the determinants of tuberculosis (tb) transmission in the canadian-born population of the prairie...

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

1989

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Status Indian

Canadian-born 'other'

Foreign-born

Annual Age and Sex-Adjusted Tuberculosis Case Rates Per 100,000 Person-Years For Status Indians, Canadian-born ‘Others’ and Foreign-born, Canada,1989-2008

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 TeamPrincipal 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 AboriginalPeoples 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”

DTT Project Timeline

13

Demographics, by Province, of Pulmonary TB Patients Participating in a Qualitative Interview

Demographic  Province  

Total No. (%)Alberta Saskatchewan Manitoba  No. No. No.  

No. Assessed 14 24 18 56 (100.0)

Age 15-34 4 14 5 23 (41.1) 35-64 10 10 13 33 (58.9)

Sex Male 8 11 8 27 (48.2) Female 6 13 10 29 (51.8)

Population Group First Nations 9 14 14 37 (66.1) Métis 5 9 4 18 (32.1) Canadian-born 'Other' 0 1 0 1 (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 - Qualitative1. “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

FN Métis CBO FB FN Métis CBO FB FN Métis CBO FBManitoba Saskatchewan Alberta

0

10

20

30

40

50

60

70

80

90

405/640

5/640

71/640

157/640

321/492

115/492

22/49234/492

60/663

15/663

77/663

511/663

%

Age- and Sex-Adjusted Incidence of TB in Status Indians by Province, 2004-2008

AB SK MB0

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20

30

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60

70

80

90

100

On-ReserveOff ReserveTotal

Incidence per 100,000 Population

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,

2004-2008

FB

SI - Off

SI - On

0 5 10 15 20 25 30 35 40 45 50

Rate Ratio

62.4/1.4 = 44.3

38.7/1.4 = 27.5

18.1/1.4 = 12.9

Age-specific TB case rates per 100 000 person-years for male (M) and female (F) First Nations (FN), Canadian-born 'other' (CBO), and Foreign-born (FB) persons, Prairie Provinces, 2004-2008

0-14 15-34 35-64 65 +0.00

10.00

20.00

30.00

40.00

50.00

60.00

70.00

80.00

90.00

100.00

SI - F

CBO - F

FB - F

SI - M

CBO - M

FB - M

“Potential TB Transmitters”, Prairies 2007-2008

• 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, 2007-2008*

*Other Aboriginal includes Métis, Non-Status Indians and Inuit

No. of Cases

SI Status IndianOA Other Aboriginal *CBO Canadian-born ‘Other’

CBO

OA

SI

CBO

OA

SI

CBO

OA

SIM

BS

KA

B

0 20 40 60 80 100 120

S+S-

2007

2008

Each of the 248 ‘potential TB transmitters’ diagnosed in 2007 and 2008 has a 30 month transmission

window

1

2

3

4

248

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 Métis 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 (2007-2008)

High Prevalence (2 or more ‘potential’ transmitters in the 2007-2008 calendar years) Reserve Communities on the

Prairies

No. of Cases

Community Number

S:   SaskatchewanM:  ManitobaA: Alberta

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21-1

1

3

5

7

9

11

13

15

S M M

M

S M

S

M A M

A M M A

S M M M M M M

S+ 64

S - 45

Community Type Smear Status Population Group†  TotalStatus Indians Other Aboriginal Non-Aboriginal

Major MetropolitanS+  23 9 13 45S-  15 1 4 20Total 38 10 17 65

Non-Major MetropolitanS+  8 3 6 17S-  7 1 1 9Total 15 4 7 26

Reserve CommunityS+  60 4 0 64S-  68 0 0 68Total 128 4 0 132

Métis SettlementS+  1 17 1 19S-  0 6 0 6Total 1 23 1 25

All Community TypesS+  92 33 20 145S-  90 8 5 103Total 182 41 25 248

    *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: www.thelancet.com DOI:10:016

Indicator Result by Community Type*

Percent of Persons above 15 years that did not graduate High School

Housing Density (% of private dwellings with a room occupied by more than one person)

Housing Quality (% of housing needing major repair)

Unemployment Rate

0 10 20 30 40 50 60 70 80

Reserve Communities (n=136)

Towns/Villages/Small Municipalities (n=136)

Percent

Socio-Economic Indicator

*All results were statistically significant at 0.05% significance (p = < 0.0001)

Indicator Result by Community Type, cont’d *

Median Annual Household Income (t-housands)

Community Well-Being Index (Composite score out of 100)

0 10 20 30 40 50 60 70 80 90

Towns/Villages/Small Municipalities n=136)

Reserves n=136

Socio-economic Indica-tor

*All results were statistically significant at 0.05% significance (p = < 0.0001)

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: 432-41

Outbreak (Reference) Year Treaty 

AreaCommunity Population

Source Case Characteristics

Total Cases

Total Culture-positive Cases

Constituent Cases by Age (Yrs)

Age Sex Population Group

Smear Status CXR‡

<15 ≥15

A( 1) 1987 8 350 25 F† FN + ve C 36 20 21 15

B(2) 1992 8 1128 22 F† FN + ve C 33 18§ 18 15

C(2) 1998 8 716 28 M FN + ve C 27 11§ 13 14

* 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, 1986-2010*

(1) CAN J INFECT DIS 1991; 2: 133-41(2) CAN J PUBLIC HEALTH 2004; 95: 249-55

Location

 No. of Source 

CasesNo. of Source Cases Causing Outbreaks

 Population Group of Source Cases Causing 

Outbreaks

No. of Secondary Cases in Each Outbreak†

  FN Métis FB CBO

On-reserve 7 4 4 0 0 0 2, 2, 3, 3

Off-reserve 83 5 0 2 3 0 2, 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, 2006 - 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

Suspecting Pulmonary TB

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)?

1 2 3 4 5 6 7

INT J TUBERC LUNG DIS 2002; 6(4):332-339

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

Sep 25 2006 

Mar 19 2007 Jun 15 2007 July 28 2007

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.

1

2

3

4

2 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

Typical Atypical0

5

10

15

20

25

30

35

Type 1Type 2Type 3

*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

No. Child

-aged

Conve

rters

/Sourc

e Cas

e

No. Child

-aged

Conve

rters

/Can

adia

n-born

Sourc

e Cas

e0

0.10.20.30.40.50.60.70.80.9

Typical

Atypical

No. Child-aged Converters0

5

10

15

20

25

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.<www.statcan.ca/english/Pgdb/demo25.htm>)

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 1991-mid2007

• 19% (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 1.3-11.11) and borderline more likely to be associated with multidrug-resistance (a OR 3.3; 95%CI 1.0-11.1)

• 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, 2008. CXRs were performed on each occasion but TB was not considered until the last visit, May 5 (delay 24 days).

Apr 10 2008 

Apr 17 2008 May 5 2008