Mycobacterium tuberculosis Beijing Genotype, the Netherlands

T Beijing genotype is found frequently in Asia (1–3) but also in outbreaks of multidrug-resistant tuberculosis (MDRTB) in various parts of the world, including Cuba, Germany, Russia, and Estonia (4–7). The largest known epidemic of MDRTB in North America was caused by the W strain, a variant of the Beijing genotype (8–9). A recent study showed this strain’s emergence and association with drug resistance in Vietnam (10). The Beijing genotype was also responsible for a recent outbreak of tuberculosis (TB) on the Canary Islands (11). The relatively high degree of genetic conservation of Beijing genotype strains found in a widespread area (12) suggests a recent dissemination and, hence, selective advantages associated with this genotype of Mycobacterium tuberculosis. Recently, Beijing genotype bacteria were reported to carry mutations in putative mutator genes, which may explain a higher adaptability of these bacteria under stress conditions such as exposure to the intracellular environment or anti-TB drugs (13). These mutations may also be the basis of differential interaction between Beijing genotype bacteria and the host immune defense system suggested in a recent study in Indonesia (14). In the Netherlands, MDRTB is affecting <1% of new TB patients, in particular immigrants (15–17). The incidence of the Beijing genotype has not yet been described. The goal of our study was to determine whether the Beijing genotype is emerging in the Netherlands and whether this genotype is associated with multidrug resistance. The Study Patient data were obtained from the Netherlands Tuberculosis Register, which is maintained by the Royal Netherlands Tuberculosis Association and has been in place since 1993. Municipal health services, which are responsible for the followup of all TB patients, send information using standardized, precoded forms on all reported TB cases to the register. The register includes information on demographic characteristics, case detection, risk groups, type of disease, treatment, and treatment outcome. Isolates obtained from all 8,210 culture-positive patients underwent restriction fragment length polymorphism (RFLP)–typing with IS6110 as a probe at the National Institute of Public Health and the Environment. The Beijing genotype was defined on the basis of spoligotype (no spacers 1–34; at least 4 of spacers 35–43) and a specific region A insertion (18). Certain IS6110 RFLPgenotype families (clades 47 and 61) were consistently found to be Beijing genotype (18). Isolates were assigned to the Beijing genotype on the basis of the IS6110 RFLP pattern (18). If any doubt about clade membership existed, we used spoligotyping for the final allocation. The RFLP results for the period 1993–2000 were matched to patient data on the basis of date of birth, postal area code, and sex, resulting in a perfect match for 5,994 (73%) patients and a near-perfect match for 835 (10%) patients; overall, 83% of the samples matched (6,829 patients). During this period, the Beijing genotype was observed in 516 cultures, representing 6% of the 8,210 patients. In the matched dataset, 415 (6%) of 6,829 were of the Beijing genotype. The number of TB cases attributable to the Beijing genotype tended to increase over time (Figure; p>0.05). This tendency was observed both among Dutch patients (r=0.66, 95% confidence interval [CI] –0.08 to 0.93) and non-Dutch patients (r=0.59, 95% CI –0.20 to 0.91) (Figure). While the increase in the number of cases among immigrants may be associated with an overall increase of immigrants to the Netherlands during