Tuberculosis

1. Tuberculosis Presented By: Dr. Aya Abdel Dayem Lecturer of Chest Diseases Faculty of Medicine Ain Shams University [ASU] Egypt

2. TB kills nearly 3 million/yr worldwide. If one includes HIV-related TB, then Tb is the leading infectious cause of death worldwide, even though it has been highly treatable for 50 years. Worldwide prevalence: 2 billion people; UK incidence: 7000/yr. 10% are drug-resistant; more in the USA.

3. Pathology Primary TB Initial Infection is usually pulmonary (by droplet spread). A peripheral lesion forms (Ghon focus), and its draining nodes are infected (Ghon complex).

4. Post-Primary TB Immunocompromise may allow reactivation, malignancy; diabetes; steroids; debilitation (esp. HIV or old age).

5. Pulmonary TB: This may be silent or present with cough, sputum, malaise, weight loss, night sweats, pleurisy, haemoptysis (may be massive), pleural effusion, or superimposed pulmonary infection. Investigation and treatment: An aspergilloma/mycetoma may form in the cavities.

6. Miliary TB: Occurs following haematogenous dissemination. Clinical features may be non-specific. CXR shows characteristic reticulonodular shadowing. Look for retinal TB. Biopsy of lung, liver, lymph nodes, or marrow may yield AFB or granulomata.

7. Meningeal TB: Subacute onset of meningitic symptoms: fever, headache, nausea, vomiting, neck stiffness, and photophobia.

8. Genitourinary TB: May cause frequency, dysuria, loin/back pain, haematuria, and, classically, sterile pyuria. Take 3 early morning urine samples (EMU) for AFB. Renal ultrasound may help. Renal TB may spread to bladder, seminal vesicles, epididymis, or fallopian tubes.

9. Bone TB: Look for vertebral collapse adjacent to a paravertebral abscess (Pott�s vertebra). Do x-rays and biopsies (for AFB stains and culture). Skin TB (lupus vulgaris): Look for jelly-like nodules, e.g. on face or neck.

10. Peritoneal TB: This causes abdominal pain and GI upset. Look for AFB in ascites (send a large volume to lab); laparotomy may be needed. Acute TB pericarditis: Think of this as a primary exudative allergic lesion.

11. Chronic pericardial effusion and constrictive pericarditis: These reflect chronic granulomata. Fibrosis and calcification may be prominent with spread to myocardium. (Giving steroids to these patients for 11 wks with their anti-TB drugs reduces need for pericardiectomy.)

12. Diagnosis Diagnosis in all suspected cases, it is important to obtain the relevant clinical samples (sputum, pleural fluid, pleura, urine, pus, ascites, peritoneum, or CSF) for culture to establish the diagnosis.

13. Microbiology: Send multiple sputum for MC&S for AFB (acid-fast bacilli), pleural aspiration and biopsy if there is an effusion. If sputum negative, bronchoscopy with biopsy and bronchoalveolar lavage may be helpful. Biopsy any suspicious lesions in liver, lymph nodes or bone marrow. AFB are bacilli that resist acid-alcohol decolourization under auramine or Ziehl-Neelsen (ZN) staining. Cultures undergo prolonged incubation (up to 12 wks) on Lowenstein-Jensen medium.

14. TB PCR: Allows rapid identification of rifampicin (and likely multi-drug) resistance. Occasionally useful for diagnosis in sterile specimens. Histology: The hallmark is the presence of caseating granulomata. Radiological Features: CXR may show consolidation, cavitation, fibrosis, and calcification pulmonary TB.

15. Tuberculin skin test: TB antigen is injected to intradermally and the cell-mediated response 48-72 h is recorded. A positive test indicates that the patient has immunity. It may indicate previous exposure of BCG. A strong positive test probably means active infection. False negative test occur in immunosuppression, including miliary TB, sarcoid, AID, lymphoma. Mantoux Test: Serial dilutions of antigens provide 1, 10, and 100, tuberculin units (TU), respectively. The test is +ve if it produces > 10mm induration, and �ve if <5 mm. This test is overrated in diagnosing TB and its use is controversial. I f active Tb is strongly suspected, use 1 TU. If it is positive, infection is likely. Otherwise, interpret in the clinical context.

16. Interactions of HIV and TB are as follows: Mantoux tests may be negative. Increased reactivation of latent TB. Presentation may be atypical. Previous BCG vaccination does not prevent development of TB. Smears may be negative for AFB.

17. Interactions of HIV and TB are as follows: (cont�d) Atypical CXR: lobar or bibasal pneumonia, hilar lymphadenopathy. Extrapulmonary and disseminated disease is much more common. More toxicity from highly-active antiretroviral therapy (HAART) and anti-TB therapy due to drug interactions. Antiretroviral therapy reconstitutes CD4 count and immune function, which may lead to a paradoxical worsening of TB symptoms, called the �immune reconstitution inflammatory response� (IRIS). Lifelong prophylaxis with isoniazid is probably not helpful (controversial) but regular clinical monitoring is vital.

18. Additional points in all those with TB: Advise HIV testing. Notify consultant in communicable disease control (CCDC) to arrange contact tracing and screening (preferably by a chest physician). Explain that prolonged treatment will be necessary. Explain that taking the tablets as prescribed is important. Monitoring of blood tests will be needed (LFTs). Explain that directly observed therapy (DOT) may be needed to ensure that the right pills are swallowed. Explain the need for respiratory isolation procedures while infectious. Check regularly for drug compliance and toxicity.

19. Treatment of Pulmonary TB Before treatment: Stress importance of compliance Check FBC, liver and renal function. Test colour vision and acuity before and during treatment ocular toxixity. Audiogram

20. Respiratory isolation is essential when TB patients are near +ve patients. hospital-acquired and MDR-TB are now major problems worldwide, affecting both HIV +ve and HIV �ve people. Mortality is ~80% in patient-to-patient spread.

21. First line antitubercular agents: Isoniazid Streptomycin Rifampicin Amikacin Pyrazinamide Kanamycin Ethambutol Capreomycin

22. Second line antitubercular agents: Ofloxacin Aminosalicylic acid Ciprofloxacin Clarithromycin Cycloserine Azithromycin Ethionamide

23. Consider DOT,sd follows: Initial Phase (8wks on 3-4 drugs): Rifampificin 600-900mg (child 15mg/kg) PO 3 times/wk. Isoniazid 15mg/kg PO 3 time/wk + pyridoxine 10mg/24h. Pyrazinamide 2.5g PO (2g if <50kg) 3 times/wk (child 50mg/kg) If resistance possible, add ethambutol 30mg/kg PO 3 times a week or streptomycin 0.75-1g/24h Im (child 15mg/kg/24h). Monitor LFT weekly.

24. Continuation Phase (4 months on 2 drugs): Riframicin and isoniazid at saem doses. (2 Rifanah 300 tablets = riframicin 600mg + isoniazid 300mg). If resistance is a problem use ethambuthol 15mg/kg PO. Give pyridoxine throughout treatment. Steroids maybe indicated in meningeal and pericardial disease

25. Stopping the spread of MDR-TB Chief goals: early identification; full treatment; isolation. Control may be linked to: Early isolation of suspected patients. A suspicious CXR or a past history of MDR-TB is enough. Don�t wait to prove the diagnosis. The ability to obtain Zeihl-Nielson (ZN)/auramine stains 24h a day. Directly observing & confirming that patients take all prescribed drugs. Wearing of special masks by staff and the patient if s/he leaves the isolation room (avoid this if possible).

26. Sputum induction/expectoration being confined to isolation rooms. Doors to isolation rooms having automatic closing devices. Providing negative air pressure in isolation rooms. Only stop isolation after > 3 sputum samples are AFB �ve on culture for MDR-TB. Frequent tuberculin skin surveillance tests for workers and contacts.

27. Chemoprophylaxis Suitable patients for chemoprophylaxis includes adult with documented recent tuberculin conversion, and young immigrants (16-34) who are heaf grade 3-4 positive without BCG vaccination.

28. This involves administration of one or two anti TB drugs for shorter periods than for symptomatic disease (e.g rifampicin and isoniazid for 3 months, or isoniazid alone for 6 months).

29. Prevention of TB in HIV +ve Indications for primary prophylaxis: If the patients has not been BCG and the Mantoux test is >5mm (Heaf 1-4). If BCG vaccinated (10>yrs ago), consider prophylaxis if Mantoux >10mm (Heaf 3-4) If there is recent exposure to someone with active TB.