Tuberculosis in the 21 st Century Scott Lindquist MD MPH Tuberculosis Medical Consultant Washington State DOH and Kitsap County Health Officer.

Tuberculosis in the 21st Century

Scott Lindquist MD MPHTuberculosis Medical Consultant

Washington State DOH

and

Kitsap County Health Officer

Feedback Poll

A. Balanced

B. Overblown

C. Confusing

D. None of the above

In my opinion, the recent media coverage of the case of drug resistant tuberculosis involving international travel was:

In the World

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

• Our story begins . . . .

Person

Reported TB Cases by Race/Ethnicity* United States, 2005

Hispanic or Latino(29%) Black or

African-American(28%)

Asian(23%)

White(18%)

American Indian or Alaska Native

(1%)

Native Hawaiian orOther Pacific Islander

(<1%)

*All races are non-Hispanic. Persons reporting two or more races accounted for less than 1% of all cases.

*Updated as of March 29, 2006.

19991998

>65

Age Group (years)

0

5

10

15

20

1993 1994 1995 1996 1997 2000 2001 2002 2003 2004 2005

<15 15–24 25–44 45–64

TB Case Rates* by Age Group United States, 1993–2005

Ca

ses

per

10

0,0

00

Estimated HIV Coinfection in Persons Reported with TB: United States, 1993–2004*

*Updated as of March 29, 2006.

Note: Minimum estimates based on reported HIV-positive status among all TB cases in the age group.

% C

oin

fect

ion

0

10

20

30

1993 1995 1997 1999 2001 2003

All Ages Aged 25–44

% w

ith

Tes

t R

es

ult

s

*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)

Reporting of HIV Test Results in Persons with TB by Age Group: United States, 1993–2004*

0

20

40

60

80

1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

All Ages Aged 25–44

Adult TB Cases by Homeless Status* 1994-2001

Adult TB case = TB in person aged >18 years * Homeless within year prior to TB diagnosis

Ho

mel

ess

0

2

4

6

8

10

1994 1995 1996 1997 1998 1999 2000 2001

%

Adult TB Cases by Correctional Facility Status,* 1993-2001

Adult TB case = TB in person aged >18 years old* Resident of correctional facility at the time of TB diagnosis

% C

orr

ecti

on

al F

ac

ility

1993 1994 1995 1996 1997 1998 1999 2000 20010

2

4

6

8

10

Selected Risk Factors: Ten-Year Period, WA 1993-2005

0

10

20

30

40

50

1994-1995 1996-1997 1998-1999 2000-2001 2002-2003 2004-2005

% o

f C

ases

UnemployedHomelessAlcoholPrevious Diagnosis

Place

TB Case Rates*: United States, 2005

< 3.5 (year 2000 target)

3.6–4.8

> 4.8 (national average)

D.C.

*Cases per 100,000.

TB Low-Incidence States,* 1990–2000

* <3.5 TB cases per 100,00 population (Year 2000 target)

Nu

mb

er

of

Lo

w-

Inci

den

ce

Sta

tes

0

5

10

15

20

25

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000

Countries of Birth of Foreign-born Persons Reported with TB: US, 2005

Mexico(25%)

Philippines(11%)

Vietnam (8%)India

(7%)China (5%)

Haiti (3%)

Guatemala(3%)

OtherCountries

(38%)

Trends in TB Cases in Foreign-born Persons: US, 1986–2005*

No. of Cases Percentage

*Updated as of March 29, 2006.

0

2,000

4,000

6,000

8,000

10,000

86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 050

10

20

30

40

50

60

No. of Cases Percentage of Total Cases

59% 63% 60%70% 72% 69% 66% 68% 67%

73%61%

0%

15%

30%

45%

60%

75%

90%

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

Proportion of Foreign-born Cases:WA, 1996-2006

Drug Resistance

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.

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.

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.

Primary Isoniazid Resistance in U.S.-Born vs. Foreign-Born Persons: US, 1993–2005*

*Updated as of March 29, 2006.

Note: Based on initial isolates from persons with no prior history of TB.

% R

esis

tan

t

02468

101214

1993 1995 1997 1999 2001 2003 2005

U.S.-born Foreign-born

Primary Anti-TB Drug Resistance: WA, 1996-2006

Note: Based on initial isolates from persons with no prior history of TB. MDR TB defined as resistance to at least isoniazid and rifampin.

0%

5%

10%

15%

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

INH MDR TB

Primary MDR TB: US, 1993–2005*

*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.

No. of Cases Percentage

0

100

200

300

400

500

93 94 95 96 97 98 99 00 01 02 03 04 05

0

1

2

3

No. of Cases Percentage

Primary MDR TB: WA,1996-2006

Note: Based on initial isolates from persons with no prior history of TB. MDR TB defined as resistance to at least isoniazid and rifampin.

No

. o

f C

ases

1.1% 2.0%0.0% 1.0% 2.0% 2.0% 0.4% 0.0% 0.4% 1.1% 2.0%

0

5

10

15

20

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

0%

10%

20%

30%

40%

50%

No. of MDR cases% of Total

Primary MDR TB in US-born vs. Foreign-born Persons with TB, 1993-2001

Note: Based on initial isolates from persons with no prior history of TB.MDR TB defined as resistance to at least isoniazid and rifampin.

% P

rim

ary

MD

R T

B

0

1

2

3

1993 1994 1995 1996 1997 1998 1999 2000 2001

US-born Foreign-born

New Diagnostics

• Quantiferon

• MTD testing

• Universal genotyping

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?

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?

The Answer

• Quantiferon

Blood-based testing method

MTD

• Mycobacterium Tuberculosis Direct Test (MTD)

• Nucleic acid amplification

• Sensitivity 85.7%–97.8%

• Criteria for use:

Smear-positive cases

Highly suspicious cases

If it will change treatment

Universal Genotyping

• All TB cultures from WA state now sent to CDC for genotyping “fingerprinting”

• Spoligotyping

• MIRU pattern

• Goal is to detect clusters

No

. C

ases

Homeless TB Cases in King County by Treatment Start Date

2002Treatment Start Date

2003 2004

0

1

2

3

4

5

6

7

8

Jan Mar May Jul Sep Nov Jan Mar May July Sept Nov Jan Mar May July Sept

Non-outbreak RFLP Outbreak RFLP

No known epi link (RFLP pending) Second RFLP clusterEpi-link (RFLP pending) Clinical case

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

Treatment Evaluation

• HIV screen

• Hep B and C (if risk factors)

• AST

• ALT

• Bilirubin

• A.Phos.

• Creatinine

• Platelets

• Vision testing (if Ethambutol used > 2 mo.)

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.

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

TB Case #1:“Doc, 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?

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

Results

• PPD 19 mm

• Cavitary right upper lobe on radiograph

• AFB smears all negative

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. . . .

Further Dilemmas

• Where can he go?

• When can he fly home?

• How certain are you that this is not XDR?

Feedback Poll

Can he fly home?

A. Yes

B. No

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:

[email protected]