Transcript Common causes of treatment mismanagement

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Common causes of treatment
mismanagement
Jean-Pierre Zellweger
Swiss Lung Association
What is mismanagement of TB?
The « ideal » TB management
Symptoms
Suspicion of TB
Bacteriological confirmation
Treatment
Cure (Thank you, doctor!)
The «real-life» TB management
Symptoms
Wrong diagnosis
Delay
Suspicion of TB
Bacteriological confirmation
Treatment
Cure (Thank you, doctor!)
The «real-life» TB management
Symptoms
Suspicion of TB
Incorrect
assessment
Bacteriological confirmation
Treatment
Cure (Thank you, doctor!)
The «real-life» TB management
Symptoms
Suspicion of TB
Bacteriological confirmation
Missing drug
sensitivity
testing
Treatment
Cure (Thank you, doctor!)
The «real-life» TB management
Symptoms
Suspicion of TB
Bacteriological confirmation
Treatment
Inappropriate
drug treatment
Failure, relapse, MDR/XDR-TB
Delayed diagnosis
Mean patient’s and HCW’s delay (days) in 42 studies
Mean total diagnostic delay: 21 – 136 days
Storla DG, BMC Public Health 2008;8:15
Patient’s delay
Patient’s delay
• Frequency of symptoms before diagnosis:
– Cough
– Sputum
– Fever
– Weight loss
– Fatigue
– Haemoptysis
– Sweating
85%
67%
65%
62%
55%
25%
35%
Factors associated with delayed health-seeking
behaviour
• Socioeconomic factors:
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Low access to health care
Rural residence
Low income, poverty
Low education
• Sociopsychological factors:
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–
Low-level health care facility
Traditional or unqualified practicioner
Private practicioner
Beliefs about TB
• Sociodemographic factors:
–
–
–
–
Old age
Female gender
Immigration
Illegal residency
Doctor’s delay
• Factors influencing delay:
– HIV
– Chronic cough
– Negative sputum
– Substance or alcohol abuse
– Smoking
– Poor health
– Coexistent disease
– Mild symptoms
– No haemoptysis
Delay associated with health-care providers
• Repeated consultations with incompetent
healthcare providers:
– Governmental primary health posts
– Private practicioners with low awareness
– Unqualified traditional practicioners
• Overcentralization of govermental TB
programme
• Repeated courses of inappropriate antibiotics
Storla DG, BMC Public Health 2008;8:15
Diagnostic deficiencies
• Misinterpretation of clinical presentation
– Other diagnosis: cancer, pneumonia, smoking, COPD
• Misinterpretation of chest X-ray
– « inactive TB »
– Incorrect interpretation : cancer, abscess
• TB diagnosis without evidence
– No bacteriological examination (lymph node
biopsies, surgical samples!)
– Diagnosis based on chest X-ray only
– Culture not available or not requested
Inappropriate treatment
• Single drug treatment of active TB
• Standard treatment (cat 1) of undetected MDR-TB
– Ovelooking risk factors for MDR-TB
• Prior treatment
• Origin from region with high rate of MDR-TB
• Addition of a single drug to a failing regimen
• Insufficient doses
• Missing doses in intermittent treatment (1weekly)
Case #13
• Woman born in Portugal,
28 years
• Coughs since 3 weeks
• CXR
• Receives moxifloxacine
Case #13
• Woman born in Portugal,
28 years
• Coughs since 3 weeks
• CXR
• Rx moxifloxacine
• Feels better
• 2nd CXR after 2 weeks
Case #13
• Woman born in Portugal, 28
years
• Coughs since 3 weeks
• CXR
• Rx moxifloxacine
• Feels better
• 2nd CXR after 2 weeks
• Recurrent symptoms 3 weeks
later
• Smear positive
Message: 3 errors
1. wrong interpretation of chest X-ray
(it was TB, not cavitating pneumonia!)
2. incorrect choice of the antibiotic
(no quinolone for possible TB!)
3. wrong interpretation of the improvement
(bactericidal effect of moxifloxacin on M.tb)
Who has primary MDR-TB?
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•
•
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•
Patients with prior TB treatment (10 times)
Foreign-born patients
Young patients
Males
HIV positives
Risk factors for MDR-TB in Europe
a) patients with previous treatment
Faustini A, Thorax 2006;61:158-63
Risk factors for MDR-TB in Europe
b) previous treatment in E and W Europe
MDR-TB in immigrants arriving in UK: risk
factors
O’Riordan Ph, PLoS One 2008,3(9):e3173
Insufficient follow-up
• Irregular controls
• Undetected adverse effects of treatment
• Erratic changes in treatment schedule due to
adverse events (replacement of H or R by
second-line drugs)
• Undetected negative evolution
Uncertain cure
• End of treatment without documentation of cure
Mismanagement and creation of
MDR/XDR-TB
Mismanagement and creation of MDR/XDR-TB
• Errors inducing MDR-TB
– Inappropriate choice of drugs
– Inappropriate regimen (twice-weekly without
supervision)
– Too low doses
– Malabsorption of drug (low blood levels)
Creation of drug resistance: effect of drugs on
mycobacteria with different growth speed
Mitchison DA , IJTLD 1998;2(1):10-15
Creation of drug resistance: growth speed of
sensitive and resistant mycobacteria
Creation of drug resistance: regrowth of of
sensitive and resistant mycobacteria
Creation of drug resistance: impact of lag phase
Mismanagement and creation of MDR/XDR-TB
• Errors inducing MDR-TB
• Induction of MDR-TB without error under
standard DOTS strategy
– Initiation of standard therapy in new patients with
undetected drug resistance
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•
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•
•
No culture available or requested
No DST
DST inappropriate
DST arriving too late (3-4 months)
DST never transmitted to clinician
Situation at initiation of treatment
Caminero JA, IJTLD 2008;12(8):869-77
Possible course of treatment
Initial resistance to H
Initial MDR-TB
Outcome of treatment and retreatment in sites with
low MDR-TB prevalence
Gninafon M, IJTLD 2004;8(19):1242-7
Outcome under correct DOTS in sites with high
prevalence of MDR/XDR-TB
• 1999 (Bakou prisons, Azerbaïjan): all prisoners
under correct treatment (cat 1, DOT)
– Mortality during treatment: 11%
– Sputum conversion obtained in 42%
– Cure rate 54% (71% in completers)
– 55% had strains resistant to 2 or more drugs
Coninx R, Lancet 1999;353:969-73
Creation of new MDR/XDR-TB under correct DOTS
• 2901 new smear + pulmonary TB under DOTS in
Vietnam
• 125 failures
• 2nd DST in 40 failure with two positive cultures and
identical RFLP pattern
– 17 had MDR-TB at beginning of treatment
– 15 without MDR at beginning developed MDR under DOTS
• 39 relapses
– No primary MDR-TB
– 3 had MDR-TB at relapse
Quy HTW, IJTLD 2003,7(7):631-36
Outcome and acquired drug resistance in 1681
new TB patients in cat 1 DOTS (Tomsk)
Seung KJ, Clin Infect Dis 2004;39:1321-8
Acquired drug resistance under DOTS
• Among 382 new pulmonary TB patients
treated by a standard DOTS regimen
– 62 were still smear positive at 2 months (with
identical strains)
– 24 had MDR-TB
– 19/62 identical strains developed new or
additional drug resistance during treatment
– 3.5% of patients with DST other than MDR
developed MDR-TB during treatment
Cox HS, Clin Inf Dis 2007;44:1421-7
Amplification of drug resistance in patients
under retreatment
• 410 patients in Uganda received retreatment
for TB according to WHO: 2HRZES/1HRZE/5HRE
– 12.5% had MDR-TB at the beginning of retreatment
– 5.2% developed additional drug resistance during
retreatment (half of them developed new MDR-TB)
– Risk of acquired drug resistance was
• 10.4 for patients with H or R resistance
• 46.1 for patients with MDR-TB
• 42.4 for patients still C+ after 5 months of treatment
Temple B, Clin Inf Dis 2008;47:1126-34
Outcome by rate of resistance and MDR in 6 sites in FSU
Bonnet M, IJTLD 2005;9(10):1147-54
Initial drug resistance and treatment failure
a) fully sensitive strains
Lew W, Ann Int Med 2008;149:123-34
Initial drug resistance and treatment failure
b) initial single drug resistance
Initial drug resistance and treatment failure
c) polyresistant strains
Initial drug resistance and treatment failure
Initial drug resistance and treatment outcome.
Duration of R treatment and outcome, by resistance
Initial drug resistance and treatment failure.
Acquired drug resistance
Rate of failure in new and retreatment cases, by
local rate of initial MDR-TB (source WHO data)
Mak A, Am J Respir Crit Care Med 2008;178:306-12
Speed of detection of MDR-TB (in immigrants)
and outcome of treatment
O’Riordan Ph, PLoS One 2008,3(9):e3173
How to treat failure and relapse cases?
• Low MDR-TB prevalence: 2HRZES/1HRZE/5HRE (?)
– Beware of any risk factor for drug resistance
– Strict DOT
– Obtain DST
• High MDR-TB prevalence:
– Obtain rapid DST
– Avoid using only first-line drugs as retreatment
schedule
– Consider using second-line drugs (injectables and
quinolones)
Conclusions: how to avoid creating MDR/XDR-TB?
• Obtain a bacteriological confirmation whenever
possible, at least in retreatment cases
• Obtain DST as soon as possible (consider using
rapid amplification technology)
• Search for all possible risk factors for drug
resistance
• Initiate appropriate drug treatment
• Supervise drug intake
The curse of MDR/XDR-TB
• « A mycobacterium for a mycobacterium »
– Your mycobacterium is my mycobacterium
– You and your children will be cursed to the seventh
generation!