Foreign-born persons account for the majority of cases reported in the U.S. 
and approximately 4 out of 5 of these cases can be attributed to reactivation TB. Cases of reactivation TB among the foreign-born account for half of all cases and represent the single largest challenge to achieving TB elimination in the U.S. This national estimate is consistent with numerous smaller, more localized studies in the United States 
and in Europe 
. This evidence suggests that the majority of reported TB cases are due LTBI acquired prior to entering the U.S. and subsequent reactivation of TB among foreign-born persons, either occurring soon before or soon after entering the U.S. Therefore, addressing the burden of LTBI in persons entering the United States through either LTBI testing and treatment or through prevention of LTBI will be essential for TB elimination. While immigration screening programs have been enhanced to improve detection and treatment of tuberculosis disease in this population, the primary purpose is to identify active TB disease, not LTBI testing and treatment among adults 
Currently, there is no policy to test for LTBI among foreign-born adults prior to or during their entry process to the U.S. 
. The only persons that are tested for LTBI during the immigration process are children aged 2–14 years from countries with TB incidence exceeding 20/100,000. The primary purpose of this testing is to identify children who need more complete evaluation for active TB disease, not to identify and treat patients with LTBI. For foreign-born persons who already reside in the United States, current guidelines recommend LTBI testing only for persons who have been in the U.S. <5 years 
To meet the goal of TB elimination in the U.S., (1 case per 1,000,000 persons per year), the burden of LTBI among the foreign-born will have to be reduced 
. There are two general approaches to doing this: 1) find and treat foreign-born persons with LTBI (either before or after they enter the United States); or 2) prevent LTBI in foreign-born persons by improving TB control in their country of origin, thereby reducing TB transmission and the risk of TB infection 
In addition to testing for LTBI, success also requires initiating and completing treatment of persons with LTBI. The current standard therapy for LTBI, isonaizid (INH), can reduce the risk of progression from LTBI to active TB by as much as 90% if taken daily for 9 months 
. Unfortunately completion rates for 9 months of INH are poor, but vary under programmatic conditions; with many programs reporting less than 50% completion 
. A new regimen, a once weekly dose of INH and rifapentine taken for 12 weeks (3HP), has the potential to improve adherence and completion of therapy 
and perhaps may influence the intent to treat LTBI among foreign-born persons. These regimens are likely to be efficacious, as only 9.4% (n
1,748) of all foreign-born person with reactivation TB had isolates that were resistant to INH, rifampicin, or both during the 5 year study period.
This study does have some important limitations. First, isolate submission to the U.S. National TB Genotyping Service (NTGS) is voluntary, thus the database, although large, did not contain all reported culture-positive TB cases for the study period. However the potential for systematic bias due to voluntary isolate submission is unlikely, as we found no statistical difference with regards to clinical, demographic, or social factor between TB cases with and those without genotyping results (data not shown). Second, spatial and genotype clustering serves only as a proxy for differentiating recent TB transmission and reactivation TB in the absence of detailed data on interpersonal connections between cases. It is possible that recent immigrants who became infected with the same genotype elsewhere and resettle in the same neighborhood in the U.S. could subsequently develop TB after resettlement and falsely be considered recent TB transmission. Third, although spoligotyping and 12-locus MIRU-VNTR have good discriminatory power, these methods may not provide the resolution necessary to differentiate evolutionarily close strains 
. Moreover, deriving the portion of reactivation TB among foreign-born persons based on genotyping methods is dependent on the genetic diversity of strains circulating in different regions of the world. The introduction of a more specific expanded panel of 24 MIRU-VNTR loci in 2009 to NTGS may reduce this misclassification in the future. It is important to note that each of these limitations would most likely underestimate the true proportion of foreign-born persons attributed to reactivation TB, further emphasizing the importance of reactivation TB in the United States.
At present, the high burden of reactivation TB is caused primarily by 1) the lack of LTBI screening among adult immigrants, both prior to arrival and after taking up residence, and 2) low initiation and completion rates for LTBI treatment 
; and 3) ongoing high rates of TB disease (and therefore infection) in many countries from which foreign-born persons come to the United States. To reduce the incidence of TB among foreign-born persons, efforts to increase testing and for those testing positive both initiation and completion of therapy must be applied both for those planning to immigrate and those already residing in the U.S., and thus needs to be combined with efforts to improve global TB control. While universal testing and treatment for LTBI among all foreign-born persons would not be cost-effective, as most would not progress to active TB disease 
, targeted, cost-effective testing strategies need to be developed that account for incidence in country of origin, travel, and medical history 
. Given the low specificity of TST, the use of interferon-gamma release assays (IGRA) might be a more suitable screening tool in these situations 
. Studies to measure the efficacy and cost-benefit of these programs should include foreign-born populations residing in the U.S. and those planning to immigrate, as failure to detect and treat LTBI in the country of origin can have costs in the U.S 
. Strategies for completion of LTBI treatment among foreign-born persons and potential immigrants also need to be developed, which might include non-traditional DOT strategies, incentives, shortened treatment regimens, and social service support. Operations research would be needed to identify the strategy that is most feasible, effective, and acceptable.
Finally, efforts to improve global TB control are needed. TB incidence remains very high in many countries, causing a very high proportion of persons living in those countries to develop LTBI. If TB incidence could be brought down, LTBI could be prevented in many persons. All of these efforts combined will be needed to substantially impact the burden of LTBI in foreign-born persons entering the United States. Without addressing that LTBI burden, it will be impossible to achieve our goal of TB elimination.