Global Approaches
Combating MDR-TB

Jing Bao, MD, PhD
Baoj@mail.nih.gov
6th Conference of International Union
Against Tuberculosis and Lung Disease, Asia Pacific Region
March 22-25, Tokyo, Japan1

Estimated number of cases of MDR-TB occurring, reported,
treated, and successfully treated among global total notified andprevalent TB cases in 2014

Estimating the global burden of multidrug-resistant tuberculosis among prevalent
cases of tuberculosis, S. Nourzad,* H. E. Jenkins,†‡ M. Milstein,§¶ C. D. Mitnick†§#

2

MDR-TB Epidemiology
 MDR-TB is a form of TB that is resistant totreatment with at least two of the most powerful
first-line anti-TB medications (drugs), isoniazidand rifampin.
 According to WHO’s Global TB Report, there
are 580,000 MDR-TB new cases in the world
and 250,00 death due to MDR-TB in 2015.

3

The three HBC lists of 30 countries each thatwill be used by WHO 2016 - 2020

http://www.who.int/tb/publications/global_report/high_tb_burdencountrylists2016-2020.pdf
4Use of highburden countrylistsfor TB by WHOin the post 2015era5Top 30 countries: absolute TB numbers and rates

6

Top 30 countries in terms of absolute numbers and rates
MDR-TBTB7

In 2015: 9557
In 2014: 9421
1.6% Increase8

Primary MDR TB,United States, 1993 – 2014*
5003%

4002%

300
200

1%

10000%
No. of Cases

Percentage*Updated as of June 5, 2015.
Note: Based on initial isolates from persons with no prior history of TB. MDR TB defined as resistance to at leastisoniazid and rifampin.

9Numbers of TB cases in England versus the US(Collaborative TB Strategy for England 2015-2010)https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/4032
1031/Collaborative_TB_Strategy_for_England_2015_2020_.pdf

The Cost Burden of Drug-Resistant
TB in the U.S.
 While MDR and XDR TB are relatively rare in

the US, their treatment comes at a terrible price expensive
 takes a long time, disrupts life, and has potentially life threatening side effects.

11

The Cost Burden of MDR-TB in the U.S.

https://www.cdc.gov/nchhstp/newsroom/docs/factsheets/costly-burden-dr-tb-508.pdf

12Preventing and Controlling MDR andXDR TB in the U.S.

Requires:13

WHO The End TB Strategy
at a glance

http://apps.who.int/iris/bitstream/10665/250441/1/9789241565394-eng.pdf ?ua=1

14

United States Government Global
TB Strategy 2015-2019https://www.usaid.gov/sites/default/files/documents/1864/Reach-Cure-Prevent-201515
2019-TBStrategy.pdf

NATIONAL ACTION PLAN FOR COMBATING
MULTIDRUG-RESISTANT TUBERCULOSIS:
Six–Month Progress Report and Future Direction

https://www.cdc.gov/globalhivtb/images/usg-mdr-napreport-2016-final.pdf

16

The U.S. NAP
On December 22, 2015, the White House National Security
Council officially released a plan to address MDR-TB)
domestically and internationally and to advance research on thiscritical public health issue through a National Action Plan for
Combating MDR-TB
 The release was followed by a launch event on January 7, 2016,
which was open to the general public.
 The NAP, which will build on the WHO END TB Strategy andthe U.S. Government’s (USG) domestic and global TB strategies,
will contribute to the success of these existing strategies.
17

Three Goals of USG NAP31Strengthen
domestic
capacity

2
Improveinternational
capacity

Acceleratebasic andappliedresearch anddevelopment

18

TB is Disease of Poverty
The world map ofpoverty

The world map oftuberculosis

Geographical Distribution of TB
in China

LX Wang, et al., Chin J Epid, Oct., 201320

A Beautiful Dancer in Shanghai

21

Multi-Drug Resistant Tuberculosis

22

Shanghai 'most popular city'
for migrants

http://www.chinadaily.com.cn/china/2014-05/19/content_17516078.htm
23

Shanghai Chest Hospital24

He Should Not Have Died
Global Health Implication of Multi-Drug Resistant
Tuberculosis
The World Is Flat, there is no country boundaries for MDR TB

MDR-TB in Belarus

http://belarusdigest.com/story/fighting-tuberculosis-western-mythsand-belarusian-reality-18541

26

Financial barriers and coping strategies: aqualitative study of accessing MDR TB and TB
care in Yunnan, China
Five focus group discussion / 47indepth interviews for sampled TB,
MDR-TB, and health care providers
2014-2015
 Financial constrains are the mostcommon barriers to accessing care
 Rural residents, farmers, and ethnic
minorities were most vulnerable.
 Patients selling assets or borrowingmoneyHutchison et al. BMC Public Health (2017) 17:221 DOI 10.1186/s12889-017-4089-y27

MDR-TB Comorbidities
Of 1970 patients with drug-resistanttuberculosis
 486(24,7%) had one or more comorbidity

 223 patient(11,3%) had liver diseases DM-104(5,2%)
 HIV-72(3,7%)
 Psychiatric diseases - 53(2,7%), Other-55(2,9%).
Comorbidities and MDR-TB treatment outcomes in Georgia- 2009-11 cohort
Marina Kikvidze, Lali Ikiashvili European Respiratory
Journal 2014 44: P1444; DOI:28MDR TB Diagnosis
GeneXpert

J Clin Microbiol. 2007 Apr; 45(4): 1081–1086.
29

30

31

MDR-TB Global Clinical Trials
 Nix-TB: A Phase 3 Study Assessing the Safetyand Efficacy of Bedaquiline Plus PA-824 Plus
Linezolid in Subjects With Drug ResistantPulmonary Tuberculosis (TBA and Janson)
Condition

Intervention

Phase

LOCATION

Pulmonary Tuberculosis
MDR / XDR

Drug: Bedaquiline
Drug: PA-824
Drug: Linezolid

Phase 36m
(optional9 m)

SA:
Cape Town
Johannesburg
Kwazulu-Natal32

THE NIX-TB TRIAL OF PRETOMANID, BEDAQUILINE AND LINEZOLID TO
TREAT XDR-TB (CROI, Feb. 27, 2017, Seattle)
Francesca Conradie1, Andreas H. Diacon2, Daniel Everitt3, Carl Mendel3, Christo van Niekerk4,Pauline Howell5, Kyla Comins6, Mel Spigelman3

61 participants have been enrolled as of 15 December 2016 at 2 sites.
 49% of the participants are HIV positive,
 79% have XDR-TB and 21% have MDR TI or Fr to prior therapy.
 34 have completed the 6 months of therapy with the drug regimen and20 have been followed to the primary endpoint at 6 m after treatment.
 All surviving patients were culture negative by 4 mos, with 74%
negative at 8 wks.
 4 participants died within the first 8 wks of therapy; 3 had multi-organ
TB on autopsy and 1 had a GI bleed due to erosive esophagitis.
 27% had serious adverse events (AE). No surviving participants havewithdrawn from the study due to any clinical AE or lab abnormalities.
 As of 15 December, 2016, there has been 1 microbiological relapse.
33

Two new drug therapies might cure every
form of tuberculosis

Together, the new treatments, called BPaMZ and BPaL, could make treating TB
much simpler and more effective

Caution needed
https://www.newscientist.com/article/2121354-two-new-drug-therapies-might-cureevery-form-of-tuberculosis/

Tipple AAA Principle
Available

Affordable

Accessible
35

Projected acceleration in the decline ofglobal tuberculosis incidence rates
to target levels

Shifting from tuberculosis control to elimination: Where are we? What are the variables andlimitations? Is it achievable?
a,1
Rosella Centis , Lia D’Ambrosioa, b, 1, Alimuddin Zumlac, Giovanni Battista Miglioria, ,36

2016 Report on TB Research Funding, TAG

37

MDR TB is a global health threat38

Joint Effort Combating MDR-TB

39

Discussion Points
 What are top 3 priorities for MDR-TB?
 How to control MDR- TB in migrant population?
 What are the major comorbidities of MDR-TB?

HIV/AIDS, DM, COPD, smoke, caner, etc.
 How to share and coordinate / partner with MDRTB National strategies?
 How to best inform WHO about country specificissues and make joint strategies?
 How to enhance efficacy and reduce cost?
 How to discover/control the most risky populations?
40