Out of Step 2015
TB Policies in 24 Countries
A survey of diagnostic and treatment practices

About Médecins Sans Frontières
Médecins Sans Frontières (MSF) is an independent international medical humanitarian organisation thatdelivers medical care to people affected by armed conflicts, epidemics, natural disasters and exclusionfrom healthcare. Founded in 1971, MSF has operations in over 60 countries today.
MSF has been involved in TB care for 30 years, often working alongside national health authorities totreat patients in a wide variety of settings, including chronic conflict zones, urban slums, prisons, refugee
camps and rural areas. MSF’s first programmes to treat multidrug-resistant TB opened in 1999, andthe organisation is now one of the largest NGO treatment providers for drug-resistant TB. In 2014, theorganisation started 21,500 patients on first-line TB treatment across projects in more than 20 countries,
with 1,800 patients on treatment for drug-resistant TB.

About the MSF Access Campaign
In 1999, on the heels of MSF being awarded the Nobel Peace Prize – and largely in response to theinequalities surrounding access to HIV/AIDS treatment between rich and poor countries – MSF launched
the Access Campaign. Its sole purpose has been to push for access to, and the development of, lifesaving and life-prolonging medicines, diagnostics and vaccines for patients in MSF programmes andbeyond.

About Stop TB Partnership
The Stop TB Partnership is leading the way to a world without TB, a disease that is curable but still kills
three people every minute. Founded in 2001, the Partnership’s mission is to serve every person who isvulnerable to TB and to ensure that high-quality treatment is available to all who need it.
The Stop TB Partnership’s programmes include the Global Drug Facility, which provides quality-assured
and affordable TB medicines to countries around the world, and TB REACH, which has helped treat over1 million people with TB by providing small grants to identify and scale up innovative approaches to TB.
Together our 1,400 partners are a collective force that is transforming the fight against TB in more than
100 countries. They include international and technical organisations, government programmes, research
and funding agencies, foundations, NGOs, civil society and community groups, and the private sector.
Stop TB Partnership operates through a secretariat hosted by UNOPS in Geneva, Switzerland, and isgoverned by a Coordinating Board that sets strategic direction for the global fight against TB.

Copyright @ 2015

Out of Step 2015
TB Policies in 24 Countries
A survey of diagnostic and treatment practices
November 2015

Table of Contents
Executive summary.................................................................................................................... 6
Methodology........................................................................................................................ 10Country snapshots and critical gaps........................................................................................... 14
TB Policies: The Five Key Steps
I. Diagnosis....................................................................................................................... 21
II. DS-TB treatment regimens.................................................................................................. 28
III. DR-TB treatment regimens.................................................................................................. 29
IV. Models of care for treatment of TB.................................................................................... 31
V. Drug regulatory environment.............................................................................................. 36
TB policies: Case studies from the field....................................................................................... 38
Conclusions and recommendations............................................................................................ 46
Glossary and abbreviations...................................................................................................... 52
References............................................................................................................................. 56
Annexes............................................................................................................................... 61
Country data tables

Out of Step: TB Policies in 24 Countries

5

Executive
summary

6

Stop TB Partnership and Médecins Sans Frontières – November 2015

Optimised TB Policies: Crucial Steps to Ending TB
This year marks a crucial crossroad in the fight against tuberculosis, which is now the leading global cause ofdeath from an infectious disease. While the Millennium Development Goal (MDG) target to halt and reverse
the spread of TB by 2015 was met, there were still 9.6 million new cases and 1.5 million deaths from TB in
2014. This year, world leaders set the most ambitious TB goals yet with the endorsement of the Sustainable
Development Goals (SDGs). The SDG target to end TB by 2030, along with the globally-endorsed milestones
and targets laid out in the World Health Organisation’s (WHO) End TB Strategy, together present botha challenge and an opportunity for the TB community to change, adapt, and take every step necessary torealise the vision of a world where no one dies from a disease that is curable and preventable.
At the current rate of progress, the world won’t reach the 2030 targets for TB incidence and death until
2182, nearly 150 years behind schedule. The Stop TB Partnership’s Global Plan to End TB 2016-2020
sets out to change this through a costed, scalable blueprint for how national TB programmes can become
significantly more ambitious and effective over the next five years to meet the 2035 targets in support of the
WHO End TB strategy. This will only be possible through a paradigm shift in how we prevent and treat TB,
coupled with optimal use of every tool available, forcefully pursued by all stakeholders. How quickly andeffectively these tools will be leveraged to boost the TB response is largely dependent upon three factors:
effective policies at the national level; full implementation of the latest WHO guidelines; and access to themost effective drugs and diagnostics.
Our survey results illustrate that the global TB response is indeed out of step with known best practices thatare essential to meeting the target of a 90% reduction in TB incidence and 95% reduction in TB mortality
by 2035. In order to achieve this long-term goal, significant improvements must be made at the national
level. These include an enabling policy framework, and an upgrade in tools, strategies, and guidelines inline with international recommendations by WHO. The global TB community also needs a set of metrics,
beyond the number of people diagnosed and cured, to monitor progress towards the goals and to help
shape demands for the accountability of national governments and global health actors.

Out of Step Report: A Survey of TB Policies in 24 Countries
Médecins Sans Frontières (MSF) published the first Out of Step Report in 2014 with an assessment of
the uptake of TB tools and the status of national TB policies in eight countries. The report identified fivedeadly gaps in areas of TB diagnosis, treatment of drug-resistant TB, models of TB care, access to new
and repurposed drugs, and funding. The survey revealed that countries need to improve their TB policies
and take bold steps in order to bend the curve of the TB epidemic downward. It found that the lagging
implementation of many policies is indicative of the challenges faced globally by low- and middle-income
countries in implementing and funding all of the various components required for a comprehensive andeffective TB programme.
The 2015 Out of Step report presents the results of a survey of 24 countries conducted by Stop TB
Partnership and MSF. Building on the previous Out of Step report, this year’s survey tracked adoption of
the latest TB policies, guidelines and tools across five areas: diagnosis and drug resistance testing; drugsensitive TB (DS-TB) treatment regimens; multidrug-resistant TB (MDR-TB) treatment regimens; models of care;and regulatory frameworks. The results of this survey provide a snapshot of the world’s readiness to defeat
the TB epidemic. Although effectively implemented policies and guidelines alone will not be sufficient, they
form the foundation for a strong and comprehensive TB response that leaves no one with TB behind.
While this report is not a comprehensive or authoritative assessment of countries’ national TB policies, it
provides an indication of the level of preparedness to implement and scale up action. The results of thesurvey show that many countries need to take bold steps to bring their policies up to date with the latest
international standards. There is a greater need to use rapid molecular tests for diagnosis of TB anddrug resistance, and to reduce out-of-pocket expenses for people with TB. This, coupled with innovative
approaches to active case finding, will help reach the nearly four million with TB missed by health systems
each year. Older treatment regimens need to be replaced with up-to-date fixed-dose combinations for

Out of Step: TB Policies in 24 Countries

7the treatment of people with TB. People with drug-resistant TB should have access to the most effective
drugs and regimens, and many countries need to change their policies to make new drugs available
through compassionate use while drugs are being registered, and to establish accelerated mechanisms
for the registration of new drugs. Updating national Essential Medicines Lists in line with the latest WHO
recommendations is also a key step.
While the overall progress towards global TB goals is clearly ‘‘out of step’’, many countries are making
rapid progress towards being in-step with the latest international recommendations. The new Sustainable
Development Goal to end TB by 2030 and the Global Plan to End TB 2016-2020 will further challengecountries to ensure that their policies are up-to-date. We recognise that the adoption and adaptation ofpolicies to national and local situations is challenging and can take time. The countries that participatedin our survey are making impressive efforts to put the latest recommended policies in place, and weare grateful for their participation and transparency, which will help inform other countries and serve asa valuable tool for further discussion and learning.
The decisions made at this critical juncture for the TB community will set us on the path to either win or lose
the race to reduce TB incidence by 90% and TB mortality by 95%. Will we continue down the same path,using outdated policies and approaches that have resulted in slow declines over the last 10 years? Or will
we step up to the challenge and make this the year that we embrace new tools and innovations in the fightagainst TB?

8Stop TB Partnership and Médecins Sans Frontières – November 2015

methodology

10

Stop TB Partnership and Médecins Sans Frontières – November 2015

Pierre-Yves Bernard/MSF

PurposeThis survey was primarily designed to assess the status of national policies in relation to the latest WHO
recommendations in five key areas: diagnosis, models of care, treatment of drug-sensitive TB (DS-TB),
treatment of drug-resistant TB (DR-TB), and the regulatory environment for TB drugs. Where possible, we
attempted to assess the extent to which diagnostic policies have been successfully implemented, although
this could only be done on a qualitative basis. This survey is a follow-up of the study conducted by MSF in
2014. This updated survey has a broader scope to survey more policy areas and expands the number ofsurveyed countries from 8 to 24.

Countries included in the surveyCountries were selected for inclusion in the survey based on their epidemiology and burden of TB and
TB/HIV coinfection, as well as the presence of an entity that could complete the survey (either an MSF ora Stop TB Partnership member). The countries represent a range of epidemiological settings for TB (highTB/HIV coinfection rates, high MDR-TB burdens), geographical scope and economic status. The 24 countries
included are: Armenia, Afghanistan, Belarus, Brazil, Cambodia, China, Democratic Republic of Congo (DRC),
Georgia, India, Indonesia, Kenya, Kyrgyzstan, Mozambique, Nigeria, Pakistan, Papua New Guinea (PNG),
Russian Federation, South Africa, Swaziland, Tajikistan, Viet Nam, Uzbekistan, Ukraine, and Zimbabwe.

Data collection and analysis
The survey consisted of a semi-structured questionnaire with five key sections related to TB diagnostics,
models of treatment delivery, treatment regimens for DS-TB, treatment regimens for DR-TB, and drug
regulatory environments. The questionnaire was sent to the nominated Stop TB partner or MSF
representative at the country level in June 2015. Clear guidance on how to conduct the policy review
was given, including what could be used as source/reference documents. The representatives conducted
the review of the policy documents and national guidance, and returned the survey by mid-July 2015.
Guidelines developed by the World Health Organisation (WHO) were taken as reference documents forthe different areas included in the survey.

Out of Step: TB Policies in 24 Countries

11

Once the completed survey was returned and the source documents were checked by the Stop TB
Partnership, the survey was sent to the National Tuberculosis Programme (NTP) managers of the responding
countries for additional fact checking and data validation. In some countries the normative guidance isstill in the process of being updated in line with global recommendations. In such cases, the content andtimeline for the updated guidance are noted, if known. This report contains the analysed data provided by
MSF projects, Stop TB Partnership members, and NTP managers.

Limitations/challenges of the study
The inclusion of countries in the study was dependent on the availability of a partner to complete thesurvey.
For the diagnostic portion of the survey, country-level information related to the number of GeneXpert
devices and their placement could not be validated and therefore has been accepted as presented by the
NTP managers and partners.
All the country NTPs were contacted for validation of the information but responses from a few of thecountries could not be elicited despite follow-up communication; these included Armenia, Belarus, Kenya,
Kyrgyzstan, Russian Federation, Swaziland, Uzbekistan and Viet Nam.
Some of the countries did not provide information for some of the survey areas, as despite the review ofsource documents and country guidelines, the information could not be found. In such cases, the response
was recorded as ‘not known’.

12

Stop TB Partnership and Médecins Sans Frontières – November 2015

Sami Siva

countrysnapshots
and critical
gaps

14

Stop TB Partnership and Médecins Sans Frontières – November 2015

CRITICAL GAPS
In order to reduce TB incidence and death in line with the ambitious targets set out in the WHO End TB
Strategy1 and The Global Plan to End TB 2016-20202, countries must work towards closing gaps andimplementing critical recommendations. Following is a summary of the key findings of the survey:

DIAGNOSIS ight countries surveyed have revised their national policies to include rapidE
molecular tests (e.g., Xpert MTB/RIF) as the initial diagnostic test for all adults andchildren with presumptive TB, replacing sputum smear microscopy (SSM).
F ourteen countries have recommended the use of rapid molecular-based testing as
the initial diagnostic test for people at risk of HIV-associated TB and MDR-TB, in linewith the WHO recommendations3.
 nly five countries have recommended Xpert MTB/RIF to be used for paediatric TB
Odiagnosis, and only four have recommended the use of Xpert MTB/RIF for extrapulmonary tuberculosis (EPTB) patients.
 ountries need to reduce significant gaps in the implementation of these policies,Cand must plan strategically to invest resources for wider coverage. Althoughquantifying the progress made in the implementation of diagnostic policies iscomplex and requires in-depth analysis of the lab network, we have considered thenumber of GeneXpert devices implemented in countries as a proxy indicator for the
implementation status of WHO's recommendation on the use of rapid molecular
tests as the initial diagnostic test (either for all TB cases or only for high-risk groups).
We found that 15 out of 24 countries have reported fewer than 50 devices
implemented.

DS-TB TREATMENT REGIMENS
 ix countries still recommend intermittent treatment for DS-TB; with widespreadSavailability of fixed-dose combinations (FDCs) for daily treatment and therecommendations of the International Standards of TB care, these should be
replaced by daily treatment.
T en countries are in line with WHO guidance from 20104, and do not recommend
empirical use of the Category II regimen for re-treatment cases.
 ost countries are in line with WHO guidance from 20025, and only threeM
countries do not have FDCs as the preferred formulation.

DR-TB TREATMENT REGIMENS nly three countries have all the medicines in the five groups of TB drugs in theirOnational Essential Medicine List (EML) and are in line with the WHO Model List of
Essential Medicines6.
F ive countries did not have a single complete group of any of the MDR-TB drugs ontheir EML.
Eleven countries have national guidelines on the use of bedaquiline.
 nly four countries have guidance on the use of delamanid – all in the Former
O
Soviet Union (FSU) region.
F ifteen countries have made new and repurposed drugs available throughcompassionate use or other mechanisms.

Out of Step: TB Policies in 24 Countries

15

Out of Step
Map
of The24

Countries Surveyed

1

Afghanistan

2

Armenia3

Belarus4

Brazil5

Cambodia

6

China

7

Democratic Republic of Congo

8

Georgia

9India

10 Indonesia
11

Kenya

12

Kyrgyzstan

13 Mozambique
14 Nigeria
15 Pakistan
16 Papua New Guinea
17 Russian Federation
18 South Africa
19 Swaziland
20 Tajikistan
21 Ukraine
22 Uzbekistan
23 Viet Nam
24 Zimbabwe

16

Stop TB Partnership and Médecins Sans Frontières – November 2015

4

17

3
21
8

22

12

2

20

6

1
15
9

5 23
14

11
7

10
16

13
24

19
18

Out of Step: TB Policies in 24 Countries

17

MODELS OF CARE eventeen countries have decentralised the initiation of DS-TB treatment at theS
primary health care level.
In half of the countries, nurses or health workers can initiate DS-TB treatment, and in
17 countries, DS-TB treatment can be initiated in facilities providing HIV care.
 alf of the countries surveyed have guidelines in place to allow the initiation of
H
DR-TB treatment at district level.
F ifteen countries surveyed do not include routine hospitalisation as part of their guidance
for the treatment of DR-TB. In countries with compulsory hospitalisation in their guidance,
the duration of hospitalisation ranges from two weeks when the treatment is being
initiated, to longer durations of eight months during the intensive phase of treatment.

DRUG REGULATORY ENVIRONMENTF ifteen countries have the necessary frameworks in place to offer early access to
new drugs through compassionate use or equivalent processes.
In 15 countries, there is a process of accelerated registration of DR-TB drugs,
including new TB drugs.
 ountries should adopt quality assurance mechanisms and standards aligned withC
the WHO recommendations.

The pivotal role of the BRICS countries (Brazil, Russian Federation, India, China,
South Africa)
Brazil, the Russian Federation, India, China and South Africa – the five countries that form the BRICS group– have a combined population of almost three billion and a combined GDP of US$16 trillion. The BRICS
countries also account for 46% of all cases of TB and 40% of all TB-related mortality.7 As such, these countries
have the power to drastically reduce the global TB burden through joint cooperation and shared approaches.8
China and India alone account for almost 40% of the estimated global burden of TB.
South Africa accounts for 30% of the estimated global number of incident cases of TB/HIV coinfection.
With regard to MDR-TB, China, India and the Russian Federation together account for more than half (56%)
of the estimated global burden. Brazil accounts for about a third of the Western Hemisphere’s estimatedburden of TB and MDR-TB.

Diagnosis
 outh Africa, Brazil and the Russian Federation have recommended rapid molecularS
testing as the initial diagnostic test for all presumptive TB cases, replacing sputum
smear microscopy. However, only South Africa has reached 100% coverage of
rapid molecular tests (e.g., Xpert MTB/RIF) in the public sector. In Brazil and theRussian Federation, implementation of this policy is still being scaled up.
India has recommended the use of rapid molecular tests as the initial test only
for people at risk of MDR-TB or HIV-associated TB. However, roll-out has been
progressing slowly, despite the establishment of clear and ambitious scale-up plans.
 hina has only recommended the use of rapid molecular tests for TB-confirmed
C
cases, with the purpose of testing for drug resistance. However, authorities havereported that they are in the process of revising their guidelines and will be
introducing rapid molecular testing as the initial diagnostic test in their new guidelines.

18

Stop TB Partnership and Médecins Sans Frontières – November 2015 ll the BRICS countries have recommended first-line drug susceptibility testing (DST)
A(including at least rifampicin and isoniazid) for all groups of patients at risk of MDRTB and second-line DST for all people with drug-resistant TB.

DS-TB treatment guidelines ategory II treatment regimens containing streptomycin are still recommended
C
by India and China despite their high burden of MDR-TB and despite
recommendations for DST for those at risk of MDR-TB.
India and China still recommend intermittent treatment for DS-TB, instead of daily
treatment.
FDCs are still not the recommended formulation in India or the Russian Federation.
 ll the BRICS countries have updated their paediatric guidance to reflect the newAdoses of first-line drugs.

DR-TB treatment guidelines
 sing the national Essential Medicine List as an indicator for the availability ofUdrugs, the inclusion of all drugs in Groups 2-5 on the national EML: RussianFederation and South Africa include all drugs in Groups 2,3 and 4; Brazil includes
all drugs in Group 3; and India includes none.
India, Russian Federation and South Africa have national guidelines in place on theuse of bedaquiline, while none of the BRICS countries have guidelines in place on
the use of delamanid.

Models of care razil, India and South Africa have a policy of decentralisation of DS-TB treatment
Binitiation at the primary health care level.
 razil and South Africa have a policy to allow nurses or health workers to initiate
B
DS-TB treatment.
 policy for TB treatment initiation in facilities providing HIV care is present in all
A
BRICS countries except for Russian Federation.
R outine hospitalisation of MDR-TB Patients is a policy in India, China and South
Africa.

Drug regulatory environment
 outh Africa, Russian Federation and China have an accelerated registration for
S
MDR-TB drugs. South Africa has taken the lead in introducing bolder policies atcountry level by introducing new TB drugs.
F our BRICS countries (Brazil, Russian Federation, India and South Africa) havea policy for new and repurposed drugs to be available through compassionate useor patient-named-basis mechanisms.

Out of Step: TB Policies in 24 Countries

19the five
key steps

20

Stop TB Partnership and Médecins Sans Frontières – November 2015

I.

Diagnosis

Key findings
 ost of the countries included in the survey have updated their national guidelines
M
for TB diagnosis to be consistent with WHO recommendations3, including
recommending rapid molecular testing (e.g., Xpert MTB/RIF) as the initial diagnostic
test for people at risk of MDR-TB and HIV-associated TB (high-risk groups).
 ery few countries have considered recommending rapid molecular testing as theVinitial test for all presumptive TB cases. Despite the upfront financial challenges
related to this strategy, countries should consider expanding access to rapid
molecular diagnostics in order to: ensure early diagnosis and early treatment
initiation; reduce the chain of transmission; reduce cost implications in the long run;and reduce the emergence of drug-resistant TB cases and the overall global burden
of TB.
 t the policy level, the main weakness is the lack of recommendations for the useAof rapid molecular testing as the initial diagnostic test for children at risk of MDR-TB
or HIV-associated TB, and for selected forms of EPTB.
 espite policies being updated in line with the latest WHO recommendations,D
countries still need to reduce significant gaps between policy and implementation,and to strategically invest resources to achieve wider coverage. Such actions areneeded to reach the targets set out by the WHO End TB Strategy and The Global
Plan to End TB.

Background
Early and accurate diagnosis of TB is key to ensuring a successful TB control programme9. Sputum smear
microscopy (SSM) and culture, used for decades, have serious limitations when compared to the rapid
molecular testing introduced in recent years. While specific results vary, in general, SSM is not very
sensitive, detecting only about 50% of all active cases of TB, and even fewer among children and people
living with HIV; SSM cannot be used to diagnose drug resistance10. While culturing is more sensitive than
SSM and can be used for drug-susceptibility testing (DST), TB culture requires expensive biosafety facilities,
trained laboratory technicians and can take up to several weeks to obtain results.
Rapid molecular tests for TB and drug-resistant TB have the potential to increase the number of MDR-TB
cases detected and decrease the turnaround time for results compared to conventional methods11. WHO
has to date recommended two such tests: the Xpert MTB/RIF assay that runs on the GeneXpert platform(Cepheid) and Line Probe Assays (LPAs). LPAs are suitable for implementation at the reference laboratorylevel12. The most widely implemented LPA (the Hain Life Science Genotype MTBDRplus) can detect
resistance to rifampicin and isoniazide, the two cornerstone drugs of DS-TB treatment.
Xpert MTB/RIF is the first molecular test that can be used for simultaneous detection of TB and rifampicin
resistance and be implemented at the decentralised level (district and sub-district laboratories). WHO
recommends Xpert MTB/RIF as the initial diagnostic test for diagnosis of pulmonary TB and rifampicin
resistance in people at risk of MDR-TB or HIV-associated TB (high-risk groups); in addition, WHO
conditionally recommends Xpert MTB/RIF as a follow-up test to SSM in settings where MDR-TB or HIV areof lesser concern, especially for further testing of smear-negative specimens. WHO recommends that Xpert
MTB/RIF be used as the initial diagnostic test (replacing SSM) in all cases of presumptive TB, if resources
can support this strategy; in addition, WHO recommends Xpert MTB/RIF as the initial test for diagnosis of
MDR-TB and HIV-associated TB in children, and for the diagnosis of extrapulmonary TB (with its use being
restricted to some selected sample types)13,14.

Out of Step: TB Policies in 24 Countries

21Despite these recent advances, significant gaps remain in the early detection of TB cases and in theimplementation of proper diagnostic work-ups for presumptive TB and DR-TB cases. In 2014, just over
6 million of the estimated 9.6 million TB incident cases were notified to national TB programmes (NTPs),
leaving about 3.6 million cases undetected (or unreported). The latest WHO data also show that little
progress has been achieved in the detection of MDR-TB.

Xpert MTB/RIF as the initial diagnostic test for persons to be evaluated for TB
The survey results show that 8 of the 24 countries surveyed (33%) have marched ahead and revised theirnational policies to include rapid molecular tests (e.g., Xpert MTB/RIF) as the initial diagnostic test for all
adults and children with presumptive TB, replacing sputum smear microscopy (SSM).
Table 1: Status of recommendation of rapid molecular testing by country
Countries that recommend rapid molecular tests (e.g.,
Xpert MTB/RIF) as the initial test for all presumptive TB
cases

Countries that recommend rapid molecular tests as theinitial test only for high-risk groups

BelarusAfghanistan

Brazil (subnational)

Cambodia

Georgia

Democratic Republic of Congo

Russian Federation

India

South Africa

Indonesia

Swaziland (implemented widely, but with technology
stock-outs)

Kenya

Tajikistan (subnational)

Kyrgyzstan

Ukraine (not widely; only at oblast level)

Mozambique
Nigeria
PakistanPapua New Guinea
Uzbekistan (subnational)
Viet Nam
Zimbabwe

Note. Georgia is in the process of updating its guidelines, which are expected to be available towards the end of 2015.

Although eight countries have already revised their policies, the extent of implementation of thesepolicies and the roll-out of rapid molecular testing vary significantly among countries. In 6 out of the
8 countries that recommend rapid molecular testing as the initial diagnostic test for all presumptive TB
cases (namely, Belarus, Brazil, Georgia, Russian Federation, Tajikistan and Ukraine), the policy has
been implemented only at the subnational level, and the roll-out has not reached nationwide coverage(see also section “Status of Xpert MTB/RIF roll-out: Policy versus implementation” for more details).
Out of the 24 countries for which data were analysed, 14 countries (namely Afghanistan, Cambodia,
Democratic Republic of Congo [DRC], India, Indonesia, Kenya, Kyrgyzstan, Mozambique, Nigeria,
Pakistan, Papua New Guinea [PNG], Uzbekistan, Viet Nam and Zimbabwe.) have recommended the useof rapid molecular-based testing (e.g., Xpert MTB/RIF) as the initial diagnostic test for people at risk of HIVassociated TB and MDR-TB, in line with the WHO recommendations. However, based on the feedback
received through our survey, the extent of implementation of this policy seems to vary significantly among
countries (see page 27 ‘Diagnostics Implementation Summary’).
In Armenia, SSM remains the initial diagnostic test. However, all people with presumptive TB are tested
for drug resistance using rapid molecular tests (sputum smear negative cases are tested by Xpert MTB/RIF,
while sputum smear positive cases are tested by LPA).

22

Stop TB Partnership and Médecins Sans Frontières – November 2015

Matthew Smeal/MSF

In China, rapid molecular testing is only recommended for use in confirmed TB cases for the purpose of
screening or testing for drug resistance. It was reported that Xpert MTB/RIF testing is recommended forsmear-positive patients only.

Patient categories for which countries recommend Xpert MTB/RIF
High-risk groups (MDR-TB and HIV-associated TB) in adult
population

Paediatric TB

EPTB

Smear negative

Afghanistan, Belarus, Brazil, Cambodia, DRC, Georgia,
India, Indonesia, Kenya, Kyrgyzstan, Mozambique,
Nigeria, Pakistan, PNG, Russian Federation, South Africa,
Swaziland, Tajikistan, Uzbekistan (TB/HIV coinfected),
Ukraine, Viet Nam, Zimbabwe

India,
Kyrgyzstan,
Nigeria,
Viet Nam,
Zimbabwe

India,
Nigeria
Pakistan,
Viet Nam

Armenia

The survey results show that only 5 out of 24 countries have recommended Xpert MTB/RIF to be used for
paediatric TB diagnosis, and only 4 out of 24 countries have recommended the use of Xpert MTB/RIF for
EPTB patients. This level of uptake is unsatisfactory.

Xpert MTB/RIF for testing or screening for the identification of drug resistanceAll of the countries included in this study, with the exception of Georgia, Kyrgyzstan and Viet Nam, reported
that they recommend rapid molecular testing (e.g., Xpert MTB/RIF) for the purpose of testing or screening for
drug resistance and for people with a confirmed TB diagnosis.

Out of Step: TB Policies in 24 Countries

23

Status of Xpert MTB/RIF roll-out: policy versus implementation
The number of Xpert MTB/RIF devices implemented in each of the 24 countries varies widely. Fifteen out of
24 countries have reported fewer than 50 devices implemented. The number of devices deployed does
not match the need and the current epidemiological situation in these countries calls for all high-risk patientsto have access to Xpert MTB/RIF testing. The number of Xpert MTB/RIF devices deployed was reported
by survey respondents and could not be verified independently from existing sources. The development of
population-based indicators (for example, taking into account TB and HIV epidemiology) would greatly
support a proper assessment of available capacity of rapid molecular testing and would help verify
whether testing capacity is realistically aligned with needs.

Countries that have recommended Xpert MTB/RIF as the initial diagnostic test for
all presumptive TB cases
Among the countries that have adopted this recommendation, there is significant variation in the extent of
implementation and the progress made in the roll-out of rapid molecular testing: outh Africa is at the forefront of Xpert MTB/RIF implementation, having opted
S
for replacing sputum smear microscopy with Xpert MTB/RIF and achieving 100%coverage in the public sector.
 waziland reports that it has adopted the policy, but the level of coverage is notSreported.
 razil and the Russian Federation have also shifted towards a diagnostic algorithm
Bthat recommends use of Xpert MTB/RIF (or other molecular-based tests in the caseof Russian Federation) as the initial diagnostic test for all presumptive TB cases, but
implementation is still in progress. Brazil’s rapid molecular test network currently covers
55% of TB cases in the country and expansion of this network is being planned.
In Belarus and Tajikistan, rapid molecular tests are recommended as the initialdiagnostic test for all presumptive TB cases, but roll-out is progressing slowly (i.e.,
only 15 Xpert MTB/RIF devices have been reported to be implemented in eachcountry).
T he situation is similar in Ukraine, where Xpert MTB/RIF roll-out has progressed very
slowly and where the use of this test as the initial diagnostic test for all presumptive
TB cases is limited to a few regions only.
In Georgia, the national guidelines are under revision and it is reported that the
new guidelines will be published by the end of 2015. For the time being, only 16
devices have been reported to be implemented in the country.

Countries that have recommended Xpert MTB/RIF only for high-risk groups
Based on survey results, the extent of implementation of this policy varies significantly among countries (seepage 27 ‘Diagnostics Implementation Summary’).

Placement of Xpert MTB/RIF devices
Seventeen countries provided data on the placement of Xpert MTB/RIF devices. Most of the countries (13out of 17) reported that the majority of Xpert MTB/RIF devices have been placed at district and subdistrictlevel or below, in line with the WHO recommendations to enable the decentralisation of DR-TB diagnosis.
By contrast, most of the devices in Armenia, China, Indonesia and Viet Nam have been placed in central
facilities.

24

Stop TB Partnership and Médecins Sans Frontières – November 2015

Table 2: Xpert MTB/RIF availability at the country level (based on country feedback)

List of countries

Reference lab(no. of devices)

Specialised
hospital(no. of devices)

Afghanistan

(1)

(1)

Armenia(2)(1)

Belarus(1)

Brazil(5)

Cambodia(3)

District level/
subdistrict level(no. of devices)

Microscopy
centre level(no. of devices

Community
outreach ormobile clinics(no. of devices)

2 machines available (1 at NRL and 1 at a private
hospital)
-

(1)

(26)

(13)

-

(17)

(126)

(23)

China

-

DRC

(1)

-

Georgia

(4)

-

India

(4 at NRL;
18 at IRL)

(35)

Indonesia

(6)

(39)

Kenya

(1)

(3)

(11)
-

-

-

(2-4)

-

-

(10)

-

(69)

-

-

-

-

-

-

(31)

-

-

Mozambique(3)

Nigeria

(2)

-

(4)

-

-

Pakistan

(6)

-

(36)

-

-

-

-

-

Russian Federation

Not known

Not known

Not known

Not known

Not known

South Africa

Not known

Not known

Not known

Not known

Not known

Swaziland--

Tajikistan(6)

Ukraine(1)(8)

Sokuluk Family Medicine Centre (FMC): 1
CTBD Bishkek: 1
Batken oblast TB centre: 1
Talas oblast TB centre: 1
Osh city TB centre: 1

A total of 131 devices implemented has beenreported, but complete information on placement is
not available

And at provincial level hospital (numbers notreported)

There are also a few public-private mix (PPM) sites-

NRL: 1
3rd level lab: 29 (28 4-module devices and 1
1-module device)
3rd level prison labs: 8 (1 4-module device in eachlab)
2nd level labs: 3 (2 4-module devices, 1 1-module
device)
1st level lab (AIDS center): 7 (1 4-module device ineach lab)
In process of installation: 3 4-module devices(1)

Uzbekistan-

Viet Nam

(6)

(37)

(3)

Zimbabwe

(2)

(13)

(71)

Legend:Penitentiary/prisons (2)Plans to cover all districts by end of 2017(950 devices)(62+2)(2)

Penitentiary/prisons (1)

(1)

(29)

Kyrgyzstan

PNG

Remarks from countries

(8)

-

-

-

(2)

Karakalpakstan: 5 at central level, 1 at district level;
By the end of 2015: 5 at central level, 3 at district
level
Tashkent: National AIDS Centers: 2; NRL: 2;
oblast (state level) and rayon level: 15

5 are at PPM sites which collaborate very well with
the NTP and these are counted under district/
sub-district level

yes

Note: number of devices placed at the different levels of the laboratory network are reported in parentheses when this information was madeavailable by countries (status as of August 2015)

Out of Step: TB Policies in 24 Countries

25

Andrea Bussotti/MSF

Use of WHO-approved rapid molecular tests for the diagnosis of TB
Countries responded that they are mostly recommending the use of WHO-approved rapid molecular tests
in the algorithms for the diagnosis of TB.
Drug-susceptibility testing (DST)

All countries included in the survey reported that their national guidelines recommend first-line DST for all
rifampicin-resistant patients and for all patients considered at risk of MDR-TB.
Seven countries have adopted a more aggressive strategy for detection of MDR-TB cases and recommend
first-line DST for all confirmed TB cases: Belarus, Georgia, Kyrgyzstan, Russian Federation, South Africa,
Tajikistan and Ukraine.
All countries included in the survey reported that their national guidelines recommend second-line DST for all
rifampicin-resistant TB (RR-TB), polydrug-resistant TB (PDR-TB) and MDR-TB patients.
However, qualitative feedback from the survey indicates that implementation of first-line and secondline testing policies varies among countries, and access to testing may not be uniformly available. The
availability of DST for first-line and second-line drugs is captured and highlighted in the table on the right.

26

Stop TB Partnership and Médecins Sans Frontières – November 2015

Belarus

Armenia

Afghanistan

Partially implemented

DRC

China

Cambodia
Fully implemented

UkraineTajikistan

SwazilandSouth Africa

Russian Federation

PNG

Pakistan

Nigeria

Mozambique

Kyrgyzstan

Kenya

Indonesia

India

Georgia

Disclaimer: This is purely based on qualitative feedback provided by key informants

Uzbekistan

Out of Step: TB Policies in 24 Countries

Not implemented

Viet NamlegendSecond-line DST (including at least
fluoroquinolones and second-line injectableagents) is recommended for all RR-TB,
polydrug-resistant (PDR)-TB and MDR-TB
cases

First-line DST (including at least rifampicin
and isoniazid) is recommended for all
rifampicin-resistant (RR)-TB cases and forpatients considered at risk of DR-TB

Rapid molecular diagnostics (e.g., Xpert
MTB/RIF) are recommended for alreadydiagnosed TB patients with the purpose of
testing or screening for identification of drug
resistance

Rapid molecular diagnostics (i.e., Xpert
MTB/RIF) are recommended as the initialdiagnostic test for adults and children at
risk of drug-resistant TB (DR-TB) and HIVassociated TB (high-risk groups)

Rapid molecular diagnostics (i.e., Xpert MTB/
RIF) are recommended as the initial diagnostic
test for all adults and children in whom TB is
presumed (i.e., symptomatics being investigated for TB), rather than sputum smear microscopy (SSM) and/or culture and DST

Diagnostics Implementation summary
Zimbabwe

Brazil27

II.

DS-TB treatment regimens

Key findings
 ountries should phase out empirical use of Category II regimens for treatment ofC
TB as rapid diagnostic tests become more widely available.
 ountries must ensure that FDC formulations, which have fewer side effects, areCrecommended and made available in the country for use.

Intermittent dosing
WHO recommends daily treatment4 wherever feasible with a high grade of evidence15.16. The
recommendations note that intermittent treatment (three times per week), although not ideal, can be usedduring the continuation phase if each dose is directly observed.
Six out of the 24 countries surveyed still use intermittent treatment. Armenia and Kyrgyzstan recommend only
for patients with side effects and under special circumstances. In Indonesia, it is recommended during thecontinuation phase for Category I and Category II treatment. In Ukraine, it is recommended for patients in
Categories I–III only during the continuation phase, except in the case of TB/HIV coinfection or paediatric
TB. In India and China, intermittent treatment is still recommended.
A recent study in India17 showed that within the intermittent treatment group there was a higher rateof people lost to follow up, which carries the associated risk of resistance generation. Although India
continues to recommend intermittent treatment, the NTP reported that daily treatment will be rolled
out in 104 districts in 2016, and since March 2015, pilot projects looking at daily treatments havebeen initiated in 30 high workload antiretroviral therapy centres for people coinfected with TB/HIV. It
is important that India’s draft policy recommending a daily treatment regimen, prepared in 2014, be
approved and implemented soon.

Category II Treatment
In the 2010 WHO guidelines4, it was predicted that the Category II re-treatment regimen would bephased out, especially with the increase in access to rapid diagnostic tests. The guidance stated thatthe use of rapid DST methods would eventually eliminate the need for a re-treatment regimen (Category
II). While this scale up of rapid DST is occurring, WHO recommends Category II treatment in only two
circumstances:In countries with limited access to rapid DST, Category II treatment is recommended
while patients who have relapsed or are returning after treatment non-completion are
awaiting DST results (if country-specific data show low or medium levels of MDR-TB in
these patients or if such data are not available).
In countries that do not yet have DST routinely available at the start of treatment
for all previously treated patients, the Category II treatment can be used for theduration of treatment on an interim basis until laboratory capacity is available.
As countries revise their diagnostic policies and implement rapid DST, there should be a corresponding
decrease in the use of Category II treatment. The target for the 2011-2015 Global TB Plan was tohave all previously treated cases receive DST for first-line drugs, but in 2014 only 58% of previously
treated cases were tested. The Category II regimen, which adds streptomycin to the DS-TB treatment
regimen, has been shown to have poor outcomes in countries with high background rates of MDR-TB
and high TB/HIV coinfection rates7. Increased levels of streptomycin resistance have been found in
China18 India19,20 Mozambique21, Uzbekistan22 and Viet Nam23 where the Category II regimen is still
recommended.

28

Stop TB Partnership and Médecins Sans Frontières – November 2015

Ten of the 24 countries in the survey no longer recommend Category II treatment. Of the remaining 14 that
continue to recommend and use Category II treatment, 10 of them are among the top 22 high-burden TB
countries and 3 have a high HIV burden. With continued scale up in access to rapid diagnostic testing in
all these countries, Category II treatment should be removed from the TB treatment guidelines. DST must
be offered as a priority to all re-treatment and high-risk cases in order to ensure that the correct treatment isprovided from the very beginning.

Fixed-dose combinations (FDCs)
The 2010 WHO guidelines recommend fixed-dose combinations for the treatment of DS-TB. FDCs simplify
the treatment regimen for patients, causing fewer side effects and reducing the pill burden24. Althoughmono-substances are available, they present more challenges for dosing, procurement and logistics.
Only three countries (India, Russian Federation and Ukraine) do not have FDCs as the preferred formulationsin their guidelines. The Russian Federation and Ukraine recommend mono-substances as the formulations
for the treatment of DS-TB. The Standards for TB Care in India (STCI)25 state that “fixed-dose combinations(FDCs) are desirable as they simplify drug procurement and logistics, the delivery of directly-observed
treatment (DOT) and may increase adherence… It was recommended that the programme undertake
operational research to assess the feasibility of implementing daily therapy using FDCs under direct
observation under programmatic settings”. These recommendations have yet to translate into nationalguidelines.
There are a number of different FDCs on the market, and it is important that the FDCs available andrecommended conform to the WHO dosing and quality recommendations. FDCs are particularly important
for the treatment of children with DS-TB. The doses for first-line drugs for children were increased in 2010
and further updates were made in the latest WHO paediatric TB guidelines26. The good news is that five
years following the interim recommendation on the paediatric first-line drug dosages, only three countries(Swaziland, Ukraine and Viet Nam; the status of Ukraine and Viet Nam are not known) have yet to update
their guidance on the doses required for the first-line treatment of children. While new FDC products thatreflect these increased dosages are being developed, there are interim recommendations regarding how
to dose children using the existing FDC products. The new FDC products are expected to be released by
the end of 2015. It is important that countries update their dosing tables so that these new products can bequickly and easily implemented by treatment providers.
In addition to updating the doses required for the treatment of DS-TB in children, WHO recently reviewed
and updated all areas of the treatment of paediatric TB in its 2014 guidance. Seven countries updated theirguidance in 2014 (namely, Belarus, Georgia, India, Mozambique, Pakistan, Tajikistan and Uzbekistan),and Brazil is currently in the process of updating its guidance. This timely updating of national policies
following the release of new and updated WHO guidance is what is required and should be the normative
process for all policy updates.

III.

DR-TB treatment regimens

Key findings
 ountries should regularly update national Essential Medicine Lists to be in line withC
the WHO Essential Medicine List.
 rugs categorised as Group 5 should be made available for patients with complex
Dforms of drug-resistant TB.
 ompassionate use or other similar mechanisms should be established to ensureC
access to new drugs while the programmatic use of the drugs is being planned.

Out of Step: TB Policies in 24 Countries

29Treatment recommendations for MDR-TB currently involve an individualised approach that compilesa regimen using drugs that the patient is sensitive to from the five groups or classes of drugs.
Table 3: TB drugs used to treat drug-resistant TB according to group (class)
Classification of TB Drugs

Drugs included in this category

Group 1pyrazinamide, ethambutol, rifabutin, isoniazid, rifampicin, rifapentineGroup 2kanamycin, amikacin, capreomycin, streptomycin

Group 3

levofloxacin, moxifloxacin, ofloxacin

Group 4para–aminosalicylic acid, cycloserine, terizidone, ethionamide, prothionamide

Group 5

bedaquiline, delamanid, clofazimine, linezolid, amoxicillin/clavulanate,thioacetazone, imipenem/cilastatin, high-dose isoniazid, clarithromycin

It is important that treatment providers have access to all drugs in each group so they can construct thebest possible regimen for the patient. Adding these drugs to national Essential Medicines Lists (EML) is one
key way to make these drugs more easily accessible. The WHO EML – a list of the most efficacious, safe
and cost–effective medicines for priority conditions that in total represents the minimum medicine needs
for a basic health care system – can guide countries in the development of their national EML. Drugs on
the EML have also been evaluated for cost–effectiveness against other alternatives in the same class of
medicines. The WHO EML is updated every two years by an expert committee made up of recognised
specialists from academia, research, and the medical and pharmaceutical professions.
In 2015, WHO added five TB drugs to the EML: bedaquiline, delamanid, linezolid, rifapentine andterizidone27. Only 3 of the 24 countries have all the drugs from Groups 1, 2, 3, 4 and 5 on their national
EML lists (Belarus, Cambodia and Ukraine). The availability of Group 5 drugs on the EML was the weakest,with the remaining countries having no or few of the Group 5 drugs on their EML. For the remaining groupsof drugs, 5 countries had just 1 complete group of drugs on their national EML, 4 countries had just 2
complete groups, and 5 countries had 3 complete groups. Five countries (India, Nigeria, Kyrgyzstan, Kenya
and Zimbabwe) did not have a single complete group of any of the MDR-TB drugs on their EML. Group 4
has two drugs from the same class with equivalent efficacy (prothionamide/ethionamide and cycloserine/
terizidone). For countries that have only one of the drugs from that class on their EML, the survey results
have been highlighted to reflect this.

New drugs for the treatment of DR-TB
For the first time in nearly 50 years, two new compounds – bedaquiline and delamanid – have been
conditionally approved for the treatment of MDR-TB in cases where an effective treatment regimen is nototherwise available. Bedaquiline (Janssen), the first new drug, received accelerated approval from the
US Food and Drug Administration (FDA) in December 201228. The second drug, delamanid (Otsuka),
received approval from the European Medicines Agency (EMA) and Japan’s Pharmaceuticals Medical
Devices Agency (PMDA) in 201429. Alongside these completely new drugs, there is growing evidence
on the potential role of repurposed medicines, including clofazimine and linezolid, which are showing
effectiveness against drug-resistant forms of TB30,31,32.
In addition to ensuring that these new medicines are on the EML (in line with the recent 2015 updateof the EML), countries also need to issue national guidance on their use. Eleven countries have nationalguidelines on the use of bedaquiline. There are an additional three countries using bedaquiline in pilot orcompassionate use programmes (in India, Pakistan and Uzbekistan) that have issued interim guidance forthe use of bedaquiline in these settings.
Only four countries have guidance on the use of delamanid – all in the FSU region (i.e., Belarus, Georgia,
Kyrgyzstan and Tajikistan). Two of these countries (Belarus and Georgia) have access to delamanid throughcompassionate use programmes. Armenia has guidance on the use of delamanid but this has yet to beincorporated into national guidelines.

30

Stop TB Partnership and Médecins Sans Frontières – November 2015

Compassionate use
Compassionate use refers to the use of an investigational drug outside of a clinical trial by patients withserious or life-threatening conditions who do not meet the enrolment criteria for the clinical trial in progress.
Compassionate use has been used as an interim solution for accessing bedaquiline and delamanid forpatients with extensively drug-resistant (XDR-TB) or failing on MDR-TB regimens. Fifteen countries havethe necessary frameworks in place to offer early access to new drugs through compassionate use orequivalent processes. Although the compassionate use programme for bedaquiline is coming to an end,
as the programmatic use of this drug is scaled up via the USAID donation programme, it remains importantthat countries consider putting in place the necessary framework to allow access to other drugs yet to beregistered to be used for the treatment of complex MDR-TB cases, for example, delamanid and pretomanid(also known as PA-824). Compassionate use programmes offer earlier access for patients who need new
drugs and the benefit of clinical experience using the new drug, but compassionate use is not a long termsolution; planning for the larger programmatic introduction of new drugs should happen in parallel.

IV.

Models of care

Key findings
 ecentralisation of all aspects of TB care can and should be implemented; thisDpatient-focused model does not affect outcomes and has positive cost implications.
Routine hospitalisation for any type of TB is not needed.
 urse-initiated treatment for DS-TB can be considered and is being used in someNcountries.

Out of Step: TB Policies in 24 Countries

31

Giorgos Moutafis

Integration of TB and HIV treatment needs to be prioritised; how and where people
receive treatment is important.

Models of care for DS-TB
Treatment for TB is a considerable burden for patients, requiring a minimum of six months of treatment
with multiple, if not daily, visits to health care services33. In order to improve adherence, infection
control and ensure the minimal disruption to patients, TB services should be decentralised as muchas possible, especially for DS-TB. Evidence has shown that moving treatment centres closer to thepatient results in decreased costs to the patient, as well as decreased costs to the programme34,35,36.
Seventeen out of 24 of the countries in the survey had DS-TB treatment starting at the primary
health care (PHC) level. In addition to moving services closer to the patient, a further step in thedecentralisation of DS-TB care is to allow nurses to initiate treatment. This approach has beenformalised in the treatment of HIV, where task shifting (i.e., the delegation of tasks performed byphysicians to staff with lower-level qualifications) is considered a crucial means of expanding access totreatment in resource-poor settings or settings with limited medical human resources, and has seen nochange in outcomes37. The challenges regarding health care worker (HCW) shortages are also present
for TB38, and task shifting should be considered an option in settings with limited resources. Half of thecountries surveyed allowed nurses or health care workers to initiate DS-TB treatment. All of the Africancountries included in this survey allow for HCW-initiated treatment. This may be due to these countries’
experience with using this model for their HIV services. Furthermore, countries with a policy regarding
HCW-initiated treatment for DS-TB also reported a complementary policy on the PHC-level initiation oftreatment. This approach enables positive steps towards the full decentralisation of DS-TB services andall the benefits that confers on patients.
Countries where nurses/HCWs can start adults on DS-TB treatment:

Brazil, Cambodia (for smear + cases), DRC, Georgia, Kenya, Mozambique, Nigeria, PNG, South Africa,
Swaziland, Viet Nam and Zimbabwe.
The status of initiation of TB treatment in other countries is highlighted in the table below.
Table 4: Status of initiation of DS-TB treatment

32

Countries where nurses
do not initiate TB
treatment

Who initiates DS-TB treatment ?

Afghanistan

Only relevant doctors can initiate treatment for DS-TB

Armenia

Nurses are only responsible for implementation of DOT

Belarus

Not specified

China

Not specified

India

PhysicianIndonesia

Not specified

Kyrgyzstan

Only TB specialists can initiate treatment following Consilium decision

Pakistan

Not specified

Russian Federation

Only TB doctors

Tajikistan

Only TB doctors can initiate treatment after confirmation of TB Council

UkraineNot specified

Uzbekistan

Not specified

Stop TB Partnership and Médecins Sans Frontières – November 2015

The following is the situation in countries that do not recommend the initiation of DS-TB at the PHC level.
Table 5: Initiation level of treatment for DS-TBCountry

Who initiates DS-TB treatment ?

Belarus

Status not known

ChinaCountry level (reported by NTP response)

Georgia

Only case detection and referral to a regional TB facility are done at the PHC
level; after diagnosis is confirmed and the patient is registered at the TB facility,
PHC nurses can give TB treatment prescribed by a TB doctor

Kyrgyzstan

Status not known

Russian Federation

After decision of central region TB medical committee

UkraineAccording to Order No. 620 (Consolidated TB protocol), patients with pulmonary
tuberculosis with positive sputum smear by bacterioscopy method have to behospitalised (in exceptional cases patients with bacteria excretion by smear canbe treated at home if conditions for infection control have been provided); under
the regulatory framework, patients may be treated in institutions that provide
primary health care, however, institutions of primary health care are not involvedin the proper management of patients with TB

Uzbekistan

TB treatment is initiated at the district/rayon level

Models of care for DR-TB
The treatment for MDR-TB is long, complex and expensive, with poor outcomes and high rates of people
lost to follow up. Two of the main variables contributing up to 90% of the costs of a DR-TB regimen are
drugs and hospitalisation39. WHO has recommended ambulatory models of care40, and decentralisationof DR-TB services could have significant impact on the total cost of treating MDR-TB. Decentralisation has
not been associated with poorer outcomes41,42,43, and is associated with decreased rates of people lost tofollow up 44 and lower costs.45,46,47
The process of decentralising DR-TB services is not as straightforward as for DS-TB, as DR-TB patients
may be more likely to require hospitalisation due to the likelihood of the patient being sicker and thecomplexities and side effects of the treatment. Despite this difficulty, it is important that hospitalisation only
be recommended based on the clinical condition of the patient and not routinely recommended or madecompulsory. Treatment initiation can still be decentralised to at least the district level. Half of the countries
surveyed have guidelines in place to allow the initiation of DR-TB treatment at district level. In five countries
in the FSU region (Armenia, Georgia, Russian Federation, Tajikistan and Uzbekistan), TB treatment decisions
are determined by a TB committee that also decides the level at which DR-TB treatment can be started.
However, Armenia has policies that recommend compulsory hospitalisation for DR-TB patients, thus
weakening the potential advantages of decentralising treatment initiation. More than half of the countries
surveyed do not include routine hospitalisation as part of their guidance for the treatment of DR-TB. In
countries with compulsory hospitalisation in their guidance, the duration of hospitalisation ranges from two
weeks when the treatment is being initiated, to longer durations of eight months during the intensive phaseof treatment. This places a large burden on both the patient and the national TB programme with regard
to the cost and infection control issues48 associated with hospitalisation. (Please refer to Table 6 for theduration of hospitalisations.)
There have been two policy changes among the countries reviewed in the 2014 Out of Step report.
The Russian Federation previously had a policy of hospitalising all forms of TB until smear conversion orfor eight weeks, whichever happened first. It changed this policy at the end of 2014 (Order of MOH
RF #951 from 29/12/2014) and routine hospitalisation is no longer required for the intensive phase of
DS-TB. The decision to hospitalise now lies with the TB Committee, based on the individual situation of thepatient. Uzbekistan changed its policy at the end of 2014, removing compulsory hospitalisation for DR-TB(although this was not required for DS-TB patients). This policy shift away from routine hospitalisation is to

Out of Step: TB Policies in 24 Countries

33

be welcomed; the next step is ensuring that these policies are implemented. Cost savings resulting fromthis policy change should be reinvested in the national TB programme in order to ensure that all patients
who need treatment can access it, and that the programme can build its capacity towards the further
decentralisation of TB care.
Countries that DO NOT RECOMMEND routine hospitalisation for the treatment of DR-TB (15/24)
Brazil, Cambodia*, DRC, Indonesia, Kenya, Mozambique, Nigeria, Pakistan, PNG, Russian Federation*,
Swaziland, Tajikistan, Ukraine, Uzbekistan*, Zimbabwe*Notes:Russian Federation: depends on the individual patient’s situation (Order of MOH RF #951 from 29/12/2014)
Cambodia: a few days may be required initially to check the tolerance of drugs
Uzbekistan: Prikaz No 383, MOH (24 October 2014)

Table 6: Duration of hospitalisation for DR-TB treatment
Country

Duration of hospitalisation

Afghanistan

Not known

Armenia

Until smear microscopy conversion to negative is achieved; two consecutive
negative smears a minimum of two weeks apart. According to the protocol (D10),
XDR-TB cases must stay in a NTC TB hospital until the end of the intensive phase

BelarusThree to four months

China

The first two months of the intensive phase

Georgia

Approximately 15 days

India

Hospitalisation time is until smear conversion and/or clinical improvement

Kyrgyzstan

Not known

South Africa

Viet Nam

MDR-TB patients are hospitalised until they are confirmed to be non-infectious.
For XDR-TB patients, the duration of stay in the hospital may vary from patient topatient, depending on the clinical response to treatment; on average, the duration
is six months
As per Programmatic Management of Drug-resistant TB (PMDT) guidelines inViet Nam, MDR-TB treatment begins with an inpatient treatment phase of about
15 days; patients are discharged when they are stable and meet other PMDT
requirements

There is a strong regional trend with regard to a more centralised system in the countries in the
Commonwealth of Independent States (CIS)49; these countries are more likely to require compulsory
hospitalisation (four out of seven for MDR-TB). In addition, these countries tend towards a centralised
approach to physician-initiated treatment, with four out of seven of these countries requiring doctors toinitiate DS-TB treatment. This centralisation is likely due to the models of financing operating in the region50.
However, Russia and Uzbekistan’s policy changes with regard to hospitalisation indicates that the policy
can be changed in a centralised setting with a similar model of health care financing.

TB/HIV coinfection
Coinfection of TB/HIV is a considerable burden in several of the countries surveyed; even countries withlow HIV burdens need to ensure that adequate provisions are made for TB/HIV coinfected patients and that
all TB patients are being screened for HIV and vice versa.
Tuberculosis is the most common presenting opportunistic disease and cause of mortality among people
living with HIV, accounting for approximately 25% of all HIV-associated deaths annually. In the presenceof HIV, TB is associated with substantially higher case fatality rates and is the most common notified
cause of death. The high mortality rate in TB/HIV coinfected patients is usually due to complications fromoverwhelming TB disease or impaired immunity from advancing AIDS. Evidence has shown that early
antiretroviral treatment (ART) initiation improves outcomes51,52. In light of this evidence, WHO policy statesthat ART should be initiated for all people living with HIV with active TB disease irrespective of CD4 cell

34

Stop TB Partnership and Médecins Sans Frontières – November 2015

count. TB treatment should be initiated first, followed by ART as soon as possible within the first eight weeks
of starting TB treatment. HIV-positive TB patients with profound immunosuppression (CD4 <50 cells/µL)
should start ART within two weeks of starting TB treatment53.
Only four of the countries surveyed did not have guidelines recommending ART initiation regardless of CD4
count. The Russian Federation has a sliding scale of guidance regarding when to start ART in coinfectedpatients, which depends on CD4 count. Pakistan has an absolute number (<400) for starting ART. For
Viet Nam and Afghanistan, no policy recommendations could be found for CD4 count.
With a high treatment burden on coinfected patients, treatment should be as closely linked as possible
to support adherence to both treatment regimens. This ideally should encompass treatment being offered
in one facility by a single team of people. The process of referral between treatment facilities can cause
considerable delays. For example, in one South African township, only 11% of HIV-infected patients with
CD4 cell counts <50 cells/µL who were referred from TB services to separate HIV services started ART
within four weeks of their TB diagnosis.54
Seventeen countries have policies regarding TB treatment initiation in facilities offering HIV care. With
regard to starting HIV care in TB facilities, a number of countries have policies allowing treatment to be
started after a patient’s case has been reviewed or discussed with an HIV specialist. Despite concerns
about the management of side effects due to the combination of TB medications and antiretrovirals (ARVs),
it is possible to successfully fully integrate TB/HIV services in one clinic to reduce delays and the burden
on patients, including opportunity costs.55 Decentralising TB/HIV care is also associated with better
outcomes56,57,58. When TB services are decentralised, the plans should consider how this complements
existing HIV services, especially in communities with high rates of coinfection. It is important that HIV
programme staff be aware and involved in patient care to ensure that appropriate follow up is arranged
once the patient has completed TB treatment.
Countries that recommend initiation of TB treatment infacilities providing HIV care (17/24)
Belarus, Brazil, China, DRC, Georgia, India,
Indonesia, Kenya, Mozambique, Nigeria, Pakistan,South Africa, Swaziland, Tajikistan, Ukraine, Viet
Nam, Zimbabwe

Countries that recommend initiation of HIV treatment infacilities providing TB care (18/24)
Afghanistan, Armenia, Belarus, China, DRC,
Georgia, Indonesia, Kenya, Kyrgyzstan, Nigeria,
PNG, Russian Federation, Swaziland, Tajikistan,
Uzbekistan, Ukraine, Viet Nam, Zimbabwe

Out of Step: TB Policies in 24 Countries

35

V.

Drug regulatory environment

Key findings
 ountries should have accelerated mechanisms in place for registration and importation
Cof key DR-TB medicines to improve access to more effective treatment regimens.
 ountries should align their quality assurance mechanisms and standards forCprocurement of TB medicines with WHO recommendations.

Accelerated approval for the registration of DR-TB medicines
Fifteen countries have an accelerated approval mechanism in place that allows swift registration of DR-TB
medicines including new drugs59. Countries should participate in the collaborative registration procedure set
by the WHO Prequalification of Medicines Programme (PQP), which allows for registration of a drug within
three months for prequalified medicines. Even though this procedure requires pharmaceutical companies
to request the registration in the first place at local regulatory agencies, it is free of charge and does notentail any dossier submission; countries can request that companies initiate the process for key medicines.
Whenever countries are part of this procedure or have a national accelerated approval mechanism inplace, they should uphold their commitment to fast-track evaluations.
Before registration takes place, it is important that countries be able to grant importation waivers to DR-TB
medicines unregistered locally, whenever they have already been prequalified by WHO or have been
granted full or conditional approvals by stringent regulatory authorities.

Local registration of DR-TB medicines and their addition to the national Essential
Medicines List (EML)
No country has registered the full set of DR-TB medicines recommended by the WHO guidelines and that
may be required to treat the different resistance patterns that could be faced in DR-TB clinics. Granting
importation waivers for unregistered DR-TB medicines is a helpful interim access strategy, but only local
registration can ensure long-term supply.
The WHO updated its EML6 in April 2015 with new DR-TB medicines (e.g., bedaquiline, delamanid) andalso with key repurposed medicines that do not have official TB indications but have sufficient supportive
data in the literature on their benefits for DR-TB (e.g., linezolid). Countries should update their national EML
with all current TB medicines listed in the WHO EML to ease importation.

Quality assurance
The source of funding for TB drugs and the procedure for countries to purchase them has a direct impact on
the quality of the medicines, especially considering the varying stringency of national medicines regulatory
authorities (NMRA) across countries. Furthermore, there is no harmonisation even within countries in terms ofthe different purchase and mixed funding mechanisms for TB medicines.
Quality criteria differ depending on whether the purchases are covered by domestic funding or external
donors like the Global Fund to Fight AIDS, TB and Malaria (GFATM), which link their grants to quality
criteria of medicines set by the Global TB Drug Facility, for instance.
The possible withdrawal of GFATM financial support from TB programmes in a series of countries maylead national TB programmes to order DR-TB medicines with government money without a clear reference
to WHO quality standards. Some countries also follow their own quality standards, but to ensure quality ofdrugs, these standards need to be aligned with the global recommendations by WHO.

36

Stop TB Partnership and Médecins Sans Frontières – November 2015

tb policies:
case studies
from the field

38

Stop TB Partnership and Médecins Sans Frontières – November 2015

Boosting scale-up of new diagnostics:
A TB REACH initiative from Uganda
In 2010, World Health Organisation (WHO) recommended a rapid molecular test, Xpert MTB/RIF, for thedetection of HIV-associated pulmonary tuberculosis (PTB) as a replacement for smear microscopy. However,
two years after the WHO recommendation, the National Tuberculosis Leprosy Programme (NTLP) of
Uganda had still not yet adopted the new diagnostic protocol.
Uganda’s national guidelines continued to recommend a chest radiograph after two negative sputum
smears in patients presumed to have PTB. This approach posed a challenge for TB screening in HIVinfected patients because smear microscopy has low sensitivity among people with HIV. Furthermore,access to chest radiography can be severely restricted. Given these resource limitations, this NTLP
diagnostic algorithm for smear-negative PTB often caused long delays prior to treatment initiation andinvolved patients making multiple visits to different health facilities. Such delays in diagnosis and treatment
can prove life threatening and increase mortality in countries such as Uganda, which have a highincidence of both HIV and TB.
To help address this situation, the Foundation for Innovative New Diagnostics (FIND) and the NTLP applied
and received funding from Stop TB Partnership through the TB REACH initiative. The initiative, which waslaunched on 15 November 2011, aimed to introduce Xpert MTB/RIF as the initial means of diagnosing
TB in HIV-infected patients at six district-level health facilities in Uganda. In addition, in order to overcome
the difficulties of people with TB being lost to follow-up prior to diagnosis, a web-based electronic
reporting system using mobile SMS for data entry and results feedback was developed and introduced incollaboration with Interactive Research and Development (IRD). This system is also being implemented asa key element of another TB REACH project in Pakistan.
Initially, Xpert MTB/RIF was successfully implemented as an add-on diagnostic test for smear-negative
HIV-positive patients presumed to have TB, at six sites serving an estimated total population of 8.6 million
people. A total of 16,224 presumptive TB individuals attending health facility outpatient departments

Out of Step: TB Policies in 24 Countries

39underwent TB sputum microscopy. Of these, 7,551 HIV-positive patients who were presumed to have TB
were tested using the Xpert MTB/RIF test. Xpert MTB/RIF found a total of 1,043 individuals to be positive
for TB. In the absence of this new technology, these individuals would not have been diagnosed asbacteriologically confirmed cases. After a year of implementation, the initiative began to use Xpert MTB/RIF
to directly test all people with HIV in need of further evaluation for TB. As of June 2015, a total of 10,013
HIV-positive patients were tested using Xpert MTB/RIF, of which 1,494 were found to be positive for TB.
The NTLP Strategic Plan 2010/11–2014/15 has now been revised, including important changes related
to collaboration between HIV and TB treatment programmes, and in particular, the need to scale up new
diagnostics in Uganda.

Compassionate use of bedaquiline to treat
extensively drug-resistant TB patients in Armenia
Multidrug-resistant tuberculosis (MDR-TB) poses a growing public health threat in Armenia, which currently
ranks among the world’s 27 countries with the highest MDR-TB burden60. In this context, extensively drugresistant tuberculosis (XDR-TB) has also emerged, accounting for approximately 10% of diagnosed MDR-TB
patients in 2011. Having worked in MDR-TB care in Armenia since 2005, Médecins Sans Frontières (MSF)
worked with Ministry of Health officials to formalise a framework to allow compassionate use of new TB
drugs for patients without any other treatment options. A committee of experts was convened to develop
a protocol for the compassionate use of the new TB medicines, which was then approved by a local
ethics committee and the Ministry of Health. A humanitarian waiver was granted to allow importation of
the necessary drugs. An agreement to access bedaquiline was signed in 2012, and in July 2013, eligible
patients began receiving treatment, with 62 patients having benefited to date. Patients receive a 24-weekcourse of bedaquiline tablets, added to a multidrug-resistant TB regimen that lasts two years.
Table 7: Chronological milestones for the initiative
Late 1990s–early
2000s

TB control strategies based on DOTS started and expanded across Armenia

September 2005

MSF begins work on MDR-TB related projects in Armenia

December 2006

National tuberculosis control programme for 2007–2015 adopted by the government

Early 2012

MSF begins work to establish compassionate use of TB drugs in Armenia

October 2012

National TB Programme signs agreement with Janssen to access bedaquiline forcompassionate use

2013

National response plan to combat drug-resistant TB 2013–2015 adopted by thegovernment

January 2013

Armenian ethics committee and Ministry of Health approves use of bedaquiline on
humanitarian grounds

February 2013

First bedaquiline request submitted to Janssen

March 2013

First bedaquiline importation through a humanitarian waiver system

April 2013

First patients begin receiving treatment with bedaquiline

April 2015
November 2015

End of compassionate use of bedaquiline and beginning of routine use of bedaquiline
supplied through the Stop TB Partnership Global Drug Facility (GDF)
Continued implementation of compassionate use initiative led by MSF for other new drugs;
Armenian government continues to implement routine use of bedaquiline through the
National TB Programme

MSF supported Armenia’s compassionate use initiative by providing guidance on technical aspects, aswell as funding, procurement of drugs, training of providers and support for local TB specialists to deliver
the new treatment. The compassionate use initiative is part of the National TB Programme’s national policy
framework for strengthening Armenia’s response to MDR and XDR-TB.

40

Stop TB Partnership and Médecins Sans Frontières – November 2015

Decentralisation of diagnosis and treatment of DR-TB
Khayelitsha, South Africa
In South Africa, tuberculosis, including DR-TB, was the leading cause of death in 2012. In Khayelitsha,
a township on the outskirts of Cape Town with a high prevalence of HIV, there are epidemic levels of DR-TB,
including multidrug-resistant and extensively drug-resistant tuberculosis (MDR/XDR-TB). MSF, in collaboration
with the local Department of Health, piloted a decentralised model of care whereby DR-TB patient care andsupport was made available at the primary health care level. The decentralised approach was started in2007 and was handed over to the Department of Health in 2013, and the outcomes were analysed posttransition. In 2014, of the 190 DR-TB cases diagnosed in Khayelitsha, 183 (96.3%) received treatment throughthis decentralised model. Although the proportion of successful treatment outcomes (defined as treatment cureor completion) largely remained the same as those reported in other sub-districts and provinces, there wasan increased proportion of prevalent DR-TB cases in the community accessing care due to decentralisation ofservices. Crucially, costing studies have determined that a fully decentralised DR-TB model of care costs 42%
less than a centralised hospital model.
In the Khayelitsha model, decentralisation has improved access to TB care and treatment and has also
resulted in reduced cost of treatment for the patient, including opportunity costs. As such, the model provides
a valuable example that can be replicated in similar settings.

The Karakalpakstan, Uzbekistan
Tuberculosis, and particularly multidrug-resistant tuberculosis, is a major public health concern in Uzbekistan.
An estimated 23% of new TB cases are MDR-TB cases. In 2010, MDR-TB treatment required compulsory
hospitalisation in centralised hospitals for the initial few months of treatment.
As the numbers of diagnosed patients increased, a waiting list developed. In addition, many patients were
not able to access the centralised services easily. In order to facilitate the decentralisation of services, reduce
waiting lists and facilitate the scale-up of drug-resistant TB treatment, the Ministry of Health in Uzbekistan,working with Médecins Sans Frontières, began to implement Ambulatory Care Day 1 (ACD1). The goal was
to initiate TB treatment in community settings closer to patients’ homes.
In order to implement this change, a new legal framework was developed in conjunction with new treatment
guidelines. Staff not previously involved in TB care management also had to be trained. Key challenges ofintegrating the diagnosis and treatment of drug-resistant and drug-sensitive TB care into primary health care
centres included:T ask shifting from central level specialists to family doctors, and the development
and training of adherence support nurses;
T he formation of district level consiliums for decision-making and case review, andto support on-the-job training;
Strengthened infection control and infrastructure investment;Introduction and scale-up of rapid molecular diagnostic tests, with improved
transportation of samples and communication of results.
Initially piloted in two districts in 2010, ACD1 has since been scaled up to all 16 districts in Karakalpakstan.
Over half of patients commencing TB treatment now start on ambulatory treatment from day one. The
time from diagnosis to commencing treatment has been reduced, and there are no longer waiting lists for
hospitalisation.

Out of Step: TB Policies in 24 Countries

41

Country perceptions on the implementation of the newmultidrug-resistant TB medicines
The current treatment for drug-resistant TB is long, complex, and associated with severe and life-threatening
side effects. Furthermore, the treatment only has successful outcomes for approximately 50% of people whostart treatment. WHO has issued interim guidance on the use61 of two new drugs registered for use intreating multidrug-resistant TB, bedaquiline and delamanid. Although these medicines offer great potential
for improving MDR-TB treatment, the scale-up of their use has been slow.
To learn countries’ perspectives on the barriers to using these new drugs, as well as to understand countries’
intentions to incorporate the new medicines into treatment regimens and policies, Stop TB Partnershipcollaborated with Médecins Sans Frontières to conduct a survey on new TB drugs in March 2015 (separate
from the survey on which the Out of Step report is based) among national TB programmes in high MDRTB burden countries. The survey was sent to 27 countries, and 25 countries had responded by June 2015
when the survey was closed.
The results showed that 24 countries were aware of the new medicines, but only 28% had registeredbedaquiline and 12% had registered delamanid for use. With regard to a framework for compassionate
use or other mechanisms to enable pre-approval access, 68% of the countries accessed bedaquiline
though such mechanisms, and 56% did so for delamanid. The most common reasons cited by countries forthe limited or non-usage of the medicines were: (i) the lack of registration of the medicines in their country;(ii) economic barriers such as the cost of the medicine and/or companion medicines; (iii) concerns about
the side effects; (iv) limited knowledge of the drugs; and (v) the lack of training for practitioners on how toadminister the drugs.
When asked whether they would recommend the use of the new medicines, most countries responded that they
were comfortable using the medicines and would strongly recommend their use for the treatment of MDR-TB.
Would countries recommend the use of new medicines?
80 %
70 %
60 %
50 %
40 %
30 %
20 %
10 %
0%

Legend:

76 %
64 %

28 %

20 %
8%

4%
bedaquiline
yesnodelamanid
I don’t know

A new approach to MDR-TB treatment
Access to diagnosis and treatment of MDR-TB is gradually being rolled out across high-burden countries.
But the treatment is lengthy (20-24 months), includes 8 months of painful daily injections, is toxic, andexpensive. In Uzbekistan, MSF is piloting a shorter treatment.
I asked Nurlan* to tell me the best thing about getting back to school. A shy 15-year old, living in
Karakalpakstan, Uzbekistan, he said he was just happy to hang out with his friends again. Nurlan had
become unwell in November 2013 and an Xpert MTB/RIF test had confirmed he had MDR-TB. Aftercounselling, Nurlan elected to trial the shortened regimen.

42

Stop TB Partnership and Médecins Sans Frontières – November 2015

The shortened regimen, developed in Bangladesh, is based on a recombination of first- and second-line
TB agents taken over 9–11 months. It lacks some of the most side-effect prone agents of the standard
treatment, such as cycloserine, known to cause psychosis. It reduces the injection phase to 4–6 months,
cuts the total number of tablets, and lowers the cost from around US$3,418 to $456 per patient. MSF
has previously used the regimen in conflict settings where a 20-month regimen is unfeasible. But morerobust evidence of its efficacy is needed. The ongoing, randomised controlled STREAM trial62 is examining
whether the shortened regimen is non-inferior to the current standard of care. But it isn’t designed to answer
the practical questions of how to implement the regimen safely, and it excludes children and regions withhigh levels of second-line drug resistance. These issues led to MSF’s decision to pilot the shortened treatment
in a prospective cohort in Uzbekistan.
Recruitment in Uzbekistan was completed in March 2015, with the enrolment of 146 patients. Full results
are due in January 2017, one year after the final patient completes treatment. So far, some patients havefound the regimen easier to tolerate. Early results63 indicate that sputum culture conversion may occur fasterthan with the standard regimen. Most importantly, patients can see an end to their treatment. The regimen
is unlikely to be a panacea, however, particularly in areas with high levels of second-line drug exposure,since it is unlikely to be effective in patients who have previously taken these drugs. Additionally, patientsstill experience nausea, headache, and joint pains. Nevertheless, a shortened regimen would reduce theimpact on patients’ lives, lessen the financial burden for programmes, and provide a simpler comparison for
newer drugs in trials, which currently must include comparison to the lengthy standard of care. Interim datafrom the MSF studies in Uzbekistan have been included in an individual patient data meta-analysis for theupcoming WHO TB guidelines revision which is due out in 2016.
Nurlan finished treatment in September 2014; the first child ever to have completed treatment with theshortened regimen. He was able to return to school just five months after starting treatment. He has now
completed 12 months of post-treatment follow-up without evidence of relapse. We wait impatiently for the
final study results, to learn whether this regimen could benefit the thousands of patients around the world like
Nurlan. TB is now the biggest infectious diseases killer globally, and one of the major causes of morbidity
and mortality in many of the countries where MSF works. There is an urgent need for improved regimens
and programme delivery to help us respond appropriately to the needs of patients and communities.

Helmut Wachter/13photo*Name changed to maintain anonymity.

Out of Step: TB Policies in 24 Countries

43

Introduction of New pAediatric FDCs: Kenya experience
The treatment course for drug-susceptible TB (DS-TB) in children has the same drugs as used for adults,
but recent changes in the doses of these medications has resulted in the current fixed-dose combination(FDC) tablets being no longer appropriate. WHO issued interim guidance in 2010 on the increased
doses and temporary dosing tables showing how to use the existing FDC products in combination withmono-substances. In 2013, the TB Alliance, in partnership with WHO Essential Medicines department,
received a UNITAID grant to develop the appropriate FDC formulations, which are easier to prescribe andadminister to children. As well as working with manufacturers to define the product, the TB Alliance worked
on identifying and mapping paediatric TB purchaser landscapes, identifying barriers to product uptake inthe 22 high-burden countries, and worked with countries to include childhood TB in national strategies/
plans, budgets, and grant applications/renewals.
In Kenya, TB Alliance supported the government in requesting the manufacturer of one of the new approved
FDCs to commence the product registration process with the Kenyan drug regulatory authority. The
registration process should be finalised by the end of 2015, when Kenya will place the first order for the
new RHZ (75/50/150) and RH (75/50) dispersible products, becoming available for use in March/April
2015. While waiting for the new products, the Kenyan NTP developed a phase-out plan for the existingolder dosage paediatric FDCs already in the country. The phase-out plan of the older formulations included
training of facility staff on use of the new paediatric FDC products, issuance of a memo to facilities on useof the new products, and review of the current treatment guidelines to ensure they match current WHO
guidelines.

44

Stop TB Partnership and Médecins Sans Frontières – November 2015

The 3P projectThe ‘3P Project’ aims to rapidly deliver affordable, effective new regimens for TB using push, pull and poolmechanisms to foster an open collaborative approach to conducting drug development and to employ
novel approaches to financing and coordinating R&D. The 3P Project implements three mechanisms tofacilitate the necessary and appropriate R&D for TB regimens:
 ull funding to incentivise R&D activities through the promise of financial rewards onp
the achievement of certain R&D objectives (i.e., through milestone prizes).
 ooling of intellectual property (IP) and data to ensure open collaborative researchpand fair licensing for competitive production of the final products.
push funding to finance R&D activities upfront (i.e., through grants).

Indicates
Combination

Hit to
Lead

Lead
Opt.

Pre-clinicalStudies

GLP
Tox

Phase
I

Phase
II

Discovery

Later Stage Preclinical

Clinical Development

Various TB Compounds
Milestone Prize

Discretionary
grant funding
throughout
the drugdevelopment
process

Grant funding
for regimen trials(phases I – III)
from existingand new
sources

Phase
III

LegendGrant funding

Large Milestone
Prize forcompounds
entering thepool for clinicaldevelopment(Phase I)

For more information, please visit msfaccess.org/3p

Out of Step: TB Policies in 24 Countries

45

conclusions andrecommendations

46

Stop TB Partnership and Médecins Sans Frontières – November 2015

With a confluence of changes affecting both the TB epidemic and the global response to it, now is the time
to capitalise on international consensus around more ambitious post-2015 targets and innovative thinking
about the future of the global TB response, including more effective and easier-to-use diagnostic andtreatment approaches.
Each country in this survey has different strengths and areas for improvement, and countries, implementersand donors must consider how to build on the strengths and address policy gaps on a country-by-country
basis. TB-endemic countries, WHO, manufacturers, donors and treatment providers must work together toclose the deadly gaps in diagnosis and treatment of people with TB.
The first step in ensuring that all patients with TB get the best possible treatment and are able to benefit
from recent advances in TB diagnostics and care is to ensure that national policies are up-to-date withinternational guidance. Once national policies are updated, then countries must tackle the more difficult
task of ensuring that these policies are implemented countrywide. Only with the right policy environment,
political will at the global and national levels, and adequate financing to support the implementationof policies can the current gaps that beset TB programmes be addressed. This will allow the necessary
paradigm shift and bending of the curves to end TB once and for all.

COUNTRIES
Increase domestic financing and high-level political commitment to ensure thatnational policies are in line with international guidance.

DIAGNOSIS:
Reduce the significant gaps between policy and implementation.
P rovide DST for all re-treatment cases, and avoid use of Category II treatment; when
DST is not available, empirical MDR-TB treatment can be considered while awaiting
DST in high MDR-TB burden areas.
 trategically invest resources to achieve wider diagnostic coverage and improveS
access to laboratory confirmed diagnosis and DST.

MODELS OF CARE:
Provide ambulatory decentralised and integrated care for DR-TB and DS-TB.
R emove policies of compulsory hospitalisation for TB patients, and have
hospitalisation depend on clinical need.
 nsure TB/HIV services are jointly planned and patients are effectively managed inEeach service.

DS-TB TREATMENT PROTOCOLS:
Ensure daily treatment for TB is the standard of care.
 dopt and promote the use of quality-assured FDCs in adults and children, byA
including FDCs in national guidelines, as well as in national EMLs in order to reduce
the use of mono-substance formulations for DS-TB treatment in adults and children.
Phase out the use of Category II re-treatment regimen.

Out of Step: TB Policies in 24 Countries

47

DR-TB TREATMENT PROTOCOLS: nsure that national TB treatment guidelines and EMLs are in line with WHOE
guidance for DR-TB and include necessary Group 2, 3, 4 and 5 drugs.
Implement the necessary legislation for compassionate use as soon as possible.
There should be parallel efforts to register new drugs so that they are available forprogrammatic use and to more patients and a sustainable supply can be set up.

DRUG REGULATORY ENVIRONMENT:
 nsure procurement and use of quality-assured (including WHO prequalified andEstringent regulatory authorities-approved) TB drugs.
P romote capacity of national medicine regulatory agencies (NMRA) to assess
quality of TB medicines.
P ut in place procedures that allow importation and dispensation of quality-assured
Group 5 medicines not yet registered.
Enable fast-track registration procedures of priority TB medicines.
 ake use of international regulatory flexibilities, such as the collaborativeM
registration process at the WHO prequalification programme, and recognisemarket authorisations granted by stringent NMRAs for priority medicines.
Implement the necessary legislation for CU as soon as possible. There should beparallel efforts to register new drugs so that they are available for programmatic use
to more patients, and so that a sustainable supply can be set up.

MANUFACTURERS
Prepare for scale-up of new treatments:
Provide access to innovative TB medicines through compassionate use.
P roactively register new medicines in countries where clinical trials take place andother high-burden TB countries, and register medicines and new compounds, evenin small markets.
 nsure an affordable, transparent price for all DR-TB medicines for all low- andE
middle-income countries.
Accelerate combined drug research to create appropriate regimens.
 nsure that intellectual property barriers (patents and test data) do not preclude
E
generic competition or development of appropriate FDCs or other formulations.
Introduce new diagnostic technologies.
 evelop diagnostic assays for rapid detection of drug resistance in decentralisedDsettings and ensure adequate distribution networks and adherence to negotiatedprices for products; offer contracts that allow for reagent rental and flexible andtransparent pricing structures for tests to allow for bundling or unbundling ofmaintenance contract costs, depending on country needs.

48

Stop TB Partnership and Médecins Sans Frontières – November 2015

DONORSIncrease political and financial support for adoption and roll-out of optimal TB/DR-TB
policies and practices, including decentralised and integrated (TB/HIV) services.
 upport the development of new innovations and assist with drug regulatoryS
policies for quality-assured TB medicines.
 ssist with determining optimal implementation models, strengthening laboratory
A
networks, referral systems and roll-out of diagnostics, and research anddevelopment including through innovative models such as the 3P project.

WORLD HEALTH ORGANISATION ontinue to issue policy guidelines for TB at international level and facilitate policyCchange at country level to support rapid adoption of international guidance into
national TB policies.
 nsure a timely and transparent process for identifying and approving newEdiagnostic technologies.
 nsure policies are relevant and translatable to countries with an appropriate levelEof technical assistance by technical partners to support the implementation ofpolicies.

Out of Step: TB Policies in 24 Countries

49

50

DIAGNOSIS

Stop TB Partnership and Médecins Sans Frontières – November 2015

DS-TB TREATMENT REGIMENSS

Swaziland

Pakistan

MozambiqueIndonesia

DRC

S

Afghanistan

DR-TB TREATMENT REGIMENS

New and repurposed drugs areavailable through compassionate useor patient-named basis mechanism

Viet Nam

National Essential Medicines List (EML)
includes drugs from Groups 2-5(Green: All groups; Amber: Three orfour; Red: Less than three in EML)

Armenia

There are national guidelines for theuse of delamanid

There are national guidelines on theuse of bedaquiline

Fixed-dose combinations (FDCs) are
the preferred formulation

Are the treatment guidelines forchildren in line with the WHO 2014
guidance?

Empirical Category II re-treatment
regimen is not recommended

BrazilDrug resistance testing (rifampicin
and isoniazid at least) recommended
for all confirmed TB cases

Uzbekistan

Xpert MTB/RIF is the recommended
initial diagnostic test for all persons tobe evaluated for TB

KEY INDICATORSKey TB Policies Dashboard
Zimbabwe
1

2,3

UkraineTajikistan

4South Africa

Russian Federation

PNG

2,3

Nigeria2

Kyrgyzstan

Kenya

3

India

Georgia

2,3

China

Cambodia

3

BelarusD

2,3

MODELS OF CARE

CambodiaBrazilDRUG
REGULATORYENVIRONMENT

2, 3 only

Indonesia
2 onlyPNG

Pakistan

DRC

BelarusAfghanistan
3 only4 only2, 3, 4 only

Tajikistan

1 only4

Ukraine

India

Georgia

China

Disclaimer: The above reflects only policy status and is not related to access or actual implementation status

No (none)3

Not known

Uzbekistan

Draft guidance

Kenya
2,3

Kyrgyzstan

2

Viet Nam

Yes (Subnational)

1

Mozambique

Yes (all)Armenia
D

South Africa

S

There is a process for accelerated
registration of DR-TB drugs, including
new TB drugs

Routine hospitalisation of MDR-TB
patients not recommended

TB treatment initiation in facilities
providing HIV care

Nurses or health workers can initiate
DS-TB treatment

Decentralisation of DS-TB treatment
initation at primary health care level

KEY INDICATORS

Zimbabwe

Swaziland

Russian Federation

NigerialegendOut of Step: TB Policies in 24 Countries

51

GLOSSARY AND
ABBREVIATIONS

52

Stop TB Partnership and Médecins Sans Frontières – November 2015

Active case finding: Strategy of actively screening and diagnosing individuals belonging to groups
at high risk for TB (e.g., people living with HIV, miners, etc.). Risk groups vary depending on theepidemiological profile of TB in a given country.
Category II (Category 2) treatment: One drug, streptomycin, is added to standard first-line drugs

and the regimen is extended to eight months. WHO has recommended that this treatment option only beconsidered in areas at low risk for MDR-TB.
Clinical trials: Sets of tests in medical research and drug development that generate safety and efficacy
data (including information about adverse drug reactions and the adverse effects of other treatments) for
health interventions (e.g., drugs, diagnostics, devices, therapy protocols).
Compassionate use: The terms “compassionate use,” “expanded access” or “special access” haveessentially the same meaning. They refer to programmes that are intended to provide potentially lifesaving
experimental treatments to patients suffering from a disease for which no satisfactory authorised therapy
exists and/or patients who cannot enter a clinical trial. Compassionate use refers to programmes that makemedicinal products available either on a named-patient basis or to cohorts of patients. Compassionate
use needs to be framed within a national legislation that establishes the conditions under which the drug
is made available. Refer to Annex 5 (Use of experimental drugs outside of clinical trials “compassionateuse”) of the “WHO guidelines for the programmatic management of drug-resistant tuberculosis: Emergency
update 2008”.
Contact tracing: The identification, screening and testing of individuals who have been in close contact

with an individual who has infectious TB, and therefore at high risk of having contracted TB. Please consult
http://apps.who.int/iris/bitstream/10665/77741/1/9789241504492_eng.pdf.
Culture: Bacterial culture is a laboratory method to multiply bacteria in order to assess whether they arepresent or not in a patient’s sample. This is done by letting the bacteria grow in a predetermined culture
medium under controlled laboratory conditions outside of the natural environment where they usually grow(e.g., for TB, the human body).
Culture-converted: A person whose last two clinical samples are no longer growing M. tuberculosis,

implying that the bacteria are no longer present.
Drug resistance: When a drug used to treat tuberculosis is in fact ineffective against a strain of M.
tuberculosis, the bacteria are said to be resistant to the drug (as opposed to drug-susceptible or drugsensitive).
Drug-susceptible/drug-sensitive TB: Bacteria are said to be sensitive to a drug when the drugs are

effective in killing or stopping the multiplication of bacteria in the body and can therefore clear the infection.
The strains of TB that are sensitive to all first-line drugs are called drug-susceptible.
Drug-resistant TB: Broad term to take in all forms of drug-resistant TB, including MDR-TB and XDR-TB.
Extensively drug-resistant TB: see XDR-TB
External quality assessment (EQA): A system for objectively checking the laboratory’s performanceusing an external agency or facility. EQA allows for the comparison of a laboratory’s testing to a source outsideof the laboratory, such as the performance of a peer group of laboratories or the performance of a referencelaboratory. Please consult http://www.who.int/ihr/training/laboratory_quality/10_b_eqa_contents.pdf
Extrapulmonary TB: A form of TB in which M. tuberculosis infects parts of the body other thanthe lungs, most commonly the lymph nodes, bones, central nervous system, and cardiovascular andgastrointestinal systems.

Out of Step: TB Policies in 24 Countries

53First-line drugs: The drugs used as the first resort to treat a disease. In the case of TB, the following four
drugs are usually chosen: isoniazid (H), rifampicin (R), ethambutol (E) and pyrazinamide (Z). These drugs arehighly effective in treating drug-susceptible TB, and patients usually tolerate them well. Streptomycin (S) is aninjectable that is used in the first-line treatment of TB meningitis.
Global Fund: The Global Fund to Fight AIDS, Tuberculosis and Malaria is an international financing

institution that invests the world’s money to save lives. It invests in 150 countries to support the largescale prevention of the three diseases through treatment and care programmes. It channels 82% of theinternational financing for TB.
Group 5 TB medicines: Anti-tuberculosis drugs with unclear efficacy or an unclear role in MDR-TB
treatment as per WHO MDR-TB guidelines (i.e., they are not recommended by WHO for routine use in
MDR-TB patients). Key medicines are clofazimine, linezolid and imipenem/cilastatin.
Low-income country (LIC): The World Bank’s income classification for economies with a gross national

income per capita of US$1,045 or less for the World Bank fiscal year 2015.
Please consult http://data.worldbank.org/about/country-and-lending-groups.
Lower-middle-income country (LMIC): The World Bank’s income classification for economies witha gross national income per capita of more than US$1,045 but less than US$4,125 for the World Bank
fiscal year 2015. Please consult http://data.worldbank.org/about/country-and-lending-groups.
Microscopy: Currently the most commonly used technique to diagnose TB. Two to three sputum samples
are taken from the patient. The sample is stained and later read under the microscope. If TB bacilli arepresent, they are visible in the form of small red rods, while the rest of the sample is blue.
Multidrug-resistant TB (MDR-TB): Patients are said to have multidrug-resistant TB, or MDR-TB, when
they are infected with strains of TB that are resistant to (at least) the two most powerful first-line antibiotics
used to treat TB, namely rifampicin and isoniazid.
Mycobacteria: Types of bacteria of the genus Mycobacterium that cause diseases such as TB andleprosy.
M. tuberculosis: Mycobacterium tuberculosis is a pathogenic bacterial species of the genus

Mycobacterium and the causative agent of most cases of TB, first discovered in 1882 by Robert Koch.
Point-of-Care testing (POC): Diagnosis is carried out as close as possible to the site of patient care.
The driving notion behind point-of-care testing is to have a test be as convenient for the patient as possible
and to give immediate results leading to the prompt initiation of treatment.
Pulmonary TB: Form of TB where M. tuberculosis bacteria infect the lungs.
Second-line drugs: Second-line drugs are used when first-line drugs are no longer effective in curing
a patient. In the case of TB, these drugs are less effective and have many more side-effects than first-line
drugs. This report looks at the sources and prices of second-line anti-TB medicines classified as WHO
Groups 2 (injectable agents), 3 (fluoroquinolones), 4 (oral bacteriostatic second-line agents) and 5 (agentswith unclear efficacy), as well as new drugs like bedaquiline.
Stringent regulatory authority (SRA): An SRA is defined as an International Committee on
Harmonisation (ICH) member country, an ICH observer or any country whose regulatory authority is
associated with an ICH member through a legally binding mutual recognition agreement, or be approvedor subject to a positive opinion under the Canada S.C. 2004, c. 23 (Bill C-9) procedure, or Art. 58 of EU
Regulation (EC9 No. 726/2004) or US FDA tentative approval. Please consult http://www.ich.org.

54

Stop TB Partnership and Médecins Sans Frontières – November 2015

Upper-middle-income country (UMIC): The World Bank’s income classification for economies witha gross national income per capita between US$4,125 and US$12,748 for the World Bank fiscal year
2015. Please consult http://data.worldbank.org/about/country-and-lending-groups.
WHO Prequalification (PQ) Programme: The Prequalification Programme, set up in 2001, isa service provided by WHO to facilitate access to medicines that meet the unified standards of quality,
safety and efficacy for HIV/AIDS, malaria and tuberculosis. Please consult http://apps.who.int/prequal/.
XDR-TB (Extensively drug-resistant TB): Patients are described as suffering from extensively drugresistant TB or XDR-TB when they have MDR-TB and also show resistance to second-line drugs, including atleast one from the class known as fluoroquinolones and one of the injectable drugs.

ABBREVIATIONS
BRICS
CIS
DR-TB
DS-TB
EQA
FDC
FSU
GFATM
HIV

Brazil, Russian Federation, India, China and South Africa
Commonwealth of Independent States
Drug-resistant tuberculosis
Drug-sensitive tuberculosis
External quality assessment
Fixed-dose combination
Former Soviet Union
Global Fund to Fight AIDS, Tuberculosis and Malaria
Human immunodeficiency virus
IRL
Intermediate Reference Laboratory
LIC
Low-income country
LMIC
Lower-middle-income country
MDR-TB Multidrug-resistant tuberculosis
MIC
Middle-income country
MSF
Médecins Sans Frontières
NGO
Nongovernmental organisation
NMRA National medicines regulatory authority
NRL
National Reference Laboratory
NTP
National Tuberculosis Programme
PPM
Public-Private Mix
STG
Standard treatment guidelines
TB
Tuberculosis
UMIC
Upper-middle-income country
USAID US Agency for International Development
WHA
World Health Assembly
WHO
World Health Organisation
XDR-TB Extensively drug-resistant tuberculosis

Out of Step: TB Policies in 24 Countries55references

56

Stop TB Partnership and Médecins Sans Frontières – November 2015

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treatment of MDR-TB. Int J Tuberc Lung Dis. 2012;16(7):955–60.
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drug-resistant tuberculosis in South Africa. Int J Tuberc Lung Dis. 2015 Feb;19(2):172–8.
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resistant Mycobacterium tuberculosis. Int J Tuberc Lung Dis. 2010;14:427–33.
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50.	Gillini L, Davtyan K, Davtyan H, et al. TB financing in East Europe promotes unnecessary hospital

admissions: The case of Armenia. J Infect Dev Ctries. 2013 Mar 14;7(3):289–92.
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following a switch to earlier anti-retroviral therapy. J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19624.
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therapy. N Engl J Med. 2010;2:697–706.
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associated tuberculosis accessing non-integrated clinical services in a South African township. BMC
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Rwanda. Program and abstracts of the 2008 HIV/AIDS Implementers’ Meeting, Kampala, Uganda;
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and outcomes. Public Health Action. 2015 Mar 21;5(1):36–44.
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use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre
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59.	WHO Prequalification of Medicines Programme (PQP), http://apps.who.int/prequal/60.	Hayrapetyan A, Qayyum S, Hewison C. Armenia: Compassionate use of new drugs. In: Dara

M, Acosta C, editors. Best practices in prevention, control and care for drug resistant tuberculosis.
Copenhagen: World Health Organisation Regional Office for Europe; 2013:10–2(http://www.euro.who.int/__data/assets/pdf_file/0020/216650/Best-practices-in-prevention,
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http://f1000research.com/slides/1000085

Disclaimer: This report does not contain individual opinions of the organisations and is based on
information from key informants. Stop TB Partnership and MSF have made every effort to ensure theaccuracy of the data in this report, but we make no representations or warranties, either expressed or
implied, as to their accuracy, completeness or fitness for a particular purpose.

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Annexes

Out of Step: TB Policies in 24 Countries61

I. DIAGNOSIS
Afghanistan

armenia

belarus

Rapid molecular diagnostics(i.e Xpert MTB/RIF) arerecommended as the initialdiagnostic test for all adults
and children in whom TB is
presumed (i.e., symptomatics
being investigated for TB),
rather than sputum smear
microscopy (SSM) and/or
culture and DST

brazil(subnational)

Rapid molecular diagnostics(i.e., Xpert MTB/RIF) arerecommended as the initialdiagnostic test for adults
and children at risk ofdrug-resistant TB (DR-TB) andHIV-associated TB (high-risk
groups)Rapid molecular diagnostics(i.e Xpert MTB/RIF) arerecommended for alreadydiagnosed TB patients withthe purpose of testing or
screening for identification of
drug resistance
The rapid moleculardiagnostics recommended
by the NTP for the testingalgorithms described inquestions 1, 2 and 3 are
WHO-approved or not
WHO-approved

WHO-approved

IF YES to question 2 or 3:
specify groups of people or
TB patient groups for whom
guidelines recommend Xpert
MTB/RIF

WHO-approved

WHO-approved

WHO-approved

Routine culture, Xpert MTB/
RIF and DST is recommended
for the following groups: failed
Category I or II treatment;
failed anti-TB treatment in theprivate sector; MDR-TB contact;
exposure to an institutionthat has MDR-TB outbreaks
or high MDR-TB prevalence;residence in area with high
MDR-TB prevalence; relapse
and return after default; historyof using anti-TB drugs of pooror unknown quality; comorbid
condition associated withmalabsorption or rapid transit
diarrhea; TB/HIV comorbidities

Every person with TB symptoms
and a smear-negative test result

Diagnosed TB patients for drug
resistance; initial diagnostic test
for adults and children at risk of
DR-TB and HIV-associated TB(high-risk groups)

Re-treatment cases; HIV-positive
people; prisoners; homelesspeople; health professionals;
indigenous populations; failureof first-line treatment; smear
positive in second month oftreatment

All RR-TB cases, to formulatesecond-line treatment

Everyone with TB symptoms
and confirmed TB cases,
either by smear microscopy ormolecular tests, is exposed
to first-line DST (after positive
culture is found); implemented
YES

Done routinely for all patients

All TB cases diagnosed throughXpert MTB/RIF should receive
culture and DST, and mainly all
people with TB symptoms witha smear microscopy diagnosis;
re-treatment cases and vulnerable populations should also besent for culture and DST.

First-line DST (including
at least rifampicin andisoniazid) is recommended
for all rifampicin-resistant(RR)-TB cases and for patients
considered at risk of DR-TB

Specify patient groups
for whom first-line DST is
recommended

Second-line DST (including
at least fluoroquinolones
and second-line injectableagents) is recommended for
all RR-TB, polydrug-resistant(PDR)-TB and MDR-TB cases

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Stop TB Partnership and Médecins Sans Frontières – November 2015

legend

Yes

No

Cambodia

china

drc

georgiaindia

WHO-approved

WHO-approved; not WHOapproved for smear negative(people with TB symptoms)
by Chinese Food and Drug
Administration

WHO-approved

WHO-approved

WHO-approved

People with MDR-TB symptoms:(i) sputum non-converters;(ii) all re-treatment cases; inaddition to(iii) symptomatic contacts ofknown DR-TB cases; and(iv) people living with HIV

For smear-positive cases;
Implemented: YES

Re-treatment cases; positive
controls after months 3 and
5 of first treatment; MDR-TB
contact cases; HIV-positive
cases; people with TB
symptoms; cases with clinicaland chest X-ray suggestive of
TB but with sputum smearnegative

Everyone with TB symptoms,
including adults and children

Paediatric cases; EPTB
samples; people who are
HIV-positive; people with
presumptive DR-TB

Re-treatment cases; sputum
non-converters (among new
smear-positive patients) atmonths 2 or 3; symptomatic
contacts of DR-TB cases;
people co-infected with TB/
HIV

High-risk groups: Category
I treatment failure; no smear
conversion at 2 months;
chronic patients; MDR-TB
contacts; relapse

All RR-TB cases and all primaryculture-positive cases

All groups, whenever culture
is positive.

Rifampicin resistance isconsidered as surrogate for
MDR-TB eligible for second-line
treatment

Out of Step: TB Policies in 24 Countries63

I. DIAGNOSIS (cont’d)Indonesia

kenya

Kyrgyzstan

Mozambique

The rapid moleculardiagnostics recommended
by the NTP for the testingalgorithms described inquestions 1, 2 and 3 are
WHO-approved or not
WHO-approved

WHO-approved

WHO-approved

WHO-approved

WHO-approved

IF YES to question 2 or 3:
specify groups of people or
TB patient groups for whom
guidelines recommend Xpert
MTB/RIF

Presumptive DR-TB cases,
including contacts; people
living with HIV presumptive for
TB; new smear-positive cases(limited scale); smear-negative
cases (limited scale); prisoners(limited scale); children (pilot for
close-contact cases)

MDR-TB Surveillance: all retreatment cases: a) failures b)
relapses c) return after default;
DR-TB contacts; smear-positive
refugees; health care workers
with TB diagnosis; HIV-positive
smear negative; diagnosis of
TB in children; TB screening
for symptomatic patients forand on isoniazid preventive
therapy (IPT)

Re-treatment cases; children;
MDR-TB contacts; severeclinical condition; HIV-positive;
unknown HIV status in high-risk
setting; migrants; prisoners;
ex-prisoners

Re-treatment cases; patientswith MTB+ at 2 months;
elderly HIV patients and otherimmunologically-depressed
patients; diabetics; health staff;
miners; prisoners; in endemic
DR-TB high prevalence areas,pregnant women and children

All RR-TB cases from all groups
in row 5 above

TB patients on re-treatment;
healthcare workers;
symptomatic contacts of DRTB patients; smear-negative
people living with HIV; patients
returning after default (retreatment after default); lack ofsmear conversion at 2 months
while on first-line treatment

All cases with laboratoryconfirmed TB require first-line
DST

People previously treated for
TB; new cases that do notconvert at 2 months; MDR-TB
contacts; people living with
HIV; health workers; prisoners;
miners; pregnant women andchildren; people from endemicareas, etc.

Rapid molecular diagnostics(i.e., Xpert MTB/RIF) arerecommended as the initialdiagnostic test for all adults
and children in whom TB is
presumed (i.e., symptomatics
being investigated for TB),
rather than sputum smear
microscopy (SSM) and/or
culture and DST
Rapid molecular diagnostics(i.e., Xpert MTB/RIF) arerecommended as the initialdiagnostic test for adults
and children at risk ofdrug-resistant TB (DR-TB) andHIV-associated TB (high-risk
groups)Rapid molecular diagnostics(i.e., Xpert MTB/RIF) arerecommended for alreadydiagnosed TB patients withthe purpose of testing or
screening for identification of
drug resistanceFirst-line DST (including
at least rifampicin andisoniazid) is recommended
for all rifampicin-resistant(RR)-TB cases and for patients
considered at risk of DR-TB

Specify patient groups
for whom first-line DST is
recommended

Second-line DST (including
at least fluoroquinolones
and second-line injectableagents) is recommended for
all RR-TB, polydrug-resistant(PDR)-TB and MDR-TB cases

64

Stop TB Partnership and Médecins Sans Frontières – November 2015

legendYes

No

Nigeria

Pakistanpng

Russian Federation

South Africa

WHO-approved

WHO-approved

WHO-approved

WHO-approved

WHO-approved

Evaluation for DR-TB:a) symptomatic contacts of
DR-TB cases; b) failure offirst-line treatment; c) failure
to convert (smear-positive tosmear-negative) after repeat
smear microscopy follow-up
examination at the end ofmonth 3 of first-line treatment;d) all patients who have beenpreviously treated for TB

All presumptive/diagnosed TB
cases with a history of previous
treatment; presumptive TB
cases under 15 years old;people who are HIV-positive,
immunecompromised or
hospitalised; healthcare
workers; presumptive EPTB
cases; and presumptive TB
cases from whom specimen
is obtained through someprocedures, e.g. bronchiallavagePeople who have beenpreviously treated; nonconverters (at the end of 2
months); HIV-positive people;
symptomatic contacts ofknown MDR-TB cases; healthfacility staff

For all (adult and children) inwhom TB is presumed

TB and DR-TB contacts;
non-contact, symptomatic
individuals; re-treatment after
relapse, failure or default

RR-TB patients following Xpert
MTB/RIF test

All detected with RR-TB on
Xpert MTB/RIF test; others at
high risk of drug resistancetested with rifampicinsusceptible test on Xpert MTB/RIFAll RR-TB cases

All TB patients

All new patients

For all RR-TB patients

Out of Step: TB Policies in 24 Countries65

I. DIAGNOSIS (cont’d)Swaziland

Tajikistan

Rapid molecular diagnostics(i.e., Xpert MTB/RIF) arerecommended as the initialdiagnostic test for all adults
and children in whom TB is
presumed (i.e., symptomatics
being investigated for TB),
rather than sputum smear
microscopy (SSM) and/or
culture and DST

ukraine(subnational)

Rapid molecular diagnostics(i.e., Xpert MTB/RIF) arerecommended as the initialdiagnostic test for adults andchildren at risk of drug-resistant
TB (DR-TB) and HIV-associatedTB (high-risk groups)
Rapid molecular diagnostics(i.e., Xpert MTB/RIF) arerecommended for alreadydiagnosed TB patients with the
purpose of testing or screening
for identification of drug
resistance
The rapid moleculardiagnostics recommended
by the NTP for the testingalgorithms described inquestions 1, 2 and 3 are
WHO-approved or not WHOapproved

IF YES to question 2 or 3:
specify groups of people or
TB patient groups for whom
guidelines recommend Xpert
MTB/RIF

WHO-approved

WHO-approved

WHO-approved

Xpert MTB/RIF test isrecommended for everyone
with TB symptoms, including
those in congregate settings(i.e., miners, ex-miners, children)

TB cases enrolled in treatment as Category I, II and III, smearpositive and/or with progressive clinical and X-ray course after
intensive phase; re-treatment cases without testing for RR-TB;
MDR-TB contacts; individuals from DR-TB risk groups (e.g.,treatment defaulters, contacts of a patient deceased due to
TB, etc.); penitentiary detainees with symptoms of TB; patientswith progressive TB; people with TB symptoms and a history of
non-standard treatment; HIV-positive individuals; TB diagnosis,
without data on drug resistance; everyone with TB symptoms;
healthcare workers and penitentiary facility staff who have TB
symptoms; migrant workers with TB symptoms; pregnant womenand postpartum women with TB symptoms; sputum smearnegative cases without positive clinical and X-ray course after
treatment with broad spectrum antibiotics

As initial test for all TB patients
who start TB treatment; for TB
patients who are smear-positive
after 90 doses

First-line DST (including for atleast rifampicin and isoniazid)is recommended for all
rifampicin-resistant (RR-TB) cases
and for patients considered atrisk of DR-TB

Specify patient groups
for whom first-line DST is
recommended

First-line DST is recommended for all RR-TB cases and patients
considered at risk of DR-TB

Positive Xpert MTB/RIF test
resultSecond-line DST (including
at least fluoroquinolones andsecond-line injectable agents)
is recommended for all RR-TB,
polydrug-resistant (PDR)-TB and
MDR-TB cases

66

Stop TB Partnership and Médecins Sans Frontières – November 2015

All people with TB symptoms; relapse; treatment failure;
From Koninklijke Nederlandse Centrale Vereniging (KNCV)[Royal Netherlands Association for Tuberculosis Control]:According to the National Guidelines on DR-TB, first-line DST
is recommended for all detected TB patients; second-line DST(including at least fluoroquinolones and second-line injectableagents) is recommended for all RR-TB, polydrug-resistant (PDR)TB and MDR-TB cases

Because of the high proportion of resistant strains among new
and recurrent cases in Tajikistan, it recommended a survey ofall MDR-TB cases. DST for first-line anti-TB drugs should be partof the diagnostic minimum. Moreover, at least it recommended
a survey of all MDR-TB strains for resistance to second-line anti-TB
drugs, using the recommended hierarchy of DST

New cases (Category I and
III) and Category II cases(previously treated cases andrelapses)legendUzbekistan

Yes

No

viet namZimbabwe

WHO-approved

WHO-approved

People co-infected with TB/HIV

See comments box

All HIV-positive patients with
TB symptoms; all HIV-negative
patients with TB symptoms
and risk factors for MDR-TB; allHIV-negative patients with TB
symptoms and who are sputum
negative on microscopy; children
with presumptive TB; allre-treatment patients; healthcare
workers with TB symptoms;
presumptive TB cases with ahistory of travel to countries witha high DR-TB burden; contacts of
DR-TB patients

Karakalpakstan: All TB patients diagnosed with
rapid molecular method who have a positive
culture;At national level: All patients with positive smear,
positive Mycobacterium tuberculosis tine test
(MBTT), rifampicin–resistant and rifampicinsensitive result by Xpert MTB/RIF, and those withpositive results by Hain ver. 2

See above, however inpractice DST is infrequent due
to inconvenience of travelling
to DST, time requirements anduser fees

Patients with no resistance tofirst-line TB drugs; people at risk
for DR-TB with positive Xpert
MTB/RIF test, but no rifampicin
resistance: perform culture andfollow first-line DST in DR-TB
guidelines page 15

May not be widely implemented(subnational)(subnational)

WHO-approved

Out of Step: TB Policies in 24 Countries

67

68

Stop TB Partnership and Médecins Sans Frontières – November 2015
BelarusNo

Not known

Cambodia

Yes

China

legendAre the increased doses of first-line
drugs(as per WHO 2010 rapid
advice) recommended?

Are the treatment guidelines forchildren in line with the WHO 2014
guidance?

Are fixed-dose combinations (FDCs)
recommended as the preferred
formulation?

Is intermittent therapy recommended?

Is Category II (re-treatment regimen
with streptomycin) recommended?

II. DS-TB Treatment Regimens
Zimbabwe
Viet Nam

Uzbekistan

UkraineTajikistan

SwazilandSouth Africa

Russian Federation

PNG

Pakistan

Nigeria

Mozambique

Kyrgyzstan

Kenya

Indonesia

India

Georgia

DRC

BrazilArmenia

Afghanistan

III. DR-TB Treatment Regimens
afghanistan
National treatment guidelines
reflect WHO drug-resistanttreatment guidelines,
including Group 5 drugs

If NO, what drugs are notincluded and/or what is
missing from the national
guidance?

armenia

belarusbrazil;Group 5 drugs are notrecommended
8 (Am-Lfx-Eto-Cys-Z-VB6)/
16 (Lfx-Eto-Cys-Z-VB6)- For cases with frequent useof fluroquinolone, paraaminosalicylic acid is added.
- For some cases withreaction or resistance toaminoglycosides, amikacin is
replaced with capreomycin

kanamycin, cycloserine,
prothionamide, thioacetazone,
clarithromycin

There are guidelines on theuse of the bedaquiline
In process

There are guidelines on theuse of delamanid
Before registration, newand repurposed drugs
are available throughcompassionate use
or expanded accessprogrammes or any otherlegal mechanisms. If
YES, which one of thesemechanisms is in place?

CU mechanism

All Group 2 drugs are on thenational Essential Medicines
List (EML)If NO, which drugs are notincluded?

kanamycin

All Group 3 drugs are on thenational EML

levofloxacin, moxifloxacin,
ciprofloxacin

If NO, which drugs are notincluded?

All Group 4 drugs are on thenational EML

If NO, which drugs are notincluded?

cycloserine, ethionamide,
prothionamide

All drugs except ethionamide,para-aminosalicylic acid andcycloserine

imipenem, cilastatin andclarithromycin are in the
EML; clofazimine, linezolid,
amoxicillin/clavulanate
and thioacetazone are notmentioned in the EMLAll Group 5 drugs are on thenational EML

If NO, which drugs are notincluded?

70

cycloserine, prothionamide

amoxicillin/clavulanate

Stop TB Partnership and Médecins Sans Frontières – November 2015

clofazimine, linezolid,
bedaquiline

amoxicillin/clavulanate,thioacetazone, imipenem/
cilastatin

legendcambodia

china

drc

Yes

No

Not applicablegeorgia

No valid Georgian National EML exists - it is in the process of
being finalised and approved; meanwhile, WHO EML is used
as a reference
No valid Georgian National EML exists - it is in the process of
being finalised and approved; meanwhile, WHO EML is used
as a reference
No valid Georgian National EML exists - it is in the process of
being finalised and approved; meanwhile, WHO EML is used
as a reference
No valid Georgian National EML exists - it is in the process of
being finalised and approved; meanwhile, WHO EML is used
as a reference
No valid Georgian National EML exists - it is in the process of
being finalised and approved; meanwhile, WHO EML is used
as a reference

terizidone

No valid Georgian National EML exists - it is in the process of
being finalised and approved; meanwhile, WHO EML is used
as a reference

No valid Georgian National EML exists - it is in the process of
being finalised and approved; meanwhile, WHO EML is used
as a reference

clofazimine, linexolid,
thioacetazone, imipenem/
cilastatinlinezolid

No valid Georgian National EML exists - it is in the process of
being finalised and approved; meanwhile, WHO EML is used
as a reference

Out of Step: TB Policies in 24 Countries

71III. DR-TB Treatment Regimens (cont’d)india

indonesia

kenya

Kyrgyzstan

National treatment guidelines
reflect WHO drug-resistanttreatment guidelines,
including Group 5 drugs
If NO, what drugs are notincluded and/or what is
missing from the national
guidance?

bedaquiline, thioacetazone,
imipenem/cilastatin,
clarithromycin

There are guidelines on theuse of the bedaquiline
There are guidelines on theuse of delamanid
Before registration, newand repurposed drugs
are available throughcompassionate use
or expanded accessprogrammes or any
other legal mechanisms.
If YES, which one of thesemechanisms is in place?
All Group 2 drugs are on thenational Essential Medicines
List (EML)If NO, which drugs are notincluded?

kanamycin, capreomycin

capreomycin

capreomycin (capreomycin
missing from the EML 2010
but is available in the market
for use)All Group 3 drugs are on thenational EML

If NO, which drugs are notincluded?

national drug registry does notinclude kanamycin, mikacin, or
capreomycin as second-line TB
drugs, but as broad-spectrum
antibiotics

but they are being used widely

levofloxacin, gatifloxacin,moxifloxacin

levofloxacin, gatifloxacin,moxifloxacin

ofloxacin, levofloxacin are
included as bovine serum
albumin (BSA)All Group 4 drugs are on thenational EML

If NO, which drugs are notincluded?

ethionamide, prothionamide,
cycloserine,
para-aminosalicylic acid,terizidone

All Group 4 drugs

ethionamide, protionamide,
cycloserine, terizidone,para-aminosalicylic acidpara-aminosalicylic acid,
cycloserine and ethionamide
are included; prothionamide
and terizidone are not included

linezolid, thioacetazone,
imipenem/cilastatinlinezolid, thioacetazone,
bedaquiline

clofazimine, linezolid,
thioacetazone, imipenem/
cilastatin

All (amoxicillin/clavulanic acidincluded as BSA)All Group 5 drugs are on thenational EML
If NO, which drugs are notincluded?

72

Stop TB Partnership and Médecins Sans Frontières – November 2015

legendMozambique

Nigeria

Pakistan

Yes

PNG

No

Not applicable

Russian Federation(Under revision)
clofazimine is not registered,but it can be used in lifethreatening conditions withspecial permission of MoH

bedaquiline, linezolid,
imipenem, meropenem andclofazimine

compassionate use

EML is being updated to cover
all DR-TB medicines
kanamycin, amikacin andcapreomycin

ofloxacinAll. levofloxacin, moxifloxacin,
gatifloxacin

ethionamide/prothionamide,
cycloserine and paraaminosalicylic acid areavailable in local market

terizidone

All: ethionamide,
prothionamide, cycloserine,
terizidone, para-aminosalicylicacid, para-aminosalicylic
sodiumterizidone

Not known

bedaquiline, delamanid,
imipenem, cilastatin,
thiacetazone, linezolid

linezolid, clofazimine,
imipenem, meropenem

bedaquiline, delamanid,
imipenem, etc.

clofazimine

Out of Step: TB Policies in 24 Countries73III. DR-TB Treatment Regimens (cont’d)South Africa

Swaziland

Tajikistan

National treatment guidelines
reflect WHO drug-resistanttreatment guidelines,
including Group 5 drugs
Although available, training
and wider availability will be
expanded from Sept 2015
onwards; regulation issues arealso not clear

If NO, what drugs are notincluded and/or what is
missing from the national
guidance?
There are guidelines on theuse of the bedaquiline
There are guidelines on theuse of delamanid
Before registration, newand repurposed drugs
are available throughcompassionate use
or expanded accessprogrammes or any otherlegal mechanisms. If
YES, which one of thesemechanisms is in place?
All Group 2 drugs are on thenational Essential Medicines
List (EML)If NO, which drugs are notincluded?

capreomycin

All Group 3 drugs are on thenational EML

If NO, which drugs are notincluded?

ofloxacin

All Group 4 drugs are on thenational EML

If NO, which drugs are notincluded?
All Group 5 drugs are on thenational EML
If NO, which drugs are notincluded?

74

clofazimine, linezolid,
amoxicillin/clavulanate,thioacetazone, imipenem/
cilastatin, clarithromycin

Stop TB Partnership and Médecins Sans Frontières – November 2015

Not knownlinezolid and clofazimine

UkrainelegendUzbekistan

Yes

Viet NamNo

Not applicable

Zimbabweterizidone (Group 4),
thioacetazone (Group 5)

Pilot in region of
Karakalpakstan

Not known

Not known

Article 75 in the Medicines
and Allied Substances Control
Act Chapter 15:03

kanamycin, capreomycin,
amikacinmoxifloxacin

All: levofloxacin, moxifloxacin,
ofloxacin

prothionamide, terizidone

terizidone, prothionamide

para-aminosalicylic acidlinezolid, thioacetazone
bedaquiline, clofazimine(registered as leprosy drugs)
imipenem, linezolid, delamanid

bedaquiline, delamanid,
imipenem, cilastatin,
thiacetazone, linezolid

linezolid, thioacetazone,
imipenem/cilastatin,
clarithromycin

Out of Step: TB Policies in 24 Countries75IV. MODELS OF CARE
Afghanistan

Armenia

Belarus

Drug-susceptible TB (DS-TB)
treatment can be started at
the primary health care level
If NO: At what level is DS-TB
treatment started?

Not known

DR-TB treatment can bestarted and dispensed fromthe district level
If NO: At what level is
DR-TB treatment started anddispensed?

Only in Afghan-Japan
Communicable Diseases
Hospital located in capital of
the country

Nurses or health workers
other than doctors can start
adults on DS-TB treatment
Routine hospitalisation is not
required for the intensive
phase of DS-TB
If NO: What time period isrecommended?

Routine hospitalisation is not
required for the intensive
phase of DR-TB

Until smear microscopy conversion to negative is achieved; twoconsecutive negative smears a minimum of 2 weeks apart

Required

If NO: What time period isrecommended?

Not known

TB treatment cannot be
started in health facilities
providing HIV careCannot be started

HIV treatment cannot be
started in health facilities
providing TB care

HIV treatment can be started in
facilities providing TB care

Same health worker provides
TB and HIV treatment at the
primary health care (PHC)
level
Is antiretroviral therapy (ART)started for all TB patients
irrespective of CD4 count?

76

Stop TB Partnership and Médecins Sans Frontières – November 2015

2 months

There is no distinction between hospitalisation for the intensive
and continuous phases; it is more related to the bacteriologicalstatus of the patient (i.e., smear positive or smear negative)
Until smear microscopy conversion to negative is achieved;
two consecutive negative smears a minimum of 2 weeks apart.
According to the protocol (D10), XDR-TB cases have to stay
until the end of the intensive phase in the National Tuberculosis
Control Center (NTC), but it is not a practical scenario, evenunder the CU programme (the guideline is not updated)

According to the protocol HIV treatment can be initiated andcontinued in TB structures (in practice HIV specialist attends TB
hospital for patient assessment and treatment initiation)

3-4 months

legend

BrazilCambodia

China

Yes

DRC

No

Not applicable

Georgia

For smear-positive TB cases
For smear-negative andextra-pulmonary: generally at
hospitals

In Brazil, DR-TB and special
scheme cases are dealt insecondary and tertiary levels

They are started at one ofabout nine active MDR-TB
treatment sites

County level

TB treatment starts at central
or regional TB facility level(in-patient or out-patient, as
required)

City level

For smear-positive TB cases

Hospitalisation time is until
smear conversion and/or
clinical improvement

Except for a few initial days
to check for tolerance to thedrugs

None; cases are hospitalised
according to other criteria

The first two months of theintensive phase

Hospitalisation time is until
smear conversion and/or
clinical improvement

It canOften

Out of Step: TB Policies in 24 Countries77IV. MODELS OF CARE (cont’d)
IndiaIndonesia

Kenya

Kyrgyzstan

Drug-susceptible TB (DS-TB)
treatment can be started at
the primary health care level
If NO: At what level is DS-TB
treatment started?

At hospital and PHC

DR-TB treatment can bestarted and dispensed fromthe district level

If NO: At what level is
DR-TB treatment started anddispensed?

In regional TB hospital

Nurses or health workers
other than doctors can start
adults on DS-TB treatment
Routine hospitalisation is not
required for the intensive
phase of DS-TB
Until smear conversion

If NO: What time period isrecommended?
Routine hospitalisation is not
required for the intensive
phase of DR-TB

It is required

If NO: What time period isrecommended?

Approx. 15 days

Not recommended

Not known

Not known

TB treatment cannot be
started in health facilities
providing HIV care

HIV treatment cannot be
started in health facilities
providing TB care

Same health worker provides
TB and HIV treatment at the
primary health care (PHC)
level
Is antiretroviral therapy (ART)started for all TB patients
irrespective of CD4 count?

78

Stop TB Partnership and Médecins Sans Frontières – November 2015

HIV treatment can be started
at TB centre with visit of HIV
specialists

Nurses do bothlegendMozambique

Nigeria

Pakistan

Yes

PNG

No

Not applicable

Russian Federation

In TB department, after
decision of central region TB
medical committee

But only as an exclusion
decision of TB committee
Treatment is started only at
Programmatic Managementof Drug-resistant Tuberculosis(PMDT) sites, where treatment
is dispensed on monthly
basis and patients are treatedthrough ambulatory care

Secondary level facility
province hospital

Mostly in Central Regional TB
department

Only TB doctors

But it depends on individual
situation of the patient anddecision of TB committee
Until smear conversion

Depends on individual
situation of the patient anddecision of TB committee
Not yet standardisedcountry-wide

Until culture conversion

Not yet, but discussed as partof the TB/HIV collaboration

Not yet in TB facilities, but isbeing discussed as part of
TB/HIV collaboration

No referral is made to HIV
sites

For all patients that are HIVpositive

HIV treatment can bestarted in health facilities
providing TB care after getting
recommendation from HIV
specialist

But TB doctor has tocoordinate all ART with HIV
specialist

Only given to patients with a
CD4 count of <400

Out of Step: TB Policies in 24 Countries

79IV. MODELS OF CARE (cont’d)South Africa

Swaziland

Tajikistan

UkraineDrug-susceptible TB (DS-TB)
treatment can be started at
the primary health care level
DS-TB treatment starts at the
special TB facility (TB clinic, TB
dispensary, TB cabinets)

If NO: At what level is DS-TB
treatment started?

Only after confirmation ofdiagnosis by the TB Council(there are national and oblast
level TB councils). Second-line
TB drugs are available in all
districts

DR-TB treatment can bestarted and dispensed fromthe district level

If 'district-level' is equivalent tooblast/province-level in Ukraine
If 'district-level' is equivalent torayon-level (a district within an
oblast) in Ukraine
DR-TB treatment can be started
at specialised TB hospitals(oblast TB dispensaries)

If NO: At what level is
DR-TB treatment started anddispensed?
Nurses or health workers
other than doctors can start
adults on DS-TB treatment

Not required: certain criteria
for hospitalisation of DR-TB
are identified in the National
TB Guidelines; for the rest ofcases, ambulatory treatment isprovidedRoutine hospitalisation is not
required for the intensive
phase of DS-TB

If NO: What time period isrecommended?

Not required: certain criteria
for hospitalisation of MDR-TB
are identified in the National
MDR-TB Guidelines; for the restof cases, ambulatory treatment
is provided

Routine hospitalisation is not
required for the intensive
phase of DR-TB

If NO: What time period isrecommended?

For MDR-TB patients:
hospitalisation of patients
until they are confirmed to
be noninfectious; for XDR-TB
patients: the duration of thestay in hospital may vary frompatient to patient dependingon the clinical response totreatment; on average it is six
monthsNot known

TB treatment cannot be
started in health facilities
providing HIV care
HIV treatment cannot be
started in health facilities
providing TB care

Not known

Same health worker provides
TB and HIV treatment at the
primary health care (PHC)
level

Not known

Is antiretroviral therapy (ART)started for all TB patients
irrespective of CD4 count?

80

Stop TB Partnership and Médecins Sans Frontières – November 2015

Not known

If both diagnoses confirmed

Not requiredlegendUzbekistan

Yes

Viet NamNo

Not applicable

Zimbabwe

District/rayon level

Only at provincial sites and in
the process of decentralisation
to district level

State level/oblast level2 months

As per ProgramaticManagement of Drug-resistant
Tuberculosis (PMDT) guidelines
in Viet Nam, MDR-TB treatment
begins with an inpatient
treatment phase for about 15
days; the patient is discharged
when stable and having met
other PMDT requirements

It can be started but only by
HIV specialists

It can be started

Out of Step: TB Policies in 24 Countries

81V. DRUG REGULATORY ENVIRONMENT
Afghanistan

Armenia

All drugs used for treatment of
MDR-TB (standard treatment)

isoniazid, pyrazinamide,ethambutol and rifabutin are
not registered; rifampicin andtubertam are registered

BelarusBrazilNot known

Non-registered drugs:
Group 2: kanamycin andcapreomycin; Group 4: paraaminosalicylic acid, cycloserine
and prothionamide; Group 5:
clofazimine and thioacetazone

There is a process foraccelerated registration of
DR-TB drugs, including new
TB drugs
What drugs are registeredin the country? Please state
which drugs in a group are
NOT registered

All Group 1 drugs

isoniazide, pyrazinamide,ethambutol tablets and rifabutin
are not registered

All Group 2 drugs
All Group 3 drugs
All Group 4 drugs

ethionamide, paraaminosalicylic acid andcycloserine

All Group 5 drugs

amoxicillin/clavulanate andclarithromycin

clofazimine and bedaquiline
are not registered

A prescription is required
to purchase/procure TB
medicines (not over thecounter)If they are all mentioned drugs
available in the pharmacy(some of them are available)

If NO: Which drugs can bebought without prescription?

NTP procures quality-assured
TB drugs according tostringent regulatory authority
or WHO standards

82

First-line TB drugs are only
available from the publichealth service and can not bepurchased; some secondline drugs are available atdrugstores, but only with adoctor's prescription. The
Unified Health System in Brazil(SUS) provides all secondline drugs to TB patients freeof charge; for procurement,
we also do not need aprescription, except for the
drugs that WHO requires

Stop TB Partnership Global
Drug Facility

Stop TB Partnership and Médecins Sans Frontières – November 2015

Only for first-line drugs

legend

Cambodia

The programme can havespecial waivers even if notregisteredChina

Not known

Yes

No

Not applicable

DRC

Georgia

India

Not known

Most of the TB drugs areregistered in the country, but
sources are not WHOprequalified.
http://pharmacy.moh.gov.ge/
Pages/Products.aspx

All drugs are legally available

Not known
Except isoniazid and rifabutin

Not known
Not known
Not known
Only cycloserine registered
Not known

Not known
All group 5 drugs areregistered except new drugs(bedaquiline and delamanid)

This is nearly zero; it is veryrare to buy anti-TB drugs overthe counter

Starting from September 2014

Not implemented widelyThis is very rare, basedon Global Drug Facility
convenience-sampling surveys

None of the TB drugs can bepurchased without prescription

Not known

Not known

Two sources: Global Drug
Facility supply & Governmentof India procurement; all drugs
procured with internal QualityAssurance system extended tostorage and distribution points

Out of Step: TB Policies in 24 Countries

83V. DRUG REGULATORY ENVIRONMENT (cont’d)Indonesia

Kenya

There is a process foraccelerated registration of
DR-TB drugs, including new
TB drugs
What drugs registered incountry? Please state whichdrugs in a group are NOT
registered

All Group 3 drugs

All Group 4 drugs

All Group 5 drugs

Mozambique

For all WHO-prequalified
drugs
Not known

Not known

All Group 1 drugs

All Group 2 drugs

Kyrgyzstan

None of the drugs in Groups
2-5 are registered for use
with TB

Not known

Not known

Not known

capreomycin

Not known

All registered in the country

gatifloxacin

No Group 4 drugs areregisteredprotionamide, terizidone
para-aminosalicylic acidNot knownlinezolid, thioacetazone,
bedaquiline

clofazimine, bedaquiline

Not known

amikacin, capreomicin

moxifloxacin, gatifloxacin

etionamide, protionamide,
cycloserine, terizidone, paraaminosalicylic acidbedaquiline, delamanid

A prescription is required
to purchase/procure TB
medicines (not over thecounter)84

If NO: Which drugs can bebought without prescription?

You can buy any drug over thecounter without a prescription

NTP procures quality-assured
TB drugs according tostringent regulatory authority
or WHO standards

Through Global Drug Facility
mainly for second-line andthird-line drugs

Stop TB Partnership and Médecins Sans Frontières – November 2015

Global Drug Facility

legendNigeria

Not known

Pakistan

Not known

Yes

PNG

Russian Federation

National Medicines Policy

bedaquiline is alreadyregistered

All drugs in current treatment
regimen are registered; newdrugs are not registeredclofazimine is not registeredNo

Not applicable

South Africa

delamanid, clofazimine,linezolid

rifambutin
Not known

kanamycin, amikacin,
capreomycin

Not known

levofloxacin, moxifloxacin,
gatifloxacin

ethionamide, prothionamide,
cycloserine, terizidone,para-aminosalicylic acid, paraaminosalicylic sodium

bedaquiline, delamanid,
imipenem, cilastatin,
thiacetazone, linezolid

terizidone

linezolid, clofazimine,
imipenem, meropenem

Not known

clofazimine is not registered

Not known

Prescription is as per National
TB Manual based on theweight of the patient guideline

None

Not known

Most drugs, including all TB
drugs and other antibiotics,
can be bought without aprescription; only certain
drugs, such as psychotropic
drugs and strong pain killers,
require prescriptions

Among all TB drugs producedin the Russian Federation, only
cycloserine is approved by
WHO standards

Not known

Not known

Out of Step: TB Policies in 24 Countries

85V. DRUG REGULATORY ENVIRONMENT (cont’d)Swaziland

Tajikistan

UkraineUzbekistan

Not known

For rifampicin/isoniazid
150/150 and 150/75 (Lupin),
the registration will expire in
2016; for the rest, registration
expired in 2015: ethambutol
100 (Fatol), isoniazid 100(McLeods), pyrazinamide 150(Lupin), rifampicin/isoniazid
60/30 and 60/60 (McLeods)
and rifampicin/isoniazid/
pyrazinamide 60/30/150(McLeods)

Not known

Not known

There is a process foraccelerated registration of
DR-TB drugs, including new
TB drugs

What drugs registered incountry? Please state whichdrugs in a group are NOT
registered.

All Group 1 drugs

Not known

All Group 2 drugs

Not known

All Group 3 drugs

Not known

All Group 4 drugs

Not known

All Group 5 drugs

Not known

A prescription is required
to purchase/procure TB
medicines (not over thecounter)

But not always followed

If NO: Which drugs can bebought without prescription?

NTP procures quality-assured
TB drugs according tostringent regulatory authority
or WHO standards

86

Not known

Since 2005, NTP procures TB
drugs through the Global Drug
Facility using GFATM funds

Stop TB Partnership and Médecins Sans Frontières – November 2015

First-line TB drugs; secondline TB drugs; linezolid andmoxifloxacin also possible

legendYes

Viet NamNo

Not applicable

Zimbabwe

The TB drugs used by the
NTP are included in theessential drug list of Viet Nam
and TB drugs are exempt
from registration and importlicensing. Furthermore, national
programmes (including theNTP) are not required toregister the drugs they use

capreomycin not registeredmoxifloxacin and ofloxacin are
not registeredpara-aminosalicylic acid,
cycloserine, terizidone,
ethionamide andprothionamide are notregistered

Not known

clofazimine, linezolid,
thioacetazone, imipenem/
cilastatin, are not registered

Only specific NTP-used anti-TB
drugs (brands) restricted frompurchase over the counterAll excluding NTP-specificanti-TB drugs

GFATM will supply first-line
drugs in 2016; MOH will startpurchasing first-line drugs at
end of 2016 for use in 2017

TB drugs are mainly purchased
through the GDF; theMedicines Control Authorityof Zimbabwe conducts ananalysis of all TB medicinesprior to in-country distribution

Out of Step: TB Policies in 24 Countries

87GENEXpert placement summary
Provide total number of GeneXpert devices implemented in the
country (in the public sector). Specify number of devices within eachcategory: 2-module, 4-module, 8-module, 16-module, 32-module,etc.

Please specify the number of GeneXpert devices implemented at thedifferent levels of the laboratory network

Afghanistan

2 devices in total: 1 8-module device at the National Reference
Laboratory (NRL) and 1 at the French Medical Institute for Children[private sector] (module information unknown)

Reference laboratory: 1
French Medical Institute for Children [private sector]: 1

Armenia

4 devices available; Under new GFATM grant, the National TB
programme will receive 13 new Xpert MTB/RIF devices (3 4-module
devices and 10 2-module devices)

Reference laboratory: 2
Specialized hospitals: 1
District/subdistrict level: 1
Microscopy centre level: 0
Community outreach or mobile clinics: 0

15 devices in total; includes 2-module and 4-module devices

Reference laboratory: 1
Specialized hospitals: 0
District/regional level: 6
Subdistrict level: 7
Microscopy centre level: 0
Community outreach or mobile clinics: 0
Penitentiary: 1

175 machines of 4 modules

Reference laboratory: 5
Specialized hospitals: 26
District/subdistrict level: 17
Microscopy centre level: 126
Community outreach or mobile clinics: 1

Not known

Not known

Not known

Reference laboratory: 372 + 160; Specialized hospitals: 340 + 16

41 devices nationwide; 25 2-module devices and 16 4-module
devices

Reference laboratory: 1
Specialized hospitals: 0
District/subdistrict level: 11
Microscopy centre level: 29
Community outreach or mobile clinics: 0

16 devices in total, all are 4-module devices

Reference laboratory: 4
Specialized hospitals: 0
District level/subdistrict level: n/a
Microscopy centre level: 10
Community outreach or mobile clinics: 0
Prison microscopy lab: 2

89 by end 2014
+30 were supposed to be put in place in March 2015
all are 4-module devices

Plans to cover all districts by end 2017 (950 devices)

43 devices in total; all are 4-module devices

Reference laboratory: 4
Specialized hospitals: 39
District/subdistrict level: n/a
microscopy centre level: n/aCommunity outreach or mobile clinics: n/a

73 devices in total; 2 2-module devices; 70 4-module devices; 116-module device

Reference laboratory: 1
Specialized hospitals: 3
District/subdistrict level: 69

Kyrgyzstan

8 devices in total; all are 4-module devices

Prison sector: 1
Kara-Suu district Hospital: 1
FMC Issykata: 1
Sokuluk FMC: 1
CTBD Bishkek: 1
Batken oblast TB centre: 1
Talas oblast TB centre: 1
Osh city TB centre: 1

Mozambique

36 devices in total; all are 4-module devices

Reference laboratory: 3
Specialized hospitals: 2
District/subdistrict level: 31

BelarusBrazilCambodia
China
Democratic
Republic of Congo

Georgia

India
Indonesia
Kenya

88

Stop TB Partnership and Médecins Sans Frontières – November 2015

Provide total number of GeneXpert devices implemented in the
country (in the public sector). Specify number of devices within eachcategory: 2-module, 4-module, 8-module, 16-module, 32-module,etc.

Please specify the number of GeneXpert devices implemented at thedifferent levels of the laboratory network

Nigeria

131 devices in total; all 4-module devices

Reference laboratories: 6 (National Reference Laboratory: 2; Zonal
Reference Laboratory: 4)

Pakistan

42 devices in total as of June 2015; 1 16-module device and therest are 4-module devices

National reference laboratory: 1
Provincial reference laboratories: 5
Programmatic Management of Drug-resistant TB (PMDT) treatmentsites: 18
District/subdistrict level: 18

PAPUA NEW GUINEA

21 devices in total; all are 4-module devices

Reference laboratory and district level hospital

Russian fedration

73 devices implemented in the country (in the public
sector). No data about number of modules.

Not known

South Africa

1294 devices in 207 sites (as of 2014)

Not known

Swaziland

38 devices in total as of Sept 2015; all are 4-module devices,
except 1 16-module device in the Mbabane Government Hospital
Laboratory

District Hospitals: 9
Health Centres (subdistrict): 5
Clinics: 3
NGOs: 6
Private: 5Some of the facilities have 2 units of 4 modules

Tajikistan

15 devices in total; 1 2-module device at the National Reference
Laboratory and the rest (14) are 4-module devices

National reference laboratory: 1
National TB center microscopy laboratory: 2
Regional TB centers: 3
Paediatric TB hospital: 1
District level microscopy center level: 8

Ukraine30 devices in total; includes 28 4-module devices and 1 2-module
device;In addition to this, GFATM purchased 10 more 4-module devices;
In the prison sector: 8 4-module devices; 10 4-module devices;
All devices procured under the GFATM are in the process of being
installed;

National Reference Laboratory:
1 3rd Level lab: 29 (28 4-module devices and 1 1-module device
3rd level prison labs: 8 (a 4-module device in each lab)
2nd level labs: 3 (2 4-module devices and 1 1-module device
1st lab level (AIDS centre): 7 (a 4-module device in each lab)
In the process of installing 3 4-module devices.

Uzbekistan

Viet namZimbabwe

25 devices in total
Karakalpakstan: 6 (plus 2 in the pipeline)
Rest of Uzbekistan: 19

Karakalpakstan:
Central level: 5; District level: 1
By the end of 2015: Central level: 5; District level: 3
Tashkent:
National AIDS centres: 2
National Reference Laboratory: 2
Oblast (state level) and Rayon level: 15

32 devices in total, of which 30 are for public use as per the
National Strategic Plan drafted in mid-2014. However, a total of
46 GeneXpert devices are mentioned as recently as December
2014 (according to the 20.20130419 WHO PMDT Monitoring
Mission Report, page 22: In 2012, 7 sites; in 2013, 17 sites; and2014-2015, 43 sites. A total of 43 GeneXpert machines are to beinstalled between 2013 and 2015).

Estimate based on 2013 GLC report.
Reference laboratory: 6 (National Lung Hospital, Pham Ngoc Thach
Hospital)Specialized hospitals: 37 (Central TB hospitals K71 & K74, Hanoi
Lung Hospital, other provincial lung disease and TB hospitals and
MDR-TB treatment sites, etc.)
District/subdistrict level: 6 (3 in each district treatment unit in Hanoi
and Ho Chi Minh City)Microscopy centre level: 0 (likely included
above)
Community outreach or mobile clinics: 0(Page 22, 20.20130419 WHO PMDT Monitoring Mission report)

96 devices in total, including 93 4-module devices and 3
16-module devices

Reference laboratory: 2
Specialized hospitals: 3
Provincial Hospitals (including 2 major city hospitals): 10
District/subdistrict level: 71
Microscopy centre level: 8
Community outreach or mobile clinics: 2

Out of Step: TB Policies in 24 Countries

89

We would like to thank the MSF field teams, Stop TB Partnership members, and NTPs
in the 24 countries who have provided us with the information on which this survey is based.
We would also like to acknowledge the contribution of Dr. Daisy Lekharu, lead analyst
and writer; Greg Paton, project manager and writer, and Sahu Suvanand, technical expert.
Front Cover Photo:© Helmut Wachter/13photo
Back Cover Photos:© Sami Siva
© Sven Torfinn© Wendy Marijnissen© Matthew Smeal/MSF

Design: Missing Element Prague
Disclaimer: Clinical decisions should not be made based on this document. Stop TB Partnershipand MSF have made every effort to ensure the accuracy of the data in this report, but we makeno representations or warranties, either expressed or implied, as to their accuracy, completenessor fitness for a particular purpose.
Copyright © 2015
All rights reserved. Reprinted May 2016.

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