Tuberculosis

YANG YUXIA
The third afflicated hospital of zhengzhou
university
 summary

Tuberculosis(TB) is a chronic infectious disease that

caused by Mycobacterium tuberculosis.
It usually affects the lung , but it can affect any
organs in the body. Such as digestive system 、 skin.
World TB Day
24 March 2001

                 

"DOTS - TB cure for All "

"DOTS : un traitement antituberculeux pour tous"
 Introduction

March 24
World TB Day
世界结核病日
Stop TB,
Fight
Poverty.
World TB Day

2002
World TB Day, March 24, 2004
World TB Day
24 March 2001

                 

"DOTS - TB cure for All "

"DOTS : un traitement antituberculeux pour tous"
 一 Etiology
The agent of tuberculosis , Mycobacteriu
m tuberculosis is member of the order Ac
tinomycetales and family Mycobacteriace
ae, weakly gram-positive , and it is an obl
igate aerobes, Mycobacteria grow slowly,
however growth can be detected in 1-3 w
eeks in selective liquid medium using radi
olabeled nutrients(BACTEC)
 Mycobacterium tuberculosis / 结核杆
菌

 Acid-Fast bacillus, AFB (Robert Koch, 1882)

抗酸染色为红色 --- 抗酸杆菌
 M. tuberculosis ( 人型结核杆菌 ) & M. bovis
（牛型结核杆菌） are two main species causi
ng tuberculosis in human.
 二： Epidemiology

（一） Source of infection

The major source of infection is the open
pulmonary tuberculosis patients.
（二） Transmission
Transmission of Mycobacterium is person t
o person, usually by airborne mucus drople
t nuclei. Transmission rarely occurs by dire
ct contact with an infected discharge or a co
ntaminated fomite (food-borne transmissio
n
Transmission an open active TB patient
（三） Susceptible population
Poverty, over-crowding, poor nutrition a
nd socioeconomic fall behind （ developm
ents slowly ） plays the major role in th
e incidence.
 三： Pathogeny
The risk for developing tuberculosis disease in
children who had contacted with bacillus
tuberculosis at first time concerned with the
Immune status of the host , the virulence and the
quantity of the bacillus tuberculosis, especially the
status of the cell-mediated immunity (CMI). After
infected bacillus tuberculosis , the body produces
the allergy and immunity at the same time .
[The allergic reaction and immunity of TB]
pathogen (Tubercle bacillus)
through infective route (respiratory
tract, alimentary canal, skin and
placenta)

child

The thymus-dependent LC be sensitized and proliferate

Delayed allergic reaction Activating factors Inhibiting factors of

(Type 4 of allergic reation)
of macrophage Macrophage movement

Activating macrophage TB is surrounded

by sensitized TLC
Engulf and kill tubercle bacillus
produce
Eptheloid cells and tubercle

Infection is focused
 Pathogenesis

Acid-Fast bacillus
进入体内（胞内寄生）
致敏 T 淋巴细胞（细胞免疫， 4~8 周）
释放 cytokines/lymphokines
激活 macrophages
吞噬和杀灭结核杆菌
 四： Diagnosis

Try to early diagnosis ．

Include ： finding focus on infection; maki
ng a decision of it’s character and scope;
whether discharge of bacteria or not; and
make sure if it is reactiveness.
• Sex: female ＞ male
• Age: ＜ 5 yrs
 ( 一 ) History:

Toxic symptom: Prolong low grade fever,

cough, night sweats, weakness, loss of weight,
loss of appetite and so on.
The history of exposure to the infectious
tuberculosis, especially the children of
contact with the infectious tuberculosis in
their home.
The history of BCG vaccination
The history with the acute infection diseases,
especially , measles 、 whooping cough,
The manifestation of hypersensitiveness of T
B: such as erythema nodosum, herpes conju
nctivitis.
 （二） Tuberculin skin tests （ TS
T）
(1) Test methods:
Assessment (Evaluation):
The diameter of induration <5 mm (-)
≥5mm (++)
≥20mm (+++)
Beside induration, there are still blister an
d necrosis (++++)
 (2 ) Clinical significance
positive result
① Bacilli Calmette-Guerin Vaccination (BCG) vac
cination

② Older children with non-clinical manifestation, t

uberculin test is (+)~ (++)(general reaction) mean
s that the TB germs are probably inactive and T
B disease not present.
③ Children < 3 yr of age, especially those who
have not vaccinated BCG, positive result
mostly represent that there is a new
tuberculosis focus in the body, with small ages
the active TB is more likely to be than old ages.
④ Strong positive usually means that there is
an active TB disease.
⑤ Negative turn into positive result or the in
duration of the diameter enlarge more then
10 mm from small 10 mm and the amplifica
tion more than 6 mm, representation newly
infected .
 The major distinguishing between nature infection and BCG
vaccination
BCG vaccination Nature

Millimeter of induration Less then 5~9mm 10~15mm

Colour of induration pink crimson

texture of induration Relatively soft; Relatively hard

edge untidiness Edge tidiness (regularity)

Last time of Shortly Relatively long

Positive reaction 2~3days More then 7~10 days

Change of Usually transient over months to years perstetur for several years ev
Positive reaction the reactivity usually wane en lifetime
in 3~5years
 negative result
1.It can mean that the person has not been infected with TB germs.

2.It can mean that the person was tested too

soon after breathing in the germs. It takes a
number of weeks(4-8weeks)after becoming
infected by the germ for the body to react to the
skin test. If this happens, the test will have to be
repeated again after 3 months.
• 3.It can mean that the person's body defenses a
re weakened and unable to react to the skin test
, even though he/she is infected. （ including mal
nutrition, immunosuppression by disease or dr
ug ,viral infections :measles mumps varicella, i
nfluenza; corticosteroid therapy ） When this
happens, another type of test is given.

• 4. Poor technique or lose efficacy of the reagent

 （三） Laboratory examine
(1) Mycobacterium Detection and Isolation

(2) Immunology and molecular biology

diagnosis
① enzyme linked immunosorbent assay (ELISA)
② Enzyme linked immuno-electrophoresis(ELIEP )
③ DNA probes

④ Polymerase Chain Reaction (PCR)

(3) Erythrocyte sedimentation rate
(ESR):
 ( 四 ) Image analysis

(1) X-ray Examine:

(2) Computerized tomography (CT):
(3) Magnetic resonance imaging (MRI)
( 五 ) Other auxiliary examination

(1) Flexible fiberoptic bronchoscopy

(2) Peripheral lymph node puncture fluid a

nd smear examination: It can find tuberc
ler and caseification
 五 . Treatment

General treatment
Antituberculosis drugs
Goals for treatment of tuberculosis
(1) To kill the Mycobacterium tuberculosi
s in focus
(2) To prevent the hematogenous spread
Therapeutic principle early, regular, enough,
combine and proper dose
(1) Early treatment
(2) Appropriate suitable dosage
(3) Disciplinary medication
(4) Omnidistance
(5) Segmentation
① drugs: INH, RFP, EMB, SM, PZA

② principles: early, regular, enough,

combine and proper dose.
 The most commonly used drugs are classifi
ed into two types
(1) Bactericidal drugs:
INH and RFP are highly bactericidal for
M.tuberculosis
STM are bactericidal for extra-cellular t
ubercle bacilli
PZA are bactericidal for intra-cellular tu
bercle bacilli
(2 ) Bacteriostatic drugs: EMB;ETH
Other drugs
The major distinguishing between nature infection and BCG vaccination
drug Dosage(kg/day) route of Major side effects
{Maximum dose} administrati
on
INH 10mg Po/im/iv.dro Hepatotoxicity; Peripheral ne
{≤300mg/day} p uritis
Hypersensitivity reaction
RFP 10mg po Hepatotoxicity;
{≤450mg/day} Gastrointestinal reactions
SM 20-30mg im Ototoxicity nepatotoxicity Hy
{≤0.75/day} persensitivity reaction
PZA 20-30mg po Hepatotoxicity; hyperuricemi
{≤0.75/day} a
Acute gouty arthritis
EMB 15-25mg po Optic neuritis
ETH 10-15mg po gastrointestinal reactions; He
patotoxicity; Peripheral neuri
tis
Therapeutic regimen
1. Standard therapy regimen:
commonly used asymptomatic primary p
ulmonary tuberclosis.
INH RFP and/or EMB (should be given
daily ) 9-12 months
2. Segmented therapy regimen:
Used for reactive tuberculosis, acute
miliary tuberculosis of the lungs,
tuberculosis meningitis.
(1) Intensification therapy phase (three-or fou
r-drug regimen):
three/four drugs combination in order to kil
l the sensitive organism and multiply activel
y organism and hypometabolic (slow-metab
olic) organism as soon as possible, preventi
ng or decreasing emergence of drug resistan
t bacteria.
(INH+RFP+SM+PZA)
3-4mo for long-term course
2 mo for short-term course
(2) Consolidation therapy stage:
In order to eliminate the Mycobacterium
of persistence..
Two antituberculosis drugs are given
during this stage.
12 to 18 months for long course, 4 month
for short course.
(3) Short course:
The tendency of current therapeutic
regimen is to increase the strength and
shorten the course.
 六． Prevention:

1. Control the sources of infection:

2. Bacilli Calmette-Guerin Vaccination (BCG)
:
 Counterindication
1. The patients of DiGeorge anormaly
（ congenital thymic aplasia ）
and severe combined immunodeficiency
2. Convalescent period of acute infectious
disease
3. There is eczema or dermatosis at injection
site
4. A positive of tuberculin skin test
 Chemoprophylaxis

(1) Purpose
① Prevention the active pulmonarytubercul
osis in children
② Prevention extrapulmonary tuberculosis
③ Prevention reactivation tuberculosis in ad
olescence children
(2) Indication
① Household close contacts with an adult of
active pulmonary tuberculosis
② ≤3yr children and have not vaccinated
BCG, however, positive skin test
③ Negative turn into positive result skin test
recently
④ A positive skin test and having the
symptom of tuberculosis disease
⑤ A positive skin test and infected measles or
whooping cough
⑥ A positive skin test and should accept the
therapy of corticosteroids or
immunosuppression drugs for a long time
(3) Method
The currently recommended regimen is
6-9mo of daily INH 10mg/kg/day
(≤300mg/d) therapy. or 3mo of daily INH
10mg/kg/day(≤300mg/d) and RFP
10mg/kg/day (≤300mg/d).
Primary Pulmonary Tuberculosis
原发型肺结核
 Definition

• Primary pulmonary tuberculosis is the majo

r type of pulmonary tuberculosis developed in
children during initial infection.
（原发型肺结核是指结核菌初次侵入肺部后发生的原
发感染，是小儿肺结核的主要类型，占儿童各型肺结
核总数的 85.3% 。）
 Pathology
• Basic pathological changes
Exudation / 渗出
Proliferation (tuberculous tubercle, tuberculous granuloma)
增殖（结核结节、结核性肉芽肿）
Necrosis (caseation)/ 坏死（干酪性坏死）
• Outcome of pathological changes
Fully Recover (Calcification/Absorption/Fibrosis)
Progression
Worsen
 Pathology

特征性病理改变：
上皮样细胞结
节 tuberculous tubercle 、 Lang
erhans 细胞浸润
 Manifestation
The manifestation of TB in children are variabl
.
 Onset of TB, chronic & hiding/ 起病常隐匿
 Asymptom cases 80%
 Upper respiratory tract infection ： dry co
ugh and mild dyspnea are the most common sy
mptoms.
 Toxic symptoms of tuberculous infection
 Malnutrition
 Manifestation
The manifestation of TB in children are variable.
 Hypersensitivity
erythema nodosum/ 皮肤结节性红斑
phlyctenular conjunctivitis / 疱疹性眼结膜炎
arthritis / 关节炎
 On occasion, the onset of TB, abrupt
 Lung symptoms
asthmatic breathing, cough, etc.
 Signs

 Superficial lymph node swell

 Lung signs
多无明显体征
叩诊可为浊音
听诊呼吸音减低
听诊少许湿罗音
 Diagnosis

 History
 Manifestations
 Physical examination
 Immunology examination
tuberculin skin test / ELISA / etc.
 Chest X-ray examination
 Fibrobronchoscope examination
 Diagnosis
 Chest X-ray
 Primary Complex ( 原发综合征 )
primary focus at the site of implantation/ 原发病灶
tuberculous lymphangitis/ 淋巴管炎
regional tuberculous lymphadenopathy/ 淋巴结炎

呈典型“哑铃状双极影
原发综合征：哑铃状双极影
 Diagnosis
 Chest X-ray
 Tuberculosis of Tracheobronchial Lymphonodu

支气管淋巴结结核
表现为：肺门影增浓
Tuberculosis of Tracheobronchial Lymphonodu
 Turnover of primary pulmonary
tuberculosis
1. Absorption and improvement :
The primary pulmonary tuberculosis
heals completely by fibrosis and/or
calcification. (but healing is usually less
complete ,Viable mycobacterium can
persist for decades within these foci)
It is the most common.
2. Progression:
3. Deterioration:
 Clinical manifestation

The symptoms and physical signs of

pulmonary tuberculosis in children are
surprisingly meager considering the
degree of radiographic changes often
seen.
More than 50% of infants and children w
ith radiographically moderate to severe p
ulmonary tuberculosis have no physical fi
ndings and are discovered only by contac
t tracing .
Infants are more likely to experience signs a
nd symptom
Nonproductive cough and mild dyspnea are
the most common symptoms.
Systemic complaints such as fever, night sw
eats, anorexia, and decreased activity occur
less often (older children may be have the s
ymptoms).
Some infants have difficulty gaining
weight or develop a true failure-to-thrive
syndrome
Peripheral lymph node enlarge in different de
grees.
Pulmonary signs are even less common. Some
infants and young children with bronchial ob
struction have localized wheezing or decrease
d breath sounds that may be accompanied by
tachypnea or rarely, respiratory distress.
If the parenchymal focus comparatively la
rge, dullness to percussion, decreased brea
th sounds. A little of dry / moist rales.
Infants may be accompanied by splenohep
atomegalia. (Hepatosplenomegaly)
 Diagnosis and differential
diagnosis
1. Diagnosis : Early diagnosis is very import
Diagnosis depend on :
( The most specific confirmation of pulmonary
tuberculosis is isolation of M.tuberculosis .But negative
cultures never exclude the diagnosis of tuberculosis in a
child, for most children, the presence of a positive
tuberculin skin test, an abnormal chest radiograph
consistent with tuberculosis, and history of exposure to an
adult with infectious tuberculosis is adequate proof that
the disease is present.)
2. Differential diagnosis ：
 Treatment:
1. General treatments and therapeutic prin
ciples are the same as those in general int
roduction
2. Antituberculosis drugs
(1) Asymptomatic primary pulmonary
(2) Active primary pulmonary
DOTS is recommended
INH+RFP+PZA/SM for 2-3mo followed
by INH and RFP/EMB to complete a
total treatment duration of 6mo
DOTS
Directly Observed Treatment, Short-course

直接督导下的短程化疗
DOTS for primary pulmonary tuberculosis

2HRZ/4HR or 9HR
 原发性肺结核治疗的注意点：

最坏的治疗是单一用药
标准化疗方案： 2HRZ/4HR
推荐日剂量顿服
提倡直接督导下服药（ DOTS ）
How to decide the reactiveness of tuberculosi
s in children?
① A strong positive of tuberculin skin test
② A positive of skin test in the children < 3 yr
of age , especially <1 yr of age and have not
been vaccinated the BCG.
③ symptoms of tuberculosis
④ Isolation of M.tuberculosis from discharge
⑤ radiographic changes means the reactiveness
of primary pulmonary tuberculosis
⑥ ESR raises and there is not another reason to
explain
⑦ Flexible fiberoptic bronchoscopy finds the
change of bronchial tuberculosis
 The tuberculous meningitis

The tuberculous meningitis is the most se

rious type of tuberculosis in children. It o
ften occurs within a year after the first in
fection of the tubercle bacillus, especially
within the 3-6 months. Tuberculous meni
ngitis is most common in children < 3 yea
r of age, about 60%.
 pathogenesis

The tuberculous meningitis is often a part

of the miliary tuberculosis of the whole b
ody, which disseminates through the bloo
d.
Pathology
 Clinical manifestation
1.The earlier stage ( prodromal stage): （ la
sts 1—2 weeks ）
The cardinal symptom is the changes for
the child‘s character
child may have fever, poor appetite, night
sweat, emaciated, emesis, constipation
the infants may frown , gaze , drowsiness
or delay of developmental. Focal neurolo
gic signs are absent.
2. The intermediate stage ( the meningeal irri
tation stage) :
The increased intracranial pressure causes
the violent headache, projectile vomiting, le
thargy, dysphorias or seizures.
The patient has obvious meningeal irritat
ion sign, neck rigidity, positive Kernig sig
n or Brudzinski sign
The infant may split of cranial sutures or
eminence of anterior fontanel
There are the dysfunction of encephalic n
erves ， most common is facial nerve, ocul
omotor nerve, abducent nerve
Some children may have signs of encephalitis
3. The advanced stage ( the coma stage):

It is marked by coma.
 Diagnosis
1. The disease history
2. The clinical feature:
3. CSF measure: It is the most important la
boratory test for the diagnosis of tubercul
ous meningitis is examination of the lumb
ar CSF.
Normal regulations check: The cerebrospinal
fluid pressure increase and the external appe
arance is transparent or like frosted glass. W
hen the subarachnoid space is obstructed, th
e CSF appearance is yellow.
Placing 12-24 hours, there will be the cobweb
thin film in the cerebrospinal fluid
The CSF leukocyte count usually ranges from
50×106/ L — 500×106/ L, lymphocytes
predominate in the majority of cases.
The glucose is typically <2.2mmol/L(40mg/dl)
but rarely < 1.1mmol/L(20mg/dl). Chlorides
and glucose are lower than the normal level,
which is the typical change of the tuberculous
meningitis.
The protein level is elevated (1.0-3.0 g/ L)
and may be markedly high 40-50 g/ L
secondary to hydrocephalus and spinal
block.
 4. Other measures:

⑴ The tubercle bacillus antigen examination

⑵ Anti- tuberculosis antibody measure
⑶ Live of the adenosine deaminase(ADA) mea
sure
⑷ Tuberculin skin- test
⑸ Mycobacterial culture of the CSF
⑹ Polymerase chain reaction( PCR)
5. X –ray CT and MRI:
 Differential diagnosis
1. The purulent meningitis:
2. The viral meningitis
3. The cryptococcal meningitis
4. The brain tumor
Complications and sequelaes
 Treatment
1. The general treatment:
2. The anti-tuberculosis treatment:
Use several drugs together which can pass
through blood-brain barrier easily
(INH+ RFP+ PZA +SM) 3-4 mo followed by
INH and RFP/EMB to complete the total
treatment duration of 12mo
3. Decrease the intracranial hypertension:
⑴ Dehydrater: 20% mannitol
⑵ Diuretic: Diamox
⑶ lateral ventricle stabbing
⑷ Lumbar puncture and note the medicine
into neurilemma
⑸ Shunting:
 5. Symptomatic treatment
⑴ Treating the convulsion:
⑵ Treating the water-electrolyte disorder
:
① Dilution hyponatremia:
② The syndrome of loses salt
③ Hypopotassaemia
6. Follow-up visit:
The follow-up visit should last at least 3-5 years
Prognosis