Epidemiology of Tuberculosis in Northeastern United States, 1993-2005

Kenneth G. Castro, M.D.Assistant Surgeon General, USPHS

Director, Division of Tuberculosis EliminationNational Center for HIV, Hepatitis, STD, and TB Prevention*

Coordinating Center for Infectious Diseases* Proposed

Northeast TB Controllers MeetingPrinceton, New Jersey

October 24, 2006

Acknowledgements• United States TB controllers, state and local health

departments

• CDC, DTBE, SEOIB and FSEB– Lori Armstrong − Sandy Althomsons– Elvin Magee − Val Robison– Tom Navin − Dave Crowder– Dan Ruggiero − John Jereb– Mark Lobato − Margaret Oxtoby– Edwin Rodriguez − Tracy Agerton– Farah Parvez − Sonal Munsiff– Vernard Green − Tom Privett– Zach Taylor

TB Cases Analyzed

• National TB Surveillance System

• Reported 1993 to 2005

• Northeastern States: Maine, New Hampshire, Vermont, Connecticut, Massachusetts, Rhode Island, New York, New Jersey

• Compared to all other states in the U.S.

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.

NE states

Reported TB Case Rates in U.S.,NE vs. Other States, 1993-2005

Year

Ra

te T

B C

as

es/

10

0,0

00

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

2000 2001 2002 2003 2004 2005

NE States All other states Nationwide

Reported TB Cases by Age Group, NE States vs. Others, 1993–2005

0

10

20

30

40

50

0-14 15-24 25-44 45-64 65+

Age at Diagnosis

NE States Other states

Pe

rce

nt

of

Cas

e C

ou

nt

Reported TB Cases by Race/Ethnicity,*NE States vs. Others, 1993–2005

Hispanic(25%) Black

(36%)

Asian(20%)

White(18%)

Amer Indian/Nat Alaskan(<1%)

Nat Hawaiian/

Pacific (<1%)

*All races are non-Hispanic. Persons reporting two or more races accounted for less than 1% of all cases. Unknown not included.

Hispanic(23%)

Black(31%)

Asian(19%)

White(25%)

NE States Other States

Amer Indian/Nat Alaskan(1%)

Nat Hawaiian/

Pacific (<1%)

Reported TB Cases by Birth Origin,NE States vs. Others, U.S., 1993–2005*

Note: Unknown not included

Birth Origin NE States

n (%)

Other States

n (%)

US-Born 21,051 (49.2) 116,601 (59.7)

Foreign-born 21,769 (50.8) 78,741 (40.3)

TB Cases, by Previous Diagnosis, NE States vs. Others, U.S., 1993–2005*

Note: Unknown and missing not included*Updated as of March 29, 2006.

NE States

n (%)

Other states

n (%)

Previous diagnosis of TB

1,695 (4.0) 10,785 (5.5)

No previous diagnosis of TB

41,153 (96.0) 183,777 (94.5)

HIV Test Results of TB Cases,NE States vs. Others, U.S., 1993–2005*

HIV Status NE States

n (%)

Other states

n (%)

HIV Positive 8,357 (19.4) 18,025 (9.2)

HIV Negative 15,180 (35.3) 64,023 (32.6)

Missing or Unknown

19,456 (45.3) 114,511 (58.2)

* Excludes unknown and missing.Directly observed therapy (DOT); Self-administered therapy (SA)

Mode of Treatment Administration in Persons Reported with TB,

NE States vs. Others, U.S., 1993–2003*

0%

20%

40%

60%

80%

100%

NE States OtherStates

DOT only DOT + SA SA only

Percent Completion of TB Therapy,* NE States vs. Others, U.S., 1993-2005

0

20

40

60

80

100

1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

NE States Other US

*Healthy People 2010 target: 90% completed in 1 yr or less.Note: Excludes persons with initial isolate resistant to rifampin and children <15 years old with meningeal, bone or joint, or miliary disease excluded.

Percent

Year

Reason Therapy Stopped in TB Cases, NE States vs. Others, U.S., 1993–2005*

010

203040

5060

7080

NE States Other States

Completed Moved Lost Uncoop/Refused Died Other Missing/Unk

Percent

MDR TB* in NE States vs. Others,U.S., 1993-2005

0

1

2

3

4

5

6

7

8

NE States Other US

% M

DR

TB

Year of Reporting

%MDR TB cases = no. of TB cases with Mycobacterium tuberculosis isolatesresistant to isoniazid and rifampin, among all cases tested to isoniazid and rifampin

MDR TB by Birth Origin, NE States vs. Others, U.S., 1993-2005

Birth Origin NE States

n (%)

Other US

n (%)

Foreign-born 390 (34.5) 1082 (64.2)

U.S.-born 735 (65.1) 589 (35.0)

Unknown origin 4 (0.4) 13 (0.8)

Total 1129 (100.0) 1684 (100.0)

TB Epidemiology Summary in NE States*• Heterogeneous states (high, medium, low incidence)

• Consistently higher rates

• Majority (58.6%) younger than 44 years

• Most (82%) racial/ethnic minorities

• Lower proportion (49.2%) U.S.-born

• Higher prevalence (19.2%) HIV infection

• Larger proportion on DOT+SA and SA only treatment

• COT improving (82%), room for improvement

• MDR decreased 1993-2000, recent stagnation

* Compared with other states, U.S., 1993-2005

Second-Line Drug Classes for MDR TB Treatment

Amikacin, Kanamycin

Ciprofloxacin, Ofloxacin

Ethionamide, ProthionamideThioamides

PAS

Polypeptides

Serine analogues

Capreomycin

WHO. Guidelines for the programmatic management of drug-resistant tuberculosis. 2006.

Aminoglycosides

Fluoroquinolones

Cycloserine

First line drugs +

Characteristics of KZN XDRTB PatientsCharacteristics No. (%)

• No prior TB Treatment 26 (51)

• Prior TB treatment– Cure or Completed treatment 14 (28)– Treatment Default or Failure 7 (14)

• HIV-infected (44 tested) 44 (100)

• Dead (Includes 34% on ARV) 52 (98)

• Identical M. tb spoligotype 26/30

* Moll A, Gandhi NR, Pawinski R, Lalloo U, Sturm AW, Zeller K, Andrews J, Friedland G.HIV associated Extensively Drug-Resistant TB (XDR-TB) in Rural KwaZulu-Natal (South Africa MRC Expert Consultation Sept 8, 2006)

Hospital

Total Cases

% HIV Infected

% Deaths

Median Wks

Dx to Death

A 65 93 72 7

B 51 100 89 16

C 70 95 77 4

D 29 91 83 4

E 7 14 43 4

F 16 82 82 4

I 13 100 85 4

J 28 96 93 4

Prison 42 98 79 4

HIV-related MDR TB Outbreak Investigations by CDC & Health Departments, USA, 1988–92

U.S. Response to TB ResurgenceNational MDR-TB Action Plan

& New ResourcesImproved Case

Identification & Training

Updated Diagnostic Labs, Real-time Drug Resistance,

& Strain Fingerprinting

Updated Infection Controland Rx Recommendations

DOT & Improved Rx CompletionRebuilt Research Capacity

AJRCCM 1994;149:1359-74

Global 7-point Action Plan to Combat XDR TBEmphasizes Essentials of Proper TB Control

1. Conduct rapid surveys of XDR-TB (determine burden)2. Enhance laboratory capacity (emphasis on rapid DST)3. Improve technical capacity of clinical and public

health practitioners to effectively respond to XDR-TB outbreaks and manage patients

4. Implement infection control precautions (PLHA focus) 5. Increase research support for anti-TB drug

development 6. Increase research support for rapid diagnostic test

development 7. Promote universal access to ARVs under joint TB/HIV

activities MRC Consultation, Johannesburg, South Africa. Sept 7, 2006

Revised WHO Case Definition for XDR TB (Oct 10, 2006)

Goals

• Public health surveillance

• Reliable DST methodology

• Clinical relevance

• Relatively simple

Resistance to at least isoniazid and rifampin(MDR) plus resistance to fluoroquinolonesand one of the second-line injectable drugs(amikacin, kanamycin, or capreomycin)

TB Treatment Outcomes, by Selected Drug Resistance Patterns, Latvia, 2000-2003*

0 10 20 30 40 50 60 70

MDR-TB All

HR+3SLD

HR+INJ+FQ

HR+AG+FQ

Cure Completion Death Default Failed Continue Tx HIV+

* Leimane V, et al. WHO XDR TB Task Force Meeting. Oct 9, 2006 (from N = 820 evaluated)

Percent

XDR(WHO) TB Cases in U.S.,Northeast vs. Other States, 1993-2005

0

2

4

6

8

10

12

14

1993 1995 1997 1999 2001 2003 2005

Other States

NE States

No. XDR TB Cases

Year of Report

XDR(WHO) TB Cases in U.S.,Foreign-born vs. U.S.-born, 1993-2005

0

2

4

6

8

10

12

14

1993 1995 1997 1999 2001 2003 2005

Foreign-born

US-born

No. XDR TB Cases

Year of Report

XDR(WHO) TB Cases in Northeast States, Foreign-born vs. U.S.-born,1993-2005

0

2

4

6

8

10

12

14

1993 1995 1997 1999 2001 2003 2005

Foreign-born

US-born

Year of Report

No. XDR TB Cases

XDR(WHO) TB Cases in Other States, Foreign-born vs. U.S.-born,1993-2005

0

2

4

6

8

10

12

14

1993 1995 1997 1999 2001 2003 2005

Foreign-born

US-born

Year of Report

No. XDR TB Cases

XDR(WHO) TB Cases in U.S.-born vs. Foreign-born Persons, 1993-2005

1993-1998 2000-2005

U.S.-born 19 3

Foreign-born 12 12

TB Clinical Development PipelineCompound Development Stage Sponsor / Coordinator

Gatifloxacin Phase IIIEC / OFLOTUB Consortium; IRD*; WHO TDR; Lupin Ltd.

Moxifloxacin Phase II / III

Bayer; TB Alliance; CDC; University College of London; Johns Hopkins University

Early Bactericidal Activity Johnson & Johnson (Tibotec)

Early Bactericidal Activity Otsuka Pharmaceutical Co., Ltd.

Phase I TB Alliance

Phase I Lupin Ltd.

* Institut de Recherche pour le Developement World Health Organization, Tropical Disease Research Centers for Disease Control and Prevention

Novel compounds, highlighted in blue boxes, are active against MDR/XDR TB

Diarylquinoline TMC207

Nitroimidazo-oxazoleOPC-67683

Nitroimidazole PA-824

Pyrrole LL-3858

Examples of Rapid Drug Resistance Methods

Test GenoType® MTBDR

INNO-LiPA Rif.TB

Company Hain Lifescience

Innogenetics

M. tuberculosis detection Yes Yes

Detection RMP resistance Yes Yes

Detection INH resistance Yes No

Strip Assay Yes Yes

DNA basis: PCR Yes Yes

Direct assay No Yes (modified version)

RMP resistance:rpoB gene Yes Yes

INH resistance:katG gene Yes No

Microscopic-Observation Drug SusceptibilityAssay for the Diagnosis of TB*

Moore DAJ, et al. N Engl J Med 2006;355:1539-50

Actual and BRDPI-Adjusted Federal Funds for TB*, CDC, 1990-2006

$0

$50

$100

$150

$200

1990

1992

1994

1996

1998

2000

2002

2004

2006

Fu

nd

ing

($ x

mil

lio

n)

112

112

Actual $

BRDPI Adjuste

d

* Adjusted to 1990 US$ by Biomedical Research & Development Price Index

** Includes TB/HIV and lab dollars