Transcript Nunn PaulAddisTBHIVMDRNov08 []

14th Meeting of the Core Group of the TB/HIV Working Group
Addis Ababa, Ethiopia
November 12, 2008
MDR and XDR-TB in the context of HIV:
What next?
Paul Nunn, Abby Wright
Ernesto Jaramillo
Matteo Zignol
Stop TB Department, WHO, Geneva
Latest global TB Estimates - 2006
Estimated
number of
cases
All forms of TB
Greatest number of cases in Asia;
greatest rates per capita in Africa
Multidrug-resistant
TB (MDR-TB)
Extensively drugresistant TB (XDR-TB)
HIV-associated TB
9.15 million
Estimated
number of
deaths
1.65 million
489,000
120,000
40,000
20,000
700,000
200,000
MDR-TB among new cases 1994-2007
* Sub-national averages applied to China, Russia, Indonesia.
< 3%
3-6 %
>6%
No data
MDR-TB is resistance to isoniazid and rifampicin
Drug susceptible TB
Cure rate 95+%
MDR-TB
Cure rate 67%
The boundaries and names shown and the designations used 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. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.
 WHO 2006. All rights reserved
% MDR among new and retreatment cases (1994-2006)
Kaliningrad Oblast, RF
Arkhangelsk Oblast, RF
Baku, Azerbaijan
Pskov Oblast, RF
Donetsk, Ukraine
Tomsk Oblast, RF
Tashkent, Uzbekistan
Kazakhstan*
Estonia
Mary El Oblast, RF
Ivanovo Oblast, RF*
Latvia
Liaoning Province, China*
Lithuania
Armenia
Orel Oblast, RF
Henan Province, China*
Inner Mongolia Province, China
Heilongjiang Province, China
0.0
10.0
20.0
30.0
40.0
50.0
60.0
70.0
80.0
0.35
450
70
400
60
0.30
0.25
50
0.20
0.25
250
40
0.15
200
30
0.30
350
300
0.20
0.10
42
51
51
64
53
50
0.15
Estonia
20
75
53
150
100
0.35
0.05
1997
10
50
0
1997
0
1998 1999 2000 2001 2002 2003 2004 2005
New DST, New MDR
p=0.6213
0.10
0.00
1999
2001
2003
0.05
1999
2001
2003
2005
2007
0.00
1997
TB notification rate
2005
p=0.6213
1999
2001
2003
2005
% MDR among new
600
120
0.35
500
100
0.30
400
80
300
60
200
40
0.25
0.20
2002
77
73
2001
95
57
2000
59
48
100
27
0.15
0
1999
2003
2004
2005
Tomskoblast
oblast
Tomsk
20
0
1998
0.10
p=0.0055
0.05
2000
2002
2004
2006
0.00
1997
1999
2001
2003
2005
2006 - eXtensively Drug Resistant
Tuberculosis - XDR-TB
XDR = Resistance to at least INH and
RIF (MDR) PLUS resistance to
fluoroquinolones, AND one of the
second-line injectable drugs (amikacin,
kanamycin, or capreomycin)
Of 17,690 isolates from 49 countries
during 2000-2004 20% were MDR
and 2% were XDR
XDR found in:
USA: 4% of MDR
Latvia: 19% of MDR
S Korea: 15% of MDR
MMWR Morb Mortal Wkly Rep 2006; 55:301-5
Countries with confirmed cases of
XDR-TB as of November 2008
Anti-TB Drug resistance:
Status as of 2008







Highest rates in FSU, with MDR rates among new cases
higher - up to 29% - as DRS expands
Across all patients in FSU – 1 in 5 has MDR-TB
Up to 10% MDR in new cases in parts of China and India
China, India and Russia account for 60% global MDR-TB
burden – but response in all 3 is inadequate
Baltics reducing the problem with targeted investment,
Estonia reducing all cases and % MDR-TB
Mortality of M and XDR-TB remains very high
What is the impact of HIV on MDR?
HIV-associated MDR TB outbreaks
1980's and 1990's outbreaks in Buenos Aires,
London, Milan, New York City etc
Periodic surveys, especially in Africa, did not
detect significantly higher rates of drug
resistance among those with HIV
XDR-TB in Tugela Ferry,
South Africa
Study characteristics (53 patients)
No. (%)
 No prior TB Treatment
 Prior TB treatment
– Cure or Completed treatment
– Treatment Default or Failure
 HIV-infected (44 tested)
 Health care workers
 Dead (includes 34% on ARV)
 Median survival
 Number of TB strains
26 (51)
14 (28)
7 (14)
44 (100)
2
52 (98)
16 days
4+
Ghandi N et al. Lancet 2006; 368:1575-80
MDR and XDR-TB cases
by month in CoSH 2005-2008
Monthly MDR and XDR cases (2005 - 2008)
35
30
25
2005
20
2006
15
2007
10
5
2008
By Dec 2007 –
MDR cases 286
XDR cases 382
December
November
October
September
August
July
June
May
April
March
February
January
0
U
eT
w
he
k
in
i
m
2
gu
1
ng Ug
un u
23 dlo
v
U
th u
24
uk
U
el
m
a
zi
ny
25
at
hi
A
m
26 aju
27
Zu ba
U
m
kh lula
nd
an
y
ak
28
ud
U
th
e
un
gu
29
l
iL u
e
43 mb
e
Si
K
s
on
ZN
pr ke
ov
in
ce
22
20
XDR / MDR
eT
he
22
kw
Um
in
i
2
gu
1
ng Ug
un u
23 dlo
v
U
24 th u
Um uke
zi la
ny
25
a
Am thi
26 aju
27
Um Zu ba
kh lula
an
nd
y
28
a
Ut kud
hu
e
ng
ul
29
iL u
e
43 mb
e
KZ Sis
o
N
n
pr ke
ov
in
ce
20
MDR cases/100k popn.
70
60
50
40
30
20
10
0
60%
50%
40%
2005
2006
2007
2005
2006
2007
30%
20%
10%
0%
MDR cases
per 100 000
population
(top)
XDR/MDR
(bottom)
(Data for
Uthungulu for
2005 excluded)
MDR-TB and HIV in Ukraine
MDR rates
(95% CLs)
Civilian sector
Previously
New cases
treated cases
n=924
n=369
15.5
41.5
(13.1 to 17.8) (36.4 to 46.5)
Penitentiary sector
Previously
New cases
treated cases
n=78
n=125
21.8
52.8
(12.4 to 31.2) (43.9 to 61.7)
 Independent predictors for MDR-TB
History of previous treatment: OR: 4.0 (95%CLs 3.1-5.1)
Imprisonment: OR: 1.5 (95%CLs 1.1-2.0)
• HIV status: OR: 1.7 (95%CLs 1.3-2.3)
Summary situation of MDR and HIV
 HIV is causing outbreaks of MDR-TB
 HIV probably increasing community
transmission of MDR-TB where prevalence of
infection with MDR-TB is high,
 Epidemics of HIV (focus Africa) and MDR (focus
Eastern Europe) now overlap
http://whqlibdoc.who.int/publications
Prevention of MDR TB in context of
HIV
 Involve community representatives in
design of care and prevention
 Ensure high quality basic TB control
 Infection control
– HIV and ART clinics
– Guidelines, and WHO policy January
2009
 Preventive therapy problematic
Management of MDR-TB in context
of HIV
 Ensuring rapid diagnosis and
management of TB in HIV clinics
– Intensified case finding
– Laboratory capacity for MDR-TB diagnosis
• Culture, solid and liquid
• Molecular tests, eg line probe assays, now
WHO policy
• DST for all patients?
 Empirical treatment for MDR-TB
– Avoid thiacetazone
Management of MDR-TB in context
of HIV - II
 ART
– When to start
– Drug interactions
– Immune reconstitution inflammatory syndrome
 HIV care and support, but remember infection
control
 Centres of excellence
 Isolation facilities
 Involuntary detention
 Care in the community
 Special teams
Policy decisions confronting many
countries in MDR-TB
 Move from pilot phase to national scale up of
MDR-TB
 Sources of finance eg GFATM
 Expansion of laboratory capacity – national
laboratory plan
 National airborne infection control plan
 Sourcing of 2nd line drugs – GLC/GDF or
national pharmaceutical industry
 Quality assurance of 2nd line drugs
 Involvement/regulation of the private care
delivery sector