Download Standard 1 (Replaced ISTC 1)

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 2011 by the author
Guidance for
implementation of TB care
in the EU: the ESTC
G. B. Migliori, G. Sotgiu
WHO Collaborating Centre for TB and Lung Disease, Fondazione S. Maugeri,
Care and Research Institute, Tradate, Italy
A. Sandgren, E. Huitric, D. Manissero
ECDC (European Centre for Disease prevention and Control), Stockolm,
Sweden
Disclaimer
• The content of this presentation has been prepared on
the basis of the evidence collected under ECDC
supported survey on management of TB-/MDR-TB
cases in the EU.
• The conclusions of this presentation are the sole
responsibility of the author (representing the ERS Task
Force) and do not represent the ECDC position on the
matter of Standards for Diagnosis and Treatment.
• ECDC has responsibility on the Public Health
Standards only
Outline
• The key areas behind the ESTC
• The pre-final EU Standards
• The supporting enablers
Key Areas (1)
• a) Surveillance.
- Information on the final outcomes of the patients discharged should
be available in the treating clinical centre as this represents a key
managerial tool.
Key areas (2)
• b) Infection control (a)
- Sufficient respiratory isolation rooms for all new patients
admitted (at least till the exact resistance pattern is identified
and/or the patient is rendered non-infectious) and adequate
isolation procedures needs to be available in all European
countries.
No evidence of secondary cases among health staff (1 case in
one country in 10 yrs).
- New European Standards need to look for the evidence and
recommend this procedure if it is really justified.
Key areas (2)
• b) Infection control (b)
- Adequate administrative and personal protection
measures (masks for patients or respirators for staff)
.
- Adequate health education practices for patients (e.g.
cough etiquette) + regular training of health staff are
necessary
.
- Respirator fit testing needs to be urgently implemented,
for all health workers wearing respirators, as evidence
exists that inadequate respirator wearing renders individual
respiratory protection useless.
Key areas (3)
• c) Clinical management of TB and MDR-TB
- needs to be strengthened so that complete information on
previous treatment(s), adequate contact tracing procedures,
adequate bacteriological diagnosis, prescription of at least 4
active drugs, correct drug choice, adequate dose prescription,
sufficient treatment duration and adequate management of AE
of treatment are urgently implemented in the EU
• d) Clinical management of HIV
- should also be strengthened, as part of the development of
the TB/HIV collaborative activities in Europe. This is particularly
relevant in the following areas: HIV-testing and counselling of
TB cases; prescription of ARVs and management of combined
TB/HIV treatment.
Clinical management
Key areas (4)
• e) Laboratory support
- including optimal laboratory practices and quality
assurance procedures, particularly for second-line
drugs remains a key priority in Europe.
• f) Diagnostic and treatment algorithms
- need to be promoted in Europe to reduce as much as
possible the existing differences. New tools (NAAT,
IGRAS, rapid MDR-TB tests) should be promoted
according to clear evidence-based guidelines.
Laboratory support
Diagnostic and
treatment
algorythms
International technical assistance
Standards for Diagnosis:
focus on rapid methods
Standard 1 (Replaced ISTC 1)
All persons presenting with signs, symptoms,
history or risk factors compatible with
tuberculosis should be evaluated for
pulmonary
and
/
or
extrapulmonary
tuberculosis.
• History
• Risk factors
• As chronich cough not necessarily is the
leading symptom
Standard 2 (Replaced ISTC 2)
All patients (adults, adolescents, and children who
are capable of producing sputum) suspected of
having pulmonary tuberculosis should have at least
two sputum specimens submitted for microscopic
examination, culture and drug susceptibility testing
(DST) in a quality-assured laboratory. When
possible, at least one early morning specimen
should be obtained. In countries, settings or
populations in which MDR-TB is suspected in a
patient, rapid testing for the identification of
rifampicin-resistance and when possible isoniazidresistance, using validated tools in a quality-assured
laboratory, should be done.
•
•
•
•
•
•
Culture + DST
Rapid test for R and H-resistance
GeneXpert and Line Probe Assays
Contacts and previoulsy treated cases!!!
Quality assured laboratory
Specialised MDR-TB management
Gene Xpert
Standard 3 (Replaced ISTC 3)
For all patients (adults, adolescents, and
children) suspected of having extrapulmonary
tuberculosis, appropriate specimens from the
suspected sites of involvement should be
obtained for microscopy, culture, DST and
histopathological examination in a qualityassured laboratory. In countries, settings or
populations, in which MDR-TB is suspected in a
patient, rapid testing for the identification of
rifampicin- and isoniazid-resistance in a qualityassured laboratory could be done.
• EP TB: same laboratory approach
• Aggressive trial to get a specimen suitable
for bacteriology
• Surgeons: not in formaline only!
Standard 4 (Replaced ISTC 4)
All persons with chest radiographic findings
suggestive of pulmonary tuberculosis should
have sputum specimens submitted for
microscopic examination, culture and DST in a
quality- assured laboratory. In countries, settings
or populations, in which MDR-TB is suspected in
a patient, rapid testing for the identification of
rifampicin-resistance and when possible
isoniazid-resistance in a quality-assured
laboratory should be done.
• When CXR is the entry point…
• …bacteriological examinations should be
done (see Standard 2)
Standard 5 (ISTC 5 valid, EU adapted
integration needed)
The diagnosis of culture-negative pulmonary tuberculosis
should be based on the following criteria: all
bacteriological tests are negative (including direct sputum
smear examinations, cultures and rapid molecular testing);
chest radiographic findings compatible with tuberculosis;
and lack of response to a trial of broad spectrum
antimicrobial agents. (Note: Because the fluoroquinolones
are active against M. tuberculosis complex and, thus, may
cause transient improvement in persons with tuberculosis,
they should be avoided.) In persons who are seriously ill or
have known or suspected HIV infection or have any
immune-compromising conditions, the diagnostic
evaluation should be expedited and if clinical evidence
strongly suggests tuberculosis, a course of antituberculosis treatment should be initiated.
Culture negative cases:
• Negative to: direct sputum smear
examinations, cultures and rapid
molecular testing
• Using all diagnostic tools to collect the
specimens
• New diagnostics: within evidence based
guidelines
Standard 6 (ISTC 6 valid until specific EU
paediatric standards are available, EU adapted
integration needed)
In all children, suspected of having intrathoracic (i.e.,
pulmonary, pleural, and mediastinal or hilar lymph node)
tuberculosis, bacteriological confirmation should be sought
through examination of appropriate biological samples (by
expectoration or induced sputum, bronchial secretions, pleural
fluid or gastric washings) for smear microscopy culture and
DST in a quality-assured laboratory. In the event of negative
bacteriological results, a diagnosis of tuberculosis should be
based on the presence of abnormalities consistent with
tuberculosis on chest radiography, a history of exposure to an
infectious case, evidence of tuberculosis infection (positive
tuberculin skin test-TST and/or interferon-gamma release
assay- IGRA), and clinical findings suggestive of tuberculosis.
For children suspected of having extrapulmonary tuberculosis,
appropriate specimens from the suspected sites of
involvement should be obtained for microscopy and for culture
and histopathological examination.
• Waiting for new paediatric ESTC, previous
ISTC valid
• Same laboratory diagnostic approach than
for adults (as per Standard 2-5)
• Try to obtain the sample!
Standards for Treatment:
attention to retreatments!
Standard 7 (ISTC 7 maintained)
Any practitioner treating a patient for tuberculosis is
assuming an important public health responsibility
to prevent ongoing transmission of the infection and
the development of drug resistance. To fulfill this
responsibility the practitioner must not only
prescribe an appropriate regimen, but also utilize
local public and/or community health services,
agencies and resources when necessary, to perform
contact investigation, to assess the adherence of the
patient and to address poor adherence when it
occurs.
• Public health “jacket” of the pratictioner
• Role of civil society and community
emphasized
Standard 8 (ISTC 8 valid, EU adapted
integration needed)
All patients (including those with HIV-infection) who
have not been previously treated and without any
risk factors for drug-resistance should receive an
internationally accepted first-line treatment regimen
using drugs of known bioavailability. The initial
phase should consist of two months of isoniazid,
rifampicin, pyrazinamide, and ethambutol. The
continuation phase should consist of isoniazid and
rifampicin given for four months (2HRZE/4HR). The
doses of antituberculosis drugs used should
conform to international recommendations. Fixed
dose combinations of two (isoniazid and rifampicin),
three (isoniazid, rifampicin, and pyrazinamide) and
four (isoniazid, rifampicin, pyrazinamide, and
ethambutol) drugs are highly recommended.
• Retreatment cases should be managed
according to the individual risk to be MDRTB until MDR is excluded
Standard 9 (ISTC 9 maintained)
To assess and foster adherence, a patient-centered approach to
administration of drug treatment, based on the patient’s needs
and mutual respect between the patient and the provider,
should be developed for all patients. Supervision and support
should be individualized and should draw on the full range of
recommended interventions and available support services,
including patient counseling and education. A central element
of the patient-centered strategy is the use of measures to
assess and promote adherence to the treatment regimen and to
address poor adherence when it occurs. These measures
should be tailored to the individual patient’s circumstances,
based on a detailed anamnesis of the patient’s clinical and
social history, and be mutually acceptable to the patient and the
provider. Such measures may include direct observation of
medication ingestion (directly observed treatment or DOT) and
identification and training of a treatment supporter (for
tuberculosis and, if appropriate, for HIV-infection) who is
acceptable and accountable to the patient and to the health
system. Appropriate incentives and enablers, including
financial, social and psycho-social supports, may also serve to
enhance treatment adherence
• Adherence
• Patient-centred approach
• DOT and treatment supporter
Standard 10 (ISTC 10 valid, EU adapted
integration needed)
Response to therapy in patients with pulmonary
tuberculosis should be monitored by follow-up
smear microscopy and culture at the time of
completion of the initial phase of treatment (two
months for drug-susceptible TB). If the sputum
smear and culture are positive at completion of
the initial phase, sputum smears should be
examined again at 3 months and, if positive,
drug susceptibility testing should be performed.
In patients with extrapulmonary tuberculosis and
in children unable to produce sputum, the
response to treatment is assessed clinically.
Treatment monitoring:
• Monthly SS and culture
Standard 11(Replaced ISTC 11, see also
ESTC 1, 2 and 3)
An assessment of the likelihood of drug resistance,
based on history of prior treatment, exposure to a
possible source case having drug-resistant
organisms, and the community prevalence of drug
resistance, should be obtained for all patients. Rapid
testing, including rapid rifampicin resistance or
rifampicin- and/or isoniazid-resistance testing
should be done for all patients suspected of
resistance as defined in standard 2 and 8.
Furthermore, patient counseling and education
should begin immediately for all TB patients, in
order to minimize the potential for transmission.
Infection control measures appropriate to the setting
should be applied as recommended in ESTC public
health standard 20.
• Rapid testing once more!
• Immediate counselling and education for
infection control purposes
• Rapid testing does not rule out the need
for DST
Standard 12 (ISTC 12 valid, EU adapted
integration needed)
Patients with, or highly likely to have, tuberculosis caused by
drug-resistant (especially MDR/XDR) organisms should be
treated with specialized regimens containing second-line antituberculosis drugs. The regimen chosen may be standardized
or based on suspected or confirmed drug susceptibility
patterns. At least four drugs to which the organisms are
known, or presumed, to be susceptible to, including an
injectable agent, should be used. Treatment should be given
for at least 20 months, the intensive phase of treatment
recommended to be 8 months beyond culture conversion
(instead of 6 months as in previous recommendations; see
below the EU Adaptations for further detail). As the treatment
of MDR/XDR-TB is the last chance for these patients to be
cured and survive and, often, as previous defaulters belong to
the socio-vulnerable groups, a full range of patient-centred
measures, including counselling, education of patients and
family members, observation of treatment, identification of
patient-entrusted treatment supporter, psycho-social support
and other incentives and enablers, are required to ensure
adherence in order to avoid development of XDR-TB.
• Specialized centres
• 4 active drugs, 20 months total, intensive
phase 8 moths beyond culture conversion
• Aggressive management of AE
• “Cosillium”
Standard 13 (ISTC 13 valid, EU adapted
integration needed)
A written record of all medications given,
bacteriologic response, and adverse reactions
should be maintained for all patients.
Standards for addressing HIV
Infection and Co-morbid
Conditions:
- universal access to
diagnosis & treatment
- remind other conditions!!!
- focus on LTBI
Standard 14 (ISTC 14 maintained)
HIV-testing and counseling should be
recommended to all patients with, or suspected
of having, tuberculosis. Testing is of special
importance as part of the routine management
of all patients in areas with a high prevalence of
HIV-infection in the general population, in
patients with symptoms and/or signs of HIVrelated conditions. Because of the close
relationship of tuberculosis and HIV-infection,
integrated approaches to prevention and
treatment of both infections are recommended.
• Setting of choice cancelled
• Integrated TB/HIV management
approaches to all cases
Standard 15 (ISTC 15 valid, EU adapted
integration needed)
All patients with tuberculosis and HIV-infection
should be evaluated to determine if antiretroviral
therapy is indicated during the course of
treatment for tuberculosis, according to the
severity of their immunodeficiency. Appropriate
arrangements for access to antiretroviral drugs
should be made for patients who meet
indications for treatment. However, initiation of
treatment for tuberculosis should not be
delayed.
• General prophylactic treatment against
other infections not relevant in the EU
Standard 16 (ISTC 16 valid, EU adapted
integration needed)
Persons with HIV-infection who, after careful
evaluation, have a positive test for presumed
latent infection with M.tuberculosis (LTBI)
(tuberculin skin test (TST) and/or IGRAs) but do
not have active tuberculosis should be treated
with isoniazid for 6-9 months.
TLTI:
• Underlined
• Not only in HIV infected, but also in all
conditions increasing probabily of
reactivation
Standard 17(ISTC 17 valid, EU adapted
integration needed)
All providers should conduct a thorough
assessment of conditions that could affect
tuberculosis treatment response or outcome. At the
time the case management plan is developed, the
provider should identify additional services that
would support an optimal outcome for each patient
and incorporate these services into an individualized
plan of care. This plan should include assessment
of, and referrals for treatment, of other illnesses with
particular attention to those known to affect
treatment outcome, for instance care for diabetes
mellitus, drug and alcohol treatment programmes,
tobacco smoking cessation programmes, and other
psychosocial support services, or to such services
as antenatal or well baby care.
• Treatment outcomes:
• Importance underlined
Standards for Public Health
and Prevention:
outcomes and infection
control!
Standard 18 (ISTC 18 valid, EU adapted
integration needed)
All providers of care for patients with tuberculosis
should ensure that persons who are in close contact
with patients who have infectious tuberculosis (e.g
in prisons), are evaluated and managed in line with
international recommendations.
The risk of TB transmission depends on the
concentration of the mycobacteria in the air, the
duration of the contact and the susceptibility of the
contact to infection and disease. The determination
of priorities for contact investigation is based on the
likelihood that a contact: 1) has undiagnosed
tuberculosis; 2) is at high risk of having been
infected by the index case; 3) is at high risk of
developing tuberculosis if infected; 4) is at risk of
having severe tuberculosis if the disease develops.
Contacts:
- Risk of transmission
- Re-modulation of priorities for contact tracing:
the contact: 1) has undiagnosed TB; 2) is at high risk of
having been infected by the index case; 3) is at high risk
of developing TB if infected; 4) is at risk of having severe
TB if the disease develops
Standard 19 (ISTC 19 valid, EU adapted
integration needed)
Children under 5 years of age and persons of
any age with HIV-infection who are close
contacts of an infectious index patient and who,
after careful evaluation, do not have active
tuberculosis, should be treated for presumed
latent tuberculosis infection with isoniazid.
• Previous ISTC confirmed
• Clinicians and PH authorities should
collaborate in contact tracing
Standard 20 (ISTC 20 valid, EU adapted
integration needed)
Each healthcare facility caring for patients who
have, or are suspected of having infectious
tuberculosis, should develop and implement an
appropriate tuberculosis infection control plan.
Infection control plan:
• Organisational activities, administrative
control, personal protection interventions
Fit test
Respiratory Fit Testing
Standard 21 (ISTC 21 valid, EU adapted
integration needed)
All providers must report both new and retreatment tuberculosis cases and their treatment
outcomes to local public health authorities, in
conformance with applicable legal requirements
and policies.
Supporting enablers to the ESTC
The following supporting enablers complementing the ESTC are
suggested to EU Countries:
• Formal adoption of ESTC, ideally translated in the country-specific
language(s) after their endorsement by National Medical Associations.
Ideally thee ESTCs should be incorporated into training curricula of
health staff.
• Development of consistent control and elimination strategies and
policies according to the principles described in the New European
Framework.
• Adoption of specific, updated, evidence-based tuberculosis and
multidrug-resistant tuberculosis guidelines, together with mechanisms
to update them on a regular basis and to monitor their implementation
(audit- and or knowledge, attitudes and practices study (KAP study)based).
• Adoption of translated ESTC + inclusion in
training curricula
• Development of consistent elimination
strategies
• Development of evidence-based
guidelines and their up-dating
Supporting enablers to the ESTC
• Planning and organisation of adequate laboratory network to ensure
that a minimum, sufficient number, of mycobacteriology laboratories are
in place, allowing implementation of the standards described in this
document (adequate coverage of the country, adequate internal and
external quality assurance procedures in place, sufficient numbers of
samples per laboratory to ensure proficiency, availability of national
laboratories with reference functions to support regional and local
laboratories etc).
• Development of policies ensuring a continuous availability of all 1st and 2nd -line drugs (e.g. through coordinated procurement with partner
countries for the drugs not registered in the country or which are
necessary in small quantities).
• Securing consistent and adequate funding for tuberculosis and
multidrug-resistant tuberculosis care, prevention and control sufficient
to run the activities mentioned above in this document, including
psycho-social support and coordination of care. This applies particularly
to patients belonging to vulnerable populations; following the
International Patients’ Charter for right to diagnosis and treatment.
• Laboratory network: less labs, more
samples!
• Availability of drugs
• Adequate funding
Conclusions 1
• The ECDC-TBNET study, based on a standardised and
validated methodology, has provided the evidence
necessary to development the EU-adapted Standards.
• Gaps in case managements are evident even in high
resource settings and in referral centres
• Progress towards further TB control (and possibly
elimination) in low/intermediate incidence settings requires
adherence to the highest standards
• A wide consultation involving international agencies (e.g.
ECDC, WHO) scientific societies (e.g. ERS, ATS), country
representatives and other stakeholders has been carried
out to draft preliminary EU-adapted standards
Experts who provided input to the ESTC
Dr. Abubakar Ibrahim
Dr. Aksamit Timothy
Prof. Blasi Francesco
Dr. Caminero Luna Jose Antonio
Dr. Centis Rosella
Prof. Cirillo Daniela Maria
Dr. D’Ambrosio Lia
Dr. Danilovits Manfred
Dr. Dara Masoud
Dr. DeVries Gerard
Dr. Dheda Keertan
Prof.Dinh-XuanAnh-Tuan
Mr. Gordon Case
Dr. Huitric Emma
Dr. Ibrahim Elmira
Dr. Kliiman Kai
Dr. Kluge Hans
Prof. Lange Christoph
Dr. Leimane Vaira
Prof. Loddenkemper Robert
Dr. Manissero Davide
Prof. Migliori GB
Prof. Nicod Laurent
Mrs. Pannetier Carine
Dr. Raviglione Mario C.
Dr. Sandgrem Andreas
Prof. Sotgiu Giovanni
Prof. Spanevello Antonio
Dr. Thomsen Vibeke Ostergaard
Dr.van der Werf Marieke
Dr.Villar Miguel
Dr. Wanlin Maryse
Prof. Wedzicha Wisia
Dr. Zellweger Jean-Pierre
Dr. Zumla Alimudin
Conclusions 2
Conclusions 2
MDR-TB
management
will very costly
and painful…
Conclusions 3
Conclusions 3
If will not not
apply high
standards!
Thank you!