Clinical Presentation and Diagnosis of Tuberculosis

Your name Institution/organization Meeting Date

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

Incremental Yield of Incremental Sensitivity Specimen smear specimens of smear specimens Number (of all smear positive) (compared with culture) 1 2 85.8% 11.9% 53.8% 11.1%

3
Total

2.4%
100%

3.1%
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%

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

Other, 13% Genitourinary, 5% Meningeal, 5%

Peritoneal, 6%

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 TB Training Modules Modules 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)
ISTC Training TB Training Modules Modules 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
Treat (empiric TB treatment before confirmed
diagnosis if severe illness)

Consider other diagnoses

ISTC TB Training Modules 2009

HIV staging

Evalutate for ARVs

CPT prophylaxis

TB Diagnostic Algorithm
SPUTUM SMEAR-NEGATIVE TB

HIV, mild/moderate illness

Broad-spectrum antimicrobials
(excluding anti-TB drugs and fluoroquinolones)

NO IMPROVEMENT Repeat clinical assessment Chest radiograph Sputum culture (or other test)

IMPROVEMENT

Clinical/radiographic findings NOT suggestive of TB Negative culture

Clinical/radiographic findings suggestive of TB Positive culture

Not TB
ISTC TB Training Modules 2009

TB
Treat

Not TB

Consider other diagnosis

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