Overcoming the Limits of Tuberculosis Prevention among Foreign-Born Individuals: Next Steps toward Eliminating Tuberculosis

In an article in this issue of Clinical Infectious Diseases, Walter et al. [1] demonstrate that the majority of tuberculosis (TB) cases among foreign-born persons in San Francisco, California, would not have been prevented, even if current guidelines were implemented perfectly. This finding, together with previously published evidence, makes it clear that TB will not be eliminated in the United States in the foreseeable future without changes to our current strategies for TB control among foreign-born persons.

From 1993 through 2006, the number of TB cases in the United States decreased by 45%, from 25,108 to 13,767. However, the decrease has occurred disproportionately among the US-born population, in which the number of cases has decreased by 66%. Over the same interval, the number of foreign-born TB cases in the United States actually increased by 5%. In 2006, 57% of all TB cases reported were among foreign-born persons [2]. If current trends continue, this proportion will continue to grow, and we could reach a point at which TB is nearly eliminated among US-born persons but is still a major problem among foreign-born individuals. Similar trends have been noted in other countries with a low burden of TB; in several European countries, >50% of TB cases occur among foreign-born persons [3].

These trends raise a fundamental question: why do current TB-control strategies have such limited impact on the foreign-born population? The article by Walter et al. [1] complements previously published evidence to provide some answers to this question and to guide future efforts to control and eliminate TB.

TB control in the United States relies on 3 main strategies: (1) early diagnosis and treatment of persons with active TB, (2) investigation of contacts of persons with active TB and treatment of those contacts who are found to have active TB or latent TB infection (LTBI), and (3) targeted LTBI testing and treatment of persons at high risk for active TB using tuberculin skin tests or other assays for Mycobacterium tuberculosis [4]. The first 2 of these priorities, which are widely implemented in the United States, largely focus on interrupting ongoing community TB transmission. The third priority, on the other hand, is not widely implemented and focuses on testing and treating populations at high risk for LTBI before they develop active TB.

Studies of TB genotypes in the United States suggest that TB among foreign-born individuals is typically attributable to activation of LTBI that was likely acquired before arrival to the United States and is less often attributable to recent TB transmission [5, 6]. Because TB-control strategies in the United States focus on interrupting recent transmission of disease, it is understandable that current US TB-prevention strategies have limited success in a large subset of foreign-born individuals, who immigrate to the United States with high rates of LTBI. This emphasizes the importance of finding and treating LTBI for TB control among the foreign-born population.

Walter et al. [1] report findings involving 223 foreign-born persons with TB disease, 85 (38%) of whom had cases in which an indication for testing existed but guidelines were not applied, 95 (43%) of whom had no indication for testing, and 43 (19%) of whom were deemed to have cases that were not preventable through finding and treating LTBI. Several lessons regarding the prevention of TB among the foreign-born population can be learned from these findings. First, even in a well-functioning TB-control program without substantial resource limitations, many patients with TB had indications for LTBI screening but were not tested. These high-risk foreign-born persons are certainly the highest yield population of persons for testing, and they should remain the top priority for targeted testing. Second, a large portion of foreign-born persons who develop TB disease do not meet current US guidelines for screening for LTBI. This finding supplements a previous study that showed that 50% of foreign-born TB cases occurred among persons who had been in the United States for >5 years and, thus, would not qualify as being at high risk for TB according to current guidelines [7]. Case rates in this population remain markedly higher than those in US-born persons; finding and treating LTBI in this group will be necessary to eliminate TB. Finally, some cases could not be prevented by finding and treating LTBI. Other strategies are needed to address this population. The following suggestions attempt to answer the question of what can be done to reduce the rate of TB in this population.

Expand indications for targeted testing and improve the yield of targeted testing programs.Nearly all populations of foreign-born persons have elevated rates of TB, even long after arrival to the United States. The benefits of LTBI treatment in these populations generally outweigh the risks of toxicity, and treatment is cost-effective [8, 9]. Extending current guidelines to include foreign-born persons from countries with a high incidence of TB who have been in the United States >5 years in the high-risk category is probably warranted. The challenge is that the population of foreign-born persons who have been in the United States >5 years is very large (∼29 million) [7]. To improve the yield of targeted testing, those foreign-born populations at highest risk for TB should be targeted first, particularly in programs that have substantial resource limitations. Recent migrants, persons from regions of the world with a high incidence of TB (e.g., sub-Saharan Africa and Southeast Asia), and those with additional risk factors for progression to active TB (e.g., HIV infection and diabetes) should be prioritized for screening and treatment.

Programs that have sufficient resources to go beyond screening only the highest risk groups (such as the program in San Francisco) should extend testing and treatment to other foreign-born persons. Likewise, we should further engage health care providers in TB prevention. Clinicians are already accustomed to disease screening and prevention, such as routine screening for hypercholesterolemia, hypertension, and cancer. Many of these conditions involve regular screening and lifetime treatment. Therefore, performing at least a one-time screening for LTBI and providing time-limited treatment seems to be quite achievable.

Develop a better test.Approximately 5% of foreign-born persons with a positive tuberculin skin test result will develop active TB during their lifetime, but the tuberculin skin test does not predict which persons are at highest risk for progressing to active TB. Research is needed to develop a better test for LTBI that would predict which persons are at the greatest risk for progression to active TB. This would allow targeting of treatment to the highest risk groups and, thus, would limit the risks of treatment to those most likely to benefit and make it easier to add measures to increase rates of treatment completion.

Improve LTBI treatment initiation and completion rates.Approximately 21% of persons who receive a diagnosis of LTBI will complete treatment [10]. Special programs, possibly including incentives, enablers, or even directly observed preventive therapy, may be needed for those patients at highest risk, such as foreign-born persons with HIV infection or chest radiograph abnormalities. In addition, a shorter regimen for LTBI treatment has great potential to increase both treatment initiation and completion rates, thereby improving the yield of targeted testing programs. More research on effective shorter regimens for LTBI is needed. If a shorter regimen were available, the feasibility of overseas LTBI testing and treatment could be explored.

Think locally, act globally.One-third of the world's population is infected with M. tuberculosis, and 8.9 million new cases of TB occur worldwide annually [11]. A commonly used mantra for TB control in the United States is to “think globally, act locally.” Because TB case rates among foreign-born persons correlate to case rates in their country of origin, global epidemiology can clearly guide domestic TB-control strategies. However, on its own, improving detection and treatment of LTBI is insufficient to eliminate TB in the United States. With TB out of control globally, the enormous global burden of multidrug-resistant TB, and the recent emergence of extensively drug-resistant TB [12], our focus should be not only on TB control within our borders but on TB control globally, as well. Thus, our new mantra must become “think locally, act globally.”

The study by Walters et al. [1] identifies a clear example of actions that can be taken outside of the borders of the United States to improve TB control within the United States. Of 231 patients with TB, 31 (14%) had presumably imported TB. Improving overseas screening and treatment of potential immigrants for TB may allow diagnosis and treatment of these persons prior to immigration. Screening may be improved by implementing more-sensitive techniques, such as mycobacterial culture, and/or by screening additional populations beyond those entering the United States on immigrant or refugee visas. Studies of the potential impact of enhanced screening in different countries or regions should guide implementation of these measures.

Finally, one study shows that, at least in some countries, investing in overseas TB control may be more cost-effective (even cost-saving) when compared with other approaches for improving TB control among foreign-born individuals [10]. Doing this also achieves the humanitarian benefit of preventing needless deaths from a treatable disease among some of the world's poorest people.

Although much of the information outlined above focuses on TB control in the United States, similar epidemiological conditions in other countries with a low burden of TB suggest that these strategies may be useful there, as well. To achieve significant improvement in domestic TB control, industrialized nations must invest in global TB control and impact the prevalence of TB beyond their borders [3]. To eliminate TB in the United States, a combination of different strategies will be needed. What is clear, both from previous evidence and from the study by Walters et al. [1], is that TB will not be eliminated in the near future if we maintain the status quo.

• Received September 4, 2007.
• Accepted September 7, 2007.

• © 2008 by the Infectious Diseases Society of America