Diagnosis Of Pulmonary Tuberculosis In Adults

3.1 DIAGNOSTIC APPROACH

The highest priority for TB control is the identification and cure of infectious cases, i.e. patients with sputum smear-positive PTB.Therefore all patients (regardless of HIV status) with clinical features suggestive of PTB must submit sputum for diagnostic sputum smear microscopy. Most TB suspects (people with symptoms or signs suggestive of TB) are ambulatory. The diagnosis of PTB is therefore usually done on an outpatient basis. Some TB suspects are severely ill and/or bed-bound and therefore need investigation as inpatients.

Clinical screening by assessment of symptoms identifies PTB suspects among patients attending health facilities. The most cost-effective method of detecting TB cases among PTB suspects in high-prevalence countries is by sputum smear microscopy.A suspect who has a positive sputum smear has sputum smear-positive PTB. The district TB officer (DTO) registers the TB patient, and treatment is started. In most cases of smear-positive PTB, a chest X-ray is unnecessary.

Sometimes a patient may be negative on sputum smear microscopy but may not improve on a broad-spectrum antibiotic. If you still suspect TB, reassess the patient and do a CXR. If the CXR is typical of PTB, register the patient with the DTO and start TB treatment. If doubtful about the CXR diagnosis of TB, e.g. if the CXR shows nonspecific pulmonary infiltrates, give the patient another course of antibiotics. If there is no clinical improvement, or if the cough disappears only to return shortly afterwards, repeat sputum smear microscopy. If you still think the patient may have TB despite, further negative sputum smears, again reassess the patient and repeat the CXR.Then decide whether the diagnosis is TB or not. In cases where diagnostic doubt persists, sputum culture may be useful if suitable facilities are available.

In populations with a high TB prevalence, the tuberculin skin test is of little value in the diagnosis of TB in adults.A positive tuberculin skin test does not by itself distinguish M. tuberculosis infection from TB disease. Previous exposure to environmental mycobacteria may also result in a false-positive test result. Conversely, the tuberculin skin test result may be negative, even when the patient has TB. Conditions often associated with a false-negative tuberculin skin test include HIV infection, severe malnutrition and miliary TB.

CLINICAL FEATURES

Symptoms

The most important symptoms in the diagnosis of PTB are the following: ° cough for more than 2 or 3 weeks; ° sputum production; ° weight loss.

Over 90% of patients with sputum smear-positive PTB develop a cough soon after disease onset. However, cough is not specific to PTB. Cough is common in smokers and in patients with acute upper or lower respiratory tract infection. Most acute respiratory infections resolve within 3 weeks.Therefore a patient with a cough for more than 2 or 3 weeks is a PTB suspect and must submit sputum samples for diagnostic microscopy.

Patients with PTB may also have other symptoms. These may be respiratory or constitutional (general or systemic). Respiratory: chest pain, haemoptysis, breathlessness. Constitutional: fever, night sweats, tiredness, loss of appetite, secondary amenorrhoea.

Weight loss and fever are more common in HIV-positive PTB patients than in those who are HIV-negative. Conversely, cough and haemoptysis are less common in HIV-positive PTB patients than in those who are HIV-negative. This is probably because there is less cavitation, inflammation and endobronchial irritation in HIV-positive patients.

Physical signs

The physical signs in patients with PTB are nonspecific.They do not help to distinguish PTB from other chest diseases.There may be general signs, such as fever, tachycardia (fast pulse rate) and finger clubbing. Chest signs (heard through a stethoscope) may include crackles, wheezes, bronchial breathing and amphoric breathing.There are often no abnormal signs in the chest.

I PRACTICAL POINT I

All PTB suspects must provide sputum samples for smear microscopy for TB case-detection.

3.3 DIAGNOSTIC SPUTUM SMEAR MICROSCOPY

Collection of sputum samples

A PTB suspect should submit three sputum samples for microscopy.The chances of finding TB bacilli are greater with three samples than with two samples or one sample. Secretions build up in the airways overnight. So an early morning sputum sample is more likely to contain TB bacilli than one taken later in the day. It may be difficult for an outpatient to provide three early morning sputum samples. Therefore in practice an out-patient usually provides sputum samples as follows:

day 1 sample 1 Patient provides an "on-the-spot" sample under supervision when presenting to the health facility. Give the patient a sputum container to take home for an early morning sample the following morning.

day 2 sample 2 Patient brings an early morning sample.

sample 3 Patient provides another "on-the-spot" sample under supervision.

Some patients cannot produce a sputum sample. A nurse or physiotherapist may help them to give a good cough and bring up some sputum. Inpatients can follow the same method as outpatients.

Terminology

Mycobacteria are "acid- and alcohol-fast bacilli" (AAFB), often shortened to "acid-fast bacilli" (AFB). The waxy coat of mycobacteria retains an aniline dye (e.g. carbol fuchsin) even after decolorization with acid and alcohol.

Ziehl-Neelsen (Z-N) stain

This simple stain detects AFB.This is how to perform the Z-N stain: ° Fix the smear on the slide.

° Cover the fixed smear with carbol fuchsin for 3 minutes. ° Heat, rinse with tapwater, and decolorize with acid-

alcohol for 3-5 seconds. ° Counterstain with methylene blue for 30 seconds. ° Rinse again with tapwater.

° Observe under the microscope (use the xI00 oil immersion lens and xI0 eyepiece lens). The bacilli appear as red, beaded rods, 2-4 ^m long and 0.2-0.5 ^m wide.

Fluorochrome stain

Use of this stain to detect TB bacilli requires a special fluorescence microscope. The fluorochrome stain is phenolic auramine or auraminerhodamine. After acid-alcohol decolorization and a methylene blue counterstain, the bacilli fluoresce bright yellow against a dark background.The advantage of this method is that smears can be scanned quickly under low magnification. It is important to check fluorochrome stain-positive smears using the Z-N stain.

Slide reporting

The number of bacilli seen in a smear reflects disease severity and patient infectivity. Therefore it is important to record the number of bacilli seen on each smear.The table below shows the standard method of reporting using 1000 x magnification.

Number of bacilli

Result reported

Number of bacilli

Result reported

no

AFB

per

100 oil immersion fields

0

1-9

AFB

per

100 oil immersion fields

scanty (or number AFB seen)

10-99

AFB

per

100 oil immersion fields

+ (1+)

1-10

AFB

per

oil immersion field

++ (2+)

> 10

AFB

per

oil immersion field

+++ (3+)

Laboratory technicians should examine all three sputum samples from each TB suspect. They must record the result of each sputum sample with the laboratory reference number in the laboratory register and on the sputum request form. Results as indicated above are made available to the clinician who can then categorize the patient. Categorizing patients as smear-positive or negative requires results from more than one smear. A guide to classification of patients with pulmonary symptoms is given below.

Smear-positive

Indeterminate

Smear negative

At least 2 smears examined and both positive, i.e. reported 1-9 per 100 fields (scanty) or greater

Several possibilities, e.g. ° only one smear examined

(whatever the grading) ° 3 smears examined but only one reported positive In either of these situations, either further sputum smears or a CXR are required before a patient can be classified.

At least two smears reported 0 (negative)

Sensitivity of sputum smear microscopy

Sputum smear microscopy for tubercle bacilli is positive when there are at least 10000 organisms present per ml of sputum.

Sputum microscopy in HIV infection

Sputum smear positivity rates in TB/HIV patients depend on the degree of immunocompromise, as shown below.

Degree of Likelihood of positive sputum smear immunocompromise mild similar to HIV-negative patient severe decreased(decreased inflammation in lungs)

False-positive results of sputum smear microscopy

A false-positive result means that the sputum smear result is positive even though the patient does not really have sputum smear-positive PTB. This may arise because of the following: red stain retained by scratches on the slide; accidental transfer of AFBs from a positive slide to a negative one; contamination of the slide or smear by environmental mycobacteria; presence of various particles that are acid-fast (e.g. food particles, precipitates, other microorganisms).

False-negative results of sputum smear microscopy

A false-negative result means that the sputum smear result is negative even though the patient really does have sputum smear-positive PTB. This may arise because of problems in collecting, processing, or interpreting sputum smears, or because of administrative errors.

A sputum smear result may be unexpectedly negative (e.g. in a patient with upper lobe cavities on CXR).Think of the possibility of a false-negative result and repeat the sputum microscopy.

Causes of false negative results of sputum smear microscopy Type of problem Example

sputum collection

patient provides inadequate sample inappropriate sputum container used sputum stored too long before smear microscopy

sputum processing

faulty sampling of sputum for smear faulty smear preparation and staining

sputum smear inadequate time spent examining smear interpretation inadequate attention to smear (poor motivation)

sputum smear inadequate time spent examining smear interpretation inadequate attention to smear (poor motivation)

administrative errors misidentification of patient incorrect labelling of sample mistakes in documentation

T^H DIFFERENTIAL DIAGNOSIS OF PULMONARY TB ^^■"PRACTICAL POTNT^^^^^^^^^^^^^^^H

A PTB suspect with 3 negative sputum smears may not have PTB. Reassess the patient for conditions that may be mistaken for PTB.

The table shows possible alternative diagnoses.

Diagnosis

Pointers to the correct diagnosis

bronchiectasis

coughing large amounts of purulent sputum

bronchial carcinoma (lung cancer)

risk factor (smoking, older age, previous mine-work)

other infections, e.g. bacterial pneumonia lung abscess Pneumocystis carinii

usually shorter history, febrile, response to antibiotic cough with large amounts of purulent sputum abscess with fluid level on CXR often dry, non-productive cough with prominent dyspnoea

congestive cardiac failure left ventricular failure

symptoms of heart failure

(dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea, haemoptysis, oedema, epigastric discomfort from hepatic congestion)

signs of heart failure

asthma

intermittent symptoms, generalized expiratory wheeze;

symptoms wake the patient at night

chronic obstructive airways disease

risk factor (smoking), chronic symptoms, prominent dyspnoea, generalized wheeze, signs of right heart failure (e.g. ankle oedema)

PRACTICAL POINT

If the patient is breathless, has continuing haemoptysis, and has negative sputum smears, listen carefully for a low-pitched, rumbling, mid-diastolic murmur, indicating mitral stenosis with pulmonary oedema.

3.5 CHEST X-RAY IN DIAGNOSIS

Indications for CXR Positive sputum smear

The first screening test for PTB suspects is sputum smear microscopy. In most cases of sputum smear-positive PTB a CXR is not necessary. In a few cases, a CXR may be necessary; the indications are as follows:

(a) suspected complications in a breathless patient, needing specific treatment, e.g. pneumothorax, pericardial effusion or pleural effusion (note that a positive sputum smear is rare in pericardial effusion and pleural effusion);

(b) frequent or severe haemoptysis (to exclude bronchiectasis or aspergilloma);

(c) only l sputum smear positive out of 3 (in this case, an abnormal CXR is a necessary additional criterion for the diagnosis of sputum smear-positive PTB).

Negative sputum smear

Reassess patients who continue to cough despite a course of broad-spectrum antibiotic, and who have had at least two (and preferably three) negative sputum smears. If you still suspect TB despite negative sputum smears, the patient needs a CXR.

RADIOGRAPHIC ABNORMALITIES SEEN IN PULMONARY TB

I PRACTICAL POINT I

No CXR pattern is absolutely typical of PTB, especially with underlying HIV infection.

The table below shows so-called "classical" and "atypical" CXR patterns. The classical pattern is more common in HIV-negative patients, and the atypical pattern in HIV-positive patients.

classical pattern

atypical pattern

upper lobe infiltrates

interstitial infiltrates (especially lower zones)

bilateral infiltrates

cavitation

intrathoracic lymphadenopathy

pulmonary fibrosis and shrinkage

no cavitation

no abnormalities

CXR changes in TB/HIV patients reflect the degree of immunocompromise. In mild immunocompromise, the appearance is often classical (with cavitation and upper lobe infiltrates). In severe immunocompromise, the appearance is often atypical.

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