Pathogenesis of Mycobacterium Tuberculosis
Introduction
Mycobacterium tuberculosis (Mtb) is a highly successful pathogen that infects approximately one-third of the world's population. Despite this high prevalence, only a small percentage of infected individuals will develop active tuberculosis (TB). This is because Mtb has evolved sophisticated mechanisms to evade the host immune system and establish a persistent, latent infection.
Transmission and Infection
- Transmission: Mtb is transmitted via airborne droplets produced by coughing, sneezing, or speaking.
- Entry: Mtb enters the body through the respiratory tract, typically the alveoli of the lungs.
- Initial Infection: Upon reaching the alveoli, Mtb encounters alveolar macrophages.
Macrophage Infection and Immune Evasion
- Macrophage Entry: Mtb can enter macrophages by phagocytosis.
- Survival and Replication: Mtb can survive and even replicate within macrophages by:
- Inhibiting Phagosome-Lysosome Fusion: Mtb secretes proteins like ESAT-6 and CFP-10 that prevent the phagosome from fusing with lysosomes, preventing degradation.
- Modulating Host Cell Signalling: Mtb alters macrophage signalling pathways, suppressing the production of pro-inflammatory cytokines and promoting their survival.
- Immune Response: The initial infection triggers an immune response, characterized by the recruitment of neutrophils and other immune cells. However, Mtb can evade the immune system by:
- Forming Granulomas: Mtb induces the formation of granulomas, which are localized areas of inflammation containing infected macrophages, lymphocytes, and other immune cells. These granulomas are a hallmark of TB infection.
- Latent Infection: In many cases, the immune response effectively contains the infection, leading to a latent infection where Mtb remains dormant within the granulomas.
Reactivation and Active Tuberculosis
- Reactivation: Latent infection can reactivate and progress to active TB under certain conditions such as:
- Immune Suppression: Weakened immune systems, due to HIV infection, malnutrition, or immunosuppressive drugs, can increase the risk of reactivation.
- Other Factors: Age, smoking, and certain genetic factors can also contribute to reactivation.
- Active TB: In active TB, Mtb multiplies and spreads within the lungs, causing damage and symptoms such as:
- Cough: Productive cough with sputum (often blood-tinged).
- Fever: High fever, particularly in the evening.
- Night Sweats: Profuse sweating at night.
- Weight Loss: Unexplained weight loss.
- Fatigue: Persistent fatigue and weakness.
- Dissemination: Mtb can spread from the lungs to other organs, leading to extra-pulmonary TB, which can affect the lymph nodes, brain, meninges, kidneys, and bones.
Treatment and Prevention
- Treatment: Active TB is treated with a combination of antibiotics for an extended period (usually 6-9 months).
- Prevention:
- Vaccination: BCG vaccine is available and is effective in reducing severe TB in children.
- Infection Control: Isolation of patients with active TB and adherence to infection control measures are crucial.
Conclusion
Mtb's complex pathogenesis involves sophisticated mechanisms for evading the host immune system and establishing a persistent infection. Understanding the intricacies of this pathogen is crucial for developing effective treatments and preventing the spread of TB.
