Tuberculosis Overview and Pathogenesis
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Questions and Answers

What is the primary causative agent of tuberculosis?

  • Escherichia coli
  • Bacillus anthracis
  • Streptococcus pneumoniae
  • Mycobacterium tuberculosis (correct)

    • Tuberculosis can be transmitted through animals.

    False

    Name one common symptom of tuberculosis.

    productive prolonged cough

    The bacteria causing tuberculosis proliferate in ______.

    <p>macrophages</p> Signup and view all the answers

    What is the global incidence of tuberculosis?

    <p>Over 2 billion people infected</p> Signup and view all the answers

    Match the following transmission methods with their distances:

    <p>Normal breathing = 1 m Respiratory exhalation = 2 m Sneezing = 6 m</p> Signup and view all the answers

    What characteristic cell wall component is found in Mycobacterium tuberculosis?

    <p>mycolic acids</p> Signup and view all the answers

    The primary infection of tuberculosis is usually symptomatic.

    <p>False</p> Signup and view all the answers

    Which drug should not be given to children younger than 8 years old?

    <p>Ethambutol</p> Signup and view all the answers

    The risk of active TB infection is increased 100 times in individuals who are HIV positive.

    <p>True</p> Signup and view all the answers

    What is the maximum dose of isoniazid during Isoniazid Preventative Therapy (IPT)?

    <p>300 mg/day</p> Signup and view all the answers

    In the treatment of MDR-TB, ________ is administered during the continuation phase.

    <p>ethambutol</p> Signup and view all the answers

    Match the following drugs with their mechanisms of action:

    <p>Isoniazid = Inhibits mycolic acid synthesis Pyrazinamide = Sterilizing activity inside acidic intracellular compartments Streptomycin = Inhibits protein synthesis Rifampicin = Inhibits RNA synthesis</p> Signup and view all the answers

    What percentage of healthy individuals are likely to develop active tuberculosis (TB)?

    <p>10%</p> Signup and view all the answers

    Active tuberculosis can be infectious if it is only extrapulmonary.

    <p>False</p> Signup and view all the answers

    Name one classic symptom of active TB infection.

    <p>Chronic cough with or without blood-tinged sputum</p> Signup and view all the answers

    The mortality rate of active tuberculosis is approximately _____%.

    <p>50</p> Signup and view all the answers

    Match the following TB detection methods with their descriptions:

    <p>Chest X-ray = Identifies pulmonary inflammation Skin test = Tests for latent TB Sputum test = Microscopic examination for TB bacilli PCR = Detects drug resistance</p> Signup and view all the answers

    Which factor is NOT a risk factor for developing tuberculosis?

    <p>Regular exercise</p> Signup and view all the answers

    Latent tuberculosis means the bacilli are actively damaging body parts.

    <p>False</p> Signup and view all the answers

    What is the primary goal of tuberculosis treatment?

    <p>Cure the patient</p> Signup and view all the answers

    Pulmonary TB involves the _____ tissue.

    <p>lung</p> Signup and view all the answers

    Which statement is true regarding the treatment of TB?

    <p>Directly observed therapy (DOT) helps ensure treatment compliance.</p> Signup and view all the answers

    What is the standard treatment regimen for new cases of tuberculosis in patients younger than 8 years old?

    <p>Isoniazid, rifampicin, pyrazinamide for a minimum of 2 months and Isoniazid and rifampicin for minimum of 4 months</p> Signup and view all the answers

    Extra pulmonary tuberculosis requires only 6 months of treatment.

    <p>False</p> Signup and view all the answers

    What is the effect of being a slow acetylator on the metabolism of isoniazid?

    <p>It has a half-life of 3 hours and increases the risk of neurotoxicity.</p> Signup and view all the answers

    Multi-drug resistant TB (MDR TB) is defined as TB disease with resistance to both _______ and _______.

    <p>isoniazid, rifampicin</p> Signup and view all the answers

    Match the following tuberculosis drugs with their activities:

    <p>Isoniazid = Bactericidal against active bacilli Rifampicin = Sterilizing activity against dormant bacilli Pyrazinamide = Inhibits fatty acid synthesis Ethambutol = Prevents cell wall synthesis</p> Signup and view all the answers

    What is the optimal frequency of dosing for tuberculosis medications?

    <p>Daily</p> Signup and view all the answers

    Drug-resistant TB is solely caused by transmission from one person to another.

    <p>False</p> Signup and view all the answers

    What is the recommended treatment duration for a patient with drug-resistant TB?

    <p>3 to 4 times longer than for standard TB treatment.</p> Signup and view all the answers

    Extensively drug resistant TB (XDR TB) includes MDR TB plus in vitro resistance to any of the ________ and at least one of the ________ second-line drugs.

    <p>fluoroquinolones, injectable</p> Signup and view all the answers

    Which drug metabolism process shows genetic control?

    <p>Isoniazid metabolism</p> Signup and view all the answers

    Study Notes

    Tuberculosis

    • Overview: Leading infectious cause of death worldwide, affects over 2 billion people. Caused by Mycobacterium tuberculosis (Mtb), a slow-growing aerobic bacillus that forms granulomatous lesions leading to tissue destruction.
    • Transmission: Transmitted between humans through airborne droplets; normal breathing: 1 meter, respiratory exhalation: 2 meters, sneezing: 6 meters.
    • Pathogenesis:
      • Bacilli proliferate in macrophages during primary infection, often asymptomatic.
      • Clinical manifestations include:
        • Central: fatigue, loss of appetite
        • Lungs: prolonged productive cough
        • Skin: night sweats, pallor
    • Incidence and Risk Factors:
      • Global incidence: one third of the world’s population infected.
        • 50-60% of those with HIV develop active TB.
        • 10% of healthy individuals develop active TB.
        • Mortality rate: approximately 50%.
      • Risk factors:
        • Immunosuppressive conditions (HIV/AIDS, cancer)
        • Silicosis
        • Diabetes mellitus
        • Prolonged corticosteroid use
    • Latent vs Active TB:
      • Infection can cause latent TB or progress to active TB.
      • Active TB: Bacilli invade and damage body parts, can be pulmonary (lung) or extrapulmonary (other organs), infectious, and presents with signs and symptoms.
      • Latent TB: Bacilli remain dormant in the lungs, non-infectious, no signs or symptoms.
    • Pulmonary vs Extra-pulmonary TB:
      • Pulmonary TB (PTB): Disease involves lung tissue; smear-positive (visible bacilli in sputum, highly infectious), smear-negative (non-visible bacilli, less infectious).
      • Extra-pulmonary TB (EPTB): Disease involves organs other than the lung (pleura, lymph nodes, abdomen, etc.), not infectious unless pulmonary TB is also present.
    • Signs and Symptoms:
      • Classic symptoms of active TB infection:
        • Chronic cough (more than 2 weeks) with or without blood-tinged sputum
        • Fever
        • Night sweats
        • Weight loss
    • Detection Methods:
      • Serological tests (antibody tests, high false-positive rate).
      • Skin test (tuberculin injected into the skin, reaction measured after 48 hours - does not distinguish between latent and active TB).
      • Sputum test (microscopic analysis, 50-60% sensitivity).
      • Chest X-ray (shows pulmonary inflammation, not specific).
    • Diagnosis of TB:
      • Active TB:
        • Requires radiology (chest x-rays), microscopic examination and microbiological culture of body fluids, and PCR to detect drug resistance.
      • Latent TB:
        • Relies on tuberculin skin tests and blood tests.
    • Morbidity and Mortality:
      • Leading cause of death due to:
        • Inadequate disease control programs
        • Multi-drug resistance
        • Co-infection with HIV
        • Decreased socioeconomic conditions (poverty, overcrowding, poor sanitation)
    • Treatment Goals:
      • Cure the patient.
      • Prevent death from active TB or its late effects.
      • Prevent relapse.
      • Decrease transmission to others.
      • Prevent development of acquired drug resistance.
    • Treatment Challenges:
      • Bacilli only vulnerable when metabolically active.
      • Small subpopulation of bacilli remain semi-dormant.
      • Transient activity for short periods.
      • Drug-resistant mutants.
      • Treatment required beyond the disappearance of clinical symptoms.
    • Treatment of TB:
      • Standardized treatment protocols with fixed-dose combination medications.
      • Standard regimen for new and previously treated patients:
        • Correct drugs for an adequate duration.
        • Directly observed therapy (DOT) to achieve treatment completion and compliance.
    • Combination Therapy:
      • Multidrug therapy with intensive and continuation phases:
        • Intensive phase: Rapidly eradicates bacilli from sputum, reduces infectiousness within 10-14 days, most patients become smear-negative after 2 months.
        • Continuation phase: Sterilizing effects, elimination of remaining bacilli, prevention of relapse.
    • Regimens:
      • For new and previously treated adults and children >18 years/30 kg:
        • 6 months of treatment (all medications in fixed-dose combinations, 7 days per week) for both pulmonary and extrapulmonary disease.
        • Extra-pulmonary disease requires a 7-month continuation phase (total 9 months).
    • First-Line Drugs:
      • Bactericidal against metabolically active bacilli, sterilizing activity against semi-dormant bacilli, and prevent the emergence of resistant strains.
    • Isoniazid:
      • Metabolized in the liver via N-acetylation.
        • Slow acetylators (longer half-life): greater therapeutic response, increased risk of neurotoxicity.
        • Fast acetylators (shorter half-life): require higher doses, increased risk of hepatotoxicity.
    • Rifampicin:
      • Inhibits RNA synthesis.
      • Note: Body fluid coloration, never use alone.
    • Pyrazinamide:
      • Sterilizing activity inside acidic intracellular compartments.
      • Adverse effects: Gout.
      • Drug Interactions: Probenecid, allopurinol.
    • Ethambutol:
      • Inhibits cell wall synthesis.
      • Contraindications: Children younger than 8 years old.
      • Adverse effects: Optic neuritis.         - Note: Can be used for isoniazid resistance.
    • Standard Treatment Regimen:
      • New cases in patients younger than 8 years old:
        • Intensive phase: Isoniazid, rifampicin, pyrazinamide (minimum of 2 months).
        • Continuation phase: Isoniazid and rifampicin (minimum of 4 months), ethambutol can replace isoniazid in case of resistance.
      • New cases in patients 8 years and older:
        • Intensive phase: All first-line drugs (minimum of 2 months).
        • Continuation phase: Isoniazid and rifampicin (minimum of 4 months).
    • Dosing Frequency:
      • Daily dosing is optimal.
      • Alternatives:
        • Intensive phase (daily) and continuation phase (3x per week).
        • Intensive and continuation phases (3x per week) for patients not living with HIV.
    • Drug Resistance:
      • Caused by inadequate or erratic treatment, transmission from one person to another.
      • Management requires specialists and individualized regimens based on susceptibility results.
      • Resistant TB treatment takes 3-4 times longer and costs 100 times more.
    • Types of Drug Resistance:
      • Mono drug resistant strains: Resistance to a single first-line anti-TB drug.
      • Multidrug-resistant TB (MDR TB): Resistance to both isoniazid and rifampicin, with or without resistance to other anti-TB drugs.
      • Extensively drug-resistant TB (XDR TB): MDR TB plus resistance to any fluoroquinolones and at least one injectable second-line drug (kanamycin, amikacin, or capreomycin).
    • Retreatment Regimens:
      • Higher likelihood of drug resistance.
      • Intensive phase (3 months):
        • All first-line drugs, streptomycin for 2 months, all first-line drugs for 1 month.
      • Continuation phase (5 months): Isoniazid, rifampicin, ethambutol.
    • Second-Line Drugs:
      • Used in multidrug-resistant TB and when first-line drugs are not effective or tolerated.
    • Streptomycin:
      • Inhibits protein synthesis.
      • Contraindications: Pregnancy, renal impairment.
      • Adverse effects: Ototoxicity, nephrotoxicity.
    • Treatment of MDR-TB:
      • Intensive Phase (6 months): High-dose isoniazid or ethambutol, pyrazinamide, moxifloxacin, ethionamide, streptomycin/kanamycin.
      • Continuation Phase (12-18 months): High-dose isoniazid or ethambutol, pyrazinamide, moxifloxacin, ethionamide.
    • TB and HIV:
      • 100x increased risk of active TB infection in HIV+ individuals.
      • Treatment of TB and HIV should not be initiated simultaneously due to:
        • Overlapping toxicities (hepatotoxicity).
        • Significant drug interactions (CYP).
        • Adherence requirements.
        • Risk of immune reconstitution inflammatory syndrome (IRIS) (11-45% within 6 weeks).
        • HAART can lead to paradoxical deterioration of TB.
    • Management of TB and HIV:
      • If TB develops during HAART, HAART must not be discontinued but modified based on safety aspects.
      • If TB develops first: Treat TB first, then introduce HAART depending on CD4 count.
    • Isoniazid Preventive Therapy (IPT):
      • For people living with HIV, excluding those with active TB.
      • Initiate IPT as soon as possible after HAART initiation.
      • Maximum dose: 300 mg/day.
      • Pyridoxine (Vitamin B6) 25 mg/day.
      • Not contraindicated in pregnancy.
      • No evidence of increased isoniazid resistance with IPT.
      • Contraindicated with alcohol abuse due to risk of liver damage (rare complication).
    • HAART Treatment with Concomitant TB:
      • Specific management strategies to address drug interactions, toxicities, and adherence requirements.
    • Summary of Mechanisms of Action:
      • Pyrazinamide: Sterilizing activity inside acidic intracellular compartments.
      • Isoniazid: Inhibits mycolic acid synthesis, administered with Vitamin B6.
      • Ethambutol: Inhibits cell wall synthesis, contraindicated in children younger than 8 years old.
      • Streptomycin: Inhibits protein synthesis, contraindicated in pregnancy and renal impairment.
      • Rifampicin: Inhibits RNA synthesis, body fluid discoloration, never use alone.
    • Take Home Questions:
      • Which drug should not be given to children younger than 8 years old? Answer: C - Ethambutol.
      • Which drug is not used for first-line treatment of Mycobacterium tuberculosis? Answer: None of the options provided are first-line drugs. The text does not state the drug for this question.

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    Description

    Explore the critical aspects of Tuberculosis, including its transmission, pathogenesis, and global incidence. This quiz covers the effects of Mycobacterium tuberculosis and highlights risk factors and clinical manifestations. Test your knowledge about this leading infectious disease.

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