California Tuberculosis Drug Resistance Update

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California Tuberculosis Drug Resistance Update

• Jennifer Flood MD MPH
• Chief, Surveillance and Epidemiology
• Center for Infectious Disease
• TB Control Branch, CDPH
• October 7, 2009

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Questions

• How common is drug resistance among TB cases in
  California?
• Is drug resistance increasing?
• Which patients in California are most likely to
  have drug resistance?
• Can rapid drug resistance testing make a
  difference in outcomes?

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Drug Resistance among TB Cases in California,
2008

• 2,695 TB cases
• 2158 culture-positive
  (80)
• 2054 first line drugs tested
  (95)
• __________________________________
• Pansusceptible 1840 (85)
• Drug resistant
• Any 1st line drug 318 (15)
• MonoINH 259 (8.0)
• MonoPZA 90 (4.3)
• MDR 30 (1.5)
• 2 or more 1st line drugs 18 (0.9)
• MonoRIF 4 (0.2)
• Not mutually exclusive categories

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INH Resistance

• No significant change in INH resistant fraction,
  1999-2008
• 2008 n2680 INH tested
• Any INH resistance 221 (10.5)
• INH mono-resistant 174 (8.3)

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Tuberculosis Cases with MDR on Initial or Final
Drug Susceptibility Testing California, 1999-2008
2
3
2
2
7
1
1
?
?
Number of MDR Tuberculosis Cases
39
34
31
36
34
41
28
33
39
30
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
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Mono-PZA Resistance Among Culture-positive
Tuberculosis Cases, 1999-2008
4.2
4.3
3.8
3.6
3.3
3.4
3.3
2.8
2.8
2.5
Number of Cases
Cases with PZA susceptibility testing
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Which TB patients have drug resistance?
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INH ResistanceCalifornia, 2004-2008
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Top Ranking Countries of Origin 2004-2008
with Any INH Resistance
Countries
Total Cases gt 100 Laos Thailand Vietnam Philippine
s S. Korea Cambodia
23 18 17 16 14 11
Total Cases lt 100 Burma Former Soviet
13 10.5
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MDR TBCalifornia, 2004-2008
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MDR TB, California 2004-2008
All Foreign-born gt100 Cases Philippines
Mexico Vietnam India China Central
America
lt100 Cases Thailand S. Korea Ethiopia
Former Soviet Union Cambodia Peru
Indonesia Laos
Chi square p0.0000001 OR 2.65 (1.86-3.76)
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M. bovis TB cases, 2007-2008 n107

• 95 Hispanic
• 74 Birth country Mexico
• 16 HIV co-infection

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Can Rapid Drug Resistance Testing Improve Time
to Effective Treatment Initiation for MDR TB
Cases?
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Time to MDR TB treatment start MB (n26) vs
nonMB (n86) group

• Started MDR TB treatment sooner

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Molecular Testing for Drug Resistance by CDPH and
CDC

• New CDC service Molecular Detection of Drug
  Resistance (MDDR)
• Uses DNA sequencing to test for genetic mutations
  associated with resistance to 6 anti-TB drugs
• INH, RIF, fluoroquinolones, kamamycin, amikacin,
  capreomycin)
• Complements molecular beacon testing by MDL for
  INH and RIF

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Comparison of Molecular Testing Services
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Criteria for Submission
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How to Submit a Specimen

• CDC requests all specimens submitted through
  state public health labs
• Contact
• Grace Lin
• 510-412-3929 grace.lin_at_cdph.ca.gov
• OR Lisa True, CDPH MDR Service Nurse Coordinator
  
• 510-620-3054 lisa.true_at_cdph.ca.gov
• OR MDR Service
• Leslie Henry, Lisa True, Cheryl Scott, Gisela
  Schecter, Pennan Barry
• 510-620-3000

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California TB Drug Resistance Highlights

• Most newly diagnosed TB cases in California are
  sensitive to all first line TB drugs
• Likelihood of INH resistance and MDR
  significantly higher if foreign-born, new
  arriver, or history of TB
• Increased frequency of mono-PZA resistance
  Mexican-born and HIV infected at risk
• Rapid drug resistance testing available at CDPH
  and CDC to identify MDR and XDR
• Rapid drug resistance assays can reduce time to
  starting effective therapy

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Update CDC Technical Instructions and
B-notification
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2007 Technical Instructions For Panel Physicians
Revised 10/09

• Major Changes
• CXR performed on children if TST gt 10mm
  (not 5 mm)
• QFT can replace TST
• Digital film can replace hard copy film
• Children lt 10 can travel if smear negative X 3
  unless extensive CXR changes
• Treatment initiation for children lt 10 depends on
  disease extent
• DOS forms for overseas recording is revised

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Source http//www.cdc.gov/ncidod/dq/panel_2007.ht
m
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Countries now operating under New TB Screening
and Treatment Instructions

• Botswana Namibia
• China Nepal Refugees (Bhutanese)
• Dominican Republic Philippines
• Ethiopia Refugees (Eritreans) South Africa
• Hong Kong Swaziland
• Japan Taiwan
• Jordan Tanzania Refugees (Burundian)
• Kenya Refugees (includes Ethiopians, Thailand
  Refugees (includes
• Somalis, and Sudanese) Burmese and Hmong
  refugees)
• Lesotho Turkey
• Macau Uganda
• Malaysia Refugees (Burmese) Vietnam
• Mexico
• Mozambique

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TB case occurrence among arrivers
with B1 classification
Significant decrease in post-enhancement
arrivers with TB disease within 6 months of US
arrival
25
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TB cases with B classification before and after
screening enhancement

• Before After
• Case characteristic Percent
• Sputum smear positive 14 9
• Sputum culture positive 81 65
• Cavitary CXR 7 0
• INH mono-resistant 15 33 MDR
  4 13
• Significant increase in fraction of INH
  resistance

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Resources

• New TB Technical Instructions http//www.cdc.gov/
  ncidod/dq/panel_2007.htm
• Phil Lowenthal
• CDPH TBCB B notification Epidemiologist
• 510-620-3045
• phil.lowenthal_at_cdph.ca.gov