occurrence of cfp in japaniocwestpac.org/files/upload_manual/l2 oshiro.pdf · 2014. 11. 12. ·...

THE 3rd IOC/WESTPAC – TMO TRAINING WORKSHOP“Technical guideline for Ciguatera study: experiences from Japan”Graduate School of Agricultural and Life Science, The University of TokyoTokyo, Japan, 5-6 November, 2013

Occurrence of CFP in Japan

Naomasa OSHIRO

Section Chief of the Second Laboratory,Division of Biomedical Food Research,

National Institute of Health Sciences

NIHS


Naomasa OSHIROwas born, bred, educated and employed in Okinawa.

joined as a section chief of Marine Biotoxin lab. (the 2nd lab. ),

Div. Biomedical Food Research, National Institute of Health.

Education

1992 Department of Chemistry, University of the Ryukyus, BSc

1994 Graduate School of Science, University of the Ryukyus, MSc

2009 Graduate School of Marine Science and Technology, Tokyo University

of Marine Science and Technology, PhD (Marine Science)

Employment

1994 Okinawa Prefectural Institute of Health and Environment

2010 Environmental Preservation Division, Okinawa Prefectural

Government

2012 Division of Biomedical Food Research, National Institute of Health

Sciences


Pathogens of Food Poisoning

• Bacteria

• Virus

• Chemical Substances

• Natural Toxins– Plant (including mushrooms)

– Animal

• Parasite

• Others

• Unknown


Collection of the food poisoning incidents.

Patients

Clinical Doctors

LocalHealth Center

Local Government

Ministry of Health, Labourand Welfare, GOJ

diagnose

report report

report


Food Poisoning Statistics, 2009.Inspection and Safety Division, Department of Food Safety, Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Welfare, Government of Japan.

Annual variation in the percentage of incidents from food poisoning by Pathogenic substance.

Bacteria

Unknown Virus

Natural Toxins

Chemicals

THE 3rd IOC/WESTPAC – TMO TRAINING WORKSHOP“Technical guideline for Ciguatera study: experiences from Japan”Graduate School of Agricultural and Life Science, The University of TokyoTokyo, Japan, 5-6 November, 2013Number of incidents, patients and death, attack rate, and fatality of food poisoning

caused by natural toxins in Japan (1989-2010)*.

Causative agentNumber of incidents

Number of people

consumed

Number of patients

Attack rate(%)

Number of death

Fatality(%)

Animal toxins

Pufferfish poisoning 651 1,644 976 59.4 56 3.4

Ciguatera 78 493 284 57.6 0 0.0

Tetramin 60 183 144 78.7 0 0.0

Palytoxin like toxin 19 119 65 54.6 1 0.8

DSP and PSP 12 136 57 41.9 1 0.7

Others** 18 96 52 － 0 －

Plant toxins

Mushroom 1,172 5,075 4,291 84.6 30 0.6

Plant 287 2,129 1,546 72.6 7 0.3

Others 54 134 128 － 0 －

* Suspected cases are also included.** escolar (wax) 1, striped Jewfish (vitamin A) 2, scavenging marine snail (TTX) 2, long shanny Stichaeus

grigorjewi (dinogunellin) 1, sea turtle 1, unidentified 11.

Toda et al., 2010


Fatal Cases of Food Poisoning in Japan (1989-2010)

自然毒, 95 細菌他, 49

56 2 30 7

0% 20% 40% 60% 80% 100%

自然毒による死者数（計95名）

全体の死者数（計144名）

フグその他（動物性）キノコ高等植物

other animal toxins ↓

Total: 144 cases

Natural toxins: 95 cases

Natural toxins: 95 bacteria: 49

pufferfish: 56 mushroom: 30

plant toxins ↓

Toda et al., 2010


Trends of natural toxin food poisoning （NTFP）in Japan, 1989–2011.

• The number of incidents of NTFP in each year has not been reduced.

• The major site for all hazards was “at home”.

• Consumer education is critically important to inform about NTFP occurrence, preventive measures and emergency treatments.

• Countermeasures for NTFPs which have never occurred in the past in Japan should be considered, because of the increasing variety of imported foods and changes resulting from the increase of sea temperature with global warming.

Toda et al., 2012


Ciguatera Fish Poisoning: CFP


Ciguatera is …

• the disease caused by ingestion of tropical finfish.

• prevalent in tropical and sub-tropical Pacific and Indian Oceans and Caribbean Sea.

• derived from Caribbean name ‘cigua’ for shellfish Turbo pica.

• most frequent seafood poisoning in the world.– 20,000 – 50,000 patients, annually

• rarely fatal.

• persistent for months or years in severe case.

• caused by ciguatoxins.

THE 3rd IOC/WESTPAC – TMO TRAINING WORKSHOP“Technical guideline for Ciguatera study: experiences from Japan”Graduate School of Agricultural and Life Science, The University of TokyoTokyo, Japan, 5-6 November, 2013Symptoms

• Incubation period ------ 1-36 hours (mostly within 24 h)

• Gastrointestinal ---------- early stage– vomiting, diarrhea, nausea, abdominal pain

• Neurological ------------- most common– dry ice sensation ----- “paradoxical” perception or reversal of

temperature perception to cold stimulus– paresthesia of extremities and circumoral region– arthralgia, pruritus, rash.

• Cardiovascular ------------- not common but severe– bradycardia, hypotension.

• most of the patients recover within 3 days

• malaise, paresthesia and pruritus may persist for weeks or even years in severe cases.


via food chain

dinoflagellate

G. toxicus

intoxication

dry ice sensation

Accumulation of ciguatoxins

herbivorous

animals

carnivorous fish


O

O

O

O

O

OO

O

O

O O

O

Me

MeOH

Me

Me

OH

MeOH

OHOH

HH H H

H H

H

H

H H HH

H H H HH

H

H

H H

H

O

OH

A B C D

E F

G

H

IJ

K

L M

1

54

52

OO

O

O

O

OO

Me

MeOH

Me

Me

Me

OH

H

HH

H HH

H

HH

H HH

H

O

O

O

OO

O

OHH H H

H

H H HH

A B C D

EF

GH

I

J

K

LM

51

49

1

Structures of ciguatoxins, CTX1B, CTX3C and C-CTX-1

CTX1B

CTX3C

C-CTX-1


Table 2. Representative studies and synonyms of ciguatoxins.

compound synonym reference m.w.Lethality to

mice (i.p.)remarks

CTX Scheuer et al. (1967) 0.5 mg/kg isolation

Legrand et al. (1989) 1110.6 0.4 μg/kg isolation, some property

Murata et al. (1989) planar structure

Murata et al. (1990) 0.35 μg/kg configuration

Satake et al. (1997b) absolute configuration

Inoue et al. (2006) 1.64 μg/kg synthesized

Hamajima and Isobe (2009) synthesized

CTX1B Satake et al. (1997a)

CTX1 Lewis et al. (1991) 1110.6 0.25 μg/kg isolation, identification

P-CTX-1 Vernoux and Lewis (1997)

54-deoxyCTX CTX-3 Lewis et al. (1991) 1095.5 0.9 μg/kg isolation, determination

P-CTX3 Vernoux and Lewis (1997)

52-epi -54-deoxyCTX CTX-2 Lewis et al. (1991) 1094.5 2.3 μg/kg isolation, planar structure

Lewis et al. (1993) configuration

P-CTX2 Vernoux and Lewis (1997)

CTX4A Satake et al. (1997a) 1060.6 2 μg/kg isolation, determination

(52-epi -CTX4B) Satake et al. (1997b) absolute configuration

scaritoxin Satake et al. (1997b) mixture of CTX4A and 4B

P-CTX4A Vernoux and Lewis (1997)

CTX4B no name Murata et al. (1989) 1060.6 isolation, planar structure

GTX4B Murata et al. (1990) 4 μg/kg configuration

CTX4B Satake et al. (1997b) absolute configuration

P-CTX4B Vernoux and Lewis (1997)

Representative studies and synonyms of ciguatoxins

THE 3rd IOC/WESTPAC – TMO TRAINING WORKSHOP“Technical guideline for Ciguatera study: experiences from Japan”Graduate School of Agricultural and Life Science, The University of TokyoTokyo, Japan, 5-6 November, 2013Representative studies and synonyms of ciguatoxins

(Table 2. continued)

CTX3C CTX3C Satake et al. (1993) 1022.6 1.3 μg/kg isolation and determination

Hirama et al. (2001) ～1.5 μg/kg synthesized

P-CTX3C Vernoux and Lewis (1997)

51-hydroxyCTX3C Satake et al. (1998a) 1038.6 0.27 μg/kg isolation and determination

Inoue et al. (2006) 0.31 μg/kg synthesized

2,3,-dihydroxyCTX3C Satake et al. (1998a) 1056.6 1.8 μg/kg isolation and determination

Caribbean ciguatoxin-1 C-CTX-1 Crouch et al. (1995) 1122.6 isolation

Vernoux and Lewis (1997) 1140.7 3.6 μg/kg isolation

Lewis et al. (1998) 1140.6 determination

Caribbean ciguatoxin-2 C-CTX-2 Vernoux and Lewis (1997) 1140.7 ～ 1 μg/kg isolation

Lewis et al. (1998) 1140.6 determination

Indian Ocean ciguatoxin-1 I-CTX-1 Hamilton et al. (2002b) 1140.6 isolation

Hamilton et al. (2002a) 1140.6 isolation

Indian Ocean ciguatoxin-2 I-CTX-2 Hamilton et al. (2002a) 1140.6 isolation




CTX1B congeners CTX3C congeners

OO

O

O

O

OO

O

O

OO

O

MeOH

Me

OH

Me

OH

OH

H H H H H H

H

H

H HH

H

H H H H HH

HH

H

H

O

Me

OH

Me OH

AB

CD

EF

G

H

I

JK

LM

1

54

52

シガトキシンCTX1B (1110)

O

O

OHOH

OH

A

LM

1

52

52-epi-54-deoxyCTX

(1094)

54

O

O

OH

A

LM

1

52

CTX4A

(1060)

OO

OH

A

LM

1

52

CTX4B

(1060)

OOH

OHOH

M-seco-CTX4A/B

(1078)1

A

L 52

OO

OHOH

OH

A

LM

1

52

54-deoxyCTX

(1094)54

OO

O

OH

OH

A

LM

51

49

1

2,3-dihydroxyCTX3C

(1056)

OO

O

OHA

L

M

51

49

1

2-hydroxyCTX3C

(1040)

O

O

O

A

LM

5149

1

49-epiCTX3C

(1022)

OO

OHO

A

LM

51

49

1

51-hydroxyCTX3C

(1038)

OO

O

O

O

OO

Me

MeOH

Me

Me

Me

OH

H

HH

H HH

H

HH

H HH

H

O

O

O

OO

O

OHH H H

H

H H HH

A B C D

EF

G

H

I

J

K

LM

51

49

1

CTX3C

(1022)

OOH

OHO

A

L 49

1

M-seco-CTX3C

(1040)

OOMe

OHO

A

L 49

1

M-seco-CTX3C methyl acetal

(1054)

54-deoxyCTX1B

(1094)

52-epi-54-deoxyCTX1B(1094)


Number of incidents and cases of CFP in Japan (1989-2010)

0

20

40

60

80

100

0

2

4

6

8

10

患者数（人）

食中毒発生件数（件）

患者数（人）発生件数（件）

Number of incidents

Number ofcases

’89 ’91 ’93 ’95 ’97 ’99 ’01 ’03 ’05 ’07 ‘09

Number ofcases

Number of incidents

Toda et al., 2012

THE 3rd IOC/WESTPAC – TMO TRAINING WORKSHOP“Technical guideline for Ciguatera study: experiences from Japan”Graduate School of Agricultural and Life Science, The University of TokyoTokyo, Japan, 5-6 November, 2013CFP incidents in Japan

(1989-2010)

OkinawaKagoshimaMiyazaki

Hyogo

Ibaraki

Kanagawa

Okinawa 70Kagoshima 3Ibaraki 1Kanagawa 1Hyogo 1Osaka* 1Miyazaki* 1

Total 78

Osaka

An incident reported as unidentified is suspected to be CFP due to consumption of Spotted Knifejaw, Oplegnathus punctatuscollected off Chiba.

Chiba

* Implicated fish was spotted Knifejaw, Oplegnathus punctatuscollected off the mainland Japan.

Toda et al., 2012


Ciguatera Incidents in Okinawa


Okinawa, also known as Ryukyu, is located in the south-westernmost end of Japan, consisting of 48 islands.

Its climate is subtropical and It has been recognized as ciguatera endemic area.

The population of Okinawa is 1.3 million.

THE 3rd IOC/WESTPAC – TMO TRAINING WORKSHOP“Technical guideline for Ciguatera study: experiences from Japan”Graduate School of Agricultural and Life Science, The University of TokyoTokyo, Japan, 5-6 November, 2013Natural toxin and chemical food

poisoning in Okinawa

puffers ciguatera

mushroom plant puffers

JAPAN

OKINAWA

histamine

others

CFP accounted for 70% of chemical or natural toxin food poisoning in Okinawa.

THE 3rd IOC/WESTPAC – TMO TRAINING WORKSHOP“Technical guideline for Ciguatera study: experiences from Japan”Graduate School of Agricultural and Life Science, The University of TokyoTokyo, Japan, 5-6 November, 2013Officially reported CFP in

Okinawa, 1997-2006.

•33 incidents were reported.

•Many cases might be remain unreported.

•Seasonality seems thin.

•Leftover foods and/or uncooked fish flesh could be obtained for analysis in 12 incidents.

0.024incidents/10,000 people/year

No. Date fish species Japanese nametoxicity

MU/g

1 18/Jan/97 6 9 67 L. monostigma イッテンフエダイ n.t.2

2 21/Sep/97 3 5 60 Lutjanus sp. フエダイ類 0.29

3 17/May/98 3 7 43 L. bohar バラフエダイ n.t.

4 17/Jun/98 3 5 60 V. louti バラハタ 0.1

5 25/Feb/99 1 1 100 E. fuscoguttatus アカマダラハタ n.t.

6 26/Feb/99 1 2 50 E. fuscoguttatus アカマダラハタ n.t.



9 03/Aug/99 1 4 25 L. monostigma イッテンフエダイ n.t.

10 31/Aug/99 3 3 100 Caranx ignobilis ロウニンアジ n.t.

11 21/Sep/99 6 6 100 unidentified 不明 n.t.

12 18/Oct/99 1 11 9 L. bohar バラフエダイ n.t.

13 16/Jan/00 7 7 100 E. polyphekadion マダラハタ 0.05


15 24/Jun/00 4 26 15 snapper フエダイ類 n.t.

16 19/May/01 3 3 100 unidentified 不明 n.t.

17 31/Aug/01 3 3 100 L. monostigma イッテンフエダイ >0.2

18 21/Jun/02 2 5 40 L. bohar バラフエダイ n.t.

19 04/Nov/02 2 2 100 P. areolatus オオアオノメアラ n.t.

20 30/Nov/02 3 3 100 L. monostigma イッテンフエダイ >0.8

21 01/Apr/03 2 5 40 O. punctatus イシガキダイ n.t.

22 03/Jul/03 4 4 100 L. monostigma イッテンフエダイ 0.2

23 22/Jul/03 3 3 100 L. monostigma イッテンフエダイ >0.2

24 06/Oct/03 4 4 100 V. louti バラハタ 0.4

25 06/Mar/04 2 3 67 moray eel ウツボ n.t.

26 18/Nov/04 3 4 75 V. louti バラハタ >0.2

27 06/Jul/05 7 9 78 V. louti バラハタ n.t.

28 10/Sep/05 6 6 100 V. louti バラハタ 0.1

29 24/Jan/06 2 2 100 V. louti バラハタ n.t.

30 18/Mar/06 2 2 100 L. bohar バラフエダイ n.t.

31 26/May/06 1 27 4 L. bohar バラフエダイ 0.1

32 29/Jun/06 4 4 100 V. louti バラハタ 0.05

33 31/Dec/06 3 8 38 V. louti バラハタ n.t.

Attack rate

(%)

Number of

people consumed

Number of

patients


speciesnumber of

outbreaks

ratio

(%)

Variola louti 8 24

Lutjanus bohar 8 24

L. monostigma 6 18

Epinephelus fuscoguttatus 2 6

Lutjanidae 2 6

Plectropomus areolatus 1 3

Oplegnathus punctatus 1 3

E. polyphekadion 1 3

surgeonfish 1 3

moray eel 1 3

unidentified 2 6

total 33

Variola louti

Lutjanus bohar

Lutjanus monostigma

Frequency of causative species inthe CFP incidents in Okinawa.


No. fish species test sampletoxicity

MU/g

2 Lutjanus sp. cooked flesh 0.29

4 V. louti raw flesh 0.1

13 E. polyphekadion cooked flesh 0.05

soup1 < 0.025

17 L. monostigma cooked flesh >0.2


22 L. monostigma raw flesh >0.2

mixed soup2 0.025

23 L. monostigma mixed soup2 >0.2


mixed soup2 0.1

26 V. louti flesh3 >0.2

V. louti flesh3 0.1


31 L. bohar cooked flesh 0.1

32 V. louti raw flesh 0.051 flesh and bones were removed and remainig were mixed.

2 bones were removed and remainig were mixed.

3 treated with boiling water

Toxicity (MU/g) of the leftover meals and/or remnant fish.

• Lowest toxicity of fish flesh0.05 MU/g (No. 13 & 32)

• Lowest toxicity of meal≦ 0.025 MU/g (No. 13 & 22)



MU/g




soup1 < 0.025




mixed soup2 0.025



mixed soup2 0.1


V. louti flesh3 0.1











MU/g




soup1 < 0.025




mixed soup2 0.025



mixed soup2 0.1


V. louti flesh3 0.1









• The maximum allowance level should be set below 0.025 MU/g

(0.175 ng CTX1B/g)



MU/g




soup1 < 0.025




mixed soup2 0.025



mixed soup2 0.1


V. louti flesh3 0.1









• The maximum allowance level should be set below 0.025 MU/g

(0.175 ng CTX1B/g)

• The minimum amount of consumption was estimated as 140 g (No. 28)

0.1 MU/g x 140 g = 14 MU＝ 98 ng CTX1B


Toxicity of Fishes from Okinawan Waters

Oshiro et al.


Lujanus argentimaculatus ゴマフエダイ

Lujanus boharバラフエダイ

Lujanus russelliiクロホシフエダイ

Lujanus monostigma イッテンフエダイ

Variola loutiバラハタ

Variola louti albimarginata オジロバラハタEpinephelus fuscoguttatus アカマダラハタ

Toxicity of Fishes from Okinawan Waters

THE 3rd IOC/WESTPAC – TMO TRAINING WORKSHOP“Technical guideline for Ciguatera study: experiences from Japan”Graduate School of Agricultural and Life Science, The University of TokyoTokyo, Japan, 5-6 November, 2013Frequency of toxic specimens in

representative fish species.

L. monostigma 226 73 32.3

E. fuscoguttatus 24 5 20.8

V. louti 49 7 14.3

L. bohar 168 20 11.9

V. albimarginata 36 1 2.8

L. russellii 74 2 2.7

L. argentimaculatus 35 0 0.0

total 612 108

speciestoxic*examined

ratio of toxic

specimen (%)

number of specimens

The species frequently implicated in CFP are highly toxic.


0

10

20

30

40

50

60

70

80

0 2 4 6 8 10 12weight (kg)

sta

nd

ard

le

ng

th (

cm

)

↑50 cm

→ 4 kg

Toxicity(%)

entire　 11.9

> 4 kg　　 37.7

> 7 kg　　 61.1

◆ nontoxic

◆ toxic

バラフエダイLutjanus bohar


0

10

20

30

40

50

60

70

80

90

0 5 10 15 20 25weight (kg)

sta

nda

rd len

gth

(cm

)

Toxicity (%)

entire 　 20.8

> 10 kg 　50.0

→ 10kg

↑70cm

◆ nontoxic

◆ toxic

アカマダラハタEpinephelus fuscoguttatus


0

10

20

30

40

50

60

0 1 2 3 4 5weight (kg)

sta

nd

ard

len

gth

(cm

)

Toxicity (%)

entire 　 14.3

> 1.5 kg 　25.0→ 1.5 kg

◆ nontoxic

◆ toxic

バラハタVariola louti


0

5

10

15

20

25

30

35

40

45

50

0.0 0.5 1.0 1.5 2.0 2.5weight (kg)

sta

nd

ard

length

(cm

)◆ nontoxic

◆ toxic

Toxicity (%)

entire 　 32.3

> 1 kg 48.0

イッテンフエダイLutjanus monostigma


Toxicity-based profiling of fish species

L. monostigma 29 4 (14) 7 (24) 8 (28) 6 (21) 4 (14)

L. bohar 20 9 (45) 6 (30) 5 (25)

V. louti 7 5 (71) 2 (29)

E. fuscoguttatus 5 4 (80) 1 (20)

* number of specimen (%)

number of toxic

specimenspecies

toxicity range*

0.025 0.05 0.1 0.2 0.4

The occurrence of strongly toxic specimens was high inL. monostigma, agreeing with the fishermen’s view thatL. monostigma was the most dangerous species.


CFP in Mainland Japan

THE 3rd IOC/WESTPAC – TMO TRAINING WORKSHOP“Technical guideline for Ciguatera study: experiences from Japan”Graduate School of Agricultural and Life Science, The University of TokyoTokyo, Japan, 5-6 November, 2013CFP incidents in Japan

(1989-2010)

OkinawaKagoshimaMiyazaki

Hyogo

Ibaraki

Kanagawa

Okinawa 70Kagoshima 3Ibaraki 1Kanagawa 1Hyogo 1Osaka* 1Miyazaki* 1

Total 78

Osaka

An incident reported as unidentified is suspected to be CFP due to consumption of Spotted Knifejaw, Oplegnathus punctatuscollected off Chiba.

Chiba

* Implicated fish was spotted Knifejaw, Oplegnathus punctatuscollected off the mainland Japan.

Toda et al., 2012


39/70

CFP in mainland Japan

Higshi-izu, Shizuoka 2007spotted Knifejaw (2.5 kg)Suspected (undiagnosed)

Katsuura, Chiba 1967Amberjack (19.5kg)

Manazuru, Kanagawa 2008spotted Knifejaw, Diagnosed but unreported

Hatijo-jima, Tokyo 2006spotted KnifejawSuspected (undiagnosed)

Minami-Ise 2008spotted Knifejaw (3 kg)Suspected (undiagnosed)

Susami, Wakayama 2007spotted KnifejawReported

Patients of three incidents were

undiagnosed at hospital.

They searched using by internet

and found CFP

CFP are supposed to be present in Mainland Japan

Katsuura, Chiba 1999spotted KnifejawReported as unkown


40

There should be many incidents.

• undiagnosed…• diagnosed but unreported…

spotted KnifejawOplegnathus punctatus


Acknowledgement

• Dr. Miou TODA (National Institute of Health Sciences)

• Prof. Takeshi YASUMOTO (Japan Food Research Center)

• Prof. Masahiro HIRAMA (Tohoku Univ.)

• Dr. Yasuo INAFUKU, Mr. Takashi UEHARA, Mr. KentaroYOGI, Ms. Satsuki SAKUGAWA, Ms. Ayuko KOJA. (Okinawa Prefectural Institute of Health and Environment)

• Dr. Hidemasa HIGA (Chibana Clinic)

• Dr. Yoshimitsu MIYAGI (Okinawa Prefectural Chubu Hospital)

occurrence of cfp in japaniocwestpac.org/files/upload_manual/l2 oshiro.pdf · 2014. 11. 12. ·...

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