Multidrug-resistant Tuberculosis in Uzbekistan and Tajikistan: Efforts to

Tackle the Challenge

Shirin KakayevaSIAPS Technical Associate

Dr. Archil SalakaiaSIAPS Portfolio Manager

• Introduction• MDR-TB: a global problem• MDR-TB in Tajikistan and Uzbekistan• Overview of TB pharmaceutical systems in

Tajikistan and Uzbekistan • SIAPS assistance in strengthening TB

pharmaceutical management systems in Tajikistan and Uzbekistan

Outline

Systems for Improved Access to Pharmaceuticals and Services (SIAPS)

• Goal• To assure the availability of quality pharmaceutical

products and effective pharmaceutical services to achieve desired health outcomes

• Objective• To promote and use a systems-strengthening

approach consistent with the Global Health Initiative that will result in a positive and sustainable health impact

SIAPS Technical Areas

WHO Global Tuberculosis Report 2014

What is MDR-TB?

• Multi-drug resistant tuberculosis (MDR-TB) is a form of TB, when Mycobacteria is resistant to at least Isoniazid and Rifampicin, the two most powerful anti-TB drugs

• Drug resistance can be detected using special laboratory tests which test the bacteria for sensitivity to the drugs

• MDR-TB is treated with at least 4 medications, but usually 5-7 drugs, which are less effective and have more severe side effects

• Duration of MDR-TB treatment is between 18 – 24 months (vs. 6-8 months for drug-sensitive TB)

• Requires resources to ensure that adequate laboratory, medical, infection control infrastructure and trained personnel are in place

MDR-TB globally

Estimated 480,000 people developed MDR-TB in 201320201313

300,000 MDR-TB among notified

136, 000 MDR-TB detected and notified

97,000 started second-line treatment for MDR-TB

Five Priority Actions to Address the Global MDR-TB Crisis

1. Prevent the development of drug resistance through high quality treatment of drug-susceptible TB

2. Expand rapid testing and detection of drug-resistant TB cases

3. Provide immediate access to effective treatment and proper care

4. Prevent transmission through infection control5. Increase political commitment with financing

WHO Global Tuberculosis Report 2014

WHO Global Tuberculosis Report 2014

WHO Global Tuberculosis Report 2014

Contributing factors of high MDR-TB rates in Eastern Europe and Central Asia

• Long history of irrational use of anti-TB medicines, specially pre-DOTS era

• Severe stock-outs of anti-TB medicines in 1990s resulting in mono-therapy

• Use of medicines with sub-optimal quality• Not adequate infection control measures• Long hospitalization of TB patients• Not adequate TB control and infection control

measures in the penitentiary systems• Labor migration

Global response to MDR-TB threat• World Health Organization (WHO) : technical leadership (strategy

guidelines, other technical documents and support to the countries)

• Global Fund to Fight AIDS, TB and Malaria (GFATM) : funding of MDR-TB control activities including procurement of SLDs

• Stop TB Partnership: • Global Drug Facility (GDF): global procurement mechanism of anti-TB

medicines• Global Drug Resistant Initiative : multi-institutional platform

organizing and coordinating the efforts of stakeholders to assist countries to build capacity for programmatic management of DR-TB (PMDT)

• Green Light Committee : PMDT technical support to the countries

Tajikistan and Uzbekistan

Source: Allcountries.org

Country Profiles Population,

2013GDP per capita, 2013

Urban/rural population (%), 2013

Tajikistan 8 million $2,512 27/73

Uzbekistan 30 million $5,163 36/64

Source: World Bank

Tuberculosis Notification Rates by Treatment History, 2003–2012

Uzbekistan Tajikistan

World Health Organization Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe.2014

MDR-TB in Tajikistan and Uzbekistan (1)

% of new TB cases with MDR-TB

% of retreatment TB cases with MDR-TB

Tajikistan13 56

Uzbekistan 23 62

Estimated Proportion of TB Cases with MDR-TB, 2013

WHO Global Tuberculosis Report 2014

Country Responses to MDR-TB Threat

Uzbekistan:• Political commitment: increased funding to improve

TB infrastructure, plan to allocate funding for procurement of anti-TB medicines

• Development of the new National TB Control Strategy (2016-2020)

• Approval policy documents and guidelines on the different aspects of TB control

• Strengthening diagnostic capabilities :TB laboratory system (including rapid molecular diagnosis)

• Integration of TB and PHC services: out-patient treatment.

Country Responses to MDR-TB Threat

Tajikistan:• Political commitment :optimization of the hospital beds

and rationalization of the TB control funding• Development of the new National TB Control Strategy

(2015-2020)• Contribution to procurement of SLDs• Strengthening TB laboratory network, including

implementation of rapid molecular tests• MDR-TB treatment implemented in the penitentiary

system• Integration of TB and PHC services in 2013• Good coordination between significant number of national

and international stakeholders.

Pharmaceutical Management

Management Sciences for Health. Toward sustainable Access to Medicines. MDS 3: Access to Medicines and Health Technologies.2011.

SelectionUzbekistan Tajikistan

Fixed-Dose Combination (FDC) medicines are used

Yes Yes

GDF type patient kits are used for FLDs

Yes Yes

Pediatric formulations of anti-TB medicines

Grant from GDF Grant from GDF

Group 5 anti-TB medicines to treat XDR-TB

Currently not used Currently not used

New medicines are used Yes (it is used by MSF in Karakalpakstan region)

Not used yet

Procurement of Anti-TB Medicines Uzbekistan Tajikistan

Current funding for procurement of first and second line anti-TB medicines

GFATM GFATM, USAID

Future funding The Government budget will be allocated for procurement of FLD in 2016

Applied for GFATM’s New Funding Model for funding of procurement of SLDs

Applied for GFATM’s New Funding Model

Forecasting and quantification of medicines is done by

DOTS Center UNDP (GFATM funded),Project HOPE (GFATM funded),KNCV (USAID funded) in coordination with NTP

Auxiliary medicines for management of side-effects of

Some medicines are procured by medical facilities

Provided by partner organizations

Customs Clearance, Storage and Distribution

Uzbekistan Tajikistan

Time for custom clearance 1-6 months (2013-2014) 1-2 weeks (2013)

Cost for warehousing on the central level

Covered by the government Covered by the partner organizations

Electronic stock management information system on the central and regional level

Not implemented Implemented

Cost for distribution Covered by the government Covered by partner organizations

Storage conditions Good on the central level, varies on regional and district levels (temperature control is a main concern)

Good on the central level, varies on regional and district levels (temperature control is a main concern)

Management and RegulationUzbekistan Tajikistan

Coordination of TB pharmaceutical management

TB pharmaceutical management working group (strategic recommendations)

TB pharmaceutical management working group (coordination function)

Logistics management Information System (LMIS)

Paper-based system for first- and second Line Drugs

Paper based system for First- and Second Line Drugs

Essential medicines list All first line and some second line medicines are included

All first and second line medicines are included

Registration of medicines Required Required

Waiver mechanism for registration Used for GDF medicines Used for GDF medicines

Availability of anti-TB medicines on open market without prescriptions

Available Not available

Assessment of the TB Pharmaceutical Management System in Uzbekistan

SIAPS supported the TB pharmaceutical management working group in conducting an indicator-based assessment of TB pharmaceutical management system

Central TB Facility Oblast TB Facility Rayon TB Facility Primary Health Care Facility

0.0%

2.0%

4.0%

6.0%

8.0%

10.0%

12.0%

5.5%

7.5%

4.7%

1.6%

9% 9%

11%

4%

First-Line MedicinesSecond-Line Medicines

Percentage of Time Out of Stock of Anti-TB Medicines in Facilities

(06/01/2013 – 05/31/2014)

What is QuanTB?• An electronic quantification and early warning tool

• Designed to improve procurement processes, ordering, and planning for TB treatments

• Free downloadable desktop application for PC and Mac (http://siapsprogram.org/tools-and-guidance/quantb/)

• Customizable: pre-loaded with WHO-recommended TB medicines and sample treatment regimens for exercises

• Allows forecasting of needs for any type of TB treatment regimen or combination of medicines for any period of time

Key Features Resulting Benefits

• Pre-loaded with the WHO list of pre-qualified medicines

• Quantification is based on combination of morbidity and consumption method - links LMIS with actual patients on treatment

• Combined methods of quantification result in a more accurate projection

Users can modify• Medicines and regimen• Buffer stock• Min. and max. months of stock• Lead time• Forecasting period• Actual number of enrolled cases

Adaptable and customizable to reflect local procurement

Ability to forecast and quantify for different scenarios, variables, and trends• Planned vs. actual case enrollment • Phase-in/phase-out of regimens and

medicines• Costs of regimens, orders, services

Features Resulting Benefits

For each medicine, QuanTB provides information on:• Estimated consumption for enrolled

and future cases• Months of stock• Last day to order• Quantity likely to expire• Quantity needed for regular and

emergency ordering

• Improved order planning, minimizing the risk of stock out and overstocking

• Better pipeline management-adjust planned and submitted orders

• Improved financial efficiency• Can serve as early warning system -

EWS timely alerts NTPs of impending problems with TB medicines supply (stock-outs, overstock, expiry)

Khorezm Region QuanTB dashboards for Entire region and two district TB Dispensaries (with and without beds)

Findings and Actions Taken District TB Dispensary with beds

Anti TB medicine

Finding Action taken

Lfx 250 mg tabs

Potential stock out before regular delivery

Accelerated order and supply of 3,300 tabs from the regional warehouse

PAS 4 g grn/sch

Potential stock out before regular delivery

Accelerated order and supply of 2,075 sachet s from the regional warehouse

Pto 250 mg tabs

Potential stock out before regular delivery

Accelerated order and supply of 5,300 tabs from facility 2, where stock is available for 19 month, with the expiry date in December 2015.

Z 500 mg tabs

Potential stock out before regular delivery

Accelerated order and supply of 2,016 tabs from facility 2, wherestock is available for 17 month, with the expiry date in November 2015.

E 400 mg tabs

Surplus of stock for 22 months, with the expiry date in December 2015.

53,760 tabs back to regional warehouse for further redistribution

District TB Dispensary without bedsAnti TB

medicineFinding Action taken

Pto 250 mg tablets

Surplus of stock for 19 months, with the expiry date in December 2015.

26,377 tabs back to regional warehouse for further redistribution

Z 500 mg tablets

Surplus of stock for 17 months, with the expiry date in November 2015.

37,500 tabs back to regional warehouse for further redistribution

Cs 250 мг таблет

Surplus of stock for 1 month, with the expiry date in June 2015

3,980 tabs back to regional warehouse for further redistribution

Use of Anti-TB Medicines

Centra

l TB fa

cility

Oblast T

B facil

ity

Rayon TB

facil

ity

Primary

Health

Facil

ity

Country Ave

rage

0%

20%

40%

60%

80%

100%

85% 86% 87%

76%

87%89% 87% 90%86% 87%

% of correct prescriptions by facility Type : First-line TB treatment

Intensive treatment phase Continuation treatment phase

Central TB Facility Oblast TB Facility Rayon TB Facility Primary Health Facility

Country average0%

20%

40%

60%

80%

100%

76%

53%58%

33%

60%

73%

100%

81%

43%

71%

% of correct prescriptions by facility Type : Second-line TB treatment

Intensive treatment phase Continuation treatment phase

Drug Use Review (DUR) Program

DUR is a quality assurance intervention that, in a step-by-step manner, identifies and remedies problems related to drug use by collecting, analyzing, and interpreting data through organized, ongoing, systematic, and criteria-based reviews

Why is It Needed for TB?

• When medicines used to treat TB are misused or patient care is mismanaged: • The patient’s health condition may worsen• Drug resistance can develop or amplify• The patient may stop taking anti-TB medicines

because of side effects• Severe side effects of anti-TB medicines may threaten

patients’ health or life, if not managed correctly• Patient can continue to spread TB • Cost of TB therapy increases

Other SIAPS Activities

Uzbekistan• Strengthening organizational and individual capacity for

pharmocovigilance system to ensure anti-TB medicines safety and therapeutic effectiveness

• Assistance in updating TB logistics management information system (LMIS) and develop capacity for its use

Tajikistan• Strengthening capacity of the NTP central unit through on-the-job

training and technical assistance• Assistance in developing capacity to use strategic information for

decision making through the use of automated tools• Assistance in capacity building for consistent and efficient use of

existing LMIS

References• World Health Organization. Global tuberculosis report. 2014. Accessed from: http

://www.who.int/tb/publications/global_report/en/• Raviglione, M. Global strategy and targets for tuberculosis prevention, care and control after 2015. World

Health Organization. 2013 Accessed from: http://www.who.int/tb/post_2015_tb_presentation.pdf?ua=1• WHO Regional Office for Europe. Extensive review of tuberculosis prevention, control and care in

Tajikistan. 2013 Accessed from: http://apps.who.int/iris/handle/10665/137463• World Health Organization. Global tuberculosis report. 2014. Accessed from: http

://www.who.int/tb/publications/global_report/en/• Raviglione, M. Global strategy and targets for tuberculosis prevention, care and control after 2015. World

Health Organization. 2013 Accessed from: http://www.who.int/tb/post_2015_tb_presentation.pdf?ua=1• WHO Regional Office for Europe. Extensive review of tuberculosis prevention, control and care in

Tajikistan. 2013 Accessed from: http://apps.who.int/iris/handle/10665/137463• World Health Organization. The global plan to stop TB: 2011-2015.2010 Accessed from: http://

www.stoptb.org/assets/documents/global/plan/tb_globalplantostoptb2011-2015.pdf• Management Sciences for Health. Toward sustainable Access to Medicines. MDS 3: Access to Medicines

and Health Technologies.2011. Arlington, VA Accessed from: http://www.msh.org/resources/mds-3-managing-access-to-medicines-and-health-technologies

• World Health Organization Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe.2014 Accessed from: http://www.ecdc.europa.eu/en/publications/Publications/tuberculosis-surveillance-monitoring-Europe-2014.pdf