1. Contact Investigation Dr. Essam Elmoghazy

2. Contact Investigations – A Crucial Prevention Strategy On average, 10 contacts are identified for each person with infectious TB. 20%–30% of all contacts have LTBI 1% of contacts have TB disease Of contacts who will ultimately have TB disease, approximately one- half develop disease in the first year after exposure Early identification means a better chance of cure and, especially, a reduction in further transmission. Furthermore, contact investigation allows identification of people who are latently infected and at high risk for active TB, who can be treated preventively. Decision to investigate an index patient depends on presence of factors used to predict likelihood of transmission – Site of disease – Positive sputum bacteriology – Radiographic findings

3. Contact Investigations – A Crucial Prevention Strategy Effective investigation of TB contacts within national TB programmes and other services can result in the detection of a significant number of cases. WHO estimates show that, worldwide, highly infectious, smear-positive pulmonary TB develops in over 4 million people annually. If we assume that each of these patients has at least three close contacts, such as in their household, and that the prevalence of active TB among the close contacts is 2.5%, the number of early TB cases that could be identified among close contacts is at least 300 000 per year. contact investigations could be particularly useful for identifying childhood TB contact investigation can help identify people who require careful follow-up, such as those who were exposed to an index case of M/XDR-TB or people infected with HIV, whose risk for rapid progression to active TB is very high.

4. Contact Investigations – A Crucial Prevention Strategy Contact investigation be conducted for household and close contacts when the index case has any of the following characteristics: has sputum smear-positive pulmonary TB, has multi-drug-resistant TB (MDR-TB or extremely-resistant TB (XDR-TB) (proven or suspected), is a PLHIV or is a child < 5 years of age. Clinical evaluation of household and close contacts for active TB be a priority on the basis of their risk for having or developing active TB or for the potential consequences of the disease if it develops. Priority should be given to: people of all ages with symptoms suggestive of TB, children < 5 years of age, people with known or suspected immunocompromising conditions (especially PLHIV) and contacts of index cases with MDR-TB or XDR-TB (proven or suspected). children < 5 years of age who are household or close contacts of people with TB and who, after an appropriate clinical evaluation, are found not to have active TB should be treated for presumed LTBI.

5. Tuberculin Skin Test (TST) Purified Protein Derivative (PPD) is injected intradermally 48 –72 hours later the size of the resultant reaction is measured - Induration (firm area) - Erythema (redness)

6. Tuberculin Skin Testing What is it? The Mantoux tuberculin skin test (TST) is the standard method of determining whether a person is infected with Mycobacterium tuberculosis. Reliable administration and reading of the TST requires standardization of procedures, training, supervision, and practice. How is the TST Administered? The TST is performed by injecting 0.1 ml of tuberculin purified protein derivative (PPD) into the inner surface of the forearm. The injection should be made with a tuberculin syringe, with the needle bevel facing upward. The TST is an intradermal injection. When placed correctly, the injection should produce a pale elevation of the skin (a wheal) 6 to 10 mm in diameter. How is the TST Read? The skin test reaction should be read between 48 and 72 hours after administration. A patient who does not return within 72 hours will need to be rescheduled for another skin test. The reaction should be measured in millimeters of the induration (palpable, raised, hardened area or swelling). The reader should not measure erythema (redness). The diameter of the indurated area should be measured across the forearm (perpendicular to the long axis). How Are TST Reactions Interpreted? Skin test interpretation depends on two factors: 1.Measurement in millimeters of the induration 2.Person’s risk of being infected with TB and of progression to disease if infected

7. Tuberculin Skin Testing What Are False-Positive Reactions? Some persons may react to the TST even though they are not infected with M. tuberculosis. The causes of these false-positive reactions may include, but are not limited to, the following: Infection with nontuberculosis mycobacteria Previous BCG vaccination Incorrect method of TST administration Incorrect interpretation of reaction Incorrect bottle of antigen used What Are False-Negative Reactions? Some persons may not react to the TST even though they are infected with M. tuberculosis. The reasons for these false-negative reactions may include, but are not limited to, the following: Cutaneous anergy (anergy is the inability to react to skin tests because of a weakened immune system) Recent TB infection (within 8-10 weeks of exposure) Very old TB infection (many years) Very young age (less than 6 months old) Recent live-virus vaccination (e.g., measles and smallpox) Overwhelming TB disease Some viral illnesses (e.g., measles and chicken pox) Incorrect method of TST administration Incorrect interpretation of reaction

8. Interferon-gamma release assays (IGRAs) Interferon-gamma release assays (IGRAs) are diagnostic tools for latent TB infection (LTBI). They indicate a cellular immune response to M. tuberculosis. IGRAs cannot distinguish between latent infection and active tuberculosis (TB) disease, and should not be used as a sole method for diagnosis of active TB, which is a microbiological diagnosis. A positive IGRA result may not necessarily indicate active TB, however a negative IGRA result rules out the possibility of both active and latent TB. Because IGRAs are not affected by BCG vaccination status, IGRAs are useful for evaluation of LTBI in BCG-vaccinated individuals, particularly in settings where BCG vaccination is administered after infancy or multiple (booster) BCG vaccinations are given. In contrast, the specificity of tuberculin skin test (TST) varies depending on timing of BCG and whether repeated (booster) vaccinations are given. QuantiFERON, also known as QFT, is an IGRA used in TB diagnosis. The QFT-GIT assay is an ELISA-based, whole-blood test that uses peptides from three TB antigens QuantiFERON-TB Gold In-Tube (QFT-GIT), is the third generation test(QFT-GIT)

9. What is QuantiFERON-TB Gold ? Whole blood test to screen for LTBI and active TB ELISA test detects a cellular mediated immune- response (CMI) to TB-infection and disease Absolutely specific for TB Detects both latent and active TB Totally unaffected by BCG vaccination

10. QuantiFERON - Gold In Tube Stage One –Blood collection and harvesting Option 1: Shipment of the blood collection tubes within 16 hours a laboratory prior to incubation. Option 2: Shipment of the blood collection within 3 days after incubation to the laboratory. Possibility to batch samples.

11. Stage 2 –interferon- γ ELISA QuantiFERON Easy “Standard”-ELISA. User-friendly software supplied free-of-charge from Cellestis. No need for new equipment.

12. Tuberculin test and Quantiferon Tuberculin testQuantiferon Requires two visits Results available in 2-3 days Requires only one visit Results available in the next day Affected by Previous BCG Vaccination BCG can cause false positive TST responses in up to 50 % of cases Unaffected by BCG Vaccination False Positive responses due to non-tuberculosis mycobacterial infections (NTM), up to 20- 40 % of responses can be due to (NTM) infections Unaffected by most non- tuberculosis mycobacterial infections (NTM) Testing Reading is Subjective: Large discrepancies between readers, different cut-off employed depending on perceived risk, induration difficult to measure Objective result: Eliminates inter-reader variability in interpretation of results

13. Risk Factors for Progression from LTBI to Active TB Disease Medical Conditions TB infection may be latent now, but many factors could increase the risk of progression  Immunosuppression  Lymphoma, leukemia  Diabetes  Renal dialysis  Malnutrition  Silicosis  Gastrectomy/ jejunoileal bypass  HIV +  Immunosuppressive drugs e.g. Steroids and cancer chemotherapy

14. Treatment for Latent TB Infection (LTBI) Anyone who has been diagnosed with latent TB infection is a candidate for treatment, if they also fulfill the following criteria:  Willing and able to complete a full course of therapy  Available to be monitored during the full course of treatment  No medical contraindications such as active liver disease Careful assessment to rule out the possibility of active TB disease is always necessary before treatment for LTBI is started.

15. Current Treatment for LTBI Preferred Regimen DrugDoseFrequencyDuration Isoniazid (INH) 300 mg Daily 9 months

16. Thank You