Human Biology: Bacteria and Tuberculosis

Bacterial Infections

• Bacteria are single-celled, microscopic prokaryotes (no nucleus or membrane-bound organelles).

• They are found everywhere: soil, water, and inside living organisms.

• They replicate efficiently through binary fission, allowing rapid population growth (e.g., some species replicate in 20 minutes).

• Only a small percentage of bacteria cause disease in humans.

• Examples of bacteria:

  • Staphylococcus aureus: normally on skin, can cause staph infections.

  • E. Coli: part of microflora, some strains cause food poisoning and UTIs.

  • Lactobacillus acidophilus: in fermented foods and the gastrointestinal tract, important for food production.

  • Streptococcus mutans: in the mouth, contributes to tooth decay.

  • Pseudomonas aeruginosa: in soil and water, known for antibiotic-resistant infections.

Virulence Factors

• Virulence factors are properties that make bacteria more likely to cause disease.

• They serve as defense strategies for bacteria.

• Examples of virulence factors:

  • Flagellum: A tail-like structure that allows bacteria to move to tissues and around the body.

  • Pili: Small hair-like structures that enable bacteria to adhere to surfaces, preventing them from being washed away; also adhere to cell structures.

  • Capsule: A polysaccharide structure that protects bacteria from phagocytosis (engulfment by immune cells).

  • Exotoxins: Toxic molecules released by bacteria that damage host cells, allowing bacteria to enter sites and impairing the immune response.

  • Endotoxins: Lipopolysaccharides associated with the capsule. Released when the cell is damaged, causing toxicity.

Classification of Bacteria

• Classification helps compare bacteria and predict behavior of newly discovered bacteria.

• Main classifications:

  • Shape:

    • Cocci: sphere-shaped.

    • Bacilli: rod-shaped.

    • Spirochetes: spiral-shaped.

  • Cell wall structure:

    • Gram stain: a diagnostic test dividing bacteria into Gram-positive and Gram-negative.

    • Gram-positive bacteria: have a thick peptidoglycan cell wall on the exterior of a cell membrane that retains crystal violet stain and appear purple.

    • Gram-negative bacteria: have a thin peptidoglycan cell wall surrounded by an outer membrane; the crystal violet stain is washed out, and they stain pink.

Tuberculosis (TB)

• Caused by the bacterium Mycobacterium tuberculosis.

• M. tuberculosis doesn't fit into Gram-positive or Gram-negative categories due to its unique cell wall structure.

• It has a cell membrane, a thin cell wall, and an outer membrane made of mycolic acid.

• Tuberculosis is a lethal infectious disease.

Global Impact of TB

• Tuberculosis is a leading cause of death worldwide.

• In 2021, it was the 10th leading cause of death.

• In individuals with HIV, deaths due to TB are often recorded as HIV-related deaths.

• In 2023, there were 10.8 million new cases of TB, and 1.25 million deaths.

• M. tuberculosis has overtaken COVID-19 as the infectious agent responsible for the most deaths.

Impact of COVID-19 on TB

• The COVID-19 pandemic disrupted healthcare services, impacting TB diagnosis and treatment.

• Travel restrictions, focus on COVID-19, and healthcare worker illness contributed to decreased TB diagnoses.

• The overlap in symptoms (e.g., cough) between COVID-19 and TB further complicated diagnosis.

• Reduced diagnoses led to increased spread and deaths from TB.

Distribution of TB

• TB is considered an epidemic, with potential for sudden outbreaks.

• The burden of TB is not evenly distributed globally.

• Most cases occur in the developing world.

• Eight countries account for two-thirds of global TB cases in 2023: Pakistan, India, Indonesia, Philippines, Bangladesh, China, Nigeria, and the Democratic Republic of The Congo.

• In Australia, most TB cases are among migrants who were infected before arriving.

• TB transmission is facilitated by living in close quarters, affecting some Aboriginal communities.

Vulnerable Populations

• Unlike malaria, adults are more affected by TB than young children.

• Males tend to get TB more often than females.

Transmission of TB

• TB spreads through airborne transmission when infected individuals cough, talk, or sing.

• The bacteria are expelled into the air and inhaled by others.

• Airborne transmission involves aerosols that linger in the air.

• M. tuberculosis has a low infectious dose (around 10 bacteria).

Pathogenesis of TB

• Inhaled bacteria are engulfed by macrophages in the lungs.

• Macrophages transport the bacteria into the lung tissue, forming granulomas (immune cell clusters).

• The infection can remain in a latent form within the granuloma for extended periods.

• Reactivation of the bacteria can occur, leading to active disease.

• In some cases, the bacteria can enter the bloodstream, causing systemic disease. However, in most cases TB remains within the lung.

Outcomes of TB Infection

• TB infection can have different outcomes:

  • Clearance by the innate or acquired immune response.

  • Latent infection: Bacteria contained in granulomas.

  • Active disease: Bacteria multiply and cause symptoms.

  • Subclinical active disease: Active disease with mild or no symptoms.

• Diagnostic tests: (skin test, interferon gamma test) indicate exposure to M. tuberculosis but cannot distinguish between latent TB and cleared infection.

• Infectiousness: People with latent TB are not infectious; those with active TB are infectious and subclinical cases are sporadically infectious.

• Symptoms: People with latent TB are asymptomatic, while those with active TB have symptoms.

Latent TB Infection

• Approximately one-quarter of the world's population is infected with TB, mostly in a latent state.

• There is a 5-10% lifetime risk of developing active TB disease, which increases with immunocompromised states.

• Active TB typically affects the lungs (pulmonary TB), but can disseminate and infect other body parts (disseminated TB), but this is much more rare.

Risk Factors for Active TB

• Risk factors for latent TB progressing to active TB:

  • HIV infection.

  • Malnutrition.

  • Alcohol use.

  • Smoking.

  • Diabetes.

  • Chemotherapy

Diagnostics of TB

• Rapid molecular tests have improved TB diagnosis, especially after the COVID-19 pandemic.

• These tests use sputum samples to detect mycobacteria DNA through PCR, providing quick results on mycobacterial presence and drug resistance.

• Other diagnostic methods include:

  • Skin tests and interferon-gamma release assays: Detect exposure to M. tuberculosis.

  • Chest X-rays: Look for lung damage, but results and somewhat subjective and not perfect.

  • Sputum culture: Gold standard for confirming active TB and monitoring drug resistance.

Symptoms and Treatment of TB

• Symptoms of active pulmonary TB:

  • Cough lasting more than three weeks.

  • Coughing up blood and sputum.

  • Chest pain.

  • Fever.

  • Night sweats.

  • Chills.

  • Loss of appetite.

  • Weakness or fatigue.

  • Weight loss.

• Without treatment, the death rate can be as high as 50%.

• Treatment involves a six-month course of four drugs:

  • Rifampicin.

  • Ethambutol.

  • Pyrazinamide.

  • Isoniazid.

• Treatment success can be as high as 85% if the full six month course is completed

• Long-term therapy can be challenging for patients, therefore non-adherence can results in further complications such as, encouraging drug resistance.

Drug-Resistant TB

• Drug resistance is a significant threat to TB control.

• Resistance to rifampicin is a major problem.

• Multi-drug resistant TB (MDR-TB) involves resistance to both rifampicin and isoniazid.

• MDR-TB requires treatment with second-line drugs, which are more toxic/require longer treatments and have lower success rates.

• In 2023, approximately 3% of new TB cases had rifampicin-resistant MDR-TB, while 16% of previously treated cases had it.

• Extensively drug-resistant TB (XDR-TB) has lower treatment success.

• There were almost 30,000 people with extensively drug resistant TB or pre-TB in 2022