1. Definition Mycobacterium Tuberculosis Infection of the lungs is referred to as Pulmonary Tuberculosis

2. Aetiology Mycobacterium Tuberculosis complex M. Tuberculosis M. Bovis M. Africans M. Nicrotis M. Caretti

3. Microbiology Tubercle bacilli are non spore forming, non-motile, pleomorphic, rods, 2-4 um long, obligate aerobes Lowenstein Jensen culture media (rich carbon and ammonium salt) Ziehl Nielsen stain

4. Transmission Via infective tiny airborne micro droplets Person to person Factors that enhance transmission –Cavitatory lesions –Copious production of sputum –Severe and forceful cough –Over crowding –Immuno suppression –Malnutrition

5. Global Burden of TB Impact of HIV epidemic Increasing poverty and malnutrition Social agitation Poor living conditions in developing countries Inadequate health coverage and poor access to health services Inefficient TB control programme Emergence of multiple drug resistance

6. Pathogenesis Lung is the portal of entry in >98% of cases Tubercle bacilli multiply initially with alveoli and alveolar ducts Some are carried via lymphatic vessels to regional lymph nodes

7. ….contd Lung parenchymatous lesion Draining lymphatics Regional lymph nodes Primary Complex

8. Parenchymal Lesion Enlarge Parenchymal lesion PneumonitisPleuritis +/- Effusion Heals by fibrosis Or calcification Regional Lymph node Primary Complex

9. Regional Lymph Nodes Enlarge Erode via Bronchial wall Obstruction of bronchus Reactivation (Adolescent) Quiescent Incompletely healed lesion Atelectasis Emphysema Pulmonary TB Discharge into lumen & dissemination Haemoptysis Erode into Blood vessel Pulmonary TB Endobronchial Tb

10. Immunology of Childhood Tb A.Innate immunity Physical and anatomic barriers –Anatomic barriers to large particle deposition –Cough –Mucociliary transport Mannan binding lectins –C type lectins –Activate the lectin pathway of complement Defensins –Antimicrobial peptides secreted by PMNL and epithelial cells –Activate complement –Stimulate chemokines and cytokines production

11. ….contd Collectins –C type lectin produced by Type II pneumocytes –Mediate agglutination of bacteria Complements –Made by alveolar macrophages and epithelial cells –Opsonise bacteria Immaturity and deficiency in young children leading to susceptibilty to MTb disease

12. ….contd B.Acquired immunity Essential to Tb immunity are –Activated macrophages which inhibit the growth of intracellular M. Tuberculosis –Dendritic cells/development of potent pathogen-directed T-cell immunity –Th 1-type T cell immunity which mediate control of MTb infection by producing IFN-y –Th 2-type T-cell immnity which is strongly associated with Tb disease

13. Critical Diff. B/w Adult & Children Relevant to Tb Immunity Deficiencies in macrophage function Deficiencies in dendritic cell function Deficincies in the development of Th 1-Type T-cells in response to pathogens The propensity for infants and young children to develop Th 2-type T-cells in response to immunogens During primary complex, delayed hypersensitivity established over 2-8 weeks on completion lead to tuberculin sensitivity

14. Clinical Features Primary Pulm Dz Signs and symptoms are few >50% of infants and children with moderate to severe primary Tb with no physical findings, non productive cough, mild dyspnoea most common Systemic complaints –Fever, night sweat, anorexia less often –Some failure to thrive Bronchial obstruction leading to localized wheezing and reduced breath sounds

15. Progressive Primary Pulm Dz Significant signs and symptoms –High fever, severe cough, weight loss, night sweat –Reduced breath sound, rales, dullness

16. Reactivation Tb Older children and adolescents –Fever, anorexia, malaise, weight loss, night sweat, productive cough, haempotysis, chest pain Physical findings are minor or absent Highly contagious if sputum production and cough are significant

17. Pleural Effusion Primary Infection – Asymptomatic local pleural effusion Disseminated Tb – clinically significant effusion months/years after primary infection Pleurisy xterized by high fever, shortness of breath, chest pain on deep inspiration and reduced breath sounds