Extensively Drug-Resistant TB
(XDR-TB)
Lynelle Phillips, RN MPH
Nurse Consultant
Heartland National TB Center
Adjunct Faculty
UM Masters of Public Health Program
Sinclair School of Nursing
March 24, 1882 – “Do we know
now, how to fight this enemy?”
 1882 Robert Koch
discovered the tubercle
bacillus, Mycobacterium
tuberculosis, the bacterium
that causes tuberculosis.
In 1890 Koch announced that
he had discovered a
substance that could protect
against tuberculosis and even
cure it. He announced the
following year, that it was a
glycerine extract of tubercle
bacille, now known as “Old
Tuberculin”. (Nobel Prize –
1905)
Smithsonian Jan 2002
TB disease treatment regimen
 1944 – Streptomycin – IM if rifampin resistant
 1952 - Isoniazid – 6 months minimum
 Also for treatment of infected contacts
 1952 – Pyrazinamide – 2 months
 1962 – Ethambutol – discontinue if
pansensitive
 1966 – Rifampin – 6 months minimum
 Also for treatment of infected contacts
A Silent Global Epidemic
1/3 of the world’s population infected
8 million new cases of active disease per year
2-3 million deaths per year
One person is newly infected every second
and one person dies every 10 seconds
 Rising incidence of drug-resistant disease
 Billions of dollars in lost productivity




Estimated TB incidence rate, 2003
Rates per 100 000, all
forms of TB
0 - 24
25 - 49
50 - 99
100 - 299
300 or more
No estimate
The designations employed and the presentation of material on this map do not imply the expression of any opinion
whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or
area or of its authorities, or concerning the delimitation of its frontiers or boundaries. White lines on maps represent
approximate border lines for which there may not yet be full agreement.
© WHO 2004
Second-Line Drug Classes for MDR TB
Treatment
Aminoglycosides
First
line
drugs
Amikacin, Kanamycin
Polypeptides
Capreomycin
Fluoroquinolones
Ciprofloxacin,
Ofloxacin
Thioamides
Ethionamide,
Prothionamide
+
Serine
analogues
Cycloserine
PAS
WHO. Guidelines for the programmatic management of drug-resistant
% Resistant
Primary MDR TB in
U.S.-born vs. Foreign-born Persons, United
States, 1993–2005*
3
2
1
0
1993
1995
1997
1999
U.S.-born
2001
Foreign-born
*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.
2003
2005
Global WHO/IUATLD/CDC
Survey
 Convenience sample (17,690 isolates)
submitted to participating international
SRL network, 2000-2004
 3520 (20%) of isolates MDR TB
 347 ( 2%) of isolates XDR TB
 XDRTB in all regions, more common
FSU and Asia (Republic of Korea)
 Denominator information unavailable
Number of MDR and XDR Cases, by Countries Submitting
≥ 1 M. tuberculosis Isolate to Participating SRLs, 2000–2004
Total MDR= 3520; XDR= 347 (~ 10% of MDR)*
E. Europe
MDR 406
XDR 55 (14%)
Ind. Nations
MDR 821
XDR 53 (6%)
Rep. Korea
MDR 1298
XDR 200 (15%)
Asia
MDR 274
XDR 4 (1%)
Latin America
MDR 543
XDR 32 (6%)
Africa, Middle East
Isolates contributed
to survey
MDR
156
XDR 1 (< 1%)
* Country unknown, MDR= 102; XDR= 2 (2%)
TB Treatment Outcomes, by Selected Drug
Resistance Patterns, Latvia, 2000-2003*
Cure
Completion
Death
Default
Failed
Continue Tx
HIV+
HR+AG+FQ
HR+INJ+FQ
HR+3SLD
MDR-TB All
0
10
20
30
40
50
60
70
Percent
* Leimane V, et al. WHO XDR TB Task Force Meeting. Oct 9, 2006 (from N = 820 evalu
KZN Hospital Background*
 119 patients in TB/ARV integration study
 14 deaths
 10 (71%) of 14 with MDRTB
 6/10 MDRTB resistant to all tested first and
second line drugs (SLD) for TB
 INH, RIF, EMB, STR, KANA, CIPRO
 Suggestive of probable extensive drug
resistant TB in this hospital
* 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)
KZN Drug Resistant TB
Survey*
 Jan 2005 − Mar 2006 cross-sectional study of
patients suspected with active TB in rural
district hospital
 Isolates collected for mycobacterial culture
(MGIT) and DST on all M. tuberculosis
cultures
 INH, RIF, EMB, STR, KANA, CIPRO
 Chart reviews of patients with strains
resistant to all tested drugs (“XDR TB”
cases)
 Molecular fingerprinting by spoligotyping on
all “XDR TB” isolates
KZN Drug Resistant TB Survey Resu
1539 isolates
tested
544 (35%) Cx+
M. tuberculosis
221(41%) MDRTB
995 (65%) Cx
Negative
323 (59%)
Susceptible
53 (10%) XDRTB
(24% of MDRTB)
* 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)
Characteristics of KZN XDRTB
Patients
Characteristics
 No prior TB Treatment
 Prior TB treatment
 Cure or Completed treatment
 Treatment Default or Failure
 HIV-infected (44 tested)
 Dead (Includes 34% on ARV)
 Identical M. tb spoligotype
No. (%)
26 (51)
14 (28)
7 (14)
44 (100)
52 (98)
26/30
Global 7-point Action Plan to Combat XDR TB
Emphasizes Essentials of Proper TB Control
1.
2.
3.
4.
5.
6.
7.
Conduct rapid surveys of XDR-TB (determine burden)
Enhance laboratory capacity (emphasis on rapid DST)
Improve technical capacity of clinical and public health
practitioners to effectively respond to XDR-TB
outbreaks and manage patients
Implement infection control precautions (PLHA focus)
Increase research support for anti-TB drug
development
Increase research support for rapid diagnostic test
development
Promote universal access to ARVs under joint TB/HIV
activities
MRC Consultation, Johannesburg, South Africa. Sept 7, 2006
Reported Tuberculosis Cases in Foreign-Born
Persons
Missouri 1985-2006
60
percent
number
50
40
30
20
10
0
8
19
5
8
19
6
8
19
7
8
19
8
8
19
9
9
19
0
9
19
1
9
19
2
9
19
3
9
19
4
9
19
5
9
19
6
9
19
7
9
19
8
9
19
9
0
20
0
0
20
1
0
20
2
0
20
3
0
20
4
0
20
5
0
20
6
0
20
7
Is there XDR TB in the U.S.?
(MMWR: 4% of MDR Cases)
XDR Analysis, 2000 – 2004
National TB Surveillance System
Based on Revised WHO
XDR TB Definition
Resistant: 13
Tested:
509
Number of Reported TB Cases
with XDR TB, U.S., 2000-2004
MMWR Definition
Revised WHO
Definition
N= 18 (9 male)
13 (6 male)
Age range 19-64
19-77
HIV (+)
2
1
HIV (−)
8
5
HIV NA/unk 3
7
CA
5
4
FL
2
0
NYC
7
5
NJ
1
1
IL, NV, TN 1 (ea) IL,NV, TX 1 (ea)
ATS/CDC Recommends 4 Drug Regimen if INH
Resistance Over 4%
INH resistant
ATS 4-drug guideline
10
8
6
4
2
20
05
20
03
20
01
19
99
19
97
19
95
0
19
93
% cases INH resistant
12
Comparison of INH resistance
between all TB cases and foreignborn TB cases - 2006
70
60
50
40
% of total INH resistant
30
% of foreign born INH
resistant
20
10
0
2000
2001
2002
2003
2004
2005
2006
1989
MDR TB outbreak
Missouri
001mo.H3514
1991
1993
1997
RFLP testing
1998
1999
2000
2001
2002
Corrections
Cx confirmed
Clinical case
Confirmed epi link
Suspect link
Inside DOC
Outside DOC
Migrants Entering U.S.
Temporary visa holders:
~ 30,175,000
Visitors without visas:
~ 30,000,000
Immigrants and
refugees:
~ 435,000
Undocumented
immigrants:
~ 275,000
N= ~ 61,200,000
Status adjusters in U.S.:
~ 305,000
Source: U.S. Department of Justice, 1998
Opportunities for TB Prevention in
Foreign-born Persons in U.S.
Immigrants and Refugees
Panel Physicians
ICE
Quarantine Stations
Status Adjusters
Civil Surgeons
Immigrants and
Refugees
Health Departments
Foreign-born Persons not Screened for
TB before U.S. "Entry”, 1998
 Visitors not requiring Visas: ~30, 000,000
 Non-Immigrant Visas:
30,174,627








Temporary Visitors:
Temporary Workers/family:
Students/family:
Transit Aliens:
Treaty traders/family:
Foreign government officials:
Other
Undocumented visitors:
27,766,580
458,519
598,520
365,607
144,572
126,543
714,286
???
Source: U.S. Department of Justice, 1998
DGMQ authority
 …had not been tested since 1963 when
a traveler suspected of small pox was
quarantined.
Do Not Board Tool
 Official request from CDC to DHS/OHA is required;
Upon DHS/OHA’s approval, DHS request TSA to add
the person to the Do Not Board list or requests
Customs and Border Protection to add the individual
to the Lookout list. The travel restrictions will prevent
an individual from boarding a plane inbound,
outbound, or within the U.S.
 Applies to aliens and U.S. citizens
 Do Not Board is NOT the same as Do Not Fly
 Do Not Fly is aimed at protecting civil aviation and the
United States from acts of terrorism
 Persons on Do Not Board are not part of the Do Not Fly
Missouri Statute 199.210
Missouri Rehabilitation Center
 July 1, 1996
MRC becomes
directly affiliated
with the University
of Missouri at
Columbia.
 Inpatient TB unit,
approximately 9
negative pressure
isolation beds.
South Africa
 Involuntary detention
 WHO – patient assumes responsibility to
isolate themselves from general public –
may be too permissive?
 Judiciaries often have the authority to issue
orders compelling involuntary confinement
 Missouri court order system
“TB Patient Chafe Under Lockdown
in South Africa”
 By Celia W. Dugger, Port Elizabeth, SA, March
25, 2008
 The Jose Pearson TB Hospital here is like a
prison for the sick. It is encircled by three
fences topped with coils of razor wire to keep
patients infected with lethal stains of TB from
escaping. But at Christmastime and again
around Easter, dozens of them cut holes in the
fences, slipped through electrified wires or
pushed through the gates in a desperate bid to
spend the holidays with their families.
Cont….
 Patients have been tracked down and forced to
return; the hospital has quadrupled the number
of guards. Many patients fear they will get out
of here only in a coffin.
 “We’re being held here like prisoners, but we
didn’t commit a crime,” Siyasanga Lukas, 20,
who has been here since 2006, said before
escaping last week. “I’ve seen people die and
die and die. The only discharge you get from
this place is to the mortuary.”
In the United States…
Take Robert Daniels, the second
most-famous TB patient these days.
He has extensively drug-resistant
Arizona TB Patient Jailed as a Public TB and is being held in an Arizona
Health Menace
hospital under court order. His case
by Richard Knox
raises even sharper questions about
how to provide complicated
treatment, protect the public, and
prevent the spread of a dangerous
new strain of TB.
Listen Now add to playlist
Robert Daniels with his wife, Alla, and their son in Moscow, before he returned to the
United States. Courtesy KJZZ 91.5 FM
Since last summer, Daniels has
been locked in a bare room on the
fourth floor of the Maricopa County
Hospital in Phoenix. It's a jail unit for
criminals who need medical care.
But Daniels has never been charged
with a crime. He's there because
he's been judged a menace to
public health.
“There are no more borders. If one
country suffers, every country suffers. If
one country has infectious disease, every
country has infectious disease”
Dr. Juxel Garcia
Deputy Director, PAHO