Tuberculosis

Anatomy of the lungs
Causes of Productive Cough
1. Based on sputum color
Lower Respiratory Tract Infections
1. Acute bronchitis
  1. adenovirus, coronavirus, parainfluenza, influenza and rhinovirus
    1. Only few cases are caused by bacterial infection
  2. is self-limiting infection
  3. It manifests as cough that sometimes could come with sputum, wheezing, fever and shortness of breath
2. Bronchiolitis
  1. self-limiting infection
  2. Respiratory syncytial virus
  3. Usually it infects children
  4. It manifests as cough, fever, runny nose, wheezing and crackles.
3. Influenza
  1. RNA virus
  2. 3 types
    1. Type A
      1. is the most common type of influenza virus
      2. infect both humans and animals
    2. Type B
      1. infect humans only
    3. Type C
      1. infect both human and pigs.
  3. Symptoms of influenza infection start 1 to 4 days after infection and it include fever, headache, runny nose, sore throat, myalgia, malaise and nonproductive cough.
4. Pneumonia
  1. Pneumonia manifests as dyspnea or shortness of breath, chest pain, productive cough ( bloody sputum or yellow green sputum), fatigue, fever, tachypnea, decreased breath sound and dullness to percussion.
  2. Caustive Agents
Classification of myobacterium
1. Non- cultivable
  1. M,leprea
2. Typical
  1. M. tuberculosis
  2. M, bovis
  3. M. africanum
3. Atypical
  1. Runyon Group I (Photochromogens)
    1. M. kansasii
    2. M. marinum
  2. Runyon Group II (Scotochromogens)
    1. M. szulgai
    2. M. xenopi
    3. M. scrofulaceum
  3. Runyon Group III (Nonchromogens)
    1. M. avium
    2. M. haemophilum
    3. M. ulcerans
  4. Runyon Group IV (Rapid Growers)
    1. M. abscessus
    2. M. chelonae
    3. M. fortuitum
Epidemiology of TB
1. infects 1/3 world population – 2 billion people
2. 95% cases are in developing world
3. 8 million new cases/yr
  1. 3 million deaths/yr
4. 80% of all TB cases occurs in Sub Sharan Africa and South East Asia
5. Globally, TB incidence is falling at about 2% per year. This needs to accelerate to a 4–5% annual decline to reach the 2020 milestones of the End TB Strategy.
6. An estimated 54 million lives were saved through TB diagnosis and treatment between 2000 and 2017.
Transmission
1. Touch
2. Ingestion
3. Airborne
Risk factors
1. Recently infected with TB
2. Those with medical conditions that weaken the immune system
  1. HIV infection (the virus that causes AIDS)\ Substance abuse\ Silicosis\ Diabetes mellitus\ Severe kidney disease\ Low body weight\ Organ transplants\ Head and neck cancer\ Medical treatments such as corticosteroids or organ transplant\ Specialized treatment for rheumatoid arthritis or Crohn’s disease
Signs and symptoms
2. Mechanism of Fever
  1. Pyrogen
    1. Macrophages and immune cells are activated
      1. IL-1, IL-6, IL-8, TNF-a, interferon gamma
        Laminae terminalis
        Pre-optic region
        Posterior hypothalamic region
        Activate phospholipase
        Induce the production of prostaglandins E2
        Prostaglandins E2 will change the temperature set point
        Body will try to increase body Tempreture by
        Peripheral vasoconstriction
        Norepinephirne increases thermogenesis in adipose tissue
        Shivering
Investigations of Tuberculosis
1. collection of a specimen
  1. Early morning sputum in case of pulmonary TB and it requires a minimum of two successive days sputum\ Bronchoalveolar lavage (BAL) \Gastric aspirate\ CSF \ Lymph node biopsy or aspirates\ Other tissue biopsies
2. Microscopy
  1. Ziehl Neelsen Staining / Acid Fast Staining
    1. Specificity of 98% / Low sensitivity < 50% /Qualitative and quantitative
  2. Fluorescent staining (Auramine-Rhodamine Fluorochrome)
    1. Rapid and more sensitive / Expensive / Dye toxicity.
3. Culture (The Gold Standard)
  1. Solid Media
    1. Agar based (Middlebrook 7H10) / Egg based (Löwenstein-Jensen medium)
    2. Culture is incubated at 35 C, 5-10% CO2 and in high humidity
    3. It takes 4-8 weeks / can be reported negative after 8 weeks.
    4. Rough, tough and buff colonies.
  2. Liquid Media
    1. BACTEC 460 / Mycobacteria Growth Indicator Tube (MGIT)
    2. Positive in 2-3 weeks / can be reported negative after 6 weeks
  3. Radiometric culture has faster results (3-4 days)
4. Molecular Methods
  1. PCR
  2. Molecular Line Probe Assays (LPA)
    1. It is a DNA-based diagnostic test that identifies multidrug-resistant TB (MDR TB).
  3. Xpert MTB/RIF Assays
    1. A new NAAT that quickly identifies possible multidrug-resistant TB (MDR TB) (Rifampicin resistance).
5. Tuberculin Test (Mantoux tuberculin skin test (TST))
  1. Delayed hypersensitivity reaction type 4.
  2. Injecting tuberculin intradermally, which contains purified protein derivative from mycobacteria tuberculosis (PPD tuberculin).
  3. Induration measured after 48-72 hours.
  4. It can be positive in case of active TB (disease), people with latent infections, and people who had received BCG vaccination.
6. Serology
  1. Interferon-Gamma Release Assays (IGRAs)
    1. Test that detects IFN-g that is released by WBC when mixed with antigens derived from M. tuberculosis.
    2. The results within 24 hours.
    3. BCG vaccination does not cause a false positive IGRA test result.
7. Investigations of TB Contacts
  1. Contacts with skin test reaction of an induration diameter of >5 mm or with any symptoms of TB disease should go for further examination and TB diagnostic tests, starting with a chest radiograph.
  2. Contacts with special vulnerability or susceptibility to TB disease should undergo for further examination and diagnostic testing regardless of whether they have a positive skin test result or are ill.
8. Evaluating Response to Treatment
  1. Clinical evaluation
    1. (Monthly / Adverse reactions to medications and to assess adherence)
  2. Bacteriological examination
    1. Positive cultures after 3 months of treatment: Reevaluated for drug-resistant disease and failure to adhere to the regimen
    2. Positive cultures after 4 months of therapy: Failure of the treatment and managed accordingly
  3. Chest radiograph
    1. Positive cultures at the diagnosis: Repeat chest radiograph after completing 2 months of therapy might be useful (not essential), while chest radiograph after completing the course of the therapy gives a baseline for comparison with any future films.
    2. Negative culture in the initial diagnosis: Chest radiograph is necessary after 2 months of treatment, and desirable at completion of treatment.
Tuberculosis (TB) Treatment & Management
1. Approach Considerations
  1. Isolate patients with possible (TB) in a private room with negative pressure\ Medical staff must wear high-efficiency disposable masks\ Continue isolation until sputum smears are negative for 3 consecutive determinations
2. Drug therapy
  2. Patients who are receiving pyrazinamide should undergo baseline and periodic serum uric acid assessments, and those who are receiving long-term ethambutol should undergo baseline and periodic visual acuity and red-green color perception testing (Ishihara test) for color blindness.
    1. After 2 months of therapy (for a fully susceptible isolate), pyrazinamide can be stopped. Isoniazid plus rifampin are continued as daily or intermittent therapy for 4 more months. If isolated isoniazid resistance is documented, discontinue isoniazid and continue treatment with rifampin, pyrazinamide, and ethambutol for the entire 6 months. Therapy must be extended if the patient has cavitary disease and remains culture-positive after 2 months of treatment.
Disease notification
Pathogenesis
2. Primary tuberculosis
  1. granuloma - macrophages, fibroblasts, lymphocytes, and neutrophils
  2. tubercles can become calcified – Ghon complex
  3. self-limiting
  4. Infants & very young have a high mortality from primary infections
3. Secondary Tuberculosis
  1. Tubercles can reactivate, proliferate, and cause additional infection and damage in the lung
  2. Re-infection from exogenous bacteria
  3. Reactivated disease occurs in areas with high oxygen tension and low lymphatic drainage such as the apices of the lungs
4. Disseminated tuberculosis
  1. bacilli can disseminate to the lymph nodes, kidneys, bones, genital tract, brain, etc
  2. prognosis is poor and the affected site suffers severe damage:
    1. renal necrosis and scarring damage to reproductive organs degeneration of spine meningitis
5. Latent TB
  1. Is a subclinical infection with tubercle bacilli without clinical, bacteriological or radiological signs of the disease
Monitoring
1. Patients diagnosed with active TB should undergo sputum analysis for Mycobacterium tuberculosis weekly until sputum conversion is documented. Monitoring for toxicity includes baseline and periodic liver enzymes, complete blood cell (CBC) count, and serum creatinine.
BCG vaccine
1. contains a live but very weakened form of a bacteria called Mycobacterium bovis
  1. prevention of severe forms of TB (tuberculous meningitis and miliary disease)
    1. Not given to immunocompromised people and pregnant
Complications
Prognosis
1. If treated > Excellent prognosis.
2. If not treated > mortality rate > 50%.
  1. Extreme ages\ Hodgkin lymphoma\ end-stage renal disease \ chronic lung disease\ malnutrition\ alcoholism
Airborne precautions
1. N95 Respirator
2. Powered Air-Purifying Respirator (PAPR)
3. Airborne Infection Isolation Room (AIIR)

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Tuberculosis

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