Rise and fall of XDR TB in Tugela Ferry - how we did

17‐Jun‐14
The rise and fall of XDR TB in Tugela Ferry –
how we did it
Gerald Friedland MD
Yale University School of Medicine
On behalf of
Tugela
g Ferryy Care and Research Collaboration
Tugela Ferry-Msinga Sub District Rural KwaZuluNatal
Tugela
uge a Ferry
e y
Durban
Msinga
• 180,000 traditional Zulu people
Extreme poverty
• Poorest sub district in South Africa
High TB and HIV burden
• TB case rate >1,000/100,000 pop
• >30% HIV in antenatal attendees
COSH- 350 bed district hospital
Philanjalo- NGO
UKZN- TB DR Laboratory
UKZN
1
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MDR/XDR TB in Tugela Ferry
2005 – 2006
• 53 cases XDR TB
– All tested HIV
HIV+
– 98% rapid mortality
– Evidence for nosocomial spread
1.1
1.0
.9
Proportion S
Surviving
.8
.7
.6
.5
.4
.3
.2
.1
0.0
-.1
0
30
60
90
120
150
180
210
240
Gandhi, Moll, Sturm, Pawinski, Govender,
Lalloo, Zeller, Andrews, Friedland
Nov 2006
3
Days since Sputum Collected
Accumulative Number of Identified Drug Resistant TB
cases
Jan 2005 and Jan 2008
696
750
700
650
Total DRTB
600
Patient Numbers
550
500
397
450
400
XDRTB
350
300
250
299
200
MDR TB
150
100
50
0
Jan-08
Nov-07
Sep-07
May-07
Jul-07
Mar-07
Jan-07
Nov-06
Sep-06
May-06
Jul-06
Mar-06
Jan-06
Nov-05
Jul-05
Sep-05
May-05
Mar-05
Jan-05
Month
4
4
2
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MMWR – March 2005
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The statistics of epidemiology are human
beings with the tears removed
6
3
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Recognition that MDR/XDR TB are
Widespread in South Africa and Beyond
•
•
•
•
XDR TB from ~ 60 KZN facilities in KZN by mid 2007
XDR TB cases found in all 9 South African provinces
– ~ 1,000 cases in 2005
2005--7 (~ 18,000 MDR TB cases)
Inpatient and outpatient survey 19 KZN hospitals 20082008-9
– 84 (15% MDR), 16 (3%) XDR TB
– Most undiagnosed
Neighboring
g
g countries affected
• Botswana
Botswana,, Mozambique, Lesotho
Lesotho,, Swaziland, 92 countries
• Full extent unknown, no denominator, culture and DST
limited
7
Confronting the Convergent Epidemics
•
In response, the KZN Department of Health, Philanjalo and
US and South African and US academic institutions and
investigators formed a collaboration, TF CARES, to combat
the convergent XDR-TB, MDR-TB and HIV epidemics
•
Describe health care facility and community based
interventions and strategies developed and implemented to
p
and highlight
g g some of pparticular
combat the epidemics
interest
•
Describe current status of MDR and XDR TB in Tugela
Ferry
.
4
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Integrated TB and HIV Interventions to Combat
Convergent Epidemics
Strengthening TB DOTS Program and resources for interventions
Improving inpatient/outpatient infection control facilities and practice
Integrating TB & HIV diagnosis, care and treatment and initiating
antiretroviral therapy
Reducing reliance on inpatient care and focusing on patient centered
community based case finding, diagnostic and therapeutic interventions
9
Slide 10
Strengthening the TB DOTS Program
Numb
ber of Resources
Department of Health TB
Resources
30
Management
25
Enrolled Nurses
20
Tracing Teams
15
TB Vehicles
P<0.01
10
5
0
Zanele Radebe KZN DOTS
5
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Strengthening the TB DOTS Program
25
100
90
80
70
60
50
40
30
20
10
0
88.1 85.0 84.5
82.5 82.5
79.9
20
16.4
61.1
15
10
5
13.7
10
9.1
7.3
7.4
4.9
0
2004 2005 2006 2007 2008 2009 2010
2004 2005 2006 2007 2008 2009 2010
P<0.01
Zanele Radebe KZN DOTS
11
Slide 12
Improving lnpatient/outpatient airborne infection
control
Comprehensive multifaceted infection control program
• D
Developing
l i andd implementing
i l
ti first
fi t policies
li i andd practice
ti in
i KZN
• Adapted to local environment
• Identifying and separating MDR and XDR TB suspects
• Performing facility assessment and improvement
• Enhancing natural ventilation
• Protecting personnel
• Staff assessment and training
• Reducing reliance on hospital care
• Monitoring and evaluating program
• Community expansion
6
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Transmission of MDR & XDR TB
Identify and separate TB suspects
Patient cough screening/ masks
•
•
•
•
•
•
Screen for TB at all hospital entrance points and high risk areas
HIV/ARV clinic- 9% coughers
g
TB + ,,incl MDR/XDR TB
OPD 6- to 10 % AFB+ among productive coughers
Separate and fast track coughing patients
Masks for all ARV clinic patients
Early diagnosis –GenXpert-Nov 2012
Barbaria, Catterick, Shah, Shenoi et al, 2010
Shenoi et al 2013
14
7
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Slide 15
Improving infection control facilities
Environmental Assessment: Effect of Natural Ventilation
Windows closed & mechanical ventilation off
< 1 ACH
Windows closed & mechanical ventilation on
~ 15 ACH
All windows open & mixer fans on
>60 ACH
Facilities Improvement
New ARV
Clinic
Pre-2008
Post-2008
16
8
17‐Jun‐14
Personal protection
• N95 Respirator in high risk areas
• Staff Screening
– All new staff screened for TB and HIV at employment
– Followed by Screening 6 monthly
– Encouraged to know HIV status
– Can be relocated from high risk area CD4<350
17
Establish a culture of good infection control practice
open windows, screen for active TB, respirators and masks for staff and patients
18
9
17‐Jun‐14
How to measure effectiveness?
Program of monitoring and evaluation
19
19
Environmental Monitoring:
Natural Ventilation
100%
80%
60%
Male TB
Open Windows
Female TB
Open Windows
40%
20%
0%
2007
2008
2010
20
20
10
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XDR TB Cases Averted Using Combinations of
Available Infection Control Strategies 2007-12
Basu, S et al, Lancet 2007
48%
37%
28%
(625)
(482)
(365)
21
0
22
11
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Community-based strategies
Early case finding,
diagnosis and entry into care
Household
contact
tracing
CBICF
Screening
Isoniazid
Preventive
Therapy
Prevention
Rapid
diagnosis
Community
based
strategies
Infection
control
Treatment
Community
based
treatment
Evaluation
/ Modelling
impact &
cost effectiveness
12
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Community Intensive Case Finding
Household contact Tracing
(n=1766)
Vella et al IJTLD 2012
Index Cases
XDR TB (382) mortality 82%
MDR TB (272) mortality 67%
Household Contacts
XDR TB (47) mortality 57%
MDR TB (26) mortality 19%
25
Community-based Integrated TB & HIV Intensive Case Finding
March 2010 - June 2012
Shenoi et al, 2013
Screened for TB
5615
HIV testing
5128 ((91.2%))
Sputum submitted
1033 (50.4%)
HIV-positive
510 (9.9%)
Microbiologically
confirmed
fi
d TB
41 (4.0%)
Median CD4
382 (IQR 260
260-552)
552)
11 (28%) M/XDR
All alive/in care
Referred for care
and ART
13
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Household contact and
Community Based Intensive Case Finding
Vella et al., IJTLD, 2011; Shenoi et al 2012
TB Results
(n=1766)
Community
ICF
(n=5613)
3624
678
2887
202
MDR/XDR TB
Household Contacts
Culture Positive
per 100,000
MDR/XDR TB
per 100,000
Large community reservoirs remain
Earlier case detection for both HIV and TB
Hint of better outcomes
27
TB- HIV Co-Infection Community ICF Setting
Compared with District Hospital
HIV -
HIV +
12%
73%
87%
27%
P<0.001
Community ICF
District Hospital
14
17‐Jun‐14
Community Based MDR TB/HIV Treatment
Brust et al, PLoS One 2011
• First patients initiated in February, 2008
• By 2011, >150 patient started treatment
 100% HIV tested
 100% Started on ARVs if HIV-positive
p
 Sputum conversion rate 89% @ 6 mos
Adherence excellent, adverse events low
 Mortality low ( 6% compared 40-50%)
 No defaults
29
Impact of combined interventions
XPT = GeneXpert
DCT = Decentralization of MDR-TB treatment
ART = expanded ART coverage
CR = improved cure rate of drug susceptible TB
IPT = 36 months of IPT
CICF = CICF coverage of 30%
ALL = all above interventions combined
Gilbert et al 2014
30
15
17‐Jun‐14
2010 67.0%
3.0%
11.0%
6.0%
6.0%
2011 72.7%
0.0%
COSH MDR/XDR DIAGNOSED 2005‐2013
0.1%
21.8%
1.8%
250
p<0.001
MDR
580
200
XDR
572
MDR
XDR
TOTAL
2005
64
114
178
150
100
2006
122
115
237
2007
94
134
228
2008
53
82
135
2009
80
60
140
2010
80
24
104
2011
66
31
97
2012
1152
35
6
41
2013
54
11
65
TOTAL
50
0
2005
2006
2007
2008
2009
2010
2011
2012
MDR
64
122
94
53
80
80
66
35
2013
54
XDR
114
115
134
82
60
24
31
6
11
TOTAL
178
237
228
135
140
104
97
41
65
Decline in MDR, XDR and total DR TB <0.001
31
Documenting the XDR/MDR epidemics
16
17‐Jun‐14
Summary and Conclusions
• Tugela Ferry 2005-2014 -What have we learned, accomplished and still need ?
•
The collision of TB, HIV and XDR/MDR TB epidemics in impoverished rural KZN,
was inevitable.
i it bl
•
Dramatically highlights local and global inadequacies in TB control, the need to
address both TB and HIV simultaneously and collaboratively and with sufficient and
sustained political will and resources.
•
Illustrates that even in resource limited rural settings, MDR TB, XDR TB and HIV
epidemics can be successfully combatted.
•
Requires addressing focusing on and implementing basic TB control, critical
t h i l needs
technical
d for
f better
b tt diagnostics
di
ti andd treatment,
t t
t but
b t also
l developing
d l i creative
ti
feasible strategies that are both health care facility and also patient and community
based.
•
Addressing poverty, inequity and health disparities which are at the root of both TB
and HIV epidemics.
33
TF CARES
Partners
Funders
Tugela Ferry Care and Research
Collaboration
Special Thanks to:
Tony Moll
Sheela Shenoi
Umzinyathi and KZN
Department of Health
Italian Cooperation
Ralph Brooks
Laurie Andrews
Theo van der Merwe
Francois Eksteen
Bruce Margot
Claudio Marra
Neel Gandhi
Sarita Shah
James Brust
AW Sturm
Jason Andrews
Mdu Mntambo
Nonhle Mtungwa
Paul Jensen
Umesh Lalloo
Tassos Kyriakides
J&J Scholars, Doris Duke ICRFs
Staff and colleagues at COSH and Philanjalo
Patients, families and community of Msinga,
Tugela Ferry
Irene Diamond
Fund
17
17‐Jun‐14
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