Tuberculosis Lecture Notes Flashcards

Tuberculosis (TB)

Introduction

• Tuberculosis is a serious disease affecting many worldwide.

• The emergence of multi-drug resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) poses a significant challenge.

• TB has been present for thousands of years, with evidence found in Egyptian mummies.

• Historically known as "consumption" due to the extreme weight loss it causes, and as the "white plague" due to the white caseation in infected organs.

Historical Context

• Sanatoria were established to treat TB patients with good food, sunlight, and fresh air to boost their immunity.

• Immunity type is crucial for controlling acid-fast bacilli like TB.

Global Impact

• Around 10% of individuals exposed to TB develop the disease.

• In 2021, 1.6 million people died from TB, including those with HIV.

• TB is a leading cause of death from infectious diseases, though malaria holds the top spot.

• Only one in three people with drug-resistant TB accessed treatment in 2021.

Disease Trends

• Measurable improvements in some diseases from 2000 to 2019, but TB reduction is insufficient.

• Diabetes increase impacts heart disease and cardiovascular problems.

• Diarrheal diseases and malaria have decreased due to interventions such as the Melinda and Bill Gates Foundation.

Robert Koch and Mycobacterium Tuberculosis

• Robert Koch, the father of microbiology, cultured Mycobacterium tuberculosis.

• Koch successfully grew the organism in culture and reproduced the disease by reinfecting animals.

• Mycobacterium tuberculosis is an acid-fast bacterium that can be grown on artificial media and infects various animals.

• Most people (90%) can overcome the infection without developing symptoms.

TB in Australia

• The Indonesian invasion of Timor in the late 1900s led to uncontrolled TB infections and spillover into Australian First Nations people.

• Monitoring maritime arrivals is crucial to prevent TB incursions from countries like Papua New Guinea.

• Migration patterns necessitate vigilant monitoring of TB cases in Australia.

Forms of TB

• Pulmonary TB: respiratory inhalation.

• Kidney: Second most common site for TB infection due to blood proximity to alveoli.

• Blood stream infection (hematogenous spread): The meninges can be seeded, often seen in infants with the less developed blood-brain barrier.

• Bone and joint tuberculosis is a result of TB spread from the lungs.

• Miliary TB: Spread of TB from the lungs.

• Skin tuberculosis requires careful diagnosis to prevent severe outcomes.

• Lymph nodes infection: Particularly with atypical mycobacteria, sometimes called scrofula when lymph nodes break down.

• Mycobacterium tuberculosis complex includes:

  • Mycobacterium tuberculosis.

  • Mycobacterium bovis: historically transmitted via unpasteurized milk.

  • BCG strain: used in vaccination.

Major Patterns of Disease

• Primary tuberculosis: initial focus of infection.

• Secondary tuberculosis: occurs when a latent lesion breaks down, leading to disseminated TB.

• TB in the spine can cause curvature, such as the hunchback of Notre Dame.

• Psoas abscesses: cold abscesses (no regular bacteria) next to the spine require special TB cultures.

• Urinary tract tuberculosis presents with sterile pyuria, requiring a special urine collection (EMU).

• CNS tuberculosis: involves raised protein lymphocytes and lower glucose in the CSF.

• Cervical nodes: always consider TB if no other organisms grow; molecular biology (16S sequencing) can help identify organisms like cat scratch disease.

Pathogenesis

• Initial infection: Macrophages ingest TB bacteria but cannot break them down.

• Tubercle formation: Lymphocytes surround the infected macrophages, creating a barrier.

• Dormancy: TB bacteria may enter dormancy inside the tubercle if conditions aren't favorable.

• Reactivation: Tubercle breakdown leads to open tuberculosis, making the individual infectious.

• Hemoptysis: Tubercle rupture into a local blood vessel causes coughing up blood.

Symptoms

• Symptoms are due to tumor necrosis factor production, an inflammatory cytokine.

• Severe weight loss accompanies the massive inflammatory response.

• Incubation period varies depending on the individual's health and age.

Importance of Cell-Mediated Immunity

• Cell-mediated immunity is crucial for controlling TB within macrophages.

• Inadequate macrophage activation leads to organism growth and necrosis.

• Calcification may occur, leading to visible lesions on chest x-rays.

• Chronic cycling post-primary tuberculosis requires monitoring due to the risk of lesion breakdown.

Diagnosis

• Molecular diagnosis offers rapid detection using kits like GeneXpert.

• Kits for detecting drug resistance are available.

• Indirect tests: assess immune response by stimulating T cells to release interferon-gamma, detected via ELISA (QuantiFERON test).

• Tuberculin skin test (Mantoux test): involves injecting purified protein from MTB under the skin and measuring the induration (hardness) after 48 hours.

  • Delayed hypersensitivity.

Diagnostic Procedures

• Follow-up chest x-ray for individuals with a large or increased Mantoux test.

• Sputum analysis to look for the organism.

• QuantiFERON test: important for definitive diagnosis when sputum isn't available.

Treatment

• Mycobacterium tuberculosis grows slowly (24-hour generation time) with a thick, fatty cell wall, requiring long treatment times.

• Intensive phase: involves four drugs (ethambutol, pyrazinamide, etc.) for the first few months.

• Continuation phase: reduces to two drugs for the next four months.

• Follow-up is crucial to prevent treatment interruption and development of multi-drug resistant TB.

• Directly Observed Treatment Strategy (DOTS): a program involving weekly clinics, incentives (e.g., $5 and a hot meal), and direct observation of medication intake.

Prevention

• Quarantine infected persons while monitoring treatment.

• BCG vaccination: effective in some populations but less so in developed countries.

• Pasteurization of milk: reduces the incidence of Mycobacterium bovis.

Final Thoughts

• Further research and efforts are needed to control and eliminate TB worldwide.

• Raising awareness and improving diagnostic and treatment strategies are essential.