Tuberculosis in the 21st Century

1
Tuberculosis in the 21st Century

• Scott Lindquist MD MPH
• Tuberculosis Medical Consultant
• Washington State DOH
• and
• Kitsap County Health Officer

2
Feedback Poll
3
In the World

• One out of every three persons has been infected
  with tuberculosis. . . .
• Our story begins . . . .

4
Person
5
Reported TB Cases by Race/Ethnicity United
States, 2005
American Indian or Alaska Native (1)
White (18)
Asian (23)
Native Hawaiian or Other Pacific Islander (lt1)
Hispanic or Latino (29)
Black or African-American (28)
All races are non-Hispanic. Persons reporting
two or more races accounted for less than 1 of
all cases.
6
TB Case Rates by Age Group United States,
19932005
20
15
Cases per 100,000
10
5
0
1999
1998
1993
1994
1995
1996
1997
2000
2001
2002
2003
2004
2005
gt65
lt15
1524
2544
4564
Age Group (years)
Updated as of March 29, 2006.
7
Estimated HIV Coinfection in Persons Reported
with TB United States, 19932004
Updated as of March 29, 2006. Note Minimum
estimates based on reported HIV-positive status
among all TB cases in the age group.
8
Reporting of HIV Test Results in Persons with TB
by Age Group United States, 19932004
with Test Results
Updated as of March 29, 2006. Note Includes
TB patients with positive, negative, or
indeterminate HIV test results and persons from
California reported with AIDS. (HIV test results
are not reported from California)
9
Adult TB Cases? by Homeless Status 1994-2001

? Adult TB case TB in person aged gt18 years
Homeless within year prior to TB diagnosis
10
Adult TB Cases? by Correctional Facility Status,
1993-2001
? Adult TB case TB in person aged gt18 years
old Resident of correctional facility at the
time of TB diagnosis
11
Selected Risk Factors Ten-Year Period, WA
1993-2005
Unemployed
Homeless
50
Alcohol
Previous Diagnosis
40
30
of Cases
20
10
0
1994-1995
1996-1997
1998-1999
2000-2001
2002-2003
2004-2005
12
Place
13
TB Case Rates United States, 2005
D.C.
lt 3.5 (year 2000 target)
3.64.8
gt 4.8 (national average)
Cases per 100,000.
14
TB Low-Incidence States, 19902000
25
20
Number of Low-Incidence States
15
10
5
0
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
lt3.5 TB cases per 100,00 population (Year 2000
target)
15
Countries of Birth of Foreign-born Persons
Reported with TB US, 2005
Mexico (25)
Other Countries (38)
Philippines (11)
Guatemala(3)
Vietnam (8)
Haiti (3)
India (7)
China (5)
16
Trends in TB Cases in Foreign-born Persons US,
19862005
No. of Cases
Percentage
10,000
60
50
8,000
40
6,000
30
4,000
20
2,000
10
0
0
86
87
88
89
90
91
92
93
94
95
96
97
98
99
00
01
02
03
04
05
No. of Cases
Percentage of Total Cases
Updated as of March 29, 2006.
17
Proportion of Foreign-born CasesWA, 1996-2006
18
Drug Resistance
19
Drug Resistance Definitions

• Primary drug resistance
• Applies to previously untreated patients who are
  found to have drug- resistant organisms,
  presumably because they have been infected from
  an outside source of resistant Mycobacterium
  tuberculosis.
• Acquired drug resistance
• Applies to patients who initially have
  drug-susceptible bacteria that become
  drug-resistant due to inadequate, inappropriate,
  or irregular treatment or, more importantly,
  because of non-adherence in drug taking.

20
Multidrug-Resistant Tuberculosis (MDR)

• Resistance to at least two of the best anti-TB
  drugs, isoniazid and rifampicin.
• These drugs are considered first line agents.

21
Extensively Drug Resistant TB (XDR TB)

• This is a rare type of multidrug-resistant
  tuberculosis.
• It is resistant to almost all drugs used to treat
  TB, including all first line agents and the best
  second-line agents fluoroquinolones and at least
  one of three injectable agents (amikacin,
  kanamycin, or capreomycin).
• There have been only 49 cases in the US since
  1993.

22
Primary Isoniazid Resistance in U.S.-Born vs.
Foreign-Born Persons US, 19932005
14
12
10
8
Resistant
6
4
2
0
1993
1995
1997
1999
2001
2003
2005
U.S.-born
Foreign-born
Updated as of March 29, 2006. Note Based on
initial isolates from persons with no prior
history of TB.
23
Primary Anti-TB Drug Resistance WA, 1996-2006
15
INH
MDR TB
10
5
0
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
Note Based on initial isolates from persons with
no prior history of TB. MDR TB defined as
resistance to at least isoniazid and rifampin.
24
Primary MDR TB US, 19932005
No. of Cases
Percentage
500
3
400
2
300
200
1
100
0
0
93
94
95
96
97
98
99
00
01
02
03
04
05
No. of Cases
Percentage
Updated as of March 29, 2006. Note Based on
initial isolates from persons with no prior
history of TB. MDR TB defined as resistance to
at least isoniazid and rifampin.
25
Primary MDR TB WA,1996-2006
20
50
No. of MDR cases
of Total
40
15
30
10
No. of Cases
20
5
10
2.0
2.0
2.0
2.0
0.4
1.1
1.1
0.4
1.0
0.0
0.0
0
0
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
Note Based on initial isolates from persons with
no prior history of TB. MDR TB defined as
resistance to at least isoniazid and rifampin.
26
Primary MDR TB in US-born vs. Foreign-born
Persons with TB, 1993-2001
3
Primary MDR TB
2
1
0
1993
1994
1995
1996
1997
1998
1999
2000
2001
US-born
Foreign-born
Note Based on initial isolates from persons with
no prior history of TB. MDR TB defined as
resistance to at least isoniazid and rifampin.
27
New Diagnostics

• Quantiferon
• MTD testing
• Universal genotyping

28
Commonly Asked TST Questions (1 of 2)

• How do you know and ensure that the medical
  community using the TST is properly trained?
• Can you place a TST on a Thursday and read on a
  Monday?
• Who needs a two-step test and why?
• What is the boosted response?

29
Commonly Asked TST Questions (2 of 2)

• What if the longitudinal reading of the TST is
  12mm and the horizontal (official reading) is
  8mm? Is that considered positive?
• Can I accept a negative reading if the patient
  said there was absolutely no reaction and there
  is no reaction on day four after the test?
• We switched products from tubersol to aplisol,
  and I noticed more positives. We retested with
  tubersol, and all were negative. Which test do I
  believe?

30
The Answer

• Quantiferon
• Blood-based testing method

31
MTD

• Mycobacterium Tuberculosis Direct Test (MTD)
• Nucleic acid amplification
• Sensitivity 85.797.8
• Criteria for use
• Smear-positive cases
• Highly suspicious cases
• If it will change treatment

32
Universal Genotyping

• All TB cultures from WA state now sent to CDC
  for genotyping fingerprinting
• Spoligotyping
• MIRU pattern
• Goal is to detect clusters

33
Homeless TB Cases in King County by Treatment
Start Date
Outbreak RFLP
Non-outbreak RFLP
No known epi link (RFLP pending)
Second RFLP cluster
Clinical case
Epi-link (RFLP pending)
8
7
No. Cases
6
5
4
3
2
1
0
Jan
Mar
May
Jul
Sep
Nov
Jan
Mar
May
July
Sept
Nov
Jan
Mar
May
July
Sept
2002
2004
2003
Treatment Start Date
34
Treatment

• DOT (consistency is key)
• Latent TB infection nine months
• Pulmonary six months
• Meningitis 12 months
• Adenopathy six months
• Bone/Joint 12 months
• Monthly weight check

35
Treatment Evaluation

• HIV screen
• Hep B and C (if risk factors)
• AST
• ALT
• Bilirubin
• A.Phos.
• Creatinine
• Platelets
• Vision testing (if Ethambutol used gt 2 mo.)

36
Ongoing Diagnostic Monitoring

• Monthly sputum collection (until two negative
  smears).
• Look for smear positive cases after initial two
  months of therapy.
• Liver function tests if abnormalities on
  screening or risk factors for hepatitis.

37
DOT or Not to DOT

• Strongly recommended.
• Patient centered approach is more successful.
• Social service support
• Treatment incentives and enablers
• Housing assistance
• Substance abuse treatment

38
TB Case 1Doc, can he fly home?

• 17-year-old male exchange student from
  Azerbaijan.
• BCG at birth.
• One month of cough, hemoptysis, weight loss, and
  acute chest pain.
• He presents to your office. . .now what do you do?

39
Feedback Poll

• What is your first step?
• A. Place a PPD and order a chest radiograph
• B. Place this patient in an N-95 mask
• C. Start four drug therapy
• D. All of the above

40
Results

• PPD 19 mm
• Cavitary right upper lobe on radiograph
• AFB smears all negative

41
The Rest of the Story

• Sputum MTD was positive
• Repeat of the AFB at state lab was positive
• INH, Rifampin, PZA and Ethambutol started
• Patient instructed not to fly home
• Held from last two days of high school
• Contact investigation begun
• Host family asks to have him removed from home. .
  . .

42
Further Dilemmas

• Where can he go?
• When can he fly home?
• How certain are you that this is not XDR?

43
Feedback Poll

• Can he fly home?
• A. Yes
• B. No

44
Contact Dr. Lindquist

• You can call Dr. Lindquist with your TB-related
  questions at
• 360-337-5237
• 206-718-2664
• Or contact him by e-mail at
• lindqs_at_health.co.kitsap.wa.us