TB

Primary Tuberculosis (TB)

• Initial infection occurs in the lungs, tonsils, or intestines, leading to a reaction termed the primary complex.
• Primary TB in lungs consists of a parenchymal component and hilar lymphadenopathy, developing within 4-6 weeks.
• Symptoms are often minimal or absent during early stages.
• Parenchymal lesions are typically located in the periphery of the upper or lower lobes.
• Hilar lymph nodes may reduce, leading to calcified Ghon's focus visible on chest X-ray, indicating healing.
• Reactivation of incompletely healed primary TB can lead to post-primary TB.

Post-primary Tuberculosis

• Refers to a new (exogenous) infection or reactivation (endogenous) in sensitized individuals, often pulmonary.
• Typically occurs at the apex of an upper lobe due to favorable oxygen conditions for Mycobacterium tuberculosis.
• Onset is insidious, developing over weeks.

Tuberculosis Definition and Etiology

• TB is a chronic bacterial infection caused by Mycobacterium tuberculosis, an intracellular pathogen.
• Caseating granulomas form after exposure, characterized by central caseation, epithelioid cells, and Langhans giant cells.
• Human Mycobacterium tuberculosis is the primary cause, with bovine Mycobacterium tuberculosis accounting for less than 1% of cases.
• Only 10-15% of infected individuals develop active TB depending on immune factors.

Allergic Reactions to TB

• Allergic responses can manifest as tuberculin hypersensitivity, erythema nodosum, pleural effusion, and epituberculosis.
• Epituberculosis arises from allergic reactions around primary TB components, potentially compressing airways.

Routes of Spread of Tuberculosis

• Bronchial Spread: Can lead to bronchogenic pulmonary TB, characterized by pneumonia, cavities, or nodular infiltration.
• Lymphatic Spread: Can cause mediastinal lymphadenopathy; compression of bronchus can lead to atelectasis or bronchiectasis.
• Hematogenous Spread: Results in miliary TB, presenting with fever, night sweats, and possibly affecting multiple organs.

Clinical Manifestations and Diagnosis

• TB symptoms include cough (dry or productive), hemoptysis, chest pain, night sweats, and weight loss.
• Physical signs may include signs of lung tissue consolidation, atelectasis, and effusion.
• Diagnosis via smear or culture (sputum, CSF, biopsy), or histology showing caseating granulomas.

Diagnostic Investigations

• Smear microscopy using the Ziehl-Neelsen method can detect acid-fast bacilli, requiring <5,000 AFB/ml for positivity.
• Common chest X-ray findings include fine, millet seed-like lesions throughout lung fields.
• Complete blood count may reveal anemia or leucopenia due to bone marrow involvement.

Differential Diagnosis

• TB symptoms overlap with various respiratory diseases; need differentiation from atypical mycobacterial infections, especially in immunocompromised individuals.
• Common atypical species include M. scrofulaceum, M. intracellulare, and M. fortuitum.

Management and Prevention

• Effective TB management includes medications targeting Mycobacterium tuberculosis.
• Preventive measures focus on infection control and minimizing exposure to TB bacilli.

Antitubercular Drugs and Their Toxicities

• Kanamycin and Streptomycin share similar nephrotoxic effects, with implications on urea and creatinine levels.
• Cycloserine can cause psychosis, personality changes, and convulsions as side effects.
• Para Amino Salicylic Acid (PAS) is associated with gastrointestinal toxicity, hepatotoxicity, and skin rash indicated by elevated SGOT/SGPT levels.
• Ethionamide exhibits toxicity similar to PAS.
• Vancomycin has a toxicity profile that mirrors streptomycin.
• Capreomycin has similar side effects to streptomycin but is contraindicated in pediatric patients.

Treatment Strategy for Tuberculosis

• Multidrug regimens are required for all cases of active tuberculosis (TB).
• Initial treatment includes four drugs: rifampin, isoniazid, pyrazinamide, and ethambutol for 2 months.
• Follow up with rifampin and isoniazid for an additional 4 months; in some cases, treatment may extend up to 9 months.
• Regimen adjustments should be made based on drug sensitivity.
• Directly Observed Therapy (DOT) is recommended by WHO for treatment adherence.

Drug Resistance in Tuberculosis

• Early unfavorable bacteriologic responses may indicate drug resistance, either primary from resistant strains or acquired through inadequate treatment.
• Drug resistance can manifest as mono-resistance or multi-drug resistance, particularly against rifampin and isoniazid.
• Multi-Drug Resistant Tuberculosis (MDR-TB) requires personalized treatment regimens based on culture and sensitivity tests.
• At least three new drugs not previously administered are included in the regimen, ensuring combination therapy with direct observation.

Latent Tuberculosis Infection

• Latent TB is characterized by a positive tuberculin skin test or IGRA without active symptoms or abnormal chest X-ray (CXR).
• The presence of mycobacteria is minimal, with a competent host immune response.

Prevention and Vaccination

• BCG vaccination, administered to 3-5 billion people, is part of the immunization program in Egypt for infants within their first three months.
• BCG does not prevent TB infection but reduces severe forms, such as miliary TB and TB meningitis.

Tuberculin Test Considerations

• Skin anergy may lead to false-negative tuberculin tests due to denaturation, improper storage, or incorrect administration technique.
• Interferon gamma release assays (IGRA), including T-spot and QuantiFERON TB Gold, detect IFN-γ from T-cells in response to MTB antigens.
• IGRA tests exhibit high sensitivity but low specificity; a negative indicates the absence of active or latent TB, while a positive cannot conclusively differentiate between the two.

Diagnostic Procedures

• In cases of high clinical suspicion yet no sputum or lymph node sample, bronchoscopy and bronchoalveolar lavage (BAL) may be necessary.

Infection Control Measures

• Patient isolation for the initial two weeks of treatment minimizes transmission risks.
• Use of masks is essential during patient contact to reduce disease spread.