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.
WHO (2013) 9 million people developed TB in 2013, most of them are from South East Asia, India alone account for 24% of these cases. 1 million cases were HIV positive. 1.5 million died from the disease including deaths among HIV-positive people. 25% to 33% of the world’s population live with silent latent M. tuberculosis infection. Prevalence in Saudi Arabia in 2012 ≈ 4900 case and 1100 deaths.
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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; resistant to dryness and phagocytosis. Slow grower: duplication time ~24 hours
Reservoir: Human. Transmission: 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. Droplet nuclei may remain suspended in the air for long time;(isolation rooms in hospitals). Droplet nuclei is ideal for bypassing the upper airways.
Pertussis, H. influenzae, influenza, Neisseria Meningitidis, Yersinia Pestis, Herpes Zoster, Measles, SARS, Tuberculosis
M. bovis Reservoir: Cattle & related animals. Transmission: o Eating or drinking contaminated, unpasteurized dairy products. o Direct contact and inhalation of aerosol droplets from infected animals. o From person to person through droplet nuclei 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 consuming. Traveling to countries with high prevalence rate.
Pathogenesis: o Do not produce exotoxins or endotoxin. o 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: Bacilli settle 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; granuloma formation) + Enlargement of lymph nodes (Ghon’s complex) › Lymphohematogenous spread: lymph nodes, vertebrae, kidneys, meninges and lung apices.
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 (little or no symptoms) 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……
Secondary Tuberculosis (Endogenous Reactivation) Occurs within 2 years of initial infection but can occur any time there after due to impairment of cellular immunity. Major causes of cellular immunity depression: malnutrition, 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 : Creation of well aerated cavity; microbial proliferation. Distribution within the lung (tuberculous pneumonia). Coughing of large numbers of bacteria. Coughing up bloody sputum.
10%90%
In cervical LN: scrofula Pott’s disease
A person with Latent TB Inf.A person with active TB Has no symptoms Has symptoms that may include: o Chronic cough lasts ˃ 3 weeks o weight loss o Fever & chills o sweating at night o coughing up blood or sputum o bad appetite o weakness & fatigue o pain in the chest 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 to prevent TB disease Needs treatment to treat TB disease n
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 diagnosis and during follow up.
Chest X-ray. Clinical specimens: Sputum, transtracheal aspiration, bronchoalveolar lavage. Mantoux skin test (Tuberculin). Microscopy: by Ziehl –Neelsen (ZN) stain, or by fluorescent microscope. Culture: Isolation & antibiotics sensitivity of mycobacterium species. 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 hours (DTH). Negative < 5 mm Intermediate reaction 5-9 mm. Positive reaction ˃ 9mm.
M. Tuberculosis appear as thin pink rods in ZN stain
o Cultured for primary isolation & antibiotic susceptibility. o Strict aerobic grows slowly (2-4 weeks). o Optimum temperature growth is 37 C. o Egg enriched medium: Löwenstein–Jensen medium (L.J) or Middle-brook medium. o The growth is enhanced by adding pyruvate and glycerol to the media. o M. tuberculosis are niacin producers.
TB Culture Culture characteristics of tubercle bacilli on LJ medium (dry, rough, cream colored colonies)
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.
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.
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.