Transcript Challenges to Diagnosis and Treatment of TB

World TB DAY 2007
The Trouble With TB
Pitfalls in the Diagnosis and
Treatment of Tuberculosis
Jon Warkentin, M.D., M.P.H.
State TB Control Officer
Tennessee Dept. of Health
Ph: (615)253-1364
[email protected]
March 13, 2007
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March 13, 2007
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Objectives
1. Explain why TB remains a critical
public health issue
2. Describe the epidemiology of TB in
Tennessee
3. List challenges to TB diagnosis and
treatment
4. Identify resources to improve TB
diagnosis and treatment
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Objective
1. TB as a critical
public health issue
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History of TB

The brilliance of Robert Koch
• Koch’s Postulates
• March 24, 1882 - First description of
slow-growing “tubercle bacillus”
• Life cycle of tubercle bacilli entailed in
human-to-human transmission
• Lungs as portal of entry
• “…my studies have been done in the
interest of public health, and I hope that
this will derive the largest profit from
them.”
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History of TB

Adventures in treatment of TB
• Rest, dietary enrichments, religious
rituals, exocism, fasting, bleeding,
purging, emetics, expulsion, execution
• Manipulating climatological variables
• Collapse therapies – “plomage”
• 1885 to WWII – Edward Livingston
Trudeau’s “Little Red Cottage” at
Saranac, NY – the age of “sanataria”
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History of TB

Curative chemotherapy
• 1944 – Lehmann – para-aminosalicylate
• 1944 – Waksman, Schatz, Hinshaw,
Feldman – streptomycin
• 1952 – Domagk, Fox, Bernstein –
isoniazid
• 1954 – first combination therapy with
INH, PAS and streptomycin produced
nearly universal, lifetime cures of TB
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TB as a critical public health issue

Biological factors
• Cellular structure
• Resilience in an intracellular habitat
• Latency and active replication
• Interpersonal transmission through air

Socioeconomic factors
• Associations with poverty, limited access
to health care, on every continent
• HIV/AIDS
• Politics and the “cycle of neglect”
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TB as a critical public health issue

2007: Tools for effective TB control
• Effective multi-drug therapeutics
• Diagnostics tools – rapid culture techniques,
NNA, susceptibility testing, genotyping, etc.
• Standards of care (ATS/CDC guidelines)

2007: Resurgence of TB
•
•
•
•
HIV co-infection, multi-drug resistance
Immigration and migration
“Out of sight, out of mind”
The “cycle of neglect” – public health resources
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Breaking the Cycle of TB
Transmission
“The best way to prevent TB is to treat
and cure people who have it.”
- The STOP TB Partnership
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TB as a critical public health issue
Worldwide Impact of TB
March 13, 2007

8,000,000 people
develop active TB
every year

Each one can infect
between 10-15
people in one year
just by breathing
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TB as a critical public health issue
Worldwide Impact of TB
March 13, 2007

Someone dies of TB
every 15 seconds

Worldwide, over
2,000,000 people die
annually from TB,
mostly in less
developed countries
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Estimated TB Incidence Rates, 2001
per 100 000 pop
< 10
10 - 24
25 - 49
50 - 99
100 - 299
300 or more
No estimate
The designations employed and the presentation of material on this map do not imply the expression of any opinion whatsoever on the part of the World Health
Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.
2007approximate border lines for which thereEast
Tennessee
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White linesMarch
on maps13,
represent
may not
yet be full agreement.
© WHO 2003
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Breaking the Cycle of TB
Transmission
Recall:

The best way to prevent TB is to treat and cure
people who have it.
Therefore,

Emergence of MDR-TB represents a failure of
public health systems to effectively treat TB
And, if the system FAILS….?
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TB emergency declared in Africa
African health ministers have announced a regional
tuberculosis emergency due to a sharp rise in the number of
cases.
The declaration was made in Mozambique at a meeting of the World
Health Organization's (WHO) African region. WHO Regional
Director for Africa Dr Luis Gomes Sambo appealed for "urgent and
extraordinary" action to prevent the situation from getting worse.
Tuberculosis, or TB, kills half a million people a year in Africa, a
quarter of the global total.
'Unprecedented proportions'
The Aids epidemic is increasing the spread of TB, which affects
people in their most productive years and kills some 1,500 Africans
every day.
Published: 2005/08/25 23:57:01 GMT
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Objective
2. The epidemiology of TB
in Tennessee
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No. of Cases
Reported TB Cases
United States, 1982–2004
28,000
26,000
24,000
22,000
20,000
18,000
16,000
14,000
12,000
10,000
1982
1987
1991
1995
Year
March 13, 2007
1999
Source: CDC
All case counts and rates for 1993–2003 have been revised based on updates received
by CDC as of April 1, 2005.
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Are We On Track?
“Without question the major reason for the
resurgence of tuberculosis was the
deterioration of the public health
infrastructure essential for the
control of tuberculosis.”
- Institute of Medicine
March 13, 2007
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Tennessee Public Health Regions
PICKETT
ROBERTSON
Lake
DYER
OBION
WEAKLEY
HOUSTON
GIBSON
3
HICKMAN
2
CHESTER
PERRY
LEWIS
MAURY
6
WASHINGTON
CARTER
GREENE
ANDERSON
JEFFERSON
ROANE
5
SEVIER
COCKE
LOUDON BLOUNT
RHEA
COFFEE
GRUNDY
MCMINN
MONROE
MOORE
LINCOLN
● West Tennessee Region
● Mid Cumberland Region
● South Central Region
● Upper Cumberland Region
● Southeast Tennessee Region
● East Tennessee Region
● North East Tennessee Region
March 13, 2007
MORGAN
VAN
WARREN BUREN
GILES
MCNAIRY
PUTNAM
CANNON
WAYNE
1
WILSON
Hawkins
UNION
DEKALB
RUTHERFORD
WHITE
WILLIAMSON
DECATUR
HAYWOOD
CLAIBORNE
CAMPBELL
JACKSON
CARROLL
CROCKETT
HANCOCK
SCOTT
OVERTON
BENTON
TIPTON
MACON
HENRY
CLAY
MARION
FRANKLIN
BRADLEY
4
POLK
Metro Reporting Areas
1. Memphis/Shelby County
2. Jackson/Madison County
3. Nashville/Davison County
4. Chattanooga/Hamilton County
5. Knoxville/Knox County
6. Sullivan County
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Tuberculosis Cases and Case Rates
Tennessee Regions, 2006
120
12
100
10
80
8
60
60
6
40
4
22
21
20
13
10
2
14
8
3
9
7
4
1
0
Case Rate§ per
100,000 Population
Number of Cases
107
0
MSC
WTR
JMC
MCR
NDC
SCR
UCR
SER
CHC
ETR
Region
KKC
NER
Cases
SUL
Case Rate
* Case Rates using July 2005 population estimates (2006 County level pop. estimates not yet available).
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Tuberculosis Cases and Case Rates
Tennessee, 2002-2006
300
10
308
285
299
279
277
8
6
200
4
100
2
0
0
2002
2003
2004
2005
Year
Case Rate per
100,000 Population
Number of Cases
400
2006
Cases
Case Rate
*Case Rates using population estimates from July of each year, respectively.
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Tuberculosis Cases by Gender
Tennessee, 2002-2006
Percent of Cases
80
70
66
66
68
66
68
60
50
Male
Female
40
30
20
10
0
2002
2003
2004
2005
2006
Year
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Tuberculosis Cases by Age Group
Tennessee, 2002-2006
Percent of Cases
40
30
20
10
0
2002
2003
2004
2005
2006
Year
0-4
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5-14
15-24
25-44
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45-64
65+
25
Tuberculosis Cases by Race/Ethnicity
Tennessee, 2002-2006
60
Percent of Cases
50
40
30
20
10
0
2002
2003
2004
2005
2006
Year
White Non-Hispanic
American Indian/Alaskan Native
Hispanic
Black Non-Hispanic
Asian/Pacific Islander
*Data do not include missing information; Race is Non-Hispanic and Hispanic is of all races.
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National Origin of Foreign-born
Tuberculosis Cases
Tennessee, 2006
Other Countries
23%
Mexico
26%
Vietnam
4%
Sudan
4%
India
12%
Kenya
4%
Ethiopia
4%
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India
7%
Guatemala
5%
Somolia
11%
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Foreign-born Tuberculosis Cases
Tennessee, 1997-2006
70
64
69
30
60
50
50
43
44
52
25
49
44
41
20
40
15
30
10
20
10
5
0
0
1997
Cases
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1998
1999
2000
Percent
2001
2002
2003
2004
2005
Percent of Cases
Number of Cases
60
2006
Year
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Risk Factors Associated with TB Infection
Tennessee, 2002-2006
TB Risk factor
2002
2003
2004
2005
2006
N (%)
N (%)
N (%)
N (%)
N (%)
Foreign-born
50 (16)
52 (18)
49 (18)
64 (21)
69 (25)
HIV Infection
30 (10)
30 (11)
23 (8)
26 (9)
21 (8)
Homeless†
28 (9)
27 (10)
27 (10)
32 (11)
15 (5)
Residing in correctional
facility‡
13 (4)
19 (7)
11 (4)
13 (4)
10 (4)
Residing in a long-term
facility‡
11 (4)
12 (4)
13 (5)
13 (4)
4 (1)
4 (1)
9 (3)
7 (3)
0 (0)
6 (2)
Non-injection drug user
31 (10)
38(13)
28 (10)
37 (12)
26 (9)
Excessive alcohol use
61 (20)
62 (22)
61 (22)
57 (19)
37 (13)
Injection drug user
† Homeless within past year
March 13, 2007
‡ Residing in facility at time of TB diagnosis
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in TN
R
M
MDR
TB
D
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MDR-TB in Tennessee - 2007
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Summary of TB Epidemiology






TB is a burgeoning global epidemic
Rate of decline in TB case rate in U.S. has
slowed, increasing in some states
Pediatric TB disease is sentinel for ongoing
TB transmission
Migration/immigration link every corner of
the globe with Tennessee
Increasing percentage of cases among
blacks, hispanics and foreign-born in TN
Substantial racial/ethnic disparities in TN
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Objective
3. Challenges to diagnosis
and treatment of TB
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Case Study

72 y.o. female presents to local
hospital c/o…
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The Cycle
of TB
Transmission
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Challenges to Diagnosis and
Treatment of TB

S: Subjective

O: Objective

A: Assessment

P: Plan
Key to diagnosis is “Thinking TB”!
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Challenges to Diagnosis and
Treatment of TB

S: Subjective
1.
2.
3.
4.
5.
6.
Chief complaint
History of present illness
Past medical history
Current medications
Social history
Review of systems
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Challenges to Diagnosis and
Treatment of TB

S: Subjective
1. Chief complaint
• “Classical” vs atypical presentations
• Mental status changes in elderly
2. History of present illness
• Cluster of key symptoms
• Index of suspicion with respiratory
symptoms
• Corroborating history by significant others
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Challenges to Diagnosis and
Treatment of TB

S: Subjective
3. Past medical history
• History of “positive skin test,” recent or
remote
• Recurrent “bronchitis” or “community
acquired pneumonia,” especially in past 6
months, refractory UTIs in elderly
• Initial improvement, worse recurrence
• Treatment with fluoroquinolones
• Conditions with high risk of LTBI progression
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Conditions with Increased Risk
of Progression to TB Disease







HIV infection / AIDS
Substance abuse
Recent infection
Previous TB
Diabetes
Silicosis
Corticosteroid tx
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






Imm. therapy
CA of head/neck
Hemato./RE diseases
ESRD
Certain GI surgeries
Malabsorption synd.
Low body wt. (10%)
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Challenges to Diagnosis and
Treatment of TB

S: Subjective
4. Current medications
• Antibiotics, especially fluoroquinolones
• Levofloxacin, Moxifloxicin
• Development of FQ-resistant TB strains
• Preemption of FQ use as first-line TB therapy
• Immunosuppressive agents (e.g., chronic
systemic steroids, TNF-alpha blockers,
Methotrexate
• High risk for progression from LTBI to active TB
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Challenges to Diagnosis and
Treatment of TB

S: Subjective
5. Social history
•
•
•
•
Known TB exposures?
Work history
Travel to countries with endemic TB
Health status of household contacts, work
and social network
• Substance abuse (esp. Etoh, crack)
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Challenges to Diagnosis and
Treatment of TB

S: Subjective
6. Review of systems
• Constitutional symptoms
• Organ systems
•
•
•
•
CNS – TB meningitis, esp. in young children, HIV
Pulmonary – may have minimal cough
Lymph nodes, especially cervical
Urinary tract – refractory UTIs
• “TB can affect any organ of the body”
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Challenges to Diagnosis and
Treatment of TB

O: Objective
1.
2.
3.
4.
Physical examination
Labs
Radiography
Special procedures
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Challenges to Diagnosis and
Treatment of TB

O: Objective
1. Physical examination
• Vital signs – fever, tachypnea
• Inspection – wasting (“consumption”),
dyspnea on exertion
• Auscultation – rales, rhonchi, decreased
breath sounds
• Percussion – dullness
• Palpation – lymphadenopathy
• Non-specific findings are common
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Challenges to Diagnosis and
Treatment of TB

O: Objective
2. Labs
• TST – false-positives, false-negatives
• Sputums for AFB smear and culture
• Always collect under supervision
• Strongly consider induction (comparable AFB yield
to bronchoscopy)
• MTD available at State Laboratory on AFB+ spec.
• CBC with diff, CMP, U.A.
• U.A.
• HIV status – critical! (see MMWR 9/22/06)
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Challenges to Diagnosis and
Treatment of TB

O: Objective
3. Radiography
• CXR (PA and lateral) – infiltrates, nodules,
calcifications, effusions, pleural thickening,
tracheal deviation with volume loss,
cavitation, perihilar adenopathy
• CXR may be normal in HIV/AIDS or other
immunocompromised patients
• CT scan – helpful for small cavities
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Challenges to Diagnosis and
Treatment of TB

O: Objective
4. Special procedures
• Bronchoscopy – BAL with washings for AFB
smear, culture, cytology; biopsy
• Other biopsies – specimens should be
cultured for Mtb (not placed in formalin!),
State Lab can probe with MTD
• Laryngoscopy
• CT-guided FNA – cytology confirming
carcinoma does not rule out concurrent TB
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Challenges to Diagnosis and
Treatment of TB

A: Assessment
1. Problem list
2. Differential
diagnosis
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
P: Plan
1. Further
diagnostics?
2. Resp. isolation
3. Medications?
4. Notify local health
department
5. Discharge
planning
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Challenges to Diagnosis and
Treatment of TB

A: Assessment
1.Problem list
• Organ systems
• Acute + chronic signs, symptoms linked?
2.Differential diagnosis
• Is active TB disease on the differential dx?
• Must have a low index of suspicion for TB
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Challenges to Diagnosis and
Treatment of TB

P: Plan
1.
2.
3.
4.
5.
Further diagnostic tests
Respiratory isolation
Medications
Notify local health department
Discharge planning
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Treatment of TB Disease

Standard DOT: 6-9 months

Initial phase:
4-drugs (INH, RIF, PZA,
ETH) for 8 wks (daily x2
wks, then 2-3x/wk)

Continuation:
2-drugs (INH, RIF) for 16
weeks (daily or 2-3x/wk)

Drug changes:
depend on culture sensitivity,
clinical response, pt. factors

Clin. monitoring:
ESSENTIAL!
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Challenges to Diagnosis and
Treatment of TB

Physicians are obliged to treat the patient
AND protect the public health
• Suspicion or confirmatin of active TB must be
reported by telephone to local health dept.
within 12 hours (statutory requirement of
physicians, labs, hospitals in TN)
• AFB+ patients should be considered to have
active TB until proven otherwise
• “TST- and AFB-” does NOT rule out TB!
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New Anti-TB Drugs
 Problems with std. 4-drug regimen for TB dz
(INH, RIF, PZA, EMB):
• toxicities, drug interactions, long tx
course, many “pills”
• challenges for completing full tx course
• increasing drug resistance
 Growing int’l awareness of need for new Rx
 Will we say goodbye to Isoniazid?
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Single-drug & MDR-TB

Primary:
infected with a resistant TB
organism

Secondary:
developed drug resistance
due to (a) inadequate
regimen, (b) sporadic
treatment, or (c) both

Cure?
Tx is long, expensive, toxic,
difficult, and impossible in
certain cases
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Impact of HIV/AIDS
HIV is the strongest risk factor for
development of TB disease if infected:
 7-10% chance per year of
developing active TB disease
 100x greater risk than person
with a normal immune system
 TB is the leading killer of persons
with HIV/AIDS worldwide
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Pearls That Work
THINK TB!

Induce & witness sputum collection
•
•
Poor specimens yield unreliable results
One neg. MTD does not rule out TB

R/O active pulmonary TB even in context
of confirmed extra-pulmonary TB

HIV+, PPD-, normal CXR, with symptoms
of active TB is active TB (not MAI) until
proven otherwise

Four-drug therapy for initiation phase
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Pearls That Work
THINK TB!

Nothing grows in formalin…
• Biopsy specimens need to be cultured for TB
• Sensitivity testing requires live TB bugs


Recurrent “CAP” – risk factors for TB?
Inappropriate FQ use can…
•
•
•
•
Delay dx of TB disease
Increase severity of TB before dx made
Create drug resistant TB organisms
Contribute to ongoing TB transmission
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Pearls That Work

Rapid reporting of TB suspect to LHD
• TN Statute requires provider phone report to
LHD within 12 hrs.
• Contact investigation starts only after report

Discharge planning starts on Hosp. Day #1
• LHD case manager works with ICN and SW

NEVER release a homeless TB pt. from the
hospital before consulting the LHD
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Objective
4. Resources in the fight
against TB
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TB Resources for the Clinician

ATS website
• TB diagnosis and classification
• TB treatment
• Community Acquired Pneumonia (CAP)

CDC website – DTBE
• Infection control in healthcare facilities
• Contact investigation


TDH website – TB Elimination Program
Dr. Jay Mehta – ETSU
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Acknowledgements









Dr. Jay Mehta
Dr. Michael Iseman
Dr. Timothy Sterling
Staff of the Sullivan County Health Dept.
Staff of Northeast TN Regional Office - TDH
Staff of Tennessee TB Elimination Program
Erin Holt, MPH – epidemiologist
American Thoracic Society
Centers for Disease Control & Prevention
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Questions?
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