korean hemorrhagic fever an ever present danger to u.s. forces korea col (ret) terry a. klein, phd...
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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
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
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
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).