention, and their actual status and mechanism of transmission have yet to be identified as clinical characteristics and disease burden. In this research, epidemiological studies are in progress targeted at the hospital cohorts of healthcare-associated infections in several key hospitals in Vietnam, including those of blood stream infections.

Project 2: Research concerning the development of therapeutic options for antimicrobial-resistant bacteria in Vietnam

At present, shortage in therapeutic options for multi-drug resistant bacteria has been pointed out around the globe, and related research activities are in progress in Europe, the U.S. and other regions. However, only a very few studies have been conducted in the Asian region and developing countries. Under these circumstances, this research is aimed at (1) clarifying specific needs for the treatment of multi-drug resistant bacteria in the Asian region, (2) identifying potential medications through microbial studies concerning multi-drug resistant bacteria, and (3) developing therapeutic options for antimicrobial-resistant bacteria that match the characteristics of Asian people and of developing countries.

Project 3: Research for clarifying microbiological epidemiology concerning advanced drug-resistant bacteria in Vietnam

While it has been uncovered that multi-drug resistant bacteria with difficulty in treatment are often isolated in medical institutions in Vietnam and other Asian countries, there is only limited microbiological information concerning multi-drug resistant bacteria. Under these circumstances, this research is aimed at (1) collecting advanced drug-resistant bacteria every year, and determining the complete genome sequence thereof, thereby identifying the types of bacteria and acquiring comprehensive epidemiological information concerning the possession of drug resistant factors; and (2) based on such epidemiological information, developing simplified test methods using antigen-antibody assays or genetic diagnosis for the types of bacteria and drug resistant factors with the highest needs.

Publications　

2016

1. Multidrug-resistant ST235 Pseudomonas aeruginosa clinical isolates producing IMP-26 with increased carbapenem hydrolyzing activities in Vietnam.
   Tada T, Nhung PH, Miyoshi-Akiyama T, Shimada K, Tsuchiya M, Phuong DM, Anh NQ, Ohmagari N, Kirikae T.
   Antimicrob Agents Chemother. 2016 Sep 6. pii: AAC.01177-16.
2. Dissemination of clonal complex 2 Acinetobacter baumannii strains co-producing carbapenemases and 16S rRNA methylase ArmA in Vietnam.
   Tada T, Miyoshi-Akiyama T, Shimada K, Nga TT, Thu le TA, Son NT, Ohmagari N, Kirikae T.
   BMC Infect Dis. 2015 Oct 15;15:433. 

2015

1. IMP-51, a novel IMP-type metallo-β-lactamase with increased doripenem- and meropenem-hydrolyzing activities, in a carbapenem-resistant Pseudomonas aeruginosa clinical isolate.
   Tada T, Nhung PH, Miyoshi-Akiyama T, Shimada K, Phuong DM, Anh NQ, Ohmagari N, Kirikae T.
   Antimicrob Agents Chemother. 2015 Nov;59(11):7090-3.
2. Evaluation of the Etest method for detecting colistin susceptibility of multidrug-resistant Gram-negative isolates in Vietnam.
   Nhung PH, Miyoshi-Akiyama T, Phuong DM, Shimada K, Anh NQ, Binh NG, Thanh do V, Ohmagari N, Kirikae T.
   J Infect Chemother. 2015 Aug;21(8):617-9.
3. The efficacy and nephrotoxicity associated with colistin use in an intensive care unit in Vietnam: Use of colistin in a population of lower body weight.
   Binh NG, Hayakawa K, Co DX, Tuan ND, Anh NH, Thuy NT, Phuong DM, Huong NT, Thuy PT, Chau NQ, Nhung PH, Gam do
   TH, Hai DT, Huong TT, Van Anh L, Takeshita N, Ohmagari N.
   Int J Infect Dis. 2015 Jun;35:18-23. doi: 10.1016/j.ijid.2015.03.020.

2014

1. Efforts Against Drug-Resistant Bacteria and Bacteremia in Vietnam.
   Takeshita N, Ohmagari N, Kirikae T, Oka S.
   Journal of Disaster Research. 2014; 9 (5), 836 

2013

1. Emergence of 16S rRNA methylase-producing Acinetobacter baumannii and Pseudomonas aeruginosa isolates in hospitals in Vietnam.
   Tada T, Miyoshi-Akiyama T, Kato Y, Ohmagari N, Takeshita N, Hung NV, Phuong DM, Thu TA, Binh NG, Anh NQ, Nga TT, Truong PH, Xuan PT, Thu le TA, Son NT, Kirikae T.
   BMC Infect Dis. 2013 May 30;13:251.

International Conference

2015

1. Binh NG, Hayakawa K, Co DX, Tuan ND, Anh NH, Thuy NT, Phuong DM, Huong NT, Thuy PT, Chau NQ, Nhung PH, Gam do TH, Hai DT, Huong TT, Van Anh L, Takeshita N, Ohmagari N.
   “The low incidence of nephrotoxicity associated with colistin use in intensive care unit in Vietnam: Tailored use of colistin in a population with low body weight.” Presented as a poster presentation at European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Copenhagen, Denmark, April, 2015.

2014

1. Nozomi Takeshita.
   Characteristic of Blood Cultures in Large Tertiary Care Hospital in North Vietnam.
   Asia Africa Research Forum 2014, Sendai, Miyagi, November 2014.