Seminario de tuberculosis

Introduction to Tuberculosis and Latent Tuberculosis

Overview of the Presentation

• The presenters introduce themselves: Juliana Casas, Natalia Centeno, Hanna, Javier Hernández, and Emanuel, along with their professor Diana Ortiz.

• They aim to discuss tuberculosis (TB), specifically focusing on latent TB and its implications.

Understanding Tuberculosis

• Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis, which can present in various forms including latent infection and active disease.

• Latent TB infection occurs when a person carries the bacteria but does not exhibit symptoms or have contagious capacity due to immune control.

Differentiating Between Types of TB

• Patients exposed to TB may test positive on immunological tests but show no symptoms; they are not infected or contagious.

• Active TB is characterized by the presence of bacteria that the immune system cannot control, leading to symptoms and contagion.

Epidemiology of Tuberculosis

Global Statistics

• According to UNODC data from 2025, there were 131 cases of TB per 100,000 people globally; about 11% were children under 15 years old.

Risk Factors for Activation

• There is a 5% risk within two years for individuals over five years old without immunocompromising conditions for latent TB to become active.

• This risk varies significantly based on age and health status; in some regions, it can rise up to 50%.

Local Data on Latent Tuberculosis

Regional Statistics

• Children exposed to active TB have a significant risk (30%-50%) of developing active disease.

• Globally, it's estimated that one-third to one-fourth of the population carries latent TB.

Specific Cases in Antioquia

• In Antioquia as of early 2026, there were reported cases: 47 in children aged 0–9 years and 206 in adolescents aged 10–19 years.

Pathophysiology of Tuberculosis Transmission

Infection Process

• Transmission begins when an individual with active pulmonary TB coughs or sneezes aerosolizing droplets containing the bacteria into the air.

Immune Response Mechanism

• These small particles evade respiratory defenses and reach alveoli where macrophages attempt phagocytosis using pattern recognition receptors (PRRs).

Survival Strategies of Mycobacterium tuberculosis

• Mycobacterium tuberculosis employs various mechanisms to avoid destruction within macrophages by inhibiting phagosome maturation.

Cellular Response and Dissemination

Formation of Primary Focus

• The uncontrolled replication leads to local inflammation characterized by cytokine release recruiting more immune cells forming a primary focus known as Ghon complex.

This structured markdown file provides a comprehensive overview while ensuring easy navigation through timestamps linked directly back to specific parts of the transcript.

Hematogenous Dissemination in Tuberculosis

Initial Infection and Lymphatic Drainage

• The initial infection leads to lymphatic drainage, primarily affecting the iliac and mediastinal lymph nodes where the bacilli are located.

• Bacilli can enter the bloodstream early, even before adaptive immunity develops.

Organ Involvement and Latency

• During hematogenous dissemination, bacilli colonize oxygen-rich organs, forming tuberculous foci in the lungs' apices, kidneys, brain, and bone metaphysis.

• This process occurs prior to adaptive immunity and can result in latent or active infection.

Adaptive Immunity and Latency Genesis

Antigen Processing by Immune Cells

• Dendritic cells and macrophages process mycobacterial antigens presenting them to CD4 T-cells via MHC class II and CD8 T-cells via MHC class I through direct presentation or cross-stimulation.

Apoptosis of Infected Macrophages

• Infected macrophages undergo apoptosis forming apoptotic bodies containing bacterial peptides that dendritic cells capture for antigen presentation.

Key Mechanisms of Immune Response

Differentiation of T-cells

• The differentiation of CD4 T-cells into TH1 cells is driven by massive release of interferon-gamma (IFN-γ) and TNF-alpha.

Activation of Macrophages

• Cytokines activate macrophages enhancing their production of reactive nitrogen intermediates aimed at destroying bacteria.

Memory T-cell Functionality

Maintenance of Latency

• Memory T-cells (CD4 & CD8 types) ensure latency over years through continuous secretion of IL-2, IFN-γ, and TNF to prevent reactivation within solid granulomas.

Cytolytic Activity Against Infected Cells

• CD8 cytotoxic T-cells secrete perforin and granzyme to directly attack infected cells by disrupting their membranes.

Reactivation Mechanisms

Factors Leading to Disease Progression

• Mechanisms such as exhaustion of T-cells or excessive regulatory effects from regulatory T-cells (Tregs), which release IL-10 and TGF-beta, can lead to loss of immune containment allowing reactivation.

Granuloma Architecture

Structure Under Immune Response

• Granulomas consist of multinucleated giant cells surrounded by a ring of lymphocytes with an outer layer synthesizing collagen for encapsulation.

Metabolic Effects on Mycobacterium

Dormancy State Induction

• Within granulomas, a low oxygen environment induces metabolic dormancy in Mycobacterium tuberculosis reducing energy consumption while utilizing host lipids for survival without replication.

Calcification Process

Formation of Ranke Complex

• Over time granulomas may undergo fibrosis leading to calcification known as Ranke complex which remains asymptomatic yet radiologically identifiable in immunocompetent children.

Diagnostic Protocol for Latent Tuberculosis

Priority Groups for Screening

• High-risk groups include individuals living with HIV, children under 5 exposed to pulmonary TB patients, those starting biological therapy for autoimmune diseases, chronic kidney disease patients on dialysis among others.

Diagnostic Steps Overview

Initial Assessment

• The first step involves ruling out active tuberculosis symptoms like prolonged cough or fever before proceeding with skin tests like tuberculin testing.

Diagnosis and Treatment of Tuberculosis in Children

Tuberculosis Testing Protocols

• A positive tuberculin test indicates the need to differentiate between active and latent tuberculosis using a chest X-ray. If no active infection is found, treatment for latent tuberculosis begins.

• For children under 5 years who have been in contact with tuberculosis cases, clinical screening is essential to rule out active disease. Symptoms must be assessed first.

• Routine clinical screening for individuals living with HIV includes evaluating symptoms like fever, cough, weight loss, and night sweats; any presence of these symptoms necessitates ruling out active tuberculosis.

Diagnostic Algorithms

• If no symptoms are present or if active infection has been ruled out, the diagnostic algorithm for latent tuberculosis continues with a tuberculin test reading considered positive at ≥5 mm induration.

• Physicians may request gamma interferon release assays to quantify immune response to Mycobacterium tuberculosis antigens as part of the diagnostic process.

Follow-Up Procedures

• A positive tuberculin test followed by a normal chest X-ray allows for initiating treatment for latent infection. If negative, a repeat test after three weeks is recommended to check for booster effect.

• Should the booster test yield a positive result, further differentiation between active and latent infections via chest X-ray is necessary before starting treatment.

Special Considerations in Treatment

• A negative booster test suggests no exposure to infection; annual testing is advised to monitor potential changes in status.

• For children under 5 years living with HIV who have contact with confirmed cases of tuberculosis, immediate treatment for latent infection should commence after ruling out active disease.

Clinical Screening Criteria

• The clinical screening process involves assessing symptoms such as persistent cough (≥15 days), fever (≥2 days), and weight loss or lack of weight gain before proceeding with further tests.

• In asymptomatic patients, both tuberculin testing and chest X-rays are performed; if results indicate positivity without alterations on X-ray, treatment for latent infection starts immediately.

Treatment Duration Based on Risk Factors

• In cases where initial tests show negative results but risk factors like immunosuppression exist, treatment duration varies: 6 months if immunosuppressed versus 3 months otherwise.

• Any initial negative tuberculin result or altered chest X-ray requires thorough investigation into possible pulmonary or extrapulmonary tuberculosis.

Important Notes on Tuberculosis Management

• Always prioritize ruling out active tuberculosis when one or more symptoms are present.

• The timing of tuberculin reading should occur within 48–72 hours post-administration; results must be reported in millimeters of induration.

Treatment Regimens Overview

• For children under 2 years old diagnosed with latent TB: daily isoniazid plus rifampicin over three months unless contraindicated due to resistance; then rifampicin alone over four months may be prescribed.

• Alternative regimens include six-month courses of isoniazid alone if short-course options aren't available; adherence improves significantly with shorter regimens.

Recommendations for Special Populations

• Short-course treatments combining isoniazid and rifampicin or rifapentine weekly over three months are recommended specifically for HIV-positive patients older than two years.

Treatment Protocols for Tuberculosis in Children

Isoniazid Treatment Guidelines

• For children weighing less than 10 kg, isoniazid is administered daily for 6 months.

• For children aged 2 to 18 years and weighing more than 10 kg, treatment includes isoniazid plus rifapentine weekly for three months.

Immunological Window Management

• Preventive treatment is not automatically given to all children exposed to active tuberculosis; it’s conditional based on age and risk factors.

• Strong recommendation for preventive treatment in children under 5 years, regardless of immunological test results within the three-month window post-exposure.

Testing and Follow-Up

• If exposure exceeds three months with negative tests, no preventive treatment should be administered.

• A follow-up test should occur between 8 to 12 weeks after exposure; if positive, complete the treatment regimen.

Dosage Information for Antitubercular Medications

Isoniazid Dosing

• Recommended dosage of isoniazid:

• For ages 2 to 11 years: 25 mg/kg.

• For ages 12 and older: maximum of 15 mg/kg up to a total of 900 mg.

Rifapentine Dosing

• Rifapentine dosing varies by weight; specific gramages are provided in accompanying materials.

Combination Therapy Details

• The ebrofloxacin regimen targets resistant tuberculosis contacts over six months at a dose of 15–20 mg/kg/day (max.1000 mg).

Importance of Vitamin B6 Supplementation

At-Risk Populations

• Vitamin B6 supplementation (25–50 mg/kg/day) is crucial for vulnerable groups such as malnourished infants or those with HIV immunosuppression during isoniazid therapy.

Understanding Tuberculosis Transmission

Transmission Mechanism

• Tuberculosis spreads via aerosols containing particles smaller than five microns, necessitating proper mask usage by infected individuals.

Mask Recommendations

• Infected patients should wear surgical masks to prevent aerosol release; non-infected individuals should use N95 masks for protection against inhaling these particles.

Challenges in Treatment Availability

Shortened Regimens Issues

• Shorter treatment regimens are often unavailable due to supply issues, leading practitioners to rely on longer courses like six months of isoniazid instead.

Clarifications on Latent vs. Active Infection

Terminology Update

• The term "latent tuberculosis" may be evolving out of common usage; discussions now focus on "infection" status which can yield false negatives in immunological testing due to physiological factors.

Testing Methods

• Repeating tests (ideally tuberculins or higras), especially among immunocompromised individuals or young children, helps avoid misdiagnosis from false positives associated with prior vaccinations.

Presentation Feedback and Conclusion

Positive Reception

• The presentation received commendations for its clarity, local data inclusion, and comprehensive coverage of tuberculosis pathophysiology and management algorithms.

Closing Remarks

• Participants were encouraged to ask questions before concluding the session with thanks from both students and instructors.