Update on Tuberculosis contact investigation Dr David Shitrit Maccabi Health Service Rehovot

TB Contact investigation

Conditions increasing the risk for progression to tuberculosis and relative odds (OR, from retrospective studies) or relative risk (RR, from prospective studies) Condition OR or RR Immune suppression HIV-positive and tuberculin skin test-positive 65-67 [C] AIDS68, 69 [C] Solid organ transplantation related to immunosuppressant therapy 70 71, 72[D] Receiving anti-TNF-alpha treatment 73-75 [B] Corticosteroids >15mg prednisolone equivalent per day for >2-4 wks 76, 77 [D*] Malignancy Haematological malignancy (leukemias, lymphomas) 78 Carcinoma of the head or neck and lung 79 Gastrectomy 80, 81 Jejunoileal bypass 82, 83 Silicosis 84-86 Chronic renal failure / haemodialysis 87, 88 Diabetes mellitus 89-92 Smoking 93-97 Underweight 98, 99 Age < 5 years (see table 3) 27 50-110 110-170 20-74 1.5-17 4.9 4-8 16 2.5-6.3 2.5 27-63 30 10-25 2-3.6 2-3 2.0-2.6 2-5

Classification of contacts around the index case according to the degree of exposure. 1st circle of contacts (inner circle) Close household contacts Those who live in the same household as the infectious case. Close non-household contacts Contacts with regular, prolonged (more than an arbitrary minimum of 40 cumulative hours) contact with the source case, sharing breathing space but who do not live in the same household or who spent eight or more cumulative hours with the source case in a confined space, such a as a car, sweat shop or prison cell. These may also include contacts such as close friends and colleagues. 2nd circle of contacts (middle circle) Casual contacts Those who spent less time with the infectious case. These may include frequent visitors to the home, friends, relatives, school or class mates, colleagues at work or leisure contacts and members of a club or team. 3rd circle of contacts (outer circle) Community contacts Those living in the same community or attending the same school, sports club or workplace who may have had sporadic contact.

High priority contacts Priority groups of contacts High priority contacts First circle contacts at increased risk of developing tuberculosis following infection Other first circle contacts Second circle contacts at increased risk of developing tuberculosis following infection Medium priority contacts Second circle contacts Third circle contacts or middle circle Low priority contacts Third circle contacts or outer circle

* When there is a history of a previous positive tuberculin skin test, tuberculosis or latent infection with M. tuberculosis, no tuberculin skin test should be administered ** BCG-vaccinated: chest X-ray only to avoid boosting of tuberculin skin test in 2d round * When there is a history of a previous positive tuberculin skin test, tuberculosis or latent infection with M. tuberculosis, no tuberculin skin test should be administered ** BCG-vaccinated: chest X-ray only to avoid boosting of tuberculin skin test in 2d round Organization and timing of evaluation of contacts of infectious tuberculosis patient. Contact group Timing < 1 wk after diagnosis (or as soon as possible) After window period (8 weeks after end infectious period) High priority Vulnerable close contacts Contacts with symptoms of tuberculosis Tuberculin skin test*/IGRA and chest X-ray ** Tuberculin skin test /IGRA and chest X-ray Other close contacts Optional, or when proved transmission among (vulnerable) close contacts: Tuberculin skin test /IGRA Medium priority Vulnerable casual contacts When proved transmission among high priority contacts: Tuberculin skin test*/IGRA and chest X-ray Other medium priority contacts   When proved transmission among high priority contacts: Low priority When proved considerable transmission among medium priority contacts: Tuberculin skin test /IGRA

The risk of progression to TB among contacts A median incubation time of 6 weeks Highest immediately after incubation time Exponentially decline during the first 7 years 60% in the first year 80% < 2 years After 7 years: 1 per 1000 person-yrs Determined by the age: 30-40% among infant 2% primary school children

Likelihood and risk of transmission Every TB patient should be interviewed promptly after diagnosis Isolated extra pulmonary TB require CXR and sputum examination to exclude concomitant pulmonary disease. The largest number of AFB is found in cavitary lesions Smear negative, culture positive: 13% of all transmissions

Parameters to assess the infectiousness of the index patient Anatomical site: pulmonary TB The production of sputum Results of sputum smear examination Results of sputum culture Cavitation coughing

Infectious period Onset of cough (or other respiratory symptom determine the onset of infectiousness Pulmonary cases with positive smear: maximum of 3 months Pulmonary cases with positive culture and 2 negative smear: 1 month Until 2 weeks of appropriate treatment

Locations of transmission Outdoors vs. Indoors Specific investigation, preferably a visit is important

Susceptibility of the contacts Risk of meningeal/ disseminated TB Risk of Pulmonary disease Age at primary infection 10-20% 30-40% <12 Months 2-5% 12-24 months 0.5% 5% 2-4 years <0.5% 2% 5-10 years >10 years

The tuberculin skin test A positive reaction after 6-8 weeks from the infection 14% anergy in TB children 25% anergy in adults with HIV Sensitivity 95-99% in PPD>5 mm 91-95% in PPD> 10 mm 67-80% in PPD> 15 mm

Specificity of PPD The longer the time since BCG and the larger PPD reaction size, the higher probability of TB Possible causes of FN PPD Age (below 6 months, above 65 yrs) Cellular immune defects Malignancy Systemic high dose seteroids Sarcoidosis

IGRA In immunocompromised persons-more specific and sensitive than PPD Less sensitive in immunocompetent pts than PPD The specificity is much superior to PPD in immunocompetent with prior BCG PPD should not perform in interval of 3 days from IGRA

Treatment regimens for Latent TB Level of evidence Efficacy Treatment regimen A 93% 12 months IZN C 90% 9 months IZN 69% 6 months IZN Unknown (>3HR) 4 months Rifampicin Equivalent to 6 IZN 3 months IZN+RIF(HR)

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