(Human Rabies Prevention and Post-Exposure Rabies Prophylaxis)

(zoonosis) rabies virus

rabies-related virus RNA virus family rhabdoviridae (genus Lyssavirus)
7 genotypes genotype 1 rabies virus rabies-related viruses
Lyssavirus genotype 2(Lagos bat virus); Lyssavirus genotype 3 (Mokola virus); Lyssavirus genotype 4
(Duvenhage virus); Lyssavirus tgenoype 5 (European bat Lassavirus biotype 1); Lyssavirus genotype 6
(European bat lyssavirus biotype 2), Lyssavirus genotype 7 (Australian bat Lyssavirus)1 rabiesrelated viruses rabies-like encephalitis ( Lyssavirus genetype 2
; Lagos bat virus )

(encephalitis)
(
) 50,000
( 2,5000-30,000
)

(intradermal injection)
2-4

( 90
) 5

(
) 6-8
9,10

1992 11,12
Lyssavirus

 (rabies-like encephalitis ) Australian bat lyssaviruses

Canidae (dogs,
wolves, foxes coyotes), Procyonidae (raccoons), Viverridae (mongooses), Mustelidae (skunks, weasels,
martens) Chiroptera (bats)
(susceptible species) foxes, coyotes, jackals, voles, kangaroo rats wolves
susceptible
moderately susceptibility ( 99 ) 6
(bites), contamination virus-laden saliva, (aerosol) ,
(transplacental route) 6,7

(nerve-tissue vaccines) semple vaccine
suckling mouse brain vaccine
300

(cell-culture rabies vaccines) (purified duck

embryo vaccine)
20 60,000
300,000-400,000 ( 0.5 100

)



30 2-3 90
(
)

(bite
prevention) 13

1.

2.2-314,15
( 95-96), ( 3-4)
16

 62 .. 2524
46% 2538 30 254316,17


80
70 96.518
oral vaccine
19
2-3
2. (pre-exposure vaccination)

( )

3.
( multiple intradermal route)
10

4. (rabies immune globulin, RIG)

20-23

( : human
RIG) (equine rabies immune globulin:ERIG)
( ) ERIG (purified ERIG)24
crude ERIG

virus strain
(mucosa)
(non-bite exposure)
( 5-80) ( 0.1-1)

( )

 ( )
25-34

(transplacental route)

25,26,35
virus strain

(5-80)
(0.1-1) 50
(
)


( ) 7 6
3 (88) 20-60 1
(96-98) 1 6 ( latent rabies) 1-7
36,37
latent rabies

( 10 ) 25,38-42
40 5-14


35-57
30,000
()

(contact route)


43 85 ( ), 10
3 (2)44
0-14
4 500

45-48
( 1) (2
1 ) (vampire)
8

(superficial
8,45-48
bite scratch)

49
1
50,51

.. 2539-2540 14,964 1 : 1
() 1-30 ( 20
10 )
44,52
WHO categories53-56 ( 1) 90
(WHO category
III) category III 57
( 60) (
) ( 60) ( 12.7)
5 ( 10)
70 44,46 53
50 3 52,57,58
WHO category III 5.1
75 (
)

90
50
(WHO
category III)
(equine rabies immune globulin; ERIG)
59-61


povidon-iodine
54,62 (active immunization) (rabies immune

globulin, RIG) (passive immunization)

15
(povidone iodine) (hibitane in water) 70%

(
) 2-3


tetanus toxoid (TT, dT dTap)

(active immunization)

(active immunization)
10-14
(passive immunization)

2
1.

(bite exposure) (non-bite exposure)

(bite exposure)

(non-bite exposure)

3 categories ( 1)
WHO category I

(pre-exposure prophylaxis)
WHO category II

 WHO category III

( 1)
2.( 1)


( )





( .. 2545-2550) ( 72) ( 20)
( 4)57,58

( 1)
24
2 fluorescent antibody test (FAT) Negri boies
fluorescent antibody test 1 FAT
mouse
inoculation test (MIT)
7 ( 21-28 )
nested polymerase chain reaction (nested PCR)
latex agglutination test antigen
63-69
FA test

8,763 FAT
99 mouse inoculation test (MIT)
FAT (false negative) 63
FAT FAT
(false negative)
FAT FAT

( , )


10 10
70

1.
2. 2
3. (provoked condition)
3 10
3
10

3-12
3 (provoked condition)
(unprovoked condition) 59
10
( 957 94 ) 10
72 ( 3-4 2
primary immunization
pre-exposure )
10
(Post-exposure rabies prophylaxis)

semple vaccine suckling mouse brain vaccine
4 HDCV (human diploid cell vaccine 1 .
), PCECV (purified chick embryo cell vaccine 1 . ) PVRV
(purified Vero cell vaccine, 0.5 . ) PDEV (purified duck embryo vaccine, 1 .
preservation)

(intramuscular)
(intradermal) ( 2) 14
rabies neutralizing antibody (Nab) 0.5 IU/.
10-14 21
25


adjuvant immunopotentiator inosoplex 72
4 ( 2)
(ESSEN regimen)

 Thai Red Cross (TRC-ID regimen modified TRC-ID regimen) 2

4,7,22,54,59,73-76

1. (standard intramuscular regimen: ESSEN)

22,54,77-83 1 (1 . 0.5 .
rabies antigen 2.5 IU/)
(deltoid muscle) (anterolateral of thigh muscle)

passive
84
immunization
1 ( 1 1/2 )
0 ( ) 3, 7, 14 28 30
immunogenicity effectiveness ESSEN
(immunocompetent host)

rabies neutralizing antibody (Nab) 25,77-85 Nab
7 10-14 Nab 0.5 IU/.
(acceptable protective level) 14 Nab
0.5 IU/. 1 80,86 1-2 97-100
(RIG) 7

( 5 ) 5

(ACIP-USA) 4 0 (
) 3, 7, 14 (http://
www.cdc.gov/vaccines/recs/provisional/downloads/rabies - July2009- 508)
2. Thai Red Cross (original TRC-ID regimen 2-2-2-0-1-1, modified TRC-ID
regimen 2-2-2-0-2-0) 2
(deltoid region) 0, 3, 7 1 28 90 (2-2-2-0-1-1)
2 28 (2-2-2-0-2-0)
0.7 IU(0.7 IU/0.1.) 73,76 TRC rabies
antigenicity 1 0.7 IU
rabies
antigenicity 1
0.5 IU (0.5 IU/0.1.)
Nab
76,82,87-93


( 2 )


2-8 o 6 - 8 94-97
preservation ( PDEV) 5 immunogenicity
2-2-2-0-2-0 2-2-2-0-1-1
(Nab) 0.5 IU/. 14, 28, 90 1
90 2 28 (modified TRC-ID regimen, 2-2-2-02-0) 98 2-2-2-0-2-0
2-2-2-0-1-1
(subcutaneous) 1 2
2 99
0.1
. HDCV ( 0.25
.) 100

2-1-1 (multisite intramuscular regimen, Zagreb) 8 (8site intradermal, oxford 8-0-4-0-1-1)

2-1-1 (multisite intramuscular regimen, Zagreb) 2
1 7 21 28 3
28 (PDEV)
rabies Nab
( 4 ) ( 3 )101
3

Zagreb
rabies Nab > 0.5 IU/. 1 50101-102
PCECV PVRV ( rabies antigenicity 10 IU/)
(human rabies immune globulin; HRIG) ERIG
2-1-1 14 rabies Nab 0.5 IU/.
0.5 IU/. 1 103-104

8 (8-site intradermal, 8-0-4-0-1-1) 0.1 .

HDCV PCECV 1 . 8
( 8 ) 4 7
1 28 90
105-109 108-109
WHO categories

3

110-112 (80-4-0-1-1) PVRV 0.05 . 1
0.05 . 1 (4-0-20-1-1) 113-116
/
/

117 (intradermal) TRC (2-2-2-0-2-0)
ESSEN TRC
.. 2549
0
3
500 rabies Nab
0 2 3, 7 1 28 90 (IM-2-2-01-1;TRC-ID) 2 0, 3, 7 1
28 90 (2-2-2-0-1-1;TRC-ID) rabies Nab 118


( )119120

(Rabies immune globulin , RIG)

passive immunization
121-123
category III
2
1. Human rabies immune globulin (HRIG)
HRIG 20 IU/ () HRIG
HRIG
2. Equine rabies immune globulin (ERIG) ERIG
40 IU/() crude ERIG
16.3 46124 ( 40)
purified ERIG ( 1.6-6.9)
purified ERIG purified ERIG 125-129 anaphylaxis
purified ERIG (crude ERIG anaphylaxis 3.8)129

 purified ERIG 130-133

human monoclonal antibody rabies virus 134-135
1
( 10-14)136
7
54,137 (active immunization)

neutralizing receptor (
)54,138,139 ( )

140 (
) 54


(
2-3 54
(Intradermal skin testing) ERIG
anaphylaxis ( IgE mediated type I hypersensitivity) serum sickness (type III hypersensitivity) 40

intradermal skin test ERIG
anaphylaxis serum sickness 129,141
intradermal skin testing (
) 129 wheal 5 .
30-40 ( 30-40
HRIG )
ERIG ( purified ERIG) 26 ERIG 0.02 .
( 1:100 ) 10
wheal flare 2
anaphylaxis serum sickness 1.41 wheal
5 . 10 . 5 . 2
negative control test wheal 5 . 25.9
HRIG wheal
10 . flare 20 . anaphylaxis
anaphylaxis



WHO category III 1

(
)

(Post-exposure prophylaxis for previously vaccinated persons)
1)
2)
3 3) rabies Nab
0.5 IU/.
(WHO category II III)54

142
14

143 2
1. 1
1 0.1 . 1 ( 0)
6 144-145 2 ( 0 3) 6 54,146
2. 4 0.1 .
(multisite intradermal injection) 4 0

PVRV 4 (0.1./) 0
PVRV 2 (03) (conventional booster regimen)
PVRV pre-exposure ID (0.1./) 1 rabies Nab ID 4
3-5 2 0 3
5 1 147 4
..2541
WHO category 2 3 4,200 WHO Category III 2,858
( 68) 220 (FAT
positive) 4 148
4
2 ( 03)

 2
149

2-14
rabies Nab T
lymphocyte 150 2

5 10
PDEV 1 0.2 . PVRV 1 2
0 3 rabies Nab 7
5-10 10
5-21 rabies Nab
151-153

4 0 1 0 3
(pre-exposure postexposure vaccination)
Special hosts


202 (59 3 )
RIG (
0.39 ) 1


1
154
HDCV, PDEV , PCECV 155-157

(immunocompromised host)
glucocorticoids
rabies Nab
2
85,158
glucocorticoids
human immunodeficiency virus(HIV)
HIV CD4+ T-lymphocyte counts 300-400/..

(PVRV) TRC ID RIG PCECV ESSEN

(rabies Nab) HIV

HIV CD4+ T lymphocyte count 300-400/..159-161 postexposure treatment HIV 2 162
2 TRC-ID (2-2-2-0-1-1) 4-4-4-0-2-2 ID
2 adjuvant tetanus toxoid (2-2-2-2-2-0;double doses ESSEN
regimen) Nab CD4+T-lymphocyte counts 200/
..162,163 multi-site intradermal injections (8-8-8-8-8) CD4+ T lymphocyte count
100/.. (69-455/.. 1 CD4+ T lymphocyte count 69/..)
CD4+ T lymphocyte count 200/.. (rabies Nab)
Briggs PJ AIDS
WHO categories II III 164 AIDS
rabies Nab
164-168 pre-exposure
vaccination HIV CD4+ T lymphocyte count ( 15%)

Nab

CD4+T-lymphocyte counts virus load HIV

169-170

171
( )




PVRV

7 ( 0.17)
29 ( 3)
20 ( 3)
( 6)
anaphylaxis PCEC


PCEC A anaphylaxis
Guillain-Barre ()172-173

 HRIG HRIG

HRIG systemic
(0.08)
2-3 174 (ERIG)
ERIG serum sickness
purified ERIG 1.6-6.9 90
1-2 ERIG
3 124-128,175 purified ERIG
15 purified ERIG
175 serum sickness
steroid

(Failure of post-exposure treatment)

(
) 1:80,000 1:12,000-1:30,000
176-179
1) WHO category III

2)

2-3

3)
(deltoid region) (anterolateral thigh)

4)

5)


178-179
( 10
)

 1 (rabies immunoglobulin, RIG)

(WHO categories)

/ RIG

II

b
10

III

/

( )

b
10

(pre-exposure vaccination)

b
3 ( 2
) 10
c

Tetanus immunization

Antibiotic treatment

WHO categories

( pre-exposure)

2
3

(FA test)

post-exposure

( pre-exposure)

post-exposure

post-exposure

post-exposure

3
1)
2) 2
3)
3
10
post-exposure

post-exposure

3
post-exposure
10

 2
Standard intramuscular regimen
Dose: one IM dose (1.0 or 0.5 .) into deltoid muscle
Day 0
3
7
14
28
5 vials
5 visits
Rabies immune globulin
2-1-1 intramuscular regimen (2-1-1)
Dose: one IM dose (1.0 or 0.5 .) into deltoid muscle
Day 0
7
Sites x2
x1

21
x1
4 vials
3 visits

+ Rabies immune globulin

2- site intradermal regimen (2-2-2-0-1-1)
Dose: 0.1 . ID per site 0.7 IU/0.1 .
Day 0
3
7
28
90
Sites x2
x2
x2
x1
x1
<2 vials
5 visits
+ Rabies immune globulin
Modified 2- site intradermal regimen (2-2-2-0-2-0)
Dose: 0.1 . ID per site 0.7 IU/0.1 .
Day 0
3
7
28
90
Sites x2
x2
x2
x2
<2 vials
4 visits
+ Rabies immune globulin
8-site Intradermal regimen (8-0-4-0-1-1)
Dose: 0.1 . ID per site
Day 0
7
Sites X8
x4

28
x1

90
x1
<2 vials
5 visits

+ Rabies immune globulin

 2 566 (intradermal skin test) wheal 5 .

purified ERIG*

wheal (.) Flare < 20 . Flare >20 . serum sickness**

>5-6
346
331
15
>6-7
181
153
28
>7-8
29
22
7
>8-9
8
3
5
>9-10
2
1
1
* ()
** serum sickness 1.41 wheal < 5 .

7
1
0
0
0


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