Tuberculosis

TB TUBERCULOSIS

1. TUBERCULOSIS Dr. Inayat Ullah PGT Paediatrics

2. TILTES Definition Statistics Etiology Epidemiology Transmission Pathogenesis Extra pulmonary TB

3. definition TB is an infectious, systemic chronic granuomatous disease caused by Mycobacterium tuberculosis (M) TB. It is an aerobic non-spore forming Acid Fast Bacilli (AFB) Two other species Mycobacterium Bovis and M.A fricanum rarely causes TB in humans

4. Definition (cont’d) New case: if child has never taken treatment for TB or has taken ATT for less than 4 weeks. Relapse: If a child declared cured, or treatment completed in the past, again has clinical, radiological or bacteriological evidence of TB. Transferred in: A child who is referred from another TB register fro completion of treatment

5. Definitions ( Cot’d ) Treatment failure: if a child on appropriate treatment has clinical, radiological or bacteriological evidence of active TB 2 or more months after start of treatment. Return after default: if a child returns to treatment after interrupting treatment for 2 or more months. Others: A child who do not meet the above criteria, such a child known to have taken ATT for more than 4 months outside program.

6. STATISTICS: global Tuberculosis (TB) is a top infectious disease killer worldwide. In 2014, 9.6 million people fell ill with TB and 1.5 million died from the disease. Over 95% of TB deaths occur in low- and middle-income countries, and it is among the top 5 causes of death for women aged 15 to 44. In 2014, an estimated 1 million children became ill with TB and 140 000 children died of TB. TB is a leading killer of HIV-positive people: in 2015, 1 in 3HIV deaths was due to TB. Globally in 2014, an estimated 480 000 people developed multidrug-resistant TB

7. Statistics: local Pakistan statistics : Pakistan ranks 8 th with 1.5 million TB cases with 300,000 new case every year 250,000 adults/year, 4.4 % smear positive patients were in age 1-14 years (2002-2004) Among these children 5-10% have disease, remaining have LTBI 8-20% deaths in children Data from Pakistan National TB Control programme NTP Guideline 2007 Revised.

8. Etiology

9. Etiology Mycobacterium Tuberculosis complex M. Tuberculosis M. Bovis M. Africanum M. Microti M. Canetti M. Tuberculosis is the most important cause of tuberculosis disease in humans

10. Tubercle Bacillus Discovered by Robert Koch in 1882 Non spore forming, non motile, pleomorphic Weakly gram positive, curved rods 2-4 µm long Appear beaded or clumped in stained specimens or culture media Obligate aerobes that grow in Loewenstein -Jensen culture media Grow at 37-41ºC

11. Tubercle Bacillus Acid fastness: capacity to form stable mycolate complexes with arylmethane dyes (crystal violet, carbolfuchsin etc). Once stained, they resist decolouration with ethanol and hydrochloric or other acids Lipid rich cell wall resistant to bactericidal actions of antibody or complement Growth on solid media ( Loewenstein Jensen): slow, 3-6 weeks, additional 4 weeks for drug susceptibility Growth on liquid media (BACTEC): 1-3 weeks, additional 3-5 days for drug susceptibility

12. Nucleic acid amplification (NAA) tests: can detect M. tuberculosis within hours eg PCR

13. Transmission

14. Transmission By airborne mucus droplet nuclei, 1-5 µm in diameter containing M. tuberculosis Rarely occurs by direct contact High chances of transmission in the following: Positive acid fast smear of sputum Extensive upper lobe infiltrate or cavity Copious production of thin sputum and severe & forceful cough Environmental factors like poor air circulation

15. Transmission (cont’d) Low chances of transmission in children: Most adults within 2 weeks after beginning adequate chemotherapy becomes non-infectious Young children (sparse tubercle bacilli in endobronchial secretions of children and lack of tussive force of cough) Children are considered infectious when they are having cavitatory lesion or draining TB wound which can aerosoliz . However adults accompanying TB children should have screening done because upto 15 % of them had TB.

16. Transmission (cont’d) M. bovis and M. africanum – airborne transmission M. bovis penetrates the GI mucosa, lymphatic tissue of oropharynx Human infection is low due to pasteurization of milk in developed countries

17. Pathogenesis

18. A. Inhalation of bacilli B. Containment in a granuloma C. Breakdown of the granuloma in less immunocompetent individuals

19. Pathogenesis Inhalation of M. tuberculosis leads to one of the three possible outcomes: Immediate clearance of the organism Latent tuberculosis infection (LTBI) Primary infection (onset of active disease)

20. Primary Disease Time between initial infection & clinically apparent disease: Disseminated & meningeal TB – 2-6 months Endobronchial TB & lymph node involvement – 3-9 months Lesions of bones & joints – several years Renal lesions – decades Extrapulmonary manifestations develop in 25-35% of children with TB, and 10% of immunocompetent adults

21. Source: Pakistan National TB Control programme NTP Guideline 2007 Revised.

22. Immunity Cell mediated immunity develops 2-12 weeks after infection along with tissue hypersensitivity The pathologic events depend on the balance among: Mycobacterial antigen load Cell mediated immunity (enhances intracellular killing) Tissue hypersensitivity (enhances extracellular killing)

23. In absence of treatment Death in 80% of cases Remaining cases develop chronic disease (repeated episodes characterized by fibrotic changes) Complete spontaneous eradication is rare

24. Natural history of tuberculosis in a newly infected (adult) contact (infection is not necessarily disease) CONTACT NO INFECTION INFECTION NO DISEASE DISEASE EARLY DISEASE LATE DISEASE Cell-mediated immunity Defenses (5%) (5%) (90%)

25. DIAGNOSIS: CMI CONTACT NO INFECTION NO DISEASE DISEASE EARLY DISEASE LATE DISEASE Defenses (5%) (5%) (90%) INFECTION cell-mediated immunity PPD positive

26. Reactivation Disease Dormant bacteria seeded at the time of primary infection Reactivation of tubercle bacilli (usually endogenous regrowth of bacilli persisting in partially encapsulated lesions) Localized lesion Little regional lymph node involvement and less caseation Typically occurs at the lung apices Disseminated disease is unusual in immunocompetent individuals

27. Reactivation Disease Rare in children Common among adolescents and young adults Risk of dissemination is high in: HIV infected persons Immunocompetent persons in highly endemic areas

28. Pregnancy and Newborn TB in a pregnant woman has increased risk of following in the neonate: Prematurity Fetal growth retardation Low birth weight Perinatal mortality Congenital TB is rare because TB of female genital tract results in infertility

29. Congenital TB Source: Primary infection in mother, transmitted through placenta (umbilical vein) just before or during delivery Tubercle bacilli first reach liver Periportal lymph node involvement Main fetal circulation → infect many organs Congenital TB can also be caused by ingestion or aspiration of infected amniotic fluid Most common cause of TB at birth is postnatal airborne transmission of disease

30. Disseminated TB pneumonia

31. MILIARY Disease Generalized Hematogenous Tuberculosis Generalized dissemination through bloodstream caseous focus ruptures into blood vessel growth of tubercle within the blood vessel may be acute, occult or chronic, liver lung nad bone marrow are uusually seeded. Uniformly fatal if not treated Rare Usually occurs in the first 4 months after primary infection Occures in vulnerable hosts those with malnutrition or immunodefeciency .

32. MILIARY Disease Millet seed appearance on X-ray Mantoux positive? Most children still have active primary complex when miliary disease strikes Most develop meningitis

33. Major sites of extra-pulmonary tuberculosis among children in the United States SITES % Avg. Age lymphatics 67 5y meninges 13 3y pleura 6 16y miliary 5 1y skeletal 4 5y other 5 Clin Chest Med 1989, Am. Rev. Resp. Dis , 1990

34. TB MENINGITIS Dreadful complication of TB High morbidity and mortality Should be treated at tertiary care facility. Common form of extrapumonary TB after lymphadenitis Commoner below 5 yr greatest risk 20% in <12months. Involes basal meninges , cerebral cortex and choroid plexus.

35. TB MENINGITIS (CONT’D) Spread of MTB is hematogenous Children have classically insidious presentation but neonate had fulminant course. Fever headache, malaise, irittability vomiting, weight loss, and neck stiffness are clue to diagnosis

36. TB MENINGITIS 40% of cases ocur within 3 months of estimated onset of TB rarely < 1 month 90% with TB menningitis PPD positive 94% of these have positive CXR’s average duration from meningitis diagnosis to death (untreated) 19.5 days

37. TB LYMPHADENITIS Most common of all extra pulmonary TB Presentation is solitary or multiple painless matted lymph nodes that do not respond to oral antibiotics. Systemic signs and symptoms may or may not be present. LN biopsy or FNAC is required for diagnosis Differential include; lymphoma, fungal infection, and bacterial infection

38. Gi tb Insidious onset with diverse signs and symptoms Diagnosis is difficult and delayed and therefore leads to high morbidity and mortality. Should be treated at tertiary care level. As many as 60% undergo laparatomy for diagnosis and reliief of obstruction