© 2007 American Thoracic Society doi: 10.1164/rccm.200707-1115ED
"Them" and "Us"The Two Worlds of Tuberculosis?McGill University, Montreal, Quebec, Canada On a sunny Friday last May, I left the Montreal Public Health Department after a research meeting. As I stepped into my car, I was summoned back for an urgent conference call with the Public Health Agency of Canada. Montreal authorities had just been alerted that a young man with suspected extensively drug-resistant tuberculosis (TB) had landed from Prague at Montreal's airport the previous afternoon, then rented a car and crossed into New York State. Public health staff scrambled to trace and screen passengers from the Prague–Montreal flight. Thanks to extensive media coverage, Andrew Speaker's name, face, and story came to symbolize TB's ability to cross borders quickly and undetected (1). Anyone involved in TB management or control needs no reminder of the key role played by human movement—across oceans, within rapidly industrializing countries, from war zones to refugee camps. We see it in the composition and trajectories of our patients, and in countless reports (2, 3). The Norwegian study reported by Dahle and colleagues in the current issue of the Journal (pp. 930–935) is no exception (4). From 1994 to 2005, Norwegian annual TB incidence increased 11%, from 5.6 to 6.2 cases per 100,000. By 2005, foreign-born individuals (7.9% of the population) accounted for 78% of Norwegian TB cases—versus 46% in 1994. This striking finding reflected declining case numbers among Norwegian-born persons, a near-doubling of the foreign-born population, and increased incidence within this group. The data suggest that the incidence of culture-positive disease decreased by over 50% among Norwegian-born individuals, while it increased by as much as 70% among foreign-born persons. There were two completely divergent epidemiologic processes, as elegantly documented earlier in San Francisco (5). Shifts in the foreign-born population were a key factor, notably more new arrivals. As elsewhere, the interval between arrival and diagnosis was generally short, with a median of 1.5 years. Any increase in the prevalence of latent TB and/or HIV infection among new entrants would also have increased TB incidence. Norway has a small population (4.6 million in 2005), so systematic, nationwide Mycobacterium tuberculosis genotyping for the 12-year study period was conducted at a single reference laboratory (4). While only 2,284 (73%) of the 3,131 notified cases during 1994–2005 were culture positive, 2,214 (97%) of the isolates from culture-positive cases underwent IS6110 restriction fragment–length polymorphism (RFLP) analysis. In population-based molecular epidemiology studies, the potential for missed transmission links increases rapidly as the proportion of genotyped cases falls (6). A strength of this report is the informative genotyping of 83% of culture-positive cases. The authors completely excluded the remaining isolates, which had fewer than five IS6110 copies. If these represent a random 17% subset of all culture-positive cases, the resultant underestimation of transmission should be modest (6). Ideally, these "low copy" isolates should have been genotyped by an alternate method. Failing that, demographic and clinical data comparing patients with "high copy" and "low copy" isolates would permit better judgment as to potential biases referable to the exclusions. Documentation of the numbers of pulmonary cases (smear-positive and smear-negative) and drug resistance would have been particularly welcome. This study's long duration and nationwide scope promote stable estimates of the extent to which TB cases reflect ongoing transmission. They reduce the impact of undetected transmission, related to missing partners diagnosed outside the temporal or geographic limits of the study (7). The long duration also reduces the emphasis on HIV-infected patients inherent in studies with a shorter duration, where detection of secondary cases hinges on rapid progression to active disease (8). The low overall proportions of matching isolates in both Norwegian- and foreign-born patients with TB are noteworthy: 19 and 21%, respectively. The incidence of "clustered" cases remained low, and clusters were small. Secondary cases referable to transmission within Norway were rare. Documented transmission (in either direction) linking foreign- and Norwegian-born patients in this study was extremely uncommon. In other countries, authorities have documented more frequent transmission within certain immigrant subgroups, but variable overlap with other community members—likely reflecting the degree of geographic and/or social separation (9–11). Instead, reactivation accounted for the progressive increase in TB incidence among foreign-born persons. Norwegian authorities may elect to review the process by which new entrants are diagnosed and treated for latent infection—notably those with medical and/or radiographic risk factors for reactivation (12). In the longer term, TB elimination in Norway will require enhanced TB control in immigrants' countries of origin (13). In the patients described by Dahle and colleagues, no clusters involved isolates of the Beijing lineage, although inference was limited in this respect. A subset of 150 isolates from 2003–2005 was further characterized by spoligotyping, so as to detect isolates of this lineage: only 19 were identified. There is a striking contrast between the 21% prevalence of IS6110 RFLP matches in Norway, and the 65% prevalence of spoligotype matches in the United States, based on preliminary data from the National TB Genotyping Network (2004–2006) (14). Despite evident differences in population and TB epidemiology, the discrepancy reinforces earlier concerns that limited specificity may hamper inference from spoligotypes in large population studies (15). In Norway, extended outbreaks are rare; no new clusters involving more than five patients have been documented since 1999. Health personnel appear to have reached an increasingly diverse population where they are able to accomplish prompt diagnosis and treatment and successful contact investigation. Patients clearly have access to providers who are attuned to the diagnosis of TB. This may be the most important lesson. For surveillance and preventive interventions, it is relevant to distinguish foreign-born from "native born" individuals. But in Norway, authorities and providers seem to recognize that, ultimately, all patients with TB and their contacts are "true" Norwegians: all deserve ready access to prompt, effective care (16). One day in Norway, foreign-born patients with TB stopped being "them," and instead became "us." I hope a similar lesson emerges from the Andrew Speaker saga. When his photograph and his story flashed across our television screens, even those who considered TB someone else's problem (if they considered it at all) were confronted by the fact that tuberculosis belongs to all of us. FOOTNOTES Conflict of Interest Statement: K.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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