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2. Contact tracing: new principles Giovanni Sotgiu and Christoph Lange Session III: Treatment and clinical management Bucharest, Friday, 25 May 2012 ERS School Course on TB and M/XDR-TB: from clinical management to control and elimination

3. Contact tracing (CT): outline* Definition and epidemiological principles. Organization of CT activities: Outbreaks in special communities -Prisons; -Schools; -Hospitals; -Air travel. * Source document: Erkens CG, Kamphorst M, Abubakar I, Bothamley GH, Chemtob D, Haas W, Migliori GB, Rieder HL, Zellweger JP, Lange C. Tuberculosis contact investigation in low prevalence countries: a European consensus. Eur Respir J. 2010;36(4):925-49.

4. TB Contact Tracing: definition Investigational activity aimed at identifying individuals with TB and LTBI

5. TB Contact Tracing: aims Ultimate goal STOP transmission TB Control Program

6. TB Contact Tracing: aims 1)To reduce morbidity and TB-related mortality (target: secondary cases and latently infected patients). 2)To arrest community/nosocomial transmission (target: secondary cases and latently infected patients). 2015: 50% reduction in TB prevalence and deaths by 2015 2050 : elimination (<1 case SS+ per million population)

7. TB Contact Tracing: aims 1)a child aged <5 yrs of age is found with TB or infection without a known source of infection; 2)a person with TB likely due to recent infection (primary tuberculosis) is found without a known source of infection; 3)a cluster of persons with TST or IGRA conversion is found in a high-risk institution.

8. TB Contact Tracing: principles Characteristics of the contacts (e.g. duration of exposure, immune system status, etc.). Characteristics of the index case (e.g. infectiousness, etc.). Index case Contact Secondary cases through CT: 1% of identified contacts (Jereb J et al. Int J Tuberc Lung Dis 2003; 7.)

9. TB Contact Tracing: principles Molecular typing yesterday/today Traditional contact tracing Identifying routes of transmission Index case today/tomorrow Traditional contact tracing

10. Spoligotyping – Complement to RFLP &/or MIRU-VNTR IS 6110 RFLP Gold standard MIRU-VNTR Up to 24 loci in genome

11. Spoligotyping IS 6110 RFLP MIRU-VNTR AdvantagesDisadvantages Highly disciminatory Time-consuming, technically demanding, interlab-comparison, low-copy n. isolates Simple, rapid, inter-lab comparison Less disciminatory – depending on n. loci analysed Low-cost, simple, reproducibility Least discriminatory, overestimates epi- links Molecular technique Molecular epidemiology

12. Identify unexpected outbreaks – unexpected links between patients Cross-jurisdictional outbreaks Identify weakness in TB Control Program (quality evaluation) Molecular epidemiology

13. TB Contact Tracing: principles The greatest risk of developing TB after a median incubation period of 6 wks. Exponential decline of the TB risk during the first 7 yrs (60% who develops TB: within 1 yr). After 7 yrs persistent low risk of developing TB (about 1 per 1,000 person-yrs). Early incidence is determined by the age at which infection is acquired 2% Primary school 30-40% Infant

14. TB Contact Tracing: principles The lifetime risk of TB= risk during the first years (age-related) and cumulative incidence during the low-incidence period (life expectancy-related)

15. TB Contact Tracing: principles Lifetime risk of a child (beyond the highest risk period) is cumulatively 10% (from Comstock). Age-weighted average risk in the UK is 12% (from Vynnycky) vs. 10-20% in Germany (from Horsburgh). Two-year risk of TB in IGRA+ is 15% in Germany (from Diel).

16. TB Contact Tracing: principles The extent of CT depends on: degree of contagiousness of the index/secondary cases, period of infectiousness of the index/secondary cases, location(s) of transmission, risk of the infected contacts to develop TB, no. of infected individuals.

17. TB Contact Tracing: infectiousness Infectiousness with pulmonary TB, but: -TB mediastinal or hilar lymphadenopathy; -Pleural effusion and other extra-pulmonary forms; -TB/HIV co-infection CT only after the confirmation of a concomitant pulmonary TB

18. TB Contact Tracing: infectiousness Ability to aerosolise bacilli and n. of aerosolised bacilli Coughing Sneezing TalkingSinging

19. TB Contact Tracing: infectiousness Ability to aerosolise bacilli and n. of aerosolised bacilli Cavitary lesions

20. TB Contact Tracing: infectiousness Assessment of the following parameters : -Pulmonary TB; -Production of sputum -Results of sputum smear examination; -Results of sputum culture; -Cavitations; -Coughing.

21. TB Contact Tracing: infectiousness Period of contagiousness: Diagnostic delay (pt- and/or healthcare system-related). Start of anti-TB treatment (2 wks?; DR strains?;  nosocomial transmission & negative-pressure isolation room; household management). Initiation of cough or of any other TB symptom.

22. TB Contact Tracing: infectiousness Period of contagiousness: 1)Pulmonary cases SS+ deemed potentially infectious for the period the patient is known to have been coughing (initially to a maximum of 3 months). The presence of radiologically identifiable cavitations increases the assumed degree of infectiousness. 2)Pulmonary cases with culture+ pulmonary TB and 2 SS- may be considered potentially infectious for 1 month before the date of TB diagnosis, where the presence of cough or a cavity increases the assumed degree of infectiousness. 3)A person with drug susceptible pulmonary TB should be considered potentially infectious until the person has completed 2 wks of appropriate treatment in the absence of any suspicion or proof of MDR-TB and has improvement from symptoms.

23. TB Contact Tracing: infectiousness Outdoor ☺Sunlight ☺Ventilation ☻Talking distance Indoor ☻ Room size ☺Ventilation ☻Household density Evaluation of the potential location

24. TB Contact Tracing: infectiousness Susceptibility of the contacts

25. TB Contact Tracing: infectiousness Susceptibility of the contacts: risk of TB after infection in children The probability of disease in children and in adults occur in the first 6– 12 months following primary infection. The longer remaining life expectancy adds to a cumulatively larger lifetime risk in children  children <5 yrs of age are a main target for CT

26. TB Contact Tracing: diagnostic algorithm Immunological diagnosis (TST, IGRA) Microbiological diagnosis (SS, NAAT) Medical History Physical examination Chest radiography

27. TB Contact Tracing: diagnostic algorithm Medical history

28. TB Contact Tracing: organization Risk assessment Infectiousness of the index case; Duration of exposure to the index case; Risk of TB in infected contacts.

29. TB Contact Tracing: organization Risk assessment: 2 strategies “Risk group” approach: I&E of high priority* contacts with a prolonged exposure, followed by I&E according to the individual risk of progression to TB; ‘‘Stone in-the-pond” approach: I&E of high priority contacts with a prolonged exposure, followed by I&E to medium-priority contacts according to the transmission pattern among high priority contacts and identification of those with a higher risk of progression to TB. * Includes those exposed to a high bacillary load for a short period.

30. TB Contact Tracing: organization Risk assessment Interview of the index case on his/her social network Degree of exposure = intensity and duration Highest risk of developing TB

31. TB Contact Tracing: organization Risk assessment

32. TB Contact Tracing: organization Risk assessment

33. TB Contact Tracing: organization

35. Chest radiography is indicated at the same time as the initial TST or IGRA if the contact: has symptoms suggestive of TB; is HIV+ or has another immunosuppressive disorder or exposed to immuno-suppressive medications; is <5 yrs of age; TST reaction size is > 5 mm or the initial IGRA is positive.

36. TB Contact Tracing: organization

37. Window period: time period between acquisition of TB infection and the point in time when an immunologic response becomes measurable. In all high-priority contacts, or in case of an initially negative TST or IGRA in a high priority contact, the evaluation should be performed or repeated when ≥8 wks (1–2 wks beyond the median window period) have passed since the last relevant exposure to the index case.

38. TB Contact Tracing: organization In children <5 yrs prophylactic treatment may be stopped if the repeat TST remains negative unless <6 months. Contacts with HIV infection or other severe immunosuppressive disorders re-evaluated after completion of 2 months of preventive therapy.

39. TB Contact Tracing: organization Expansion of CT? Risk group approach: other vulnerable contacts Concentric-circles approach: evidence of recent transmission among the high priority contacts.  Contacts with TST or IGRA conversions.  Young children with a positive TST or IGRA.  Contact with TB.  The observed prevalence of infection is higher than the Expected prevalence.

40. TB Contact Tracing: organization Expansion of CT? Evaluation of medium-priority contacts after the first screening of the high-priority contacts (examined once after the window period). No evaluation of low-priority contacts unless there has been transmission among medium-priority contacts (examined once after the window period).

41. TB Contact Tracing: M&E Aims 1)assess whether all persons with an increased risk of having become infected have been informed and/or screened; 2)assess whether other exposed groups need to be targeted for CT; 3)Evaluate the organisation, performance and effectiveness of procedures; 4)provide data for evidence based guidelines on CT.

42. TB Contact Tracing: M&E

43. TB Contact Tracing: communication Absence of any ‘‘medical emergencies’’ for CT vs. urgency due to anxiety of potential contacts and of their families (increased by media). It is crucial to provide correct information and reassurance to the contacts and authorities ASAP. To reduce the negative impact of misleading and incorrect messages, health authorities should prepare a press release.

44. TB Contact Tracing: outbreak Occurrence of ≥ 2 TB cases, outside the household setting, with an epidemiological and/or molecular link occurring within 1 yr. Outbreak control committee: a respiratory physician, public health specialists, a microbiologist and administrative members.  communication, coordination and epidemiological analysis

45. TB Contact Tracing: outbreak DNA fingerprint technology enables the identification of molecular clusters (laboratory cross-contamination). Confirmation with information on epidemiological and social relationships.

46. TB Contact Tracing: outbreak Congregate settings Large groups of individuals are confined to areas with limited air circulation. Need of large CT depends on: -infectiousness of the source case, -degree of overcrowding (shelters for the homeless), -susceptibility of the population.

47. TB Contact Tracing: outbreak Prisons Prevention: Early detection (screening of detainees upon incarceration), infection control measures, adequate treatment of susceptible- and MDR-TB cases, case-holding after release from prison. Higher risk due to IVDUs, alcohol abusers, homeless, mentally ill, foreign-born persons and former prisoners.

48. TB Contact Tracing: outbreak Schools Lower threshold for widening the investigation. Transmission can affect a substantial number of contacts. Communication of prevention and control procedures to staff, parents and the general public to prevent anxiety and media misleading info.

49. TB Contact Tracing: outbreak Hospitals Causes: delays in diagnosis and failures in infection control. Focus on risk of exposure of immunocompromised patients and hospital staff (including lab staff). Infection control plan and coordination of CT activities.

50. TB Contact Tracing: outbreak Air travel Exposure to SS+ pt on a flight of ≥8 hrs within the preceding 3 months. I&E of passengers sitting in the same row and the two rows ahead and behind the source case.

51. TB Contact Tracing: critical features Lack of evidence on the cost-effectiveness of the interventions. Lack of accurate tools predicting the risk of developing TB. Effective preventive therapy. Adherence to preventive therapy Molecular investigation.