Download Frequency of recurrence among MDR-TB cases

INT J TUBERC LUNG DIS 6(10):858–864
© 2002 IUATLD
Frequency of recurrence among MDR-TB cases ‘successfully’
treated with standardised short-course chemotherapy
G. B. Migliori,* M. Espinal,† I. D. Danilova,‡ V. V. Punga,§ M. Grzemska,† M. C. Raviglione†
* WHO Collaborating Centre for Tuberculosis and Lung Diseases, Fondazione Salvatore Maugeri, Care and Research
Institute, Tradate, Italy; † World Health Organization, Geneva, Switzerland; ‡ Ivanovo TB Dispensary, Ivanovo,
§ Central Tuberculosis Research Institute, Moscow, Russian Federation
SUMMARY
S E T T I N G : Ivanovo Oblast, Russian Federation, 300 km
north-east of Moscow, where a pilot DOTS TB control
programme was implemented in October 1995.
O B J E C T I V E : To determine the frequency of TB recurrence among MDR (multidrug-resistant) patients who
achieved treatment ‘success’ on standard short-course
chemotherapy.
M E T H O D S : All patients with MDR tuberculosis, defined
as resistance to at least isoniazid and rifampicin, who
were declared ‘cured’ or ‘treatment completed’, were
identified using the district register and traced whenever
possible. Eligible patients underwent medical examination and, if necessary, chest radiography, sputum smear
examination, culture and susceptibility testing. If the
patient had died, the relatives were interviewed to try to
determine the reasons for death.
R E S U L T S : Of 18 patients eligible for analysis, five
(27.8%) were documented to have recurrence (two of
seven patients resistant to HRSE, one of five patients
resistant to HRS and two of six patients resistant to
HR). Patients receiving the Category I regimen were
more likely to relapse than those receiving the Category
II regimen (40% vs. 12.5%). The median time to relapse
was 8 months; 2.46 recurrences were observed in 100
person-months (3.17 in category I and 1.3 in Category II
patients).
C O N C L U S I O N S : The frequency of TB recurrence among
MDR-TB patients declared ‘cured’ after short-course
chemotherapy is high. Improvements in treatment success, after removal of programme-related pitfalls in the
treatment delivery process, must incorporate methods
for early detection of MDR, along with adequate treatment regimens including second-line drugs. Culturebased bacteriological confirmation at the end of treatment is recommended.
K E Y W O R D S : tuberculosis; MDR; recurrence; Russia
THE WORLD HEALTH ORGANIZATION (WHO)
tuberculosis (TB) control strategy (the DOTS strategy), emphasises assessment of treatment results.1
According to guidelines published by the WHO and
the IUATLD (International Union Against Tuberculosis and Lung Disease), a patient is defined as ‘successfully’ treated when the final outcome is ‘cured’ (bacteriological conversion at the end of treatment) or
‘treatment completed’ (documented treatment completion, but no evidence of sputum smear microscopy
or culture conversion at the end of treatment).2
Multidrug-resistant (MDR) TB is considered a
threat to TB control, as TB patients infected with
MDR strains are difficult to cure, their treatment is
expensive, and there are frequent severe adverse drug
events.3,4 Previous reports suggest that standard shortcourse chemotherapy (SCC) achieves treatment ‘success’ in less than 60% of MDR-TB patients,5 compared to a success rate of more than 85% in patients
with drug-susceptible TB. The concern is that even
‘cured’ (or ‘treatment completed’) patients may frequently relapse. However, no information is available
on the chance of recurrence among patients with
MDR-TB who have been treated and declared ‘cured’
with standard SCC.
The aim of this study is to determine the proportion of MDR patients developing recurrent TB after
achieving treatment ‘success’ with standard SCC.
METHODS
Setting
A pilot DOTS TB control programme was implemented in Ivanovo Oblast in October 1995. Ivanovo
Oblast is located 300 km north-east of Moscow. It
has a population of 1.3 million people, and an economy based on industry (mainly textile) and agriculture. Deep economic recession and high inflation have
Correspondence to: Dr Giovanni Battista Migliori, WHO Collaborating Centre for Tuberculosis and Lung Diseases,
Fondazione Salvatore Maugeri, Care and Research Institute, via Roncaccio 16, 21049, Tradate (VA), Italy. Tel: (39) 0331
829404. Fax: (39) 0331 829402. e-mail: [email protected]
Article submitted 1 March 2002. Final version accepted 26 June 2002.
Recurrence of MDR-TB cases in Russia
resulted in a rapid increase in unemployment, poverty, malnutrition and alcohol abuse, generating
patient- and programme-related factors favouring
spread of MDR-TB.6–9 At the time of the study,
human immunodeficiency virus (HIV) infection was
infrequent in this setting.6 WHO reports (available on
request) show that the success rates achieved between
the fourth quarter of 1995 and the first quarter of
1999 in sputum smear-positive cases ranged from
43.5% to 65.1%, with a high proportion of defaulters (from 6.3% to 24%) and failures (from 5.6% to
28.3%). In new cases, the prevalence of MDR ranged
from 1.9% to 20% during this period.
Prior to the implementation of the project, standard
WHO training workshops were organised addressing
project managers and medical and laboratory staff. A
protocol to be used by all health staff participating in
the project was jointly prepared by international WHO
staff and consultants, and national staff from the Central Tuberculosis Research Institute, Moscow, and the
Oblast TB Dispensary, Ivanovo. No incentives or
enablers were provided to patients and health staff.
Treatment cards, forms and registers for recording
and reporting following WHO standards were made
available in the Russian language.10 Sufficient antituberculosis drugs to cover the estimated annual burden of patients were provided to the TB units involved
through the Oblast TB Dispensary (quality-proven triple fixed-dose combinations of isoniazid [H], rifampicin [R] and pyrazinamide [Z], and double combinations of R and H were provided free of charge by the
then Marion-Merrel Dow; streptomycin [S] and ethambutol [E] were available from national sources).
Organisation of control activities
Diagnosis
According to the protocol, detection of TB among
symptomatic individuals self-referring to the health
services was the main method of case finding. Microbiological examinations (acid-fast bacilli smear microscopy, culture and drug susceptibility testing) were
coupled with chest radiography during the initial
screening. Regular proficiency testing of the drug susceptibility tests carried out in a variety of local laboratories was organised by the laboratories of the Oblast
TB Dispensary and the Central TB Research Institute,
Moscow, as well as by laboratories belonging to the
network of supranational reference laboratories in the
WHO/IUATLD Global Project on Antituberculosis
Drug Resistance Surveillance.11–13 Quality control for
direct sputum smear examination was performed by
blind re-reading of all positive and 10% of negative
slides at Oblast level. The quality control process was
evaluated by WHO experts during monitoring missions.
Treatment
Treatment was standardised into three categories of
patients. The Category I regimen (new smear-positive
859
pulmonary TB and other newly diagnosed seriously
ill patients with severe forms of TB) consisted of: 2
months of daily S, H, R and Z followed by 4 months
of HR administered three times a week. The Category
II regimen (relapse and failure smear-positive TB cases)
consisted of: 2 months of daily SHRZE plus 1 month
of HRZE followed by 5 months of HRE administered
three times a week. The Category III regimen (new
smear-negative pulmonary TB and other newly diagnosed patients not included in Category I) consisted
of: 2 months of daily HRZ followed by 4 months of
HR administered three times a week.
Patients were given daily treatment during the
intensive phase at the hospital. The intermittent continuation phase was designed to facilitate directly
observed therapy (DOT) at Raion (county) level.
In order to limit deviations from the standard treatment, the protocol did not include specific instructions
on the management of drug-resistant cases. An ad hoc
committee composed of senior staff was established
at the Oblast TB Dispensary to decide when modifications of the treatment regimen were necessary.
Definitions
All definitions used were derived from published
WHO recommendations.2,10,14–16 The main definitions were as follows: a ‘new case’ was a patient who
had never received treatment for TB or who had
taken anti-tuberculosis drugs for less than 4 weeks. A
‘cured’ patient was a patient whose sputum smears
were negative on two occasions at the end of treatment or in the presence of a documented culture conversion during the continuation phase. ‘Treatment completed’ was recorded if there was documented treatment
completion, but no sputum smear microscopy/culture
conversion at the end of treatment.
The ‘treatment success rate’ was defined as the sum
of patients whose outcome was ‘cured’ and ‘treatment
completed’ divided by the total number of patients registered for treatment, expressed as a percentage. Multidrug resistance was defined as resistance to at least H
and R.
For the purposes of this study, in the absence of
restriction fragment length polymorphism (RFLP)
analysis to distinguish true relapse from re-infection,
the term ‘recurrence’ was used to indicate all cases
who suffered a new episode of TB after having been
considered ‘cured’ or after having completed a previous treatment regimen for the first disease episode.
Search of patients
All newly and previously treated culture positive
patients with MDR-TB diagnosed in Ivanovo Oblast
since the beginning of the pilot project (from October
1995 to March 1999) were identified using the computerised district register. MDR patients declared
‘cured’ and ‘treatment completed’ were identified, and
whenever possible, traced by the physician in charge of
860
The International Journal of Tuberculosis and Lung Disease
the Ivanovo Dispensary. Follow-up started in April
1999.
Eligible patients underwent a medical examination
and, if necessary (if they had cough, loss of weight, or
any clinical reason to suspect recurrence of TB), chest
radiography, sputum smear examination, culture and
susceptibility testing.
If the patient had died, the relatives were interviewed to try to determine the reasons for death (TB
or other).
Data analysis
The data available on individual information on
demographics, risk factors, bacteriology at diagnosis
and during treatment, drug resistance, side effects,
treatment prescribed and taken (including the number of doses) and treatment outcome were analysed
by descriptive statistics.
Kaplan-Meier survival curves were used to illustrate the recurrence-free periods observed during
follow-up using SPSS 10.1 software (Statistical Package for Social Sciences, Chicago, IL, USA).
Proportions were compared with the two-tailed 2
test (or Fisher’s exact test where appropriate) using
Epi-Info (version 6.02, Centers for Disease Control
and Prevention, Atlanta, GA). Mean values of continuous variables were compared using Student’s t-test
for unpaired data.
RESULTS
The prevalence of MDR in Ivanovo in 1998 was 9%
among newly diagnosed patients and 25.9 % among
retreatment patients.11
Out of 76 MDR patients identified from the register in Ivanovo Oblast during the period October 1995
to March 1999, 21 had been declared ‘cured’ (bacteriologically confirmed) or ‘treatment completed’.
Three patients could not be located, leaving 18 eligible for analysis (16 males and two females, mean
age SD, 40.2 12.6 years, median 42 years). Eight
were alcohol abusers, two were ex-prisoners and two
had mental impairment (oligophrenia).
Of the 18 patients, 10 were diagnosed as culturepositive/sputum smear-positive and eight were culturepositive/sputum smear-negative. All of these patients
were hospitalised during the intensive phase of treatment at the Oblast TB Dispensary except for two
(patients 1 and 2) who were admitted for the entire
treatment period due to a psychiatric condition. All of
the 18 patients were classified in the TB register as
‘cured’ after treatment with SCC (16 based on culture
and two based on sputum smear results).
The Kaplan-Meier curves describing the cumulative recurrence-free survival of MDR cases are summarised in the Figure. Overall, 2.46 recurrences were
observed in 100 person-months (3.17 in Category I
and 1.30 in Category II patients).
Figure Cumulative recurrence-free survival during follow-up
of 18 MDR-TB patients whose treatment outcome was ‘treatment success’.
The median follow-up time (from the end of treatment to the time of evaluation) was 6.5 months
(mean value SD, 11.3 10.1 months). In the
patients with recurrence of their TB (see below)
the median follow-up was 6 months (mean value SD, 11.2 10.6 months), while in patients without
recurrence the median follow-up was 9 months (mean
value SD, 11.6 10.0 months).
Of the 18 patients, five had a recurrence: two
(28.6%) of seven patients resistant to HRSE, one
(20%) of five patients resistant to HRS, and two
(33.3%) of six patients resistant to HR (Table 1). The
mean time to recurrence was 10.4 10.7 months
(median 8 months, range 1–28 months).
All of the recurrent cases (all males) were confirmed by culture, except for one (patient n 3), who
was diagnosed based on chest radiography and clinical findings; after completing a full re-treatment regimen the nodular infiltrate disappeared and there was
significant clinical improvement.
Data on the 13 patients who did not experience a
recurrence of their TB are summarised in Table 2. At
diagnosis, six had received Category I and seven Category II regimens. Six were new patients. Six patients
had their treatment regimens modified once drug
resistance was identified (Table 2). Patients n 8, 10,
11 and 12 underwent surgery in addition to drug
treatment. Case n 10 had negative smear and culture
results at months 3 and 5, while at the end of treatment only sputum smear examination was performed
(three negative results). He had no recurrence after 7
months of follow-up. Case n 6 died in a car accident,
and according to relatives was healthy at the time of
death.
The treatment length ranged from 6 to 11 months
in Category I and from 8 to 16 months in Category II
Recurrence of MDR-TB cases in Russia
Table 1
N
861
Individual profiles of five ‘successfully’ treated MDR patients who had a recurrence of their tuberculosis
Age
(years)
Sex
Follow-up
(months)
New
case
WHO
regimen
Drug
resistance
Treatment
Doses
Doses
duration Individualised Intensive Continuation
(months)
regimen
phase
phase
Outcome
1
54
M
8
Yes
Category I
HRSE
6
No
Mental impairment; after recurrence: C; SS; CXR (nodule); DST: susceptible; final outcome: Cured
2
49
M
1
Yes
Category I
HRSE
6
No
Mental impairment; after relapse: C; SS; CXR (cavity); DST: HRSE; final outcome: died
3
39
M
12
Yes
Category I
HR
10
No
Unemployed; after recurrence: C; SS; CXR (nodule); DST: negative; final outcome: tr. completed
4
40
M
9
No
Category II
HRS
9
No
Alcohol abuse; after recurrence: C; SS; CXR (nodule); DST: negative; final outcome: cured
5
42
M
28
Yes
Category I
HR
6
No
Alcohol abuse; after recurrence: C; SS; CXR (nodule); DST: RSE; final outcome: cured.
60
122
Cured
62
75
Cured
70
105
Cured
90
114
Cured
70
105
Cured
MDR multidrug-resistant; WHO World Health Organization; M male; Category I/Category II regimens—see Methods section; H isoniazid; R rifampicin; S streptomycin; E ethambutol; positive result; negative result; C culture; SS sputum smear; CXR chest radiography; DST drug susceptibility testing.
regimens. No significant differences were found comparing age, duration of follow-up, and number of
doses of the intensive and continuation phases of
treatment between the five MDR patients with and
the 13 without TB recurrence. However, patients who
received Category I regimens at the time of their first
episode were more likely to have recurrent TB than
those who received Category II regimens (4/10 [40%]
vs. 1/9 ([12.5%], P NS). The treatment duration of
the patients who had a recurrence was longer than for
those who did not (P 0.05).
DISCUSSION
This observational study provides the first known evidence regarding longer-term outcome of TB patients
Table 2
with MDR-TB considered as ‘cured’ after successful
SCC: at least 27.8% of MDR patients declared
‘cured’ had recurrent TB.
The study was performed in a setting characterised
by a high prevalence of drug resistance. The results of
the DOTS programme in the Oblast were generally
sub-optimal, with a proportion of ‘successfully’ treated
patients lower than 85%. In the period 1994–1996,
among new patients, treatment success was 75% in
pan-susceptible strains, 54% in patients with any
resistance (but excluding MDR) and 11% in MDR
patients.5
In a recent case-control study in Ivanovo Oblast
performed between January 1996 and October 1998,
a significant increase in MDR prevalence (from 3.8%
to 9.4%) was observed among civilian patients who
Individual profile of 13 ‘successfully’ treated MDR patients who had no recurrence of their tuberculosis
Follow-up New
Sex (months) case
WHO
regimen
Treatment
Drug
duration
resistance (months)
N
Age
(years)
1
2
3
4
5
6
7
8
9
10
20
44
23
47
30
42
63
52
51
32
M
M
M
M
M
M
F
M
M
M
4
6
6
6
28
12
20
37
5
7
Yes
No
No
Yes
Yes
Yes
Yes
No
No
Yes
Category I
Category II
Category II
Category I
Category I
Category I
Category I
Category II
Category II
Category I
HRS
HRSE
HR
HRS
HR
HRSE
HRSE
HR
HRS
HRSE
11
8
10
11
8
6
6
12
11
15
11
50
M
4
No
Category II
HR
16
12
13
21
25
M
F
6
4
No
No
Category II
Category II
HRSE
HRS
12
12
Modified
regimen
No
No
Yes (intensive phase)*
Yes (last month)†
No
No
No
No
Yes (last month)‡
Yes
(continuation phase)§
Yes
(continuation phase)¶
No#
Yes
(continuation phase)**
Doses
Doses
Intensive Continuation
phase
phase
Outcome
60
90
90
60
60
60
60
80
90
60
171
111
152
74
114
120
90
163
107
276
Cured
Cured
Cured
Cured
Cured
Cured
Cured
Cured
Cured
Cured
90
120
Cured
142
120
140
237
Cured
Cured
MDR multidrug-resistant; WHO World Health Organization; H isoniazid; R rifampicin; S streptomycin; E ethambutol; Z pyrazinamide; M male; Category I/ Category II regimens—see Methods section.
* Intensive phase: intravenous R and intramuscular H.
† Last month: intravenous H.
‡ Last month: oral Z replaced H.
§ Last 2 months of continuation phase: HR from oral to intravenous intramuscular kanamycin.
¶ Surgery after one year of standard regimen; after surgery additional ethionamide.
# Surgery performed after 6 months; regimen not modified.
** Last 3 months: kanamycin and ofloxacin added.
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The International Journal of Tuberculosis and Lung Disease
had never previously been treated, suggesting an
increased circulation of MDR strains.6 To complicate
matters, a high prevalence of alcohol abuse, previous
incarceration, unemployment and history of homelessness were described among both drug-susceptible
and drug-resistant TB patients.6
Although the phenomenon deserves further investigation, both patient-related (social factors linked to
poverty and detention) and programme-related factors (sub-optimal co-ordination of TB control activities within and outside prisons; low staff salaries,
leading to poor motivation impairing treatment delivery) have probably contributed to the spread of MDR
strains within the community.
The aim of this study was to identify the proportion of MDR patients previously deemed as ‘successfully’ treated who had recurrent TB. The assumption
was that standard SCC could be inadequate to cure
MDR-TB and result in an increased risk of relapse
among patients who were apparently cured at the end
of treatment. The study results indicate that the proportion of MDR-TB patients declared ‘cured’ who
had recurrent TB is high, at at least 27.8%.
Our study has several limitations. 1) The sample
size was small and the follow-up period short. In an
attempt to discourage the traditional long-term followup of all cases after cure, it was decided to perform
the study by re-calling eligible patients, and patients
were told to report if new symptoms occurred. 2) The
13 patients who had no recurrence when the assessment was done (except the case who died) still have a
potential risk of relapse later, and thus the true proportion of recurrent TB cases may be higher than
shown here. 3) The proficiency testing performed
during the initial period of the study (1995–1997) did
not strictly follow the principles of the WHO/
IUATLD Global Project on Anti-tuberculosis Drug
Resistance Surveillance.11–13 Hence, there is a risk of
misinterpretation of drug susceptibility pattern. 4)
The lack of RFLP analysis prevented any assessment
of the reason for recurrence between exogenous reinfection and reactivation of a previous strain. A previous study has indicated that exogenous re-infection
may be the leading cause of recurrence in some settings.17 5) In two patients (who were both sputum
smear and culture-positive at diagnosis) the definition
of ‘cure’ was based on three negative smear results, as
culture was not done. It is possible that case n 3
(Table 1) had transient sputum smear-negative results,
or that the quality of the sputum smear examination
was poor. Clearly, the evaluation of the final outcome
based on culture results, as performed in four out of
five patients with recurrence and in 12 out of 13 cases
without, is more reliable.
Although Category I patients were more likely to
have recurrent TB than those in Category II, statistical significance was not reached because of the limited number of cases.
A previous study based on a large number of MDR
patients treated by standard regimens demonstrated
that Category I and II regimens are not adequate for
the treatment of MDR patients, and, as expected, the
proportion of success in MDR patients is related to
the overall success rate among all cases.5
In the period 1995–1999, only first-line drugs were
available in Ivanovo for the majority of patients. The
use of standard Category I regimens is unlikely to
guarantee that at least two, and preferably three
drugs are active to prevent further development of
drug resistance in MDR cases. Although prescribed to
cases who did not develop recurrence (patients n 10
and 11), the addition of a single drug to a potentially
failing regimen is to be considered a programmerelated pitfall.
Further, four of 10 Category I patients had a treatment duration of longer than 9 months. In Russia it is
common practice to treat TB cases until cavity closure
is radiologically documented. The reason why some
cases had no recurrence during the follow-up period
can be explained by the following: 1) drugs were sufficient to achieve cure, especially among cases that
were not resistant to all four drugs; 2) inconsistency
between laboratory results and the in vivo action
of the drugs; 3) partial resistance; and 4) the capacity
of the immune system to guarantee an adequate
response even with a relatively small contribution by
drugs.
There is evidence that properly designed regimens
(including second-line drugs) can achieve higher success rates,18,19 although the cost per case cured is, at
present, very high.20 However the recently established
Green Light Committee has achieved a reduction in
second-line drug prices of over 90%.21
Institution of appropriate treatment was the factor
most strongly associated with a favourable outcome.18,19 It has been argued that the DOTS strategy
alone is not sufficient to solve the problems of TB
control in Russia.7 Others have called for action to
resolve the Russian paradox of centralisation of TB
services coupled with individualisation of casemanagement.8 The spread of MDR strains from the
prison system, where monotherapy was the prevailing intervention for TB in the recent past due to lack
of resources, is presently affecting the epidemiology
of TB in the civilian population.8 In the absence of
significant improvements, there is a high risk of not
being able to control TB in this and other settings.
The study results suggest that the present definition of treatment success2 is likely to overestimate the
true results, at least among MDR cases. The Kaplan
Meier analysis of cumulative recurrence-free survival
indicates that the majority of events took place in the
first 12 months of follow-up. A stricter use of a culturebased bacteriological monitoring at the end of treatment is necessary to define cure.
In our study, 13 out of 18 MDR cases did not
Recurrence of MDR-TB cases in Russia
experience recurrence during follow-up (Table 2, Figure). Some of these patients might have acquired
resistance to any first-line drugs to which their infecting strain was still susceptible.22–25
Adequate regimens with second-line drugs are crucial to improve patient outcome, although this
approach could lead to the development of resistance
to additional drugs if patients are not closely monitored to avoid drug mismanagement. As second-line
drugs are the last resort to cure patients with MDRTB, both programme quality and patient compliance
must be taken into consideration before initiating a
similar approach. The use of adequate re-treatment
regimens, including at least two, and preferably three,
active second-line drugs, can reduce this risk. However, regimens containing second-line drugs must be
used only after ensuring that programme-related pitfalls are minimised through implementation of quality DOTS programmes.22–25
Acknowledgements
The authors wish to thank Dr Rosella Centis, WHO Collaborating
Centre for Tuberculosis and Lung Diseases, for her invaluable help
in data analysis, Dr Kenneth Castro, Division of Tuberculosis Elimination, CDC, Atlanta, for his useful comments on the manuscript,
Dr N V Kutulina, Chief Mycobacteriology Laboratory, Ivanovo
Dispensary for help in analysing laboratory data, and Dr A
Morandi, University of Pavia, Italy, for the statistical analysis.
The project was supported by the WHO through a grant from
the United Kingdom.
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RÉSUMÉ
Oblast d’Ivanovo, Fédération de Russie, à
300 km au nord-est de Moscou où un projet-pilote (Programme de Lutte contre la TB par le DOTS) a été mis en
œuvre en octobre 1995.
O B J E C T I F : Déterminer la fréquence de la rechute de TB
parmi les patients à germes MR (multirésistance aux
médicaments) qui avaient été traités avec succès par chimiothérapie standardisée de courte durée.
CONTEXTE :
Tous les patients atteints de tuberculose
MR (définie comme une résistance au moins à l’égard de
l’isoniazide et de la rifampicine) et qui ont été classés
comme « guéris » ou « traitement achevé » ont été identifiés en utilisant le registre de district et recherchés lorsque
c’était possible. Les patients éligibles ont subi un examen
médical et, si nécessaire, un cliché thoracique, une bacilloscopie des expectorations, une culture et un test de
MÉTHODES :
864
The International Journal of Tuberculosis and Lung Disease
sensibilité. Si le patient était décédé antérieurement, les
membres de la famille ont été interviewés de façon à tenter de déterminer les causes du décès.
R É S U L T A T S : Sur 18 patients éligibles pour l’analyse,
cinq (27,8%) ont été documentés comme ayant rechuté
(deux des sept patients résistants à HRSE, un des cinq
résistants à HRS et deux des six résistants à HR). Les
patients ayant reçu un régime de catégorie I étaient plus
susceptibles de rechute que ceux ayant reçu un régime de
catégorie II (40% vs. 12,5%). La durée médiane jusqu’à
la rechute était de 8 mois ; 2,46 rechutes ont été observées
pour 100 mois-personne (3,17 chez les patients de
catégorie I et 1,3 chez les patients de catégorie II).
La fréquence de la rechute de TB parmi
les patients TB-MR declarés comme « guéris » par une
chimiothérapie de courte durée est élevée, même s’ils
sont considérés comme guéris. Des améliorations dans
les succès du traitement, après le retrait des pièges liés au
programme dans le processus d’administration du traitement, doivent incorporer des méthodes pour la détection
précoce de la MR en même temps que des régimes de
traitement adéquats comportant des médicaments de
deuxième ligne. Une confirmation basée sur la culture
est recommandée à la fin du traitement.
CONCLUSIONS :
RESUMEN
D E R E F E R E N C I A : Oblast de Ivanovo, Federación Rusa, a 300 km al noreste de Moscú, donde se
implementó un proyecto piloto de Programa de Control
de la Tuberculosis (TB) con DOTS, en octubre de 1995.
O B J E T I V O : Determinar la frecuencia de la recaída de
TB en los pacientes que presentan una multirresistencia
a los medicamentos (MR), que habían sido tratados con
éxito con una quimioterapia de corta duración.
M É T O D O : Todos los pacientes con TB-MR (definida
como resistente por lo menos a la isoniacida y a la
rifampicina) que habían sido declarados « curados » o
« tratamiento completado », fueron identificados gracias
al registro de distrito y localizados cuando era posible.
Los pacientes elegibles fueron sometidos a un examen
médico y, cuando era necesario, a una radiografía de
tórax, a una baciloscopia, a un cultivo de expectoración
y a un test de sensibilidad. Si el paciente había fallecido
previamente, los miembros de la familia eran entrevistados para tratar de determinar la causa del fallecimiento.
R E S U L T A D O S : De 18 pacientes elegibles para análisis,
cinco (27,8%) fueron documentados como habiendo
MARCO
tenido una recaída (dos de siete pacientes resistentes a
HRSE, uno de cinco pacientes resistentes a HRS y dos de
seis pacientes resistentes a HR). Los pacientes que recibieron un esquema de categoría I tenían más probabilidades de recaer que aquellos que recibieron un esquema
de categoría II (40% vs. 12,5%). La mediana del tiempo
de recaída fue de 8 meses ; 2,46 recaídas fueron observadas en 100 mesos-persona (3,17 en pacientes de categoría I y 1,3 en pacientes de categoría II).
C O N C L U S I Ó N : La frecuencia de recaída en los pacientes
con TB-MR declarados « curados » con una quimioterapia de corta duración es elevada, aun si son declarados
como curados. Después de remover las trampas relacionadas con el programa, en el proceso de administración del tratamiento, los mejoramientos del éxito del
tratamiento deben incorporar métodos de detección precoz de la MR, así como esquemas adecuados de tratamiento, incluyendo los fármacos de segunda línea. Una
confirmación basada sobre la cultura es recomendada al
fin del tratamiento.