Sarah Phillips MPH Candidate

Beijing Strain of Tuberculosis in the State of Florida from

2008 - 2011: an Analysis of Clinical Data

Sarah Phillips

MPH Candidate

DISCLOSURESI have no conflicts of interest

Background | TB in the World


1/3of theworldhas TB


Nine million convert from latent infection to active disease annually

Background | Trends in TB: Foreign vs US –born persons

Source: National TB Surveillance System* Per 100,000 population.

*

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

http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000160


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


Background | The Beijing Strain of TB

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]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374453/




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

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

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

Data | Source & MethodsData Analysis

Frequency Statistics

Univariate Analysis

95% Confidence Intervals and p-values (α=0.05)

Multivariate Logistic Regression

Odds Ratios, beta coefficients

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

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)

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)

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)

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)

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)

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)

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)

Demographics | Sex

Male Female0

100200300400500600700800900

10001100

73 33

946

488

Distribution of Spoligotype by Sex

Non-BeijingBeijing

Sex

Cases (

n)

(n = 1540)

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)

Results | Genotyping Lineage

East Asian100%

BeijingAfricanum

0%Bovis1%

East African Indian2%

East Asian0%

Euro-American

88%

IndoOceanic8%

Non-Beijing

(n = 106) (n = 1434)

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

Results | Origin

BeijingNon-

Beijing

Foreign 55 676

US 51 758


Note: 89 missing

Results | Age

BeijingNon-

Beijing

<25 Years 15 91

25+ Years 158 1276


Results | Previous TB

BeijingNon-

BeijingPrevious

TB 4 37

No Previous TB 102 1396


Results | Multidrug Resistance

BeijingNon-

Beijing

MDR 2 13

No MDR 101 1390


Note: 29 missing

Results | Race

BeijingNon-

Beijing

Asian 26 113

White 33 349

OR = 2.4395% Confidence Interval (1.40, 4.24)P-Value < 0.002

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

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

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

Results | Geographical Clustering: Beijing vs Non-Beijing

Results | Geographical Clustering:Foreign vs US -Born

DiscussionHow this study compares with others of the

Beijing strainStrengths and limitationsGeneralizabilityRecommendations for future research

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


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

Beijing in the World

18 Studies of Beijing Prevalence

Beijing in the World

19 Studies of Beijing Prevalence

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

Thank you for your time and attention

Feel free to contact me with questions regarding my internship or special project!

email: [email protected]

Sarah Phillips MPH Candidate

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