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Tuberculosis Screening in Internationally Adopted Children: The Need for Initial and Repeat Testing

^a Department of Pediatrics
^c International Adoption Center, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
^b Department of Pediatrics, Washington University and St Louis Children's Hospital, St Louis, Missouri

	ABSTRACT

TOP ABSTRACT METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 
OBJECTIVE. Because most internationally adopted children come from areas of high tuberculosis prevalence, an initial tuberculin skin test is recommended after arrival to the United States. We evaluated whether repeat testing of children 3 months after arrival to the United States would identify additional children with latent tuberculosis infection.

METHODS. Internationally adopted children who were seen at our International Adoption Center and had a tuberculin skin test within 2 months of arrival to the United States were eligible for the study. Children not diagnosed with tuberculosis with initial testing were retested at least 3 months later. The prevalence of tuberculosis on arrival and after repeat testing was determined, and potential risk factors for infection were examined.

RESULTS. Of the 527 internationally adopted children with an initial tuberculin skin test completed, 111 (21%) had evidence of latent tuberculosis infection. Repeat tuberculosis testing was complete for 191 internationally adopted children (46.9% of those who had an initially negative tuberculin skin test). Latent tuberculosis infection was found in 20% of those who were retested. No children were found to have active tuberculosis disease. Children with an initially positive tuberculin skin test result had slightly higher weight-for-age z scores at their initial clinic visit, whereas those whose tuberculin skin test result was positive after repeat testing had slightly lower weight-for-age z scores. A strong correlation between BCG immunization and tuberculin skin test result was observed.

CONCLUSIONS. Latent tuberculosis infection is common in internationally adopted children. A high proportion of internationally adopted children had an initially false-negative tuberculin skin test. Repeat tuberculosis testing of all internationally adopted children with an initially negative tuberculin skin test should be the standard of care for identifying tuberculosis infection and preventing tuberculosis disease in this high-risk population.

Key Words: tuberculosis • screening • international adoption • BCG • malnutrition

Abbreviations: IAC—internationally adopted children • TB—tuberculosis • TST—tuberculin skin test • LTBI—latent tuberculosis infection • NTM—nontuberculous mycobacteria • PCP—primary care provider • CDC—Centers for Disease Control and Prevention • WHO—World Health Organization • OR—odds ratio • CI—confidence interval

Nearly 21000 children were adopted into the United States in 2006 from countries around the world, >3 times as many as 15 years earlier.¹ Initial health screening of internationally adopted children (IAC) is recommended,² but screening often varies by provider and by the country of origin of the child. Primary care providers and subspecialists have few evidence-based guidelines available to direct optimal diagnostic and therapeutic strategies for newly IAC.

The majority of IAC come from developing countries in which tuberculosis (TB) is endemic.¹ TB rates in the United States are highest among foreign-born individuals.^3,4 Children are a particularly high-priority group for treatment as a result of their increased risk for severe disease and their lifetime risk for reactivation of tuberculosis.⁵ Case reports of children,⁶ including IAC,⁷ serving as index cases for widespread transmission of TB further highlight the need for aggressive screening for TB in IAC.

Screening for TB by using a tuberculin skin test (TST) is recommended for all immigrants from high-prevalence countries shortly after arrival into the United States.⁴ For IAC, it is suggested that the TST be repeated once the child is better nourished if malnutrition is initially suspected,² although no specific evidence justifying this recommendation has been published. Although some evidence suggested that the receipt of the BCG vaccine should be considered when interpreting TST results,⁸ consensus guidelines^2,9–11 continue to recommend that TST results be interpreted without regard to BCG history, a recommendation that continues to be validated by recent studies.¹²

Although screening for TB shortly after adoption from a high-prevalence country is important for diagnosing both active and latent TB infection (LTBI),¹³ there is the possibility that relying only on early screening alone may not identify all children with TB. Factors such as undernourishment, concomitant infections, live vaccines, and immunosuppression have been linked to an anergic response to tuberculin, thereby limiting the delayed-type hypersensitivity reaction necessary to elicit a positive TST result.¹¹ Furthermore, because TB has a relatively long incubation period, the TST has poor sensitivity in identifying those with very recent exposure to TB.¹⁰ Thus, we hypothesized that repeating the TST months later for IAC who had an initially negative TST result immediately after entry into the United States may identify additional IAC with TB. Although current recommendations do suggest repeat screening at a later time for children with suspected malnutrition,² these guidelines do not quantify the number of cases of LTBI that may be missed with initial screening or which factors may be related to missed cases of TB. Although a nonspecific booster response to common mycobacterial antigens has been reported as a result of repeated TST, BCG vaccination, or exposure to nontuberculous mycobacteria (NTM),¹⁴ this response is less likely when the interval between tests exceeds 2 months.¹⁵ For this study, we sought to determine both the proportion of IAC with TB diagnosed on initial health screening shortly after arrival into the United States and also to determine whether additional infected children could be identified by repeat testing months later. We also examined whether specific factors such as age, birth country, BCG history, and nutritional status were associated with the TST result.

	METHODS

TOP ABSTRACT METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 
Study Setting
This study was conducted at Cincinnati Children's Hospital Medical Center's International Adoption Center. The International Adoption Center was established in November 1999 and provides both preadoption counseling and postadoption medical and developmental evaluation of IAC. Families are encouraged to have a postadoption evaluation performed within the first 2 weeks after arrival of their adopted child to the United States. At that visit, a comprehensive medical and developmental evaluation is completed, and screening tests, including an HIV test and TST, are performed. A follow-up postadoption visit is strongly encouraged for all IAC 6 months after the initial visit, unless medical, social, or developmental concerns warrant an earlier visit. The Cincinnati Children's Hospital Medical Center institutional review board approved this study by using a limited data set agreement for this research.

Study Population
IAC who were evaluated at the International Adoption Center at Cincinnati Children's Hospital Medical Center for an initial postadoption visit between November 1999 and June 2004 were included in this study when they were seen within 2 months after their arrival to the United States and had their first postadoption TST during this visit. Demographic and anthropometric information was collected routinely on all children, and the child's medical history was obtained through examination of medical charts from the child's birth country and by interviewing the child's adoptive parents. Immunization and medical charts were reviewed for identification of documentation of BCG vaccine, and the child's entire body was examined for the characteristic BCG scar. For the purposes of this study, children who had either a BCG scar or written documentation of BCG vaccination were considered to have evidence of BCG immunization. Children who were known to have received a measles-containing vaccine 6 weeks before the visit did not have a TST and, therefore, were not eligible for the study because measles vaccines can temporarily suppress tuberculin reactivity.¹¹

Tuberculin Skin Testing
The Mantoux method of tuberculin skin testing was used for all children.¹⁶ Five tuberculin units of purified protein derivative (0.1 mL; Aplisol [Parkedale Pharmaceuticals Inc, Rochester, MN]) were injected intradermally into the volar or dorsal aspect of each child's forearm¹⁰ by 1 of 3 trained advanced practice nurses at our International Adoption Center. Only children whose TST was read by a physician or a nurse 48 to 72 hours after placement were included in the analysis. A TST result was considered positive when there was at least 10 mm of induration, consistent with recommendations for recent immigrants from high-prevalence countries.¹⁰ All children with a positive TST result had chest radiographs performed for assessment for active TB disease. When no signs of TB were demonstrated by chest radiograph or physical examination, the child was given a diagnosis of LTBI and a 9-month course of isoniazid was prescribed.

For children who had a negative initial TST result, detailed written instructions were sent to the child's adoptive parents and designated primary care provider (PCP) recommending a repeat TST at least 3 months after the initial TST, either in their PCP's office or during a follow-up visit to the International Adoption Center. Anthropometric data were again recorded when this repeat TST was performed. TSTs that were performed or read by the PCP were obtained via telephone calls and letters to the PCP's office.

Statistical Analysis
Data were abstracted from each patient's chart into a TELEform (Cardiff Software Inc, Vista, CA), and these forms were then digitally scanned into a computerized database. Other relevant data from the child's chart included each child's age in days, birth country, time elapsed since adoption, the presence or absence of evidence suggesting receipt of BCG vaccination (scar or vaccination record),¹⁷ and weight at the time of initial evaluation in our clinic. Each child's weight was converted to z scores on the basis of Centers for Disease Control and Prevention (CDC) growth charts^18–21 and on the World Health Organization (WHO) growth charts.²² The weight-for-age z scores were used as a marker for potential effects of malnutrition on growth. Birth country was also analyzed as a possible confounder because of potentially varying rates of TB exposure in each country, which may also be a predictor of the rate of BCG immunization in the population. For birth countries with 10 children, IAC were grouped by geographic region rather than by country for maintaining anonymity.

Multivariable regression analyses were also performed to investigate the possible association between TST result and malnutrition while accounting for birth country and BCG vaccination as possible confounders. For these analyses, a weight-for-age z score >2 SDs below the mean was used as a marker for malnutrition. Because of the relatively small numbers of IAC from most individual countries, this regression analysis focused on the subset of 432 IAC from Russia, China, Guatemala, Kazakhstan, and South Korea. Because Guatemala had the highest proportion of children with a positive initial TST result (32% at initial visit), this country was used as the reference group in this multivariable regression when analyzing country of origin as a possible confounder.

All statistical analyses were conducted by using Excel 2003 (Microsoft Corp, Redmond, WA) and SAS 9.1 (SAS Institute, Inc, Cary, NC). Means with SDs and medians with ranges are reported for continuous variables. Crude associations between TST results and possible continuous covariates were tested by using either the Student's t test or the Wilcoxon rank-sum test as appropriate. The Pearson's ² test was used to test associations between TST result and categorical variables. Logistic regression was used to model the relationship between TST result and covariates and/or confounders. Results from the logistic models are reported as odds ratios (ORs) with 95% confidence intervals (CIs).

	RESULTS

TOP ABSTRACT METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 
Study Population
A total of 769 IAC were seen for initial visits at the International Adoption Center between November 1999 and June 2004. Of those seen, 549 (71%) had their first TST performed at the center within 2 months of arrival to the United States and, thus, met eligibility criteria for inclusion in the study (Table 1). The mean age of study children was 23 months, and 54% were female. Eligible children came from 29 different countries, with 81% coming from Russia, China, Guatemala, Kazakhstan, or South Korea, an adoption pattern very representative of that seen nationally.¹ The majority (81%) of IAC had evidence of BCG vaccination, with children from South Korea being notable outliers with only 15% with evidence of BCG. Very few children (n = 8) had documentation of receipt of multiple BCG vaccinations with dates (1 child had 3 documented vaccinations, the rest had 2). These children were from Kazakhstan (n = 3), Eastern Europe (n = 2), Russia (n = 2), and China (n = 1). A large number of children were also noted to have an initial weight that fell 2 SDs below their age- and gender-normalized mean on the CDC growth charts.¹⁸ None of the children tested positive for HIV infection.

View larger version (25K): [in this window] [in a new window]   FIGURE 1 Initial and repeat TST results.

The mean (SD) weight-for-age z score in the study population was –1.44 (1.34). The median (range) was –1.32 (–7.00 to 3.90). Malnutrition (defined as a z score less than –2.0) was seen in 158 (30%) children. The median (range) weight-for-age z score for IAC with a positive TST result was slightly higher than those with a negative TST result (–1.13 [–5.40 to 1.31] vs –1.38 [–7.00 to 3.94]; P = .06). Children with an initially negative TST result were more likely to be malnourished, compared with children who had an initially positive TST result (31% vs 22%; P = .06). We did not find institutionalization status to be related to TST result, as has been postulated by others.¹³ IAC who had lived in an orphanage or hospital at any time had a positive TST result 19.7% of the time, those who had lived in an orphanage for at least 6 months were positive 19.5% of the time, and those who had resided in a foster home were positive 24.1% of the time.

Multivariable regression analysis of children from the 5 countries with the most IAC in our study (Table 4) also showed that malnourished children were less likely to have a positive TST result at the initial visit, compared with children with a z score of –2.0 or more (OR: 0.58 [95% CI: 0.33–1.02]; P = .06). We also analyzed these data using WHO z scores and found no significant change in the effect sizes (ORs) reported in the logistic regression models. Children with initial weight-for-age z scores that were >2 SDs below the mean were still less likely to have had a positive TST result at the initial visit, with virtually the same effect sizes (OR: 0.53 instead of 0.58). Children who were older than 10 years were omitted from this analysis because no WHO z score was available for them.

Repeat TST Results
A repeat TST at least 3 months after the initial TST was recommended for IAC whose initial TST result was negative or not read. Despite numerous reminders to adoptive parents and primary care providers, only 191 (46%) of the 416 IAC with an initially negative TST result had a repeat TST performed and read at least 3 months after their initial test (Fig 1). Of these, 38 (20%) were found to be positive for LTBI. Thirty-five (92%) of these 38 IAC had TST indurations that increased by 10 mm at repeat testing; the other 3 had indurations that increased by 2 mm, 5 mm, and 9 mm. Whereas the average (SD) weight-for-age z score at the initial visit for this subset of children with a repeat TST was –1.70 (1.50), the average (SD) z score at the time of repeat TST was –0.85 (1.10).

Children with a repeat TST (n = 191) had a slightly higher median (range) age of adoption in months compared with children (n = 225) who did not have a repeat TST (14.1 [3.9–101.0] vs 12.5 [1.2–200.0]; P = .01]. IAC who had a repeat TST were slightly more likely to be male (51% vs 41%; P = .05) and more likely to be malnourished (37% vs 26%; P = .02) compared with those who did not return for a repeat TST.

The mean (SD) age of adoption for the 191 children who had a repeat TST performed and read in the appropriate time frame was 22.1 (18.6) months. The median (range) was 14.1 (3.9–101.0) months. The median (range) age of adoption in months in the group with a positive TST result (n = 38) compared with those with a negative TST result (n = 153) was not significantly different (15.2 [5.6–97.2] vs 14.1 [3.9–101.0]; P = .68).

We compared the relationship between weight at the initial postadoption visit with the result of a repeat TST for IAC for whom this repeat TST was indicated. The mean (SD) weight-for-age z score for children with a repeat TST was –1.70 (1.49). The median (range) was –1.57 (–7.0 to 3.9). Malnutrition (z score less than –2.0) was seen in 70 (37%) children. In contrast to the results observed with initial TST, the group of children who had a positive repeat TST result had a lower median (range) weight-for-age z score at the initial visit, compared with children who had a negative repeat TST result (–1.99 [–4.7 to –0.09] vs –1.55 [–7.0 to –3.94]; P = .007). Children with a positive repeat TST result were more likely to be malnourished at the initial visit, compared with children who had a negative repeat TST result (50% vs 33%; P = .06). These results were again very similar when using WHO growth parameters instead of CDC parameters.

Of the 191 IAC who had a repeat TST performed after having an initially negative TST result, 175 (91.6%) had an initial TST with no induration, and 31 (17.7%) of these children had a repeat TST result that was positive. In contrast, 16 (8.4%) of the 191 initially had 1 to 9 mm of induration, and 7 (43.8%) of these had a positive repeat TST result (P = .03).

Multivariable regression analysis (Table 5) was performed using the subset of IAC from Russia, China, Guatemala, and Kazakhstan (n = 144), because no IAC from South Korea had a positive TST result at the follow-up visit. In contrast to what was found with the initial TST, malnourished children were more likely to have a positive repeat TST result compared with children who were not malnourished, although this finding was not statistically significant (OR: 1.7 [95% CI: 0.75–3.8]; P = .20). Children with evidence of BCG vaccination were again more likely to have a positive repeat TST result than those without evidence of vaccination (OR: 7.1 [95% CI: 0.90–56.0]; P = .06). There did not seem to be any relationship between having a positive repeat TST result and country of birth.

	DISCUSSION

TOP ABSTRACT METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

Some of the earliest data on TB screening among IAC were presented by Hostetter et al,^25,26 who showed a TB prevalence of 3% in their series. It is not entirely clear why our results differ from the results of these 2 studies. One reason may be that the countries of origin differ remarkably between our cohort and theirs; for example, 41% of their subjects were from South Korea, a country with a relatively low prevalence of TB. Another reason may be who read the TST. In out study, we included only IAC whose TST was read by a health care provider. This has been shown to increase significantly the accuracy of TST interpretation, although even trained heath care providers are also subject to "underreading" of the TST.^27,28 In the Hostetter series, it was not described whether the TST was read by a health care provider. Three other published studies used IAC that were from similar birth countries and adopted during a similar time period.^19,20,29 Saiman et al²⁹ showed a rate of LTBI of 19% in their population, similar to our rate. In their study, it was stated that a health care provider read each child's TST. Miller et al,^19,20 in contrast, reported rates of positive TST results of 6% to 7% in their studies; however, they did not specify who read the TST. A more recent study by Mandalakas et al¹³ found a prevalence of 11.9% in 880 IAC who were evaluated between 1986 and 2001; however, the origins of the children evaluated was different from in our study and what is seen nationally, with a higher proportion of children from South Korea (18.4%) and India (12.1%) and a lower proportion from China (10%), which may account for the overall lower prevalence that they observed. These methodologic differences may explain the difference in observed LTBI prevalence between our study and the others. At the same time, we also acknowledge that in our study the repeat TSTs were placed and read by either the International Adoption Center or the PCP and that this variability may also have led to underreading of the repeat TSTs.

These previous studies also did not comment on when (relative to their arrival to the United States) their children were tested for TB. In our series, we included only children who were initially tested within 2 months after arrival. This allowed us the unique opportunity to retest at a later date many children whose TST result was initially negative to assess the role that repeat testing should play in the care of IAC. To our knowledge, this is the first study to explore the issue of retesting children with an initially negative TST result and the risk factors related to TST results.

Our most striking observation was that a large percentage of children with LTBI are not identified by an initial TST performed shortly after arrival. When those with an initially negative TST result were retested at least 3 months after their initial test, 20% had a positive repeat TST result. Presumably, these children were not exposed to TB in the United States but instead at this later date were better able to mount an appropriate delayed hypersensitivity response to the TST. The hypothesis that this is perhaps a result of improved nutrition is supported by our data showing that those with an initially positive TST result had a higher weight-for-age z score (–1.13 vs –1.38; P = .06). This is further supported by examination of the initial weights of IAC who had a repeat TST performed after having had an initially negative TST result: in these children, the weight-for-age z scores were lower in those with a repeat TST result that was positive (–1.99 vs –1.55; P = .007), suggesting that they did indeed have LTBI at the time of initial testing but were unable initially to mount a sufficient immune response to have a positive TST result. Nevertheless, because weight is not an ideal proxy for immune status or the ability to mount a response to the TST and because a large number of IAC with weights in the reference range did have a positive TST result on repeat screening, we believe that guidelines for the care of IAC should include recommendations for retesting all IAC with an initially negative TST result, not just those considered "malnourished," at least 3 months after their initial test.

A limitation of our study was the relatively low rate of repeat TST performed in IAC whose initial TST result was negative or not read (Fig 1), despite recommending repeat testing to adoptive parents and their PCPs. Even among the highly motivated population of adoptive parents who brought their children to our International Adoption Center despite the time and commitment required, only 49% followed up with a repeat TST after an initially negative TST result. Extrapolating our finding that 20% of IAC who had a repeat TST performed had LTBI to those in whom a repeat TST was not performed or not read would give us an overall prevalence of LTBI of almost 37% in our population of IAC. Of these, only 57% would have been discovered without repeat testing.

Other factors that are postulated to be related to initial and repeat TST result were also examined. Some physicians and adoption professionals recommend against TST for IAC until after 1 year of age because of concerns about the link between BCG and TST; however, we found no significant correlation between the age of adoption or age at testing and the likelihood of having a positive TST result, either initially (P = .32) or at follow-up (P = .68). We also observed that IAC from South Korea were the only children (among the 5 most represented countries) to be statistically less likely to have a positive TST result in our logistic regression analysis.

The final variable of interest to us was the association between BCG immunization status and TST result. Although BCG continues to provide valuable and cost-effective protection against TB for children in high-prevalence countries worldwide,^30,31 the interpretation of TST in children with BCG continues to be controversial, with some investigations showing an association^8,32 and others not showing an association.^{12,17,33–35} In IAC, our study found a strong association between BCG immunization status and a positive TST result, similar to that seen by Saiman et al²⁹; however, our results still do not clarify whether the positive TST results observed are a result of BCG immunization or a response to previous exposure to mycobacteria (either TB or NTM).

Several studies have also examined the booster effect in repeat TB testing.^36–38 In a study design that was similar to ours with regard to repeat TB testing in an immigrant population,³⁶ 664 Indochinese refugees had a TST placed and 46% were found to have an initially positive TST result. A repeat TST was placed 60 days later in the 217 with initially negative TST results, and 43% converted. The average age was 21 years with a range of 1 to 80 years, far older than our population. No significant association was found with age or BCG vaccination, and the role of malnutrition was not examined. In a different population of Canadian students, in which many of the students had documentation of BCG vaccination, 2-step testing was performed to examine whether a booster effect would be observed.³⁷ Overall, there were 1542 participants, and 6.6% had a positive TST result. Of the 1435 students with an initially negative TST result, a second test was placed and 5.2% had a positive reaction. Unlike our study, they found a significant association with older age. Similar to our study, however, a significant association with a large initial reaction and previous BCG vaccination was found. In a final study,³⁸ 69 TST-negative healthy volunteers received BCG vaccine and had serial TSTs performed to determine the prevalence, persistence, and boosting of TST reactions. Overall, 10% had persistent reactions 15 mm, and 3% had boosting of 15 mm 1 to 3 years later. Although this study does demonstrate the effect of BCG on the TST response, it is unclear how to use this information in a population of BCG-vaccinated children who are at high risk for TB exposure, infection, and disease.

New technologies using interferon- release assays show promise in helping to resolve this limitation of the TST.³⁹ Until these or other screening methods become standard for TB detection in children, we continue to support the current practice guidelines, which recommend that a history of BCG not be a contradiction to placement of a TST and that interpretation of the TST should not be influenced by a history of BCG immunization.^2,9

	CONCLUSIONS

TOP ABSTRACT METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 
Our experience with TB over several years at our International Adoption Center shows a high rate of LTBI in IAC. Furthermore, a large percentage of LTBI goes undiagnosed because of failure to repeat the TST for children whose initial TST result was negative or not read. Additional investigation is warranted to inform better whether TB screening guidelines for immigrant children and adults in general^4,40,41 should include a recommendation for repeat testing when the initial TST result is negative or not read in these high-risk populations.

	ACKNOWLEDGMENTS

 
We thank Marina Bischoff, Vanessa Florian, Emilie Grube, Tyler Browning, Elizabeth Roberts, Rotimi Okunade, and Kristen Frommeir for assistance with this study. We are indebted to all of the wonderful children and their families who participated in this study, helping to improve the health of internationally adopted children in the future.

	FOOTNOTES

 
Accepted Jan 4, 2008.

Address correspondence to Mary Allen Staat, MD, MPH, Cincinnati Children's Hospital Medical Center, Division of Infectious Diseases, 3333 Burnet Ave, Cincinnati, OH 45229-3039. E-mail: mary.staat{at}cchmc.org

Portions of this work were presented at the annual meeting of the Pediatric Academic Societies; May 17, 2005; Washington, DC.

The authors have indicated they have no financial relationships relevant to this article to disclose.

What's Known on This Subject Several studies have been conducted to assess the prevalence of TB infection in internationally adopted children and have shown that these children are at high risk for TB.

 

What This Study Adds Retesting internationally adopted children for TB after they have been home for a period of time identifies additional children who have TB infection and would have otherwise been missed.

 

	REFERENCES

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1. US Department of State. Immigrant visas issues to orphans coming to U.S. Available at: http://travel.state.gov/family/adoption/stats/stats_451.html. Accessed December 19, 2007
2. Pickering LK, Baker CJ, Long SS, McMillan JA, eds. Red Book: 2006 Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics;2006
3. Nelson LJ, Schneider E, Wells CD, Moore M. Epidemiology of childhood tuberculosis in the United States, 1993–2001: the need for continued vigilance. Pediatrics.2004; 114 (2):333 –341[Abstract/Free Full Text]
4. Taylor Z, Nolan CM, Blumberg HM; American Thoracic Society; Centers for Disease Control and Prevention; Infectious Diseases Society of America. Controlling tuberculosis in the United States. Recommendations from the American Thoracic Society, CDC, and the Infectious Diseases Society of America [published correction appears in MMWR Morb Mortal Wkly Rep. 2005;54(45):1161]. MMWR Recomm Rep.2005; 54 (RR-12):1 –81[Medline]
5. Horsburgh CR Jr. Priorities for the treatment of latent tuberculosis infection in the United States. N Engl J Med.2004; 350 (20):2060 –2067[Abstract/Free Full Text]
6. Phillips L, Carlile J, Smith D. Epidemiology of a tuberculosis outbreak in a rural Missouri high school. Pediatrics.2004; 113 (6). Available at: www.pediatrics.org/cgi/content/full/113/6/e514
7. Curtis AB, Ridzon R, Vogel R, et al. Extensive transmission of Mycobacterium tuberculosis from a child. N Engl J Med.1999; 341 (20):1491 –1495[Abstract/Free Full Text]
8. Bozaykut A, Ipek IO, Ozkars MY, Seren LP, Atay E, Atay Z. Effect of BCG vaccine on tuberculin skin tests in 1–6-year-old children. Acta Paediatr.2002; 91 (2):235 –238[CrossRef][ISI][Medline]
9. American Thoracic Society, Centers for Disease Control and Prevention. Diagnostic standards and classification of tuberculosis in adults and children. Am J Respir Crit Care Med.2000; 161 (4 pt 1):1376 –1395[Free Full Text]
10. American Thoracic Society. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR Recomm Rep.2000; 49 (RR-6):1 –51[Medline]
11. Pediatric Tuberculosis Collaborative Group. Targeted tuberculin skin testing and treatment of latent tuberculosis infection in children and adolescents. Pediatrics.2004; 114 (4 suppl):1175 –1201[Abstract/Free Full Text]
12. Sleiman R, Al-Tannir M, Dakdouki G, Ziade F, Assi NA, Rajab M. Interpretation of the tuberculin skin test in Bacille Calmette-Guerin vaccinated and nonvaccinated school children. Pediatr Infect Dis J.2007; 26 (2):134 –138[CrossRef][ISI][Medline]
13. Mandalakas AM, Kirchner HL, Iverson S, et al. Predictors of Mycobacterium tuberculosis infection in international adoptees. Pediatrics.2007; 120 (3). Available at: www.pediatrics.org/cgi/content/full/120/3/e610
14. Menzies D. Interpretation of repeated tuberculin tests: boosting, conversion, and reversion. Am J Respir Crit Care Med.1999; 159 (1):15 –21[Free Full Text]
15. Cauthen GM, Snider DE Jr, Onorato IM. Boosting of tuberculin sensitivity among Southeast Asian refugees. Am J Respir Crit Care Med.1994; 149 (6):1597 –1600[Abstract]
16. Centers for Disease Control and Prevention, Division of Tuberculosis Elimination. Tuberculin skin testing. Available at: www.cdc.gov/tb/pubs/corecurr/Chapter4/Chapter_4_Skin_Testing.htm. Accessed December 19, 2007
17. Santiago EM, Lawson E, Gillenwater K, et al. A prospective study of bacillus Calmette-Guerin scar formation and tuberculin skin test reactivity in infants in Lima, Peru. Pediatrics.2003; 112 (4). Available at: www.pediatrics.org/cgi/content/full/112/4/e298
18. National Center for Health Statistics. NHANES: CDC growth charts: United States. Available at: www.cdc.gov/nchs/about/major/nhanes/growthcharts/datafiles.htm. Accessed December 19, 2007
19. Miller LC, Hendrie NW. Health of children adopted from China. Pediatrics.2000; 105 (6). Available at: www.pediatrics.org/cgi/content/full/105/6/e76
20. Miller L, Chan W, Comfort K, Tirella L. Health of children adopted from Guatemala: comparison of orphanage and foster care. Pediatrics.2005; 115 (6). Available at: www.pediatrics.org/cgi/content/full/115/6/e710
21. Miller LC, Tseng B, Tirella LG, Chan W, Feig E. Health of children adopted from Ethiopia. Matern Child Health J.2007; Aug 22
22. World Health Organization. The WHO child growth standards. Available at: www.who.int/childgrowth/standards/en/index.html. Accessed December 19, 2007
23. Nelson LJ, Wells CD. Tuberculosis in children: considerations for children from developing countries. Semin Pediatr Infect Dis.2004; 15 (3):150 –154[CrossRef][Medline]
24. Lange WR, Warnock-Eckhart E, Bean ME. Mycobacterium tuberculosis infection in foreign born adoptees. Pediatr Infect Dis J.1989; 8 (9):625 –629[ISI][Medline]
25. Hostetter MK, Iverson S, Dole K, Johnson D. Unsuspected infectious diseases and other medical diagnoses in the evaluation of internationally adopted children. Pediatrics.1989; 83 (4):559 –564[Abstract/Free Full Text]
26. Hostetter MK, Iverson S, Thomas W, McKenzie D, Dole K, Johnson DE. Medical evaluation of internationally adopted children. N Engl J Med.1991; 325 (7):479 –485[Abstract]
27. Ozuah PO, Burton W, Lerro KA, Rosenstock J, Mulvihill M. Assessing the validity of tuberculin skin test readings by trained professionals and patients. Chest.1999; 116 (1):104 –106[CrossRef][ISI][Medline]
28. Carter ER, Lee CM. Interpretation of the tuberculin skin test reaction by pediatric providers. Pediatr Infect Dis J.2002; 21 (3):200 –203[CrossRef][ISI][Medline]
29. Saiman L, Aronson J, Zhou J, et al. Prevalence of infectious diseases among internationally adopted children. Pediatrics.2001; 108 (3):608 –612[Abstract/Free Full Text]
30. Soysal A, Millington KA, Bakir M, et al. Effect of BCG vaccination on risk of Mycobacterium tuberculosis infection in children with household tuberculosis contact: a prospective community-based study. Lancet.2005; 366 (9495):1443 –1451[CrossRef][ISI][Medline]
31. Trunz BB, Fine P, Dye C. Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness. Lancet.2006; 367 (9517):1173 –1180[CrossRef][ISI][Medline]
32. Young J, O'Connor ME. Risk factors associated with latent tuberculosis infection in Mexican American children. Pediatrics.2005; 115 (6). Available at: www.pediatrics.org/cgi/content/full/115/6/e647
33. Karalliedde S, Katugaha LP, Uragoda CG. Tuberculin response of Sri Lankan children after BCG vaccination at birth. Tubercle.1987; 68 (1):33 –38[ISI][Medline]
34. al-Kassimi FA, Abdullah AK, al-Orainey IO, et al. The significance of positive Mantoux reactions in BCG-vaccinated children. Tubercle.1991; 72 (2):101 –104[CrossRef][ISI][Medline]
35. Young TK, Mirdad S. Determinants of tuberculin sensitivity in a child population covered by mass BCG vaccination. Tuber Lung Dis.1992; 73 (2):94 –100[CrossRef][ISI][Medline]
36. Morse DL, Hansen RE, Swalbach WG, Redmond SR, Grabau JC. High rate of tuberculin conversion in Indochinese refugees. JAMA.1982; 248 (22):2983 –2986[Abstract]
37. Menzies R, Vissandjee B, Rocher I, St Germain Y. The booster effect in two-step tuberculin testing among young adults in Montreal. Ann Intern Med.1994; 120 (3):190 –198[Abstract/Free Full Text]
38. Hoft DF, Tennant JM. Persistence and boosting of Bacille Calmette-Guerin-induced delayed-type hypersensitivity. Ann Intern Med.1999; 131 (1):32 –36[Abstract/Free Full Text]
39. Detjen AK, Keil T, Roll S, et al. Interferon-gamma release assays improve the diagnosis of tuberculosis and nontuberculous mycobacterial disease in children in a country with a low incidence of tuberculosis. Clin Infect Dis.2007; 45 (3):322 –328[CrossRef][ISI][Medline]
40. Centers for Disease Control and Prevention. Recommendations for prevention and control of tuberculosis among foreign-born persons: report of the Working Group on Tuberculosis among Foreign-Born Persons. MMWR Recomm Rep.1998; 47 (RR-16):1 –29[Medline]
41. Barnett ED. Infectious disease screening for refugees resettled in the United States. Clin Infect Dis.2004; 39 (6):833 –841[CrossRef][ISI][Medline]

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