Dominant Mycobacterium tuberculosis lineages in elderly patients born in Norway

Abstract

Background: During the previous century Norway had a high incidence of tuberculosis, but no molecular epidemiological studies could be performed and these previously epidemic strains have been disappearing during the last decades. Currently, tuberculosis among native Norwegians is in the elimination phase, and it is still not known what type of M. tuberculosis was so efficiently controlled during the second half of the 20th century. However, many elderly Norwegian-born people still develop TB that cannot be clustered to imported or recently transmitted strains of M. tuberculosis. Thus, the majority of these cases are results of reactivation of disease that was transmitted many decades ago.

Methodology/principal findings: A total of 213 strains of M. tuberculosis isolated during 1998-2005, from patients born in Norway before 1950 were genotyped in the current study. The findings demonstrated a highly homogenous M. tuberculosis population among the patients. A total of 40% belonged to the T-family, were 35% were assigned to T1 sub- family (T2 = 0, 93%, T3 = 1, 4% and T4 = 2, 3%). As many as 35% of the isolates belonged to the Haarlem family, were 15% were assigned to Haarlem1 and 19% to Haarlem3. The remaining 25% belonged to 15 different other families. The RFLP-patterns indicated that the isolates were not a result of recent transmission, but rather represented well established strains that apparently dominated in Norway many decades ago.

Conclusions/significance: The T 1, Haarlem 1, and Haarlem 3 families of M. tuberculosis were abundant among patients born in Norway before 1950. The M. tuberculosis cases represented reactivated disease that had been acquired before 1994 and were likely to have been latent for several decades. Thus, the current study indicated that the T 1, Haarlem 1, and Haarlem 3 families may have been common in Norway, when tuberculosis represented a serious public health threat during the first half of the 20th century.

Figure 1. Incidence of tuberculosis and distribution of birth-year of patients from where the current M. tuberculosis strains originated.

The incidence of pulmonary tuberculosis in Norway 1910–1990 (dotted line) is presented in a logarithmic scale (left axis). The distribution of year of birth of the patients from whom the current M. tuberculosis population had been isolated during 1998–2008 (solid line) is given in percent (right axis).

Figure 2. The diversity of spoligopatterns in M. tuberculosis isolates from patients born in Norway between 1910 and 1950.

Percent homology, spoligopatterns, family assignment, and number of isolates carrying each pattern, among M. tuberculosis strains isolated from Norwegian-born patients during 1998–2008. All cases were considered reactivation of remote infection. Abbreviations: EAI: East African Indian-family, LAM: Latin American Mediterranean-family, T: T-family, H: Haarlem-family, S: S-family, X: X-family, CAS: Central Asian-family .

Figure 3. Diversity and RFLP patterns observed among M. tuberculosis strains, sex, and year of birth of patients from whom these were isolated.

Genetic diversity and IS6110- RFLP patterns of the isolates assigned to the T- family from patients born in Norway 1910-1950.

Figure 4. Diversity and RFLP patterns observed among M. tuberculosis strains, sex, and year of birth of patients from whom these were isolated.

Genetic diversity and IS6110- RFLP patterns of the isolates assigned to the Haarlem- family from patients born in Norway 1910–1950.