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Origin of Plasmodium vivax in the Republic of Korea (South Korea): An approach using haplotype Network analysis based on mitochondrial DNA sequences of the parasite Origin of Plasmodium vivax in the Republic of Korea (South Korea): An approach using haplotype Network analysis based on mitochondrial DNA sequences of the parasite Moritoshi Iwagami a , Megumi Fukumoto a, b , Weon-Gyu Kho c , Shigeyuki Kano a, b Moritoshi Iwagami a , Megumi Fukumoto a, b , Weon-Gyu Kho c , Shigeyuki Kano a, b JITMM 2009, Bangkok, 3-4, Dec, 2009 a Research Institute, International Medical Center of Japan b Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan c Department of Malariology, Paik Institute of Clinical Research and Department of Parasitology, Inje University, College of Medicine, Korea

Republic of Korea (South Korea): An approach using haplotype … · Weon-Gyu Khoc, Shigeyuki Kanoa, b a a, b c, Shigeyuki Kanoa, b JITMM 2009, Bangkok, 3-4, Dec, 2009 aResearch Institute,

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Page 1: Republic of Korea (South Korea): An approach using haplotype … · Weon-Gyu Khoc, Shigeyuki Kanoa, b a a, b c, Shigeyuki Kanoa, b JITMM 2009, Bangkok, 3-4, Dec, 2009 aResearch Institute,

Origin of Plasmodium vivax in the Republic of Korea (South Korea):An approach using haplotype Network analysis based on mitochondrial DNA sequences of the parasite

Origin of Plasmodium vivax in the Republic of Korea (South Korea):An approach using haplotype Network analysis based on mitochondrial DNA sequences of the parasite

Moritoshi Iwagamia, Megumi Fukumotoa, b,Weon-Gyu Khoc, Shigeyuki Kanoa, b

Moritoshi Iwagamia, Megumi Fukumotoa, b,Weon-Gyu Khoc, Shigeyuki Kanoa, b

JITMM 2009, Bangkok, 3-4, Dec, 2009

aResearch Institute, International Medical Center of JapanbGraduate School of Comprehensive Human Sciences,

University of Tsukuba, JapancDepartment of Malariology,

Paik Institute of Clinical Research and Department of Parasitology, Inje University, College of Medicine, Korea

Page 2: Republic of Korea (South Korea): An approach using haplotype … · Weon-Gyu Khoc, Shigeyuki Kanoa, b a a, b c, Shigeyuki Kanoa, b JITMM 2009, Bangkok, 3-4, Dec, 2009 aResearch Institute,

World Health Organization 2008

JITMM 2009, Bangkok, 3-4, Dec, 2009

World Distribution of MalariaWorld Distribution of Malaria

Page 3: Republic of Korea (South Korea): An approach using haplotype … · Weon-Gyu Khoc, Shigeyuki Kanoa, b a a, b c, Shigeyuki Kanoa, b JITMM 2009, Bangkok, 3-4, Dec, 2009 aResearch Institute,

Demilitarized zone (DMZ) in South Korea

Trends Parasitol (2007) 24:143-150

JITMM 2009, Bangkok, 3-4, Dec, 2009

Malaria endemic area in South KoreaMalaria endemic area in South Korea

Page 4: Republic of Korea (South Korea): An approach using haplotype … · Weon-Gyu Khoc, Shigeyuki Kanoa, b a a, b c, Shigeyuki Kanoa, b JITMM 2009, Bangkok, 3-4, Dec, 2009 aResearch Institute,

Trends Parasitol (2007) 24:143-150JITMM 2009, Bangkok, 3-4, Dec, 2009

Num

ber o

f pat

ient

s

4500

4000

3500

3000

2500

2000

1500

1000

500

1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

Annual number of vivax malaria patients reported in South Korea (1993–2006)

Annual number of vivax malaria patients reported in South Korea (1993–2006)

Page 5: Republic of Korea (South Korea): An approach using haplotype … · Weon-Gyu Khoc, Shigeyuki Kanoa, b a a, b c, Shigeyuki Kanoa, b JITMM 2009, Bangkok, 3-4, Dec, 2009 aResearch Institute,

Proportion of P. vivax malaria patients in South Korea (1993–2007)

Proportion of P. vivax malaria patients in South Korea (1993–2007)

Korean J Parasitol (2009) 47:S39-50

SoldiersVeteransCivilians

93 94 95 96 97 98 99 00 01 02 03 04 05 06 070

20

40

60

80

100Pe

rcen

t (%

) out

of t

he to

tal p

atie

nts

JITMM 2009, Bangkok, 3-4, Dec, 2009

Page 6: Republic of Korea (South Korea): An approach using haplotype … · Weon-Gyu Khoc, Shigeyuki Kanoa, b a a, b c, Shigeyuki Kanoa, b JITMM 2009, Bangkok, 3-4, Dec, 2009 aResearch Institute,

Map of Korean peninsular and JapanMap of Korean peninsular and Japan

Demilitarized ZoneDemilitarized Zone

Google MapJITMM 2009, Bangkok, 3-4, Dec, 2009

2002

Page 7: Republic of Korea (South Korea): An approach using haplotype … · Weon-Gyu Khoc, Shigeyuki Kanoa, b a a, b c, Shigeyuki Kanoa, b JITMM 2009, Bangkok, 3-4, Dec, 2009 aResearch Institute,

ObjectiveObjective

The objective of this study is to estimate the origin of the Plasmodium vivax (Pv) population in South Korea by phylogenetic analyses based on mitochondrial (mt) DNA sequences of Pv isolates from South Korea and other countries in the world.

JITMM 2009, Bangkok, 3-4, Dec, 2009

Page 8: Republic of Korea (South Korea): An approach using haplotype … · Weon-Gyu Khoc, Shigeyuki Kanoa, b a a, b c, Shigeyuki Kanoa, b JITMM 2009, Bangkok, 3-4, Dec, 2009 aResearch Institute,

Materials and MethodsMaterials and Methods

• 11 South Korean Pv isolates• 10 other Pv isolates (Southeast Asia, South Asia,

Western Pacific, Middle East, South America, Africa)• 282 Pv isolates (including 1 North Korean isolate) from

GenBank database

DNA Analysis• Mitochondrial (mt) DNA analysis (PCR & Sequencing)Phylogenetic Analyses• A neighbor-joining tree• A haplotype network tree (Median-joining method)

Materials

Methods

JITMM 2009, Bangkok, 3-4, Dec, 2009

Page 9: Republic of Korea (South Korea): An approach using haplotype … · Weon-Gyu Khoc, Shigeyuki Kanoa, b a a, b c, Shigeyuki Kanoa, b JITMM 2009, Bangkok, 3-4, Dec, 2009 aResearch Institute,

A Y 7 9 1 5 7 1 P h i l i p p i n e s A Y 7 9 1 6 4 4 P a p u a N e w G u i n e a

A Y 7 9 1 6 2 6 I r a n A Y 7 9 1 6 3 6 P a p u a N e w G u i n e a A Y 7 9 1 5 6 4 S o l o m o n I s l a n d s A Y 7 9 1 6 3 9 P a p u a N e w G u i n e a A Y 7 9 1 6 3 0 I n d i a A Y 7 9 1 5 6 6 V a n u a t u A Y 7 9 1 5 6 5 V a n u a t u

A Y 7 9 1 6 3 7 P a p u a N e w G u i n e a A Y 7 9 1 6 3 2 P a p u a N e w G u i n e a

A Y 7 9 1 6 4 3 P a p u a N e w G u i n e a A Y 7 9 1 6 3 5 P a p u a N e w G u i n e a

A Y 7 9 1 6 9 2 M e l a n e s i a A Y 7 9 1 6 4 1 P a p u a N e w G u i n e a

A Y 7 9 1 6 5 0 P a p u a N e w G u i n e a A Y 7 9 1 6 5 7 P a p u a N e w G u i n e a

A Y 7 9 1 6 3 4 P a p u a N e w G u i n e a A Y 5 9 8 1 1 6 S o l o m o n I s l a n d s

A Y 7 9 1 6 2 5 I r a n A Y 7 9 1 6 7 7 P a p u a N e w G u i n e a

A Y 7 9 1 6 5 2 P a p u a N e w G u i n e a A Y 7 9 1 6 8 6 P a p u a N e w G u i n e a A Y 7 9 1 6 4 8 P a p u a N e w G u i n e a A Y 7 9 1 6 4 6 P a p u a N e w G u i n e a

A Y 7 9 1 6 5 9 P a p u a N e w G u i n e a A Y 7 9 1 5 5 5 B o r m e o

P N G I M C J A Y 7 9 1 5 3 8 B r a z i l A Y 5 9 8 0 9 0 B r a z i l A Y 7 9 1 5 3 9 B r a z i l A Y 5 9 8 0 9 4 B r a z i l

A Y 5 9 8 0 7 6 B r a z i l B r a z i l I M C J A Y 7 9 1 5 4 8 P a n a m a A Y 7 9 1 5 4 7 C o l o m b i a A Y 7 9 1 5 4 3 E l S a l v a d o r A Y 7 9 1 5 3 1 B r a z i l A Y 5 9 8 0 7 5 B r a z i l A Y 7 9 1 5 4 1 N i c a r u a g u a A Y 5 9 8 0 7 4 B r a z i l A Y 7 9 1 5 4 2 P a n a m a A Y 7 9 1 5 4 5 H o n d u r a s A Y 7 9 1 5 2 9 B r a z i l

A Y 7 9 1 5 5 0 S . C . A m e r i c a A Y 7 9 1 5 5 1 E l S a l v a d o r A Y 7 9 1 5 4 4 D o m i n i c a n R e p u b l i c

A Y 7 9 1 5 3 0 B r a z i l A Y 5 9 8 1 1 8 S o l o m o n I s l a n d s

A Y 5 9 8 0 9 3 B r a z i l A Y 5 9 8 0 8 4 B r a z i l A Y 5 9 8 0 8 5 B r a z i l A Y 7 9 1 5 1 7 A f r i c a A Y 7 9 1 6 2 9 P a k i s t a n

A Y 7 9 1 6 0 9 I n d i a I r a n I M C J A Y 7 9 1 5 1 9 A f r i c a

A Y 7 9 1 5 2 7 N . W . A f r i c a A Y 7 9 1 5 2 1 E t h i o p i a

A Y 7 9 1 5 7 5 S r i L a n k a A Y 7 9 1 6 2 1 I n d i a

A Y 7 9 1 5 2 5 E t h i o p i a A Y 7 9 1 6 1 0 I n d i a

A Y 7 9 1 6 2 4 I n d i a I n d i a I M C J

A Y 7 9 1 5 1 8 A f r i c a A Y 7 9 1 5 5 7 S r i L a n k a

A Y 5 9 8 1 2 0 I n d i a A Y 7 9 1 6 0 8 I n d i a A Y 7 9 1 6 0 7 I n d i a

A Y 7 9 1 6 2 8 I n d i a A Y 7 9 1 6 2 3 B a n g l a d e s h

A Y 7 9 1 6 2 7 P a k i s t a n A Y 5 9 8 0 5 5 T h a i l a n d

A Y 5 9 8 1 2 6 V i e t n a m A Y 5 9 8 1 1 2 B a n g l a d e s h

A Y 5 9 8 1 2 5 V i e t n a m A Y 5 9 8 0 6 0 T h a i l a n d

A Y 5 9 8 1 1 0 B a n g l a d e s h A Y 5 9 8 0 4 0 T h a i l a n d A Y 5 9 8 0 3 8 T h a i l a n d A Y 5 9 8 1 1 1 B a n g l a d e s h A Y 5 9 8 0 4 9 T h a i l a n d A Y 5 9 8 1 2 2 V i e t n a m A Y 7 9 1 5 8 4 V i e t n a m

A Y 5 9 8 0 6 8 T h a i l a n d A Y 5 9 8 0 6 9 T h a i l a n d A Y 5 9 8 1 1 4 B a n g l a d e s h

A Y 5 9 8 0 3 7 T h a i l a n d A Y 5 9 8 0 4 8 T h a i l a n d A Y 5 9 8 0 7 0 T h a i l a n d A Y 5 9 8 0 3 6 T h a i l a n d

A Y 5 9 8 0 5 7 T h a i l a n d A Y 5 9 8 1 2 7 V i e t n a m A Y 5 9 8 0 4 4 T h a i l a n d A Y 5 9 8 0 3 5 T h a i l a n d

A Y 5 9 8 0 4 3 T h a i l a n d A Y 5 9 8 0 4 6 T h a i l a n d

A Y 5 9 8 0 6 5 T h a i l a n d A Y 7 9 1 5 9 4 G u a n g X i . C h i n a A Y 7 9 1 5 9 9 G u a n g X i . C h i n a

A Y 7 9 1 6 0 0 G u a n g X i . C h i n a K o r e a A 4 A Y 5 9 8 1 3 3 S o u t h e r n . C h i n a K o r e a A 2 K o r e a A 3 K o r e a A 1 A Y 5 9 8 1 3 2 S o u t h e r n . C h i n a K o r e a B 1 A Y 5 9 8 1 3 9 S o u t h e r n . C h i n a

K o r e a A 5 A Y 7 9 1 5 6 3 I n d o n e s i a A Y 7 9 1 5 8 1 V i e t n a m

A Y 7 9 1 5 6 2 I n d o n e s i a A Y 7 9 1 6 9 0 P a p u a N e w G u i n e a / S o l o m o n I s l a n d I n d o n e s i a I M C J A Y 5 9 8 1 0 0 I n d o n e s i a A Y 5 9 8 0 9 9 I n d o n e s i a A Y 5 9 8 1 0 1 I n d o n e s i a A Y 5 9 8 1 0 8 I n d o n e s i a

A Y 7 9 1 5 7 2 I n d o n e s i a A Y 5 9 8 0 9 8 I n d o n e s i a A Y 7 9 1 5 7 3 E a s t T i m o r A Y 7 9 1 5 6 7 I n d o n e s i a

A Y 7 9 1 5 8 5 Y u n n a n . C h i n a A Y 7 9 1 5 8 6 Y u n n a n . C h i n a A Y 7 9 1 5 8 9 G u a n g X i . C h i n a A Y 7 9 1 5 9 3 G u a n g X i . C h i n a

A Y 7 9 1 5 9 0 G u a n g X i . C h i n a K o r e a B 5 A Y 5 9 8 1 2 8 S o u t h e r n . C h i n a A Y 7 9 1 5 8 8 G u a n g X i . C h i n a K o r e a B 4 A Y 7 9 1 5 9 5 G u a n g X i . C h i n a K o r e a B 2 K o r e a B 3

A Y 7 9 1 5 5 4 N o r t h K o r e a A m a m o t o

A Y 7 9 1 5 9 2 G u a n g X i . C h i n a K o r e a I C

0.0001

Neighbor-Joining Tree Neighbor-Joining Tree Papua New Guinea Western Pacific

Central & South America

South AsiaMiddle EastAfrica

Southeast Asia (Indochina peninsula)

Southern China Group A

Indonesia

• Kimura 2-parameter model • P. vivax mtDNA sequences• 145 isolates

(124 isolates: GenBank,21 isolates: Present Study)

63

The numbers for interior branch represent the bootstrap values (%) of 500 replications (> 50)

68

50

54

51

85

Southern China Group B

MEGA ver. 3.1JITMM 2009, Bangkok, 3-4, Dec, 2009

South Korea South Korea Group A

South Korea Group BSouth Korea South Korea

Page 10: Republic of Korea (South Korea): An approach using haplotype … · Weon-Gyu Khoc, Shigeyuki Kanoa, b a a, b c, Shigeyuki Kanoa, b JITMM 2009, Bangkok, 3-4, Dec, 2009 aResearch Institute,

Haplotype Network TreeHaplotype Network Tree

P. vivax mtDNA haplotype network tree (Median-joining method) 303 isolates (282 isolates: GenBank, 21 isolates: Present Study) JITMM 2009, Bangkok, 3-4, Dec, 2009

Network ver. 4.5.1.0

Papua New GuineaPapua New GuineaSouth Asia, Middle EastSouth Asia, Middle East

Southern ChinaSouthern China

AfricaAfricaSouth and Central AmericaSouth and Central America

Southeast Asia (Indochina)Southeast Asia (Indochina)

South Korea, North KoreaSouth Korea, North Korea

IndonesiaIndonesia

North KoreaNorth Korea

South Korea BSouth Korea BSouthern China BSouthern China B

Southern Southern China BChina B

Southern Southern China BChina B

Southern Southern China BChina B

Group B complex

South South Korea AKorea A

Southern Southern China AChina A

South South Korea AKorea A

Group A complex

Page 11: Republic of Korea (South Korea): An approach using haplotype … · Weon-Gyu Khoc, Shigeyuki Kanoa, b a a, b c, Shigeyuki Kanoa, b JITMM 2009, Bangkok, 3-4, Dec, 2009 aResearch Institute,

ResultsResults• In South Korea, there were two groups (i.e. SK group

A and B) in the Pv population.

• In Southern China, there were also two groups (i.e. SC group A and B).

• The North Korean isolate was included in the group B complex.

• The direct origin of the Pv population in South Korea is thought to be from North Korea via the DMZ, but the true origin of Pv populations in Korean peninsular is now suggested to be from Southern part of China. The Chinese Pv populations have two different origins.

JITMM 2009, Bangkok, 3-4, Dec, 2009

ConclusionConclusion

Page 12: Republic of Korea (South Korea): An approach using haplotype … · Weon-Gyu Khoc, Shigeyuki Kanoa, b a a, b c, Shigeyuki Kanoa, b JITMM 2009, Bangkok, 3-4, Dec, 2009 aResearch Institute,

AcknowledgementsAcknowledgements

• S. Looareesuwan: Mahidol University, Bangkok, Thailand

• Disease Control and Prevention Center, International MedicalCenter of Japan

• This study was supported by

Health and Labour Sciences Research Grants for Research on Emerging and Re-emerging Infectious Diseases from the Ministry of Health, Labour, and Welfare of Japan (H18-SHINKOU-IPPAN-009)

A Grant-in-Aid for Scientific Research (B) (19406013) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan

JITMM 2009, Bangkok, 3-4, Dec, 2009