Diagnosis of Pulmonary

Tuberculosis
Presenter: 4A Ri 范綱志
Sep. 29,2008
 Why diagnosis important?
• Diagnosis of tuberculosis in most cases
– clinical diagnosis based upon the clinical presentation
(hx & PE)
• In 15-20% of p’t with suspected TB
– lab confirmation never obtained
• Early diagnosis and initiation of effective
therapy
– reducing morbidity and mortality from TB
– minimize the spread of infection
 Outline
• Screening for prior infection
– Tuberculin skin test
• Diagnosis of pulmonary TB
– Medical history
– Physical examination
– Chest radiograph
– Bacteriologic exam
Screening for prior infection
Tuberculin skin test

篩出感染者
 Screening for prior infection
• Whom to screen
– High prevalence and high risk population
(HIV)
• How to screen
– Mantoux tuberculin test (ie, purified protein
derivative or PPD, tuberculin skin test)
• How to interpret
– Determine maximum diameter of induration
by palpation
 Mantoux Tuberculin Test
• Preferred method of testing for TB
infection in adults and children
• Tuberculin skin testing useful for
– Examining person who is not ill but may be
infected
– Determining how many people in group are
infected
– Examining person who has symptoms of TB
Mantoux test
• Inject intradermally
0.1 ml of 5TU PPD
tuberculin
• Produce wheal 6 mm
to 10 mm in diameter
• Represent DTH
(delayed type
hypersensitivity)
 Reading of Mantoux test
• Read reaction 48-72
hours after injection
• Measure only
induration
• Record reaction in
mm
 Classifying the tuberculin reaction

• >5 mm is classified as positive in

– HIV-positive persons
– Recent contacts of TB case
– Persons with fibrotic changes on CXR
consistent with old healed TB
– Patients with organ transplants and other
immunosuppressed patients
 Classifying the tuberculin reaction

• >10 mm is classified as positive in

– Recent arrivals from high-prevalence countries
– Injection drug users
– Residents and employees of high-risk settings
– Mycobacteriology laboratory personnel
– Persons with clinical conditions that place them
at high risk
– Children <4 years, or children and adolescents
exposed to adults in high-risk categories
 Classifying the tuberculin reaction

• >15 mm is classified as positive in

– Persons with no known risk factors for TB
 Factors may affect TST
• False negative
– Faulty application
– Anergy
– Acute TB (2-10 wks to convert)
– Very young age (< 6 months old)
– Live-virus vaccination
– Overwhelming TB disease
• False positive
– BCG vaccination (usually <10mm by adulthood)
– Nontuberculous mycobacteria infection
 Boosting
• Some people with LTBI may have
negative skin test reaction when tested
years after infection
• Initial skin test may stimulate (boost)
ability to react to tuberculin
• Positive reactions to subsequent tests may
be misinterpreted as a new infection
 Two-Step Testing
• Use two-step testing for initial skin testing
of adults who will be retested within 1-3
weeks
– If first test (+), consider the person infected
– If first test (-), give second test 1-3 weeks later
– If second test (+), consider person infected
– If second test (-), consider person uninfected
 Screening for prior infection

• 台灣早年結核病盛行率高
• 50 年前 20 歲以上成人
– 80% TST 為陽性
• 年齡越大 ,TST 對結核病的診斷幫助越小
Diagnosis of Pulmonary TB
 Diagnosis of disease

• Medical history
• Physical examination
• Chest radiograph
• Bacteriologic exam
– AFS
– Culture
Medical History
 Medical History
• Symptoms of disease
• History of TB exposure, infection, or
disease
• Past TB treatment
• Demographic risk factors for TB
• Medical conditions that increase risk for
TB disease
 Medical History
• High prevalence population
– More likely to be exposed to and infected with
bacillus
• Immigrant from high prevalence area
• Resident or worker in jail
• Long term care facility
• Close contact to p’t with active TB
 Medical History
• High risk population
– More likely to progress from infection to active TB
• HIV (+) or other immunodeficiency
• CRF
• DM
• IVDA
• Alcoholics
• Malnourished
• Malignancy
• Gastrectomy
Physical Examination
 Physical Examination
• Productive, prolonged cough
– duration of ~3 weeks
• Chest pain
• Hemoptysis
• Fever/Chills
• Night sweats
• Appetite loss
• Weight loss
• Easily fatigued
Chest radiography
 Chest radiography
• Classical radiograph appearance
– Infiltration
– Cavitation
– Fibrosis with traction
– Enlargement of hilar and mediastinal lymph node
• In reactivaiton TB
– Classically fibrocavitary apical disease
• Primary TB
– Middle or lower lobe consolidation
 Chest radiography
• Abnormalities often
seen in apical or
posterior segments of
upper lobe or
superior segments of
lower lobe
• May have unusual
appearance in HIV-
positive persons
• Cannot confirm
diagnosis of TB!!
cavity in patient‘s RUL
classic" for adult-type, reactivation tuberculosis
 Classic adult TB CXR

• PA view
– diffuse parenchymal
disease with multiple
cavities and bulla
formation on the left
– Sputum smear was
positive for AFB
 Chest radiography
• No chest X-ray pattern is absolutely
typical of TB
• 10-15% of culture-positive TB patients not
diagnosed by X-ray
• 40% of patients diagnosed as having TB
on the basis of x-ray alone do not have
active TB
 X-ray-based evaluation causes
over-diagnosis of TB
100
Over-
80 diagnosis
60
40
20
0
Diagnosed by X- Actual cases
ray alone

NTI, Ind J Tuberc, 1974

Bacteriologic Exam
 Specimen Collection
• Obtain 3 sputum specimens for smear
examination and culture
• Persons unable to cough up sputum
– induce sputum
– bronchoscopy
– gastric aspiration
• Follow infection control precautions
during specimen collection
 Three Specimens
• Three specimens optimal
• Spot specimen on first visit; sputum container
given to patient
• Early morning collection by patient on next
day
• Spot specimen during second visit
Three sputum smears are optimal

100%
100% 93%
Cu mu la tive P o s itivity

81%

50%

0%
First Second Third
 Number of sputum samples required

• overall diagnostic yield for sputum

examination related to
– the quantity of sputum (at least 5 mL)
– the quality of sputum
– multiple samples obtained at different times
to the laboratory for processing
• 3 samples obtained at least eight hours apart with
at least one sample obtained in the early morning
Number of sputum samples required
• several studies have suggested that only two
samples may be sufficient to capture the
majority of cases:
– Retrospective study
• Nelson, SM, Deike, MA, Cartwright, CP. Value of examining multiple sputum speci
mens in the diagnosis of pulmonary tuberculosis. J Clin Microbiol 1998; 36:467.

– overall, 92 percent of cases would have been

detected with two specimens
• Craft, DW, Jones, MC, Blanchet, CN, et al. Value of examining three acid-fact bacillus s
putum smears for the removal of patients suspected of having tuberculosis from the "ai
rborn precautions" category. J Clin Microbiol 2000; 38:4285.

– a third sputum smear was of no additional

value
 Smear Examination
• Strongly consider TB in patients with
smears containing acid-fast bacilli (AFB)
• Results should be available within 24
hours of specimen collection
• Presumptive diagnosis of TB
• Not specific for M. tuberculosis
 AFB Smear
• Sensitivity: 40-70%
• Specificity: 90%
 AFB smear

AFB (shown in red) are tubercle bacilli

Reporting on AFB Microscopy

Number of bacilli seen Result reported

None per 100 oil immersion fields Negative

1-9 per 100 oil immersion fields Scanty, report

exact number

10-99 per 100 oil immersion fields 1+

1-10 per oil immersion field 2+

> 10 per oil immersion field 3+

 Proportion of patients with pulmonary
TB who have positive AFB smears

AFB positivity in
70 HIV
TB patients
Negative
60
Early HIV
50
40
Late HIV
30
20
10
0
 Open tuberculosis

• A tuberculous ulceration or other form of

tuberculosis in which tubercle bacilli are
present in the excretions or secretions.
• Pulmonary tuberculosis, especially with
cavitation.
• 開放性結核就是在病人咳出的痰液中有結
核桿菌的存在
 Cultures
•Gold standard for TB diagnosis
•Use to confirm diagnosis of TB
•Culture all specimens, even if smear negative
•Results in 4 to 14 days when liquid medium
systems used

Colonies of M. tuberculosis growing on media

 Cultures
• Sensitivity: 80-85%
• Specificity: 98%
• Times needed:
– Solid medium
• 4-8 wks
– Liquid medium
• 2 wks
 AFB smear vs. Cultures
• AFB smear
– 可檢測到每 ml 標本有 5000-10000 隻細菌
– 染色陰性並不能排除結核病
– Rapid diagnosis
• Cultures
– 每 ml 標本只需有 10-100 隻細菌便可檢測到
– More sensitive
– Allows drug susceptivity test
Microscopy is more objective
and reliable than X-ray

Inter-observer
98%
100 agreement
80 70%

60

40

20

0
AFB Microscopy X-ray
Microscopy is a more specific test than
X-ray for TB diagnosis

100 98%
Specificity
80

60 50%

40

20

0
AFB Microscopy X-ray
 Diagnosis of Pulmonary TB
Cough 3 weeks
If 1 positive,
AFB X 3 If 2/3 positive:
X-ray and Anti-TB Rx
evaluation
If negative:
Broad-spectrum antibiotic 10-14 days
If symptoms persist, repeat AFB smears, X-ray

If consistent with TB
Anti-TB Treatment
Diagnosis of pulmonary TB
Recommended Diagnostic Approach
 Take Home Message
• 診斷結核病必須綜合
– 臨床表現
• Non-specific symptoms
– 放射學變化
• Often over diagnosis
– 實驗室細菌學診斷
• AFB smear
– Rapid diagnosis, presumptive diagnosis
• Culture
– Gold standard, more sensitive

• 只要強烈懷疑 TB 可先開始進行抗結核治療
 Source
• UpToDate, Diagnosis of pulmonary
tuberculosis, 2008, John Bernardo,MD
• 行政院衛生署疾病管制局 , 結核病診治指
引 , Taiwan Guidelines on TB Diagnosis &
Treatment, Edition 3, 主編陸坤泰
Thanks for your attention!