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Tuberculosis Dr Anindo K. Banerjee Consultant Respiratory Physician Southampton General Hospital.

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Presentation on theme: "Tuberculosis Dr Anindo K. Banerjee Consultant Respiratory Physician Southampton General Hospital."— Presentation transcript:

1 Tuberculosis Dr Anindo K. Banerjee Consultant Respiratory Physician Southampton General Hospital

2 History repeating itself “The weariness, the fever and the fret Here, where men sit and hear each other groan; Where palsy shakes a few, sad, last grey hairs, Where youth grows spectre-thin, and dies.” Ode to a nightingale

3 TB incidence

4 TB regional incidence

5 Southampton incidence

6 TB incidence by ethnic group 2011

7 TB incidence by age 2011

8 Non-UK born incidence by age 2011

9 UK born incidence by age 2011

10

11 TB site of disease 2011 Site of disease*Number of casesPercentage** Pulmonary460351.6 Extra-thoracic lymph nodes190621.4 Intra-thoracic lymph nodes91910.3 Other extra-pulmonary6337.1 Pleural6687.5 Gastrointestinal4364.9 Bone – spine3784.2 Cryptic/miliary2683.0 Bone – other2052.3 CNS – meningitis1912.1 Genitourinary1451.6 CNS – other871.0 Laryngeal140.2 Unknown extra-pulmonary150.2 *With or without disease at another site **Percentage of cases with known sites of disease (8916) CNS - Central Nervous System Total percentage exceeds 100% due to infections at more than one site

12 TB pathogenesis

13 Natural history Live inside cells including Type II pneumocytes Lifelong risk 5-10% Greatest in first 2 years

14 Natural history of active TB infection

15 Non-UK born incidence TB by time after entry to UK

16 Incidence of TB in exposed patients

17 At risk patients (latent TB) HIV positive IVDU Solid organ transplant Haematological malignancy Jujunoileal bypass Chronic renal failure or haemodialysis Gastrectomy Anti-TNF therapy Silicosis

18 Symptomatology of TB

19 What do you do next?

20 Clinical specimens for TB MicroscopyCulture Sputum naturalHigh (50-80%)High (>80%) Sputum inducedModerate Bronchial washModerateModerate (25-90%) Nasopharyngeal aspModerate Pleural fluidLow (<5-10%)Low (<25-50%) CSFLow (<5-10%)Moderate (30-90%) Peritoneal fluidLow (<5%)Low (20%) Pericardial fluidLow Synovial fluidLowModerate (<80%) BloodNot applicableLow Bone marrowNot applicableModerate-high

21 CSF in meningeal TB Clear80-90% Pressure>2550% White cells5-1000 x10 3 ml -1 Neutrophils10-70% Lymphocytes30-90% Protein0.45-3 Lactate5-10 CSF / blood glucose<95%

22 To help diagnosis: meningeal TB 10ml CSF for analysis (at least 6ml) Long look at smear (45mins) Image chest and abdomen: other signs TB PCR: good sensitivity if smear positive, not evaluated in smear negative disease Not useful –CSF Adenosine deaminase –Tuberculin skin test –Interferon assay

23 Biopsy for TB MicroscopyCulture Peripheral lymph nodeModerate Pleural biopsyLow (10-50%)High Pericardial biopsyHigh Invasive tissue biopsyLowmoderate Skin biopsyLow AbscessLowModerate StoolLow

24

25 What if it doesn’t culture?

26 Mantoux test Equivalent to 5IU worldwide. From Denmark If BCG>15mm No BCG >5mm False –ve HIV Prednisolone>20mg OD Old age Immunosuppression Overwhelming TB Weak +ve Atypical mycobacteria. BCG

27 Factors leading to negative Mantoux The person being tested –Infections Viral (measles, mumps, chickenpox) Bacterial (typhoid fever, brucelosis, typhus, pertussis, overwhelming TB, Fungal (South American blastomycosis) –Live virus vaccinations (MMR) –Metabolic derangements (chronic renal failure) –Nutritional factors (severe protein depletion) –Diseases of lymphoid organs (Hodgkin’s lymphoma, CLL, sarcoidosis) –Drugs (corticosteroids, other immunosuppressive agents) –Age (newborn, elderly) –Recent overwhelming infection with M. tuberculosis –Stress (surgery, burns, mental illness, graft versus host reactions) Tuberculin used Method of administration Reading the test and recording results

28 Interferon Gamma Release Assay THEORY: A person’s T-cells that previously were sensitized to TB antigen produce high levels of IFN-gamma when re- exposed to the same mycobacterial antigen.

29 Specific antigens in IGRA Not present in BCG

30 Mycobacteria & IGRA antigens

31 Available IGRA tests T-SPOT TB ® The peripheral blood mononuclear cells (PBMC) are washed, isolated and stimulated with ESAT-6 & CFP-10. Incubate overnight: number of T-cells producing IFN-γ “counted ” Not many indeterminates: more laboratory intensive Quantiferon Gold ® –Blood exposed to ESAT-6, CFP-10 and TB7.7 antigens. –Incubated overnight –Plasma removed and assayed for IFN-γ levels by ELISA. –Arbitrary cutoff for level of positives: more indeterminate results.

32 Uses of IGRA testing Detection of mycobacterium tuberculosis infection Useful in –Immunocompromised (indeterminate results in lymphopoenia) –HIV Not useful to diagnose active disease May help to exclude active disease Not useful in monitoring disease response May differentiate non-tuberculous mycobacteria from TB Useful in outbreak investigations (contact tracing)

33 Latent TB infection

34 Risk factors for drug resistance History of prior TB drug treatment Prior TB treatment failure Contact with known case drug-resistant TB Birth / residence county with high incidence resistance HIV infection Residence in London Age: highest rates age 25-44 Male gender

35 Drug resistance by age group *Culture confirmed cases with drug susceptibility results for at least isoniazid and rifampicin **First line drugs - isoniazid, rifampicin, ethambutol, pyrazinamide Age Group IsoniazidMulti-drugResistant to any Total* resistant first line drug** n%n%n% 0-1466.311.166.395 15-443029.0732.233710.03,368 45-65616.270.7676.8989 65+192.800.0213.1675

36 Drug resistance after previous diagnosis TB *Cases with unknown previous history of tuberculosis are excluded. ** Culture confirmed cases with drug susceptibility testing results for at least isoniazid and rifampicin ***First line drugs - isoniazid, rifampicin, ethambutol, pyrazinamide Previous history TB IsoniazidMulti-drugResistant to any Total** resistant first line drug*** n%n%n% Yes2611.1135.63113.3234 No3387.4611.33718.24549

37 Where Drug resistance comes from Place of birth IsoniazidMulti-drug Resistant to any Total** resistant first line drug*** n%n%n% UK born726.140.3796.71187 Non-UK born2958.0762.13268.83689 Central Europe97.710.997.7117 East Asia46.223.146.265 East Europe2038.51426.92038.552 East Mediterranean37.500.037.540 North Africa411.800.0411.834 North America and Oceania00.00 0 2 South Asia1607.4432.01818.42157 South East Asia2012.821.32113.4157 South, Central America & Caribbean711.111.6711.163 Sub-Saharan Africa637.2121.4728.3873 West Europe22.700.022.774

38 Multi-drug-resistant TB

39 Extensively drug resistant TB

40 Drug resistance therapies

41 Isolation and infection control

42 Any questions?

43 Any drug resistance

44 Multi-drug resistance

45 MDR TB worldwide

46 Example PyrazinamideEthambutol AmikacinMoxifloxacin Prothionamide or Cycloserine or PAS Example PyrazinamideEthambutol AmikacinMoxifloxacin Prothionamide or Cycloserine or PAS Treatment of MDR TB At least 4 drugs to which susceptible at least 18 months post culture conversion (usually 24 months total) Use at least: –1 injectable at least 6 months & 4 months after culture conversion –1 quinolone Never add a single drug Side-effects are a big problem

47 Countries with XDR TB

48 Prevalence of XDR TB

49 Treatment of XDR TB Wait for sensitivities No quinolones or injectables As many drugs as possible all second-line May need surgery to debulk disease Treatment regimens typically 2 years or more High incidence of treatment failure

50 Any drug resistance

51 Extensively drug resistant TB

52 Countries with XDR TB

53 Prevalence of XDR TB

54 Treatment of XDR TB Wait for sensitivities No quinolones or injectables As many drugs as possible May need surgery to debulk disease

55

56

57

58 Multidrug-resistant TB

59 Extensively drug-resistant TB

60 HIV prevalence in TB

61 TB and HIV testing

62 Thoracic TB

63 Infection control

64 Features suggestive of TB

65 Ghon focus

66 Typical Chest x-ray features

67 Pleural effusion

68 Miliary disease

69 Other organs

70

71 Use four drugs for 6 months For active respiratory TB use the standard recommended regimen 6 months2 months isoniazid and rifampicin pyrazinamide and ethambutol

72 Treat meningeal TB longer * or another fourth drug Plus glucocorticoid (dose = prednisolone equivalent) adults on rifampicin 20–40 mg adults not on rifampicin 10–20 mg children1–2 mg/kg, maximum 40 mg Gradually withdraw glucocorticoid starting within 2–3 weeks 12 months2 months isoniazid and rifampicin pyrazinamide and ethambutol*

73 Directly observed therapy Consider risk factors for adherence to treatment. Directly observed therapy may be needed for: Street- or shelter-dwelling homeless people with active TB Patients with likely poor adherence, in particular those who have a history of non-adherence

74 World TB prevalence

75 World TB incidence

76 Time course of active TB

77 Results

78 Pathologically

79 Control of TB Effective treatment of disease in clinically affected adults Preventive treatment of infected individuals Protection by BCG Education of community regarding relevant symptoms Active case finding in high risk groups Case contacts Immigrants from high risk countries Homeless and substance abusers HIV positive individuals Subjects with predisposing conditions (renal failure, DM)

80 Screening contacts


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