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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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2007
2008
0.0
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30.0
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80.0
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
10
20
30
40
50
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