..

2556
 .. 2556
1 2556 3,000
2 () 2556
19,000

116 ()
. 10120




ISBN 978-616-11-1866-2

.. 2556
2 ()

.. 2556




1-12

.. 2556 2 ()

( )

.. 2556 2 ()


(Abbreviation)
1 1
1.1 3
1.2 4
1.3 5
2 11
2.1 14
2.2 The Stop TB Strategy 14
2.3 15
3 19
3.1 21
3.2 23
3.2.1 23
3.2.2 25
3.2.3 25
3.2.4 27
3.2.5 28
4 (DOT) 31
4.1 33
4.2 36
4.3 37
4.4 41
4.5 43
4.6 45
4.7 (refer & transfer) 49
4.8 49
4.9 50
4.10 51
4.11 (DOT) 53

.. 2556 2 ()
 5 57
5.1 59
5.2 60
5.3 61
5.4 62
5.5 64
5.5.1 BCG 64
5.5.2 65
6 71
6.1 73
6.2 73
6.3 74
6.3.1 75
6.3.2 75
6.3.3 79
7 85
7.1 87
7.2 88
7.3 88
7.4 MDR-TB 95
7.5 97
7.6 MDR-TB 100
7.7 101
7.8 MDR-TB 102
7.9 XDR-TB 102
8 107
8.1 109
8.1.1 109
8.1.2 110
8.1.3 111
8.1.4 112
8.1.5 112
8.1.6 113

.. 2556 2 ()
 8.2 113
8.2.1 115
8.2.2 115
8.2.3 115
9 119
9.1 121
9.2 122
9.2.1 122
9.2.2 124
9.2.3 126
9.3 127
9.4 127
10 131

10.1 134
10.2 135
10.3 / 136
11 141
11.1 143
11.2 145
11.3 145
11.4 147
153
1 155
2 / 175
3 / 178
1
4 / 180
2
5 (ISTC) 181
.. 2556 184
2 ()
.. 2555 186

.. 2556 2 ()


1 ZN staining 24
2 Fluorescence acid-fast staining 24
3 AFB 24
4 36
5 40
6 40
7 4FDC 41
8 2FDC 41
9 43

10 45
11 48
12 52
13 SLD 63
14 97
15 99
16 144
17 146

.. 2556 2 ()


1 4
2 50
3 67
(Contact investigation and management)
4 MDR-TB 90
Direct smear Xpert MTB/RIF
5 MDR-TB 91
Direct smear Xpert MTB/RIF
6 MDR-TB 92
Direct smear
Xpert MTB/RIF LPA LPA
7 MDR-TB 93
Xpert MTB/RIF
8 5 150

.. 2556 2 ()
 (Abbreviation)
AFB acid- fast bacilli DST drug susceptibility testing
AFRIMS Armed Forces Research Institute DTC district TB coordinator
of Medical Sciences E ethambutol
AIDS acquired immunodeficiency EFV efavirenz
syndrome ELISA enzyme-linked immunosorbent
ALT alanine transaminase assay
Amk amikacin EPI expanded program on
Amx amoxycillin immunization
ART anti-retro viral therapy EPTB extrapulmonary tuberculosis
AST aspartate transaminase Eto ethionamide
BCG Bacille Calmette-Guerin FDC fixed dose combination
BSC biological safety cabinet FLD first line drug
CBC complete blood count FLDST first-line drug susceptibility testing
CD4 CD4 lymphocyte H, INH isoniazid
CDC-US Centers for Disease Control and HAART highly active anti retroviral
Prevention (USA) therapy
Cfz clofazimine HEPA high-efficiency particulate air filter
Cln cinlastatin HIV human immunodeficiency virus
Clr clarithromycin IC infection control
Clv clavulanate IC Nurse infectious control nurse
Cm capreomycin ICF intensified case finding
CPT co-trimoxazole preventive IFN- interferon gamma
therapy IGRA interferon gamma release assay
CrCl creatinine clearance IOM International Organization for
Cs cycloserine Migration
CSF cerebrospinal fluid Ipm imipenem
CXR chest x-ray IPT isoniazid preventive therapy
CYP 450 cytochrome p 450 IRIS immune reconstitution
DOT directly observed treatment inflammatory syndrome
DOTS the internationally agreed ISTC international standards for
strategy for TB control tuberculosis care

.. 2556 2 ()
IUATLD International Union Against
Tuberculosis and Lung Disease
K, Km kanamycin
LED light-emitting diode
Lfx levofloxacin
L-J lowenstein-Jensen
LPA line probe assay
LTBI latent tuberculosis infection
Lzd linezolid
MAC mycobacterium avium complex
MDGs millennium development goals
MDR-TB multidrug resistant tuberculosis
Mfx moxifloxacin
MOTT mycobacterium other than
tuberculosis
MTBC mycobacterium tuberculosis
complex
NNRTIs non-nucleoside reverse
transcriptase inhibitors
NTM nontuberculous mycobacterium
NTP National tuberculosis control
programme
NVP nevirapine
O, Ofx ofloxacin
P, PAS para-aminosalicylic acid
PCP pneumocystis carinii pneumonia
PITC provider-initiated HIV testing and
counseling
PMDT programmatic management of
drug resistant TB
PPD purified protein derivative
.. 2556 2 ()
PPM public-public or
public-private mix
PTB pulmonary tuberculosis
PTC provincial TB coordinator
Pto prothionamide
R rifampicin
RTC regional TB coordinator
S, Sm streptomycin
SGOT serum glutamic- oxaloacetic
transaminase
SGPT serum glutamic- pyruvate
transaminase
SLD second line drug
SLDST second-line drug susceptibility
testing
TAD treatment after default
TAF treatment after failure
TB/HIV HIV-related TB
TLTI treatment of latent tuberculosis
infection
Trd terizidone
TST tuberculin skin test
UNAIDS Joint United Nations Programme
on HIV/AIDS
UVGI ultraviolet germicidal irradiation
WHO World Health Organization
XDR-TB extensively drug resistant
tuberculosis
Z, PZA pyrazinamide
ZN Ziehl Neelsen
 1

1
.. 2556 2 ()
 1

(Tuberculosis TB) Mycobacterium

Mycobacterium Mycobacterium
tuberculosis ( 80)


Mycobacterium tuberculosis complex (MTBC)
Mycobacterium africanum Mycobacterium bovis

Mycobacterium Mycobacterium
Atypical Mycobacterium Mycobacterium other than tuberculosis (MOTT)
Nontuberculous Mycobacteria (NTM) 50


Mycobacterium avium complex (MAC)

Mycobacterium

1.1

(droplets)
droplets

3
.. 2556 2 ()
1.2 (TB infection and TB disease)
droplets

(TB infection)

90
10 (TB disease) 5%
2 5 %

50 2
1

(Exposure to TB)

70% 30%
(TB infection)

* 90% 10% (Active TB)

(Latent Infection) 2 5%
2 5%

50

*
Source: State Government of Victoria, Department of Health Services, Australia.
4
.. 2556 2 ()
 (primary tuberculosis)

primary focus
Ghons focus (mid-zone)

(lymphatic vessels) (hilar lymph node)
primary focus primary complex
(pleural effusion)
(atelectasis)
(bronchiectasis) (broncho-pneumonia)

(secondary or post-primary tuberculosis)



10

30-40 1 50-70 5-7

1.3




.. 2536 (.. 1993) (global
emergency)
5
.. 2556 2 ()
 1 3
(prevalence) 12
(infectious) (incidence) 8.6
1.3
22 .. 2541
(.. 1998) 80
1
.. 2555 (.. 2012)
80,000 119
30



60,000 50

.. 2537 (.. 1994) 9

.. 2543 (.. 2000) 15-40
6 2-7
.. 2542 (.. 1999)
2.4 .. 2544-2553
(.. 2001-2010) 1-2


112
.. 2550-2552 (.. 2007-2009) 855, 826 862
93
3.4

6
.. 2556 2 ()

20-37
.. 2555
(.. 2012) 8.6 1.1 12.8
1.3 320,000 ( 24.6)

.. 2554 (
27 2555) 91
15
90 68
15



Thai Working Group A2* (The Asian Epidemic Model (AEM) Projection for HIV/AIDS in
Thailand: 2005-2025) .. 2553 (.. 2010)
1,138,020
641,633 499,324
10,853

3
1 .. 2540 -
2541 (.. 1997-1998)
25.4 (multidrug resistant tuberculosis: MDR-TB)
2.01 2 .. 25442545 (.. 20001-2002)
14.8
(MDR-TB) 0.93 3 .. 2548-2549 (.. 2005-2006)
15.7
1.65

7
.. 2556 2 ()

/

5-7

.. 2555 (.. 2012) (MDR-TB)
1,760 ( 800 960 )


.. 2553 (.. 2010) 400 300
100
2 (second line drugs)

1. . :
. 2 :
, 2546.
2. 2540-2549 . .
3. 2550-2555 .
.
4. 2553 . .
5. 2550-2552 .
.
6.
2548-2552 - .. 2554.
7. . 2550-2552.
2554: 32(2): 92-100.
8. Akksilp S, Wattanaamornkiat W, Kittikraisak W, Nateniyom S, et al. Multi-drug resistant
TB and HIV in Thailand: overlapping, but not independently associated risk factors. The
Southeast Asian Journal of Tropical Medicine and Public Health 2009: 40(5): 1264-78.

8
.. 2556 2 ()
9. Hemhongsa P, Tasaneeyapan T, Swaddiwudhipong W, et al. TB, HIV-associated TB and
multi-drug resistant TB on Thailands border with Myanmar, 2006-2007. Journal of
Tropical Medicine and International Health 2008: 13(10): 1288-96.
10. Tuberculosis: Epidemiology and Control. World Health Organization, 2002.
11. WHO report 2013. Global tuberculosis report 2013 : Geneva, World Health organization.
(WHO/HTM/TB/2013.11).

9
.. 2556 2 ()
 2

11
.. 2556 2 ()
 2

(The internationally
agreed strategy for TB control: DOTS strategy) .. 2539 (.. 1996)
The Stop TB Strategy .. 2549 (.. 2006)


(Millennium Development Goals: MDG)
8
6 (combat HIV/AIDS, Malaria and
other diseases) 2 23
24 (case detection)

(The Stop TB Strategy) .. 2554 (.. 2011)
(The Global Plan to Stop TB 2011-2015) .. 2554-2558
4 (1)
DOTS (2) (3)
(4)

13
.. 2556 2 ()
2.1
1. 80
(success rate) 90 .. 2558 (.. 2015)
2. 50 .. 2558 (.. 2015)
.. 2533 (.. 1990)

2.2 The Stop TB Strategy 6

1
(DOTS)


(DOT)

2

/

14
.. 2556 2 ()

(International standards for tuberculosis care: ISTC)
5




6


6

2.3
1)



national tuberculosis control
programme: NTP
NTP


2) (.)


NTP

15
.. 2556 2 ()
3) (.)




NTP
4) (.)



5) / /

1. (Intensified case finding: ICF)
2.

1. (ISTC)
2. .

BCG (Bacille Calmette-Guerin)
(Expanded Program on Immunization: EPI)
/



(.)

16
.. 2556 2 ()
 .
1. first line drugs second line drugs

2. /

3. electronic

1. .
2549. 2549.
2. .
2558. 2 :
, 2554.
3. .
.. 2550. 1 : , 2550.
4. . .
http://www.undp.or.th/thai/focusareas/mdgprogramme.html.
5. An expanded DOTS framework for effective tuberculosis control. WHO/CDS/TB/2002.27.
6. Framework for effective tuberculosis control. WHO/TB/94.179.
7. http://mdgs.un.org/unsd/mdg/Host.aspx?Content=Indicators/OfficialList.htm.
8. The global plan to STOP TB 20062015. Actions for life towards a world free of
tuberculosis. WHO/HTM/STB/2006.35.
9. The global plan to STOP TB 20112015. Transforming the fight towards elimination of
tuberculosis.
10. The STOP TB strategy. Building on and enhancing DOTS to meet the TB-related
Millennium Development Goals. WHO/HTM/TB/2006.368.
11. United Nations Development Programme. The Millennium Development Goals. Fast facts.
http://content.undp.org/go/cms-service/download/asset?asset_id=2883030.

17
.. 2556 2 ()
12. United Nations site for the MDG Indicators. United Nations Statistic Division. Official list
of MDG indicators.
13. What is DOTS? A guide to understanding the WHO-recommended TB control strategy
known as DOTS. WHO/CDS/CPC/TB/99.270.
14. WHO launches new stop TB strategy to fight the global tuberculosis epidemic. http://
www.who.int/mediacentre/news/releases/2006/pr12/en/.

18
.. 2556 2 ()
 3

19
.. 2556 2 ()
 3

3.1

3.1.1 (patient-initiated pathway) passive case finding





/





21
.. 2556 2 ()
 3.1.2 (screening pathway)
(intensified case finding: ICF)
patient-initiated

1) (contacts of TB cases) (
5 )
2) (clinical risk groups)
(silicosis) (chronic obstructive
lung disease) (malnutrition)
3) (risk populations)

3
( 6
8 )

(active case finding)

(TB preva-
lence survey)

2
( )
(hemoptysis) 2

(TB suspect)

(specimen)

22
.. 2556 2 ()

3 2
50


2
1 (spot sputum)

2 (collected sputum)

EQA (external quality assurance) smear
microscopy

3.2
3.2.1


(..)

1,100 (light microscopy)
smear Ziehl Neelsen (ZN)
LED (fluorescent light-emitting diode)

23
.. 2556 2 ()
 1 ZN staining

Grading
()
0 AFB/100 Negative - 200
1- 9 AFB /100 actual cell counts actual cell counts 100
( AFB ) ( AFB )
10 - 99 AFB /100 Positive 1+ 100
1-10 AFB / Positive 2+ 50
>10 AFB / Positive 3+ 20
: acid-fast bacilli: AFB

2 fluorescence acid-fast staining

AFB
0 AFB / 30 Negative
1 - 29 AFB / 30 AFB
>29 AFB / 30 1+
1 - 10 AFB / 2+
>10 AFB / 3+
3 AFB
MICROSCOPY SYSTEM USED
LIGHT MICROSCOPY
SCALE FLUORESCENCE MICROSCOPY (Fluorescent Stain)
(ZN Stain)
(1,000 x field = HPF)
1,000 x magnification: 1 200-250 x magnification: 1 400 x magnification: 1 length
length = 100 HPF length = 30 fields = 40 fields
Negative 0 AFB/1 length or 100 HPF 0 AFB/1 length or 30 fields 0 AFB/1 length or 40 fields
Scanty 1-9 AFB/1 length or 100 HPF 1-29 AFB/1 length or 30 fields 1-19 AFB/1 length or 40 fields
1+ 10-99 AFB/1 length or 100 HPF 30-229 AFB/1 length or 30 fields 20-199 AFB/1 length or 40 fields
2+ 1-10 AFB/1 HPF on average 10-100 AFB/1 length on average 5-50 AFB/1 length on average
3+ >10 AFB/1 HPF on average >100 AFB/1 field on average >50 AFB/1 field on average
: WHO IUATLD

24
.. 2556 2 ()
 24
AFB

AFB

AFB 10,000 / 1
smear
AFB

(laboratory register book)

treatment card primary default

(scanty actual number)

1
(sputum smear positive case)
3.2.2 (chest x- ray: CXR)




3.2.3 (culture)


74

1
(drug susceptibility testing for first line drug) 33
2 (drug susceptibility testing for second line drug) 4

25
.. 2556 2 ()

1. (sputum smear negative pulmonary tuberculosis)
2. MDR-TB
2
3.


culture
(decontamination)
2
1.
decontamination
2.

biological safety cabinet (BSC)
BSC class II

decontamination procedure
aseptic technique cerebrospinal fluid (CSF)
Lowenstein Jensen (L-J) culture

L-J 2% Ogawa medium
BBL MGIT
Bactec MGIT 960 Oxygen consuming

26
.. 2556 2 ()


4 8
(No growth) Bactec MGIT 960
2 6 No growth
(drug susceptibility testing: DST)

1.
2.
3.
4.
5. 3
1
12-14
3.2.4 (molecular examination; nucleic acid amplification)
Rapid identification Mycobacterium tuberculosis
(M. tuberculosis)
AFB

Xpert MTB/RIF real-time
polymerase chain reaction (cartridge)
rifampicin
()
() rifampicin
100 99
Xpert MTB/RIF

Xpert MTB/RIF
3

27
.. 2556 2 ()
 1. relapse, TAF

2.
3.
Genotype MTBDR (HAIN Test) line probe assay (LPA)
isoniazid rifampicin
2
98 3
Xpert MTB/RIF
3.2.5
(tuberculin skin test: TST)
BCG BCG
TST
TST 5
BCG
BCG

interferon gamma release assay (IGRA)
(latent TB infection) Incubate purified protein
derivative (PPD) control antigen interferon gamma
(IFN-) lymphocyte sensitized
enzyme-linked immunosorbent assay (ELISA)
(active tuberculosis disease )

1. . . . .
5 : 2546: ISBN 974-331-083-5.
2. . . :
, 2529.

28
.. 2556 2 ()
3. .
.
, 2552.
4. .
. 4 : 2547: ISBN 974-297-224-9.
5. Kawai M., and Fujiki A. Minimum essential of laboratory procedure for tuberculosis control.
6. Kubica GP., Dye WE., Cohn ML., and Middlebrook G. Sputum digestion and decotamination
with N-acetyl-L-cystein-soduim hydroxide for culture of mycobacteria. Am Rev Respir
Dis 1963: 87: 775-9.
7. Kubica GP., Kaufman AJ., and Dye WE. Comments on the use of the new mucolic agent,
N-acetyl-L-cystein, as a sputum digestant for the isolation of mycobacteria. Am Rev Respir
Dis 1964: 89: 284-6.
8. Petroff, SA. A new and rapid method for the isolation and cultivation of tubercle bacilli
directly from the sputum and fecae. J Exp Med 1915: 21: 38-42.
9. The Research Institute of Tuberculosis, JATA, 1988: p.53-4.
10. Van Deun A. and F. Portaels. Limitation and requirement for quality control of sputum
smear microscopy for acid-fast bacilli. Int J Tuberc Lung Dis 1998: 2(9):756 76.
11. Vestal A.L. Procedure for the isolation of mycobacteria DHEW publication No. (CDC)
79-8230 U.S. Dept of Health Education and Welfare Public Health Service. Atlanta, Georgia.
1978.P.129-30.
12. World Health Organization. Early detection of tuberculosis: An overview of approaches,
guidelines and tools. WHO/HTM/STB/PSI/2011.21. World Health Organization 2011.

29
.. 2556 2 ()
 4


(Directly observed treatment: DOT)

31
.. 2556 2 ()
 4

(Directly observed treatment: DOT)

4.1

1) (TB suspect)
2
( ) / (
)
2) (TB Case) (definite case)


3) (Definite case) Mycobacterium
tuberculosis complex culture molecular line probe
assay M. tuberculosis
AFB smear 1 definite case

1.
(pulmonary tuberculosis: PTB)
miliary TB
(mediastinal and/or hilar lymph node)
(Pleural effusion)

33
.. 2556 2 ()
 (extrapulmonary tuberculosis: EPTB)




2.

M. tuberculosis
(PTB+)
smear 1
(PTB-)
smear 2


smear 2 culture
M. tuberculosis

65 50
/
(PTB sputum smear not done)


3.


6

34
.. 2556 2 ()
1. (new)

1

2. (relapse) recurrent
(true relapse) (re-infection)

smear culture
3. (treatment after failure)
(new patient regimen)
5 (remained positive)
(became positive)
2
4. (treatment after default)
2
smear culture
5. (transfer in)

6. (other)

1




(bacteriologically negative
relapse) (bacteriologically negative extrapulmonary TB)

35
.. 2556 2 ()
 4

+ - -
+

+
+
+ -
+ -

4.2

100

1)

(initial phase intensive phase)

(continuation phase) 2
dormant form
2)


3) (6
8 9 )

4)

(DOT)

36
.. 2556 2 ()


(Daily package) (Fixed Dose Combination: FDC)





DOT
4.3
2
1. 1 (First line drugs: FLD)
(Isoniazid: H, INH)
(Rifampicin: R, RMP)
(Pyrazinamide: Z, PZA)
(Ethambutol: E, EMB)
(Streptomycin: S, Sm)
FDC HR HRZ HRZE FDC


30-70

2. 2 (Second line drugs: SLD)

(Kanamycin: K, Km)
(Levofloxacin: Lfx)
(Ethionamide: Eto)
(Para-aminosalicylic acid: P, PAS)
(Cycloserine: Cs)
(Ofloxacin: O, Ofx)

37
.. 2556 2 ()

2010
3
1. (new patient regimen)

2HRZE / 4HR

1
culture (DST)
2 4 H, R, Z, E 4
2 H, R

1 (1HRZE)
( 2)
relapse failure H
(pre-treatment isoniazid resistance)

(delay response)
9-12

6-9
9-12
2. 1 (re-treatment regimen with first-line drugs)

2HRZES / 1HRZE / 5HRE

(treatment after default) (relapse)

culture DST
38
.. 2556 2 ()
 3 2 5 H, R, Z, E S 3
4 1 5
3 H, R, E
:
1 3

DST
3. (Empirical MDR regimen)

> 6Km5LfxEtoCs + PAS / > 12 LfxEtoCs + PAS

MDR-TB
DST MDR-TB molecular test
MDR-TB Empirical MDR-TB culture DST
DST (individualized or
tailored regimen)
( 5 ) 6
4 (
4 Fluoroquinolone 1 )
18
8
4 20
18

empirical MDR regimen DOT

( 7 )
: K S
( 14 )
( 5) ( 6)

39
.. 2556 2 ()
 5

././ ././
(maximum dose)
H 4-6 5 300 ./
R 8-12 10 600 ./
Z 20-30 25 2000 ./
E 15-20 15 1600 ./
S 12-18 15 1000 ./
S
S 15 ././

6
(.)*

H R Z E
**(.)
4-6 ./ 8-12 ./ 20-30 ./ 15-20 ./
***35-49 300 450 1,000 800
50-59 300 600 1,500 1,000
60-69 300 600 1,500 1,200
70 300 600 2,000 1,200
*

**

*** 35 ( 5)

40
.. 2556 2 ()
 7 4FDC
4FDC (H75 R150 Z400 E275)
H R Z E

(.) (.) (.) (.)
30-37 . 2 150 300 800 550
38-54 . 3 225 450 1200 825
55-70 . 4 300 600 1600 1100
8 2FDC (H75R 150, H100 R150, H150 R300)
H R
2FDC
(.) (.)
30-37 . H75 R150 2 150 300
38-54 . H75 R150 3 225 450
H100 R150 3 300 450
55-70 . H75 R150 4 300 600
H150 R300 2 300 600

4.4
(2 )


4.4.1 (2HRZE/4HR)
1) culture DST DST
MDR-TB treatment failure MDR-TB
DST
2)
( 2 )

2 HR
2 *
41
.. 2556 2 ()
 *

(drug-to-drug/drug-to-food

interaction)

(immuno-compromised host)

NTM

HR HRZE
1
3
3) 3
( 2 )
3 HR 4
3
Culture DST Liquid media Rapid test
HR
4) 5
HR
culture DST
liquid media rapid test (Molecular test)

treatment failure MDR-TB empirical MDR
regimen DST
5)
4.4.2 (2HRZES/1HRZE/5HRE)
culture DST DST
MDR-TB treatment failure MDR-TB
DST

42
.. 2556 2 ()
 1) ( 3
)
3 HRE
3 DST
culture DST
HRE
2) 5
5 HRE
5 culture, DST rapid (molecular) test
treatment failure MDR-TB
empirical MDR regimen
DST
3)

4.4 (Drug
(Drug to drug Interaction)
to food Interaction)
9


H - - - -

- 1
-

2
-

R - - -

1

2

-

43
.. 2556 2 ()
 9 ()


Z
E - - - - -

-

-
4
-
2




Ofx -
20%


2
Eto - - - -







-




Cs - -

B12 folic
acid

44
.. 2556 2 ()
 9 ()


PAS - - - -

4.6


2
1. major side effect
2. minor side effect

10



S
(vertigo nystagmus) S
() H, R, Z

() E
purpura R
S

Z, R, H
Z, E Aspirin NSAIDS Paracetamol
H Pyridoxine 50-75
H
Intermittent dosing R
45
.. 2556 2 ()

3

prednisolone
systemic steroid
prednisolone 40-60 .



H R E Z
1/3 1/2 2-3



/

H, R Z bilirubin
aspartate transaminase (AST) serum glutamic- oxaloacetic

46
.. 2556 2 ()
transaminase (SGOT)/alanine transaminase (ALT) serum glutamic- pyruvate transaminase
(SGPT) R


> 60


AST/ALT total bilirubin

AST/ALT total bilirubin 1-2
1


AST/ALT > 3 H, R Z
AST/ALT 3
3

total bilirubin > 3 ./. AST/ALT 3 R
AST/ALT < 5 1
AST/ALT > 5 H, R Z
re-challenge
fulminant hepatitis
AST/ALT < 2 total bilirubin < 1.5 ./.
H, R Z

AST/ALT total bilirubin 1

re-challenge AST/ALT total bilirubin

47
.. 2556 2 ()
 (optic neuritis, retrobulbar neuritis)
E H
(dyschromatopsia, - -)
(central scotoma)


50
E

(visual acuity)
E
E 15 ././ 20 ././




H H
11

H 2RZE/10RE, 6-9RZE
R 2SHE/10 HE, 2-3HZEQ/9-10HEQ
Z 2HRE/7HR
E ZHRE/6HE
: Quinolone (Q)
( ofloxacin 600-800 ./ ) rifampicin ofloxacin
effux pump

48
.. 2556 2 ()
4.7 (refer & transfer)
(refer)

(transfer)

(TB09)
(refer)
(transfer) (transfer-out)
(transfer-in)

4.8
1 1

( AFB culture)
2



( )

49
.. 2556 2 ()
 2
*
(Treatment after interruption)

* ,

4.9
4.9.1
Sputum convert
Sputum not convert
Sputum not examined
Died
Defaulted > 2
Transferred out

50
.. 2556 2 ()
 4.9.2

1. (cured):
2
2. (treatment completed):

3. (treatment failed):
3.1
5
3.2 2
3.3
MDR-TB
4. (died):
5. (default): 2
6. (transfer out):
(treatment success)

4.10
4.10.1


H 6 (pyridoxine) 50-100
./



aminoglycosides
(ototoxic)
fluoroquinolone

51
.. 2556 2 ()
 4.10.2
(haemodialysis)
haemodialysis H R
creatinine clearance (CrCl) / ()
(increase the dosing interval)
(too low peak serum concentration) CrCl

12
(CrCl<30 ./
)

Isoniazid
Rifampicin
Pyrazinamide 20-30 ././ 3
Ethambutol 15-20 ././ 3
Streptomycin
Amikacin
Kanamycin
Capreomycin
Ofloxacin 600-800 ./ 3
Levofloxacin 750 ./ 3
Moxifloxacin
PAS
Ethionamide

Prothionamide
Cycloserine 250 . 500 . 3
Clofazimine
Linezolid
250-500 . 12
Amoxycillin/Clavulanate
CrCl<10 ml/min 250-500 .
Clarithromycin 250-375 . 2
Imipenem/Cilastatin 250-500 . 6

52
.. 2556 2 ()
 4.10.3
.

.
AST/ALT 3 2HRE(S)/7HR


2SHE/10-16HE
AST/ALT 3 2SHE/16HE
. Acute hepatitis Jaundice S E Jaundice
H R Active TB
Quinolone ( Ofx) S E 2-3
Ofx, S E
4.11 (DOT)
R
(M/XDR TB)

R

1. (acceptance)
2. (accessibility)
3. (accountability)



1.
2. (.)
3.

53
.. 2556 2 ()
 DOT

1.
. .. 2555.
1 : 2555:
ISBN 978-616-11-1839-6
2. , . .
. 5 :
2546: ISBN 974-331-083-5.
3.
.
. 3 2545.
4. American Journal of Respiratory and Critical Care Medicine. American Thoracic Society1905,
Vol.167, No.4, February 15, 2003.
5. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases
Society of America: Treatment of Tuberculosis Am J Respir Crit Care Med 2003: 67: 603-62.
6. An expanded DOTS framework for effective tuberculosis control. WHO/CDS/TB/2002.27.
7. Centers for Disease Control and Prevention. Treatment of Tuberculosis, American Thoracic
Society, CDC, and Infectious Diseases Society of America. MMWR 2003: 52(No. RR-11):
177.
8. Crofton J, Horne N, Miller F. Clinical Tuberculosis. The Macmillan press, Hong Kong, 1992.
9. Drug Information Handbook with International Trade names index 2008-2009. 17th edition.
American Pharmacist Association. Senior Editor: Charles F Lacy, Lora L Armstrong, Morton
P Goldman, Loonard L Lance.

54
.. 2556 2 ()
10. Fox W Ellard G A Mitchison D A : Studies on the treatment of tuberculosis undertaken
by the British Medical Research Council Tuberculosis Units, 1946-1986, with relevant
subsequent publications, Int J Tuberc Lung Dis 1999: 3(10): S231 - S279 (supplement).
11. Gail E.L, Robin M.W, Nicolaas C.GVP, Posalba L, Adelina J, Rogelio H-P, et. All. Rifampicin
reduces susceptibility to ofloxacin in rifampicin-resistant Mycobactetium tuberculosis
through efflux. Am J Respir Crit Care Med 2011: 184: 269-76.
12. Porter J.D.H., Mc Adam K.P.W. Tuberculosis Back to the Future John Wiley + Sons,
England, 1994.
13. Raviglione M : XDR-TB: entering the post-antibiotic era?, Int J Tuberc Lung Dis 2006: 10(11):
1185-7.
14. The Sanford Guide to Antimicrobial Therapy 2009. 39th edition. Editors: David N Gilbert,
Robert C Moollering Jr, George M Eliopoulos, Henry F(Chip) Chambers, Michael S Saag.
15. Toman K. Tuberculosis Case-finding and Chemotherapy (Questions and answers). WHO,
Geneva, 1979.
16. WHO: An expanded DOTS framework for effective tuberculosis control Int J Tuberc Lung
Dis 2002: 6(5): 378-8.
17. WHO: A Guide for Tuberculosis Treatment Supporters Document WHO/CDS/TB/ 2002.300
WHO Geneva 2002.
18. WHO: What is DOTS : A guide to understanding the WHO-recommended TB Control
strategy Know as DOTS WHO/CDS/CPC/TB/99.270.
19. World Health Organization 2010. Treatment of tuberculosis: Guidelines. 4th edition. WHO/
HTM/TB/2009.420.
20. WHO Model Formulary 2008. Available at http://www.who.int/selection_medicines/list/
WMF 2008.pdf.
21. WHO Report 2012 : Global Tuberculosis Control : Surveillance Planning Financing World
Health Organization, Geneva.

55
.. 2556 2 ()
 5

57
.. 2556 2 ()
 5

5.1

1.
50
2.
(increased intracranial pressure)


1,000/..






haematuria, sterile pyuria
miliary
59
.. 2556 2 ()
5.2

5.2.1

1.


(military) (cavity)
2. >10 . ()
BCG M. tuberculosis
(
> 5 .)
IGRA
3.
60-80%
30-40%
3
5.2.2

(definite diagnosis)




()

60
.. 2556 2 ()
5.3

5.3.1

1.
2-3
2.

3.
4. BCG
Mantoux test
2-3 0.1 .. 48 72

1) > 5 .
steroid
2) >10 .

4
3) >15 . BCG
BCG 5
80-90 <10 . 10-15 80-90
BCG > 10 . 10-14 .
BCG > 15 .

5.3.2 Interferon gamma

BCG

M. tuberculosis Interferon gamma

61
.. 2556 2 ()
 ELISPOT (T-spot TB) 96 100
BCG
ELISPOT
Quanti FERON-TB Gold (QTF-G) 90
95 Latent Tuberculosis Infection Active TB
QTF-G
QTF-G
5.3.3

PCR
1-2 90 Primer PCR

PCR
( PCR )

5.4

intermittent regimen
E 25 ././
(DOT)

5.4.1
Rapid Advice WHO/HTM/
TB/2010.13 Guideline for the programmatic management of drug-resistant tuberculosis
WHO/HTM/TB/2011.6

62
.. 2556 2 ()
 1. FLD
* isoniazid
H*: 10 ./. (10-15 ./.) max 300 ./ 1
R: 15 ./. (10-20 ./.) max 600 ./ 1
Z: 35 ./. (30-40 ./.) 1
E: 20 ./. (15-25 ./.) 1
2.
(new patient regimen) H R, Z E 2
H R 4 (2HRZE/4HR)


2HRZE/10HR Eto E
(retreatment regimen) H
R, Z, E S 2 H R, Z E 1
H R E 5 (2HRZES/1HRZE/5HRE)
default 2
(gastric aspirate)

(MDR regimen)
(MDR-TB)
4 fluoroquinolone 1
> 6Km5LfxEtoCs+PAS / > 12 LfxEtoCs+PAS
13 SLD

././ ()
(.<50 .) (.>50 .)
Eto 15-20 2 500 . 1
PAS 150 2-3 8 12
Cs 10-20 1 500 . 1
Km 15-30 1 750 . 1
Lfx 7.5-10 2 800 . 800 .
63
.. 2556 2 ()
 5.4.2
1-2 80 3
90 4 10-12
6
2-3
2-3

95 relapse 1
5.5

BCG
5
5.5.1 BCG
BCG
1,200 BCG
50 64
78
primary, reactivation exogenous cell
wall antigen recombinant technology BCG
BCG .. 2496-2499
(.. 1953-1956) 2 .. 2497-2509 (.. 1954-1966) 6 .. 2510
(.. 1967) 5-10
1-2 .. 2520 (.. 1977) EPI < 4
BCG 100% BCG 2

64
.. 2556 2 ()
 BCG

BCG 10-14
(Prevalence) (
40/100,000 ) .. 2549 (.. 2006) 62/100,000
BCG
BCG
BCG
1 BCG
7 (. 1) BCG
( BCG
)


5.5.2
(Treatment of Latent Tuberculosis Infection: TLTI)
3
( )
1-2

12 8
120


(
) (Latent Tuberculosis Infection:

65
.. 2556 2 ()
LTBI)
(TB elimination)
1 40-50 2
10-15
5-10
BCG
>10 . >15 .
2 .. 2538-2540 (.. 1995-1997) .. 2542-2543 (.. 1999-2000)
5 BCG
9.1 8.2
>15 . 22.6 18.7 2
(retrospective) (prospective) .. 2547-2549 (.. 2004-2006)
1.64 61.4
1 20-30
(: LTBI)
90 19
recent infection

1. (infectious index case)

( contact investigation)

66
.. 2556 2 ()
 3 (Contact investigation and
management)

DOTS

DOTS

<5 >5 HIV+

Isoniazid TST > 15 Isoniazid 6-9 Isoniazid 9

6-9 TST 10-14

:




<5 H 10 ././ 6-9 (

)
>5 >15 . H 10 ././

6-9 10-14 .
H <10 .

8 -10
>10 . 6 .
(recent converter) H 6-9
67
.. 2556 2 ()

H < 5


H 9
H H R 3 R
6
(MDR-TB)

[:
2 R Z (2RZ)

]
2. ( 3
TB elimination) H 6-9
< 5 >15 . ( BCG)
corticosteroid
>5 . ( corticosteroid
>10 .)
old fibrotic lesion
>10 .
recent converter 2

(MDR-TB) 2

68
.. 2556 2 ()

1. . .. 2551.
5 : 2552 : ISBN 974-297-547-7.
2.
. .. 2555.
1 : 2555: ISBN 978-616-
11-1839-6.
3. , .
.. 2553.
4. . . .
. 5 :
2546: ISBN 974-331-083-5.
5. , .
. 2550: 28: 185-9.
6. . .
2551: 29: 115-3.
7. . .
2542: 2: 10-8.
8. American Academyof Pediatrics/Committee on Infectious Diseases. Tuberculosis.
ln:PickeringLK,ed 2000 red book: report of the Committee on Infectious Diseases. 25th
ed. Elk grove Village , II : AmericanAcademy of Pediattics 2000: 595-611.
9. American Thoracic Society/Centers of Disease Control and Prevention/ Infectious Disease
Society of America Treatment of tuberculosis, management of common side effects. Am
J Respir and Criti Care Med 2003: 167: 636-7.
10. G.A.Colditz T.F. Brewer.C.S.Berkey,M.E Wilson. E. Burdick H.V. Fineberg.F.Mosteller.
Efficacy of BCG vaccine in the prevention of tuberculosis Meta- analysis of the published
literature JAMA, 271: 698-702.
11. Graf P, Tuberculosis control in high-prevalence countries. Ln Davies PDO (ed) Clinical
Tuberculosis 1st ed. Chapman & Hall Medical 1994: 3259.

69
.. 2556 2 ()
12. Guidedance for national tuberculosis programmeson the management of tuberculosis
in children. WHO/HTM/TB/2006.
13. Guidelines for the investigation of contacts of persons with infectious tuberculosis :
Reccommendation from the National Tuberculosis Controller Association and CDC MMWR
2005: 54(RR15): 1-37.
14. Hames A, Maher D , Uplekar M Prevention of TB A Clinical manual for south east Asia
World Health Organization 1997: 133-8 WHO/TB/96.200(SEA).
15. International Union Against Tuberculosis Committee on Prophylaxis. Efficacy of
variousdulations of isoniazid preventive therapy for tuberculosis five years of follow-up
in the IUAT trial. Bull lnt UnionTuberc Lung Dis 1982: 60: 555-64.
16. Rapid advice Treatment of tuberculosis in children WHO/HTM/TB/2010 : 13.
17. Rieder HL Contacts of Tuberculosis patients in high incidence countries, Int J Tuberc
Lung Dis 2003, 7, S333-S336.
18. Srinavin S, Chotipitayasumondh T, Suwanjutha S. et al. BCG Efficacy,Pediatric Infect Dis
1991: 10: 359-65.
19. Starke JR Tuberculosis in children. Diagnosis and treatment Annals Nestle1997: 55: 10-23.
20. Treatment of Tuberculosis, Guidelines, 3rd Edition 2003/WHO/CDS/TB/2003.313.
21. Treatment of Tuberculosis, Guidelines, 4th Edition WHO/HTM/TB/2009:420.
22. VilarinoME , What is the role of treatment of latent tuberculosis infection in a tuberculosis
control programme ? ln.Frieden T.(ed ) Toman,sTuberculosis case detection treatment
and monitoring 2 ndedition WHO 2004 : 220-5 WHO/HTM/TB/2004-334.
23. WHO.Guideline for the programmatic management ofdrug-resistance tuberculosis WHO/
HTM/TB 2006, 361.
24. WHO report The Stop TB Strategy, Building on and enhancing DOTS to meet the TB
related Millenium Development Goals WHO/HTM/TB/2006: 368(2006).
25. WHO Treatment of Tuberculosis Guidelines for National Programme, Clinical
presentration, approach to diagnosis and management of tuberculosis in children
WHO2003: 61-5.

70
.. 2556 2 ()
 6

71
.. 2556 2 ()
 6

6.1


1.


10
2. (recurrent tuberculosis)
(endogenous reactivation or true relapse)
(exogenous re-infection)
/

6.2

1. (susceptibility)


73
.. 2556 2 ()
 2.

3.

4.
5.

6.
7.


1. /
2. /
3. /
4. /
5. /
6.3

.. 2543 (.. 2000)
12
.. 2547 (.. 2004)


72 .. 2548
(.. 2005)

74
.. 2556 2 ()


UNAIDS

1
5 3

6.3.1
1.
2.


3.
4.
6.3.2
3 I /

1. (ICF)
/
/


/


..

75
.. 2556 2 ()


(Counselor)
(..)

cluster of differentiate
4 (CD4) > 200 cells/mm3 CD4



CD4 < 50 cells/mm3




4
1. (any cough)
2. 1
3. 5% 1
4. 3 1



(
7.82% [83/1061])

76
.. 2556 2 ()
 (culture)
Xpert MTB/RIF nucleic acid amplification, complete blood
count (CBC), CSF ultrasound

1. ()
.
.
. 5
.
2.
.



.


ultrasound
. 5-10

77
.. 2556 2 ()
 .







3 4
TB/HIV 01 3
(suspected tuberculosis)
1

..

6 ( 9
)
2. H
(isoniazid preventive therapy: IPT)
(LTBI)

(CDC-US) H
(LTI)
H 9
(>5 )
H

78
.. 2556 2 ()


3.
(infection control: IC)




/ (
9 )
6.3.3
1.


1-2

provider-initiated HIV testing
and counseling (PITC)




PITC
3 C
1) informed consent
2) counseling
3) confidentiality

79
.. 2556 2 ()


CD4 count







2.

80
.. 2556 2 ()
 3. (co-trimoxazole
preventive therapy: CPT)
AIDS-defining illness
co-trimoxazole CD4 lymphocyte

4. (anti-retro viral therapy: ART)

CD4

CD4
2 CD4 < 50 cells/mm3
2 IRIS drug interaction

()

1) rifampicin (R) cytochrome P

450 (CYP 450) efflux multi transporter P-glycoprotein
NNRTIs Pls
2) IRIS

IRIS IRIS
3)
4)
5)

1) WHO (
CD4 )
2) R

81
.. 2556 2 ()
 3) R efavirenz (EFV) 600 mg/day
60 kg 800 mg/day 60 kg
4) EFV nevirapine (NVP)
(400 mg/day) R ( lead-in NVP)
5) EFV NVP
R
Pls-based regimen
6) NVP-containing Highly Active Anti Retrovial Therapy (HAART)
R NVP
EFV

5.
2
1. (comprehensive care)

2. (continuous care)

1. . 2548:
ISBN 974-297-378-4.
2. .
.. 2549/2550: ISBN 978-974-297-626-2.
3. .
: , 2550.
4. .. 2553.
1. : , 2553.

82
.. 2556 2 ()
5. . , 2549: Orane group
086 924 3434.
6. 2554.
.
7. Interim Policy on Collaborative TB/HIV Activities, World Health Organization 2004.
8. Self-study modules on tuberculosis, US-Center for Disease Control and Prevention,
p 19, March 1995.
9. WHO policy on collaborative TB/HIV activities. Guidelines for national programmes and
other stakeholders. WHO 2012.
10. World Health Organization. Guidelines for intensified tuberculosis case-finding and
isoniazid preventive therapy for people living with HIV in resource-constrained settings,
department of HIV/AIDS and Stop TB department, ISBN 978 92 4 150070 8, World Health
Organization, Geneva, Switzerland : 2011.
11. World Health Organization. Policy on TB infection control in health-care facilities,
congregate settings and households, WHO 2009.
12. World Health Organization. Management of TB: Training for health facility (A: Introduction).
WHO/CDS/TB/2003.314a. Geneva, Switzerland: WHO, 2003.
13. World Health Organization. Strategic framework to decrease the burden of TB/HIV. WHO/
CDS/TB/2002.296. Geneva, Switzerland: WHO, 2002.
14. World Health Organization & UNAIDS. Guidance on Provider-initiated HIV testing and
Counseling in health facilities. HIV/AIDS Programme, strengthening health services to
fight HIV/AIDS, ISBN 978 92 4 159556 8, WHO 2007.

83
.. 2556 2 ()
 7

85
.. 2556 2 ()
 7

.. 2528 (.. 1985) 6

isoniazid (H) streptomycin (S)
rifampicin (R)
(multidrug resistant tuberculosis: MDR-TB)


(extensively drug resistant tuberculosis: XDR-TB)

7.1
mono-resistance
poly drug- resistance H R
multidrug-resistance (MDR) 2 H R

extensive drug- resistance (XDR) 4
H R aminoglycoside
fluoroquinolone
87
.. 2556 2 ()
7.2
(culture)
(drug susceptibility testing: DST)

1.

2 (treatment after
default sputum smear positive)

(treatment after failure)
2. 3
3.
MDR-TB
MDR-TB

(migrants)
7.3

culture DST
(MDR-TB)

MDR-TB DST
culture DST
MDR-TB

1 (first-line DST: FLDST)

MDR-TB 2
(second-line DST: SLDST) XDR-TB

88
.. 2556 2 ()


Xpert MTB/RIF molecular test
R Xpert MTB/RIF
R MDR-TB
R R H
MDR-TB Xpert MTB/RIF
2 R
( culture DST
solid media liquid media line probe assay)

Xpert MTB/RIF
MDR-TB MDR-TB
Xpert MTB/RIF
1. MDR-TB
1.1

1.2 3 5
1.3 MDR-TB
Xpert MTB/RIF, LPA /

4 MDR-TB
direct smear Xpert MTB/RIF
5 MDR-TB
direct smear Xpert MTB/RIF
6 MDR-TB
direct smear Xpert MTB/
RIF LPA LPA
7 MDR-TB
Xpert MTB/RIF

89
.. 2556 2 ()
 4. Algorithm for MDR-TB suspects (high risk of MDR-TB), smear positive

90
For sites with Xpert MTB/RIF

.. 2556 2 ()
 5. Algorithm for MDR-TB suspects (high risk of MDR-TB), smear negative
For sites with Xpert MTB/RIF

.. 2556 2 ()
91
 For sites without Xpert MTB/RIF
6. Algorithm for MDR-TB suspects (high risk of MDR-TB)

92
.. 2556 2 ()
 7. Algorithm for PLWHA and other MDR suspects (not high risk of MDR-TB)
7.1 For sites with Xpert MTB/RIF

.. 2556 2 ()
** use 2nd specimen for Repeat Xpert, and request one more specimen for Standard Test
- Repeat Xpert shows indeterminate or invalid or error again, request Standard Test

93
 94
7.2 For sites without Xpert MTB/RIF

Xpert MTB/RIF
MTB detected, RIF resistance detected R
MTB detected , RIF resistance not detected R
MTB not detected R
MTB detected, RIF resistance indeterminate R
invalid error

.. 2556 2 ()
7.4 MDR-TB
MDR-TB DST MDR-TB DST
MDR-TB (TB03)
MDR TB
1. MDR-TB: new 1 DST
MDR-TB ( 2 3 DST
MDR-TB MDR-TB DST
MDR-TB : new )
2. MDR-TB: relapse FLD
DST MDR-TB
3. MDR-TB: treatment after default (TAD) FLD
> 2 DST
MDR-TB
4. MDR-TB: treatment after failure (TAF) of new patient regimen
FLD ( 5 )
DST MDR-TB
5. MDR-TB: treatment after failure (TAF) of retreatment regimen
FLD 5 DST MDR-TB
6. MDR-TB: transfer in (SLD)
(transfer out)
7. MDR-TB: others 1-6
. ( )
.

.

95
.. 2556 2 ()
 2

1.
2.
3.
4. (DOT)
(first line drugs: FLD)
5.
6. SLD

96
.. 2556 2 ()
7.5

14

Group 1: First-line oral anti-tuberculosis agents
Pyrazinamide (Z) 20-30 2,000 ./
(500 .) 1 ././
Ethambutol (E) 15-20 1,600 ./
(400,500 .) 1 ././
Group 2: Injectable anti-tuberculosis agents
Streptomycin (S) 15 ././ 1,000 ./
1
Amikacin (Amk) 15 ././ 1,000 ./

1
Kanamycin (Km) 15 ././ 1,000 ./
1
Capreomycin (Cm) 15 ././ 1,000 ./
1
Group 3: Fluoroquinolones
Levofloxacin (Lfx) 7.5-10 ././ 1,000 ./
(250, 500 .) 1
Moxifloxacin (Mfx) 7.5-10 ././ 400 ./
(400 .) 1

97
.. 2556 2 ()
 14 ()

Group 4: Oral bacteriostatic second-line anti-tuberculosis agents
Ethionamide (Eto) 15-20 ././ 1,000 ./
(250 .) 2
Prothionamide (Pto) 15-20 ././ 1,000 ./
(250 .) 2
Cycloserine (Cs) 10-20 ././ 1,000 ./
(250 .) 2 ( 12 .)
Para-Amino Salicylic acid (PAS) 150-200 ././ 12,000 ./
(1 ) 3-4
Group 5: Anti-tuberculosis agents with unclear efficacy
Clofazimine (Cfz) 100 ././ 100 ./
(50,100 .)
Linezolid (Lzd) 600 ././ 1,200 ./
(600 .)
Amoxycillin (Amx)/Clavulanate (Clv) 4 . Amx/
875/125 . 2 250-400 . Clv
Clarithromycin (Clr) (500 .) 500 . 2 1,000 .
Imipenem/Cinlastatin (Ipm/Cln) 4 . 50 ././
500-1,000 . 6 . ()
High-dose Isoniazid (High-dose H) 10-15 ././ NA

98
.. 2556 2 ()
 mono-drug resistance poly-drug resistance
culture DST
MDR-TB

15


()
H ( S) R, Z E 69
fluoroquinolone
H Z R, E fluoroquinolone 9-12
H E R, Z fluoroquinolone 9-12
R H, E, fluoroquinolone 12-18
Z 2
R E (S) H, Z fluoroquinolone 18
2-3 (6 )
R Z (S) H, E fluoroquinolone 18
2-3 (6 )
H, E, Z (S) R, fluoroquinolone 18
1 (6 )
2-3
MDR-TB
MDR-TB
DST MDR-TB molecular test
MDR-TB Empirical MDR-TB culture DST
DST (individualized or
tailored regimen)

> 6Km5LfxEtoCs+PAS / > 12 LfxEtoCs+PAS

99
.. 2556 2 ()
 ( 5 ) 6
4
18
8
4 20
18

(MDR-TB regimen) DOT

MDR-TB
(central
nervous system)
H, Z, Pto, Eto 100% Cs
80-100%
R 10-20%
E PAS

Km, Am, S aminoglycoside

7.6 MDR-TB

smear culture
2
DST
6
culture conversion culture 2
30 (culture conversion)

100
.. 2556 2 ()
7.7
7.7.1 (Interim outcome)
6
culture 6 culture 2
30
(died) > 2 (defaulted)
(transfer out)
7.7.2 (final outcome)
1. (cured) culture 5
12 30

2. (completed) culture 12

3. (failed)
culture 2 5 12

culture 1 3


4. (died)
5. > 2 (defaulted ) 2
6. (not evaluated)
smear culture
2 3 6 6
2

101
.. 2556 2 ()
7.8 MDR-TB
(close contact) MDR-TB
(indoor living space)

4
MDR-TB MDR-TB
TST (tuberculin skin test)
IGRA Test smear, culture DST

MDR-TB 2

7.9 XDR-TB
XDR-TB
1. 1 (Z, E Rifabutin)
2. (12 )

3. Fluoroquinolone generation Moxifloxacin
4. 4 ( Eto/ Pto, Cs, PAS)
5. 5 (Clofazimine, Linezolid, Thioacetazone, high-dose H, Clarithomycin)
2
6. H DST
7. (localized disease)
8. (Infection control )
9.
10.
XDR-TB

( 11 )
102
.. 2556 2 ()

1. 3. 2549-2550 .
2. 2546: 24:
95-100.
3.
.. 2543-2544 2546: 24:
221-228.
4. . (A guide on recording and
reporting forms and registers of Programmatic Management of Drug-resistant TB: PMDT).
(2556).
5. Amatayakul N. MDR-TB in hospital-based. Thai J Tuberc Chest Dis 1998: 19:73-80.
6. Annelies Van Rie, Robin Warren, Madalene Richardson et al. Classification of drug-resistant
tuberculosis in an epidemic area. Lancet 2000: 356: 22-25.
7. Anti- tuberculosis drug resistance in the world third global report the WHO/IUATLD global
project on anti -tuberculosis drug resistance surveillance 1999-2002.
8. Anti- tuberculosis drug resistance in the world. Report No.4. WHO 2008. WHO/HTM/
TB/2008.
9. Cepheid. Xpert MTB/RIF two-hour detection of MTB and resistance to rifampicin: Go from
test and wait to test and treat. Rev A, April 2009.
10. Cohn ML., Kovitz C, Oda U, Middlebrook G. Studies on isoniazid and tubercle bacilli, II: the
growth requirements, catalase activities, and pathogenic properties of isoniazid-resistant
mutants. Am Rev Ruberc 1954: 54: 641-664.
11. Cole ST, Telenti A. Drug resistance in Mycobacterium tuberculosis. Eur Respir J 1995: 8:
Suppl. 20, 701s-s713s.
12. Crofton J, Chaulet P, Maher D. Guidelines for the management of drug-resistant
tuberculosis. Geneva, World Health Organization, 1997.14.
13. Guildance for national tuberculosis programmes on the management of tuberculosis in
children: 2006. WHO/HTM/TB/2006.371.
14. Guidelines for the programmatic management of drug-resistant tuberculosis: Emergency
update 2008. WHO/HTM/TB/2008. 402. ISBN 978 92 41 547581.
103
.. 2556 2 ()
15. Guidelines for the programmatic management of drug-resistant tuberculosis, WHO 2006.
WHO/HTM/TB/2006.361.
16. Guidelines for the programmatic management of drug-resistant tuberculosis, 2011 update.
WHO/HTM/TB/2011.
17. Iseman MD. Management of multidrug-resistant tuberculosis. Chemotherapy 1999: 45
(suppl 2): 3-11.
18. JoseA Caminero Luna. A Tuberculosis Guide for Specialist Physicians. 2003 IUATLD.
19. Micromedex [Database on the internet]. Colorado: Thomson Reuters (Healthcare):
C1947-2012. DRUGDEX Evaluation. Amikacin,Kanamycin:[cited 2012 Sep 13]. Available
from:http://www.thomsonhc.com. Supscription required to view.
20. Mukherjee Js, Rich ML, Socci AR, Joseph JK, et al. Programmes and principles in treat-
ment of multidurg-resistant tuberculosis. Lancet, 2004 Feb 7: 363(9407): 474-81.
21. Pablos-Mendez A, et al. Global surveillance for antituberculosis drug resistance. N Engl
J Med 1998: 338: 1641-1649.
22. Pleumpanupat W, Jittimanee S, Akarasewi P, et al. Resistance to anti-tuberculosis drugs
among smear-positive cases in Thai prisons 2 years after the implementation of the DOTS
strategy. Int J Tuberc Lung Dis 2003: 7: 472-477.
23. Reechaipichitkul W. Multidrug-resistant tuberculosis at Srinagarind hospital, Khon Kaen,
Thailand. Southeast Asian. J Trop Med Public Health. 2002 Sep: 33(3): 570-4.
24. Roland Nau, Fritz Sorgel and Helmut Eiffert. Penetration of drug though the blood-cer-
ebrospinal fluid/blood-brain barrier for treatment of central nervous system infection.
Clinical microbiology reviews 2010: 23:858-83.
25. Siriarayapon P, Yanai H, Glynn J R, Yanpaisarn S, Uthaivoravit W. The evolving epidemiol-
ogy of HIV infection and tuberculosis in Northern Thailand. J AIDS 2002: 3: 80-89.
26. Snider DE, Kelly GD, Cauthen GM, Thompson NJ, Kilburn JO. Infection and disease among
contacts of tuberculosis cases with drug-resistant and drug-susceptible bacilli. Am Rev
Respir Dis 1985: 132: 125-132.
27. Suarez PG, Floyd K, Portocarrero J, Alarcon E, et al. Feasibility and cost-effectiveness
of standardised second-line drug treatment for chronic tuberculosis patients: a national
cohort study in Peru. Lancet. 2002 Jun 8: 359(9322): 1980-9.

104
.. 2556 2 ()
28. The use of molecular line probe assay for the detection of resistance to second-line
anti-tuberculosis drugs. Expert group meeting report. Geneva: February 2013.
29. Treatment of tuberculosis guidelines: Fourth edition. WHO 2009. WHO/HTM/TB/2009.420.
ISBN 978 92 4 154783 3.
30. Wing Wai Yew, Chi Kuen Chan, Chi Hung Chau, et al. Outcomes of patients with multidrug-
resistant pulmonary tuberculosis treated with ofloxacin/levofloxacin-containing regimens.
CHEST 2000: 117: 744-751.
31. XDR & MDR Tuberculosis Global Response Plan 2007-2008.
32. Yoshiyama, Takashi, Supawitkul, Somsak, Kunyanone, Naowarat et al. Prevalence of
drug-resistant tuberculosis in an HIV endemic area in northern Thailand. Int J Tuberc &
Lung Disease 2001: 5: 32-39.

105
.. 2556 2 ()
 8

107
.. 2556 2 ()
 8

8.1



18 2551 (..
2008)

.. 2539 (.. 1996)

(144 ) 2544 (.. 2001)
(Tuberculosis Coalition for Technical Assistance and International
Committee of the Red Cross, 2009 (.. 2552))
8.1.1



(screening pathway)


( 1 ) 1

109
.. 2556 2 ()
 (screening method)
.) (symptom screening)
2 1
1
1
1
6
2

.)




2


()
2

(patient initiative pathway)

(screening method)
8.1.2


2550 (.. 2007) 70
110
.. 2556 2 ()


13

(DOT)

8.1.3 (collaborative TB/HIV activities)

41

2551 (.. 2008)
71
.
(pre-test counseling) (post-test
counseling)
.
pre-test post-test counseling
.

co-trimoxazole

111
.. 2556 2 ()
 CD4


CD4
CD4

1-2

3-8

6
8.1.4 (TB recording reporting)
(TB03)
4 TB07, TB07/1, TB08 TB/HIV01 M/XDR-TB
PMDT 03, PMDT 07 PMDT 07/1
5

8.1.5 (referral system)

10-16
(discharge planner)

(discharge planner)

112
.. 2556 2 ()


8.1.6 (supervision, monitoring and evaluation)

(on the job training)
2





(mentor)




3 5

(TB prevalence survey)
(TB drug resistant surveillance)

8.2


(migrant worker)
(cross - border population)
carrier

113
.. 2556 2 ()


.. 2539 43 1,451 372,242
390 100,000 5-6

1.

2.

3. (referral system)
4.



1. (registered migrant worker)
( )

114
.. 2556 2 ()
 2. ( )
3. (illegal migrant worker)
4. cross border population



8.2.1
1.



2.

3.

4. (screening pathway)


8.2.2

(NTP)

()
8.2.3 (monitoring and evaluation)

115
.. 2556 2 ()

1. . DOTS (Public-Private
Partnership for TB control). :
9-11
2547 .
2. . . :
. 2546.
2 - 4 2546
.
3. . DOTS: .
:
9-11 2547
.
4. .
1 . :
9-11 2547
.
5. .
.. 2545.
:
9 - 11 2547
.
6. . . :
2551: ISBN 978-974-297-771-9.
7. . 2549-2550.
: 2552: ISBN 978-974-297-861-7.
8. Braun MM, Truman BI, Maguire B, et al. Increasing incidence of tuberculosis in prison
inmate population. JAMA 1989 : 261 : 393-7.
9. Drobniewski F. Tuberculosis in prison - the forgotten plaque. Lancet 1995 : 346: 948-9.

116
.. 2556 2 ()
10. Jittimanee, SX., Boonpha S., Ngamtrairai, N. et al (Submitted). Improving TB medication
completion upon being released from prison in Thailand.
11. Jittimanee, SX., Ngamtrairai, N., White, M. & Jittimanee, S. (2007). A prevalence survey
for smear-positive tuberculosis in Thai prisons. International Journal of Tuberculosis and
Lung Disease, 11 (5), 556-561.
12. Nateniyom, S., Jittimanee, S., Ngamtrairai, N., et al (2004) Implementation of Directly
Observed Treatment, Short-course (DOTS) in prisons at provincial levels, Thailand.
International Journal of Tuberculosis and Lung Disease, 8 (7), 848-854.
13. Snider DE Jr, Hulton MD. Tuberculosis in Correctional Institutions. JAMA 1989: 261 : 436-7.
14. Tuberculosis Coalition for Technical Assistance and International Committee of the Red
Cross (2009). Guidelines for control of tuberculosis in prison.
15. White MC., Tulsky JP., Goldenson J., Portillo CJ., Kwamura LM. & Menendez E (2002).
Randomized controlled trial of interventions to improve follow-up for latent tuberculosis
infection after release from jail. Archived Internal Medicine, 162, 1044-1050.
16. White MC., Tulsky JP., Menendez E., Arai S., Goldenson J. & Kawamura LM (2005).
Improving tuberculosis therapy completion after jail: translation of research to practice.
Health Education Research, 20 (2), 163-174.

117
.. 2556 2 ()
 9

119
.. 2556 2 ()
 9

10

9.1

particle droplet nuclei
1-5
(alveoli)
alveolar macrophages
(dormant bacilli) (latent TB infection)
( 5-10 )

121
.. 2556 2 ()











(recent infection)
10

silicosis
9.2




3
1.
2.
3.
9.2.1

(expose)

122
.. 2556 2 ()

1)




2)


3)

7
3.1
3.2
3.3
3.4
3.5
3.6
3.7
4)
(TB suspect)

2



5)

123
.. 2556 2 ()


6)




2-3


7)



8)
MDR-TB
surgical mask
2

9)


9.2.2

124
.. 2556 2 ()
 1)


(natural ventilation)
( )

(mechanical ventilation)

)



)


)
high-efficiency particulate air (HEPA) filter
(ultraviolet germicidal irradiation UVGI)
)

2)


(direct ultraviolet germicidal irradiation
fixture)

125
.. 2556 2 ()
 (upper room or shielded
ultraviolet germicidal irradiation fixture)






3) HEPA

9.2.3




MDR-TB bronchoscopy


1. surgical mask
mask
surgical mask (
)

126
.. 2556 2 ()
 2.
1 HEPA mask, N95 bronchoscopy

9.3


1.
2.
(tuberculin skin test)
2.1
6 1
2.2 1-3 (two-step test) 2
boosted reaction 2.1 2
tuberculin 1-2
(tuberculin conversion) 1-2



1
6

9.4

(risk assessment, development of the TB infection-control plan and periodic reassessment)

127
.. 2556 2 ()


128
.. 2556 2 ()
 (drug
susceptibility testing)

1. .
. , 2529: 17: 131-6.
2. 2540-2549 . .
3. . .
. :
2550.

129
.. 2556 2 ()
4. . .
.. 2554. :
.
5. .
. .. 2553, :
.
6. .
. .. 2549.
7. .
. : 2552.
8. American Thoracic Society, Diagnostic Standards and Classification of Tuberculosis
in Adults and Children, in Am J Respir Crit Care Med. 2000. p. 1376-1395.
9. American Thoracic Society, C., Infectious Diseases Society of America, Controlling
Tuberculosis in the United States. Am J Respir Crit Care Med, March 2005. 172: p. 1169-1227.
10. Centers for Disease Control and Prevention, TB Elimination. May 2007, Centers for Disease
Control and Prevention. p. 1-3.
11. Centers for Disease Control and Prevention (CDC), Tuberculosis Infection Control in the
Era of Expanding HIV care and Treatment. 2006.
12. Worlld Health Organization, Guidelines for the Prevention of tuberculosi in Health Care
Facilities in Resource-Limiied Setting. 1999.
13. World Health Organization, Tuberculosis Care with TB-HIV Co-management. 2007.
14. World Health Organization, WHO Policy on TB Infection Control in ealth-Care Facilities,
Congregate Setting and Households. 2009.
15. World Health Organization, Natural Ventilation for Infection Control in Health-Care
Setting. 2009.
16. World Health Organization, Treatment of tuberculosis guideline. 2009.
17. World Health Organization, Infection control abd control of epidemic-and pandemic-
prone acute respiratory disease in health care. June 2007, World Health Organization.

130
.. 2556 2 ()
 10

131
.. 2556 2 ()
 10

The Stop TB Strategy

6
(Engage all care providers)
(Public-Private Mix: PPM)
(ISTC)


()

/
DOTS

133
.. 2556 2 ()


()

10.1

10.1.1


( 3 )
10.1.2



( 11 )
10.1.3
(NTP)

134
.. 2556 2 ()
 10.1.4



10.1.5
DOT

(Multidrug-Resistant Tuberculosis: MDR-TB)
DOT
10.1.6
6- 8

2 (refer) (transfer)

10.2
1.


/

1 3
2. (hospital TB coordinator)
(infectious
control nurse: IC nurse)

135
.. 2556 2 ()
 3. /
3.1 /
/
/
/

3.2
./


3.3 /

4. /



5.

/

6.

/
10.3 /
(public private mix: PPM)



136
.. 2556 2 ()




1.


/




2.

3.


4. (TB
network meeting/DOTS meeting)

3 4 /
5.



6.
3

137
.. 2556 2 ()

1. DOTS (Public-Private
Partnership for TB control) :
. 9-11
2547 .
2. :
.
2546. 2-4 2546
.
3. DOTS
:
. 9-11 2547
.
4.
:
. 9-11
2547 .
5.
.. 2545
:
9-11 2547
.
6. . 2553. :
.
7. .
2551. 5 : 2552: ISBN 974-297-547-7.
8. .
2558. 2 :
2554.

138
.. 2556 2 ()
9. .
.. 2550. 1 : . 2550.
10. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases
Society of America: Treatment of tuberculosis. Am J Respir Crit Care Med 2003: 67:603
662.
11. Centers for Disease Control and Prevention. Treatment of Tuberculosis, American Thoracic
Society, CDC, and Infectious Diseases Society of America. MMWR 2003: 52(No. RR-11):177.
12. Drug Information handbookh with International Trade names index 2008-2009. 17th
edition. American Pharmacist Association. Senior Editor: Charles F Lacy, Lora L Armstrong,
Morton P Goldman, Loonard L Lance.
13. The Sanford Guide to Antimicrobial Therapy 2009. 39th edition. Editors: David N Gilbert,
Robert C Moollering Jr, George M Eliopoulos, Henry F(Chip) Chambers, Michael S Saag.
14. Up To Date. Available at http://www.uptodate.com/index Micromedex.
15. World Health Organization 2003. Treatment of Tuberculosis: Guidelines for National
Programmes. 3rd Edition. WHO, Geneva, 2003. WHO/CDS/TB/2003.313WHO Model
Formulary 2008.
16. Treatment of Tuberculosis:Guidelines for National Programmes. 3rd Edition. WHO 2003,
Geneva. WHO/CDS/TB/2003.313 WHO Model Formulary 2008.
17. WHO Model Formulary 2008.
18. World Health Organization 2010. Treatment of tuberculosis: Guidelines. 4th edition. WHO/
HTM/TB/2009.420

139
.. 2556 2 ()
 11

141
.. 2556 2 ()
 11

(supervision) (monitoring) (evaluation)

(supervision)
3







(evaluation)
1
interim evaluation
11.1

11.1.1
1

(quality) (reliability)
(verification)
143
.. 2556 2 ()
 11.1.2 (.)
. 1 3

.



(on the job training)



1.
2.
3. ()
16

RTC 4
PTC+RTC 4
.. DTC/TB clinic 4
:
1. RTC (Regional TB Coordinator: )
PTC (Provincial TB Coordinator: )
DTC (District TB Coordinator: )
TB Clinic:
2. RTC PTC ()
..
3. .. DTC TB clinic
DTC TB clinic ..

144
.. 2556 2 ()
11.2



3



)

)

11.3

145
.. 2556 2 ()
 17

1.
(case detection
rate for all form of TB)


2. ( (
(sputum ) )
conversion rate)

3. ( (
(treatment suc- ) )
cess rate)
4. ( (
(defaulted rate) ) )
2


5. ( (
(failure rate) ) )

6. (death rate) ( (
) )

died
7. ( (
(transferred out rate) ) )

8.
(HIV testing () ()
rate)
(
)

146
.. 2556 2 ()
 17 ()

9.
(HIV posi-
tive rate)
10.
(ART rate) () ()
(
( )

)
11. CD4 < 200
co-trimoxazole () cell/ mm3
(CPT rate) co-tri- ( CD4
moxazole )
12.

(TB screening rate) 4

13.

4

11.4

1. (DOT Card)
DOT
DOT 1 1 DOT

2. (TB 01)


147
.. 2556 2 ()

.. ..


DOT
(TB 09)
3. (TB 03)

(DTC)
TB Clinic DTC
3 4 ( TB 07)
( TB 07/1)
( TB 08) ( TB-HIV01)

1. DTC

2. 1

TB clinic
3. -
( )
3.1 ()
2
3.2 6
3.3
3.4 5

3.5
3.6
3.7 HIV CD4
3.8

148
.. 2556 2 ()
 4. (TB 04)

././.
TB clinic
5. (TB 05)
5.1

1: 2 (3) 5
6 (PTB-)
2
2: 3 (4) 5
8
5.2 (TB05/1)
6. 3
4
( TB 07) (
TB 07/1) ( TB 08)
3-6 (TB-HIV01)
( TB 07) DTC
(3 )



7

( TB 07/1) DTC

( )
/
(3 ) 6-9
()

149
.. 2556 2 ()
 ( TB08) DTC
2
TB/HIV+ TB/HIV- unknown
(3 )
12-15
3-6 (TB-HIV01)
36

2
/
4
4 3 1 4 (quarterly report)
1 : 1 31
2 : 1 31
3 : 1 30
4 : 1 30
5
3
5
8 5
1/2555 2/2555 3/2555 4/2555 1/2556
1 ..31 .. 1 ..31 1 .30 1 ..30 .. 1 ..31 ..
54 ..55 ..55 55 55
1-7 ..56
1 (TB 07)
4 (TB/HIV01)
2 (TB07/1)
3 (TB08), PMDT 07

150
.. 2556 2 ()
 1. 3 0-3 (case finding
on new and previously treated of tuberculosis patients)
3
/

() ()
3


2. 3
6-9 (sputum conversion rate)
3

()
3. 3 12-15
(treatment outcome)
3
: /

:
()
4. 3
3-6 (TB-HIV01)
3 /

5.
M/XDR TB
(TB03)
TB03
M/XDR TB
/ (M/XDR TB register PMDT 03) M/XDR-TB

151
.. 2556 2 ()
 1 . . .
.
. DST
.
. M/XDR-TB
3
1. M/XDR TB PMDT 07 3
(detection) (enrollment) M/XDR TB
1 12-15
2. (interim results) PMDT 07/1
6 6 M/XDR TB
1 18-24
3. (final outcomes) PMDT 08 12
M/XDR TB
1 36-48
(A guide on recording
and reporting forms and registers of Programmatic Management of Drug-resistant TB: PMDT)

1. .
.
: 2553.
2. . ..
2551. 5 : 2552: ISBN 974-297-547-7
3. . (A guide on recording
and reporting forms and registers of Programmatic Management of Drug-resistant
TB: PMDT). (2556).
4. Management of tubercolosis training for district TB coordinators monitor and
evaluate TB control WHO 2005 (WHO/HTM/TB/2005.347g).

152
.. 2556 2 ()


153
.. 2556 2 ()
 1

(DOT Card)

155
.. 2556 2 ()


156
.. 2556 2 ()
 3 - 6

157
.. 2556 2 ()
158
.. 2556 2 ()
 159
.. 2556 2 ()
160
.. 2556 2 ()
 161
.. 2556 2 ()
162
.. 2556 2 ()
 163
.. 2556 2 ()
164
.. 2556 2 ()
 165
.. 2556 2 ()
166
.. 2556 2 ()
 167
.. 2556 2 ()
168
.. 2556 2 ()
 169
.. 2556 2 ()
170
.. 2556 2 ()
 171
.. 2556 2 ()
172
.. 2556 2 ()
 TB 09

/ ...................................................................................................................................
/ .....................................................................................................................................
.........................................................................................................................................................................
...........................................................................................................................................................................................
...................................................................................................................................................................................................
District TB No. .........................................................................
1.
2.


3. 1

4. ...........................................................................................
5. ......../........./............................
...........................................................................................................................................................
...............................................................................
(........................................................................)
..................................................................
()

/ ..................................................................................................................................
.......................................................................................................................................................................
.............................................................................. ................................................................................
....................................................................................................................................................................................................
District TB No. .........................................................................
......................................................................................................................................................................................
...............................................................................
(........................................................................)
..................................................................
173
.. 2556 2 ()
 2
/

(Culture)
/
1 (NTRL)
2 ()
3
4
5
6
7
8
9
10
11 .
12 1
13
14
15 2
16
17
18
19

175
.. 2556 2 ()
 /
20
21 3
22
23
24
25
26
27
28 4
29
30
31
32
33
34
35
36
37 5
38
39
40
41
42 6
43
44
45
46 7
47
48

176
.. 2556 2 ()
 /
49 8
50 9
51
52 10
53
54
55
56
57
58
59
60
61
62
63 11
64
65
66
67
68 12 ( 12 )
69
70
71
72
73
74 IOM
: .. 2556 (.. 2013)

177
.. 2556 2 ()
 3
/

1 (FLDST)
/
1 (NTRL)
2 ()
3
4
5
6
7
8
9
10 .
11
12 1
13
14 2
15 3
16
17
18 4
19
20 5

178
.. 2556 2 ()
 /
21
22 6
23
24 7
25 8
26 9
27 10
28
29
30 11
31 12 ( 12 )
32 (AFRIMS)
33 IOM
: .. 2556 (.. 2013)

179
.. 2556 2 ()
 4
/

2 (SLDST)
/
1 (NTRL)
2
3
4
: .. 2556 (.. 2013)

180
.. 2556 2 ()
 5

ISTC
1.
1 2-3
2 2
1

3

4
5 2
( 1 )
(:
Fluoroquinolone )


6 ( )
( Gastric aspirate Induced sputum)


( Interferon- gamma release assay)

181
.. 2556 2 ()
2.
7



8 ()
bioavailability
2 isoniazid, rifampicin, pyrazinamide ethambutol
isoniazid rifampicin 4

9


( )
(Directly Observed Treatment: DOT)

10 (2 )
(2 ) 3


11

3

isoniazid rifampicin


12 ( MDR/XDR-TB)

4
18-24

13

182
.. 2556 2 ()
3.
14

15

co-trimoxazole
16
isoniazid 69
17

4.
18

1.
2.
3.
4.


5

(Multi Drug Resistance/Extensively Drug Resistance Tuberculosis:
MDR/XDR-TB)

19 5
isoniazid
20

21

183
.. 2556 2 ()
 .. 2556
2 ()

184
.. 2556 2 ()

.

12

.. 2556

185
.. 2556 2 ()

.. 2555

186
.. 2556 2 ()
 187
.. 2556 2 ()