Rie Roselyne YOTSU, M.D., M.I.P.H., Ph.D.

Department of Dermatology National Center for Global Health and Medicine, Tokyo, Japan

Norihisa ISHII, M.D., Ph.D.

Koichi SUZUKI, Ph.D. Yoshihiko HOSHINO, M.D., Ph.D.

Kazue NAKANAGA, Ph.D.

Leprosy Research Center National Institute of Infectious Diseases, Tokyo, Japan

WHO Buruli Ulcer Meeting, 25-27 March 2013: Geneva, Switzerland

History

1st case reported in 1982

• 19 y/o female with no history of int’l travel

• 1st case reported from Asia

• Isolate: Mycobacterium ulcerans subsp. shinshuense

Map: Köppen-Geiger climate classification; modified from Peel et al (2007)

Total of 36 cases reported as of Dec 2012

Surveillance System in Japan

Patient

Local medical institute

Leprosy Research Center*

WHO

Information

Statistics

Operational research

Reporting BU

cases

*LRC: Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan

Early diagnosis

Treatment

Specimen sent to

identify/diagnose BU

Reporting results

Therapeutic advice

Inquiry/

Diagnostics

Feedback/

Therapeutics

Insertion sequence (IS)2404

Cannot differentiate between M. ulcerans

and M. ulcerans subsp. shinshuense

Definite diagnosis of M. ulcerans subsp. shinshuense Cannot differentiate from M. marinum

HE stain

Ziehl-Neelsen stain Liquid culture medium (Mycobacteria Growth Indicator Tube(MGIT))

Ogawa slant

Ziehl-Neelsen

stain

Buruli Ulcer?

Clinical samples, isolates, etc.

Direct smear Culture PCR Histopathology

DDH 16S rRNA gene sequencing

Geographical Distribution of Buruli Ulcer in Japan

No. of cases

0

1

2

8

Leprosy Research

Center, NIID, Tokyo

Total of 22 cases (Dec 2010)

Geographical Distribution of Buruli Ulcer in Japan

Leprosy Research

Center, NIID, Tokyo

No. of cases

0

1

2

3

4

9

Total of 22 cases (Dec 2010)

Okayama: 9 cases

Leprosy Research

Center, NIID, Tokyo

3

1

1

M. ulcerans subsp. shinshuense

2％ Ogawa medium

M. ulcerans isolated from Japanese cases：

All patients with BU are without international travel, so the species is believed to be domestic to Japan. *Photo: a courtesy of Dr. Kazue Nakanaga, National Leprosy Research Center, NIID

0

1

2

3

4

5

6

7

8

9

10

1980200420052006200720082009201020112012

Cases

WHOReportYear

60-89

15-59

0-14

Age grp Total

10

18

8

Age Group Distribution by Year

0

1

2

3

4

5

6

7

8

9

10

1980200420052006200720082009201020112012

Cases

WHOReportYear

Female

Male

Sex Distribution by Year

Sex Total

24

12

5(14%)

2(6%)

10(28%)

19(53%)

Spring

Summer

Autumn

Winter

Seasonal Distribution

Clinical Presentation

+ Clinical forms

+ Category

Non-ulcerative Ulcerative

Africa 26% 74%

Australia 3% 97%

Japan 6% 94%

Category I Category II Category III

Africa 32% 35% 33%

Australia 95% 5% 0%

Japan 81% 19% 0%

Less than 10% are diagnosed before ulceration in Japan. Once it ulcerates, then approximately 80% are diagnosed before they enter into the severe stage.

Characteristics of Cases Reported in Japan

• Known isolate: Mycobacterium ulcerans subsp. shinshuense

• Not related to international traveling; endemic

mycobacterium

• Association with aquatic environment?

• Regional bias – awareness of dermatologists?

• Seasonal bias – autumn & winter; unclear incubation

period

• Unknown mode of transmission

• Pain may be more outstanding in Japanese cases? * With pain: 16/36 (44%) cases

1.Elucidate the candidate vector and/or mode

of transmission in Japan.

2.Accumulate cases treated with levofloxacin

(12 mg/kg), clarithromycin (16 mg/kg),

rifampicin (10 mg/kg).

3.Establish a nation-wide system for improved

awareness and diagnoses.

4.Expanding the network to other Asian

countries that may be endemic.

Future Mission in Japan

Thank you for

your kind

attention !!