Page 15 - Epidemiological studies on tuberculosis control and respiratory viruses

VNTR clustering in relation to the M. tuberculosis population
(16%) were clustered by VNTR and nonclustered by RFLP. In contrast, among 2,646 Euro-American isolates, 263 (10%) were clustered by VNTR and nonclustered by RFLP (Table 2).
This study shows the lineage-dependent degree of reliability of the inference
on transmission. Classification of lineage type was based on the geographical 2 association between patient origin and strain lineage, defined as Euro-American
and non-Euro-American. Among nonclustered native Dutch TB cases, Euro-American
lineages were most frequently isolated. Domination of these lineages among native
TB cases has also been shown in other European populations (19, 20), suggesting that
these lineages have been circulating in Europe for centuries (21). In contrast, recent-
immigrant cases caused by nonclustered non-Euro-American strains originated from
distant geographical areas.
Risk factors for recent transmission, as determined by VNTR clustering, were reduced in the non-Euro-American lineages compared to the Euro-American lineages, indicating the lineage dependence. This was further visible when testing the effect of tolerating single-locus variants in the cluster definition, as the increase in clustered non-Euro-American strains was twice as high as that among Euro-American strains, reflecting the clonality of the former strains in the study population. Furthermore, the magnitude of association between risk factors and clustering decreased after allowing single-locus variants, especially among cases with non-Euro-American isolates, thus increasing overestimation of recent transmission for cases caused by non-Euro-American lineages.
In conclusion, to remain useful in TB control practice, the definition of a cluster on the basis of VNTR typing should be a fully identical 24-locus VNTR typing result. This study further indicated limits in the interpretation of recent transmission based on clustering by VNTR typing in the recent-immigrant population. Our findings are in particular relevant for other European low-incidence countries having similar forms of immigration.
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