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3 Frances Jamieson, MD, Liane Macdonald, MD, and John Minnery, PhD March 15 th, Photo: U.S. Centres for Disease Control and Prevention

4 Objectives Identify TB- and NTM-related resources and scientific support available from different areas of PHO (e.g., TB and Mycobacteriology Laboratory, Communicable Disease Prevention and Control, Environmental and Occupational Health). Describe upcoming changes to the PHO laboratory mycobacteria diagnostic testing algorithm and OUT- TB Web.

5 Objectives (cont d) Discuss a current issue in NTM in Ontario, e.g., the Mycobacterium avium increase and methods used to test for correlations between drinking water quality and risk of NTM infection. Consider how the new PIDAC-Communicable Diseases TB and NTM Working Groups may be relevant to your area(s) of practice / research.

6 The Tuberculosis and Mycobacteriology Laboratory: Public Health Policy Environment Connecting the Dots Guidelines Mycobact Cell and molecular science Surveillance + Epidemiology PHOL TB + Mycobacteriology Lab Diagnostics Health Outcomes Chronic Disease Human host Internat l Collab ns Knowledge Translation + educat n Infection prevent n + control Tools Public Health Investig ns Health Economics 4

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8 Tuberculosis: A Global Problem WHO Estimates (2014 data): 9.6 million New Infections 1.5 million Deaths 6

9 Worldwide distribution of different nontuberculous mycobacteria from pulmonary samples in a) Mycobacterium avium complex; b) M. kansasii; c) M. xenopi; d) M. malmoense; e) M. abscessus; and f) M. fortuitum. Wouter Hoefsloot et al. Eur Respir J 2013;42: by European Respiratory Society

10 TB and Mycobacteriology Labs in Ontario Public Health Lab Network PHL-Toronto and 3 Regional PHLs Ottawa Hospital Dynacare (community lab) Timmins Ottawa TORONTO London

11 By the Numbers Largest TB and Mycobacteriology laboratory in North America (by volume) - avg ,000 specimens processed annually Provide >95% of diagnostic testing and 100% of reference testing for Ontario Over 180 AFB smears read daily (one primary reader and one secondary) - Toronto Over 250 culture positive specimens and referred cultures identified weekly - Toronto

12 2014 PHL Toronto Total Specimens: 46,000 (2.5% TB +, 11.9% NTM +) Smear Positives (5.2%) Mtb Complex NTM No growth 66.4% of sm +, culture + 15% 56% TB NTM 29% 33.6% of sm +, culture +

13 % Total Identifications 2014 (n=8627) 9% 6% 1% 18% Mtb MAC (M. avium and M. intracellulare)** 10% M xenopi Common Rapid growers (non-pigmented)* Other NTM 56% M. kansasii *M. fortuitum, M. chelonae, M. abscessus group, M. peregrinum, M. mucogenicum, M. senegalense **M. avium 88.4% and M. intracellulare 10.9% of MAC isolates 11

14 Number 7000 Proportion of MtbC and NTM Isolated 2014 PHL Toronto Total positive NTM TB Year 12

15 Smear Laboratory Testing Algorithm Current and New Culture Incubate up to 7 wks Mtb and MAC real-time PCR NAAT New smear positive, New smear smear positive, negative smear on Daily negative on M, W, M-F request F request DST; report in 8-10 days Smear read and reported in 24 hours TB rapid ID by lat flow TB NTM probe, ID by or MALDI- NTM ID by TOF line-probe 13 and report ID

16 Mtb Complex and M avium complex detection from specimens by real-time PCR Replaces the AMTD and the TB PCR assays, and detects MtbC and MAC directly in specimens Original assay developed by Wadsworth Laboratory, NY AFB Positive (%) AFB Negative (%) All Specimens (%) MtbC: Sensitivity Specificity PPV NPV MAC: Sensitivity Specificity PPV NPV

17 Other Services INH and RIF molecular drug R detection (line-probe assay) PCR for M. leprae Identification of NTM directly in specimens 15

18 TB CSI : Tracking Tuberculosis In Ontario 16

19 OUT-TB WEB ON-LINE SERVICE DELIVERY Ontario Universal Typing of Tuberculosis: Web-based Surveillance and Communication System Demonstration video:

20 Using Whole Genome Sequencing to analyze 7 M. abscessus isolates from three CF patients, Sick Kids January NC_ SNVs Purple text = patient AB; Orange text = patient NM; Blue text = patient SK; Green text = reference strain

21 Clinical Issue: Sustained Increase in M. avium positive cultures 19

22 The Tuberculosis and Mycobacteriology Laboratory: Public Health Policy Environment Connecting the Dots Guidelines Mycobact Cell and molecular science Surveillance + Epidemiology PHOL TB + Mycobacteriology Lab Diagnostics Health Outcomes Chronic Disease Human host Internat l Collab ns Knowledge Translation + educat n Infection prevent n + control Tools Public Health Investig ns Health Economics 20

23 Chest 2014;146(3):563 Brode and colleagues make an important contribution to our understanding of the epidemiology of NTM infections and they point the way to important avenues of future research Neil Schluger, editorial, Chest 2014;146(3):529 21

24 The Tuberculosis and Mycobacteriology Laboratory: Public Health Policy Environment Connecting the Dots Guidelines Mycobact. cell and molecular science Surveillance + Epidemiology PHOL TB + Mycobacteriology Lab Microbiome Diagnostics Health Outcomes Chronic Disease Human host Internat l Collab ns Infection Knowledge prevent n + Public Translation control Tools Health + educat n Investig ns? Health Economics 22

25 Kevin May and PHOL TB and Mycobacteriology Lab staff Alex Marchand-Austin and LSDM staff Carla Duncan, Jennifer Ma, Jenn Guthrie, Carolina Mehaffy and Research staff 23

26 WHAT S NEW IN TUBERCULOSIS AT PHO?

27 Outline Overview and PHO Communicable Disease team TB functions Provincial TB epidemiology Updates on selected current provincial TB initiatives 25

28 Our aim: Advice and support to enable action to achieve societal outcomes Transmission of TB. Progression of latent TB infection (LTBI) to active TB. Incidence of drug-resistant TB. Capacity of community partners and health care providers (HCPs) to effectively manage TB. Access to diagnosis and treatment of TB. Public aware of TB and its prevention. 26

29 Provincial TB surveillance, together with PHOL PHO Communicable Disease Team TB functions Scientific and technical advice and support to inform TB prevention and control practice and policy On request for single and multi-jurisdictional case, contact and outbreak investigations Provincial TB working groups and initiatives Facilitating interjurisdictional notifications (IJNs) and referrals via PHAC; collaboration with other F/P/T partners as needed TB medical surveillance, travel IJNs Collaborating across PHO (including PHOL) and with external partners on applied research and evaluation, professional development and knowledge exchange E.g., PHO Rounds, TB managers teleconference, Central TB network participation, TOPHC/Lung Association conferences 27

30 Recent provincial TB surveillance products rio_provincial_report_2012.pdf PHO_Monthly_Infectious_Diseases_Surveillance_Report_- _March_2015.pdf 28

31 Recent issues involving PHO CD TB scientific advice/support Source: Source: 29

32 PROVINCIAL TB EPIDEMIOLOGICAL UPDATE 30

33 Incidence of TB; Ontario and Canada, Ontario Cases: MOHLTC, integrated Public Health Information System (iphis) database, extracted [2015/05/13]. Ontario Population: Population Estimates [ ], Statistics Canada, distributed by MOHLTC, received [2014/07/03]. Canadian Rates: Public Health Agency of Canada, Canadian Notifiable Disease Section, received by PHO [2015/07/10]; national data available up to 2013.

34 Incidence of TB by age and sex: Ontario, 2014 Ontario Cases: MOHLTC, integrated Public Health Information System (iphis) database, extracted [2015/05/13]. Ontario Population: Population Estimates [2013], Statistics Canada, distributed by MOHLTC, received [2014/07/03]. 32

35 TB cases by country of birth: Ontario, Country of Birth Total (N) Total (%) Born outside Canada % Born in Canada % Inuit 9 0.2% Non-Aboriginal % Registered/Status Indian,Other Aboriginal % Unknown** 6 0.2% Origin unknown/missing % TOTAL % 33

36 Incidence of TB by public health unit of residence: Ontario,

37 UPDATES ON SELECTED PROVINCIAL INITIATIVES 35

38 Provincial Migrant TB Post-landing Surveillance Task Group Implementation: How is TBMS being conducted in Ontario? What is perceived to be working well, need improvement? Impact: To what extent has TBMS in Ontario achieved its intended public health objectives? Options: What evidence-informed policy changes to migrant post-landing TBMS in Ontario could improve its efficiency and/or effectiveness? 36

39 TBMS evidence review components Jurisdictional scan Literature review iphis data analysis PHU survey, Clinician interviews 37

40 TBMS Task Group stages Task Group convened, work planning March - April 2015 Evidence review, primary data collection May-Aug 2015 Analysis, developing evidenceinformed advice Sept-Dec 2015 Completing report with evidenceinformed advice to CMOH Jan-spring

41 PIDAC-Communicable Diseases Tuberculosis Working Group (PIDAC-CD TBWG) 39

42 Voting members: PIDAC-CD TBWG members Dr. Elizabeth Rea, Toronto Public Health (Chair) Dr. Kamran Khan, SMH/UoT Dr. Ian Kitai, HSC/UoT Dr. Nicola Mercer, Wellington-Dufferin Guelph Public Health Ms. Glenna Murray, Region of Waterloo Public Health Ms. Ha Nguyen, Region of Peel Public Health Dr. Rob Stirling, Dalla Lana School of Public Health, UoT Dr. Geetika Verma, Queen s University Dr. Wendy Wobeser, Queen's University Non-voting members: Dr. Liane Macdonald, PHO (Scientific Lead) Dr. Fran Jamieson, PHO Dr. Erika Bontovics, Ministry of Health and Long-Term Care 40

43 PIDAC-CD TBWG mandate Mandate Advising PIDAC-CD on evidenceinformed guidelines and advice related to the public health prevention and control of TB Activities Reviewing and critically evaluating the scientific literature on TB, and existing guidelines and practices Term Initial: 24 months; option to extend 41

44 Proposed TBWG work plan initiatives TB screening in long-term care LTBI screening (TST v. IGRA; specific settings / populations) iphis data quality improvement Provincial consultation mechanisms (clinical, public health) 42

45 Looking for TB advice or support? We are here to provide scientific and technical advice and support on TB prevention and control as needed. This advice and support can include facilitating linkages to experts within and across PHO (e.g., Laboratories, EOH, as well as CD), as well as drawing on existing networks of external experts in the public health and clinical aspects of TB management as needed. There is no wrong door please feel free to contact us: Liane Macdonald, Public Health Physician ) Emily Karas, Manager, Communicable Diseases ) Communicable Diseases team enquiries 43

46 Acknowledgements Ontario s 36 PHUs and their TB prevention and control teams Fran Jamieson, Doug Sider, Bryna Warshawsky, Matthew Root PHO CD team (including Cecilia Fung, Andrea Saunders, Michael Whelan) and manager (Emily Karas) PIDAC-CD members and chair, Scott Weese PIDAC-CD TBWG members and chair, Elizabeth Rea MOHLTC colleagues, including Erika Bontovics TB Migrant Post-landing Surveillance Task Group members and co-chair, Lawrence Loh Genevieve Cadieux, PHPM resident 44

47 Additional TB resources MOHLTC s TB Prevention and Control Protocol ards/docs/tuberculosis_prevention_control.pdf MOHLTC s Infectious Disease Protocol ards/docs/tb_chapter.pdf ards/docs/tb_cd.pdf OHA/OMA TB Surveillance Protocol for Ontario Hospitals ol%20revised%20aug% pdf Canadian TB Standards, 7 th Edition 45

48 Drinking Water and NTM Infection OVERVIEW Geocoding water systems based on census Dissemination Areas, we will determine if attributes of drinking water treatment, source, and/or quality correlate with address of patient s with NTM infection or disease. Regression of observed cases over expected cases, adjusted for sex and age will reveal potential associations. Study includes the largest municipal drinking water systems in the province (~75 of the largest distinct Drinking Water Systems across ~45 Municipalities). Population-served by these drinking water systems range from approximately 34,000 to over 2 million. Five (5) year window (May 1, 2010 to June 30, 2015). "Wasserhahn" by Matthew Bowden Licensed under Attribution via Commons - ahn.jpg 46

49 Ministry of the Environment and Climate Change Programs Environmental Data Sources - Drinking Water and NTM Infection Drinking Water Information System Water quality data from May 1, 2010 to June 30, 2015 Parameters: EC, TC, HPC, THM, Nitrate+Nitrite (~1,000,000 data points/dws) Sample location: Treated and Distribution Technologies (i.e. Unit Operation) DWS List (n =~ 75 systems) Point locations Municipal Drinking Water Licensing Program (n= ~ 45 Licences) Drinking Water Works Permit (equipment, processes by subsystem) Municipal Drinking Water Licence (Water Taking Locations, Subsystems, Rated Capacities, Pathogen Removal Requirements) Drinking Water Distribution Description (image of distribution map) Municipal Drinking Water Licensing Program Annual Reports ( O.Reg 170 Reports ) Interviews with operating authorites 47

50 Environmental Attributes - Drinking Water and NTM Infection Source Water Type Surface (Lake, River) Groundwater (secure, or under the influence of surface water) Mixed (blend of surface and groundwater) Secondary Disinfection Type Chlorine or Chloramine Level of Treatment for Pathogens Relative to Regulated Minimum Regular (e.g. Surface Water = coagulation + filtration + Cl 2 ) Extra (e.g. Membrane Filtration replaces media filters + Cl 2 ) Excess (e.g. Membranes + Ultraviolet + Cl 2 ) 48

51 Treatment Unit Operations Environmental Attributes (cont.) - Drinking Water and NTM Infection Chlorination, chloramination, UV, coagulation, flocculation, sedimentation, filtration (any), membrane (MF or UF), alkalinity, ph, GAC, PAC, BAC, O 3, Fe, Zebra Mussel, Taste&Odour, Stripping, Orthophosphate, de-cl 2, or O 3 -quench, Advanced (e.g. H 2 O 2 + UV) Water Quality Metrics Trihalomethanes, Nitrate+Nitrite, e.coli (presence/absence), Total Coliform, Heterotrophic (CFU/100mL) Spatial Demarcation Polygons built from Dissemination Areas best resembling images of distribution system. 49

52 Literature on Environmental Correlates of NTM NTM grow in plumbing; in biofilm; some f(temperature, flow, nutrients, organics, surface). Resist disinfection: 500x +more resistant than e.coli, more resistant than Giardia. Can live and proliferate inside amoeba Found in soil, produce (food), dust, surface water, aerosols, hot tubs, drinking water. DNA fingerprint of isolates in water correlate with isolates in AIDS patients. Prevalence of positive NTM in raw water appears to correlate with levels in water in the distribution system. Prevalence in biofilm is higher than in water. Prevalence in biofilm relative to water varies by species (e.g. M.avium vs M. intracellulare). Both groundwater and surface water may contain 20,000 CFU/L. Levels of NTM correlate with turbidity and assimilable organic carbon Conventional Water treatment reduces levels by 2- to 4-log. 50

53 Analysis and Limitations Analysis From province wide data, determine the expected prevalence: a standardized period prevalence adjusted for age and sex. Determine the expected, age- and sex-adjusted, number of cases for each water system polygon using population data from the assembly of DAs. Conduct regression analysis with observed cases, expected cases and water system (source, treatment and quality) variables in the model. Limitations Ecological exposure assessment. Existing data not designed for NTM analysis (e.g. THMs are surrogate for organics). DAs may include areas not served by community water system. Water systems knowledge may not be complete. 51

54 Drinking Water Polygons-South Central Ontario 52

55 Drinking Water and NTM Infection - Drinking Water Polygons -GTA 53

56 Drinking Water and NTM Infection -Drinking Water Polygon with Distinct Subsystem Ground Water With Standard Treatment Surface Water with Extra Treatment 54

57 Acknowledgements Lizzy Andrews Theodore K. Marras - University Health Network and Mount Sinai Hospital, Assistant Professor of Medicine, University of Toronto, Toronto Western Hospital James Johnson, Elaina MacIntyre, Lennon Li, Sean Marshall, Steven Johnson, Kelsie Jagt, Alex Marchand-Austin, Ray Copes Public Health Ontario. Rekha Chetlur, Gayathry Krishnakumar, Aziz Ahmed, Aleksandra (Ola) Sokolowski - Ministry of the Environment & Climate Change, Safe Drinking Water Branch and Drinking Water Programs Branch 55

58 56