Clinical Presentation

and Diagnosis of
Tuberculosis
Makiyatul M
BBKPM Surakarta

International Standards 1-5

Clinical Presentation and Diagnosis of TB

Objectives: At the end of this presentation,
participants will be able to:
Describe the signs/symptoms and risk factors that
should raise suspicion for the diagnosis of TB
Understand the importance of sputum smear
microscopy, as well as the need to obtain
specimens for microbiologic examination from
extrapulmonary sites
Recognize that CXR alone is not sufficient for the
diagnosis of TB
List criteria used for the diagnosis of smearnegative TB
ISTC TB Training Modules 2009

Clinical Presentation and Diagnosis of TB

Overview:
General considerations
Signs and symptoms
Role of AFB smear
Radiographic
presentation
AFB smear-negative
diagnosis
International Standards 1, 2, 3, 4, and 5
ISTC TB Training Modules 2009

Standards for Diagnosis

ISTC TB Training Modules 2009

Fundamental Principles
Rapid, accurate

diagnosis is essential
for individual and
public health
Despite technical
advances, clinical
acumen with a high
index of suspicion
remains vital to the
diagnosis of TB
ISTC TB Training Modules 2009

Think TB

Classic TB Clinical Presentation

Insidious onset and chronic course
Chest symptoms
Cough (usually productive)
Hemoptysis
Chest pain (usually pleuritic)

Nonspecific constitutional symptoms

(more common in children and HIV)
Extrapulmonary symptoms (if involved)

ISTC TB Training Modules 2009

Nonspecific Systemic Symptoms

Fever in 65-80% of cases
Chills/night sweats
Fatigue/malaise
Anorexia/weight loss
However, 10-20% of TB cases have no
symptoms at the time of diagnosis

ISTC TB Training Modules 2009

Diagnosis of TB in HIV
Cannot rely on typical indicators of TB
Fever and weight loss are important
symptoms
Cough is less common
Chest radiographic pattern more variable
More extrapulmonary and disseminated TB
Differential diagnosis is broader

ISTC TB Training Modules 2009

Standard 1: Prolonged Cough

All persons with
otherwise
unexplained
productive cough
lasting two-three
weeks or more
should be
evaluated for
tuberculosis
ISTC TB Training Modules 2009

Prolonged Cough
Think TB: Prolonged Cough (2-3 weeks)
Cough may not be specific for TB,
however, long duration raises likelihood of
TB diagnosis
Criterion for suspecting TB in most
national and international guidelines
Percentage of AFB smear-positive sputum
increases with increasing duration of
cough
Will not identify all TB cases; use best
clinical judgment
ISTC TB Training Modules 2009

Clinical Presentation: Risk Factors

Risk for Recent Infection
Contact with active TB case
Occupational risk e.g. healthcare worker
Crowded conditions e.g. jails, institutional
residences
Recent stay in a healthcare facility

ISTC TB Training Modules 2009

Clinical Presentation: Risk Factors

Risk of Progression to Active TB
HIV infection
Abnormal CXR suggestive of prior TB (with
inadequate treatment)
Children (less than 5 years of age)
Underlying medical conditions

Immunosuppressive therapy
Malnutrition
Diabetes, renal failure, and other conditions
Tobacco use, injection drug use (?)

ISTC TB Training Modules 2009

Clinical Presentation: Physical Examination

May be normal in mildmoderate disease
Chest: rales, rhonchi; absent breath sounds
and dullness to percussion if pleural fluid is
present
Extrapulmonary (site specific): adenopathy,
skin lesions, bone tenderness, neck stiffness,
etc.
The physical examination is nonspecific, but
it is helpful to identify extrapulmonary sites of
involvement
ISTC TB Training Modules 2009

Standard 2: Sputum Microscopy

All patients (adults,
adolescents, and
children who are
capable of producing
sputum) suspected
of having pulmonary
TB should have at
least two sputum
specimens obtained
for microscopic
examination in a quality-assured laboratory.
When possible, at least one early morning
specimen should be obtained.

ISTC TB Training Modules 2009

Sputum Microscopy
To prove a diagnosis of TB, every effort must
be made to identify the causative agent
The AFB smear in high-prevalence areas is:
Highly specific for TB
Most rapid method for determining TB diagnosis
Identifies those at greatest risk of dying from TB
Identifies those most likely to transmit disease

ISTC TB Training Modules 2009

Performance of Sputum Microscopy

Specimen
Number

Incremental Yield of Incremental Sensitivity

smear specimens
of smear specimens
(of all smear positive) (compared with culture)

85.8%

53.8%

11.9%

11.1%

2.4%

3.1%

Total

100%

68.0%

Average yield of single early morning specimen: 86.4%

Average yield of single spot specimen: 73.9%
Mase SR, Int J tuberc Lung Dis 2007;11(5): 485-95
ISTC TB Training Modules 2009

Can this be TB?

54-year-old man with
three months of focal
low-back pain

ISTC TB Training Modules 2009

Can this be TB? Extrapulmonary

54-year-old man with
three months of focal
low-back pain

Potts disease
Signs and symptoms of extrapulmonary TB are site
specific
Sampling of extrapulmonary sites for smear, culture, and
histopathology may confirm diagnosis

ISTC TB Training Modules 2009

Standard 3: Extrapulmonary Specimens

For all patients
(adults, adolescents,
and children)
suspected of having
extrapulmonary TB,
appropriate
specimens from the suspected sites of
involvement should be obtained for
microscopy, culture, and
histopathological examination.

ISTC TB Training Modules 2009

Example of Extrapulmonary Sites

Incidence/site may vary TB can involve any organ
More common in HIV/TB
Both, 9%
Extrapulmonary, 20%
Pleural, 18%
Lymphatic, 42%

Other, 13%

Pulmonary, 71%
Bone/joint, 11%
TB Cases by Form of Disease,
United States, CDC, 2008
ISTC TB Training Modules 2009

Peritoneal, 6%

Genitourinary, 5%
Meningeal, 5%

Extrapulmonary Tuberculosis

ISTC TB Training Modules 2009

Radiographic
Presentation
of TB

ISTC TB Training Modules 2009

Standard 4: Evaluation of Abnormal CXR

All persons with

chest radiographic
findings suggestive
of tuberculosis
should have sputum
specimens
submitted for
microbiological
examination.
ISTC Training
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Modules
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2008
2009

Can this be TB?

ISTC TB Training Modules 2009

Can this be TB?

Typical Pattern:
Reactivation,
Post-primary TB
Distribution
Apical / posterior
segments of upper lobes
Superior segments of
lower lobes
Isolated anterior segment
involvement is unusual
ISTC TB Training Modules 2009

Reactivation/Post-primary TB
Patterns of disease
Air-space consolidation
Cavitation, cavitary
nodule
Miliary
Fibro-nodular densities
Nodule (Tuberculoma)
Pleural effusions

ISTC TB Training Modules 2009

Can this be TB?

ISTC TB Training Modules 2009

Can this be TB?

Atypical pattern:
Primary TB
Distribution: Any lobe
involved (slight lower
lobe predominance)
Air-space consolidation
Cavitation is uncommon
(< 10%)
Adenopathy is common
(esp. in children and HIV)
Miliary pattern
ISTC TB Training Modules 2009

Can this be TB?

ISTC TB Training Modules 2009

Can this be TB? Miliary TB

ISTC TB Training Modules 2009

Can this be TB?

ISTC TB Training Modules 2009

Can this be TB?

Findings suggestive of
prior TB
Ca+ granuloma Ghon
lesion
Ca+ granuloma and hilar
node calcification Ranke
complex
Apical pleural
thickening
Fibrosis and
volume loss
ISTC TB Training Modules 2009

CXR Issues
Reliance on chest radiograph alone
results in both over-diagnosis and missed
diagnosis of TB and other diseases
Radiography needs to be held to high
standards of technical quality and
interpretation
Results of poor imaging quality may be
harmful to patient care

ISTC TB Training Modules 2009

Evaluation of Abnormal CXR

Study from India:
2229 outpatients evaluated by CXR/culture
Of 227 cases deemed TB by CXR alone
36% had negative sputum cultures for TB

Of 177 culture-positive cases of TB

18% would have been missed based on CXR
alone

CXR alone is not enough

Nagpaul DR, Proceedings of the 9th Eastern Region Tuberculosis Conference
and 29th National Conference on Tuberculosis and Chest Diseases. 1974 Delhi,
as cited in Tomans tuberculosis. Case detection, treatment and monitoring,
2nd Edition: World Health Organization, 2004

ISTC TB Training Modules 2009

Standard 5: Smear-negative Diagnosis

The diagnosis of sputum smear-negative pulmonary
tuberculosis should be based on the following criteria:
At least two negative sputum smears (including at
least one early morning specimen)
Chest radiography findings consistent with
tuberculosis
Lack of response to a trial of broad-spectrum
antimicrobial agents
(Note: Because the fluoroquinolones are active against M.
tuberculosis complex, and thus may cause transient improvement in
persons with tuberculosis, they should be avoided.)
(1 of 2)
ISTC TB Training Modules 2009

Standard 5: Smear-negative Diagnosis

(Continued)
For such patients, sputum cultures should
be obtained.
In persons who are seriously ill or have
known or suspected HIV infection, the
diagnostic evaluation should be expedited
and if clinical evidence strongly suggests
tuberculosis, a course of antituberculosis
treatment should be initiated.
(2 of 2)
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Modules
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2008
2009

TB Diagnostic Algorithm
SPUTUM SMEAR-NEGATIVE TB

Clinical assessment, HIV test1,

sputum smear microscopy

At least 2 sputum specimens AFB negative

HIV + and/or severe illness2

HIV-, mild/moderate illness2

1. Recommended in countries or areas with adult HIV prevalence >1% or

prevalence among TB cases >5%
2. Severe illness = respiratory rate >30 breaths/min, temperature >39C, pulse
>120 beats/min, unable to walk unaided, symptoms/signs progressing rapidly
ISTC TB Training Modules 2009

TB Diagnostic Algorithm
SPUTUM SMEAR-NEGATIVE TB

HIV + and/or severe illness

Repeat clinical assessment
Chest radiograph
Sputum culture (or other test)

Parenteral broad-spectrum
antimicrobials (excluding
fluoroquinolones)

Clinical/radiographic findings
NOT suggestive of TB
Negative culture

Clinical/radiographic findings
suggestive of TB
Positive or negative culture

Not TB

TB

Consider other diagnoses

Treat (empiric TB treatment before confirmed

HIV staging

ISTC TB Training Modules 2009

Evalutate for ARVs

diagnosis if severe illness)

CPT prophylaxis

TB Diagnostic Algorithm
SPUTUM SMEAR-NEGATIVE TB

HIV, mild/moderate illness

Broad-spectrum antimicrobials

(excluding anti-TB drugs and fluoroquinolones)

NO IMPROVEMENT

IMPROVEMENT

Repeat clinical assessment

Chest radiograph
Sputum culture (or other test)
Clinical/radiographic findings
NOT suggestive of TB
Negative culture

Clinical/radiographic
findings suggestive of TB
Positive culture

Not TB

TB

Consider other diagnosis

Treat

ISTC TB Training Modules 2009

Not TB

Clinical Presentation and Diagnosis of TB

Additional points:
Symptoms/severity: none to overwhelming
Tempo of illness: ranges from indolent to fast
TB can involve any organ or tissue
Signs/symptoms may be both local and
systemic
Consider HIV testing in the diagnostic
evaluation

TB is capable of presenting in many ways

ISTC TB Training Modules 2009

Clinical Presentation and Diagnosis of TB

Summary: Think TB
A prolonged duration of cough should raise TB
suspicion and trigger a diagnostic evaluation
TB risk factors and exposure increase level of
suspicion
AFB smear in high-prevalence areas is highly
specific and most rapid tool for diagnosing TB
Radiographic patterns may help in TB diagnosis
if suspicion high and AFB smear is negative, but
a radiograph alone is not enough to make
diagnosis
ISTC TB Training Modules 2009

Summary: ISTC Standards Covered*

Standard 1: Unexplained productive cough lasting
2-3 weeks or more should be evaluated for
tuberculosis.
Standard 2: All TB suspects should have at least
2 sputum specimens obtained for microscopic
examination (at least one early morning
specimen if possible) in a quality-assured
laboratory.
Standard 3: Specimens from suspected
extrapulmonary TB sites should be obtained for
microscopy, culture and histopathological exam.

* Abbreviated versions

ISTC TB Training Modules 2009

Summary: ISTC Standards Covered*

Standard 4: All persons with chest radiographic
findings suggestive of TB should have sputum
specimens submitted for microbiological
examination.
Standard 5: The diagnosis of smear-negative
pulmonary TB should be based on the following:
at least two negative sputum smears (including at
least one early morning specimen); CXR finding
consistent with TB; lack of response to broadspectrum antibiotics (avoid fluoroquinolones), and
culture data. Empiric treatment if severe illness.
* Abbreviated versions
ISTC TB Training Modules 2009

Alternate Slides

ISTC TB Training Modules 2009

Purpose of ISTC

ISTC TB Training Modules 2009

ISTC: Key Points

21 Standards (revised/renumbered in 2009)
Differ from existing guidelines: standards
present what should be done, whereas,
guidelines describe how the action is to be
accomplished
Evidence-based, living document
Developed in tandem with Patients Charter
for Tuberculosis Care
Handbook for using the International
Standards for Tuberculosis Care
ISTC TB Training Modules 2009

ISTC: Key Points

Audience: all health care practitioners,
public and private
Scope: diagnosis, treatment, and public
health responsibilities; intended to
complement local and national guidelines
Rationale: sound tuberculosis control
requires the effective engagement of all
providers in providing high quality care and
in collaborating with TB control programs

ISTC TB Training Modules 2009

Questions

ISTC TB Training Modules 2009

Clinical Presentation and Diagnosis of TB

1. A 32 year-old man complains of cough and
malaise for the past three weeks. His wife is
currently being treated for active tuberculosis. Of
the following choices, your first step would be:
A. Begin an empiric trial of treatment with a
fluoroquinolone antibiotic for a possible communityacquired pneumonia
B. Obtain a chest film to confirm your suspicion for TB
which will make sputum testing unnecessary
C. Obtain two sputum specimens for AFB microscopy
(including at least one early morning specimen)
D. Both answers A and C
ISTC TB Training Modules 2009

Clinical Presentation and Diagnosis of TB

2. In high prevalence areas, the AFB sputum
microscopy smear:
A. Is highly specific for TB
B. Identifies those at greatest risk of dying from TB
C. Identifies those most likely to transmit disease
D. All of the above

ISTC TB Training Modules 2009

Clinical Presentation and Diagnosis of TB

3. A 54 year-old woman complains of cough, fever,
and unexpected weight loss over the past
month. She admits smoking 10 cigarettes per
day for over 20 years. Two sputum smears were
negative for AFB. You would consider each of
the following except:
A. An empiric trial of antibiotics (non-fluoroquinolone)
B. Obtaining a chest film for further evaluation
C. A trial of bronchodilator medication alone and
follow-up in 3 months
D. Sending sputum specimens for AFB culture
ISTC TB Training Modules 2009