Introduction

Five years ago, in alignment with policies of the Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics (AAP), The Medical Advisory Committee for the Elimination of Tuberculosis ( MACET) recommended implementation of risk-based tuberculosis skin testing of infants and children in Massachusetts ( 1). More recently, CDC ( 2) and MACET ( 3) have again focused attention on targeted tuberculosis testing and urged that greater effort be devoted to the treatment of latent tuberculosis infection.

As a result, MACET undertook a review of its 1996 recommendations on infants and children. The current report reiterates the earlier recommendations and modifies them in the light of recent data.

New Definitions

Latent tuberculosis infection is the currently-accepted term for the stage of Mycobacterium tuberculosis infection that is asymptomatic, dormant and non-contagious; the patient is not sick in any way and has a normal chest x-ray. A positive tuberculosis skin test is the only evidence of latent tuberculosis infection. This stage may continue for the patient's entire lifetime or, in a matter of weeks to years, may progress to the stage of active disease called tuberculosis that can affect the lung or other parts of the body (lymph nodes, miliary, meningitis, bone and joint) and may be contagious to others. Treatment of latent tuberculosis infection, previously called preventive treatment or prophylaxis, aims to prevent the future development of active disease.

Background

Tuberculosis skin testing of infants and children in Massachusetts underwent a paradigm shift in 1996. Before then, the Massachusetts Department of Public Health recommended that all children 0-5 years of age have a tuberculosis skin test and that every child living in a city or town with a tuberculosis case rate that exceeded the state average be tested in the preschool period or upon school entry and again in the eighth grade. Multiple puncture tests, such as Tine and Mono-vacc, although not endorsed by the Massachusetts Department of Public Health, were widely used. In 1996 the Massachusetts Department of Public Health, following the direction of MACET ( 1), changed its recommendations to a more selective, focused use of tuberculosis skin tests that required each child be assessed for risk of tuberculosis and only those at high risk be tested. Only the Mantoux test (5 TU - intermediate PPD) was deemed acceptable.

In the intervening five years, health care providers, child welfare agencies, day care centers and school systems in Massachusetts have come to accept risk-based testing for tuberculosis, although some barriers to implementation remain.

Between 1994 and 2000 the rate of tuberculosis in Massachusetts has fallen 14% from 5.2 to 4.5 cases/100,000 population, and the rate in children remains low. As the overall rate of tuberculosis has dropped, the proportion of tuberculosis cases in foreign-born individuals has steadily increased, currently reaching 71%. Foreign birth, as well as household contact with foreign-born family members and visitors, and prolonged stays in countries with high rates of tuberculosis, constitute the major risk factors for tuberculosis in Massachusetts today.

With a goal of tuberculosis elimination, The Centers for Disease Control and Prevention (CDC) has renewed its call for using risk-based tuberculin skin testing and making treatment of latent tuberculosis infection a high priority. In addition, CDC has endorsed several new, shorter treatment regimens for adults with latent tuberculosis infection and has urged new initiatives to deal with the problem of tuberculosis among foreign-born persons ( 4).

MACET, therefore, presents the following update on screening infants and children for tuberculosis.

Recommendations

1. We Continue To Recommend That Health Care Providers In Massachusetts Not Use Multiple Puncture Tests.

Compared with the Mantoux test, multiple puncture tests (e.g. Tine and Mono-vacc) show highly variable accuracy. In a population with a low prevalence of tuberculosis infection, such as Massachusetts, a positive multiple puncture test has a very poor predictive value. The problem is further compounded by faulty interpretation of test results by parents.

The use of multiple puncture tests in Massachusetts cannot be defended on grounds of ease of use and convenience. They are simply too inaccurate.

2. We Continue To Recommend That The Mantoux Test Be The Only Method Used For Tuberculosis Skin Testing.

The Massachusetts Department of Public Health should supply intermediate (5 TU) PPD solution to health care providers free of charge.

All test results (positive or negative) must be read by qualified medical personnel. Mail-in or telephone responses of readings by parents are not acceptable.

Each office, health center and clinic administering the Mantoux test should design a system for reading test results that is fast and convenient for the patient and minimizes paperwork for the health care provider. Staff need to be trained in proper intradermal administration of the Mantoux test, reading in mm. of induration measured at right angle to the long axis of the arm at 48-72 hours after placement and risk-based interpretation ( TABLE 1) of the test result. Recent studies ( 5, 6) show that children exposed to adults who have AIDS or HIV infection, are homeless, use illicit drugs, or were recently incarcerated are not more likely to have latent tuberculosis infection, so we have deleted these as risk factors for purposes of skin test interpretation in TABLE 1.

We urge each office, health center and clinic to maintain its own statistics on tests done and proportion read at 48-72 hours. These statistics can serve as the basis for monitoring and continually improving skin test follow-up rates.

Many infants and children from countries with a high prevalence of tuberculosis were previously vaccinated with bacille Calmette-Guerin (BCG). They can receive a Mantoux test and results should be interpreted without regard to previous BCG vaccination. While it is highly effective in preventing serious disseminated forms of disease, such as tuberculous meningitis and miliary tuberculosis in children, BCG does not prevent latent tuberculosis infection. Moveover, while it may induce a small reaction to the Mantoux test, BCG seldom causes induration of >10 mm in an uninfected person. Thus, a positive Mantoux test in a child from a country with a high prevalence of tuberculosis who has received BCG vaccine is far more likely to be due to latent tuberculosis infection than to BCG vaccine.

3. We Recommend That Screening For Risk Of Tuberculosis Should Be An Essential Function Of Primary Health Care For All Children.

Risk of exposure to tuberculosis should be determined on entry into the health care system and at regular intervals thereafter. Depending on circumstances, a health care provider may decide to determine the risk of tuberculosis exposure through individual clinical history taking or by administering a simple tuberculosis risk questionnaire such as the newly revised one attached. ( APPENDIX 1. CHILDREN WHO SHOULD BE TESTED FOR TUBERCULOSIS).

We have modified our previous tuberculosis risk questionnaire, based on recent data from a large validation study of a similar questionnaire, two case-control studies of young children with latent tuberculosis infection and two studies specifically examining the risk of latent tuberculosis infection during travel to countries with a high prevalence of tuberculosis ( 5- 9).

Foreign birth, visiting or traveling in a country with a high prevalence of tuberculosis, having household visitors from a high prevalence country, having contact with an adult with active tuberculosis, or a relative with a positive tuberculin skin test were validated as risk factors. A household contact with a positive tuberculin skin test is not the source of infection for a child, but his or her presence may indicate that a child is at increased risk of exposure to contagious tuberculosis from other sources. On the other hand, exposure to adults who have AIDS or HIV infection, are homeless, use illicit drugs, or were recently incarcerated is not predictive of latent tuberculosis infection in children. The duration of foreign travel or residence that presents a risk of acquiring latent tuberculosis infection is unknown. For our questionnaire, we have arbitrarily selected the duration of one month, although the type of living conditions, (e.g., living in a household) and activity (e.g., health care work) while abroad may be more important than the length of the stay.

Health care providers taking a clinical history or using a questionnaire to determine a child's risk of tuberculosis exposure will need to know which countries have a high prevalence of tuberculosis and which do not ( TABLE 2). As the global epidemiology of tuberculosis changes in the future, the Massachusetts Department of Public Health must keep health care providers informed about the prevalence of tuberculosis in specific countries.

Recent studies have shown that low household income is not an independent predictor of skin test positivity ( 5, 6, 10) and should not be considered a risk factor for screening decisions.

4. We Continue To Recommend Tuberculosis Skin Testing Only For Infants And Children Who Are At Risk Of Exposure To Tuberculosis.

Selective testing allows time, energy and resources to be focused on the population at high risk of latent tuberculosis infection, the population for whom treatment will have the greatest beneficial impact. If testing is restricted to high risk infants and children, the incentive for test reading and follow-up is greater than with universal testing.

Prompt skin testing of all infants and children exposed to a case of active tuberculosis must be given the highest priority. If the initial tuberculosis skin test of an infant or child exposed to a case of active tuberculosis is negative, it should be repeated in three months; early in the course of infection, the skin test may be negative. During these three months, until the second skin test is negative, infants and children less than four years of age and those who have HIV infection or other immunosuppressive conditions should receive treatment.

TABLE 3 shows a modified version of the American Academy of Pediatrics recommendations on the frequency of tuberculosis skin testing. If the risk of exposure continues, a child should be tested annually or every 2-3 years, depending on the type of risk. If a child has a negative tuberculosis skin test three or more months after the risk has ceased, then further skin tests are unnecessary. In light of recent studies ( 5, 6), we no longer recommend testing children solely on the basis of exposure to adults who have AIDS or HIV infection, are homeless, use illicit drugs or were recently incarcerated.


5. We Continue To Recommend That Low Risk Infants And Children Not Receive A Tuberculosis Skin Test.

In a population with a low prevalence of infection, more than half of the children with a "positive" Mantoux test result may be uninfected and given treatment unnecessarily. By not testing infants and children at low risk of infection, the risks associated with treatment of those not infected are minimized.

This recommendation requires that health care providers ascertain the risk of tuberculosis exposure in low risk populations at regular intervals to be certain that risk factors have not changed.

6. We Continue To Recommend That Requirements For Tuberculosis Skin Tests Not Be Based On City Or Town Of Residence (So Called "Geographic Risk" Or "At Risk" Communities) In Massachusetts.

In 2000, the tuberculosis case rates per 100,000 population were 5.8 for the United States and 4.5 for Massachusetts. Immigration from countries with a high prevalence of tuberculosis accounted for the majority (71%) of cases in Massachusetts. The highest rates were in Chelsea (22.8), Malden (16.0), Lowell (14.3) and Boston (13.9). Within Boston, the city with the largest number of cases, rates ranged from 0 in the North End and Charlestown to 17.1 in Dorchester and 44.8 in the South End. In view of these
numbers, it becomes clear that screening all school children, even in the Massachusetts cities and the sections of Boston with the highest tuberculosis rates, means testing far too many who are not at risk of exposure.

The AAP recommends that "children without specific risk factors who reside in high-prevalence areas…should be considered for tuberculin skin testing at 4-6 and 11-16 years of age. Public health officials or local tuberculosis experts should help physicians identify areas with appreciable tuberculosis rates ( 11)."

We find that no city or town in Massachusetts has a high enough prevalence of tuberculosis to justify Mantoux skin tests for all children in the community. There may be circumscribed neighborhoods where testing is reasonable, but it should be stringently defined and narrowly applied.

Several studies ( 12- 14) likewise concluded that tightly targeted screening of high risk, foreign-born, school age children is much less costly than mass screening and is more efficient in prevention of tuberculosis.

7. We Continue To Recommend That Completion Of Treatment For Latent Tuberculosis Infection Be Given High Priority.

Because the prime purpose of tuberculosis skin testing of healthy infants and children is to identify those who have latent tuberculosis infection and whose future risk of active disease can be markedly reduced by treatment, a tuberculosis skin testing program is without value unless it is accompanied by a program that ensures that those identified as having latent tuberculosis infection complete treatment in a timely manner. By preventing active tuberculosis, spread of tuberculosis to others will be decreased and the prospect of tuberculosis elimination will be enhanced. Thus, treatment of latent tuberculosis infection benefits both the individual and the community.

It should be noted that new shorter courses of treatment for latent tuberculosis infection in adults ( 2) have not yet been approved for use in children. Nine months of treatment with isoniazid is the only regimen currently recommended for infants, children and adolescents younger than 18 years of age at the present time.

We believe that treatment of latent tuberculosis infection is best carried out by primary health care providers. However, when the child with latent tuberculosis infection is not in a primary health care setting or when the primary health care provider does not feel that he or she is able to treat latent tuberculosis infection, the child should be referred for treatment to one of the tuberculosis clinics run in locations throughout the state by the Massachusetts Department of Public Health (call the Division of Tuberculosis Prevention and Control for locations and times: 617-983-6970).

We urge each office, health center and clinic administering Mantoux tests to maintain its own statistics on the number of infants and children found to have latent tuberculosis infection and the proportion who complete a course of treatment whether on site or at a state tuberculosis clinic. These statistics can serve as the basis for continually monitoring and improving treatment completion rates.

8. We Recommend That Increased Resources Be Devoted To Training Health Care Workers In Tuberculosis Screening And Latent Tuberculosis Infection Treatment.

The Massachusetts Department of Public Health needs to put more effort into developing and disseminating innovative, useful training tools and providing more educational opportunities, so that primary health care providers are better equipped to do risk assessment; administer, read and interpret the Mantoux test; and treat latent tuberculosis infection in infants and children.

Highlights Of Tuberculosis Screening Recommendations

  • Screening for risk of tuberculosis exposure by clinical history taking or tuberculosis risk questionnaire is an essential part of routine well-child care.
  • Tuberculin skin test for infants and children at high risk of exposure to tuberculosis.
  • Continuing risk: Test annually or every 2-3 years, depending on type of risk.
  • No further risk: Retest only if risk recurs.
  • Do not tuberculin skin test infants and children at low risk for tuberculosis.
  • Use only Mantoux test (intermediate PPD).
  • Infants and children identified as having latent tuberculosis infection should receive treatment. Isoniazid (INH) for nine months is recommended.

Conclusion

We recommend periodic screening for risk of tuberculosis exposure as an integral part of routine primary health care, selective skin testing for tuberculosis for those at high risk, and treatment of those found to have latent tuberculosis infection as a top priority. In this way, we will make the best use of our resources, provide the greatest benefit to the infants and children of Massachusetts, and help us reach the goal of eliminating tuberculosis.

November, 2001

Citations

( 1) Screening infants and children for tuberculosis: Recommendations of the Medical Advisory Board of the Massachusetts Committee for the Elimination of Tuberculosis.1996; Boston, MA.

( 2) Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR 2000; 49 (No. RR-6):1-51.

( 3) The Medical Advisory Committee for the Elimination of Tuberculosis (MACET). Latent tuberculosis infection: A guide for Massachusetts providers. 2000; Boston, MA.

( 4) 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 1998; 47 (No. RR-16): 2-29.

( 5) Froehlich H, Ackerson LM, Morozumi PA. Targeted testing of children for tuberculosis: Validation of a risk assessment questionnaire. Pediatrics 2001; 107: e54.

( 6) Saiman L, San Gabriel P, Schulte J et al. Risk factors for latent tuberculosis infection among children in New York City. Pediatrics 2001; 107: 999-1003.

( 7) Besser RB, Pakiz B, Schulte JM et al. Risk factors for positive Mantoux tuberculin skin tests in children in San Diego, California: Evidence for boosting and possible food-borne transmission. Pediatrics 2001; 108: 305-310.

( 8) Lobato MN, Hopewell PC. Mycobacterium tuberculosis infection after travel to or contact with visitors from countries with a high prevalence of tuberculosis. Am J Respir Crit Care Med 1998; 158: 1871-1875.

( 9) Cobelens FGJ, van Duetekom H, Draayer-Jansen IWE et al. Risk of infection with Mycobacterium tuberculosis in travelers to areas of high tuberculosis endemicity. Lancet 2000; 356: 461-465.

( 10) Sewint JR, Hall BS, Baldwin RM, Virden JM. Outcomes of annual tuberculosis screening by Mantoux test in children considered to be at high risk: Results from one urban clinic. Pediatrics 1997; 99: 529-533.

( 11) American Academy of Pediatrics. Report of the Committee on Infectious Diseases. Red Book 2000. 25th Edition. Elk Grove Village, IL; 2000: 597.

( 12) Mohle-Boetani JC, Miller B, Halpern M,, et al. School-based screening for tuberculosis infection. A cost-benefit analysis. JAMA 1995; 274: 613-619. See also the accompanying editorial Starke JR. Universal screening for tuberculosis infection. School's out! 652-653.

( 13) Adhikari N, Menzies R. Community-based tuberculin screening in Montreal: A cost-outcome description. Am J Public Health 1995; 85: 786-790.

( 14) Driver CR, Vbalway SE, Cantwell MF, Onorato IM. Tuberculin skin test screening in schoolchildren in the United States. Pediatrics 1996; 98: 97-102.

About MACET

The Medical Advisory Committee for the Elimination of Tuberculosis (MACET) is an independent panel appointed by the Commissioner of Public Health to guide the Massachusetts Department of Public Health in its effort to eliminate tuberculosis in the Commonwealth

MACET Members

Stephen J. Lerman, MD, MPH (Chair)
Timothy F. Brewer, MD, MPH (Vice-Chair)
Carlos Alvarez, MA
Jennifer S. Daly, MD
C. Robert Horsburgh, MD
Robert Husson, MD
Joel Piton, MD, Med

Ex-Officio Members

Jennifer Cochran, MPH
Alfred DeMaria, MD
Sue Etkind, RN, MS
Kathleen Hursen, RN
Edward Nardell, MD
Linda Singleton, RN. MPH

This information is provided by Tuberculosis Prevention and Control Program within the Department of Public Health.