Published online August 31, 2007
PEDIATRICS Vol. 120 No. 3 September 2007, pp. e610-e616 (doi:10.1542/peds.2006-2817)
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ARTICLE

Predictors of Mycobacterium tuberculosis Infection in International Adoptees

Anna M. Mandalakas, MDa, H. Lester Kirchner, PhDa, Sandra Iverson, MS, RN, CPNPb, Mary Chesney, MS, RN, CPNPb, Mary Jo Spencer, BSN, RN, CPNPb, Angela Sidler, MDb and Dana Johnson, MD, PhDb

a Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio
b Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVE. The objective of this study was to measure the factors that are associated with Mycobacterium tuberculosis infection in international adoptees.

METHODS. A retrospective chart review was conducted on 880 international adoptees who presented to the International Adoption Clinic at the University of Minnesota between 1986 and 2001. Five tuberculin units of purified protein derivative were placed intradermally on the left forearm. The largest diameter of induration was measured in millimeters between 48 and 72 hours. Nutritional status was assessed using anthropometric measures at initial screening. Data on age, birth country, and year of adoption were assessed.

RESULTS. Adoptees (mean age: 26 months; range: 1–200 months; 62% female) came from 33 birth countries. Twenty-eight percent and 5% had evidence of chronic and acute malnutrition, respectively. Twelve percent had evidence of M tuberculosis infection. The odds of M tuberculosis infection increased 7% for each subsequent year during the period studied, increased 142% with each additional year of age for children ≤24 months of age at baseline screening, and increased 15% with each additional year of age for children >24 months of age at the time of evaluation. Tuberculin skin test induration response was not associated with nutritional status or birth region.

CONCLUSIONS. Our study demonstrated a high prevalence of M tuberculosis infection and malnutrition in internationally adopted children, placing them at considerable risk for progression to tuberculosis disease. These findings also support current guidelines recommending completion of tuberculin screening immediately after adoption.

Key Words: tuberculin test • malnutrition • tuberculosis • adoption • immigrants • pediatrics

Abbreviations: TST—tuberculin skin test • BCG—bacille Calmette-Guérin • OR—odds ratio • CI—confidence interval • aOR—adjusted odds ratio • PPD—purified protein derivative

The number of children who were adopted internationally increased dramatically in the past 2 decades. Since 1990, the United States has issued 226546 immigrant visas to orphans.1 In 2005 alone, American families internationally adopted nearly 23000 children, representing a three-fold increase since 1989.2 During this same period, the clinical characteristics of these children have changed dramatically. Rather than adopting infants from well-established foster care or small orphanage settings in Korea, India, the Philippines, and Latin America,3 the majority of American families now adopt children from resource-poor, state-run orphanages in the former Soviet Union and China.4 The quality of care and living conditions that are experienced by these children before adoption varies significantly and often place adoptees at considerable risk for a number of health problems, including tuberculosis.3,5–14

Reported incidence of Mycobacterium tuberculosis infection in international adoptees have ranged from 0.6% to 19%.6,10,13–15 Several factors are likely to contribute to this high risk for infection, including age; origin from countries with a high prevalence of tuberculosis6; and residence in institutional settings that favor M tuberculosis transmission, including close contact with orphanage workers, who are seldom screened for tuberculosis. To date, no study has examined these risk factors in international adoptees or other institutionalized children. We conducted a retrospective study of foreign-born adoptees who presented to the International Adoption Clinic at the University of Minnesota during a 15-year period to identify factors that are associated with tuberculosis infection.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
A retrospective chart review was conducted on all international adoptees who completed tuberculosis screening at the International Adoption Clinic of the University of Minnesota between 1986 and 2001. This clinic is a regional referral center for foreign-born children who are adopted by families in Minnesota and neighboring states. During the period studied, the routine policy of the clinic was to complete tuberculosis screening, including a tuberculin skin test (TST), on all children on initial evaluation within 1 month of arrival to the United States. Children were excluded from TST screening when a previous TST had been completed since arrival, a draining and/or inflamed BCG vaccination site was noted, or parental consent was not obtained. The clinic routinely collected demographic data regarding age, gender, and birth country. All children were routinely screened for infection with HIV. The clinic also recommended that the child's primary care physician complete a repeat TST 6 months after arrival.

Institutional approval was obtained from the institutional review boards of University Hospitals of Cleveland and the University of Minnesota. Informed consent was obtained from parents or legal guardians of all children.

TST
As part of the clinic's routine evaluation, children completed a TST with 5 TU of purified protein derivative (PPD; Tubersol; 5 TU/0.1 mL; Connaught, Swiftwater, PA) placed intradermally (Mantoux method) on the left forearm. All TSTs were placed by 1 of 2 clinic staff who had completed formal training and used standardized methods. Health care professionals including the clinic staff and primary care providers read the TSTs within 48 to 72 hours of placement. Results were recorded in millimeters of induration and categorically as positive or negative. TST induration responses ≥10 mm were considered positive and indicative of M tuberculosis infection.16,17

Nutritional Assessment
With the use of standardized, calibrated measuring equipment, anthropometric measurements were obtained at the time of TST placement, including weight, height, and length. Recumbent length was measured in children who were ≤18 months of age. In children who were older than 18 months, standing heights were measured.18 Length and height were rounded off to the nearest millimeter. Weight was rounded off to the nearest 100 g.

BMI, acute malnutrition (wasting), and chronic malnutrition (stunting) were assessed.19 Moderate to severe wasting was defined as a weight-for-height z score of less than or equal to –2. Moderate to severe stunting was defined as a height-for-age z score of less than or equal to –2. Weight-for-age z scores (a composite measure of acute and chronic malnutrition) were also calculated and defined in a similar manner.19 Z scores were calculated using the 2006 World Health Organization Child Growth Standards20 for children up to 5 years of age and the 2000 Centers for Disease Control and Prevention growth charts reference population for children who were older than 5 years.21 The expression in z scores uses SD of the reference distribution as the unit for a given height, length, or weight at specific ages. By convention, children with z scores between –3 and less than or equal to –2 are considered to have moderate malnutrition, and children with z scores of less than –3 are considered to have severe malnutrition.19,22

Case Management
Children with a positive TST (≥10 mm) were referred to their regional tuberculosis clinic for additional evaluation of tuberculosis disease and treatment as appropriate for both active tuberculosis and latent tuberculosis infection. Previously published analyses describing a subset of our cohort identified 4 cases of tuberculosis disease in 293 children, yielding a tuberculosis disease prevalence of 13.7 per 1000.23 On the basis of these published data, we conservatively estimated that within the larger cohort described in this study, 12 children would have had active tuberculosis disease.

Statistical Analysis
Descriptive statistics including mean and SD for continuous variables and frequency and percentage for categorical variables are presented. Comparisons between groups of children (eg, positive TST versus negative TST) were performed using Wilcoxon rank sum and Kruskal-Wallis nonparametric tests for continuous and contingency table analyses for categorical data. The contingency table analyses consisted of Pearson's {chi}2 for 2 x 2 tables and nominal-level variables and the Mantel-Haenszel {chi}2 tests for ordinal-exposure variables. The association between TST positivity and variables of interest are expressed as an odds ratio (OR) with a 95% confidence interval (CI). Logistic regression was used to adjust this association for age. Analyses were performed using SAS 9.1 (SAS Institute, Inc, Cary, NC).


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Description of Sample
During the period studied, 880 children completed a TST for M tuberculosis infection at the clinic. Eleven children were excluded from analysis: 7 because of unknown TST results and 4 because of extreme weight-for-age z scores (>9.0) because these measurements were likely to be erroneous.

Characteristics of the study sample (N = 869) are presented in Table 1. All of the children arrived from countries that routinely recommend BCG vaccination at birth. There was considerable variation in birth region during the period studied, with an increasing proportion of children coming from China in later cohort years. During the period studied, Korea was the only country that provided family-based foster care. Thus, the majority (80%) of children in our study were adopted from an orphanage setting. None of the children included in our sample received a diagnosis of HIV infection.


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  		TABLE 1 Characteristics of the Study Sample

 
TST
A total of 11.9% of children had TST induration responses ≥10 mm. There was no association between TST induration response and any measure of nutritional status. The frequency of TST induration responses ≥10 mm did not differ between birth regions (Table 2). The median age of children with TST induration responses ≥10 mm was significantly higher than children with TST induration responses <10 mm (P < .0001). During the period under review, the proportion of children with TST induration responses ≥10 mm increased significantly over time, demonstrating a cohort effect (P < .0001). Logistic regression was used to examine simultaneously TST induration response relative to year and age (Figs 1 and 2). When controlling for the effect of age, the odds for M tuberculosis infection increased 7% for each subsequent year during the period studied (adjusted OR [aOR]: 1.07; 95% CI: 1.02–1.13; P = .01). This analysis also demonstrated that while controlling for the effect of the year adopted (the cohort effect), the odds for infection with M tuberculosis increased 142% (aOR: 2.42; 95% CI: 1.57–3.72; P < .0001) with each additional year of age for children who were younger than 24 months and increased 15% (aOR: 1.15; 95% CI: 1.06–1.25; P < .0008) with each additional year of age for children who were ≥24 months of age at the time of evaluation.


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  		TABLE 2 Prevalence of M tuberculosis Infection

 

Figure 1
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  		FIGURE 1 Estimated prevalence (solid line) and 95% CIs (dashed lines) of M tuberculosis infection during period studied.

 

Figure 2
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  		FIGURE 2 Estimated prevalence (solid line) and 95% CIs (dashed lines) of M tuberculosis infection at children's age of adoption and evaluation.

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
In 869 children who were internationally adopted between 1986 and 2001, we evaluated TST results and found a high prevalence of M tuberculosis infection (11.9%). The risk for M tuberculosis infection significantly increased with increasing age of the child and with each subsequent year during the period studied. Children who were younger than 2 years were at greatest risk for acquiring M tuberculosis infection. Nutritional status and birth region were not associated with M tuberculosis infection status.

Our study demonstrated that the risk for having M tuberculosis infection was age dependent and the risk for acquiring M tuberculosis was highest in children who were younger than 24 months. This association was not modified by birth region or nutritional status. The high risk for acquiring M tuberculosis infection in children who were younger than 2 years may be attributable to several factors related to the orphanage organization and caregiving patterns. As compared with older children who live in orphanage settings, children who were younger than 2 years spend the greatest amount of time indoors and in close contact with caregivers.24 Therefore, young children have more risk for prolonged exposure to caregivers who may have active tuberculosis. In addition, most orphanages house children within age groups, so children who are younger than 24 months do not significantly interact with older children. Therefore, it is likely that these young children are infected with M tuberculosis during close contact with their caregivers rather than other children and adolescents. The risk for progression to tuberculosis is exceptionally high in children who are younger than 2 years25 and in malnourished children.26,27 Therefore, children who reside in or are adopted from orphanages may greatly benefit from improved tuberculosis control efforts that include regular tuberculosis screening and appropriate treatment of caregivers to reduce M tuberculosis transmission to children. In addition, our study did not find a statistically significant difference in the prevalence of tuberculosis infection between children who had spent the majority of their lives in orphanages as opposed to foster care. Hence, children may also benefit from routine screening of foster care providers and their families.

We found the age-adjusted risk for M tuberculosis infection to increase with each subsequent year during the period studied. This progressive increase was not associated with the birth country but was present in all regions, likely reflecting the high burden of childhood tuberculosis in the majority of the countries from which children in our study were adopted. Fifty-nine percent of the children in our study were adopted from 1 of 22 countries with the highest burden of tuberculosis disease.1,28 Our findings suggest that the risk for tuberculosis transmission to children within orphanage settings consistently increased from 1986 through 2001. Although this increase mirrors global trends in childhood tuberculosis documented during the same period,29 the degree of increase is substantially greater and highlights the need to identify factors within the orphanage that contribute to these children's risk for infection.

Limited information is available regarding internationally adopted children's exposure to caregivers with active tuberculosis. Our data suggest that a significant portion of children who live in orphanages are exposed to infectious adults with active tuberculosis. In children with exposure to an infectious adult, the TST should be interpreted as positive when TST indurations are ≥5 mm.16 Therefore, our study likely underestimates the number of children who would receive a diagnosis of M tuberculosis infection if the history regarding tuberculosis exposure were available. In addition, children with recently acquired M tuberculosis infection may not have fully developed their immune response and associated TST response. Consideration of these clinically relevant issues suggests that additional screening, such as chest radiography and a repeat TST 3 to 6 months after arrival, may be warranted in internationally adopted children with TST indurations ≥5 mm.

M tuberculosis infection produces a T cell–driven delayed-type hypersensitivity reaction to specific antigenic components of the M tuberculosis bacillus, including PPD. Previous studies have shown that malnourished children with associated impairment in T-cell function may be anergic (nonresponsive) to the TST27,30–32; this association may be most evident in children with severe malnutrition.27 The ages of internationally adopted children may be inaccurately reported to reflect a younger age and improve a child's chance of being adopted. This reporting bias would introduce a differential bias that would lead to an underestimation of malnutrition. Therefore, our data may underestimate the degree of M tuberculosis infection in children with severe malnutrition and children with inaccurately reported ages. Although <1% of our study cohort had evidence of severe malnutrition, it is impossible to validate children's ages. Although our study did not demonstrate a statistically significant association between nutritional status and TST reactivity, this lack of association reflects the small number of children defined as severely malnourished in our study and the resultant limitations in power to complete nutritionally stratified analysis. In addition, we found no association between TST reactivity and chronic malnutrition. Although a larger portion of children (12%) had evidence of severe chronic malnutrition as defined in our study, our assessment of chronic malnutrition may be confounded by the presence of psychosocial short stature secondary to chronic neglect that is commonly found in international adoptees. Because malnutrition is known to be associated with anergic TST responses and difficult to assess in internationally adopted children, there may be a potential role for anergy testing when screening internationally adopted for children M tuberculosis infection.

Several factors are associated with a false-positive TST and decreased specificity. Because some antigens in the PPD are shared with nontuberculous Mycobacterium and BCG vaccine, exposure to these can lead to false-positive reactions.33 There is no reliable method of distinguishing TST reactions that are induced by BCG from responses that are induced by other mycobacteria. The degree of BCG-induced TST reactivity is inversely associated with the child's age and years since BCG vaccination.34–37 Accordingly, if a child is not infected with mycobacteria, then a decrease in the degree of PPD reactivity is expected during the first few years of life as the degree of BCG-induced TST reactivity wanes. Unexpected, our study demonstrated a significant increase in the prevalence of infection in children who were younger than 2 years as compared with older children. These findings further emphasize infants' and toddlers' high risk for tuberculosis exposure in the orphanage setting. There was no association between birth region and TST reactivity, suggesting that variations in regional exposure to nontuberculous mycobacterium did not affect our results.

Although widely used, the TST has limited diagnostic accuracy for M tuberculosis infection. TST specificity is reduced in populations such as international adoptees who have been exposed to environmental mycobacteria and/or M bovis BCG vaccination. TST sensitivity is particularly limited in children with compromised immune status as a result of young age and/or severe malnutrition. T cell–based immune diagnostic testing using M tuberculosis–specific antigens offers improved specificity for M tuberculosis infection, especially in children with exposure to environmental mycobacterium and/or routine vaccination with BCG.38,39 Studies also suggest that immune diagnostic testing offers enhanced sensitivity compared with the TST in immunocompromised adults.40,41 However, very limited data are available on the utility of these tests for detecting M tuberculosis infection in children, especially in HIV-infected and other immunocompromised children.42,43 More studies to guide the interpretation of these tests in malnourished children from countries or settings with high risk for tuberculosis exposure are needed.

Several factors may have introduced bias into our study. The nature of the international adoption process inherently selects healthier children who are from orphanages with more resources. Therefore, children in our study may have been healthier than their orphanage peers, suggesting that our study may underestimated the prevalence of M tuberculosis infection in children who remain in the orphanages. Conversely, sampling children who were referred to a specialty clinic may have introduced a referral bias, resulting in a sample of children who were less healthy than other foreign-born adoptees. Nevertheless, the high prevalence of wasting (acute malnutrition), stunting (chronic malnutrition), and M tuberculosis infection is similar to reported data from other studies.5,10,12,13,15 The geographic distribution of birth countries also paralleled trends seen in international adoption during that period.1 These comparisons suggest that our study sample was representative of foreign-born adoptees who joining US families from the mid-1980s to 2000. Although we did not examine interrater and intrarater reliability of the TST result, a limited number of well-trained clinic staff placed the TST in a standardized manner, thereby reducing variability in placement. We cannot make an accurate assumption on how measurement error, if any, has contributed to the proportion of positive TST results. However, errors in measuring are unlikely to change over time, and the inclusion of TST readings as measured by community physicians allows our findings to be generalized to foreign-born adoptees who receive community care and provide a realistic estimate of the incidence of the diagnosis of M tuberculosis infection in these children after immigration to the United States. Finally, the large sample size lends to robust findings that are less likely to have been affected by variability in measures. This study was not designed to examine the prevalence or diagnostic impact of tuberculosis disease. Accordingly, an analysis and discussion of tuberculosis disease is beyond the scope of this article.


   CONCLUSIONS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
Our study demonstrated high rates of M tuberculosis infection and malnutrition in internationally adopted children, placing them at considerable risk for progression to active tuberculosis. Hence, our findings support completion of tuberculin screening soon after adoption.16 In addition, because of the risk for a false-negative TST after recent exposure to M tuberculosis or secondary to malnutrition,31,32 clinicians should consider repeating the TST 3 to 6 months after children arrive in their adoptive countries and when nutrition has improved.16 Effective and timely identification, screening, and treatment of M tuberculosis infection and disease not only may improve long-term health outcomes for internationally adopted children but also is consonant with public health imperatives.44 Our study also highlights the opportunity to improve the health of children who live within orphanages worldwide by improving institutional tuberculosis control.


   ACKNOWLEDGMENTS
 
We thank Drs Thomas M. Daniel, Jeffrey Starke, and Anneke Hesseling for insightful review of the manuscript.


   FOOTNOTES
 
Accepted Jun 30, 2007.

Address correspondence to Anna M. Mandalakas, MD, 11100 Euclid Ave, Cleveland, OH 44106-7052. E-mail: amm13{at}po.cwru.edu

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


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

  1. US Department of State. Immigrant Visas Issued to Orphans Coming to the US. Washington, DC: US Department of State Bureau of Consular Affairs; 2006
  2. Placek PJ. National adoption data. In: Marshner C, ed. Adoption Factbook III. Washington, DC: National Council for Adoption; 1999:24–32
  3. Jenista JA. The risks are many, but the joys are great. Pediatr Ann. 2000;29 :208 –209[Web of Science][Medline]
  4. Mandalakas A, Groza V. International adoption. In: Stolley K, Bullough V, eds. Historical and Cross-Cultural Encyclopedia of Adoption. Westport, CT: Greenwood Publishing Group; 2006: 331–336
  5. Albers LH, Johnson DE, Hostetter MK, Iverson S, Miller LC. Health of children adopted from the former Soviet Union and Eastern Europe: comparison with preadoptive medical records. JAMA. 1997;278 :922 –924[Abstract/Free Full Text]
  6. Aronson J. Medical evaluation and infectious considerations on arrival. Pediatr Ann. 2000;29 :218 –223[Web of Science][Medline]
  7. Faber S. Behavioral sequelae of orphanage life. Pediatr Ann. 2000;29 :242 –248[Web of Science][Medline]
  8. Hostetter MK. Infectious diseases in internationally adopted children: findings in children from China, Russia and Eastern Europe. Adv Pediatr Infect Dis. 1999;14 :147 –161[Medline]
  9. Johnson DE, Miller LC, Iverson S, et al. The health of children adopted from Romania. JAMA. 1992;268 :3446 –3451[Abstract/Free Full Text]
  10. Johnson DE, Traister M, Iverson S, Dole K, Hostetter MK, Miller LC. Health status of US adopted Chinese orphans. Pediatr Res. 1996;39 :135A
  11. Johnson DE. Long-term medical issues in international adoptees. Pediatr Ann. 2000;29 :234 –241[Web of Science][Medline]
  12. Miller LC. Initial Assessment of growth, development, and the effects of institutionalization in internationally adopted children. Pediatr Ann. 2000;29 :224 –232[Web of Science][Medline]
  13. Saiman L, Aronson J, Zhou J, et al. Prevalence of infectious diseases among internationally adopted children. Pediatrics. 2001;108 :608 –612[Abstract/Free Full Text]
  14. Jenista JA. Infectious disease and the internationally adopted child. Curr Opin Infect Dis. 1993;6 :576 –584[CrossRef][Web of Science]
  15. Johnson DE, Albers LH, Iverson S, et al. Health Status of Eastern European orphans referred for adoption. Pediatr Res. 1996;39 :134A
  16. American Academy of Pediatrics. Tuberculosis. In: Pickering LK, ed. Red Book: 2006 Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006:678–698
  17. Childhood TB Sub-group (including A Mandalakas). Guidance for National Tuberculosis Programmes on the Management of Tuberculosis in Children. Geneva, Switzerland: World Health Organization; 2006
  18. World Health Organization Multicentre Growth Reference Study Group. WHO child growth standards based on length/height, weight and age. Acta Pediatr. 2006;450 :76 –85
  19. Boelaert M, Davis A, Le Lin B, et al. Nutrition Guidelines. 1st ed. Paris, France: Medecins Sans Frontieres; 1995
  20. World Health Organization Multicentre Growth Reference Study Group. WHO Child Growth Standards: Length/Height-for-Age, Weight-for-Age, Weight-for-Length, Weight-for-Height and Body Mass Index-for-Age: Methods and Development. Geneva, Switzerland: World Health Organization; 2005
  21. Centers for Disease Control and Prevention. CDC growth charts: United States. Available at: www.cdc.gov/growthcharts. Accessed June 19, 2007
  22. WHO. Use and interpretation of anthropometric indicators of nutritional status. Bull World Health Organ. 1986;64 :929 –941[Web of Science][Medline]
  23. Hostetter MK, Iverson S, Thomas W, McKenzie D, Dole K, Johnson DE. Medical evaluation of internationally adopted children. N Engl J Med. 1991;325 :479 –485[Abstract]
  24. Daunhauer LA, Cermak S. Time-use by Romanian orphanage children. Occup Ther J Res. 2005;25 :33 –40
  25. Marais BJ, Gie RP, Schaaf HS, et al. The natural history of childhood intra-thoracic tuberculosis: a critical review of literature from the pre-chemotherapy era. Int J Tuberc Lung Dis. 2004;8 :392 –402[Web of Science][Medline]
  26. World Health Organization, Communicable Diseases Working Group on Emergencies. Communicable Diseases and Severe Food Shortage Situations. Geneva, Switzerland: World Health Organization; 2005
  27. Singh M, Myanak ML, Kumar L, Mathew JL, Jindal SK. Prevalence and risk factors for transmission of infection among children in household contact with adults having pulmonary tuberculosis. Arch Dis Child. 2005;90 :624 –628[Abstract/Free Full Text]
  28. Corbett EL, Watt CJ, Walker N, et al. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch Intern Med. 2003;163 :1009 –1021[Abstract/Free Full Text]
  29. Nelson LJ, Wells CD. Global epidemiology of childhood tuberculosis. Int J Tuberc Lung Dis. 2004;8 :636 –647[Web of Science][Medline]
  30. Hesseling AC, Schaaf HS, Gie RP, Starke JR, Beyers N. A critical review of diagnostic approaches used in the diagnosis of childhood tuberculosis. Int J Tuberc Lung Dis. 2002;6 :1038 –1045[Web of Science][Medline]
  31. Lloyd A. Tuberculin test in children with malnutrition. Br Med J. 1968;3 :529 –531[Abstract/Free Full Text]
  32. Sinha DP, Bang FB. Protein and caloric malnutrition, cell mediated immunity, and BCG vaccination in children from rural west Bengal. Lancet. 1976;2 :531 –534[CrossRef][Web of Science][Medline]
  33. Mandalakas A, Starke JR. Tuberculosis. In: Chernick V, Boat T, eds. Kendig's Disorders of the Respiratory Tract in Children. 7th ed. Philadelphia, PA: Saunders; 2006:507–529
  34. Karalliedde S, Katugaha LP, Uragoda CG. Tuberculin response of Sri Lankan children after BCG vaccination at birth. Tubercle. 1987;68 :33 –38[Web of Science][Medline]
  35. Menzies R, Vissandjee B, Amyot D. Factors associated with tuberculin reactivity among the foreign-born in Montreal. Am Rev Respir Dis. 1992;146 :752 –756[Web of Science][Medline]
  36. Menzies R, Vissandjee B. Effect of bacille Calmette-Guerin vaccination on tuberculin reactivity. Am Rev Respir Dis. 1992;145 :621 –625[Web of Science][Medline]
  37. Tissot F, Zanetti G, Francioli P, Zellweger JP, Zysset F. Influence of bacille Calmette-Guerin vaccination on size of tuberculin skin test reaction: to what size. Clin Infect Dis. 2005;40 :211 –217[CrossRef][Web of Science][Medline]
  38. Hill PC, Brookes RH, Fox A, et al. Large-scale evaluation of enzyme-linked immunospot assay and skin test for diagnosis of Mycobacterium tuberculosis infection against a gradient of exposure in The Gambia. Clin Infect Dis. 2004;38 :966 –973[CrossRef][Web of Science][Medline]
  39. Hill PC, Fox A, Jeffries DJ, et al. Quantitative T cell assay reflects infectious load of Mycobacterium tuberculosis in an endemic case contact model. Clin Infect Dis. 2005;40 :273 –278[CrossRef][Web of Science][Medline]
  40. Chapman AL, Munkanta M, Wilkinson KA, et al. Rapid detection of active and latent tuberculosis infection in HIV-positive individuals by enumeration of Mycobacterium tuberculosis-specific T cells. AIDS. 2002;16 :2285 –2293[CrossRef][Web of Science][Medline]
  41. Lalvani A, Nagvenkar P, Udwadia Z, et al. Enumeration of T cells specific for RD1-encoded antigens suggests a high prevalence of latent Mycobacterium tuberculosis infection in healthy urban Indians. J Infect Dis. 2001;183 :469 –477[CrossRef][Web of Science][Medline]
  42. Pai M, Lewinsohn DM. Interferon-gamma assays for tuberculosis: is anergy the Achilles' heel? Am J Respir Crit Care Med. 2005;172 :519 –521[Free Full Text]
  43. Starke JR. Use of the new TB test in children should be limited. AAP News. 2006;27 :14 –15[Free Full Text]
  44. Curtis AB, Ridzon R, Vogel R, et al. Mycobacterium tuberculosis from a child. N Engl J Med. 1999;341 :1491 –1495[Abstract/Free Full Text]
PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics

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TB Infection and Malnutrition Are Prevalent Among Internationally Adopted Children
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