Interim

Draft Module 4 - September 2008

Case Finding and Diagnosis

Project Partners
Collaborative project

Funded by the United States Agency for International Development (USAID)

Module Overview
Case Finding Steps in Diagnosing TB
Medical History Bacteriologic Examination Drug Susceptibility Testing Radiographic Exam Sputum smear-negative patient
International Standards 1, 2, 3, 4, and 5

Learning Objectives
At the end of this presentation, participants will be able to:
List the steps involved in diagnosing tuberculosis Describe the role of sputum smear microscopy in the diagnosis of tuberculosis Recognize the role of culture and drug sensitivity testing in the diagnosis and management of tuberculosis

Case Finding
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 tuberculosis.

THINK TB

Question

Opportunities for Case Finding

TB Chest Clinics Hospitals (Public) Public Health Clinics Drug Rehab Centres HIV Care facilities Private medical clinics

Voluntary Counselling Occupational Health and Testing (VCT) facilities clinics Long term care Prevention of Mother facilities and shelters to Child Transmission (PMTCT) clinics Correctional facilities (prisons, jails)

Steps in Diagnosing TB
Medical History Bacteriologic examination Drug Susceptibility Testing Radiographic exam Other examinations based on site(s)/location(s) involved

Medical History
Known exposure to a person with infectious pulmonary TB Symptoms of TB disease and approximate date symptoms started

Previous treatment for latent TB infection or active TB disease Other medical conditions that might affect treatment approach

Question

Standard 1: Prolonged Cough

All persons with an unexplained productive cough lasting two or more weeks should be evaluated for tuberculosis

International Standards for Tuberculosis Care, 2006

Prolonged Cough
Think TB: Prolonged Cough (2 or more weeks)
Cough may not be specific for TB, however, long duration raises the likelihood of TB diagnosis Is criterion for suspecting TB in most national and international guidelines The likelihood of AFB smear-positive sputum increases with increasing duration of cough Will not catch all TB cases; use best clinical

judgment

Classic TB Clinical Presentation

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

Nonspecific constitutional symptoms

Extrapulmonary symptoms (if involved)

Typical Systemic Symptoms

Fever in 65-80% of cases Night sweats Fatigue/malaise Anorexia/weight loss

10-20% of TB cases have no

symptoms at the time of diagnosis

Clinical Presentation
Physical Examination (PE):
May be normal in mildmoderate disease Lungs: 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 PE is most useful when assessing for

non-pulmonary sites of TB

Bacteriologic Examination

Standard 2: Sputum Microscopy

All patients suspected of having pulmonary TB who can produce sputum should have at least two sputum specimens obtained for microscopic examination. When possible, at least one early morning specimen should be obtained.
International Standards for Tuberculosis Care, 2006

Sputum Microscopy
To confirm 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

Performance of Sputum Microscopy

Specimen Number 1 2 Incremental Yield (of all smear positive) 85.8% 11.9% Incremental Sensitivity (of all culture positive) 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

Culture and Drug Susceptibility Testing

Obtaining culture and drug susceptibility testing (DST) offers significant advantages in the diagnosis and management of TB: Increases case detection Earlier diagnosis Identification of drug resistance

Culture: Advantages
Higher sensitivity than smear microscopy (culture can make diagnosis despite fewer bacilli in specimen) If TB disease is suspected and sputum smears are negative, culture may provide diagnosis Allows for identification of mycobacterial species Allows for drug susceptibility testing

Culture: Disadvantages
Cost Technical complexity May take weeks to get results Requires ongoing quality assurance

Therefore, culture testing is more likely to be found in major referral centers. Avoid delaying appropriate TB treatment in suspicious cases while awaiting results.

Case 1
A 32 year old man presents to the clinic with complaint of cough x 1 month. He is not severely ill and can be evaluated in an ambulatory setting

What other history do you ask him about? What other signs will you look for during your examination to aide in diagnosis?

Case 1 (2)
Patient gives further history of feeling poorly for several months now; reports weight loss (about 3-4kg) and cough has gotten progressively worse. Patient denies smoking. His brother was treated for tuberculosis last year. Patient was not evaluated for TB at that time. What laboratory tests would do you order?

Case 1 (3)
Among the results you receive, one of three sputum smears is positive for acid fast bacilli (AFB) on direct microscopy.

What would you do next?

Case 1 Summary
Collect additional 3 sputa for AFB smear and culture Obtain chest X-ray If chest X-ray result consistent with tuberculosis, treatment for TB should be initiated without delay Might also consider adding broadspectrum antibiotic (non-fluoroquinolone)

Standard 3: Extrapulmonary Specimens

For all patients suspected of having extrapulmonary TB, appropriate specimens from the suspected sites of involvement should be obtained for microscopy. Where facilities and resources are available, specimen should also be sent for culture and histopathological examination.
International Standards for Tuberculosis Care, 2006

Clinical Presentation: Extrapulmonary

Incidence/site may vary TB can involve any organ More common in HIV/TB (co-infection)
Both, 9%

Lymphatic, 42% Extrapulmonary, 21%

Pleural, 18%

Pulmonary, 70%
Bone/joint, 11%
TB Cases by Form of Disease, United States, CDC, 2005

Other, 12% Genitourinary, 5% Meningeal, 6%

Peritoneal, 6%

Extrapulmonary Tuberculosis

Radiographic Examination

Standard 4: Evaluation of Abnormal CXR

All persons with chest radiographic findings suggestive of tuberculosis should have sputum specimens submitted for microbiological examination.
International Standards for Tuberculosis Care, 2006

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 162 culture-positive cases of TB

20% 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

Chest Radiography
Purpose:
Provides additional evidence to aide in diagnosis of TB disease when only 1 sputum smear is positive Check for lung abnormalities in people who have symptoms of TB; especially in those with HIV coinfection Evaluate and rule out TB disease in persons with a newly positive tuberculin skin test (Mantoux)

Chest X-ray alone cannot confirm TB disease

Chest Radiography (2)

Chest X-ray findings suggestive of active PTB disease include:
Acute upper lobe pneumonia Unresolving pneumonia

Cavitation, cavitary lesion

Pleurisy, pleural effusion Lung infiltrate, especially in upper lung zones Hilar node enlargement or adenopathy

International Standards for Tuberculosis Care, 2006

Chest Radiography (3)

Chest X-ray findings suggestive of previous or presumed inactive PTB include:
Apical fibrosis Upper lobe fibronodular abnormality

Pleural calcification
Upper lung zone bronchiectasis Thoracoplasty or partial pneumonectomy Healed primary lesion (Ghon focus/complex)

Can this be TB?

Can this be TB? Miliary TB

Can this be TB?

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

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

Sputum Smear-Negative Patient

Criteria for diagnosis:
At least 3 negative sputum smears Cultures must be attempted Chest X-ray consistent with TB

Lack of response to broad-spectrum (non-fluoroquinolone) antibiotic

Standard 5: Smear-negative Diagnosis

The diagnosis of sputum smear-negative PTB should be based on the following criteria:
At least three negative sputum smears (including at least one early morning specimen) Chest radiography findings consistent with TB

Lack of response to a trial of broad-spectrum antimicrobial agents (avoid use of fluoroquinolone)

For such patients, if facilities for culture are available, sputum cultures should be obtained. In persons with known or suspected HIV infection, the diagnostic evaluation should be expedited.
International Standards for Tuberculosis Care, 2006

TB Diagnostic Algorithm: HIV Negative or Low Prevalence Area

All Pulmonary TB Suspects
Sputum AFB Microscopy Assess for HIV
2 or 3 smears + Only 1 smear +
No Rx: Non-anti TB antibiotics Improvement?

2 or 3 smears -

Repeat AFB Order culture 1 or more smear + All smears CXR & medical officers judgment

Yes

Yes TB*

Yes TB*

No TB

TB Diagnostic Algorithm: High HIV Prevalence

Ambulatory TB Suspects
AFB smears/culture, HIV test HIV positive or ? AFB Positive*
Treat for TB; CPT HIV care if positive

AFB Negative * TB likely

AFB smears/culture, CXR, TST, clinical evaluation

TB not likely
Reassess for TB

No or poor response

Treat for bacterial infection and/or PCP HIV care if positive; CPT Reassess if symptoms recur

CPT = cotrimoxazole prophylaxis

Response

Clinical Presentation and Diagnosis of TB

Remember:
Symptoms/severity (can be)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

Can this be TB?

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

Clinical Presentation and Diagnosis of TB

Summary:
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

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 2-3 sputum specimens obtained for microscopic examination (at least one early morning specimen if possible). Standard 3: Specimens from suspected extrapulmonary TB sites should be obtained for microscopy, and if possible, for culture and histopathological exam.
* Abbreviated versions

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; and lack of response to broad-spectrum antibiotics (avoid fluoroquinolones). Obtain cultures as available.

Think TB

* Abbreviated versions

Additional Cases

Can this be TB?

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 (think M. avium complex or other disease)

Reactivation/Post-primary TB
Patterns of disease
Air-space consolidation Cavitation, cavitary nodule Endobronchial spread Miliary Bronchostenosis Tuberculoma Pleural effusions

Can this be TB?

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