Tuberculosis is a chronic respiratory tract disease established by Mycobacterium tuberculosis complex infection and represented clinically as primary,

Tuberculosis

• Tuberculosis is a chronic respiratory tract disease established by Mycobacterium tuberculosis complex infection and represented clinically as primary, secondary disease, or latency.

• Mycobacterium tuberculosis complex: M. tuberculosis, M. bovis, and M. africanum.

Mycobacterium tuberculosis • was identified and described on 24 March

1882 by a German physician Robert Koch.

• Morphology: slightly curved to straight bacillus.

• Obligate aerobic, acid fast, non motile, non spore forming bacilli.

• Contains mycolic acid in their cell wall.

• Slow grower: duplication time ~24 hours

WHO (2012) ≈ 9 million people developed TB. 1.3 million died from the disease (including

320 000 deaths (25%) among HIV-positive people).

25% to 33% of the world’s population with silent latent infection with M. tuberculosis.

Prevalence in Saudi Arabia in 2012 ≈ 4900 case and 1100 deaths.

WHO report for incidence of T.B in 2011: N

Transmission of Mycobacterium species:

Mycobacterium tuberculosis:o Reservoir: Human.o T.B spread from person to person through

the air by droplet nuclei (0.5-5µm in diameter) which can be produced by coughing , sneezing, or to a lesser extent speaking or singing.

o Droplet nuclei may remain suspended in the air for long time;(isolation rooms in hospitals).

M. bovis Reservoir: Cattle & related animals. Transmission: oEating or drinking contaminated,

unpasteurized dairy products. oDirect contact and inhaling of aerosol

droplets from infected animals. Infected cattle must be culled. Symptoms of TB disease caused by M.

bovis are similar to those of M. tuberculosis.

Risk factors for rapid spreading of Mycobacterium tuberculosis:

• Crowded living conditions.

• HIV infection.

• Excess alcohol.

• Traveling to area with high prevalence rate.

Pathogenesis:o Do not produce exotoxins or endotoxin.o Tubercle bacilli are able to survive inside

the macrophages (chronic granulomatous inflammation).

o Tissue damage is induced by the host immune response.

o Clinical presentations are divided to:• Primary infection.• Latent infection.• Secondary infection

Primary infection: In the middle lung zones; where airflow is

greatest. Inhaled bacilli are engulfed by alveolar

macrophage where they continue to multiply leading to rupture of macrophage, reals of bacilli and infection of other macrophage (active primary T.B).

Infected macrophages are carried by lymphatics to regional tracheobronchial lymph nodes:

› Activation of lymphocytes (TH1: cell mediated immune response).

› Enlargement of lymph nodes.

›Ghon’s Complex: inflammation of infected lung area associated with enlarged lymph nodes.

Outcome of Primary Infection:

• In 90% of cases, (children ˃ 5 years old, teens and adults): strong immunity: delayed type hypersensitivity: latent dormant tuberculosis with granuloma formation.

• In 10 % of cases (infants and children younger than 5 years old, elderly persons and HIV patients): weak immunity: little or no hypersensitivity immune reaction:

• progressive primary tuberculosis.

• lympho-hematogenous dissemination (meninges, bone, apices of lungs, kidneys……

A Person with Latent TB Inf.

A Person with active TB

Has no symptoms •Has symptoms that may include:o Chronic cough that lasts ˃ 3

weeks o weight losso pain in the chesto coughing up blood or

sputumo weakness & fatigueo bad appetiteo Fever & chillso sweating at night

Cannot spread infection to others

May spread infection to others

Usually positive skin test or blood test

Usually positive skin test or blood test.

Has a normal chest x-ray and a negative sputum smear

May have an abnormal chest x-ray and positive sputum smear or culture

Needs treatment for latent TB infection to prevent TB disease

Needs treatment to treat TB disease

n

Secondary Tuberculosis (Endogenous Reactivation)• It occurs within 2 years after the initial infection but

can occur any time there after due to impairment of cellular immunity.

• Major causes of depression of cellular immunity: immunosuppressive drugs: corticosteroids, malignancy, HIV (the most important cause).

• Most common site of reactivation is the lung apex; granulomatous lesions become necrotic (caseous necrosis), enlarge, liquefy, rupture and discharge their content into bronchi creating well aerated cavity:• Microbial proliferation.• Distribution within the lung (tuberculous pneumonia).• Coughing up bloody sputum

N

End result of primary tuberculosis:

Primary Tuberculosis90% Latent

dormant tuberculosis

Living bacteria &granuloma

25% arrested granuloma

Fibrosis or calcification.Enlarged tracheobronchial lymph nodes .

3% Breaks down

granuloma

-Caseous material discharged; necrosis-Cavity creation.

Tuberculous pneumonia

Lympho-Hemo

Apical lung cavities Meningitis

Osteomyelitis

10% Progressive active infection

AIDS, old, children

95 % No disease

75%

Living- bacteria, granuloma

90%

10%

Other Body Parts which Can be Affected by Tuberculosis

In cervical LN: scrofula

Pott’s disease

HIV and Tuberculosis:• HIV infection inhibit cellular immunity.• Patients with HIV infection can be infected by

MTC (Mycobacterium tuberculosis complex), or MOTT (Mycobacterium other than tuberculosis). MOTT: M. avium, M. intracellulare, and M. kansasii.

• Tuberculosis is an AIDS defining condition. It is the leading cause of death among adults living with HIV/AIDS.

• The WHO recommends TB screening at HIV infection is diagnosed and during follow up.

Diagnosis Chest X-ray. Mantoux skin test (Tuberculin). Microscopy: acid-fast bacilli by Ziehl –

Neelsen (ZN) stain, or by fluorescent microscope.

Culture: Isolation of mycobacterium species.• Löwenstein–Jensen medium (L.J medium)

PCR: Highly sensitive. Detection of mycobacterial genetic material and to determine antibiotic susceptibility.

Chest X-ray

Cavitation in the right lung and fibrosis in the left.

Tuberculin skin tests (Mantoux test):o Delayed type hypersensitivity (DTH)o Purified protein derivative (PPD) injected

intradermally. o Results: Induration is measured after 48-

72 hours (DTH).• Negative < 5 mm• Intermediate reaction 5-9 mm.• Positive reaction ˃ 9mm.

N

N

Microscopy:Clinical specimens: Sputum, transtracheal aspiration, bronchoalveolar lavage. ZN stain: Mycobacteria are acid fast bacilli: resist decolorization with acid (2% H2SO4 or 3% HCl ) and alcohol due to the waxy capsule.

M. Tuberculosis appear as thin pink rods in ZN stain

Culture and colony morphology

o Cultured for primary isolation & antibiotic susceptibility.

o Strict aerobic grows slowly (2-4 weeks).o Optimum temperature growth is 37 Cᴼ.o Egg enriched medium: LJ medium, giving

dry creamy colored colonies.o The growth is enhanced by adding

pyruvate and glycerol to the media.o M. tuberculosis are niacin producers.

TB Culture

Cultivation and culture characteristics of tubercle bacilli on LJ medium (dry cream colored colonies)

N

Difference between M. tuberculosis and MOTT :(M. avium, M. intracellulare, and M. kansasii).

• M. tuberculosis is a non chromogenic bacteria.

• Does not grow on media contain p-nitrobenzoic acid.

N

Antibiotics sensitivity test:-Other selective media as Middle-brook are used for primary isolation and for antibiotic susceptibility test.

n

Treatment of T.B:• Extensive time periods (6-9 months).• Direct observation treatment (DOT). • Combined multidrug treatment to reduce anti

tuberculous resistance.• First line Anti-T.B drugs: Isoniazid (INH),

rifampin (RIF), pyrazinamide (PZA), and ethambutol.

• Phases of Treatment:

-Initial phase: The four drugs for 2 months.

-Continuation phase: INH and RIF for four or seven months.

N

Vaccination:

Bacillus Calmette – Guérin (BCG) vaccine:• Live attenuated low virulent M. bovis

strain.• Effective in protection of children from

serious forms of disease such as meningitis.• Not so effective to protect adults.

Direct Observation Treatment