During the last 10 years, the annual in-cidence of active TB in Belgium was un-changed, with about 1.0 new cases per 100,000 inhabitants. This stability was observed, despite an expected decrease in TB incidence (figure 6).
In 005, 1,144 TB patients were detected in Belgium (11/100,000). About 77 % of these cases were defined as new TB. This is less than the proportion observed for the Central and Western European Union (). Most TB cases were diagnosed after a medical visit requested by the patient (8.7 %), and 9.6 % were detected upon active screening in high-risk groups (im-migrants from high-incidence areas, prisoners, homeless and low-income individuals). More than 50 % of TB cases concerned migrants. Accordingly, with-in large agglomerations such as Brussels and Antwerpen, where migrants rep-resent a substantial proportion of resi-dents, TB disease concerns migrants in up to 70 % of cases. Therefore, local TB incidence in Brussels is increased three-fold in comparison to the national inci-dence (4.1/100,000 in 005).
If they are younger than 5 years, non-Belgian children represent a very sensi-tive population. The incidence of TB of this group is more than 18 times that of the national incidence of the corre-sponding Belgian paediatric popula-tion (6.5/100,000 vs. .5/100,000). This observation clearly illustrates the risk of recent transmission of the disease in the community, because TB disease among these young children is most probably the result of a primary infection and not a re-activation. Therefore, the incidence
in this vulnerable group may serve as an indicator of TB control efficacy. Up to now, it has been shown that the control of TB transmission remains inadequate.
In this context, the detection of M. tu-berculosis infection (latent and active) has to be urgently optimized.
In 005, most TB cases (7.0 %) were pul-monary TB cases, followed by a signifi-cant proportion of extra-thoracic lymph node TB (8.4 %) and of pleural TB (6.7 %).
Among the pulmonary disease in 005, 48.0 % of the 85 patients were smear-positive for acid-fast bacilli and are thus considered as infectious. This propor-tion of smear positive TB is not very dif-ferent from that previously observed in Belgium or from that globally observed in Europe (44.7 % of 445,000 patients) (0).
More recently, multi-resistance (MDR) to drugs has rendered more complex both management and control of the disease. MDR is defined as a resistance to the (or more) key anti-TB drugs (iso-niazid and rifampicin). In Belgium, MDR strains are occasionally detected in 1.4
% of the TB patients both in 005 and 004. No statistical evolution has been observed during the last 5 years with an incidence varying between 1.1 % (00) and .4 % (001). However, resistance to isoniazid (alone or combined with other resistances) remains significant with 5.5 and 5.1 % of the TB cases in 005 and 004, respectively. Even if this propor-tion tends to decrease since 00 (7.7
%), it is recommended to treat TB pri-marily with 4 anti-mycobacterial drugs, if the resistance profile of the strain is unknown (isoniazid, rifampicin, pyrazi-namid and ethambutol). The incidence of MDR and/or of isoniazid resistance is
more frequent in the group of foreign-born in comparison to native Belgians (.4 % vs. 0. % and 6.8 % vs. . %, re-spectively), similar to the global resist-ance incidence of TB.
In addition to MDR strains, extensive drug resistant TB (XDR-TB) has now been described and defined as MDR TB, which is also resistant to three or more of the six classes of second-line drugs (aminoglycosides, polypeptides, fluo-roquinolones, thioamides, cycloserine and para-aminosalicylic acid). XDR-TB finds its origin in the poor management of MDR-TB cases, which are themselves derived from suboptimal management of TB. Therefore, countries with high incidence of TB and low incomes are at higher risk for emergence of XDR-TB. Indeed, XDR-TB has been identified in all regions of the world, but is most
1980 1985 1990 1995 2000 2005
Incidence /100.000 hab.
measured values projection
Figure 6. Unrefined rates of tuberculosis incidenceinBelgiumbetween1980and2003.
A regular decrease of tuberculosis incidence is noted until 199. Since 199, the rate of incidence remained steady for 10 years and slightly diminished in 00 reaching an incidence of 10.9/100,000 inhabitants. Based on statistical projections, the expected rate of incidence in 00 should have been 7.0/100,000 inhabitants.
Microbiology
Generalities (34, 35)
M. tuberculosis is a member of the genus Mycobacterium, the only genus of the family of Mycobacteriaceae in the Ac-tinomycetales order (figure 7 adapted from reference (5)). Members of the genus Mycobacterium are distinguish-able by main characteristics: 1) acid-fastness which is defined by resistance to destaining of carbol-fuchsin staining by hydrochloric acid-ethanol solution, ) presence of distinct mycolic acids and finally ) a guanine-cytosine rich DNA (60-70%). Mycolic acids are responsible of the acid-fastness, which allows for the identification of the “red snapper”
after counterstaining the slide with methylene-blue (Ziehl-Neelsen – see below). Other morphological properties are that mycobacteria are non-spore forming and non-motile rod shaped mi-crobes with a size varying between 1 to 4 µm in length for M. tuberculosis. In part due to genetic particularities in ribos-omal RNA genes (6), M. tuberculosis is a slow growing pathogen. Its generation time ranges from 1 to 4 hours.
The sequence of the genome from the most widely used laboratory strain, M.
tuberculosis H7Rv, has been completely defined in 1998 (7). Subsequently, in addition to the phylogenetic considera-tions, the genomic approach had also led to the characterization of notable biological activities (8). One of these observations is that numerous genes code for enzymes involved in the me-tabolism of lipids that are present in high quantities in the cell wall (see be-low). A significant proportion of these
enzymes are also capable to catalyse fatty acid degradation. Therefore, M. tu-berculosis is able to exploit lipids from the host cells for its own metabolism.
The analysis of the genome also told us that molecules responsible for both aerobic and anaerobic metabolisms are encoded. This confirms the great capacities of M. tuberculosis to adapt it-self to poorly oxygenated conditions as found in granulomas. Taken as a whole, deepened genome sequence analysis has allowed for a better characteriza-tion of the metabolism of M. tuberculosis and may yield new targets for diagnosis, treatment and vaccination.
Habitat
Mycobacteria are facultative intracel-lular organisms and, their growth is closely correlated to the availability of oxygen. With a tropism for the lungs, M. tuberculosis preferentially targets resting alveolar macrophages in order to establish its first habitat. However, invasion of non-professional phago-cytic cells by the bacillus has also been described. For instance, M. tuberculo-sis was demonstrated to infect several cell types, such as epithelial cells, en-dothelial cells, fibroblasts and, more recently, adipocytes (14, 9). Strikingly, the probability to encounter these non-professional phagocytic cells, especially epithelial cells, is substantially higher than that to encounter an alveolar mac-rophage. There are only to 4 alveolar macrophages for 1,000 type-I pneumo-cytes and about to 7 macrophages for 100 type-II pneumocytes. Moreover, mycobacterial invasion of such non-professional phagocytic cells may play a
significant role in persistence and there-fore in the risk of reactivation (14).