Download - Sarah Phillips MPH Candidate
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Beijing Strain of Tuberculosis in the State of Florida from
2008 - 2011: an Analysis of Clinical Data
Sarah Phillips
MPH Candidate
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DISCLOSURESI have no conflicts of interest
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Background | TB in the World
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Background | TB in the World
1/3of theworldhas TB
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Background | TB in the World
Nine million convert from latent infection to active disease annually
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Background | Trends in TB: Foreign vs US –born persons
Source: National TB Surveillance System* Per 100,000 population.
*
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M. tuberculosis evolutionary scenario (out of Mesopotamia)
Wirth T, Hildebrand F, Allix-Béguec C, Wölbeling F, et al. (2008) Origin, Spread and Demography of the Mycobacterium tuberculosis Complex. PLoS Pathog 4(9): e1000160. doi:10.1371/journal.ppat.1000160 http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000160
Background | Origin and Spread of TB
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Time to the most recent common ancestor (TMRCA), time elapsed since the last expansion began (ta) and growth rate estimates
based on the MSVAR software
Wirth T, Hildebrand F, Allix-Béguec C, Wölbeling F, et al. (2008) Origin, Spread and Demography of the Mycobacterium tuberculosis Complex. PLoS Pathog 4(9): e1000160. doi:10.1371/journal.ppat.1000160http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000160
Background | Strains of TB
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Background | The Beijing Strain of TB
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Research | Rationale
Current literature on the Beijing strain indicates variation among clinical features in different populations, sometimes finding no difference between strains1 and other times finding significant differences in incidence of fever, pulmonary cavitation, night sweats, and duration of cough2
1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374453/
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1552074/
Less symptomatic[Infection progresses
undetected]
Delayed diagnosis[Delay in managed
treatment]
Greater exposure to contacts
[Increase in transmission]
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Research | Rationale
The purpose of this study was to identify cases of TB in the state of Florida caused by the Beijing strain of Mycobacterium tuberculosis and determine key etiological properties in its clinical presentation at diagnosis
Less symptomatic?[Infection progresses
undetected]
Delayed diagnosis[Delay in managed
treatment]
Greater exposure to contacts
[Increase in transmission]
Make informed recommendations regarding vulnerable populations
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Research | QuestionObjective
To determine whether there is a delay in diagnosis of TB among cases of the Beijing strain as evidenced by indication of more advanced disease at diagnosis
Exposure of Interest
Beijing spoligotype
Primary Outcome of Interest
X-ray cavitation
Hypothesis
Positive X-ray cavitation at diagnosis of tuberculosis will be positively correlated with the Beijing spoligotype
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Data | Source & MethodsEvery case was de-identified and completely confidential
TB Cases: Health Management System (HMS) & the Tuberculosis Information Management System (TIMS)
Cases in Florida from 2008 to 2011
n=1540
Sputum and Culture Data: Florida Bureau of Laboratories
Fully HIPAA compliant disease registries: Florida Department of Health
Statistical Software: SAS 9.3
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Data | Source & MethodsData Analysis
Frequency Statistics
Univariate Analysis
95% Confidence Intervals and p-values (α=0.05)
Multivariate Logistic Regression
Odds Ratios, beta coefficients
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Data | Source & MethodsStudy approved by UF IRB and by the FDOH
We conducted a retrospective cross-sectional study of culture-confirmed M. TB cases gathered by physician visits
Our sample included de-identified demographic, epidemiological, and laboratory from 2008 to 2011
Strain information was determined by spoligotyping, which is both sensitive and specific for the Beijing family
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Dataset | VariablesVARIABLE SAMPLE DEMOGRAPHICS n MISSING
Race American Indian (0.3%); Native Hawaiian (0.3%); Asian (9.0%); White (24.8%); Hispanic (25.7%); Black (40.0%)
0
Age 0-4 (1.1%); 5-14 (0.5%); 15-24 (9.7%); 25-44 (31.8%); 45-64 (38.4%); 65+ (18.5%)
0
Sex Female (33.9%); Male (66.2%) 0
Foreign Born Yes (47.5%); No (52.5%) 0
Previous TB Infection
Yes (2.7%); No (97.3%) 0
MDR Yes (1.0%); No (98.4%); Unknown (0.6%) 29
Spoligotype Beijing (6.9%); NonBeijing (93.1%) 46
Country of Origin
74 Countries 89
X-ray Cavitation
Yes (28.4%); No (68.0%); Unknown (3.6%) 258
Genotyping Lineage
Africanum Type (0.2%); Bovis Type (0.9%); East African Indian (1.7%); East Asian (7.7%); IndoOceanic (7.9%); EuroAmerican (81.8%)
262
Sputum Smear
Positive (40.7%); Negative (39.9%); Unknown (19.4%) 307
Sputum Culture
Positive (70.0%); Negative (8.8%); Unknown (1.2%) 319
1587 total observations (n = 1540)
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Demographics | Race
Amer
ican
Indi
an
Hawai
ian
Asia
n
Whi
te
Hispa
nic
Blac
k0
100200300400500600700
0 126 33 27 19
4 3113
349 369
596
Distribution of Race by Strain Type
Non-BeijingBeijing
Race
Cases (
n)
(n = 1540)
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Demographics | Race
Amer
ican
Indi
an
Hawai
ian
Asia
n
Whi
te
Hispa
nic
Blac
k0
100200300400500600700
0 126 33 27 19
4 3113
349 369
596
Distribution of Spoligotype by Race
Non-BeijingBeijing
Race
Cases (
n)
1:4
1:11 1:14
1:32
(n = 1540)
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Beijing Non-Beijing0
5
10
15
20
25
30
35
40
45
0.0 0.30.9 0.2
17.9
41.6
24.5
7.9
25.5 25.7
31.1
24.3
Distribution of Race by Spoligotype
American IndianHawaiianBlackAsianHispanicWhite
Spoligotype
Perc
ent
(%)
Race
Demographics | Race(n = 1540)
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0 - 4 5 - 14 15 - 24 25 - 44 45 - 64 65+0
100
200
300
400
500
600
1 113 25 47 19
16 7 135
457
552
267
Distribution of Spoligotype by Age
Non-BeijingBeijing
Age (years)
Cases (
n)
Demographics | Age(n = 1540)
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0 - 4 5 - 14 15 - 24 25 - 44 45 - 64 65+0
100
200
300
400
500
600
1 113 25 47 19
16 7 135
457
552
267
Distribution of Spoligotype by Age
Non-BeijingBeijing
Age (years)
Cases (
n)
Demographics | Age
1:10
1:18
1:14
1:12
(n = 1540)
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Beijing Non-Beijing05
101520253035404550
0.9 1.10.9 0.5
12.39.4
23.6
31.9
44.3
38.5
17.9 18.6
Distribution of Age by Spoligotype
0 - 45 - 1415 - 2425 - 4445 - 6465 +
Spoligotype
Perc
ent
(%)
Age (years)
Demographics | Age(n = 1540)
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Demographics | Sex
Male Female0
100200300400500600700800900
10001100
73 33
946
488
Distribution of Spoligotype by Sex
Non-BeijingBeijing
Sex
Cases (
n)
(n = 1540)
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Demographics | Sex
Male Female0
100200300400500600700800900
10001100
73 33
946
488
Distribution of Spoligotype by Sex
Non-BeijingBeijing
Sex
Cases (
n)
1:13
1:15
(n = 1540)
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Results | Genotyping Lineage
East Asian100%
BeijingAfricanum
0%Bovis1%
East African Indian2%
East Asian0%
Euro-American
88%
IndoOceanic8%
Non-Beijing
(n = 106) (n = 1434)
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Results| Variable ORs and 95% CIsin a Univariate Analysis
Non-In-travenous Drug Use (Yes|No)
X-ray Cav-itation (P-resense| Absense)
Sex (Fe-male| Male)
Origin (Foreign|
US -Borne)
Age (<25|25+)
Previous TB (Yes|
No)
MDR (Yes|No)
Race (Black| White)
Race (Asian| White)
UL 1 2 3 4 5 6 7 8 9
0.51.52.53.54.55.56.57.58.59.5
10.5
P > 0.10 > 0.10 > 0.50 > 0.10 > 0.10 > 0.10 > 0.10 < 0.001 <0.001
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Results | X-ray Cavitation
BeijingNon-
Beijing
Cavitation 20 346
No Cavitation 67 809
OR = 0.7095% Confidence Interval (0.42, 1.17)P-Value > 0.05
Note: 251 missing
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Results | Origin
BeijingNon-
Beijing
Foreign 55 676
US 51 758
OR = 1.2195% Confidence Interval (0.89, 1.65)P-Value > 0.05
Note: 89 missing
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Results | Age
BeijingNon-
Beijing
<25 Years 15 91
25+ Years 158 1276
OR = 1.3395% Confidence Interval (0.77, 2.29)P-Value > 0.05
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Results | Previous TB
BeijingNon-
BeijingPrevious
TB 4 37
No Previous TB 102 1396
OR = 1.4895% Confidence Interval (0.52, 4.24)P-Value > 0.05
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Results | Multidrug Resistance
BeijingNon-
Beijing
MDR 2 13
No MDR 101 1390
OR = 2.1295% Confidence Interval (0.45, 10.05)P-Value > 0.05
Note: 29 missing
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Results | Race
BeijingNon-
Beijing
Asian 26 113
White 33 349
OR = 2.4395% Confidence Interval (1.40, 4.24)P-Value < 0.002
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Results | Race
BeijingNon-
Beijing
Black 19 596
White 33 349
OR = 0.3495% Confidence Interval (0.19, 0.60)P-Value < 0.001
Note: missing
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Results| Variable ORs and 95% CIsin a Multivariate Analysis
X-ray
Cavit-
ation (Ab-nor-mal | Nor-mal)
Sex (Fem-ale|
Male
)
Ori-gin
(For-eign |US -Born
e)
Age (<25
|25+)
Prev-ious TB
(Yes|No)
MDR (Yes|No)
Corr Inst
(Yes)
Long term Care
Home-
less
HIV Sta-tus
SP Cul-ture
SP Smear
Sta-tus
Non-In-tra-ve-
nous Drug Use (Yes|No)
In-tra-ve-
nous Drug User
Race (Black| White)
Race (Asia
n| White)
UL
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
-3.25
-2.25
-1.25
-0.25
0.75
1.75
2.75
3.75
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Results| Variable ORs and 95% CIsin a Multivariate Analysis
Black Hispanic Asian
UL 1 2 3
0.25
0.75
1.25
1.75
2.25
2.75
3.25
3.75
P 0.0002 0.31 0.0072
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Results | Geographical Clustering: Beijing vs Non-Beijing
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Results | Geographical Clustering: Beijing vs Non-Beijing
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Results | Geographical Clustering:Foreign vs US -Born
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Results | Geographical Clustering:Foreign vs US -Born
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DiscussionHow this study compares with others of the
Beijing strainStrengths and limitationsGeneralizabilityRecommendations for future research
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DiscussionHow this study compares with others of the
Beijing strainStrengths and limitationsGeneralizabilityRecommendations for future research
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DiscussionHow this study compares with others of the
Beijing strainStrengths and limitationsGeneralizabilityRecommendations for future research
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DiscussionHow this study compares with others of the
Beijing strainStrengths and limitationsGeneralizabilityRecommendations for future research
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ConclusionThe purpose of this study was to identify cases of TB in the state of Florida caused by the Beijing strain of Mycobacterium tuberculosis and determine key etiological properties in its clinical presentation at diagnosis
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ConclusionThe purpose of this study was to identify cases of TB in the state of Florida caused by the Beijing strain of Mycobacterium tuberculosis and determine key etiological properties in its clinical presentation at diagnosis
In addition to naming the Asian race a significant risk factor, we identified the Black race as a significant protective factor against having the Beijing TB strain and discovered high rates of geographical clustering of Beijing cases
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ConclusionThe purpose of this study was to identify cases of TB in the state of Florida caused by the Beijing strain of Mycobacterium tuberculosis and determine key etiological properties in its clinical presentation at diagnosis
While we failed to reject our null hypothesis, we can now contribute to the limited but sorely needed data on clinical presentation of Beijing spoligotype TB cases
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Beijing in the World
18 Studies of Beijing Prevalence
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Beijing in the World
19 Studies of Beijing Prevalence
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My mentors: Dr. Lauzardo and Jennifer Hosford
The entire SNTC Staff
My advisor: Dr. CottlerOur internship coordinator: SlandeThe UF College of Public Health and Health Professions
Acknowledgements
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Thank you for your time and attention
Feel free to contact me with questions regarding my internship or special project!
email: [email protected]