2nd Meeting of the WHO Task Force on XDR-TB, Geneva, April 9th 2008

Progress in implementing the global response to MDR-TB and XDR-TB

Paul NunnStop TB Department, WHO, Geneva

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 MDRLatvia: 19% of MDRS Korea: 15% of MDR

MMWR Morb Mortal Wkly Rep 2006; 55:301-5

The rise of XDR-TB in 2006

Latest global TB Estimates - 2006

Estimated number of

cases

Estimated number of

deaths

1.65 million1.65 million9.15 million9.15 million

120,000489,000

All forms of TB Greatest number of cases in Asia; greatest rates per capita in Africa

Multidrug-resistant TB (MDR-TB)

Extensively drug-resistant TB (XDR-TB) 40,000 20,000

HIV-associated TB700,000 200,000

Global level response

Coordination of Partnership activities – the MDR Working Group Global strategy and policies directed at better prevention and control of MDR/XDR-TBRegional and country supportMonitoring and evaluationAdvocacy and resource mobilisation for countries and partners

Partnership activities

MDR Working GroupTbilisi meeting, September 2007New Chair and Vice ChairCore Group meetingsSub-groups

• Drug management• Advocacy and resource mobilization• Research• Green Light Committee (Expanded and reformed)

Newsletter

Strengthening of basic TB and HIV prevention, care and control in countries

Country programme reviews International staff deployed

Lesotho, Mozambique, South Africa, Swaziland, WHO African region

Global Fund Round 7, 16 of 21 approved countries included MDR-TB activities ($77m) -TBTEAM partnersGlobal Fund Round 8, 60 countries will apply -TBTEAM partnersPEPFAR addressing TB/HIV (over $150m in 2007)US Congress – PEPFAR reauthorization bill contains TB ($4 bn)

Strengthening management of MDR and XDR-TB

Extension of UNITAID support to 2nd line drugsWHO and partners, regional and country support:

19 countries, Russia (lab assessment with World Bank), Ukraine (lab),

Plans for 2008:22 countries so far

GLC Initiative: 51 countries and 95 program sites were approved to treat 30,206 patients, as of December 2007, 36% increase in programme sites and 18% increase in the number of patients approved for treatment, compared to 2006

0

10

20

30

40

50

2004 (101,25%)

2005 (106,48%)

2006 (108,78%)

2007 (112,80%)

2008 (116,86%)

non-GLCGLC

Notified cases of MDR-TB (2004–2006) and projected patients to be treated (2007–2008)

4647

231818

Global plan target for number of MDR-TB patients to be enrolled on treatment:2006: 14 thousand2007: 48 thousand2008: 98 thousand

Strengthening management of MDR and XDR-TB

Revision of the Guidelines for Programmatic Management of Drug resistant TBGlobal Plan to Stop TB, 2006-2015: revision of the MDR component ($5.8bn to $14.4bn)Drug resistance links with private sector activitiesClarification of ethical and legal issues

Laboratory strengthening,deployment of new, rapid diagnostics

Establishment of TB Global Laboratory Initiative integrating SLCS and SRLNExpansion of WHO Laboratory Team (planned)Development of laboratory norms and standards, technical resourcesRecommendation by WHO Expert Group for use of molecular line probe assays for rapid R resistance screeningApproval of GLI/FIND/GDF proposal to UNITAID for expanded MDR-TB diagnostics in 16 priority countries

Infection controlInfection control sub-WG establishedInternational consultation, October 2007Framework for national level programmatic implementation of TB infection control in developmentPlanning framework for TB and HIV Global Fund proposals Generic training materials, being developed Training courses Indicators and standardized methods for monitoring and evaluation, will be developed

IVth Global Report on anti-TB Drug Resistance Surveillance

Patients with drug resistance in 2004 resistant to more drugs than in 1994MDR increasing in several countries, XDR-TB emergingMDR rates in new cases approaching 25% in several Eastern European countries2 population based surveys HIV+ TB more likely to have MDR-TB

Previous reportsNew data report 4Never previously reported

No data

* Sub-national coverage in India, China, Russia, Indonesia.

New data report 4

No dataPrevious reportsNew data report 4

No data

!! ! ! ! !

! ! ! ! ! ! ! !! ! ! ! ! ! ! !

! ! ! ! ! ! ! !! ! ! ! ! ! ! !! ! ! ! ! ! !! ! ! ! !

! !

! ! ! ! ! ! ! ! !! ! ! ! ! ! ! ! ! ! ! ! ! !! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! !

! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! !! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! !

! ! ! ! ! ! ! ! ! !! ! ! ! ! ! ! !

!! ! !

! ! ! !! ! ! !

! ! ! ! !! ! !

! ! ! !! ! ! ! ! !

! ! ! !!

!! !! !

!! !

! ! ! ! !! ! ! ! !

! ! !!

! !!

! !! ! ! !! ! ! ! !

! ! !! !

! ! ! ! !! ! ! ! ! !

! ! ! ! ! ! !! ! ! ! ! ! !

! ! ! ! ! ! ! !! ! ! ! ! ! ! !

! ! ! ! !!

!! ! ! ! !! ! ! ! ! !

! ! ! ! !! ! !

!

!! ! ! ! !

! ! ! ! ! ! ! !! ! ! ! ! ! !! ! ! ! ! !

! ! ! ! ! !! ! ! ! ! ! ! !

! ! ! ! ! ! ! !! ! ! ! ! ! ! !

! ! ! ! !

! !! !!!

! ! ! ! ! !! ! ! ! ! !! ! ! ! ! !

! ! ! ! !! ! !! ! ! !

! ! !! ! !! ! !

! !! ! ! !! ! ! ! !! ! ! ! !! ! ! ! ! !! ! !

! !! ! ! !

! ! ! ! ! !! ! ! ! ! ! ! ! !! ! ! ! ! ! ! !

! ! ! ! ! ! !! ! ! ! ! !! ! ! ! ! ! !

! ! ! ! ! !

! ! !! ! !

! !

! !! ! ! !! ! ! !

! ! !

! ! !! ! !! ! !

! ! ! !! ! ! !

! ! ! ! ! ! !

!

!

!

! !! !!

!! ! !! ! !

! !! ! !

! !! ! ! ! ! ! !! ! ! ! ! ! ! ! ! !

! ! ! ! ! ! ! ! ! ! ! ! ! ! !! ! ! ! ! ! ! ! ! ! ! ! ! ! ! !! ! ! ! ! ! ! ! ! ! ! ! ! !

! !

! ! ! ! !! ! ! ! ! !! ! ! ! ! ! !! ! ! ! ! ! ! !

! ! ! ! ! ! !! ! ! !

! !

! !! ! ! ! ! !! ! ! ! ! !

! ! ! ! !! ! ! ! !! ! ! ! !

! ! !!

! !! ! ! !! ! ! ! !

! ! !! ! ! ! !

! ! ! ! ! ! ! !! ! ! ! ! ! ! ! !! ! ! ! ! ! ! ! !

! ! ! ! ! ! ! ! ! !! ! ! ! ! ! ! ! ! ! !

! ! ! ! ! ! ! ! ! ! ! ! ! !! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! !! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! !! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! !! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! !

! ! ! ! ! ! ! ! ! ! ! ! ! !! ! ! ! ! ! ! ! ! ! !! ! ! ! ! ! ! ! !

! ! ! !

! ! ! ! ! ! !! ! ! ! ! ! ! ! ! !! ! ! ! ! ! ! ! ! !! ! ! ! ! ! ! !

!

! ! ! !! ! ! ! !

! ! ! ! ! !! ! ! ! ! !

! ! ! ! ! ! !! ! ! ! ! ! ! !

! ! ! ! ! ! !! ! ! ! ! ! ! !! ! ! ! ! ! !

! ! ! ! ! !

Global Project Coverage 1994-2007

* shaded areas indicate survey planned or ongoing

"Rapid" XDR surveys: Botswana, Lesotho, Malawi, Swaziland, Zambia, Myanmar, Bangladesh, DR Congo, Burundi, Rwanda

Advocacy and communicationsXDR-TB – Media response unprecedented

TB strain with extreme resistance to drugs creates nightmare scenario

WHO urges South Africa to curb TB killer super-bug

TB experts will grapple with deadly new strains: WHO

Experts call for urgent steps to battle virulent TB strain

Deadly TB strain spreading across globe

Global alert over deadly new TB strains

Africa: "Extreme" TB Bug Prompts Calls for Rapid Action

South Africa: Action plan developed to combat drug resistant TB

Google news timeline – 2000-2007Searching key words "drug resistant" and TB

What no amount of congressional lobbying

could have achieved. And in the end – no harm

done.

Promote research and development

Subgroup on research of the MDR-TB WG formedDiscussion initiated during the UNION Conference in Cape Town, November 2007, to promote clinical trials to improve MDR-TB treatment regimensWorkshop in Boston, 10-12 June 2008Research agenda in press and on Stop TB website

HIV/TB collaborationIncrease in implementation of TB/HIV collaborative activities3Is meeting:

Isoniazid preventive therapyIntensified TB case findingInfection control

UNAIDS Programme Coordinating Board –TB/HIVUN Special Envoy, Global Leadership Forum on TB/HIV, 9th June 2008UNGASS will address TB/HIV, June 10-11, 2008

Resource mobilizationEstimated costs in Million US$

2007 2008 TotalResources needed by countries 673 1,046 1,719

Drugs for treatment 291 465 756 Hospitalization costs 81 121 202

Capacity-building and other operational costs 193 288 481 Infection control costs 40 72 112

Laboratory costs 68 100 168

Technical assistance 42 60 102

Research and development (including OR) 167 167 334

Total 882 1,273 2,155

Global level resources for MDR and XDR-TB

US GovernmentOGAC/PEPFARCDCUSAID

Lilly Partnership DfIDItalian CooperationCanadian International Development AgencyBill and Melinda Gates Foundation

Observations

Too few countries establishing MDR and XDR-TB management programmes, with too few patientsMDR and XDR-TB treatment rates well below targets, and further below the needExternal funding directed at Africa, not Eastern EuropeMDR and XDR-TB increasingNew technology creating opportunities

Conclusions

We are observing the early stages of the replacement of our epidemic of drug susceptible TB with MDR and XDR-TBWe will be judged by how well we control all TBChina and India must do more; Russia and South Africa must continue investment

AcknowledgementsErnesto JaramilloPaulette AshongPatricia LangFuad MirzayevMartins PavelsonsIrina SahakyanAbby WrightMatteo Zignol

Lynne HarropFabio ScanoEva NathansonRose PrayKarin WeyerGlenn ThomasMalgosia GrzemskaKatherine FloydColleen Daniels