KOREAN HEMORRHAGIC FEVER An Ever Present Danger to U.S. Forces Korea COL (Ret) Terry A. Klein, PhD Regional Emerging Infectious Disease Consultant Force.

KOREAN HEMORRHAGIC FEVER

An Ever Present Danger to U.S. Forces Korea

COL (Ret) Terry A. Klein, PhDRegional Emerging Infectious Disease ConsultantForce Health Protection, 18th Medical Command

13 February 2007

Collaborators

• Dr. Jin-Won Song, Korea University• Dr. Luck-Ju Baek, Korea University• Dr. Heung-Chul Kim, 5th MED DET• LTC William Sames, 18th MEDCOM• LTC Douglas Burkett, Air Force• LTC Monica O’Guinn, USAMRIID• MAJ John Lee, USAMRIID• MAJ Anthony Schuster, CHPPM• Commanders and Personnel, MED DETS

Rodent-borne Disease Surveillance

Purpose: Reduce the impact of rodent-borne diseases

Background: >400 cases of HFRS annually Problem: Rodent-borne diseases often

“epidemic”. Benefits: Increase “early warning” potential Surveillance: HFRS, murine typhus, scrub

typhus, and leptospirosis Environmental modifications: Affects

population and disease potential of emerging infectious diseases

• Hantaviruses are worldwide

• HFRS (KHF) is a viral disease

• Maintained by rodent reservoirs

• Ranges in severity from mild to fatal

• Prevention is the best measure

• If prevention fails, requires rapid treatment/supportive care (ribovirin)

• Risks related to occupation and behavior

• No US approved vaccine

Introduction

• Respiratory via aerosolized rodent secreta/excreta (3 - 8% mortality)

• No horizontal human to human transmission

• 2,422 US cases during Korean war

• Prevention requires good field sanitation

• Early supportive treatment required

HFRS Transmission

6 9 6 0 2 0 8 4 1 4 9 3 4 3 0 3 0 4 0

55 58

10685 76

109132

89118 104

215196 203

323 336

392427 431 415

95 10379

52 50 6126 27 23 23 37 24 16 15 9

4610 0 00

50

100

150

200

250

300

350

400

450

500

'88 '89 '90 '91 '92 '93 '94 '95 '96 '97 '98 '99 '00 '01 '02 '03 '04 '05 '06

USFK *ROK CivilianROK Military

Number of Korean Hemorrhagic Fever Cases in ROK Personnel, 1986 - 2006

Nu

mbe

r of

Rep

orte

d C

ases

Number of HFRS Cases in USFK Personnel*, 1986 – 2005

14

56

9

6

0

2

0

9

4

12

4

12 2

0

3

0

4

00

2

4

6

8

10

12

14

16

'86 '87 '88 '89 '90 '91 '92 '93 '94 '95 '96 '97 '98 '99 '00 '01 '02 '03 '04 '05 '06Year

* USFK includes US soldiers and KATUSAs; #One case during 2001 due to Seoul virus contracted at Yongsan Garrison

#

HFRS Patients by Area, 2005

KHF Patients by Area in ROK-2005

GangwondoGyonggidoInchonsi

Chungbuk

ChungnamGyongbuk

Junnam

JunbukGyongnam

Busan

DaeguGwangju

Daejun

Seoul

Jeju

No. of patients01 - 2627 - 3940 - 4950 - 80

KHF Patients by Area, ROK Military

Figure 1. Apodemus agrarius, the primary reservoir of Hantaan virus

Rattus norvegicus

Apodemus peninsulae

Figure 3. A. peninsulae, primary reservoir of Soochong virus

Figure 2. Rattus norvegicus, the primary reservoir of Seoul virus

Apodemus agrarius

Rodents & Hantaviruses of Korea

Rodent-borne disease surveillance at selected US military training sites near the DMZ, 2000 - 2006

North Korea

South Korea

1

2

1

2

1

1

HFRS Risk High Risk Moderate Risk Low Risk HFRS Cases

2

1

(A) Overview of training site. (B) Rice paddies associated with tall grasses bordering training area. (C) Road leading through a “tank trap” to the main training area (A). (D). Tall grassy intermittent stream bed.

A

C

B

D

Rodent-borne disease surveillance at Dagmar North Training Area

Changing Seasons, FP-60

Early Fall

Spring Early Summer

WinterEarly Fall

Habitat Modification, FP-60

Number of Small Mammals Captured Near the DMZ, 2001 – 2005

Dagmar North

1722

381

10

66

20

11

1

Apodemus agrarius Crosidura lasiuraCricetulus triton Micromys minutusMicrotus fortis Mus musculusRattus norvegicus Rattus rattusEothenomys regulus

`

FP 10

493

211

1

4

6

Apodemus agrarius Crosidura lasiura

Micromys minutus Microtus fortis

Mus musculus Rattus norvegicus

`

LTA 130

2 1

2

38

3110

313

Apodemus agrarius Crosidura lasiuraCricetulus triton Micromys minutusMicrotus fortis Mus musculusRattus norvegicus Rattus rattusEothenomys regulus

`

FP 60

695

59

6 43

2

2

112

Apodemus agrarius Crosidura lasiuraCricetulus triton Micromys minutusMicrotus fortis Mus musculusRattus norvegicus Rattus rattusEothenomys regulus

`

Patient # 1 # 2 # 3 # 4

Onset of 5 Oct 3 Nov 6 Nov 12 Nov

Symptoms

Training 20-29 Sep 8-21 Oct 8-15 Oct 8-21 Oct

Dates

Training LTA 320, 36, 37 Twin Bridges Twin Bridges Twin Bridges

Sites FP 60 Rodriguez Rodriguez

Watkins Watkins

Incubation 27 – 36 Days 26 – 39 Days 29 – 35 Days 35 – 48 Days

Period

Virus FP 60 Twin Bridges Twin Bridges Twin Bridges

Match South North South

Table 1. Summary of patient histories for four patients that acquired HFRS infections while training at US and ROK operated military training sites near the DMZ.

NJ Tree based on 281-bps nucleotides of G2-M segment of HTNV from USFK HFRS patient #1-4, 2005

HTN/04-182 FP60HTN/04-618 FP60HTN/04-1293 FP60

HTN/04-1332 FP60HTN/04-1282 FP60HTN/04-1325 FP60USFK patient #1

HTN/05-1459 TBHTN/05-1465 TBUSFK patient #3

HTN/05-1410 TBHTN/05-1411 TB

HTN/05-1437 TBUSFK patient #2USFK patient #4

HTN/YJ89-13HTN/05-1438 TB

HTN/05-1458 TBHTN/05-1439 TB

HTN/04-1257 FP10HTN/01-425 FP10 HTN/01-431 FP10HTN/01-542FP10 HTN/02-185FP10

HTN/WC98-181HTN/HC97-91HTN/YC98-44

HTN/IJ97-100HTN/HoJo

HTN/LEEHTN/PC89-43

HTN/JH96-25HTN/SN94-2

HTN/76-118HTN/NS94-20

HTN/Jiang13 ChinaHTN/Bao9 China

HTN/AA1028 RussiaSOO/SOO-1

SOO/SOO-3DOB

SEO/80-39 0.01 substitutions/site

63

60

76

100

100100

100

89

Figure 10. NJ Tree based on 281-bps nucleotides of the G2-M segment of the HTNV from USFK HFRS Patients 1-4, 2005.

FP60

FP10

TBTA-N

TBTA-S

Firing Point 60, Rodent Habitat/Activities

Firing Point 60, Rodent Habitat/Activities

Primary Rodent Trapping Lines

Patients # 2-05and # 4-05

Patient # 3-05

Twin Bridges TA – Rodent Habitat

Potential Infected

Dust

Rodent Foraging and Migration

Fighting Position

Dirt Road Adjacent to Fighting Positions Virus Laden

Rodent Feces

Virus Laden Rodent Feces

Training SiteDirt Road

Rodent Activity

Twin Bridges TA – Rodent Habitat

b b

b

b

b

b

b

b

b

b

bb

bb

Paju-si

Cheorwon-gun

Pocheon-gun

Gapyeong-gun

Yeoncheon-gun

Yangju-gun

Uijeongbu-si

Dongducheon-si

Cp Howze

cp CASEY

Cp Hovey

Cp Giant

Cp Castle

Cp Greaves

Cp Stanley

Cp Essayons

Cp Red Cloud

Cp Gary Owen

MPRC

Chaparral

LTA 130

Dagmar North

Story Range

Warrior Base VERY HIGHHIGHMODERATELOWNOT DONE

RISK CATEGORY

Hanta Virus Risk - 2005

Monkey 7

FP 10

FP 60

TBTA

N

EW

S

#

Fig. 12. Dust created by wheeled vehicles along a dirt road and tracked vehicles at barren training site associated with tall grass habitats.

Fig. 13. Wetting down dirt roads to reduce dust.

Fig. 14. Discarding of refuse adjacent to primary rodent habitat (tall grasses).

Dagmar North