The Determinants of Tuberculosis (TB) Transmission in the Canadian-Born Population of the Prairie Provinces (The “DTT Project”) Primary Care Provincial TB Meeting Saskatoon, SK. October, 28, 2011 Richard Long, MD

Annual Age and Sex-Adjusted Tuberculosis Case Rates Per 100,000 Person-Years For Status Indians, Canadian-born ‘Others’ and Foreign-born, Canada,

The DTT Project is a: CIHR (Aboriginal Peoples Health Institute) and Health Canada (First Nations and Inuit Health Branch) co-funded, mixed-method (quantitative and qualitative) study of tuberculosis transmission on the Canadian prairies It began on April 1, 2006

Scientific Team Principal Investigator: Richard Long, MD, University of Alberta Co-Investigators:Malcom King, PhD, Univ of Alberta Maria Mayan, PhD, Univ of Alberta Dennis Kunimoto, MD, Univ of Alberta Vernon Hoeppner, MD, Univ of Saskatchewan Sylvia Abonyi, PhD, Univ of Saskatchewan Pam Orr, MD, Univ of Manitoba Martha Ainslie, MD, Univ of Manitoba Dick Menzies, MD, MSc, McGill Univ Current Co-ordinators: Courtney Heffernan (Project Manager) and Kathy McMullin Database Manager: Bill Chroniaris Past-co-ordinators: Jody Boffa and Carmen Lopez

How Do We Eliminate Tuberculosis? 1.Interrupt Transmission Altogether All population groups but First Nations, Inuit, and Métis in particular 2. Prevent Disease in those Already Infected All population groups but foreign-born in particular

Transmission indices were significantly higher for males and Aboriginal Peoples and lower for those > 64 years of age

PEDIATR INFECT DIS J 2005; 24:538-41

DTT Stakeholders and Collaborating Organizations

Objectives Objective 1: “To characterize the occurrence and spread of Beijing/W TB strains in Aboriginal peoples and to understand the potential role of clinical and environmental determinants of TB transmission” Objective 2: “To identify prospectively the determinants of TB transmission in the Canadian- born population, with emphasis on Aboriginal peoples”

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Demographic Province Total No. (%) AlbertaSaskatchewanManitoba No. No. Assessed (100.0) Age (41.1) (58.9) Sex Male (48.2) Female (51.8) Population Group First Nations (66.1) Métis59418 (32.1) Canadian-born 'Other'0101 (1.8)

Qualitative Studies 1.“OLD KEYAM” - J ABORIGINAL HEALTH 2.“THE TIPPING POINT” - SOC SCI MED 3.“RESTORING BALANCE” - CAN J PUBLIC HEALTH 4.‘Potential TB Transmitters on the Canadian Prairies with and without Transmission Events; a mixed-method study” - Jessica Grant, MSc, Usask 5.“TB in the First Nations and Métis of the Canadian Prairies versus the Maori and Pacific Islanders of New Zealand – a comparative qualitative study” - Jessica Grant, MSc, USask

Major Satellite Projects - Qualitative 1.“Addressing TB Control in a high incidence First Nations Communities in Alberta.” Jessica Moffatt PhD (c ) Funding: - Alberta Innovates – Health Solutions (AHFMR) - PHAC - FNIHB, Alberta Region 2.“Tuberculosis Education in Canadian-born Aboriginal and non-Aboriginal youth: an historical, socio-cultural and public health promotional curriculum” Kathleen McMullin MEd (Project Manager) Funding: - Lung Health Program, Phase II PHAC/CLA

TB on the Prairies Between 2004 and 2008 there were 1795 cases of TB on the prairies; 640 (36.7%) in Manitoba, 492 (27.4%) in Saskatchewan and 663 (36.9%) in Alberta.

Population Group and Province

Age- and Sex-Adjusted Incidence of TB in Status Indians by Province,

Age and Sex-adjusted TB incidence in Status Indians (SI) persons (on and off reserve) and foreign-born (FB) persons, relative to Canadian-born “other” persons, Prairie Provinces,

Age-specific TB case rates per person-years for male (M) and female (F) First Nations (FN), Canadian-born 'other' (CBO), and Foreign-born (FB) persons, Prairie Provinces,

“Potential TB Transmitters”, Prairies Between 2007 and 2008 there were 248 Canadian- born adults (age>14 years) with culture-positive pulmonary TB on the Prairies; 145 (58.5%) sputum smear-positive, 103 (41.5%) sputum smear- negative Of the ‘Potential TB Transmitters’ 89.9% were Aboriginal Peoples

Canadian-born ‘Potential’ TB Transmitters by Province, Population Group, and Smear Status, Prairies, * * Other Aboriginal includes Métis, Non-Status Indians and Inuit No. of Cases SI Status Indian OA Other Aboriginal * CBO Canadian-born ‘Other’

All DNA Fingerprinting was performed by NML using 12 or 24 loci MIRU-VNTR supplemented as necessary by spoligotyping. All Alberta isolates were also DNA fingerprinted with RFLP.

North: 9 (69.2%) South: 4 (30.8%) North: 57 (89.1%) South: 7 (10.9%) North: 66 (86.8%) South: 10 (13.2%) On-Reserve Status Indian and In-Settlement M étis Potential Transmitters Prairie Provinces: North 132 (86%) South 21 (14%)

Frequency Distribution of Canadian-born TB Transmitters on the Prairies by Sputum Smear and Community Type ( )

High Prevalence (2 or more ‘potential’ transmitters in the calendar years) Reserve Communities on the Prairies No. of Cases Community Number S: Saskatchewan M: Manitoba A: Alberta

Community TypeSmear Status Population Group † Total Status IndiansOther AboriginalNon-Aboriginal Major Metropolitan S+S S-S Total Non-Major Metropolitan S+S S-S Total Reserve Community S+S S-S Total Métis Settlement S+S S-S Total All Community Types S+S S-S Total *Abbreviations: S smear † Other Aboriginal includes Métis, non-Status Indians and Inuit ‘POTENTIAL’ TB TRANSMITTERS ON THE PRAIRIES BY COMMUNITY TYPE, SMEAR STATUS AND POPULATION GROUP*

LANCET 2010: Available at: DOI:10:016www.thelancet.com

Indicator Result by Community Type* *All results were statistically significant at 0.05% significance (p = < )

Indicator Result by Community Type, cont’d * *All results were statistically significant at 0.05% significance (p = < )

Indicators of Well-Being in reserves with TB transmitters as compared to reserves without TB transmitters

Indicators of Well-Being in high-incidence reserves as compared to reserves without TB transmitters

“There appear to be three main factors necessary for the development of an epidemic (“outbreak”) of tuberculosis. These are: a predominantly tuberculin negative population the introduction of potent sources of infection an environment suitable for the spread of infection” GRYZBOWSKI S. AM REV TUBERC 1957; 75:

Outbreak (Reference) Year Treaty Area Community Population Source Case Characteristics Total Cases Total Culture- positive Cases Constituent Cases by Age (Yrs) AgeSex Population Group Smear Status CXR ‡ <15≥15 A( 1) F†F† FN+ veC B(2) F†F† FN+ veC3318 § 1815 C(2) MFN+ veC2711 § 1314 * Abbreviations: F female, M male; FN First Nations; C cavitary † Both women were post-partum ‡ Cases# 1 and 2 had far-advanced cavitary pulmonary TB; Case #3 moderately-advanced cavitary pulmonary TB § M. tuberculosis isolates from outbreaks #1 and #2 were confirmed to share the same DNA fingerprint Large Reported, On-reserve Outbreaks of Tuberculosis on the Canadian Prairies, * (1)CAN J INFECT DIS 1991; 2: (2)CAN J PUBLIC HEALTH 2004; 95:

Location No. of Source Cases No. of Source Cases Causing Outbreaks Population Group of Source Cases Causing Outbreaks No. of Secondary Cases in Each Outbreak † FNMétisFBCBO On-reserve , 2, 3, 3 Off-reserve , 2, 2, 3, 4 * Abbreviations: FN First Nations; FB foreign-born; CBO Canadian-born 'other' † Secondary Cases were of 3 types: type 1 - identified by conventional epidemiology and confirmed by molecular epidemiology; type 2 - identified by conventional epidemiology but unconfirmed by molecular epidemiology (culture-negative); type 3 - identified by molecular epidemiology and linked to the source case spatially and temporally. Adult (Age >14 years) Sputum Smear-positive Pulmonary TB (Source Cases) and Outbreaks of TB in Alberta (January 1, June 30, 2008) *

The convergence of factors necessary for the occurrence of an outbreak in a reserve community

Chest X-ray on the Outbreak Case

Cluster Cases by Population Group and Community; Outbreak Timelines

No. of Features Probability of TB 7. Is there an upper lung zone infiltrate (cavitary or non-cavitary) on CXR; is the leucocyte count normal; is there an anemia of chronic disease? 6. Is there a high risk medical condition? 5. Has there been a failure to respond to broad spectrum antibiotics? 4. Are symptoms subacute or chronic? 3. Is there a relative absence of dyspnea? 2. Are there pulmonary symptoms (cough, sputum, hemoptysis, chest pain) in combination with constitutional symptoms (fever, night sweats, weight loss, fatigue)? 1. Is there an epidemiologic risk (TB contact; high risk population group)?

INT J TUBERC LUNG DIS 2002; 6(4):

This patient is a young male Status Indian who was a close contact of a patient with infectious TB in August, A TST was positive; a CXR was normal (September, 2006). Treatment of LTBI was recommended but not completed. CXRs between March 19 th and July 28 th, 2007 demonstrated a progressive left upper lobe nodular process. TB was not considered until July 28 th, 2007 (delay 130days). Sep Mar Jun July

1 DISTRIBUTION : Commentary: (i) airspace interstitial process involving the apical-posterior segment of the upper lobe and/or the superior segment of the lower lobe, (ii) may be bilateral; if not the contra-lateral lung may be used for comparison CAVITATION : Commentary: (i) at site of airspace/interstitial disease (present in 50% of cases), (ii) usually round (the broncho-cavitary junction behaves as a check-valve) and thick walled, (iii) may be multiple, (iv) air-fluid levels are uncommon. 3 VOLUME LOSS: Commentary: (i) local, at the site of disease, with relative preservation of total lung volume, (ii) shift of upper mediastinum, retraction of ipsilateral hilum, (iii) bronchiectasis, iv) fibrotic lesions alone are usually sharply defined and irregular, (v) possible pleural thickening. 4 ENDOBRONCHIAL SPREAD : Commentary: (i) acinar shadows - multiple poorly defined nodules 4-10 mm in diameter, (ii) at site of disease, in the dependent lung or in the contra-lateral lung, (iii) lesions are not discrete as in interstitial lung disease.

Public Health Consequences (Secondary Cases) of Smear Positive Pulmonary TB According to CXR Category and Close Contact group *Type 1 secondary cases are identified by conventional epidemiology and confirmed by molecular epidemiology; Type 2 secondary cases are identified by conventional epidemiology but are unconfirmed by molecular epidemiology (culture-negative); Type 3 secondary cases are identified by molecular epidemiology and linked to the source case spatially and temporally

Public Health Consequences (TST Conversions ) of Smear Positive Pulmonary TB According to CXR Category and Close Contact group

Conclusion The interruption of TB transmission in Aboriginal peoples on the Prairies is an enormous challenge; a single approach is unlikely to succeed; a multitude of well considered approaches is unlikely to succeed without greater engagement of the Aboriginal community

Percent of Immigrants from Europe and Asia/Africa to Canada by Time Period (Source: Citizenship and Immigration Canada. Canadian Statistics: Immigrant Population. 05/12/03. )

Beijing/W Family of Strains in Alberta Determined the M. tuberculosis lineage of 98.6% (n=1826/1852) of archived culture-positive isolates recovered from patients diagnosed between mid % (n=350) of isolates were Beijing/W lineage strains The foreign-born contributed 94.3% of Beijing/W isolates, the vast majority (90%) being born within the Western Pacific (e.g. China, Vietnam, Korea) Only 3.2% (n=20/632) of Canadian-born TB cases were Beijing/W strains Only 5 Beijing/W strains among First Nations peoples Annual incidence rates of Beijing/W strains have declined since 1994

Beijing/W Family of Strains in Alberta Beijing/W strains were significantly more likely to be associated with polyresistance (a OR 3.7; 95%CI ) and borderline more likely to be associated with multidrug-resistance (a OR 3.3; 95%CI ) Other than these differences in drug resistance, Beijing strains appeared to present no more of a public health threat than non-Beijing strains

Beijing/W Family of Strains in Alberta Beijing/W strains do not result in any more clustering or more frequent recent transmission than non-Beijing/W strains in a setting with effective TB control practices.

Patient B is a middle aged foreign-born male who presented to a tertiary care ED on three occasions, April 10, 17, and May 5, CXRs were performed on each occasion but TB was not considered until the last visit, May 5 (delay 24 days). Apr Apr May