1. Tuberculosis (TB) PHCL 442 Lab Discussion Jamilah Al-Saidan, M.Sc

2. Topics we will cover in TB.. Tuberculin PPD skin test Booster phenomenon BCG vaccine TB & pregnancy TB & Lactation TB & pediatrics

3. Tuberculin PPD Skin Test Also known as Mantoux method Detects infection with M.tuberculosis & not necessary for diagnosis of active TB PPD = Purified Protein Derivative of M.tuberculosis

4. Tuberculin PPD Skin Test Done by injecting 0.1 ml of 5-TU PPD intradermally into the dorsal surface of forearm If a patient has previously been infected with M.tuberculosis sensitized T cells are recruited to the skin site where they release cytokines These cytokines induce an induration (raised area) through vasodilatation, edema, fibrin deposition, and other inflammatory cells to the area. Measure the diameter of the induration to interpret the results TU = Tuberculin Unit

5. Reaction best to be interpreted 48-72 hours. Measure the diameter of the induration in millimeters to interpret the results

6. PPD Skin Test

8. Reading PPD Skin Test ≥ 5 mm≥10 mm≥15 mm Recent contact to someone with active TB Patient with DM No risk factor for TB Patient with fibrotic changes on the CXR consistent with old TB Patient with CRF Organ transplant patientPatient with leukemia or lymphoma HIV patient Recent immigration <5 years from area with high prevalence of TB Immunosuppressed patientEmployee of high risk settings Children < 4 years Mycobacteriology lab personnel Injection drug abusers The person's medical risk factors determine at which increment (5 mm, 10 mm, or 15 mm) of induration the result is considered positive

9. Does a Positive Test Indicate a TB Diagnosis?? No- hence the term false-positive To confirm diagnosis must obtain a culture AFB (sputum smear) AFB = Acid Fast Bacilli

10. False Positive Results Previous administration of BCG vaccine Cross reaction with other mycobacterial species Qualified, experienced person must read the test BCG= Bacillus of Calmette-Guerin

11. Does a Negative Test Eliminate a TB Diagnosis?? No 25% false negative results during initial evaluation of patients with active TB False –ve results can occur in: 1. In persons who have had no prior infection with M.tuberculosis 2. Who have only recently been infected 3. Who are anergic

12. Anergy Decreased ability to respond to Antigens Caused by: 1.Old age/ newborns 2.Corticosteroids 3.Immunosuppressive drugs 4.HIV infection 5.Recent viral infection 6.Malnutrition Does a Negative Test Eliminate a TB Diagnosis??

13. False Negative Results Factors due to the person being tested Factors due to administration Factors due to tuberculin used Factors due to reading the test Live virus vaccinationSQ injectionImproper storage In-experienced reader CRF Injecting too little antigen ContaminationError in recording Recent TB infection (within 8- 10 weeks of exposure) Corticosteroids & immunosuppressant agents age (less than 6 months old, elderly) Bacterial, viral or fungal infection

14. Booster Phenomenon When a person experience a significant increase in the size of a tuberculin skin test reaction that may not be caused by M.tuberculosis Could be due to:  PPD skin test performed every 1-2 years  Prior BCG vaccine  Other mycobacteria

15. Booster Phenomenon Use two-step testing for initial skin testing of adults who will be retested periodically (e.g., health care workers). The incidence of this phenomenon appears to increase with age. This ensures that any future positive tests can be interpreted as being caused by a new infection. Done for new employees. 1.Return to have first test read 48-72 hours after injection If first test is positive, consider the person infected. If first test is negative, give second test 1-3 weeks after first injection 2. Return to have second test read 48-72 hours after injection If second test is positive, consider person previously infected If second test is negative, consider person uninfected A person who is diagnosed as "infected" on two-step testing is called a "tuberculin converter".

16. BCG Vaccine Derived from an attenuated strain of M.bovis Vaccine efficacy only ≤80% More effective if given in childhood Not recommended during pregnancy or for HIV infected individuals Prior vaccination can cause positive PPD skin test Side effects: prolonged ulceration at the vaccination site, lupoid reactions & death BCG: Bacillus of Calmette and Guerin Vaccine

17. TB & Pregnancy Untreated TB represents a greater risk to a pregnant women and her fetus than treatment INH, rifampin, ethambutol & streptomycin have all been reported to be teratogenic in animals but no human reports Studies have shown that INH, rifampin, & ethambutol are safe in pregnancy & can be used to treat TB and treatment should be continued for 9 months

18. TB & Pregnancy All pregnant women on INH should receive pyridoxine 25 mg /day to prevent CNS toxicity Pyrazinamide have no enough data to support its use in pregnancy, only reserved for cases of drug resistance Streptomycin is used only as a last resort due to fear of ototoxicity in infants INH = Isoniazide CNS = Central Nervous System

19. TB & Lactation Only minimum amounts are excreted in breast milk Lactation is safe during anti-TB treatment

20. TB & Pediatrics Whenever a diagnosis is suspected start treatment due to risk of disseminated TB in children Same drugs for adults can be used Examine routinely for signs and symptoms of hepatitis, increase in LFT 2-3 times normal are common but benign and often transient. Except for ethambutol not because it is more toxic but its more difficult to assess visual acuity in children

21. TB & Pediatrics In pediatrics three drugs are enough for treating TB Start with INH 10 – 15 mg/kg/day + Rifampin 10 – 20 mg/kg/day + Pyrazinamide 15 – 30 mg/kg/day  2 months Continue with INH 20-30 mg/kg/dose + Rifampin 10-20mg/kg /dose (two or three times weekly)  4 months Use ethambutol 15 – 20 mg/kg/day or streptomycin 20 – 40 mg/kg/day in cases of resistance only