New Approaches in Tuberculosis Management for the Primary Care Provider

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New Approaches in Tuberculosis Management for the
Primary Care Provider

• Scott Lindquist, MD, MPH
• Tuberculosis Medical Consultant
• Washington State Department of Health and
• Kitsap County Health Officer

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Reported TB Cases United States, 19822007
No. of Cases
Year
Updated as of April 23, 2008.
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Reported TB Cases by Race/Ethnicity United
States, 2007
American Indian or Alaska Native (1)
White (17)
Asian (26)
Native Hawaiian or Other Pacific Islander (Hispanic or Latino (29)
Black or African-American (26)
All races are non-Hispanic. Persons reporting
two or more races accounted for less than 1 of
all cases.
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TB Case Rates by Race/Ethnicity United States,
19932007
Cases per 100,000
All races are non-Hispanic. In 2003,
Asian/Pacific Islander category includes persons
who reported race as Asian only and/or Native
Hawaiian or Other Pacific Islander
only.Updated as of April 23, 2008.
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TB Case Rates by Race/Ethnicity Washington
State, 1996-2007
All races are non-Hispanic. In 2003,
Asian/Pacific Islander category includes people
who reported race as Asian only and/or Native
Hawaiian or Other Pacific Islander only
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TB Case Rates by Age Group Washington State,
1996-2007
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TB Case Rates by Age Group,WA 1993-2005
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Estimated HIV Coinfection in Persons Reported
with TB, United States,19932006
Coinfection
2006
Updated as of April 23, 2008. Note Minimum
estimates based on reported HIV-positive status
among all TB cases in the age group.
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Estimated HIV Coinfection in Persons Reported
with TB, Washington State,1995-2007
Note Minimum estimates based on reported
HIV-positive status among all TB cases in the age
group.
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Reporting of HIV Test Results in Persons with TB
by Age GroupUnited States, 19932006
with Test Results
2006
Updated as of April 23, 2008. Note Includes
TB patients with positive, negative, or
indeterminate HIV test results. Persons from
California reported with AIDS only through 2004.
(HIV test results are not reported from
California)
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Adult TB Cases by Homeless Status, 1994-2001
Adult TB case TB in person aged 18 years
Homeless within year prior to TB diagnosis
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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
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Selected Risk FactorsTen-Year Period, WA
1993-2005
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TB Case Rates, United States, 2007
D.C.
3.64.4
4.4 (national average)
Cases per 100,000.
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Tuberculosis Incidence Rates, Washington State,
1988-2007
Healthy People 2010 Objective (100,000)
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Reported TB Cases by County, Washington State,
2007
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Number of TB Cases inU.S.-born vs. Foreign-born
Persons United States, 19932007
No. of Cases
Updated as of April 23, 2008.
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Trends in TB Cases in Foreign-born Persons,
United States, 19872007
No. of Cases
Percentage
Updated as of April 23, 2008.
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Percentage of TB Cases Among Foreign-born
Persons, United States
1997
2007
DC
50
2549
Updated as of April 23, 2008.
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Countries of Birth of Foreign-born Persons
Reported with TB United States, 2007
Mexico (24)
Other Countries (39)
Philippines (12)
Rep. Korea (3)
Viet Nam (7)
Haiti (2)
India (8)
China (5)
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Number of TB Cases in U.S.-born vs. Foreign-born
Persons, WA State, 1995-2007
22
Tuberculosis Cases by Country of Origin,
Washington State, 2007
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Primary Anti-TB Drug Resistance United States,
19932007
Resistant
Updated as of April 23, 2008. Note Based on
initial isolates from persons with no prior
history of TB. Multidrug resistant TB (MDR TB) is
defined as resistance to at least isoniazid and
rifampin.
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Primary MDR TBUnited States, 19932007
No. of Cases
Percentage
Updated as of April 23, 2008. Note Based on
initial isolates from persons with no prior
history of TB. MDR TB defined as resistance to
at least isoniazid and rifampin.
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Primary Isoniazid Resistance in U.S.-born vs.
Foreign-born Persons United States, 19932007
Resistant
Updated as of April 23, 2008. Note Based on
initial isolates from persons with no prior
history of TB.
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XDR TB Case Count Defined on Initial DST by
Year, 19932007
Case Count
Year of Diagnosis
Drug susceptibility test. Reported incident
cases as of April 23, 2008. Extensively
drug-resistant TB (XDR TB) is defined as
resistance to isoniazid and rifampin, plus
resistance to any fluoroquinolone and at least
one of three injectable second-line anti-TB
drugs.
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Primary Anti-TB Drug Resistance Washington
State, 1995-2007
Resistant
Note Based on initial isolates from persons with
no prior history of TB. MDR TB defined as
resistance to at least isoniazid and rifampin.
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New Diagnostics

• Interferon Gamma Release Assays (IGRAs)
• Quantiferon
• Elispot
• MTD testing
• Universal Genotyping
• Rapid Molecular Amplification (NAAT)

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Commonly Asked TST Questions (1)

• 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 2-step test and why?
• What is the boosted response?

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Commonly Asked TST Questions (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 4 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?

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The Answer

• Quantiferon or Elispot
• Blood based testing method

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MTD

• Mycobacterium tuberculosis direct test
• Nucleic acid amplification
• Sensitivity 85.7-97.8
• Criteria for use
• Smear positive cases
• Highly suspicious cases
• Will it change your treatment?

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Universal Genotyping

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

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Homeless TB Cases in King County
by Treatment Start Date
No. Cases
2004
2002
2003
Treatment Start Date
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How long does it take to find out if a strain is
resistant?

• 2 days?
• 2 weeks?
• 4 weeks?
• 6 weeks?
• 8 weeks?

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Turnaround Time for M. tb Drug Susceptibility
Testing

• From receipt of specimen to 1st drug
  susceptibility by culture method 4 weeks
• 2nd line drugs? 2 additional weeks by MGIT (6
  weeks) or an additional month by agar proportion
  (8weeks)
• Molecular methods (nucleic acid amplification
  detection of mutations) can be done within a day
  or two

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NAAT to Detect Drug Resistance As Well As
Presence of M. tb

• Line probe assays
• Commercially available in Europe, but not cleared
  yet by U.S. FDA
• Molecular beacons assay
• Not a commercial product
• Available as a home brew test at CA Microbial
  Diseases Laboratory

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Beyond Epidemiology and LabsPhysical Exam
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Signs of Pulmonary TB (1)

• Sign Infants Children
  Adolescents
• Rales Common Uncommon
  Rare
• Wheezing Common Uncommon
  Uncommon
• Fremitus Rare Rare
  Uncommon
• Dullness to Rare Rare
  Uncommon
• percussion
• Decreased Common Rare
  Uncommon
• breath
• sounds

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Signs of Pulmonary TB (2)

• Symptom Infants Children
  Adolescents
• Fever Common Uncommon
  Common
• Night sweats Rare Rare
  Uncommon
• Cough Common Uncommon Common
• Productive Rare Rare
  Common
• Hemoptysis Never Rare
  Rare
• Dyspnea Common Rare
  Rare

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Chest Radiographs

• Characteristic Adults Children
• Location Apical Anywhere
• (25 multilobar)
• Adenopathy Rare Usual (30-90)
• (except HIV)
  
• Cavitation Common
  Rare (except adolescents)
• Signs symptoms Consistent Relative paucity

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Treatment

• DOT (consistency is key)
• Latent TB infection 9 months
• Pulmonary 6 months
• Meningitis 12 months
• Adenopathy 6 months
• Bone/joint 12 months
• Monthly weight check

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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.)

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Ongoing Diagnostic Monitoring

• Monthly sputum collection (until 2 negative
  smears)
• Looking for smear positive cases after initial 2
  months of therapy
• Liver function tests if abnormalities on
  screening or risk factors for hepatitis

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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

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Mode of Treatment Administration, Washington
State, 1994-2007
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Case 1The Start of It All

• 10 y/o Filipino female moves to the U.S. with an
  extended family in 1999
• History of 6 months of INH in 1995 for LTBI
• Positive TST 15 mm
• Normal CXR
• Now has a 1 year history of cough
• Worse cough over last month
• Multiple rounds of antibiotics for pneumonia
• Weight loss

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Case 1
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Case 1

• Sputum AFB negative
• Gastric aspirate AFB negative
• Bronchoscopy wash AFB
• Started on INH, Rif, PZA, EMB
• Sputum cultures positive.

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Case 1

• Contact investigation
• Mom TST/CXR normal, received INH in Guam
• Sister TST/CXR normal
• Brother in law TST/CXR normal
• Sister TST x 2
• Nieces x 2 negative TST
• Bottom line large mobile family with movement
  back and forth to Guam and US

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Case 1

• Cultures grow M. tuberculosis resistant to INH
• What about LTBI regimen for those here in U.S. or
  back in Guam?
• Treatment for this patient
• Rifampin
• PZA
• EMB all for 9 months total

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Case 1Happy Ending40

• No visual problems despite ethambutol
• No hepatitis
• Clearing of disease..
• BUT this is not the end of the story

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Case 2Eight Years Later

• 30 year old sister (Filipino) and mother of 4
  children who immigrated to the U.S. in 2003
• Cough x 1 month
• Abdominal mass on CT
• Incidental left lung infiltrate on CXR
• 15 pound weight loss
• Night sweats
• Fever

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Case 2

• TST since age 8 y/o and received 12 months of
  INH
• Sent to UW for w/u of abdominal mass and LTBI
• Sputum culture positive for AFB
• Cecum biopsy positive for AFB

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Case 2Contact InvestigationLooking for Kids

• 10 y/o TST 0 mm and CXR normalno RX
• 7 y/o TST 0 mm and CXR normalno RX
• 4 y/o TST 0 mm and CXR normalINH?
• 20 m/o TST 14 mm and CXR pending

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Case 2 Contact Investigation Looking for
Symptoms

• MAKE A HOME VISIT!
• Father coughing
• 20 m/o coughing and boy is this kid skinny!

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Case 3Use Hardly Any Tools

• 20 month old Filipino male (born in U.S.)
• Mom with Active TB Disease (smear positive)
• Cough
• TST 14 mm
• No BCG
• Poor weight gain

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Case 3
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Case 3
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Case 3

• Chest CT demonstrates multiple subcarinal and
  right hilar nodes measuring 10mm x 18mm and
  matted together
• AST 60 (0-50)
• ALT 54 (0-50)
• HIV negative
• Do we need a gastric aspirate?

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Case 4Use Every Tool You Got

• 10 month old Native American child
• Exposed to an active case of TB in uncle
• No symptoms except wheezing and runny nose with
  cough.
• Good weight gain
• TST negative

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Case 4
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Case 4
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Case 4

• Gastric Aspirate x 3negative
• MTD negative.but results vary with smear
  negative specimens
• Child is improving
• Good growth

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Case 4

• No change clinically
• Quantiferon negativebut do you trust it?

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Case 4
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Case 4Now What?