T.B by Dr. Zenawit..................pptx

Tb

1. Tuberculosis Zenawit.A ( Assistant professor in pediatics and child health )

2. Outline Key epidemiological data: Global, Ethiopia What do we mean by contact? Is cough important for TB transmission? Extent of transmission? Who is at risk? Diagnostic modalities TB-Prevention Treatment

3. Tuberculosis TB has been there for >4,000 yrs (studies of human skeleton) First recognized as a clinical entity by Schönlein , who used the term tuberculosis in 1830 , tubercle means lesion of consumption March 22, 1882, Dr.Robert Koch discovered Mycobacterium Tuberculosis (World TB day) 1.7 billion of world population infected; 5-10% of adults and up to 40% of children will develop the disease.

4. Key facts 1.4 million died from Tb in 2019, including 208,000 HIV+ people 10 million people fell ill with TB – 5.6 million men – 3.2 million women – 1.2 million children TB is one of the 10 top causes of deaths

5. Countries with high burden of TB Eight countries accounted for 2/3 of the global burden: India (27%), China (9%) Indonesia (8%), Philippines (6%), Pakistan (6%), Nigeria (4%), Bangladesh (4%) and South Africa (3%). A total of 30 countries accounted for 87% of the world’s cases. Ethiopia is among the first 20 high burden countries

6. TB Classification

7. Classification based on anatomical site Pulmonary TB (PTB): TB involving the lung parenchyma or the tracheobronchial tree. Miliary TB is classified as PTB. TB intrathoracic lymphadenopathy ( mediastinal and/or hilar ) or pleural effusion, without CXR abnormalities in the lungs , is a case of extrapulmonary TB. A patient with both pulmonary and extrapulmonary TB should be classified as a case of PTB.

8. Extrapulmonary TB (EPTB): involving organs other than the lungs , e.g. pleura, lymph nodes, abdomen, GUT, skin, joints and bones, meninges .

9. Classification based on Hx of previous TB Tx New patients have never been treated for TB or have taken anti-TB drugs for < 1 month. Previously treated patients : received anti TB ≥ 1 month further classified by the outcome as follows: – Relapse/re-infection patient diagnosed with an episode of TB after declared cured or Tx completed

10. _ Treatment failure are those who have previously been treated for TB and whose Tx failed at the end of most recent Tx _ T reatment after loss to follow-up (LTFU) patients : previously treated for TB and were lost (previously known as Tx default ) – Other previously treated patients : treated for TB but whose outcome after their most recent Tx is unknown or undocumented

11. Classification based on drug resistance Monoresistance : resistance to one first-line anti-TB drug only . Multidrug resistance (MDR TB) : resistance to at least both isoniazid and rifampicin . Polydrug resis tance: resistance to >1 first-line antiTB drug (other than both INH and rifampicin ). Extensive drug resistance(XDR TB) : resistance to any fluoroquinolone and to at least one of three second-line inject able drugs ( capreomycin , kanamycin and amikacin ), in addition to MDR.

12. … based on resistance Rifampicin resistance (RR TB) : resistance to rifampicin with or without resistance to other anti-TB drugs.(Mono-RR, MDR, PolyDR , XDR) . Patients found to have an RR-TB or MDR-TB : should be started on second-line drug regimen

13. Lab Diagnosis Acid fast stains AFS : Detected > 100 yrs ago * Ziehl–Neelsen stain * Kinyoun stain does not need heating * Auramine – rhodamine staining in the US * 10,000 organisms/ml are required for smear positivity * Sensitivity of sputum AFS is 60% compared with culture

14. Why collection of 3 sputum sample ? Detection of a single bacilli is highly suggestive Detection of 10 bacilli per slide is optimal Sensitivity increases: * By 10% with the collection of the 2 nd sample * By 2% with the 3 rd sample

15. What fluids can be collected ? Any biologic fluid or material can be examined: Pleural fluid, Peritoneal fluid CSF Urine Gastric aspirate Sputum Pus aspirate etc thin fluids are best examined after sedimentation by centrifugation.

16. Tb-Culture Gold standard Mycobacterium grow very slowly: rate 1/20 compared with the growth of conventional bacteria Bacteria generation time 12-24 hrs Cultured on Löwenstein -Jensen culture media growth will take 3-6 wks( up to 12 wks)

17. Fluid samples vs Biopsies yield for Tb culture Pleural fluid <30% are culture positive Pleural Biopsies 40-80% are culture positive Peritoneal fluid <20% are culture positive Peritoneal Biopsies >60% % are culture positive

18. Molecular tests 1. Rapid molecular test: Xpert MTB /RIF assay * Provide result in 2 hrs * Better accuracy than microscopy * Positive when > 10 bacteria/ml * Costly and needs trained Lab staffs 2. First line Probe assay(LPAs) (2008): tests for RIF and INH 3 . Second line probe assay(2016 ): tests for flouroquinolones and injectable anti- Tbs

19. Transmission Routes: – Inhalation of airborne droplet nuclei – Rarely by direct contact with infected discharge or contaminated fomite – Ingestion : M.bovis – Trans placental route Droplet nuclei.: particles 1–10 mcm in diameter, the dried residue formed by evaporation of droplets c oughed or sneezed into the atmosphere are also infective.

20. Transmission increases… A single bacilli is enough to infect ! When source case has/is older child / adult with: * Smear positive sputum * Copious thin sputum * Extensive upper lobe /cavity * Forceful cough * Patients who are not yet Txed or Tx for < 2wks Most children rarely infect others: bacilli are sparse and do not have forceful coughing

21. Is cough a prerequisite ? Coughing, sneezing, singing, simply talking The site and the mechanism of aerosolization is important

22. Transmission rate With prolonged exposure to smear + ve patient 10-50% of contacts are infected * 30% develop primary TB * 70% Latent TB * 5-10% develop secondary TB Pulmonary >80% 70% are smear positive Extra-pulmonary <20%

23. Who is at risk ? M:F= 2:1 Children < 5years of age HIV + Malnutrition Immune deficiency conditions: Cancer patients Immune suppressive therapies DM High risk behaviors: Household contact to smear positive/ cavitary TB patient

24. Pathogenesis

25. Clinical course of TB Disease Time varies between initial infection and apparent disease: Pulmonary TB in 70-75% of cases: with in weeks Disseminated and meningeal TB : within 2-6 mo. Lymph node or endobronchial TB: within 3-9 mo. Bones and joints: several years

26. Renal TB : decades after infection. Extrapulmonary manifestations are more common in children, develop in 25-35% of children with TB, compared to 10% of immunocompetent adults. Reactivation TB: rare in children, common among adolescents and young adults.

27. C/F: Primary pulmonary disease Commonly : Nonproductive cough and mild dyspnea fever , night sweats, anorexia and decreased activity Failure-to-thrive; not improving with nutrition alone Pts with bronchial obstruction have localized wheezing or decreased breath sounds, accompanied by tachypnea or, rarely, respiratory distress. These Sxs & Sns are occasionally alleviated by antibiotics, suggesting bacterial super infection. 50% of children with CXR finding do not have P/E finding

28. Figure: Left Pleural effusion: Obliterated costo-phrenic and cardio- phrenic angles, opaque left lung

29. C/F: Progressive Primary Pulmonary Disease: High fever, severe cough with sputum , weight loss, and night sweats are common. P/E diminished breath sounds, rales , and dullness or egophony over the cavity.

30. C/F: Reactivation Tuberculosis: Common in children who acquire the initial infection when they are older than 7 yr of age. most common sites are the apical seedings (Simon foci) More Sxic than children with primary pulmonary Tb. Sxs : fever , anorexia, malaise, weight loss, night sweats, productive cough, hemoptysis , and chest pain

31. CXR : Extensive infiltrates or thick walled cavities in the upper Lobes Pleural Effusion : from a sub-pleural pulmonary focus or caseated lymph node.

32. Summary of Ghon complex

33. C/F:Miliary disease • Lympho-haematogenous dissemination to spleen, liver, lung, lymph nodes, skin, bones, joints, kidneys, p eritoneum, pericardium and meninges • Common in immune compromised/malnourished Sxs : pt gravely ill with Sx complex of TB, Sns : TST non reactive in 40% of pts, hepatosplenomegaley , emaciation, Sns of meningitis, peritonitis etc Resolution is slow with Tx , steroids for Sxic relief Excellent prognosis with early Tx

34. C/F: Cardiac TB Rare, only in 0.5-4% of TB cases in children: The most common form of cardiac TB is pericarditis . Either from direct invasion or from subcarinal lymph nodes. Sxs : low-grade fever, malaise, Wt loss ; chest pain is unusual. Sns : pericardial friction rub or distant heart sounds with pulsus paradoxus .

35. Pericardial fluid: serofibrinous or hemorrhagic, AFS -smear rarely + ve , but cultures are positive in 30-70% of cases. Pericardial biopsy: culture + histology ( granulomas ). Partial or complete pericardiectomy may be required when constrictive pericarditis develops.

36. C/F: Upper airway TB Larynx: croup like, sore throat , dysphagia Middle ear : painless unilateral otorrhea , Dx difficult since AF stain and culture from ear discharge are usually – ve

37. Lymph node Tb occurs with in 6-9 months of infection , Tonsillar , anterior cervical , submandibular , and supraclavicular nodes become involved secondary to extension of upper lung fields or abdomen.

38. Inguinal, epitrochlear , or axillary regions : from tuberculosis of the skin or skeletal system. CXR normal in 70% Culture from lesion positive in 50% of cases May heal by itself or ceseat and heal by Fibrosis Dx FNAC /Biopsy

39. CNS TB CNS Tb : Follow lympho-hematogenous dissemination of primary TB, Complicates 0.3% of children, common between age 6mo to 4 yrs – The brainstem is often the site of greatest involvement , with dysfunction of cranial nerves III, VI, and VII. – The exudate interferes with the flow of CSF > > communicating hydrocephalus

40. – The vasculitis , infarction, cerebral severe edema, and hydrocephalus results in the CNS damage gradually or rapidly . – Profound abnormalities in electrolyte metabolism from salt wasting or the SIADH

41. TB meningitis: Stage 1 : lasts 1-2 wk ; nonspecific Sxs : fever, headache, irritability, drowsiness, and malaise. Stage-2 : lethargy, nuchal rigidity, seizures, + ve meningeal Sns , hypertonia , vomiting, cr.nerve palsies, and other focal neurologic signs Stage 3 : is marked by coma, hemi- or paraplegia, hypertension, decerebrate posturing, deterioration of vital signs, and eventually death

42. Dx : high index of clinical suspicion! CSF WBC 10-500 with initial neutrophil predominance, Glucose low, Protein high, CSF AFS + ve in 30%, Culture + ve in 50-70% TST – ve in 50%, CXR normal in 20-50%

43. Tuberculoma Tumor-like mass resulting from aggregation of caseous tubercles, manifest as brain tumor . Accounts for 30% of brain tumors In adults : supertentorial ; In childre n ; infratentorial Mostly singular , but may be multiple Sxs : head ache , fever , focal deficit , convulsion TST is usu reactive , CXR is normal CT: discrete lesions with surrounding oedema CT with contrast: ring enhancing lesions Tx : antiTB + steroids resolve most lesions +/-surgical excision

44. Paradoxical development of tuberculomas in patients with TB meningitis receiving anti Tb with out failure has been recognized. This phenomenon should be considered whenever a child with tuberculous meningitis deteriorates or develops focal neurologic findings while on treatment. Corticosteroids can alleviate severe clinical Sns & Sxs . These lesions can persist for months or years.

45. MRI of 3 years old child with multiple ring enhancing lesions: pontine Tuberculoma

46. Bone and joint TB disease Skeletal TB account for 10% of all TB cases and spinal TB account for 50% of these Onset varies from 2 weeks to several years Cold abscesses of paraspinal tissues or psoas muscle may protrude under the inguinal ligament and may erode into the perineum or gluteal area ( Scarpa’s triangle).→

47. Pott’s disease The lower thoracic vertebrae in 40-50%, Lumbar spine in 35-45%. Cervical spine in 10% Neurologic abnormalities occur in 50% Almost all patients have some degree of spine deformity ( kyphosis ). Only 10-38% of cases of Pott disease are associated with extraskeletal tuberculosis

48. Typical TB spondylitis signs

49. GIT TB Most common is painless ulcer on the mucosa, palate or tonsils TB of oral cavity, pharynx and parotid unusual Esophageal TB: secondary t o tracheoesophageal Fistula TB peritonitis with involvement of mesenteric lymph nodes (doughy irregular non tender abdomen ) TB enteritis : secondary to haematogneous diss. o r swallowing of sputum Sxs : shallow ulcers causing pain, diarrhea, constipation & wt loss

50. GUS TB Renal Tb : Rare in children has long incubation period Small caseous foci develop in the renal parenchyma and release M. tuberculosis into the tubules. A large mass develops near the renal cortex that discharges bacteria through a fistula into the renal pelvis. Infection then spreads locally to the ureters , prostate, or epididymis

51. Early stages : often clinically silent in its, marked only by sterile pyuria and microscopic hematuria . Hydronephrosis or ureteral strictures are complications Urine cultures for M. TB are + ve in 80-90% of cases, and AFS of large volumes of urine sediment are + ve in 50-70% TB salpingitis , endometritis , oophoritis , and cervisitis can occur in pubertal girls Epididymitis and orchitis in boys

52. Patients who need hospital admission

53. Pregnancy and new born Congenital TB: Is rare because the most common result of female GUT-TB is infertility . Secondary to haematogenous or aspiration of amniotic fluid Especially when the mother has primary infection Increased risk for prematurity, IUGR, LBW, and perinatal mortality. Manifest by 2-3 wks of age. Sxs : resp distress, hepatosplenomegaley DDX sepsis, other TORCH infections

54. TB Treatment 1. Chemotherapy 2 . Nutritional rehabilitation 3. Adjutant 4.Preventive therapy

55. Anti TB regimens

56. Pediatrics Drug formulations

57. Additional TX for TB Corticosteroids for : TB meningitis, Airway obstruction by enlarged lymph nodes and Pericardial TB. Prednisone: 2 mg/kg daily, (4 mg/kg daily for seriously ill children) with a max. dosage of 60 mg/day for 4 weeks, then taper over 1–2 weeks.

58. Pyridoxine supplementation INH may cause Peripheral neuropathy because of pyridoxine deficiency, particularly in children with SAM and HIV + ve on ART. Pyridoxine 5–10 mg/day Surgical intervention when necessary

59. Nutritional support Do proper nutritional assessment and treat Accordingly BF should continue for 24 months of age.

60. Follow up End of 2 nd month Anti TB assess if : - has no symptom resolution/worsening symptoms ; - shows continued weight loss; - Sputum smear/gastric aspirate is p ositive

61. Poor adherence is a common cause of “ Tx failure”. Tx failure suggests MDR-TB Tx failure more common in children living with HIV . If the child is doing good on 2 nd month, he will have investigative evaluations on 5 th month

62. TB Prevention

63. Latent tuberculosis infection (LTBI) LTBI: A state of persistent immune response to stimulation by M. Tb Ags with no evidence of clinically active TB. No gold standard test to identify M.TB infection in humans . LTBI Tx is offered to individuals who are considered to be at risk for TB disease

64. Who are at risk ? T h o s e living i n high TB burden countries with immune risk factors and Children <5 years who have contact with patient with Open/ cavitary TB

65. High/Low Tb country Low-TB-incidence country: Country with a WHO-estimated TB incidence rate of < 10 / 100,000 population • High-TB-incidence country: A country with a WHO-estimated TB incidence rate of ≥ 100/100,000 Ethiopia is here

66. Any Ixs for LTBI? Tuberculin Skin Test (TST) TST is false negative in malnouritioned , immune compromised children, children with measels , mumps, varicella , influenza ; and sever forms of TB TST false positive after other mycobacterial infections(MAC etc) Interferon Gamma Release Assay (IGRA) Their absence should not limit IPT

67. Interferon-Gamma Release Assays (IGRAs) IGRAs: whole-blood tests that can aid in diagnosing M.tuberculosis infection. IGRA do not help differentiate LTBI from Active TB. What IGRA is: WBCs from most persons infected with M. TB will release interferon-gamma (IFN-g) when mixed with antigens derived from M. tuberculosis

68. What are the advantages of IGRAs? Requires a single patient visit to conduct the test. Results can be available within 24 hours. Does not boost responses measured by subsequent tests. Prior BCG vaccination does not cause a false positive IGRA test result.

69. What are the limitations of IGRAs? Blood samples must be processed within 8-30 hours after collection while WBCs are still viable. Errors in collecting or transporting blood specimens or in running and interpreting the assay can decrease the accuracy of IGRAs. Limited data on the use of IGRAs to predict who will progress to TB disease in the future.

70. Limited data on the use of IGRAs for: – Children younger than 5 years of age; – Persons recently exposed to MTb – Immuno -compromised persons; and – Serial testing. Tests may be expensive .

71. What to give INH for 6 months INH+RIF for 3-4 months for low TB burden countries ( caution!!! in HIV positives)

72. BCG Vaccine Bacille Calmette -Guerin (BCG) is a live attenuated vaccine derived from M.bovis . Protection rate varies among settings In children who are known to be HIV-infected, BCG vaccine should not be given for fear of disseminated BCGitis HIV exposed infants whose HIV status is unknown and who lack symptoms suggestive of HIV, BCG vaccine should be given

73. BCG and TST 50% of children who are BCG vaccinated will not have reaction to TST Of those who react, they start to wean with in 2-3 years, most loose it 5-10 years If it persists it is usually < 10 mm of indurations

74. THANK YOU ! ! !