PEDIATRICS Vol. 114 No. 4 October 2004, pp. 1084-1086 (doi:10.1542/peds.2004-1525)
COMMENTARY |
New Guidelines About Latent Tuberculosis Infection in Children and Adolescents: A Welcome Advancement
Division of Tuberculosis Elimination
National Center for HIV, STD, and TB Prevention
Centers for Disease Control and Prevention
Atlanta, GA 30333
Abbreviations: LTBI, latent tuberculosis infection • TB, tuberculosis
In a supplement to this month’s issue of Pediatrics, comprehensive new guidelines are being published on finding and treating latent tuberculosis infection (LTBI) in children and adolescents.1 The collaborative group responsible for the guidelines is composed of health professionals from US health departments, the National Tuberculosis Model Centers, academic institutions, and the Centers for Disease Control and Prevention.
With these guidelines, pediatricians have a single comprehensive reference about preventing tuberculosis (TB) in their patients. The guidelines are founded on a paradigm that is evolving with the TB epidemiology for US children and adolescents. Although TB rates have been declining overall since 1992, infections and cases have become even more concentrated among high-risk groups such as children born outside the United States. Thus, these guidelines recommend that children should be screened for risk factors for TB and LTBI and tested with the tuberculin skin test only if at least 1 risk factor is present. These guidelines discourage the use of administrative or mandated tuberculin skin tests for entry to child care, school, or summer camp, because these they are likely to consume limited resources but yield very little in finding current cases or preventing future ones. For these settings and most others, testing should be undertaken only if (1) preceded by screening for risk factors as described in the guidelines and (2) coupled to systems that start children who have LTBI on treatment and help them to complete it.
The authors of the guidelines begin by reviewing the recent epidemiology of TB in children and adolescents, and they situate pediatric TB prevention within a hierarchy of TB-control activities managed by health departments. They provide the scientific rationale, with references, for the recommendations. They define differences among contact, source-case, and associate investigations, and they summarize research on risk-assessment questionnaires; a sample questionnaire is included in the article.1 They review new data on the TB risks for internationally adopted children, particularly those from orphanages in China and Russia. They also highlight the lack of risk-factor data specific to adolescents; because of this lack of data, some risk-assessment questionnaires have performed relatively poorly when applied to this population.
Low rates of TB disease (<0.02%) and LTBI (<2%) were found in recent studies of universal school-based screening. However, several studies have found rates of LTBI that were 6 to 24 times higher for foreign-born students, particularly older children and adolescents.2,3 Associate investigations, which include close contacts of children with LTBI, generally have found a low rate of active TB disease but a substantial rate of LTBI. These contrasts reinforce the importance of methodically planning testing programs and interpreting the epidemiologic implications of the results.
Evaluation for LTBI has distinct significance for children and adolescents who are at high risk of developing disease if infected. Medical conditions that predispose to progression of TB infection include human immunodeficiency virus infection, diabetes, organ transplantation, chronic renal failure, and malignancies. In addition, medications such as high-dose steroids and other immunosuppressive medications (eg, infliximab) enhance the likelihood that LTBI will progress to active TB. Children who have these risks should receive a tuberculin skin test and treatment for LTBI if infected.
The tuberculin skin test is notorious for its limitations, and the authors present background on both its characteristics and the factors associated with false-positive and false-negative results. The rationale for the 3 cut-off levels (
5, 10, and 15 mm) to improve test sensitivity and specificity is provided. Newer tests for Mycobacterium tuberculosis infection such as QuantiFERON-TB1 might prove to have better sensitivity and specificity, but they have been inadequately studied in children and adolescents and they have not been approved yet for use in this population.4
The authors describe the diagnostic work-up for children with LTBI to rule out active TB disease. In particular, they contrast the utility of chest radiography with that of computed tomography, a diagnostic study not recommended for routine management of LTBI.
A 9-month regimen of isoniazid currently is recommended for children who have LTBI believed to be susceptible to isoniazid or when the specific source of infection is unknown. The treatment recommendations are based on trials done by the US Public Health Service, which are reviewed in the text of the guidelines. Alternative regimens and the treatment of LTBI with drug-resistant organisms are covered also. The section on treatment regimens covers drug toxicity as well as strategies to improve adherence.
The public health aspects of TB prevention are crucial, and in the guidelines, the roles of the health department, other health care providers, and school-based programs are delineated. Annual skin tests are recommended only for children with human immunodeficiency virus/acquired immunodeficiency syndrome and for incarcerated adolescents. The latter recommendation is not supported by published evidence for adolescents. A skin test should be administered before starting immunosuppressive therapy, because these children have a high risk of developing disease if infected and immunosuppressive therapy can cause loss of sensitivity to tuberculin later on. Priorities for future research are also outlined in detail.
For adolescents specifically, few data exist for guiding recommendations about TB prevention, and to some extent we still are left to create amalgams from the current recommendations for children and those for adults. Adolescents probably differ from younger children in risk factors for TB infection/disease, in clinical manifestations of TB, and in social issues related to treatment. We need more research to allow for specific recommendations for this population.
Besides their value to pediatricians, the new guidelines provide a valuable reference for other groups with an interest in preventing TB in children and adolescents, including health departments, schools, general primary care providers, and a wide variety of organizations (such as summer camps, child care facilities, international adoption organizations, and juvenile detention facilities). However, putting these comprehensive guidelines into practice is certain to present challenges. As the authors make clear, specific risk factors for LTBI vary by geographic settings and by groups of children, which necessitates the use of locally tailored risk-assessment questionnaires as well as locally tailored strategies that are founded on epidemiologic analysis.
A TB-prevention strategy that is based on diagnosing and treating LTBI is unfeasible in the resource-poor countries that suffer most of the global TB burden. The intricacy of the new pediatric guidelines reinforces the discrepancies of what can be offered to children in resource-rich and resource-poor countries. Widespread BCG vaccination has failed to bring the global TB epidemic under control, but recent vaccine discoveries give us greater hope of preventing TB among children worldwide.5
Although LTBI and active TB in children are sentinel events for recent M tuberculosis transmission, health departments (as well as other agencies) must set priorities for their diverse TB-control activities while they adjust for their increasingly limited resources. Thus, we all will be challenged to make use of these valuable new guidelines when formulating local strategies. Children with LTBI represent the future reservoir from which adult cases will arise, and detecting and treating LTBI in children and adolescents will contribute to the long-term goal of TB elimination in the United States.
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ACKNOWLEDGMENTS |
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This work was funded by the Division of Tuberculosis Elimination, Centers for Disease Control and Prevention.
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FOOTNOTES |
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Accepted Jul 16, 2004.
Reprint requests to (L.J.N.) Division of TB Elimination, Centers for Disease Control and Prevention, 1600 Clifton Rd, MS E-10, Atlanta, GA 30333. E-mail: lnelson{at}cdc.gov
The use of trade names does not imply endorsement by the US Public Health Service or the Department of Health and Human Services.
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REFERENCES |
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 TOP REFERENCES |
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- Pediatric Tuberculosis Collaborative Group. Targeted tuberculin skin testing and treatment of latent tuberculosis infection in children and adolescents. Pediatrics. 2004;114(4 pt 3); 1175 –1201
- Driver CR, Valway SE, Cantwell MF, Onorato IM. Tuberculin skin test screening in schoolchildren in the United States.
Pediatrics. 1996;98
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[Abstract/Free Full Text] - Mohle-Boetani JC, Miller B, Halpern M, et al. School-based screening for tuberculosis infection: a cost-benefit analysis.
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[Abstract/Free Full Text] - Centers for Disease Control and Prevention. Guidelines for using the QuantiFERON-TB test for diagnosing latent Mycobacterium tuberculosis infection. MMWR Recomm Rep. 2003;52(RR-2) :15 –18
- Fruth U, Young D. Prospects for new TB vaccines: Stop TB Working Group on TB Vaccine Development. Int J Tuberc Lung Dis. 2004;8 :151 –155[Web of Science][Medline]
PEDIATRICS (ISSN 1098-4275). ©2004 by the American Academy of Pediatrics
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