1. Tuberculosis (TB)
PHCL 442 Lab
Discussion 4
Raniah Al-Jaizani 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 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 to the area
Reaction best seen after hrs
Measure the diameter of the induration to interpret the results
TU = Tuberculin Unit

5. PPD Skin Test

6. PPD Skin Test

7. Reading PPD Skin Test
The person's medical risk factors determine at which increment (5 mm, 10 mm, or 15 mm) of induration the result is considered positive
≥ 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 patient
Patient with leukemia or lymphoma
HIV patient
Recent immigration <5 years from area with high prevalence of TB
Immunosuppressed patient
Employee of high risk settings
Children < 4 years
Mycobacteriology lab personnel
Injection drug users

8. Does a Positive Test Indicate a TB Diagnosis??
To confirm diagnosis must obtain a culture
AFB
AFB = Acid Fast Bacilli

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

10. Does a Negative Test Eliminate a TB Diagnosis??
25% false negative results
False –ve results 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

11. Does a Negative Test Eliminate a TB Diagnosis??
Anergy
Decrease ability to respond to Ag
Caused by:
Old age
Corticosteroids
Immunosuppressive drugs
HIV infection
Resent viral infection
Malnutrition

12. 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 vaccination
SQ injection
Improper storage
In-experienced reader
CRF
Injecting too little antigen
Contamination
Error 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

13. 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

14. Booster Phenomenon
Use two-step testing for initial skin testing of adults who will be
retested periodically (e.g., health care workers).
This ensures that any future positive tests can be interpreted as being
caused by a new infection.
Return to have first test read 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 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".

15. BCG Vaccine Derived from an attenuated strain of M.bovis
Vaccine efficacy only ≤80%
More effective if given in childhood
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

16. 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

17. 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

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

19. TB & Pediatrics
Whenever a diagnosis is suspected start treatment due to risk of disseminated TB in children
Same drugs for adults can be used
Except for ethambutol not because it is more toxic but its more difficult to assess visual acuity in children

20. 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 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