* Provisional data which are subject to
revision
** By ³ 1 month of curative treatment with
combined antituberculosis drugs
In countries where information on previous treatment is not reported. a
previous tuberculosis diagnosis is considered as a previous treatment)
Streptomycin was not tested systematically with other
drugs in Iceland, Norway, Slovenia, and Switzerland, so results of
streptomycin susceptibility are not presented for these four countries.
All culture positive cases were supplied with results for isoniazid,
rifampicin, and ethambutol susceptibility by Iceland, the Netherlands, and
Sweden, compared with 96% of culture positive cases by Norway, 93% by
Denmark, 88% by Slovenia, 77% by Switzerland, 72% by Finland, 64% by
Estonia, and 28% by Romania.
Proportions of isolates with drug resistance varied
widely by country. Two groups were defined according to the proportion of
isolates with multidrug resistance (MDR) among all culture positive
patients:
- in eight countries (Denmark, Finland, Iceland, Netherlands, Norway,
Slovenia, Sweden, and Switzerland) MDR accounted for 0% (Iceland) to
1.1% (Sweden and Switzerland);
- in Romania and Estonia MDR accounted for 3.4% and 13.0%,
respectively.
In the first group of countries, higher proportions of
patients of foreign origin had resistant isolates than nationals. The
proportions of isolates with isoniazid resistance were higher in patients
from Asia (9.2%), Africa (9.6%), or foreign European countries (3.7%),
than in nationals (2.3%), as was observed for streptomycin resistance
(10.1%, 12.9%, 2.8%, and 2.0%, respectively) and for MDR (1.3%, 1.3%,
0.6%, and 0.1%, respectively (figure). These differences by geographic
origin were seen in all countries apart from Slovenia and were found both
in patients who had and who had not been treated previously.
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All countries but Finland reported whether patients had
been treated for or diagnosed with tuberculosis previously. Among the nine
countries, the proportions of drug resistant isolates were higher among
patients previously treated than among those never treated (table). There
were a few exceptions, however: the proportions of resistant isolates were
higher in patients never treated than in patients previously treated in
Denmark (for all drugs), in Sweden (for streptomycin), and in Norway (for
isoniazid and rifampicin). This was attributable to the large proportions
of foreign-born patients (70% in Denmark, 68% in Sweden, 53% in Norway)
among culture positive patients never previously treated, in whom the
proportions of resistant isolates were much higher than in nationals.
Among patients never treated and originating from the
country of diagnosis, the proportions of isolates resistant to isoniazid
and rifampicin were lower in younger (<35 years) than in older
patients. Exceptions were Romania and Estonia, however, where high
proportions of drug resistant isolates, and particularly high proportions
of isolates resistant to rifampicin and of MDR, were observed in younger
patients (higher than in older patients in Estonia).
Discussion
These data provide a preliminary sketch of
antituberculosis drug resistance in Europe. Results are geographically
limited, however, and should not be taken as definitive: since the
feasibility study, additional data from the same period have been added in
some countries (Denmark, Finland).
Comparisons between countries should be
made with caution because of differences in the proportions of
tuberculosis cases for whom results were available (this proportion was
particularly low in Romania). In addition, comparisons are difficult to
make since they are often based on very small numbers, particularly among
patients previously treated.
Since antituberculosis drug resistance results from the
selection of drug resistant mutant bacilli following inadequate use of
drugs (4), high proportions of drug resistant isolates reflect present and
past misuse of antituberculosis drugs. The high proportions of isolates
with resistance observed in Estonia and Romania may reflect problems in
treatment delivery, as occurred in some republics of the former Soviet
Union (5). Furthermore, the high proportions of drug resistant isolates
among young patients who had not been treated before suggest that
transmission of drug resistant bacilli has been occurring recently in the
community or in some institutions.
In contrast, the relatively low levels of drug
resistance found in the five Scandinavian countries, the Netherlands,
Slovenia, and Switzerland, and particularly the low proportions of
resistance among nationals, probably indicate a good quality of
tuberculosis treatment. In all of these countries except Slovenia, the
epidemiology of drug resistance appears to be influenced largely by
patients of foreign origin, who made up a large proportion of cases with
drug resistant infections. Patients originating from some countries (such
as in Asia or Africa) may be at high risk of infection with drug resistant
bacilli as well as for acquiring drug resistance during treatment in their
countries of origin. There may also be specific problems in case
management and/or difficult living conditions, however, which expose
immigrants to the risk of both primary and acquired drug resistance in the
country of diagnosis.
These results show that it is feasible to integrate the
surveillance of drug resistance within the tuberculosis notification
system. The linkage of drug susceptibility results with data of the
notification allows the representativeness of data to be assessed and the
relevant information (particularly age, previous history of tuberculosis
treatment, and patient’s geographic origin) to be analysed. EuroTB is
planning to increase its collection of data on drug resistance in future
years.
EuroTB is funded by the Directorate
General Health and Consumer Protection (DG SANCO/F4) of the Commission of
the European Communities. |