Chapter 1

INRODUCTION

1.1 Background

Pulmonary tuberculosis (TB) is caused by the bacteria Mycobacterium tuberculosis (M. tuberculosis). You can get TB by breathing in air droplets from a cough or sneeze of an infected person. This is called primary TB.

In the United States, most people will recover from primary TB infection without further evidence of the disease. The infection may stay asleep or non-active (dormant) for years. However, in some people it can reactivate.

Most people who develop symptoms of a TB infection first became infected in the past. However, in some cases, the disease may become active within weeks after the primary infection.

1.2. Definition

Tuberculosis (TB) is a chronic bacterial infection that primarily affects the lung, although it may involve any part of the body.

1.3. Epidemiology

Currently estimated about half of the world's population (3.1 billion) is infected with Mycobacterium tuberculosis

Estimated from the year 2000 to 2020, nearly one billion people will be newly infected, 200 million people will get sick, and 35 million will die from TB - if control is not further strengthened.

1.4. Etiology

Primarily, Pulmonary Tuberculosis is caused by Mycobacterium Tuberculosis. Mycobacterium Tuberculosis shape is long, slender, straight or curved rods. It is an aerobic which usually colonizes on high oxygen area part of human body and that is apex of the lung. It is decolorized by acid or alcohol which was then called by the name of “acid fast bacilli”. Incubation period for the organism 4-6 weeks after initial contact.

1.5. Transmission

Optimal conditions for transmission include the overcrowding of places, poor personal hygiene, poor public hygiene. People with active disease (bacilli) expel them into the air by coughing, sneezing, shouting, singing or any other way that will expel bacilli into the air.

Direct invasion through mucous membranes or breaks in the skin may occur, but extremely rare. It can also be transmit via ingestion theoretically if the milk of the infected animal is ingested but rarely occur.

1.6. Clinical Categories

Primary TB Post primary TB (Secondary/reinfection TB)

Disseminated TB (extrapulmonary TB)

Milliary TB

1.7. Primary Tuberculosis

1st infection in a person without specific immunity to TB and is called “childhood TB”. The initial focus of infection is a small subpleural granuloma accompanied by granulomatous hilar lymph node infection. Together, these make up the Ghon complex.

In nearly all cases, these granulomas (fibrocalcific nodules) resolve and there is no further spread of the infection. The patient will heal and a scar will appear in the infected loci. There will also be a few viable bacilli/spores may remain in these areas (particularly in the lung). The bacteria at this time goes into a dormant state, as long as the person's immune system remains active and functions normally.

1.8. Secondary Tuberculosis

Result from reactivation of primary infection or re- infection. Seen mostly in adults, particularly when health status declines or immunocompromise person. Spreads by lymphatics and delayed hypersensitivity reaction occurs.

The granulomatous inflammation is much more florid and widespread. Lesions are often bilateral and usually cavitated and most connected to fibrocalcific scars. Typically, the upper lung lobes (posterior/apical segment) are most affected.

1.9. Miliary Tuberculosis

Acute diffuse dissemination of tubercle bacilli occurs through the bloodstream. Numerous small granulomas (contain mycobacteria) form in many organs, with the highest number found in the lungs. Usually it is from the result of a delay in diagnosis or commencement of treatment. Result from the consequence of either primary or secondary TB and universally fatal without treatment.

1.10. Signs and Symptoms

Main symptoms:

Prolonged cough (non-productive/productive ) >> 3 weeks Hemoptysis

Chest pain

Additional symptoms:

Fever Malaise

Chills

Night Sweats

Loss of appetite

Loss of weight

Easy fatigability

1.11. Diagnosis

A working diagnosis can be made by:

Medical history Physical examination

Chest radiograph

Tuberculin test / Mantoux Test

Bacteriologic exam

AFS

Culture (Gold Standard)

PCR

Bronchoscopy is useful if no sputum is available.

Biopsy from pleura, lymph nodes and solid lesions within lung may be necessary.

1.11.1. Tuberculin Test or Mantoux Test

It is used as a diagnostic tool for tuberculosis. Used to detect latent Tuberculosis infection, to detect recent infection (as shown by conversion of the Mantoux from negative to positive) and as part of the diagnosis of Tuberculosis disease.  Not recommended for those who had a past Mantoux reaction of 15 mm or greater or in people who have had previous Tuberculosis disease.

1.11.2. Chest X-Ray

Classical radiograph appearance Infiltration, cavitation, fibrosis with traction, enlargement of hilar and mediastinal lymph node.

In reactivation of TB Classically fibrocavitary apical disease

Primary TB Middle or lower lobe consolidation

But no chest X-ray pattern is absolutely typical of TB. At about 10-15% of culture-positive TB patients is not diagnosed by X-ray. And 40% of patients diagnosed as having TB on the basis of x-ray alone do not have active TB.

1.11.3. Acid Fast Bacilli/Stain (AFS/AFB)

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.

The result is:

Not specific for M. Tuberculosis Sensitivity: 40-70%

Specificity: 90%

1.11.4. Culture

It is gold standard for TB diagnosis which is use to confirm diagnosis of TB.Culture all specimens, even if smear is negative. Results in 4 to 14 days when liquid medium systems used.

Sensitivity: 80-85% Specificity: 98%

Times needed:

Solid medium 4-8 wks

Liquid medium 2 wks

1.12. Differential Diagnosis

Lung Cancer Lung metastasis

Bronchiecstasis

Pneumonia

Solitary pulmonary nodule

1.13. Prevention

BCG vaccination 0.1ml intradermal dose

Decrease the risk of developing TB up to 70%

Once vaccinated subsequent Tuberculin test will be (+ve)

Contact tracing

Tracing of close cantacts to limit spread of the disease as well to identify at an early stage

1.14. Treatment

1st line Drugs

Isoniazid (H)

Rifampicin (R)

Pyrazinamide (Z)

Ethambutol (E)

Streptomycin (S)

2nd line Drugs

Cycloserine

P-aminosalicylic acid

Ethionamide

Amikacin/Kanamycin

Capreaomycin

Levofloxacin

Moxifloxacin

Gatifloxacin

Treatment Regime:

Divided into :i. Initial or extensive phase

○ At least 2 months

ii. Continuation or maintenance phase

○ At least 4 months

Intensive Phase:

2 months of daily doses 2 SHRZ @ 2 EHRZ @ 2HRZ

H 5mg/kg/day (max 300mg daily)

R 10mg/kg/day (max 600mg daily)

S 15mg/kg/day (max 1000mg daily)

E 15-25mg/kg/day (max 1200mg daily)

Z 25mg/kg/day (max 2000mg daily)

Don’t give/limit S and E for babies, young child, elderly and severe renal impairment.

Continuation Phase:

S, H and R All 15mg/kg biweekly (2/52)

S and H max 1000mg/kg

R max 600mg/kg