Tuberculosis (TB)Tuberculosis (TB)

PHCL 442 Lab Discussion

Jamilah Al-Saidan, M.Sc

Topics we will cover in TB..Topics we will cover in TB..

• Tuberculin PPD skin test

• Booster phenomenon

• BCG vaccine

• TB & pregnancy

• TB & Lactation

• TB & pediatrics

Tuberculin PPD Skin TestTuberculin 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

Tuberculin PPD Skin TestTuberculin 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 resultsTU = Tuberculin Unit

• Reaction best to be interpreted 48-72 hours.

• Measure the diameter of the induration in millimeters to

interpret the results

PPD Skin TestPPD Skin Test

PPD Skin TestPPD Skin Test

Reading PPD Skin TestReading PPD Skin Test

≥ 5 mm≥10 mm≥15 mm

Recent contact to someone with active TB

Patient with DMNo 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 patientRecent 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

Does a Positive Test Indicate a TB Diagnosis??

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

False Positive ResultsFalse 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

Does a Negative Test Eliminate a TB Diagnosis??

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

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??

Does a Negative Test Eliminate a TB Diagnosis??

False Negative ResultsFalse 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 storageIn-experienced reader

CRFInjecting 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

Booster PhenomenonBooster 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

Booster PhenomenonBooster 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".

BCG VaccineBCG 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 & deathBCG: Bacillus of Calmette and Guerin Vaccine

TB & PregnancyTB & 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

TB & PregnancyTB & 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 = IsoniazideCNS = Central Nervous System

TB & LactationTB & Lactation

• Only minimum amounts are excreted in breast milk

• Lactation is safe during anti-TB treatment

TB & PediatricsTB & 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

TB & PediatricsTB & 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